Nonmelanoma Skin Cancer

An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.

This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.

“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.

The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.

Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.

Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.

Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.

Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.

Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.

Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”

Subsequent treatment was unsuccessful, and the patient died from his disease.

“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.

The investigators did not report conflicts of interest.

SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.

An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.

This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.

“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.

The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.

Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.

Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.

Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.

Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.

Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.

Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”

Subsequent treatment was unsuccessful, and the patient died from his disease.

“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.

The investigators did not report conflicts of interest.

SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.

An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.

This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.

“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.

The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.

Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.

Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.

Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.

Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.

Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.

Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”

Subsequent treatment was unsuccessful, and the patient died from his disease.

“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.

The investigators did not report conflicts of interest.

SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.

What does your patient need to know at the first visit?  

A patient may be scheduled for a total-body skin examination (TBSE) through several routes: primary care referral, continued cancer screening for an at-risk patient or patient transfer, or patient-directed scheduling for general screening regardless of risk factors. At the patient's first visit, it is imperative that the course of the appointment is smooth and predictable for patient comfort and for a thorough and effective examination. The nurse initially solicits salient medical history, particularly personal and family history of skin cancer, current medications, and any acute concerns. The nurse then prepares the patient for the logistics of the TBSE, namely to undress, don a gown that ties and opens in the back, and be seated on the examination table. When I enter the room, the conversation commences with me seated across from the patient, reviewing specifics about his/her history and risk factors. Then the TBSE is executed from head to toe.  

Do you broadly recommend TBSE? 

Firstly, TBSE is a safe clinical tool, supported by data outlining a lack of notable patient morbidity during the examination, including psychosocial factors, and it is generally well-received by patients (Risica et al). In 2016, the US Preventative Services Task Force (USPSTF) outlined its recommendations regarding screening for skin cancer, concluding that there is insufficient evidence to broadly recommend TBSE. Unfortunately, USPSTF findings amassed data from all types of screenings, including those by nondermatologists, and did not extract specialty-specific benefits and risks to patients. The recommendation also did not outline the influence of TBSE on morbidity and mortality for at-risk groups. The guidelines target primary care practice trends; therefore, specialty societies such as the American Academy of Dermatology issued statements following the USPSTF recommendation outlining these salient clarifications, namely that TBSE detects melanoma and keratinocyte carcinomas earlier than in patients who are not screened. Randomized controlled trials to prove this observation are lacking, particularly because of the ethics of withholding screening from a prospective study group. However, in 2017, Johnson et al outlined the best available survival data in concert with the USPSTF statement to arrive at the most beneficial screening recommendations for patients, specifically targeting risk groups--those with a history of skin cancer, immunosuppression, indoor tanning and/or many blistering sunburns, and several other genetic parameters--for at least annual TBSE. 

The technique and reproducibility of TBSE also are not standardized, though they seem to have been endearingly apprenticed but variably implemented through generations of dermatology residents going forward into practice. As it is, depending on patient body surface area, mobility, willingness to disrobe, and adornments (eg, tattoos, hair appliances), multiple factors can restrict full view of a patient's skin. Recently, Helm et al proposed standardizing the TBSE sequence to minimize omitted areas of the body, which may become an imperative tool for streamlined resident teaching and optimal screening encounters.  

How do you keep patients compliant with TBSE? 

During and following TBSE, I typically outline any lesions of concern and plan for further testing, screening, and behavioral prevention strategies. Frequency of TBSE and importance of compliance are discussed during the visit and reinforced at checkout where the appointment templates are established a year in advance for those with skin cancer. Further, for those with melanoma, their appointment slots are given priority status so that any cancellations or delays are rescheduled preferentially. Particularly during the discussion about TBSE frequency, I emphasize the comparison and importance of this visit akin to other recommended screenings, such as mammograms and colonoscopies, and that we, as dermatologists, are part of their cancer surveillance team. 

What do you do if patients refuse your recommendations? 

Some patients refuse a gown or removal of certain clothing items (eg, undergarments, socks, wigs). Some patients defer a yearly TBSE upon checkout and schedule an appointment only when a lesion of concern arises. My advice is not to shame patients and to take advantage of as much as the patient is able and comfortable to show us and be present for, welcoming that we have the opportunity to take care of them and screen for cancer in any capacity. In underserved or limited budget practice regions, lesion-directed examination vs TBSE may be the only screening method utilized and may even attract more patients to a screening facility (Hoorens et al). 

In the opposite corner are those patients who deem the recommended TBSE interval as too infrequent, which poses a delicate dilemma. In my opinion, these situations present another cohort of risks. Namely, the patient may become (or continue to be) overly fixated on the small details of every skin lesion, and in my experience, they tend to develop the habit of expecting at least 1 biopsy at each visit, typically of a lesion of their choosing. Depending on the validity of this expectation vs my clinical examination, it can lead to a difficult discussion with the patient about oversampling lesions and the potential for many scars, copious reexcisions for ambiguous lesion pathology, and a trend away from prudent clinical care. In addition, multiple visits incur more patient co-pays and time away from school, work, or home. To ease the patient's mind, I advise to call our office for a more acute visit if there is a lesion of concern; I additionally recommend taking a smartphone photograph of a concerning lesion and monitoring it for changes or sending the photograph to our patient portal messaging system so we can evaluate its acuity. 

What take-home advice do you give to patients? 

As the visit ends, I further explain that home self-examination or examination by a partner between visits is intuitively a valuable screening adjunct for skin cancer. In 2018, the USPSTF recommended behavioral skin cancer prevention counseling and self-examination only for younger-age cohorts with fair skin (6 months to 24 years), but its utility in specialty practice must be qualified. The American Academy of Dermatology Association subsequently issued a statement to support safe sun-protective practices and diligent self-screening for changing lesions, as earlier detection and management of skin cancer can lead to decreased morbidity and mortality from these neoplasms.  

Resources for Patients

American Academy of Dermatology's SPOT Skin Cancer

Centers for Disease Control and Prevention: What Screening Tests Are There?
 

What does your patient need to know at the first visit?  

A patient may be scheduled for a total-body skin examination (TBSE) through several routes: primary care referral, continued cancer screening for an at-risk patient or patient transfer, or patient-directed scheduling for general screening regardless of risk factors. At the patient's first visit, it is imperative that the course of the appointment is smooth and predictable for patient comfort and for a thorough and effective examination. The nurse initially solicits salient medical history, particularly personal and family history of skin cancer, current medications, and any acute concerns. The nurse then prepares the patient for the logistics of the TBSE, namely to undress, don a gown that ties and opens in the back, and be seated on the examination table. When I enter the room, the conversation commences with me seated across from the patient, reviewing specifics about his/her history and risk factors. Then the TBSE is executed from head to toe.  

Do you broadly recommend TBSE? 

Firstly, TBSE is a safe clinical tool, supported by data outlining a lack of notable patient morbidity during the examination, including psychosocial factors, and it is generally well-received by patients (Risica et al). In 2016, the US Preventative Services Task Force (USPSTF) outlined its recommendations regarding screening for skin cancer, concluding that there is insufficient evidence to broadly recommend TBSE. Unfortunately, USPSTF findings amassed data from all types of screenings, including those by nondermatologists, and did not extract specialty-specific benefits and risks to patients. The recommendation also did not outline the influence of TBSE on morbidity and mortality for at-risk groups. The guidelines target primary care practice trends; therefore, specialty societies such as the American Academy of Dermatology issued statements following the USPSTF recommendation outlining these salient clarifications, namely that TBSE detects melanoma and keratinocyte carcinomas earlier than in patients who are not screened. Randomized controlled trials to prove this observation are lacking, particularly because of the ethics of withholding screening from a prospective study group. However, in 2017, Johnson et al outlined the best available survival data in concert with the USPSTF statement to arrive at the most beneficial screening recommendations for patients, specifically targeting risk groups--those with a history of skin cancer, immunosuppression, indoor tanning and/or many blistering sunburns, and several other genetic parameters--for at least annual TBSE. 

The technique and reproducibility of TBSE also are not standardized, though they seem to have been endearingly apprenticed but variably implemented through generations of dermatology residents going forward into practice. As it is, depending on patient body surface area, mobility, willingness to disrobe, and adornments (eg, tattoos, hair appliances), multiple factors can restrict full view of a patient's skin. Recently, Helm et al proposed standardizing the TBSE sequence to minimize omitted areas of the body, which may become an imperative tool for streamlined resident teaching and optimal screening encounters.  

How do you keep patients compliant with TBSE? 

During and following TBSE, I typically outline any lesions of concern and plan for further testing, screening, and behavioral prevention strategies. Frequency of TBSE and importance of compliance are discussed during the visit and reinforced at checkout where the appointment templates are established a year in advance for those with skin cancer. Further, for those with melanoma, their appointment slots are given priority status so that any cancellations or delays are rescheduled preferentially. Particularly during the discussion about TBSE frequency, I emphasize the comparison and importance of this visit akin to other recommended screenings, such as mammograms and colonoscopies, and that we, as dermatologists, are part of their cancer surveillance team. 

What do you do if patients refuse your recommendations? 

Some patients refuse a gown or removal of certain clothing items (eg, undergarments, socks, wigs). Some patients defer a yearly TBSE upon checkout and schedule an appointment only when a lesion of concern arises. My advice is not to shame patients and to take advantage of as much as the patient is able and comfortable to show us and be present for, welcoming that we have the opportunity to take care of them and screen for cancer in any capacity. In underserved or limited budget practice regions, lesion-directed examination vs TBSE may be the only screening method utilized and may even attract more patients to a screening facility (Hoorens et al). 

In the opposite corner are those patients who deem the recommended TBSE interval as too infrequent, which poses a delicate dilemma. In my opinion, these situations present another cohort of risks. Namely, the patient may become (or continue to be) overly fixated on the small details of every skin lesion, and in my experience, they tend to develop the habit of expecting at least 1 biopsy at each visit, typically of a lesion of their choosing. Depending on the validity of this expectation vs my clinical examination, it can lead to a difficult discussion with the patient about oversampling lesions and the potential for many scars, copious reexcisions for ambiguous lesion pathology, and a trend away from prudent clinical care. In addition, multiple visits incur more patient co-pays and time away from school, work, or home. To ease the patient's mind, I advise to call our office for a more acute visit if there is a lesion of concern; I additionally recommend taking a smartphone photograph of a concerning lesion and monitoring it for changes or sending the photograph to our patient portal messaging system so we can evaluate its acuity. 

What take-home advice do you give to patients? 

As the visit ends, I further explain that home self-examination or examination by a partner between visits is intuitively a valuable screening adjunct for skin cancer. In 2018, the USPSTF recommended behavioral skin cancer prevention counseling and self-examination only for younger-age cohorts with fair skin (6 months to 24 years), but its utility in specialty practice must be qualified. The American Academy of Dermatology Association subsequently issued a statement to support safe sun-protective practices and diligent self-screening for changing lesions, as earlier detection and management of skin cancer can lead to decreased morbidity and mortality from these neoplasms.  

Resources for Patients

American Academy of Dermatology's SPOT Skin Cancer

Centers for Disease Control and Prevention: What Screening Tests Are There?
 

What does your patient need to know at the first visit?  

A patient may be scheduled for a total-body skin examination (TBSE) through several routes: primary care referral, continued cancer screening for an at-risk patient or patient transfer, or patient-directed scheduling for general screening regardless of risk factors. At the patient's first visit, it is imperative that the course of the appointment is smooth and predictable for patient comfort and for a thorough and effective examination. The nurse initially solicits salient medical history, particularly personal and family history of skin cancer, current medications, and any acute concerns. The nurse then prepares the patient for the logistics of the TBSE, namely to undress, don a gown that ties and opens in the back, and be seated on the examination table. When I enter the room, the conversation commences with me seated across from the patient, reviewing specifics about his/her history and risk factors. Then the TBSE is executed from head to toe.  

Do you broadly recommend TBSE? 

Firstly, TBSE is a safe clinical tool, supported by data outlining a lack of notable patient morbidity during the examination, including psychosocial factors, and it is generally well-received by patients (Risica et al). In 2016, the US Preventative Services Task Force (USPSTF) outlined its recommendations regarding screening for skin cancer, concluding that there is insufficient evidence to broadly recommend TBSE. Unfortunately, USPSTF findings amassed data from all types of screenings, including those by nondermatologists, and did not extract specialty-specific benefits and risks to patients. The recommendation also did not outline the influence of TBSE on morbidity and mortality for at-risk groups. The guidelines target primary care practice trends; therefore, specialty societies such as the American Academy of Dermatology issued statements following the USPSTF recommendation outlining these salient clarifications, namely that TBSE detects melanoma and keratinocyte carcinomas earlier than in patients who are not screened. Randomized controlled trials to prove this observation are lacking, particularly because of the ethics of withholding screening from a prospective study group. However, in 2017, Johnson et al outlined the best available survival data in concert with the USPSTF statement to arrive at the most beneficial screening recommendations for patients, specifically targeting risk groups--those with a history of skin cancer, immunosuppression, indoor tanning and/or many blistering sunburns, and several other genetic parameters--for at least annual TBSE. 

The technique and reproducibility of TBSE also are not standardized, though they seem to have been endearingly apprenticed but variably implemented through generations of dermatology residents going forward into practice. As it is, depending on patient body surface area, mobility, willingness to disrobe, and adornments (eg, tattoos, hair appliances), multiple factors can restrict full view of a patient's skin. Recently, Helm et al proposed standardizing the TBSE sequence to minimize omitted areas of the body, which may become an imperative tool for streamlined resident teaching and optimal screening encounters.  

How do you keep patients compliant with TBSE? 

During and following TBSE, I typically outline any lesions of concern and plan for further testing, screening, and behavioral prevention strategies. Frequency of TBSE and importance of compliance are discussed during the visit and reinforced at checkout where the appointment templates are established a year in advance for those with skin cancer. Further, for those with melanoma, their appointment slots are given priority status so that any cancellations or delays are rescheduled preferentially. Particularly during the discussion about TBSE frequency, I emphasize the comparison and importance of this visit akin to other recommended screenings, such as mammograms and colonoscopies, and that we, as dermatologists, are part of their cancer surveillance team. 

What do you do if patients refuse your recommendations? 

Some patients refuse a gown or removal of certain clothing items (eg, undergarments, socks, wigs). Some patients defer a yearly TBSE upon checkout and schedule an appointment only when a lesion of concern arises. My advice is not to shame patients and to take advantage of as much as the patient is able and comfortable to show us and be present for, welcoming that we have the opportunity to take care of them and screen for cancer in any capacity. In underserved or limited budget practice regions, lesion-directed examination vs TBSE may be the only screening method utilized and may even attract more patients to a screening facility (Hoorens et al). 

In the opposite corner are those patients who deem the recommended TBSE interval as too infrequent, which poses a delicate dilemma. In my opinion, these situations present another cohort of risks. Namely, the patient may become (or continue to be) overly fixated on the small details of every skin lesion, and in my experience, they tend to develop the habit of expecting at least 1 biopsy at each visit, typically of a lesion of their choosing. Depending on the validity of this expectation vs my clinical examination, it can lead to a difficult discussion with the patient about oversampling lesions and the potential for many scars, copious reexcisions for ambiguous lesion pathology, and a trend away from prudent clinical care. In addition, multiple visits incur more patient co-pays and time away from school, work, or home. To ease the patient's mind, I advise to call our office for a more acute visit if there is a lesion of concern; I additionally recommend taking a smartphone photograph of a concerning lesion and monitoring it for changes or sending the photograph to our patient portal messaging system so we can evaluate its acuity. 

What take-home advice do you give to patients? 

As the visit ends, I further explain that home self-examination or examination by a partner between visits is intuitively a valuable screening adjunct for skin cancer. In 2018, the USPSTF recommended behavioral skin cancer prevention counseling and self-examination only for younger-age cohorts with fair skin (6 months to 24 years), but its utility in specialty practice must be qualified. The American Academy of Dermatology Association subsequently issued a statement to support safe sun-protective practices and diligent self-screening for changing lesions, as earlier detection and management of skin cancer can lead to decreased morbidity and mortality from these neoplasms.  

Resources for Patients

American Academy of Dermatology's SPOT Skin Cancer

Centers for Disease Control and Prevention: What Screening Tests Are There?
 

The Diagnosis: Merkel Cell Carcinoma 

An excisional biopsy revealed that the dermis was mostly replaced by a malignant neoplastic infiltrate morphologically resembling small cell carcinoma (Figure 1). The cells had uniform hyperchromatic nuclei with fairly even chromatin and generally inconspicuous nucleoli. There was a tendency for smudgy artifacts at the periphery of the infiltrate, and the cells had relatively scant cytoplasm with slight streaming. Occasional apoptotic forms were present. Immunohistochemistry showed strong dotlike staining with cytokeratin 20 and moderate positivity with synaptophysin and chromogranin A (Figure 2). Unusually, there also was weak staining in a few tumor cells with thyroid transcription factor 1, a marker usually indicative of small cell carcinoma of the lungs that typically is negative in Merkel cell carcinoma (MCC). A second thyroid transcription factor 1 monoclonal antibody used in a double immunostain for lung adenocarcinomas was completely negative. This second antibody is more specific but less sensitive than the stand-alone version. The skin biopsy results confirmed the diagnosis of MCC. Given the patient's frailty and comorbidities, wide local excision was not performed and the patient was referred to radiation oncology. He died several months later from metastatic MCC. 

Merkel cell carcinoma is an uncommon skin malignancy that can be easily mistaken for other conditions if the clinician is not familiar with its typical presentation. It most commonly is found on the head and neck in elderly individuals, most often aged 60 to 80 years,¹ with a notable history of sun exposure and/or immunosuppression. It is an aggressive skin cancer that originally was thought to be due to pathogenic changes of Merkel cells,² which are specialized touch receptors located at the dermoepidermal junction of the skin; however, newer evidence has suggested that MCC arises from malignant changes to skin stem cells.³ It shares more characteristics with extracutaneous neuroendocrine tumors and is more aptly labeled by pathologists as a primary neuroendocrine carcinoma of the skin.⁴  

The frequency of MCC is highest in Australia, likely due to intense sun exposure, where the age-adjusted incidence rate reported in Queensland was 1.6 per 100,000 individuals from 2006 to 2010.⁵ The lowest incidence rates were reported in Finland (0.11 and 0.12 per 100,000 males and females, respectively)⁶ and Denmark (2.2 cases per million person-years).⁷ The clinical features of MCC are summarized by the mnemonic AEIOU: asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than 50 years, UV-exposed site on a person with fair skin.⁸ In a 2008 study of 195 patients, 89% of primary MCC lesions met 3 or more criteria, 32% met 4 or more criteria, and 7% met all 5 criteria.⁸  

The classic presentation of MCC is a pink-red to violaceous nodule on the head or neck in an elderly patient, but there is a need to maintain suspicion of malignancy when examining a presumed infected cystic lesion, especially when a round of antibiotics has not ameliorated the symptoms. According to Heath et al,⁸ of 106 patients treated for MCC, 56% of first clinical impressions were benign. A PubMed and Scopus search was performed with the MeSH headings Merkel cell carcinoma +/- presentation to uncover similar unusual presentations between 1970 and the present day. Merkel cell carcinoma has been misdiagnosed as seemingly benign lesions including lipoma,⁹ allergic contact dermatitis,¹⁰ and atheroma.¹¹ The differential diagnosis of MCC also includes cysts, amelanotic melanoma, basal cell carcinoma, dermatofibrosarcoma protuberans, squamous cell carcinoma, fungal kerion, leiomyosarcoma, neurothekeoma, abscesses, and cutaneous lymphoma.  

Merkel cell polyomavirus has been implicated in the malignant transformation of MCC. It is a small, human, nonenveloped, double-stranded DNA virus1 and is found in approximately 70% to 80% of MCC cases.¹² Merkel cell polyomavirus is a respiratory tract pathogen that is acquired by immunocompetent infants; it integrates itself into the host's genome and then enters a long latency period to later reactivate in immunocompromised adults.¹³ 

Wide local excision down to fascia is the mainstay of treatment of MCC, with recommended margins of 1 to 2 cm.¹⁴ Mohs micrographic surgery also can be considered.¹⁵ Similar to other neuroendocrine tumors, MCC is considered a radiosensitive tumor; radiation likely improves local control and is recommended in early-stage disease.^16,17 It also has been described as the sole treatment modality in patients who are not candidates for surgery. The role of chemotherapy is more controversial, as responses do not appear to be long-lasting but should be considered in patients with advanced disease.^14,18 There have been major advances in immunotherapy with the recent approvals of avelumab, an anti-PD-L1 inhibitor,¹⁹ and pembrolizumab,²⁰ an anti-PD-1 inhibitor, for metastatic MCC. Clinical trials for MCC using kinase inhibitors and somatostatin analogues currently are ongoing.²¹  

Several studies have demonstrated high rates of occult nodal disease in clinically node-negative patients, which has led to widespread use of sentinel lymph node biopsies^.22,23 A sentinel lymph node biopsy is recommended at the time of surgery to aid with treatment decisions and prognosis.²⁴  

Merkel cell carcinoma is highly aggressive, and more than one-third of patients die from their disease, making it twice as lethal as melanoma. Overall survival rates remain low (5-year overall survival, 0%-18%) for advanced disease.⁵ Unfortunately, progression to metastasis is common and most often occurs within 2 years of diagnosis.^17,25 Follow-up after treatment of MCC is crucial, with the 2019 National Comprehensive Cancer Network (NCCN) guidelines suggesting a physical examination with complete skin and complete lymph node examination every 3 to 6 months for 3 years and every 6 to 12 months thereafter.¹⁵ 

This case is an important reminder to include MCC in the differential diagnosis of presumed infected cysts, particularly on sun-exposed sites in elderly patients, as our patient was treated with antibiotics twice without improvement. An infected cyst with a lack of response to antibiotics should alert clinicians to the potential of malignancy.  

The Diagnosis: Merkel Cell Carcinoma 

An excisional biopsy revealed that the dermis was mostly replaced by a malignant neoplastic infiltrate morphologically resembling small cell carcinoma (Figure 1). The cells had uniform hyperchromatic nuclei with fairly even chromatin and generally inconspicuous nucleoli. There was a tendency for smudgy artifacts at the periphery of the infiltrate, and the cells had relatively scant cytoplasm with slight streaming. Occasional apoptotic forms were present. Immunohistochemistry showed strong dotlike staining with cytokeratin 20 and moderate positivity with synaptophysin and chromogranin A (Figure 2). Unusually, there also was weak staining in a few tumor cells with thyroid transcription factor 1, a marker usually indicative of small cell carcinoma of the lungs that typically is negative in Merkel cell carcinoma (MCC). A second thyroid transcription factor 1 monoclonal antibody used in a double immunostain for lung adenocarcinomas was completely negative. This second antibody is more specific but less sensitive than the stand-alone version. The skin biopsy results confirmed the diagnosis of MCC. Given the patient's frailty and comorbidities, wide local excision was not performed and the patient was referred to radiation oncology. He died several months later from metastatic MCC. 

Merkel cell carcinoma is an uncommon skin malignancy that can be easily mistaken for other conditions if the clinician is not familiar with its typical presentation. It most commonly is found on the head and neck in elderly individuals, most often aged 60 to 80 years,¹ with a notable history of sun exposure and/or immunosuppression. It is an aggressive skin cancer that originally was thought to be due to pathogenic changes of Merkel cells,² which are specialized touch receptors located at the dermoepidermal junction of the skin; however, newer evidence has suggested that MCC arises from malignant changes to skin stem cells.³ It shares more characteristics with extracutaneous neuroendocrine tumors and is more aptly labeled by pathologists as a primary neuroendocrine carcinoma of the skin.⁴  

The frequency of MCC is highest in Australia, likely due to intense sun exposure, where the age-adjusted incidence rate reported in Queensland was 1.6 per 100,000 individuals from 2006 to 2010.⁵ The lowest incidence rates were reported in Finland (0.11 and 0.12 per 100,000 males and females, respectively)⁶ and Denmark (2.2 cases per million person-years).⁷ The clinical features of MCC are summarized by the mnemonic AEIOU: asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than 50 years, UV-exposed site on a person with fair skin.⁸ In a 2008 study of 195 patients, 89% of primary MCC lesions met 3 or more criteria, 32% met 4 or more criteria, and 7% met all 5 criteria.⁸  

The classic presentation of MCC is a pink-red to violaceous nodule on the head or neck in an elderly patient, but there is a need to maintain suspicion of malignancy when examining a presumed infected cystic lesion, especially when a round of antibiotics has not ameliorated the symptoms. According to Heath et al,⁸ of 106 patients treated for MCC, 56% of first clinical impressions were benign. A PubMed and Scopus search was performed with the MeSH headings Merkel cell carcinoma +/- presentation to uncover similar unusual presentations between 1970 and the present day. Merkel cell carcinoma has been misdiagnosed as seemingly benign lesions including lipoma,⁹ allergic contact dermatitis,¹⁰ and atheroma.¹¹ The differential diagnosis of MCC also includes cysts, amelanotic melanoma, basal cell carcinoma, dermatofibrosarcoma protuberans, squamous cell carcinoma, fungal kerion, leiomyosarcoma, neurothekeoma, abscesses, and cutaneous lymphoma.  

Merkel cell polyomavirus has been implicated in the malignant transformation of MCC. It is a small, human, nonenveloped, double-stranded DNA virus1 and is found in approximately 70% to 80% of MCC cases.¹² Merkel cell polyomavirus is a respiratory tract pathogen that is acquired by immunocompetent infants; it integrates itself into the host's genome and then enters a long latency period to later reactivate in immunocompromised adults.¹³ 

Wide local excision down to fascia is the mainstay of treatment of MCC, with recommended margins of 1 to 2 cm.¹⁴ Mohs micrographic surgery also can be considered.¹⁵ Similar to other neuroendocrine tumors, MCC is considered a radiosensitive tumor; radiation likely improves local control and is recommended in early-stage disease.^16,17 It also has been described as the sole treatment modality in patients who are not candidates for surgery. The role of chemotherapy is more controversial, as responses do not appear to be long-lasting but should be considered in patients with advanced disease.^14,18 There have been major advances in immunotherapy with the recent approvals of avelumab, an anti-PD-L1 inhibitor,¹⁹ and pembrolizumab,²⁰ an anti-PD-1 inhibitor, for metastatic MCC. Clinical trials for MCC using kinase inhibitors and somatostatin analogues currently are ongoing.²¹  

Several studies have demonstrated high rates of occult nodal disease in clinically node-negative patients, which has led to widespread use of sentinel lymph node biopsies^.22,23 A sentinel lymph node biopsy is recommended at the time of surgery to aid with treatment decisions and prognosis.²⁴  

Merkel cell carcinoma is highly aggressive, and more than one-third of patients die from their disease, making it twice as lethal as melanoma. Overall survival rates remain low (5-year overall survival, 0%-18%) for advanced disease.⁵ Unfortunately, progression to metastasis is common and most often occurs within 2 years of diagnosis.^17,25 Follow-up after treatment of MCC is crucial, with the 2019 National Comprehensive Cancer Network (NCCN) guidelines suggesting a physical examination with complete skin and complete lymph node examination every 3 to 6 months for 3 years and every 6 to 12 months thereafter.¹⁵ 

This case is an important reminder to include MCC in the differential diagnosis of presumed infected cysts, particularly on sun-exposed sites in elderly patients, as our patient was treated with antibiotics twice without improvement. An infected cyst with a lack of response to antibiotics should alert clinicians to the potential of malignancy.  

The Diagnosis: Merkel Cell Carcinoma 

An excisional biopsy revealed that the dermis was mostly replaced by a malignant neoplastic infiltrate morphologically resembling small cell carcinoma (Figure 1). The cells had uniform hyperchromatic nuclei with fairly even chromatin and generally inconspicuous nucleoli. There was a tendency for smudgy artifacts at the periphery of the infiltrate, and the cells had relatively scant cytoplasm with slight streaming. Occasional apoptotic forms were present. Immunohistochemistry showed strong dotlike staining with cytokeratin 20 and moderate positivity with synaptophysin and chromogranin A (Figure 2). Unusually, there also was weak staining in a few tumor cells with thyroid transcription factor 1, a marker usually indicative of small cell carcinoma of the lungs that typically is negative in Merkel cell carcinoma (MCC). A second thyroid transcription factor 1 monoclonal antibody used in a double immunostain for lung adenocarcinomas was completely negative. This second antibody is more specific but less sensitive than the stand-alone version. The skin biopsy results confirmed the diagnosis of MCC. Given the patient's frailty and comorbidities, wide local excision was not performed and the patient was referred to radiation oncology. He died several months later from metastatic MCC. 

Merkel cell carcinoma is an uncommon skin malignancy that can be easily mistaken for other conditions if the clinician is not familiar with its typical presentation. It most commonly is found on the head and neck in elderly individuals, most often aged 60 to 80 years,¹ with a notable history of sun exposure and/or immunosuppression. It is an aggressive skin cancer that originally was thought to be due to pathogenic changes of Merkel cells,² which are specialized touch receptors located at the dermoepidermal junction of the skin; however, newer evidence has suggested that MCC arises from malignant changes to skin stem cells.³ It shares more characteristics with extracutaneous neuroendocrine tumors and is more aptly labeled by pathologists as a primary neuroendocrine carcinoma of the skin.⁴  

The frequency of MCC is highest in Australia, likely due to intense sun exposure, where the age-adjusted incidence rate reported in Queensland was 1.6 per 100,000 individuals from 2006 to 2010.⁵ The lowest incidence rates were reported in Finland (0.11 and 0.12 per 100,000 males and females, respectively)⁶ and Denmark (2.2 cases per million person-years).⁷ The clinical features of MCC are summarized by the mnemonic AEIOU: asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than 50 years, UV-exposed site on a person with fair skin.⁸ In a 2008 study of 195 patients, 89% of primary MCC lesions met 3 or more criteria, 32% met 4 or more criteria, and 7% met all 5 criteria.⁸  

The classic presentation of MCC is a pink-red to violaceous nodule on the head or neck in an elderly patient, but there is a need to maintain suspicion of malignancy when examining a presumed infected cystic lesion, especially when a round of antibiotics has not ameliorated the symptoms. According to Heath et al,⁸ of 106 patients treated for MCC, 56% of first clinical impressions were benign. A PubMed and Scopus search was performed with the MeSH headings Merkel cell carcinoma +/- presentation to uncover similar unusual presentations between 1970 and the present day. Merkel cell carcinoma has been misdiagnosed as seemingly benign lesions including lipoma,⁹ allergic contact dermatitis,¹⁰ and atheroma.¹¹ The differential diagnosis of MCC also includes cysts, amelanotic melanoma, basal cell carcinoma, dermatofibrosarcoma protuberans, squamous cell carcinoma, fungal kerion, leiomyosarcoma, neurothekeoma, abscesses, and cutaneous lymphoma.  

Merkel cell polyomavirus has been implicated in the malignant transformation of MCC. It is a small, human, nonenveloped, double-stranded DNA virus1 and is found in approximately 70% to 80% of MCC cases.¹² Merkel cell polyomavirus is a respiratory tract pathogen that is acquired by immunocompetent infants; it integrates itself into the host's genome and then enters a long latency period to later reactivate in immunocompromised adults.¹³ 

Wide local excision down to fascia is the mainstay of treatment of MCC, with recommended margins of 1 to 2 cm.¹⁴ Mohs micrographic surgery also can be considered.¹⁵ Similar to other neuroendocrine tumors, MCC is considered a radiosensitive tumor; radiation likely improves local control and is recommended in early-stage disease.^16,17 It also has been described as the sole treatment modality in patients who are not candidates for surgery. The role of chemotherapy is more controversial, as responses do not appear to be long-lasting but should be considered in patients with advanced disease.^14,18 There have been major advances in immunotherapy with the recent approvals of avelumab, an anti-PD-L1 inhibitor,¹⁹ and pembrolizumab,²⁰ an anti-PD-1 inhibitor, for metastatic MCC. Clinical trials for MCC using kinase inhibitors and somatostatin analogues currently are ongoing.²¹  

Several studies have demonstrated high rates of occult nodal disease in clinically node-negative patients, which has led to widespread use of sentinel lymph node biopsies^.22,23 A sentinel lymph node biopsy is recommended at the time of surgery to aid with treatment decisions and prognosis.²⁴  

Merkel cell carcinoma is highly aggressive, and more than one-third of patients die from their disease, making it twice as lethal as melanoma. Overall survival rates remain low (5-year overall survival, 0%-18%) for advanced disease.⁵ Unfortunately, progression to metastasis is common and most often occurs within 2 years of diagnosis.^17,25 Follow-up after treatment of MCC is crucial, with the 2019 National Comprehensive Cancer Network (NCCN) guidelines suggesting a physical examination with complete skin and complete lymph node examination every 3 to 6 months for 3 years and every 6 to 12 months thereafter.¹⁵ 

This case is an important reminder to include MCC in the differential diagnosis of presumed infected cysts, particularly on sun-exposed sites in elderly patients, as our patient was treated with antibiotics twice without improvement. An infected cyst with a lack of response to antibiotics should alert clinicians to the potential of malignancy.  

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

msullivan@mdedge.com

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

msullivan@mdedge.com

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

msullivan@mdedge.com

Isolated limb perfusion (ILP) for the adjuvant treatment of melanoma involves isolating the blood flow of a limb from the rest of the body to allow for high concentrations of chemotherapeutic agents locally. Chemotherapy with nitrogen mustard is the preferred chemotherapeutic agent in ILP for the adjuvant treatment of locally advanced melanoma.¹ Systemic exposure to nitrogen mustard has shown to be carcinogenic, and its topical application has been associated with the development of actinic keratosis, basal cell carcinoma (BCC), and squamous cell carcinoma.^2,3 However, the long-term effects of ILP with nitrogen mustard are not well defined. In 1998, one of the authors (R.L.M.) described a patient with melanoma of the left leg that was treated with ILP with nitrogen mustard who subsequently developed numerous BCCs on the same leg.⁴ This same patient has since been successfully managed with only topical chemotherapeutic agents for the last 21 years.

An 86-year-old man with a history of melanoma underwent wide resection, lymph node dissection, and adjuvant ILP with nitrogen mustard for the treatment of melanoma of the medial left thigh approximately 50 years ago. He denied any prior radiation treatment. He subsequently presented years later to our dermatology clinic with many biopsy-proven superficial and nodular BCCs of the left leg over the course of the last 30 years. On physical examination, the patient had several pink papules and macules on the left lower leg (Figure). The patient had previously undergone multiple invasive excisions with grafting for the treatment of BCCs by a plastic surgeon prior to presentation to our clinic but has since had many years of control under our care with only topical chemotherapeutic agents. His current medication regimen consists of 5-fluorouracil twice daily, which he tolerates without serious side effects. He also has used imiquimod in the past.

Treatment modalities for NMSC include surgical excision with defined margins, Mohs micrographic surgery, radiotherapy, electrodesiccation and curettage, cryotherapy, photodynamic therapy, and topical therapy. Our patient experienced such a high volume of superficial BCCs that the decision was made to avoid frequent surgical procedures and to treat with topical chemotherapeutic agents. He had an excellent response to topical 5-fluorouracil, and the treatment has been well tolerated. This case is valuable for clinicians, as it demonstrates that topical chemotherapy can be a well-tolerated option for patients who present with frequent superficial BCCs to prevent numerous invasive surgical treatments.

Isolated limb perfusion (ILP) for the adjuvant treatment of melanoma involves isolating the blood flow of a limb from the rest of the body to allow for high concentrations of chemotherapeutic agents locally. Chemotherapy with nitrogen mustard is the preferred chemotherapeutic agent in ILP for the adjuvant treatment of locally advanced melanoma.¹ Systemic exposure to nitrogen mustard has shown to be carcinogenic, and its topical application has been associated with the development of actinic keratosis, basal cell carcinoma (BCC), and squamous cell carcinoma.^2,3 However, the long-term effects of ILP with nitrogen mustard are not well defined. In 1998, one of the authors (R.L.M.) described a patient with melanoma of the left leg that was treated with ILP with nitrogen mustard who subsequently developed numerous BCCs on the same leg.⁴ This same patient has since been successfully managed with only topical chemotherapeutic agents for the last 21 years.

An 86-year-old man with a history of melanoma underwent wide resection, lymph node dissection, and adjuvant ILP with nitrogen mustard for the treatment of melanoma of the medial left thigh approximately 50 years ago. He denied any prior radiation treatment. He subsequently presented years later to our dermatology clinic with many biopsy-proven superficial and nodular BCCs of the left leg over the course of the last 30 years. On physical examination, the patient had several pink papules and macules on the left lower leg (Figure). The patient had previously undergone multiple invasive excisions with grafting for the treatment of BCCs by a plastic surgeon prior to presentation to our clinic but has since had many years of control under our care with only topical chemotherapeutic agents. His current medication regimen consists of 5-fluorouracil twice daily, which he tolerates without serious side effects. He also has used imiquimod in the past.

Treatment modalities for NMSC include surgical excision with defined margins, Mohs micrographic surgery, radiotherapy, electrodesiccation and curettage, cryotherapy, photodynamic therapy, and topical therapy. Our patient experienced such a high volume of superficial BCCs that the decision was made to avoid frequent surgical procedures and to treat with topical chemotherapeutic agents. He had an excellent response to topical 5-fluorouracil, and the treatment has been well tolerated. This case is valuable for clinicians, as it demonstrates that topical chemotherapy can be a well-tolerated option for patients who present with frequent superficial BCCs to prevent numerous invasive surgical treatments.

Isolated limb perfusion (ILP) for the adjuvant treatment of melanoma involves isolating the blood flow of a limb from the rest of the body to allow for high concentrations of chemotherapeutic agents locally. Chemotherapy with nitrogen mustard is the preferred chemotherapeutic agent in ILP for the adjuvant treatment of locally advanced melanoma.¹ Systemic exposure to nitrogen mustard has shown to be carcinogenic, and its topical application has been associated with the development of actinic keratosis, basal cell carcinoma (BCC), and squamous cell carcinoma.^2,3 However, the long-term effects of ILP with nitrogen mustard are not well defined. In 1998, one of the authors (R.L.M.) described a patient with melanoma of the left leg that was treated with ILP with nitrogen mustard who subsequently developed numerous BCCs on the same leg.⁴ This same patient has since been successfully managed with only topical chemotherapeutic agents for the last 21 years.

An 86-year-old man with a history of melanoma underwent wide resection, lymph node dissection, and adjuvant ILP with nitrogen mustard for the treatment of melanoma of the medial left thigh approximately 50 years ago. He denied any prior radiation treatment. He subsequently presented years later to our dermatology clinic with many biopsy-proven superficial and nodular BCCs of the left leg over the course of the last 30 years. On physical examination, the patient had several pink papules and macules on the left lower leg (Figure). The patient had previously undergone multiple invasive excisions with grafting for the treatment of BCCs by a plastic surgeon prior to presentation to our clinic but has since had many years of control under our care with only topical chemotherapeutic agents. His current medication regimen consists of 5-fluorouracil twice daily, which he tolerates without serious side effects. He also has used imiquimod in the past.

Treatment modalities for NMSC include surgical excision with defined margins, Mohs micrographic surgery, radiotherapy, electrodesiccation and curettage, cryotherapy, photodynamic therapy, and topical therapy. Our patient experienced such a high volume of superficial BCCs that the decision was made to avoid frequent surgical procedures and to treat with topical chemotherapeutic agents. He had an excellent response to topical 5-fluorouracil, and the treatment has been well tolerated. This case is valuable for clinicians, as it demonstrates that topical chemotherapy can be a well-tolerated option for patients who present with frequent superficial BCCs to prevent numerous invasive surgical treatments.

Nonablative laser therapy is emerging as an effective noninvasive treatment option for basal cell carcinoma (BCC) with reduced adverse effects and good cosmetic outcomes compared to surgery. Vascular lasers, such as the pulsed dye laser (PDL), are thought to work by selectively targeting the tumor’s vascular network while preserving normal surrounding tissue.^1,2 Although high energy and multiple passes might be required, adjunctive use of dynamic cooling reduces the risk for nonselective thermal injury vs ablative lasers, which destroy the tumor itself through vaporization of tissue water.²

With no established laser management guidelines for the treatment of BCC, earlier studies using a 595-nm PDL varied highly in their protocol.^3-8 Pulsed dye laser parameters ranged from a spot size of 7 to 10 mm, fluence of 7.5 to 15 J/cm², and pulse duration of 0.5 to 3 milliseconds. Follow-up ranged from 12 days to 25 months after the final laser treatment. The number of lesions in prior studies ranged from 7 to 100 BCCs, with the clinical clearance rate ranging from 71.4% to 75% for facial BCC and 78.6% to 95% for nonfacial BCC.^3-8 Studies with histologic confirmation had a clearance rate of 66.6% for facial BCC and 25% to 92.3% for nonfacial BCC.^3-5,7,8 Most studies examined BCCs on the trunk and extremities with few investigating facial BCC,^3-8 which is especially important given that the head and neck are the most common and cosmetically sensitive anatomic locations.^9-13

Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) can assist with the diagnosis and treatment monitoring of BCC. These devices enable in vivo visualization of tissue in both cross-sectional and en face views and therefore can reduce the need for diagnostic biopsy. Reflectance confocal microscopy enables near-histologic visualization of the epidermis and superficial dermis with a resolution of 0.5 to 1 μm.¹⁴ Optical coherence tomography uses an infrared broadband light source that allows users to view skin architecture as deep as 1.5 to 2 mm with a resolution of 5 μm.¹⁵

When used synergistically, both devices can enhance the efficacy of nonablative laser treatment. With its increased depth and wider field of view, OCT is an optimal tool for repetitive evaluation of the same site over time and for following biopsy-confirmed tumors undergoing management.¹⁶ In addition to delineating tumor margins before treatment, imaging improves the detection of residual skin cancers, despite clearance on clinical and dermoscopic examination. Noninvasive imaging and nonsurgical management with laser therapy allow the physician to leave the skin intact and avoid scar tissue that might otherwise make it more difficult to detect and manage recurrence. The ability of OCT and RCM to monitor the efficacy of nonsurgical therapies for skin cancer has been demonstrated with imiquimod, photodynamic therapy, vismodegib, and ablative laser therapy.^17-20

With limited data on nonablative laser management of BCC, several gaps in the literature exist. First, in previously published studies the number of treatments was either determined to be an arbitrary set number or based on clinical clearance, which has the potential to miss residual tumor. Second, many follow-ups were limited to shortly after the final treatment, which limits the accuracy of the clearance rate, given that inflammation and scars can hide residual tumor.^21-23 Third, because many studies excised the treated area, long-term follow-up for recurrence was obscured. Last, only a few studies involved facial BCC, which is the most common and cosmetically concerning anatomic location.¹³

Our study attempted to address these gaps by evaluating the use of noninvasive imaging to guide management of primarily facial BCC. The objective was to perform a retrospective chart review on a subgroup of patients with BCC who were treated with combined nonablative PDL and fractional laser treatment with an extended follow-up period.

Methods

Study Design
We performed a retrospective chart review of 68 patients with 93 BCCs who had been treated with nonablative laser therapy as an alternative to surgery at the Mount Sinai Faculty Practice Associates between February 2011 and December 2018. Patients were followed throughout this period for assessment of clinical and subclinical recurrence. The Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects provided institutional review board approval.

Patients
Inclusion criteria included the following: (1) BCC diagnosed by biopsy (see eTable 1 for subtypes) and (2) treated with a nonablative laser due to patient preference and eligibility by the principal investigator (PI). As a retrospective study, lesions were included irrespective of tumor subtype or size. Although the risk for perineural invasion (PNI) is extremely low with BCC (<0.2%), none of the cases demonstrated PNI on diagnostic biopsy and none exhibited clinical evidence of PNI, such as paresthesia, pain, facial paralysis, or diplopia.²⁴

Eligibility determined by the PI included limited clinical ulceration or bleeding, or both, and a safe distance from the eye when wearing an external eye shield (ie, outside the orbital rim). Patients who had Mohs micrographic surgery (MMS) or excision (or both) with recurrence at the treatment site were included. Detailed and thorough clinical and dermoscopic skin examination was critical in early detection of these cancers, allowing for treatment of less advanced tumors. The PI’s diagnostic approach utilized the published diagnostic color wheel algorithm,²⁵ which encompasses both clinical and dermoscopic colors and patterns for early diagnosis (ie, ulceration, pink-white to white shiny areas, absence of pigmented network, leaflike structures, large blue-gray ovoid nests or globular structures, spoke wheel structures, a crystalline pattern, a singular vascular pattern of arborizing vessels), combined with OCT or RCM, when necessary.²⁶ All lesions were imaged with OCT prior to laser treatment to confirm residual tumor following biopsy.

Although postsurgical patients were included, lesions receiving concurrent or prior nonsurgical therapy, such as a topical immunomodulator or oral hedgehog inhibitor (eg, vismodegib), were excluded.

Treatment Protocol
All patients received thorough information about the treatment, treatment alternatives, and potential adverse effects and complications. Lesions were selected based on clinical and dermoscopic findings and were biopsy confirmed. Clinical and dermoscopic photographs were taken at every visit. A camera was used for clinical photographs and a dermatoscope was attached for all contact polarized dermoscopic images. All lesions were imaged with OCT prior to laser therapy to delineate tumor margins and to confirm residual disease following biopsy to preclude biopsy-mediated regression.

Laser treatment consisted of a 595-nm PDL followed by fractional laser treatment with the 1927-nm setting. The range of PDL settings was similar to published studies of PDL for BCC (spot size, 7–10 mm; fluence, 6–15 J/cm²; pulse duration, 0.45–3 milliseconds).^3-8 The fractional laser also was used at settings similar to earlier studies for actinic keratosis (fluence, 5–20 mJ; treatment density, 40%–70%).²⁷ Laser treatment was performed by 1 of 5 medically trained providers who were fellows supervised by the PI.

All tumors received 1 to 7 treatments (average, 2.89) at 1- to 2-month intervals. Treatment end point (complete clearance) was judged on the absence of skin cancer clinically, dermoscopically on OCT, or histologically by biopsy, or a combination of these modalities. Recurrence was defined as a new histologically confirmed BCC occurring in an area that was previously documented as clear. Patients returned for follow-up 1 to 2 months after the final treatment to monitor tumor clearance and subsequently every 6 to 12 months for tumor recurrence. Posttreatment care included application of a thick emollient, such as a petrolatum-based product, until the area completely healed.

Data Collection
Clinical photographs, dermoscopic photographs, OCT scans, RCM scans, and biopsy reports were reviewed for each patient, as applicable. All patients were given an unidentifiable number; no protected health information was recorded. Data recorded for each patient included age, tumor subtype and location, tumor size, classification of the tumor as primary or a recurrence, number of treatments, treatment duration, lesion clearance, and length of follow-up.

Results

Patient and Lesion Characteristics
Sixty-eight patients with 93 BCCs (77 facial; 16 nonfacial) were included. The median age of patients was 70 years (range, 31–91 years). All 93 BCCs demonstrated residual tumor on OCT after diagnostic biopsy. Four BCCs had been treated earlier with MMS and were biopsy-proven recurrences. Most BCCs were of the nodular subtype; however, sclerosing, superficial, pigmented, morpheaform, and infiltrative subtypes also were included (eTable 1). Eight BCCs were obtained at outside institutions with no subtype provided. Facial BCCs had a mean (SD) clinical and dermoscopic diameter of 6.75 (4.71) mm (range, 2–24 mm). Patients were followed for 2.53 months to 6.03 years (mean follow-up, 2.43 years) and assessed for clinical and subclinical recurrence.

Tumor Clearance
Most lesions were effectively treated, with 89 of 93 BCCs (95.70%) demonstrating complete tumor clearance. Complete tumor clearance following laser therapy was reported in 74 of 77 facial BCCs (96.10%) and 15 of 16 nonfacial BCCs (93.75%)(eTable 2). Successfully treated BCCs underwent an average of 2.88 laser treatments over a mean duration of 3.54 months (range, 1 week to 1.92 years). Four incomplete responders underwent an average of 3.25 laser treatments over a mean duration of 3.44 months (range, 1.13–6.87 months). Of the 4 lesions that did not clear, 2 were nodular, 1 was pigmented, and 1 was sclerosing.

• Lesions receiving 3 or fewer treatments had a clearance rate of 96.05% (73/76) for all BCCs, 96.72% (59/61) for facial BCCs, and 93.33% (14/15) for nonfacial BCCs.

• Lesions receiving more than 3 laser treatments had a clearance rate of 94.12% (16/17) for all BCCs, 93.75% (15/16) for facial BCCs, and 100% (1/1) for nonfacial BCCs.

The relationship between facial BCC tumor diameter and number of treatments required for clearance had a positive correlation coefficient (Pearson r=0.319), indicating that larger BCCs required more laser treatments (eTable 3).

Comment

High Tumor Clearance Rates With OCT
This study yielded a clearance rate of 95.70% for all BCCs, 96.10% for facial BCCs, and 93.75% for nonfacial BCCs. This rate is higher than the clinical or histologic clearance rate (or both) of earlier studies on facial and nonfacial BCCs, which ranged from 25% to 95%.^8-11 In this study, we were able to utilize OCT and histology to confirm clearance. Optical coherence tomography, which has been shown to have a high sensitivity ranging from 86% to 95.7%, is therefore optimally used in treatment monitoring.^19,26,28 Optical coherence tomography has a broader specificity range of 75.3% to 98% and was not utilized for diagnostic purposes in this study. Combining OCT with a color wheel dermoscopic approach was helpful in confirming treatment efficacy of nonsurgical therapies and is significantly more accurate than clinical analysis alone (P<.01).^19,26,28

We suspect that the higher clearance rates observed in our study were due to the OCT-guided treatment protocol. Optical coherence tomography was used for margination while providing a modality for tailored treatment through visualization of residual tumor on clinically and dermoscopically clear follow-ups, given that several studies found residual tumor at the lateral edge of the tumor margin on histopathologic analysis.⁵ Utilizing noninvasive imaging technology to delineate tumor margins before treatment can improve efficacy and limit unnecessary treatment to the surrounding normal skin (eFigure 2).²⁹

After grouping lesions by number of laser treatments, the clearance rate remained similar among facial BCCs with 3 or fewer treatments (59/61 [96.72%]), but there was a slightly decreased clearance rate for facial BCCs with more than 3 treatments (15/16 [93.75%]), which may be explained by the need for more laser treatments for larger BCCs (eTable 3). The relationship between facial BCC size and number of laser treatments was found to correlate positively (Pearson r=0.319). The largest lesion (24 mm) was successfully treated with 5 treatments (Figure). The number of nonfacial lesions was limited in this study and was not statistically significant.

• The third was a BCC on the nose of a nonadherent patient, which may have contributed to the lack of clearance. We defined nonadherent patients as those who did not follow-up within the appropriate periods and who therefore ran the risk for tumor growth in between treatments.

The nonfacial BCC that did not clear had histologic features of focal sclerosing BCC, a more aggressive subtype of basal cell skin cancer.

Tumor Recurrence
Only 4 of 89 BCCs (4.49%) recurred, with a 5.41% (4/74) recurrence rate among facial BCCs. All recurrences lacked clinical and dermoscopic evidence of BCC but were found on follow-up OCT scan and confirmed with RCM. All recurrences were found 1.5 to 3.9 years posttreatment.

Recurrent tumors following MMS required, on average, more laser treatments than primary tumors to achieve successful tumor clearance, which we attribute to scar tissue from prior therapy obscuring recurrence, resulting in delayed diagnosis, and to inflammation and fibrosis masking residual tumors (eFigure 1). An added benefit of laser treatment is that all 4 recurrent tumors demonstrated improved cosmetic appearance of the original MMS scar.

The benefit of using OCT scans to check for recurrences is that OCT can find residual skin cancers despite the area looking clinically clear, which is especially important during clinical evaluation of a healed postsurgical scar for recurrence because OCT imaging allows us to look as deep as 2 mm under the skin. Nonsurgical treatments also enable us to leave skin intact and avoid creating scar tissue, which makes it easier to detect and manage recurrence.

Limitations
There were several important limitations of this retrospective study:

• Patients were treated by 1 of 5 medically trained fellows. Although the fellows worked under the supervision of the PI, variation in their work from one to another might have led to different end points.

• All patients who appeared clinically clear were offered biopsy to confirm clearance on histology. Some patients agreed to biopsy, but many did not because they were pleased with the cosmetic outcome, which is similar to other studies exhibiting only clinical clearance rates without providing histologic clearance following nonsurgical therapy.⁶ We believe that imaging with OCT circumvents this problem and offers more accurate confirmation than clinical or dermoscopic correlation alone, or the combination of the 2 modalities.

• Lack of treatment standardization and short length of follow-up can result in underestimation of the recurrence rate. In particular, most patients were followed up with OCT in less than 6 months. These are unavoidable features in a retrospective study and we are currently addressing this problem in a new prospective study.

Extended Follow-up
Although this study is not a prospective design, it does provide recurrence data over extended follow-up for the nonablative laser management of BCCs (eTables 4 and 5). Studies have demonstrated that MMS has a 5-year cure rate as high as 99% for BCC.³² Given the limited follow-up period of prior nonablative laser management studies, recurrences might not have been fully evaluated. Our study had a 4.49% recurrence rate for all BCCs and a 5.41% recurrence rate for facial BCCs but was not detectable by clinical examination combined with dermoscopic findings alone. All recurrences required the utilization of OCT or RCM or a combination of these modalities to be diagnosed. In 1 patient with recurrence, we were able to see residual tumor on both OCT and RCM without any inflammation obscuring the scan, given that 3 years had passed. Although 2 months is an optimal follow-up time for OCT, we have not found an optimal follow-up time for RCM, which is another reason why OCT might be preferable to other imaging modalities, such as RCM and high-definition OCT, that have higher resolution but provide less depth on imaging. Although only 40 of 89 patients (4.49%) had follow-up ranging from 3 years to greater than 5 years, long-term follow-up to date has been limited in prior studies.

We believe the high clearance rates and limited recurrence are secondary to the utilization of noninvasive imaging, as the majority of these recurrences would not have been diagnosed based on clinical and/or dermoscopic information alone. Additionally, the 4 biopsy-proven post-MMS recurrence patients that were treated in this study also may not have been diagnosed this early without the use of additional noninvasive imaging. In our opinion, although laser management can be used without noninvasive imaging guidance—dermoscopy, OCT, and/or RCM—this technology is critical not only for early detection but also for proper management of patients.

Conclusion

This study showed a 95.70% clearance rate for all BCCs and a 96.10% clearance rate for facial BCCs. Although we had a zero clinical recurrence rate, 4.49% of all BCCs and 5.41% of facial BCCs had recurred on subsequent monitoring with noninvasive imaging. Given the large size of the study and extended follow-up, we found nonablative laser management to be a reliable treatment alternative with improved cosmetic outcome (Figure) and minimal short-term adverse effects compared to surgery.

Tailored care for the individual patient is based on a variety of options and patient preference, including ease of compliance, number of follow-up visits, invasive vs noninvasive diagnosis and monitoring, and downtime for healing. The use of noninvasive imaging also allowed us to find a more standardized treatment regimen using this nonablative laser combination. We found that 3 or fewer and more than 3 treatments had similar efficacy in tumor clearance. We recommend a standard laser protocol of 3 treatments every 4 to 6 weeks with follow-up 2 months after the final treatment to assess for clearance with OCT.

Larger BCCs might require additional treatments; therefore, we caution against laser therapy without concomitant use of OCT imaging to visualize residual tumor. Utilizing other noninvasive modalities, such as dermoscopy, in combination with thorough skin examination also is critical in the early detection of skin cancers to improve the efficacy of this less-aggressive, nonablative, and cosmetically optimal treatment protocol.

Acknowledgement—We would like to acknowledge Dimitrios Karponis, BSc, from the Impirial College London, England, for his assistance with a portion of the statistical analysis.

Nonablative laser therapy is emerging as an effective noninvasive treatment option for basal cell carcinoma (BCC) with reduced adverse effects and good cosmetic outcomes compared to surgery. Vascular lasers, such as the pulsed dye laser (PDL), are thought to work by selectively targeting the tumor’s vascular network while preserving normal surrounding tissue.^1,2 Although high energy and multiple passes might be required, adjunctive use of dynamic cooling reduces the risk for nonselective thermal injury vs ablative lasers, which destroy the tumor itself through vaporization of tissue water.²

With no established laser management guidelines for the treatment of BCC, earlier studies using a 595-nm PDL varied highly in their protocol.^3-8 Pulsed dye laser parameters ranged from a spot size of 7 to 10 mm, fluence of 7.5 to 15 J/cm², and pulse duration of 0.5 to 3 milliseconds. Follow-up ranged from 12 days to 25 months after the final laser treatment. The number of lesions in prior studies ranged from 7 to 100 BCCs, with the clinical clearance rate ranging from 71.4% to 75% for facial BCC and 78.6% to 95% for nonfacial BCC.^3-8 Studies with histologic confirmation had a clearance rate of 66.6% for facial BCC and 25% to 92.3% for nonfacial BCC.^3-5,7,8 Most studies examined BCCs on the trunk and extremities with few investigating facial BCC,^3-8 which is especially important given that the head and neck are the most common and cosmetically sensitive anatomic locations.^9-13

Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) can assist with the diagnosis and treatment monitoring of BCC. These devices enable in vivo visualization of tissue in both cross-sectional and en face views and therefore can reduce the need for diagnostic biopsy. Reflectance confocal microscopy enables near-histologic visualization of the epidermis and superficial dermis with a resolution of 0.5 to 1 μm.¹⁴ Optical coherence tomography uses an infrared broadband light source that allows users to view skin architecture as deep as 1.5 to 2 mm with a resolution of 5 μm.¹⁵

When used synergistically, both devices can enhance the efficacy of nonablative laser treatment. With its increased depth and wider field of view, OCT is an optimal tool for repetitive evaluation of the same site over time and for following biopsy-confirmed tumors undergoing management.¹⁶ In addition to delineating tumor margins before treatment, imaging improves the detection of residual skin cancers, despite clearance on clinical and dermoscopic examination. Noninvasive imaging and nonsurgical management with laser therapy allow the physician to leave the skin intact and avoid scar tissue that might otherwise make it more difficult to detect and manage recurrence. The ability of OCT and RCM to monitor the efficacy of nonsurgical therapies for skin cancer has been demonstrated with imiquimod, photodynamic therapy, vismodegib, and ablative laser therapy.^17-20

With limited data on nonablative laser management of BCC, several gaps in the literature exist. First, in previously published studies the number of treatments was either determined to be an arbitrary set number or based on clinical clearance, which has the potential to miss residual tumor. Second, many follow-ups were limited to shortly after the final treatment, which limits the accuracy of the clearance rate, given that inflammation and scars can hide residual tumor.^21-23 Third, because many studies excised the treated area, long-term follow-up for recurrence was obscured. Last, only a few studies involved facial BCC, which is the most common and cosmetically concerning anatomic location.¹³

Our study attempted to address these gaps by evaluating the use of noninvasive imaging to guide management of primarily facial BCC. The objective was to perform a retrospective chart review on a subgroup of patients with BCC who were treated with combined nonablative PDL and fractional laser treatment with an extended follow-up period.

Methods

Study Design
We performed a retrospective chart review of 68 patients with 93 BCCs who had been treated with nonablative laser therapy as an alternative to surgery at the Mount Sinai Faculty Practice Associates between February 2011 and December 2018. Patients were followed throughout this period for assessment of clinical and subclinical recurrence. The Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects provided institutional review board approval.

Patients
Inclusion criteria included the following: (1) BCC diagnosed by biopsy (see eTable 1 for subtypes) and (2) treated with a nonablative laser due to patient preference and eligibility by the principal investigator (PI). As a retrospective study, lesions were included irrespective of tumor subtype or size. Although the risk for perineural invasion (PNI) is extremely low with BCC (<0.2%), none of the cases demonstrated PNI on diagnostic biopsy and none exhibited clinical evidence of PNI, such as paresthesia, pain, facial paralysis, or diplopia.²⁴

Eligibility determined by the PI included limited clinical ulceration or bleeding, or both, and a safe distance from the eye when wearing an external eye shield (ie, outside the orbital rim). Patients who had Mohs micrographic surgery (MMS) or excision (or both) with recurrence at the treatment site were included. Detailed and thorough clinical and dermoscopic skin examination was critical in early detection of these cancers, allowing for treatment of less advanced tumors. The PI’s diagnostic approach utilized the published diagnostic color wheel algorithm,²⁵ which encompasses both clinical and dermoscopic colors and patterns for early diagnosis (ie, ulceration, pink-white to white shiny areas, absence of pigmented network, leaflike structures, large blue-gray ovoid nests or globular structures, spoke wheel structures, a crystalline pattern, a singular vascular pattern of arborizing vessels), combined with OCT or RCM, when necessary.²⁶ All lesions were imaged with OCT prior to laser treatment to confirm residual tumor following biopsy.

Although postsurgical patients were included, lesions receiving concurrent or prior nonsurgical therapy, such as a topical immunomodulator or oral hedgehog inhibitor (eg, vismodegib), were excluded.

Treatment Protocol
All patients received thorough information about the treatment, treatment alternatives, and potential adverse effects and complications. Lesions were selected based on clinical and dermoscopic findings and were biopsy confirmed. Clinical and dermoscopic photographs were taken at every visit. A camera was used for clinical photographs and a dermatoscope was attached for all contact polarized dermoscopic images. All lesions were imaged with OCT prior to laser therapy to delineate tumor margins and to confirm residual disease following biopsy to preclude biopsy-mediated regression.

Laser treatment consisted of a 595-nm PDL followed by fractional laser treatment with the 1927-nm setting. The range of PDL settings was similar to published studies of PDL for BCC (spot size, 7–10 mm; fluence, 6–15 J/cm²; pulse duration, 0.45–3 milliseconds).^3-8 The fractional laser also was used at settings similar to earlier studies for actinic keratosis (fluence, 5–20 mJ; treatment density, 40%–70%).²⁷ Laser treatment was performed by 1 of 5 medically trained providers who were fellows supervised by the PI.

All tumors received 1 to 7 treatments (average, 2.89) at 1- to 2-month intervals. Treatment end point (complete clearance) was judged on the absence of skin cancer clinically, dermoscopically on OCT, or histologically by biopsy, or a combination of these modalities. Recurrence was defined as a new histologically confirmed BCC occurring in an area that was previously documented as clear. Patients returned for follow-up 1 to 2 months after the final treatment to monitor tumor clearance and subsequently every 6 to 12 months for tumor recurrence. Posttreatment care included application of a thick emollient, such as a petrolatum-based product, until the area completely healed.

Data Collection
Clinical photographs, dermoscopic photographs, OCT scans, RCM scans, and biopsy reports were reviewed for each patient, as applicable. All patients were given an unidentifiable number; no protected health information was recorded. Data recorded for each patient included age, tumor subtype and location, tumor size, classification of the tumor as primary or a recurrence, number of treatments, treatment duration, lesion clearance, and length of follow-up.

Results

Patient and Lesion Characteristics
Sixty-eight patients with 93 BCCs (77 facial; 16 nonfacial) were included. The median age of patients was 70 years (range, 31–91 years). All 93 BCCs demonstrated residual tumor on OCT after diagnostic biopsy. Four BCCs had been treated earlier with MMS and were biopsy-proven recurrences. Most BCCs were of the nodular subtype; however, sclerosing, superficial, pigmented, morpheaform, and infiltrative subtypes also were included (eTable 1). Eight BCCs were obtained at outside institutions with no subtype provided. Facial BCCs had a mean (SD) clinical and dermoscopic diameter of 6.75 (4.71) mm (range, 2–24 mm). Patients were followed for 2.53 months to 6.03 years (mean follow-up, 2.43 years) and assessed for clinical and subclinical recurrence.

Tumor Clearance
Most lesions were effectively treated, with 89 of 93 BCCs (95.70%) demonstrating complete tumor clearance. Complete tumor clearance following laser therapy was reported in 74 of 77 facial BCCs (96.10%) and 15 of 16 nonfacial BCCs (93.75%)(eTable 2). Successfully treated BCCs underwent an average of 2.88 laser treatments over a mean duration of 3.54 months (range, 1 week to 1.92 years). Four incomplete responders underwent an average of 3.25 laser treatments over a mean duration of 3.44 months (range, 1.13–6.87 months). Of the 4 lesions that did not clear, 2 were nodular, 1 was pigmented, and 1 was sclerosing.

• Lesions receiving 3 or fewer treatments had a clearance rate of 96.05% (73/76) for all BCCs, 96.72% (59/61) for facial BCCs, and 93.33% (14/15) for nonfacial BCCs.

• Lesions receiving more than 3 laser treatments had a clearance rate of 94.12% (16/17) for all BCCs, 93.75% (15/16) for facial BCCs, and 100% (1/1) for nonfacial BCCs.

The relationship between facial BCC tumor diameter and number of treatments required for clearance had a positive correlation coefficient (Pearson r=0.319), indicating that larger BCCs required more laser treatments (eTable 3).

Comment

High Tumor Clearance Rates With OCT
This study yielded a clearance rate of 95.70% for all BCCs, 96.10% for facial BCCs, and 93.75% for nonfacial BCCs. This rate is higher than the clinical or histologic clearance rate (or both) of earlier studies on facial and nonfacial BCCs, which ranged from 25% to 95%.^8-11 In this study, we were able to utilize OCT and histology to confirm clearance. Optical coherence tomography, which has been shown to have a high sensitivity ranging from 86% to 95.7%, is therefore optimally used in treatment monitoring.^19,26,28 Optical coherence tomography has a broader specificity range of 75.3% to 98% and was not utilized for diagnostic purposes in this study. Combining OCT with a color wheel dermoscopic approach was helpful in confirming treatment efficacy of nonsurgical therapies and is significantly more accurate than clinical analysis alone (P<.01).^19,26,28

We suspect that the higher clearance rates observed in our study were due to the OCT-guided treatment protocol. Optical coherence tomography was used for margination while providing a modality for tailored treatment through visualization of residual tumor on clinically and dermoscopically clear follow-ups, given that several studies found residual tumor at the lateral edge of the tumor margin on histopathologic analysis.⁵ Utilizing noninvasive imaging technology to delineate tumor margins before treatment can improve efficacy and limit unnecessary treatment to the surrounding normal skin (eFigure 2).²⁹

After grouping lesions by number of laser treatments, the clearance rate remained similar among facial BCCs with 3 or fewer treatments (59/61 [96.72%]), but there was a slightly decreased clearance rate for facial BCCs with more than 3 treatments (15/16 [93.75%]), which may be explained by the need for more laser treatments for larger BCCs (eTable 3). The relationship between facial BCC size and number of laser treatments was found to correlate positively (Pearson r=0.319). The largest lesion (24 mm) was successfully treated with 5 treatments (Figure). The number of nonfacial lesions was limited in this study and was not statistically significant.

• The third was a BCC on the nose of a nonadherent patient, which may have contributed to the lack of clearance. We defined nonadherent patients as those who did not follow-up within the appropriate periods and who therefore ran the risk for tumor growth in between treatments.

The nonfacial BCC that did not clear had histologic features of focal sclerosing BCC, a more aggressive subtype of basal cell skin cancer.

Tumor Recurrence
Only 4 of 89 BCCs (4.49%) recurred, with a 5.41% (4/74) recurrence rate among facial BCCs. All recurrences lacked clinical and dermoscopic evidence of BCC but were found on follow-up OCT scan and confirmed with RCM. All recurrences were found 1.5 to 3.9 years posttreatment.

Recurrent tumors following MMS required, on average, more laser treatments than primary tumors to achieve successful tumor clearance, which we attribute to scar tissue from prior therapy obscuring recurrence, resulting in delayed diagnosis, and to inflammation and fibrosis masking residual tumors (eFigure 1). An added benefit of laser treatment is that all 4 recurrent tumors demonstrated improved cosmetic appearance of the original MMS scar.

The benefit of using OCT scans to check for recurrences is that OCT can find residual skin cancers despite the area looking clinically clear, which is especially important during clinical evaluation of a healed postsurgical scar for recurrence because OCT imaging allows us to look as deep as 2 mm under the skin. Nonsurgical treatments also enable us to leave skin intact and avoid creating scar tissue, which makes it easier to detect and manage recurrence.

Limitations
There were several important limitations of this retrospective study:

• Patients were treated by 1 of 5 medically trained fellows. Although the fellows worked under the supervision of the PI, variation in their work from one to another might have led to different end points.

• All patients who appeared clinically clear were offered biopsy to confirm clearance on histology. Some patients agreed to biopsy, but many did not because they were pleased with the cosmetic outcome, which is similar to other studies exhibiting only clinical clearance rates without providing histologic clearance following nonsurgical therapy.⁶ We believe that imaging with OCT circumvents this problem and offers more accurate confirmation than clinical or dermoscopic correlation alone, or the combination of the 2 modalities.

• Lack of treatment standardization and short length of follow-up can result in underestimation of the recurrence rate. In particular, most patients were followed up with OCT in less than 6 months. These are unavoidable features in a retrospective study and we are currently addressing this problem in a new prospective study.

Extended Follow-up
Although this study is not a prospective design, it does provide recurrence data over extended follow-up for the nonablative laser management of BCCs (eTables 4 and 5). Studies have demonstrated that MMS has a 5-year cure rate as high as 99% for BCC.³² Given the limited follow-up period of prior nonablative laser management studies, recurrences might not have been fully evaluated. Our study had a 4.49% recurrence rate for all BCCs and a 5.41% recurrence rate for facial BCCs but was not detectable by clinical examination combined with dermoscopic findings alone. All recurrences required the utilization of OCT or RCM or a combination of these modalities to be diagnosed. In 1 patient with recurrence, we were able to see residual tumor on both OCT and RCM without any inflammation obscuring the scan, given that 3 years had passed. Although 2 months is an optimal follow-up time for OCT, we have not found an optimal follow-up time for RCM, which is another reason why OCT might be preferable to other imaging modalities, such as RCM and high-definition OCT, that have higher resolution but provide less depth on imaging. Although only 40 of 89 patients (4.49%) had follow-up ranging from 3 years to greater than 5 years, long-term follow-up to date has been limited in prior studies.

We believe the high clearance rates and limited recurrence are secondary to the utilization of noninvasive imaging, as the majority of these recurrences would not have been diagnosed based on clinical and/or dermoscopic information alone. Additionally, the 4 biopsy-proven post-MMS recurrence patients that were treated in this study also may not have been diagnosed this early without the use of additional noninvasive imaging. In our opinion, although laser management can be used without noninvasive imaging guidance—dermoscopy, OCT, and/or RCM—this technology is critical not only for early detection but also for proper management of patients.

Conclusion

This study showed a 95.70% clearance rate for all BCCs and a 96.10% clearance rate for facial BCCs. Although we had a zero clinical recurrence rate, 4.49% of all BCCs and 5.41% of facial BCCs had recurred on subsequent monitoring with noninvasive imaging. Given the large size of the study and extended follow-up, we found nonablative laser management to be a reliable treatment alternative with improved cosmetic outcome (Figure) and minimal short-term adverse effects compared to surgery.

Tailored care for the individual patient is based on a variety of options and patient preference, including ease of compliance, number of follow-up visits, invasive vs noninvasive diagnosis and monitoring, and downtime for healing. The use of noninvasive imaging also allowed us to find a more standardized treatment regimen using this nonablative laser combination. We found that 3 or fewer and more than 3 treatments had similar efficacy in tumor clearance. We recommend a standard laser protocol of 3 treatments every 4 to 6 weeks with follow-up 2 months after the final treatment to assess for clearance with OCT.

Larger BCCs might require additional treatments; therefore, we caution against laser therapy without concomitant use of OCT imaging to visualize residual tumor. Utilizing other noninvasive modalities, such as dermoscopy, in combination with thorough skin examination also is critical in the early detection of skin cancers to improve the efficacy of this less-aggressive, nonablative, and cosmetically optimal treatment protocol.

Acknowledgement—We would like to acknowledge Dimitrios Karponis, BSc, from the Impirial College London, England, for his assistance with a portion of the statistical analysis.

Nonablative laser therapy is emerging as an effective noninvasive treatment option for basal cell carcinoma (BCC) with reduced adverse effects and good cosmetic outcomes compared to surgery. Vascular lasers, such as the pulsed dye laser (PDL), are thought to work by selectively targeting the tumor’s vascular network while preserving normal surrounding tissue.^1,2 Although high energy and multiple passes might be required, adjunctive use of dynamic cooling reduces the risk for nonselective thermal injury vs ablative lasers, which destroy the tumor itself through vaporization of tissue water.²

With no established laser management guidelines for the treatment of BCC, earlier studies using a 595-nm PDL varied highly in their protocol.^3-8 Pulsed dye laser parameters ranged from a spot size of 7 to 10 mm, fluence of 7.5 to 15 J/cm², and pulse duration of 0.5 to 3 milliseconds. Follow-up ranged from 12 days to 25 months after the final laser treatment. The number of lesions in prior studies ranged from 7 to 100 BCCs, with the clinical clearance rate ranging from 71.4% to 75% for facial BCC and 78.6% to 95% for nonfacial BCC.^3-8 Studies with histologic confirmation had a clearance rate of 66.6% for facial BCC and 25% to 92.3% for nonfacial BCC.^3-5,7,8 Most studies examined BCCs on the trunk and extremities with few investigating facial BCC,^3-8 which is especially important given that the head and neck are the most common and cosmetically sensitive anatomic locations.^9-13

Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) can assist with the diagnosis and treatment monitoring of BCC. These devices enable in vivo visualization of tissue in both cross-sectional and en face views and therefore can reduce the need for diagnostic biopsy. Reflectance confocal microscopy enables near-histologic visualization of the epidermis and superficial dermis with a resolution of 0.5 to 1 μm.¹⁴ Optical coherence tomography uses an infrared broadband light source that allows users to view skin architecture as deep as 1.5 to 2 mm with a resolution of 5 μm.¹⁵

When used synergistically, both devices can enhance the efficacy of nonablative laser treatment. With its increased depth and wider field of view, OCT is an optimal tool for repetitive evaluation of the same site over time and for following biopsy-confirmed tumors undergoing management.¹⁶ In addition to delineating tumor margins before treatment, imaging improves the detection of residual skin cancers, despite clearance on clinical and dermoscopic examination. Noninvasive imaging and nonsurgical management with laser therapy allow the physician to leave the skin intact and avoid scar tissue that might otherwise make it more difficult to detect and manage recurrence. The ability of OCT and RCM to monitor the efficacy of nonsurgical therapies for skin cancer has been demonstrated with imiquimod, photodynamic therapy, vismodegib, and ablative laser therapy.^17-20

With limited data on nonablative laser management of BCC, several gaps in the literature exist. First, in previously published studies the number of treatments was either determined to be an arbitrary set number or based on clinical clearance, which has the potential to miss residual tumor. Second, many follow-ups were limited to shortly after the final treatment, which limits the accuracy of the clearance rate, given that inflammation and scars can hide residual tumor.^21-23 Third, because many studies excised the treated area, long-term follow-up for recurrence was obscured. Last, only a few studies involved facial BCC, which is the most common and cosmetically concerning anatomic location.¹³

Our study attempted to address these gaps by evaluating the use of noninvasive imaging to guide management of primarily facial BCC. The objective was to perform a retrospective chart review on a subgroup of patients with BCC who were treated with combined nonablative PDL and fractional laser treatment with an extended follow-up period.

Methods

Study Design
We performed a retrospective chart review of 68 patients with 93 BCCs who had been treated with nonablative laser therapy as an alternative to surgery at the Mount Sinai Faculty Practice Associates between February 2011 and December 2018. Patients were followed throughout this period for assessment of clinical and subclinical recurrence. The Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects provided institutional review board approval.

Patients
Inclusion criteria included the following: (1) BCC diagnosed by biopsy (see eTable 1 for subtypes) and (2) treated with a nonablative laser due to patient preference and eligibility by the principal investigator (PI). As a retrospective study, lesions were included irrespective of tumor subtype or size. Although the risk for perineural invasion (PNI) is extremely low with BCC (<0.2%), none of the cases demonstrated PNI on diagnostic biopsy and none exhibited clinical evidence of PNI, such as paresthesia, pain, facial paralysis, or diplopia.²⁴

Eligibility determined by the PI included limited clinical ulceration or bleeding, or both, and a safe distance from the eye when wearing an external eye shield (ie, outside the orbital rim). Patients who had Mohs micrographic surgery (MMS) or excision (or both) with recurrence at the treatment site were included. Detailed and thorough clinical and dermoscopic skin examination was critical in early detection of these cancers, allowing for treatment of less advanced tumors. The PI’s diagnostic approach utilized the published diagnostic color wheel algorithm,²⁵ which encompasses both clinical and dermoscopic colors and patterns for early diagnosis (ie, ulceration, pink-white to white shiny areas, absence of pigmented network, leaflike structures, large blue-gray ovoid nests or globular structures, spoke wheel structures, a crystalline pattern, a singular vascular pattern of arborizing vessels), combined with OCT or RCM, when necessary.²⁶ All lesions were imaged with OCT prior to laser treatment to confirm residual tumor following biopsy.

Although postsurgical patients were included, lesions receiving concurrent or prior nonsurgical therapy, such as a topical immunomodulator or oral hedgehog inhibitor (eg, vismodegib), were excluded.

Treatment Protocol
All patients received thorough information about the treatment, treatment alternatives, and potential adverse effects and complications. Lesions were selected based on clinical and dermoscopic findings and were biopsy confirmed. Clinical and dermoscopic photographs were taken at every visit. A camera was used for clinical photographs and a dermatoscope was attached for all contact polarized dermoscopic images. All lesions were imaged with OCT prior to laser therapy to delineate tumor margins and to confirm residual disease following biopsy to preclude biopsy-mediated regression.

Laser treatment consisted of a 595-nm PDL followed by fractional laser treatment with the 1927-nm setting. The range of PDL settings was similar to published studies of PDL for BCC (spot size, 7–10 mm; fluence, 6–15 J/cm²; pulse duration, 0.45–3 milliseconds).^3-8 The fractional laser also was used at settings similar to earlier studies for actinic keratosis (fluence, 5–20 mJ; treatment density, 40%–70%).²⁷ Laser treatment was performed by 1 of 5 medically trained providers who were fellows supervised by the PI.

All tumors received 1 to 7 treatments (average, 2.89) at 1- to 2-month intervals. Treatment end point (complete clearance) was judged on the absence of skin cancer clinically, dermoscopically on OCT, or histologically by biopsy, or a combination of these modalities. Recurrence was defined as a new histologically confirmed BCC occurring in an area that was previously documented as clear. Patients returned for follow-up 1 to 2 months after the final treatment to monitor tumor clearance and subsequently every 6 to 12 months for tumor recurrence. Posttreatment care included application of a thick emollient, such as a petrolatum-based product, until the area completely healed.

Data Collection
Clinical photographs, dermoscopic photographs, OCT scans, RCM scans, and biopsy reports were reviewed for each patient, as applicable. All patients were given an unidentifiable number; no protected health information was recorded. Data recorded for each patient included age, tumor subtype and location, tumor size, classification of the tumor as primary or a recurrence, number of treatments, treatment duration, lesion clearance, and length of follow-up.

Results

Patient and Lesion Characteristics
Sixty-eight patients with 93 BCCs (77 facial; 16 nonfacial) were included. The median age of patients was 70 years (range, 31–91 years). All 93 BCCs demonstrated residual tumor on OCT after diagnostic biopsy. Four BCCs had been treated earlier with MMS and were biopsy-proven recurrences. Most BCCs were of the nodular subtype; however, sclerosing, superficial, pigmented, morpheaform, and infiltrative subtypes also were included (eTable 1). Eight BCCs were obtained at outside institutions with no subtype provided. Facial BCCs had a mean (SD) clinical and dermoscopic diameter of 6.75 (4.71) mm (range, 2–24 mm). Patients were followed for 2.53 months to 6.03 years (mean follow-up, 2.43 years) and assessed for clinical and subclinical recurrence.

Tumor Clearance
Most lesions were effectively treated, with 89 of 93 BCCs (95.70%) demonstrating complete tumor clearance. Complete tumor clearance following laser therapy was reported in 74 of 77 facial BCCs (96.10%) and 15 of 16 nonfacial BCCs (93.75%)(eTable 2). Successfully treated BCCs underwent an average of 2.88 laser treatments over a mean duration of 3.54 months (range, 1 week to 1.92 years). Four incomplete responders underwent an average of 3.25 laser treatments over a mean duration of 3.44 months (range, 1.13–6.87 months). Of the 4 lesions that did not clear, 2 were nodular, 1 was pigmented, and 1 was sclerosing.

• Lesions receiving 3 or fewer treatments had a clearance rate of 96.05% (73/76) for all BCCs, 96.72% (59/61) for facial BCCs, and 93.33% (14/15) for nonfacial BCCs.

• Lesions receiving more than 3 laser treatments had a clearance rate of 94.12% (16/17) for all BCCs, 93.75% (15/16) for facial BCCs, and 100% (1/1) for nonfacial BCCs.

The relationship between facial BCC tumor diameter and number of treatments required for clearance had a positive correlation coefficient (Pearson r=0.319), indicating that larger BCCs required more laser treatments (eTable 3).

Comment

High Tumor Clearance Rates With OCT
This study yielded a clearance rate of 95.70% for all BCCs, 96.10% for facial BCCs, and 93.75% for nonfacial BCCs. This rate is higher than the clinical or histologic clearance rate (or both) of earlier studies on facial and nonfacial BCCs, which ranged from 25% to 95%.^8-11 In this study, we were able to utilize OCT and histology to confirm clearance. Optical coherence tomography, which has been shown to have a high sensitivity ranging from 86% to 95.7%, is therefore optimally used in treatment monitoring.^19,26,28 Optical coherence tomography has a broader specificity range of 75.3% to 98% and was not utilized for diagnostic purposes in this study. Combining OCT with a color wheel dermoscopic approach was helpful in confirming treatment efficacy of nonsurgical therapies and is significantly more accurate than clinical analysis alone (P<.01).^19,26,28

We suspect that the higher clearance rates observed in our study were due to the OCT-guided treatment protocol. Optical coherence tomography was used for margination while providing a modality for tailored treatment through visualization of residual tumor on clinically and dermoscopically clear follow-ups, given that several studies found residual tumor at the lateral edge of the tumor margin on histopathologic analysis.⁵ Utilizing noninvasive imaging technology to delineate tumor margins before treatment can improve efficacy and limit unnecessary treatment to the surrounding normal skin (eFigure 2).²⁹

After grouping lesions by number of laser treatments, the clearance rate remained similar among facial BCCs with 3 or fewer treatments (59/61 [96.72%]), but there was a slightly decreased clearance rate for facial BCCs with more than 3 treatments (15/16 [93.75%]), which may be explained by the need for more laser treatments for larger BCCs (eTable 3). The relationship between facial BCC size and number of laser treatments was found to correlate positively (Pearson r=0.319). The largest lesion (24 mm) was successfully treated with 5 treatments (Figure). The number of nonfacial lesions was limited in this study and was not statistically significant.

• The third was a BCC on the nose of a nonadherent patient, which may have contributed to the lack of clearance. We defined nonadherent patients as those who did not follow-up within the appropriate periods and who therefore ran the risk for tumor growth in between treatments.

The nonfacial BCC that did not clear had histologic features of focal sclerosing BCC, a more aggressive subtype of basal cell skin cancer.

Tumor Recurrence
Only 4 of 89 BCCs (4.49%) recurred, with a 5.41% (4/74) recurrence rate among facial BCCs. All recurrences lacked clinical and dermoscopic evidence of BCC but were found on follow-up OCT scan and confirmed with RCM. All recurrences were found 1.5 to 3.9 years posttreatment.

Recurrent tumors following MMS required, on average, more laser treatments than primary tumors to achieve successful tumor clearance, which we attribute to scar tissue from prior therapy obscuring recurrence, resulting in delayed diagnosis, and to inflammation and fibrosis masking residual tumors (eFigure 1). An added benefit of laser treatment is that all 4 recurrent tumors demonstrated improved cosmetic appearance of the original MMS scar.

The benefit of using OCT scans to check for recurrences is that OCT can find residual skin cancers despite the area looking clinically clear, which is especially important during clinical evaluation of a healed postsurgical scar for recurrence because OCT imaging allows us to look as deep as 2 mm under the skin. Nonsurgical treatments also enable us to leave skin intact and avoid creating scar tissue, which makes it easier to detect and manage recurrence.

Limitations
There were several important limitations of this retrospective study:

• Patients were treated by 1 of 5 medically trained fellows. Although the fellows worked under the supervision of the PI, variation in their work from one to another might have led to different end points.

• All patients who appeared clinically clear were offered biopsy to confirm clearance on histology. Some patients agreed to biopsy, but many did not because they were pleased with the cosmetic outcome, which is similar to other studies exhibiting only clinical clearance rates without providing histologic clearance following nonsurgical therapy.⁶ We believe that imaging with OCT circumvents this problem and offers more accurate confirmation than clinical or dermoscopic correlation alone, or the combination of the 2 modalities.

• Lack of treatment standardization and short length of follow-up can result in underestimation of the recurrence rate. In particular, most patients were followed up with OCT in less than 6 months. These are unavoidable features in a retrospective study and we are currently addressing this problem in a new prospective study.

Extended Follow-up
Although this study is not a prospective design, it does provide recurrence data over extended follow-up for the nonablative laser management of BCCs (eTables 4 and 5). Studies have demonstrated that MMS has a 5-year cure rate as high as 99% for BCC.³² Given the limited follow-up period of prior nonablative laser management studies, recurrences might not have been fully evaluated. Our study had a 4.49% recurrence rate for all BCCs and a 5.41% recurrence rate for facial BCCs but was not detectable by clinical examination combined with dermoscopic findings alone. All recurrences required the utilization of OCT or RCM or a combination of these modalities to be diagnosed. In 1 patient with recurrence, we were able to see residual tumor on both OCT and RCM without any inflammation obscuring the scan, given that 3 years had passed. Although 2 months is an optimal follow-up time for OCT, we have not found an optimal follow-up time for RCM, which is another reason why OCT might be preferable to other imaging modalities, such as RCM and high-definition OCT, that have higher resolution but provide less depth on imaging. Although only 40 of 89 patients (4.49%) had follow-up ranging from 3 years to greater than 5 years, long-term follow-up to date has been limited in prior studies.

We believe the high clearance rates and limited recurrence are secondary to the utilization of noninvasive imaging, as the majority of these recurrences would not have been diagnosed based on clinical and/or dermoscopic information alone. Additionally, the 4 biopsy-proven post-MMS recurrence patients that were treated in this study also may not have been diagnosed this early without the use of additional noninvasive imaging. In our opinion, although laser management can be used without noninvasive imaging guidance—dermoscopy, OCT, and/or RCM—this technology is critical not only for early detection but also for proper management of patients.

Conclusion

This study showed a 95.70% clearance rate for all BCCs and a 96.10% clearance rate for facial BCCs. Although we had a zero clinical recurrence rate, 4.49% of all BCCs and 5.41% of facial BCCs had recurred on subsequent monitoring with noninvasive imaging. Given the large size of the study and extended follow-up, we found nonablative laser management to be a reliable treatment alternative with improved cosmetic outcome (Figure) and minimal short-term adverse effects compared to surgery.

Tailored care for the individual patient is based on a variety of options and patient preference, including ease of compliance, number of follow-up visits, invasive vs noninvasive diagnosis and monitoring, and downtime for healing. The use of noninvasive imaging also allowed us to find a more standardized treatment regimen using this nonablative laser combination. We found that 3 or fewer and more than 3 treatments had similar efficacy in tumor clearance. We recommend a standard laser protocol of 3 treatments every 4 to 6 weeks with follow-up 2 months after the final treatment to assess for clearance with OCT.

Larger BCCs might require additional treatments; therefore, we caution against laser therapy without concomitant use of OCT imaging to visualize residual tumor. Utilizing other noninvasive modalities, such as dermoscopy, in combination with thorough skin examination also is critical in the early detection of skin cancers to improve the efficacy of this less-aggressive, nonablative, and cosmetically optimal treatment protocol.

Acknowledgement—We would like to acknowledge Dimitrios Karponis, BSc, from the Impirial College London, England, for his assistance with a portion of the statistical analysis.

Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer in the United States. It develops most often on sun-exposed skin, including the face and neck. Although BCCs are slow-growing tumors that rarely metastasize, they can cause notable local destruction with disfigurement if neglected or inadequately treated. Basal cell carcinoma arising on the legs is relatively uncommon.^1,2 We present an interesting case of delayed diagnosis of BCC on the left knee due to earlier misdiagnoses of a dermoid cyst and bursitis.

Case Report

A 67-year-old man with no history of skin cancer presented with a painful growing tumor on the left knee of approximately 2 years’ duration. The patient’s primary care physician as well as a general surgeon initially diagnosed it as a dermoid cyst and bursitis. The nodule failed to respond to conservative therapy with nonsteroidal anti-inflammatory drugs and continued to grow until it began to ulcerate. Concerned about the possibility of septic arthritis, the patient’s primary care physician referred him to the emergency department. He was subsequently sent to the dermatology clinic.

On examination by dermatology, a 6.3×4.4-cm, tender, mobile, ulcerated nodule was noted on the left knee (Figure 1A). No popliteal or inguinal lymph nodes were palpable. Basal cell carcinoma, squamous cell carcinoma, or atypical infection (eg, Leishmania, deep fungal, mycobacterial) was suspected clinically. The patient underwent a diagnostic skin biopsy; hematoxylin and eosin–stained sections revealed lobular proliferation of basaloid cells with peripheral palisading and central tumoral necrosis, consistent with primary BCC (Figure 2).

Comment

Exposure to UV radiation is the primary causative agent of most BCCs, accounting for the preferential distribution of these tumors on sun-exposed areas of the body. Approximately 80% of BCCs are located on the head and neck, 10% occur on the trunk, and only 8% are found on the lower extremities.¹

Giant BCC, the finding in this case, is defined by the American Joint Committee on Cancer as a tumor larger than 5 cm in diameter. Fewer than 1% of all BCCs achieve this size; they appear more commonly on the back where they can go unnoticed.² Neglect and inadequate treatment of the primary tumor are the most important contributing factors to the size of giant BCCs. Giant BCCs also have more aggressive biologic behavior, with an increased risk for local invasion and metastasis.³ In this case, the lesion was larger than 5 cm in diameter and occurred on the lower extremity rather than on the trunk.

This case is unusual because delayed diagnosis of BCC was the result of misdiagnoses of a dermoid cyst and bursitis, with a diagnostic skin biopsy demonstrating BCC almost 2 years later. It should be emphasized that early diagnosis and treatment could prevent tumor expansion. Physicians should have a high degree of suspicion for BCC, especially when a dermoid cyst and knee bursitis fail to respond to conservative management.

Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer in the United States. It develops most often on sun-exposed skin, including the face and neck. Although BCCs are slow-growing tumors that rarely metastasize, they can cause notable local destruction with disfigurement if neglected or inadequately treated. Basal cell carcinoma arising on the legs is relatively uncommon.^1,2 We present an interesting case of delayed diagnosis of BCC on the left knee due to earlier misdiagnoses of a dermoid cyst and bursitis.

Case Report

A 67-year-old man with no history of skin cancer presented with a painful growing tumor on the left knee of approximately 2 years’ duration. The patient’s primary care physician as well as a general surgeon initially diagnosed it as a dermoid cyst and bursitis. The nodule failed to respond to conservative therapy with nonsteroidal anti-inflammatory drugs and continued to grow until it began to ulcerate. Concerned about the possibility of septic arthritis, the patient’s primary care physician referred him to the emergency department. He was subsequently sent to the dermatology clinic.

On examination by dermatology, a 6.3×4.4-cm, tender, mobile, ulcerated nodule was noted on the left knee (Figure 1A). No popliteal or inguinal lymph nodes were palpable. Basal cell carcinoma, squamous cell carcinoma, or atypical infection (eg, Leishmania, deep fungal, mycobacterial) was suspected clinically. The patient underwent a diagnostic skin biopsy; hematoxylin and eosin–stained sections revealed lobular proliferation of basaloid cells with peripheral palisading and central tumoral necrosis, consistent with primary BCC (Figure 2).

Comment

Exposure to UV radiation is the primary causative agent of most BCCs, accounting for the preferential distribution of these tumors on sun-exposed areas of the body. Approximately 80% of BCCs are located on the head and neck, 10% occur on the trunk, and only 8% are found on the lower extremities.¹

Giant BCC, the finding in this case, is defined by the American Joint Committee on Cancer as a tumor larger than 5 cm in diameter. Fewer than 1% of all BCCs achieve this size; they appear more commonly on the back where they can go unnoticed.² Neglect and inadequate treatment of the primary tumor are the most important contributing factors to the size of giant BCCs. Giant BCCs also have more aggressive biologic behavior, with an increased risk for local invasion and metastasis.³ In this case, the lesion was larger than 5 cm in diameter and occurred on the lower extremity rather than on the trunk.

This case is unusual because delayed diagnosis of BCC was the result of misdiagnoses of a dermoid cyst and bursitis, with a diagnostic skin biopsy demonstrating BCC almost 2 years later. It should be emphasized that early diagnosis and treatment could prevent tumor expansion. Physicians should have a high degree of suspicion for BCC, especially when a dermoid cyst and knee bursitis fail to respond to conservative management.

Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer in the United States. It develops most often on sun-exposed skin, including the face and neck. Although BCCs are slow-growing tumors that rarely metastasize, they can cause notable local destruction with disfigurement if neglected or inadequately treated. Basal cell carcinoma arising on the legs is relatively uncommon.^1,2 We present an interesting case of delayed diagnosis of BCC on the left knee due to earlier misdiagnoses of a dermoid cyst and bursitis.

Case Report

A 67-year-old man with no history of skin cancer presented with a painful growing tumor on the left knee of approximately 2 years’ duration. The patient’s primary care physician as well as a general surgeon initially diagnosed it as a dermoid cyst and bursitis. The nodule failed to respond to conservative therapy with nonsteroidal anti-inflammatory drugs and continued to grow until it began to ulcerate. Concerned about the possibility of septic arthritis, the patient’s primary care physician referred him to the emergency department. He was subsequently sent to the dermatology clinic.

On examination by dermatology, a 6.3×4.4-cm, tender, mobile, ulcerated nodule was noted on the left knee (Figure 1A). No popliteal or inguinal lymph nodes were palpable. Basal cell carcinoma, squamous cell carcinoma, or atypical infection (eg, Leishmania, deep fungal, mycobacterial) was suspected clinically. The patient underwent a diagnostic skin biopsy; hematoxylin and eosin–stained sections revealed lobular proliferation of basaloid cells with peripheral palisading and central tumoral necrosis, consistent with primary BCC (Figure 2).

Comment

Exposure to UV radiation is the primary causative agent of most BCCs, accounting for the preferential distribution of these tumors on sun-exposed areas of the body. Approximately 80% of BCCs are located on the head and neck, 10% occur on the trunk, and only 8% are found on the lower extremities.¹

Giant BCC, the finding in this case, is defined by the American Joint Committee on Cancer as a tumor larger than 5 cm in diameter. Fewer than 1% of all BCCs achieve this size; they appear more commonly on the back where they can go unnoticed.² Neglect and inadequate treatment of the primary tumor are the most important contributing factors to the size of giant BCCs. Giant BCCs also have more aggressive biologic behavior, with an increased risk for local invasion and metastasis.³ In this case, the lesion was larger than 5 cm in diameter and occurred on the lower extremity rather than on the trunk.

This case is unusual because delayed diagnosis of BCC was the result of misdiagnoses of a dermoid cyst and bursitis, with a diagnostic skin biopsy demonstrating BCC almost 2 years later. It should be emphasized that early diagnosis and treatment could prevent tumor expansion. Physicians should have a high degree of suspicion for BCC, especially when a dermoid cyst and knee bursitis fail to respond to conservative management.

The incidence of nonmelanoma skin cancer (NMSC) is steadily increasing, and it accounts for more annual cancer diagnoses than all other malignancies combined.^1,2 For NMSCs of the head and neck, Mohs micrographic surgery (MMS) has become a preferred technique because of its high cure rates, intraprocedural margin control, and improved tissue preservation in cosmetically sensitive areas.³ The nose and ears are especially sensitive anatomic locations given their prominent positions and relative lack of skin reservoir and laxity compared to other areas of the head and neck. For the nose and ears, both patients and referring providers may question who is best suited to surgically remove a malignancy and repair the defect with positive functional and cosmetic results, as a large portion of the defects following tumor extirpation will require a flap or graft for repair.

The notion of plastic surgery is strongly associated with supreme cosmesis for many patients and providers, as the specialty trains in several surgical and nonsurgical elective techniques to preserve and improve appearance. Consequently, patients commonly ask dermatologists if they should be referred to a plastic surgeon for skin cancer removal in cosmetically sensitive areas, especially areas that may require more complex surgical repairs. However, recent Medicare data indicate that dermatologists perform the vast majority of reconstructive skin surgeries, with more than 15 times the number of intermediate and complex closures and more than 4 times the number of flaps and grafts as the next closest specialty.⁴ Earlier studies using Medicare data revealed similar findings, with dermatologic surgeons performing more reconstructions of head and neck skin than both plastic surgeons and otorhinolaryngologists.⁵ However, these studies did not address the characteristics of the tumor, defects, or repairs performed by the specialties for comparison.

We sought to compare the quantity and characteristics of flaps or grafts performed for skin cancer on the nose or ears by fellowship-trained Mohs surgeons and plastic surgeons at 1 academic institution.

Methods

We performed a retrospective chart review of all skin cancer surgeries requiring a flap or graft on the nose or ears at Baylor Scott & White Health (Temple, Texas) from October 1, 2016, to October 1, 2017. This study was approved by the Baylor Scott & White Health institutional review board.

Data Collection
The analysis included full-time, fellowship-trained Mohs surgeons and all full-time plastic surgeons who accepted skin cancer surgery patient referrals as part of their practice and performed all procedures within our hospital system. We reviewed individual provider schedules for both outpatient consultation and operating room notes to capture each procedure performed. To ensure we captured all procedures for both Mohs and plastic surgeons, we used billing codes for any flap or graft repair done on the nose or ears to cross-reference and confirm the cases found by chart review. The total number of flaps or grafts on the nose or ears were collected. Data also were collected regarding the anatomic location of the skin cancer, final defect size prior to the repair, skin tumor type, repair type (flap or graft), and flap (transposition vs advancement) or graft (full thickness vs partial thickness) type. All surgical data were collected from operative notes. Demographic data, including age, race, and sex, also were collected. We also collected data on the specialty of the physicians who referred patients for surgical management of biopsy-proven skin malignancy.

Statistical Analysis
Sample characteristics were described using descriptive statistics. Frequencies and percentages were used to describe categorical variables. Medians and ranges were used to describe continuous variables due to nonsymmetrically distributed data. χ² tests (or Fisher exact tests when low cell counts were present) for categorical variables and Wilcoxon signed rank tests for continuous variables were used to test for associations in bivariate comparisons between MMS and plastic surgery.

Results

A total of 7 physicians (1 fellowship-trained Mohs surgeon and 6 plastic surgeons) at our institution met the inclusion criteria. The Mohs surgeon performed a significantly higher number of flaps and grafts (n=276) than the plastic surgeons (n=17 combined; average per plastic surgeon, 2.83) on the nose or ears in a 12-month period (P<.05)(Table). The median final defect size was not significantly different between MMS (1.5 cm) and plastic surgery (1.8 cm)(P=.306). Flap repairs were more common in patients undergoing MMS (80%) vs plastic surgery (53%)(P=.022)(Figure). For flap repair, advancement flaps were used more commonly (MMS, 53%; plastic surgery, 35%) than transposition flaps (MMS, 27%; plastic surgery, 12%) by both specialties.

Patient age was similar between MMS (median, 74 years) and plastic surgery (median, 73 years) patients (P=.382), but a greater percentage of women were treated by plastic surgeons (53%) compared with Mohs surgeons (33%). The predominant skin tumor type for both specialties was basal cell carcinoma (MMS, 85%; plastic surgery, 76%). Dermatology was the largest referring specialty to both MMS (98%) and plastic surgery (53%). Family medicine referrals comprised a much larger percentage of cases for plastic surgery (24%) compared to MMS (1%).

Comment

This study supports and adds to recent studies and data regarding the utilization of MMS for the treatment of NMSCs. Although the percentage of all skin cancer surgery is increasing for dermatology, little has been reported on more complex repairs. This study highlights the volume and complexity of skin surgery performed by Mohs surgeons compared to our colleagues in plastic surgery.

Defect Size
The defect sizes prior to repair were not statistically different between the 2 types of surgeries, though the median size was slightly larger for plastic surgery (1.8 cm) compared to MMS (1.5 cm). These non–statistically significant differences may be explained by potentially larger tumors requiring repair by plastic surgeons in an operating room. Plastic surgeons, however, may be more likely to take a larger margin of clinically unaffected tissue as part of the initial layer. Plastic surgeons also may be less likely to curette the lesion prior to excision to obtain more clear tumor margins, possibly leading to more stages and a subsequently larger defect. Knowing the clinical sizes of these NMSCs prior to biopsy would have been beneficial to our study, but these data often were not available from the referring providers.

Repair Type
Most patients who underwent MMS had surgical defects repaired with a flap vs a graft, and a much higher percentage of patients who had undergone MMS vs surgical excision with plastic surgery had their defects repaired with flaps. Using a visual analog scale score and Hollander Wound Evaluation Scale, Jacobs et al⁶ found flaps to be cosmetically superior to grafts following tumor extirpation on the nose. The more frequent use of grafts by plastic surgeons could be at least partially explained by larger defect size or by a few outlier larger lesions among an otherwise small sample size. Larger studies may be needed to see if a true discrepancy in repair preferences exists between the specialties.

Referring Specialty
Primary care physician referral comprised a much larger percentage of cases sent for treatment with plastic surgery (24%) compared to MMS (1%). This statistic may represent a practice gap in the perception of MMS and its benefits among our primary care colleagues, particularly among female patients, as a much higher percentage of women were treated with plastic surgery. Important potential benefits of MMS, particularly tissue conservation, cure rates for skin cancer, and the volume of repairs performed by Mohs surgeons, may need to be emphasized.

Scope of Practice
Our colleagues in plastic surgery are extremely gifted and perform numerous repairs outside the scope of most Mohs surgeons. They are vital to multidisciplinary approaches to patients with skin cancer. Although Mohs surgeons focus on treating skin cancers that arise in a narrower range of anatomic locations, the breadth and variety of surgical procedures performed by plastic surgeons is more diverse. Skin cancer surgery may account for a smaller portion of procedures in a plastic surgery practice.

Limitations
There are several limitations to this study. We did not compare cosmesis or wound healing in patients treated by MMS or plastic surgery. The sample size, particularly with plastic surgery, was small and did not allow for a larger, more powerful comparison of data between the 2 specialties. Finally, our study only represents 1 institution over the course of 1 year.

Conclusion

To provide the best care possible, it is imperative for referring physicians to possess an accurate understanding of the volume of cases and the types of repairs that treating specialties perform on a regular basis for NMSCs. This knowledge is particularly important when there is a treatment overlap among specialties. Our data show Mohs surgeons are performing more complex repairs and reconstructions on even the most cosmetically sensitive areas; therefore, primary care physicians and other specialists may be more likely to involve dermatology in the care of skin cancer.

The incidence of nonmelanoma skin cancer (NMSC) is steadily increasing, and it accounts for more annual cancer diagnoses than all other malignancies combined.^1,2 For NMSCs of the head and neck, Mohs micrographic surgery (MMS) has become a preferred technique because of its high cure rates, intraprocedural margin control, and improved tissue preservation in cosmetically sensitive areas.³ The nose and ears are especially sensitive anatomic locations given their prominent positions and relative lack of skin reservoir and laxity compared to other areas of the head and neck. For the nose and ears, both patients and referring providers may question who is best suited to surgically remove a malignancy and repair the defect with positive functional and cosmetic results, as a large portion of the defects following tumor extirpation will require a flap or graft for repair.

The notion of plastic surgery is strongly associated with supreme cosmesis for many patients and providers, as the specialty trains in several surgical and nonsurgical elective techniques to preserve and improve appearance. Consequently, patients commonly ask dermatologists if they should be referred to a plastic surgeon for skin cancer removal in cosmetically sensitive areas, especially areas that may require more complex surgical repairs. However, recent Medicare data indicate that dermatologists perform the vast majority of reconstructive skin surgeries, with more than 15 times the number of intermediate and complex closures and more than 4 times the number of flaps and grafts as the next closest specialty.⁴ Earlier studies using Medicare data revealed similar findings, with dermatologic surgeons performing more reconstructions of head and neck skin than both plastic surgeons and otorhinolaryngologists.⁵ However, these studies did not address the characteristics of the tumor, defects, or repairs performed by the specialties for comparison.

We sought to compare the quantity and characteristics of flaps or grafts performed for skin cancer on the nose or ears by fellowship-trained Mohs surgeons and plastic surgeons at 1 academic institution.

Methods

We performed a retrospective chart review of all skin cancer surgeries requiring a flap or graft on the nose or ears at Baylor Scott & White Health (Temple, Texas) from October 1, 2016, to October 1, 2017. This study was approved by the Baylor Scott & White Health institutional review board.

Data Collection
The analysis included full-time, fellowship-trained Mohs surgeons and all full-time plastic surgeons who accepted skin cancer surgery patient referrals as part of their practice and performed all procedures within our hospital system. We reviewed individual provider schedules for both outpatient consultation and operating room notes to capture each procedure performed. To ensure we captured all procedures for both Mohs and plastic surgeons, we used billing codes for any flap or graft repair done on the nose or ears to cross-reference and confirm the cases found by chart review. The total number of flaps or grafts on the nose or ears were collected. Data also were collected regarding the anatomic location of the skin cancer, final defect size prior to the repair, skin tumor type, repair type (flap or graft), and flap (transposition vs advancement) or graft (full thickness vs partial thickness) type. All surgical data were collected from operative notes. Demographic data, including age, race, and sex, also were collected. We also collected data on the specialty of the physicians who referred patients for surgical management of biopsy-proven skin malignancy.

Statistical Analysis
Sample characteristics were described using descriptive statistics. Frequencies and percentages were used to describe categorical variables. Medians and ranges were used to describe continuous variables due to nonsymmetrically distributed data. χ² tests (or Fisher exact tests when low cell counts were present) for categorical variables and Wilcoxon signed rank tests for continuous variables were used to test for associations in bivariate comparisons between MMS and plastic surgery.

Results

A total of 7 physicians (1 fellowship-trained Mohs surgeon and 6 plastic surgeons) at our institution met the inclusion criteria. The Mohs surgeon performed a significantly higher number of flaps and grafts (n=276) than the plastic surgeons (n=17 combined; average per plastic surgeon, 2.83) on the nose or ears in a 12-month period (P<.05)(Table). The median final defect size was not significantly different between MMS (1.5 cm) and plastic surgery (1.8 cm)(P=.306). Flap repairs were more common in patients undergoing MMS (80%) vs plastic surgery (53%)(P=.022)(Figure). For flap repair, advancement flaps were used more commonly (MMS, 53%; plastic surgery, 35%) than transposition flaps (MMS, 27%; plastic surgery, 12%) by both specialties.

Patient age was similar between MMS (median, 74 years) and plastic surgery (median, 73 years) patients (P=.382), but a greater percentage of women were treated by plastic surgeons (53%) compared with Mohs surgeons (33%). The predominant skin tumor type for both specialties was basal cell carcinoma (MMS, 85%; plastic surgery, 76%). Dermatology was the largest referring specialty to both MMS (98%) and plastic surgery (53%). Family medicine referrals comprised a much larger percentage of cases for plastic surgery (24%) compared to MMS (1%).

Comment

This study supports and adds to recent studies and data regarding the utilization of MMS for the treatment of NMSCs. Although the percentage of all skin cancer surgery is increasing for dermatology, little has been reported on more complex repairs. This study highlights the volume and complexity of skin surgery performed by Mohs surgeons compared to our colleagues in plastic surgery.

Defect Size
The defect sizes prior to repair were not statistically different between the 2 types of surgeries, though the median size was slightly larger for plastic surgery (1.8 cm) compared to MMS (1.5 cm). These non–statistically significant differences may be explained by potentially larger tumors requiring repair by plastic surgeons in an operating room. Plastic surgeons, however, may be more likely to take a larger margin of clinically unaffected tissue as part of the initial layer. Plastic surgeons also may be less likely to curette the lesion prior to excision to obtain more clear tumor margins, possibly leading to more stages and a subsequently larger defect. Knowing the clinical sizes of these NMSCs prior to biopsy would have been beneficial to our study, but these data often were not available from the referring providers.

Repair Type
Most patients who underwent MMS had surgical defects repaired with a flap vs a graft, and a much higher percentage of patients who had undergone MMS vs surgical excision with plastic surgery had their defects repaired with flaps. Using a visual analog scale score and Hollander Wound Evaluation Scale, Jacobs et al⁶ found flaps to be cosmetically superior to grafts following tumor extirpation on the nose. The more frequent use of grafts by plastic surgeons could be at least partially explained by larger defect size or by a few outlier larger lesions among an otherwise small sample size. Larger studies may be needed to see if a true discrepancy in repair preferences exists between the specialties.

Referring Specialty
Primary care physician referral comprised a much larger percentage of cases sent for treatment with plastic surgery (24%) compared to MMS (1%). This statistic may represent a practice gap in the perception of MMS and its benefits among our primary care colleagues, particularly among female patients, as a much higher percentage of women were treated with plastic surgery. Important potential benefits of MMS, particularly tissue conservation, cure rates for skin cancer, and the volume of repairs performed by Mohs surgeons, may need to be emphasized.

Scope of Practice
Our colleagues in plastic surgery are extremely gifted and perform numerous repairs outside the scope of most Mohs surgeons. They are vital to multidisciplinary approaches to patients with skin cancer. Although Mohs surgeons focus on treating skin cancers that arise in a narrower range of anatomic locations, the breadth and variety of surgical procedures performed by plastic surgeons is more diverse. Skin cancer surgery may account for a smaller portion of procedures in a plastic surgery practice.

Limitations
There are several limitations to this study. We did not compare cosmesis or wound healing in patients treated by MMS or plastic surgery. The sample size, particularly with plastic surgery, was small and did not allow for a larger, more powerful comparison of data between the 2 specialties. Finally, our study only represents 1 institution over the course of 1 year.

Conclusion

To provide the best care possible, it is imperative for referring physicians to possess an accurate understanding of the volume of cases and the types of repairs that treating specialties perform on a regular basis for NMSCs. This knowledge is particularly important when there is a treatment overlap among specialties. Our data show Mohs surgeons are performing more complex repairs and reconstructions on even the most cosmetically sensitive areas; therefore, primary care physicians and other specialists may be more likely to involve dermatology in the care of skin cancer.

The incidence of nonmelanoma skin cancer (NMSC) is steadily increasing, and it accounts for more annual cancer diagnoses than all other malignancies combined.^1,2 For NMSCs of the head and neck, Mohs micrographic surgery (MMS) has become a preferred technique because of its high cure rates, intraprocedural margin control, and improved tissue preservation in cosmetically sensitive areas.³ The nose and ears are especially sensitive anatomic locations given their prominent positions and relative lack of skin reservoir and laxity compared to other areas of the head and neck. For the nose and ears, both patients and referring providers may question who is best suited to surgically remove a malignancy and repair the defect with positive functional and cosmetic results, as a large portion of the defects following tumor extirpation will require a flap or graft for repair.

The notion of plastic surgery is strongly associated with supreme cosmesis for many patients and providers, as the specialty trains in several surgical and nonsurgical elective techniques to preserve and improve appearance. Consequently, patients commonly ask dermatologists if they should be referred to a plastic surgeon for skin cancer removal in cosmetically sensitive areas, especially areas that may require more complex surgical repairs. However, recent Medicare data indicate that dermatologists perform the vast majority of reconstructive skin surgeries, with more than 15 times the number of intermediate and complex closures and more than 4 times the number of flaps and grafts as the next closest specialty.⁴ Earlier studies using Medicare data revealed similar findings, with dermatologic surgeons performing more reconstructions of head and neck skin than both plastic surgeons and otorhinolaryngologists.⁵ However, these studies did not address the characteristics of the tumor, defects, or repairs performed by the specialties for comparison.

We sought to compare the quantity and characteristics of flaps or grafts performed for skin cancer on the nose or ears by fellowship-trained Mohs surgeons and plastic surgeons at 1 academic institution.

Methods

We performed a retrospective chart review of all skin cancer surgeries requiring a flap or graft on the nose or ears at Baylor Scott & White Health (Temple, Texas) from October 1, 2016, to October 1, 2017. This study was approved by the Baylor Scott & White Health institutional review board.

Data Collection
The analysis included full-time, fellowship-trained Mohs surgeons and all full-time plastic surgeons who accepted skin cancer surgery patient referrals as part of their practice and performed all procedures within our hospital system. We reviewed individual provider schedules for both outpatient consultation and operating room notes to capture each procedure performed. To ensure we captured all procedures for both Mohs and plastic surgeons, we used billing codes for any flap or graft repair done on the nose or ears to cross-reference and confirm the cases found by chart review. The total number of flaps or grafts on the nose or ears were collected. Data also were collected regarding the anatomic location of the skin cancer, final defect size prior to the repair, skin tumor type, repair type (flap or graft), and flap (transposition vs advancement) or graft (full thickness vs partial thickness) type. All surgical data were collected from operative notes. Demographic data, including age, race, and sex, also were collected. We also collected data on the specialty of the physicians who referred patients for surgical management of biopsy-proven skin malignancy.

Statistical Analysis
Sample characteristics were described using descriptive statistics. Frequencies and percentages were used to describe categorical variables. Medians and ranges were used to describe continuous variables due to nonsymmetrically distributed data. χ² tests (or Fisher exact tests when low cell counts were present) for categorical variables and Wilcoxon signed rank tests for continuous variables were used to test for associations in bivariate comparisons between MMS and plastic surgery.

Results

A total of 7 physicians (1 fellowship-trained Mohs surgeon and 6 plastic surgeons) at our institution met the inclusion criteria. The Mohs surgeon performed a significantly higher number of flaps and grafts (n=276) than the plastic surgeons (n=17 combined; average per plastic surgeon, 2.83) on the nose or ears in a 12-month period (P<.05)(Table). The median final defect size was not significantly different between MMS (1.5 cm) and plastic surgery (1.8 cm)(P=.306). Flap repairs were more common in patients undergoing MMS (80%) vs plastic surgery (53%)(P=.022)(Figure). For flap repair, advancement flaps were used more commonly (MMS, 53%; plastic surgery, 35%) than transposition flaps (MMS, 27%; plastic surgery, 12%) by both specialties.

Patient age was similar between MMS (median, 74 years) and plastic surgery (median, 73 years) patients (P=.382), but a greater percentage of women were treated by plastic surgeons (53%) compared with Mohs surgeons (33%). The predominant skin tumor type for both specialties was basal cell carcinoma (MMS, 85%; plastic surgery, 76%). Dermatology was the largest referring specialty to both MMS (98%) and plastic surgery (53%). Family medicine referrals comprised a much larger percentage of cases for plastic surgery (24%) compared to MMS (1%).

Comment

This study supports and adds to recent studies and data regarding the utilization of MMS for the treatment of NMSCs. Although the percentage of all skin cancer surgery is increasing for dermatology, little has been reported on more complex repairs. This study highlights the volume and complexity of skin surgery performed by Mohs surgeons compared to our colleagues in plastic surgery.

Defect Size
The defect sizes prior to repair were not statistically different between the 2 types of surgeries, though the median size was slightly larger for plastic surgery (1.8 cm) compared to MMS (1.5 cm). These non–statistically significant differences may be explained by potentially larger tumors requiring repair by plastic surgeons in an operating room. Plastic surgeons, however, may be more likely to take a larger margin of clinically unaffected tissue as part of the initial layer. Plastic surgeons also may be less likely to curette the lesion prior to excision to obtain more clear tumor margins, possibly leading to more stages and a subsequently larger defect. Knowing the clinical sizes of these NMSCs prior to biopsy would have been beneficial to our study, but these data often were not available from the referring providers.

Repair Type
Most patients who underwent MMS had surgical defects repaired with a flap vs a graft, and a much higher percentage of patients who had undergone MMS vs surgical excision with plastic surgery had their defects repaired with flaps. Using a visual analog scale score and Hollander Wound Evaluation Scale, Jacobs et al⁶ found flaps to be cosmetically superior to grafts following tumor extirpation on the nose. The more frequent use of grafts by plastic surgeons could be at least partially explained by larger defect size or by a few outlier larger lesions among an otherwise small sample size. Larger studies may be needed to see if a true discrepancy in repair preferences exists between the specialties.

Referring Specialty
Primary care physician referral comprised a much larger percentage of cases sent for treatment with plastic surgery (24%) compared to MMS (1%). This statistic may represent a practice gap in the perception of MMS and its benefits among our primary care colleagues, particularly among female patients, as a much higher percentage of women were treated with plastic surgery. Important potential benefits of MMS, particularly tissue conservation, cure rates for skin cancer, and the volume of repairs performed by Mohs surgeons, may need to be emphasized.

Scope of Practice
Our colleagues in plastic surgery are extremely gifted and perform numerous repairs outside the scope of most Mohs surgeons. They are vital to multidisciplinary approaches to patients with skin cancer. Although Mohs surgeons focus on treating skin cancers that arise in a narrower range of anatomic locations, the breadth and variety of surgical procedures performed by plastic surgeons is more diverse. Skin cancer surgery may account for a smaller portion of procedures in a plastic surgery practice.

Limitations
There are several limitations to this study. We did not compare cosmesis or wound healing in patients treated by MMS or plastic surgery. The sample size, particularly with plastic surgery, was small and did not allow for a larger, more powerful comparison of data between the 2 specialties. Finally, our study only represents 1 institution over the course of 1 year.

Conclusion

To provide the best care possible, it is imperative for referring physicians to possess an accurate understanding of the volume of cases and the types of repairs that treating specialties perform on a regular basis for NMSCs. This knowledge is particularly important when there is a treatment overlap among specialties. Our data show Mohs surgeons are performing more complex repairs and reconstructions on even the most cosmetically sensitive areas; therefore, primary care physicians and other specialists may be more likely to involve dermatology in the care of skin cancer.

In February 2019, Dayanara Torres announced that she had been diagnosed with metastatic melanoma. Ms. Torres, a Puerto Rican–born former Miss Universe who has more than 1 million followers on Instagram (@dayanarapr), seemed an unlikely candidate for skin cancer, which often is associated with fair-skinned and light-eyed individuals. She shared the news of her diagnosis in an Instagram video that has now received more than 850,000 views. In the video, Ms. Torres described a new mole with uneven surface that had developed on her leg and noted that she had ignored it, even though it had been growing for years. Ultimately, she was diagnosed with melanoma that had already metastasized to regional lymph nodes in her leg. Ms. Torres concluded the video by urging fans and viewers to be mindful of new or changing skin lesions and to be aware of the seriousness of skin cancer. In March 2019, Ms. Torres posted a follow-up educational video on Instagram highlighting the features of melanoma that has now received more than 300,000 views.

Since her announcement, we have noticed that more Hispanic patients with concerns about skin cancer are presenting to our dermatology clinic, which is located in a highly diverse city (New Brunswick, New Jersey) with approximately 50% of residents identifying as Hispanic.¹ Most Hispanic patients typically present to our dermatology clinic for non–skin cancer–related concerns, such as acne, rash, and dyschromia; however, following Ms. Torres’ announcement, many have cited her diagnosis of metastatic melanoma as a cause for concern and a motivating factor in having their skin examined. The diagnosis in a prominent celebrity and Hispanic woman has given a new face to metastatic melanoma.

Although melanoma most commonly occurs in white patients, Hispanic patients experience disproportionately greater morbidity and mortality when diagnosed with melanoma.² Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis. The Hispanic community encompasses a wide variety of individuals with varying levels of skin pigmentation and sun sensitivity.³ However, Hispanics report low levels of sun-protective behaviors. They also may have misconceptions that sunscreen is ineffective in preventing skin cancer and that little can be done to decrease the risk for developing skin cancer.^4,5 Additionally, Hispanic patients often have lower perceptions of their personal risk for melanoma and report low rates of clinical and self-examinations compared to non-Hispanic white patients.^6-8 Many Hispanic patients have reported that they were not instructed to perform self-examinations of their skin regularly by dermatologists or other providers and did not know the signs of skin cancer.⁷ Furthermore, a language barrier also may impede communication and education regarding melanoma risk.⁹

Similar to white patients, superficial spreading melanoma is the most common histologic subtype in Hispanic patients, followed by acral lentiginous melanoma, which is the most common subtype in black and Asian patients.^2,4 Compared to non-Hispanic white patients, who most commonly present with truncal melanomas, Hispanic patients (particularly those from Puerto Rico, such as Ms. Torres) are more likely to present with melanoma on the lower extremities.^4,10 Additionally, Hispanic patients have high rates of head, neck, and mucosal melanomas compared to all other racial and ethnic groups.²

Hispanic patients diagnosed with melanoma are more likely to present with thicker primary tumors, later stages of disease, and distant metastases compared to non-Hispanic white patients, all of which are associated with poor prognosis.^2,4,11 Five-year survival rates for melanoma are lower in Hispanic patients compared to non-Hispanic white patients.¹² Although the Hispanic community is diverse in socioeconomic and immigration status as well as occupation, lack of insurance also may contribute to decreased access to care, delayed diagnosis, and ultimately worse survival.

These disparities have spurred suggestions for increased education about skin cancer and the signs and symptoms of melanoma, encouragement of self-examinations, and routine clinical skin examinations for Hispanic patients by dermatologists and other providers.⁸ There is evidence that knowledge-based interventions, especially when presented in Spanish, produce statistically significant improvements in knowledge of skin cancer risk and sun-protective behavior among Hispanic patients.¹² Similarly, we have observed that the videos shared by Ms. Torres regarding her melanoma diagnosis and the features of melanoma, in which she spoke in Spanish, have compelled many Hispanic patients to examine their own skin and have led to increased concern for skin cancer in this patient population. In our practice, we refer to the increase in spot checks and skin examinations requested by Hispanic patients as “The Dayanara Effect,” and we hypothesize that this same effect may be taking place throughout the dermatology community.

In February 2019, Dayanara Torres announced that she had been diagnosed with metastatic melanoma. Ms. Torres, a Puerto Rican–born former Miss Universe who has more than 1 million followers on Instagram (@dayanarapr), seemed an unlikely candidate for skin cancer, which often is associated with fair-skinned and light-eyed individuals. She shared the news of her diagnosis in an Instagram video that has now received more than 850,000 views. In the video, Ms. Torres described a new mole with uneven surface that had developed on her leg and noted that she had ignored it, even though it had been growing for years. Ultimately, she was diagnosed with melanoma that had already metastasized to regional lymph nodes in her leg. Ms. Torres concluded the video by urging fans and viewers to be mindful of new or changing skin lesions and to be aware of the seriousness of skin cancer. In March 2019, Ms. Torres posted a follow-up educational video on Instagram highlighting the features of melanoma that has now received more than 300,000 views.

Since her announcement, we have noticed that more Hispanic patients with concerns about skin cancer are presenting to our dermatology clinic, which is located in a highly diverse city (New Brunswick, New Jersey) with approximately 50% of residents identifying as Hispanic.¹ Most Hispanic patients typically present to our dermatology clinic for non–skin cancer–related concerns, such as acne, rash, and dyschromia; however, following Ms. Torres’ announcement, many have cited her diagnosis of metastatic melanoma as a cause for concern and a motivating factor in having their skin examined. The diagnosis in a prominent celebrity and Hispanic woman has given a new face to metastatic melanoma.

Although melanoma most commonly occurs in white patients, Hispanic patients experience disproportionately greater morbidity and mortality when diagnosed with melanoma.² Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis. The Hispanic community encompasses a wide variety of individuals with varying levels of skin pigmentation and sun sensitivity.³ However, Hispanics report low levels of sun-protective behaviors. They also may have misconceptions that sunscreen is ineffective in preventing skin cancer and that little can be done to decrease the risk for developing skin cancer.^4,5 Additionally, Hispanic patients often have lower perceptions of their personal risk for melanoma and report low rates of clinical and self-examinations compared to non-Hispanic white patients.^6-8 Many Hispanic patients have reported that they were not instructed to perform self-examinations of their skin regularly by dermatologists or other providers and did not know the signs of skin cancer.⁷ Furthermore, a language barrier also may impede communication and education regarding melanoma risk.⁹

Similar to white patients, superficial spreading melanoma is the most common histologic subtype in Hispanic patients, followed by acral lentiginous melanoma, which is the most common subtype in black and Asian patients.^2,4 Compared to non-Hispanic white patients, who most commonly present with truncal melanomas, Hispanic patients (particularly those from Puerto Rico, such as Ms. Torres) are more likely to present with melanoma on the lower extremities.^4,10 Additionally, Hispanic patients have high rates of head, neck, and mucosal melanomas compared to all other racial and ethnic groups.²

Hispanic patients diagnosed with melanoma are more likely to present with thicker primary tumors, later stages of disease, and distant metastases compared to non-Hispanic white patients, all of which are associated with poor prognosis.^2,4,11 Five-year survival rates for melanoma are lower in Hispanic patients compared to non-Hispanic white patients.¹² Although the Hispanic community is diverse in socioeconomic and immigration status as well as occupation, lack of insurance also may contribute to decreased access to care, delayed diagnosis, and ultimately worse survival.

These disparities have spurred suggestions for increased education about skin cancer and the signs and symptoms of melanoma, encouragement of self-examinations, and routine clinical skin examinations for Hispanic patients by dermatologists and other providers.⁸ There is evidence that knowledge-based interventions, especially when presented in Spanish, produce statistically significant improvements in knowledge of skin cancer risk and sun-protective behavior among Hispanic patients.¹² Similarly, we have observed that the videos shared by Ms. Torres regarding her melanoma diagnosis and the features of melanoma, in which she spoke in Spanish, have compelled many Hispanic patients to examine their own skin and have led to increased concern for skin cancer in this patient population. In our practice, we refer to the increase in spot checks and skin examinations requested by Hispanic patients as “The Dayanara Effect,” and we hypothesize that this same effect may be taking place throughout the dermatology community.

In February 2019, Dayanara Torres announced that she had been diagnosed with metastatic melanoma. Ms. Torres, a Puerto Rican–born former Miss Universe who has more than 1 million followers on Instagram (@dayanarapr), seemed an unlikely candidate for skin cancer, which often is associated with fair-skinned and light-eyed individuals. She shared the news of her diagnosis in an Instagram video that has now received more than 850,000 views. In the video, Ms. Torres described a new mole with uneven surface that had developed on her leg and noted that she had ignored it, even though it had been growing for years. Ultimately, she was diagnosed with melanoma that had already metastasized to regional lymph nodes in her leg. Ms. Torres concluded the video by urging fans and viewers to be mindful of new or changing skin lesions and to be aware of the seriousness of skin cancer. In March 2019, Ms. Torres posted a follow-up educational video on Instagram highlighting the features of melanoma that has now received more than 300,000 views.

Since her announcement, we have noticed that more Hispanic patients with concerns about skin cancer are presenting to our dermatology clinic, which is located in a highly diverse city (New Brunswick, New Jersey) with approximately 50% of residents identifying as Hispanic.¹ Most Hispanic patients typically present to our dermatology clinic for non–skin cancer–related concerns, such as acne, rash, and dyschromia; however, following Ms. Torres’ announcement, many have cited her diagnosis of metastatic melanoma as a cause for concern and a motivating factor in having their skin examined. The diagnosis in a prominent celebrity and Hispanic woman has given a new face to metastatic melanoma.

Although melanoma most commonly occurs in white patients, Hispanic patients experience disproportionately greater morbidity and mortality when diagnosed with melanoma.² Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis. The Hispanic community encompasses a wide variety of individuals with varying levels of skin pigmentation and sun sensitivity.³ However, Hispanics report low levels of sun-protective behaviors. They also may have misconceptions that sunscreen is ineffective in preventing skin cancer and that little can be done to decrease the risk for developing skin cancer.^4,5 Additionally, Hispanic patients often have lower perceptions of their personal risk for melanoma and report low rates of clinical and self-examinations compared to non-Hispanic white patients.^6-8 Many Hispanic patients have reported that they were not instructed to perform self-examinations of their skin regularly by dermatologists or other providers and did not know the signs of skin cancer.⁷ Furthermore, a language barrier also may impede communication and education regarding melanoma risk.⁹

Similar to white patients, superficial spreading melanoma is the most common histologic subtype in Hispanic patients, followed by acral lentiginous melanoma, which is the most common subtype in black and Asian patients.^2,4 Compared to non-Hispanic white patients, who most commonly present with truncal melanomas, Hispanic patients (particularly those from Puerto Rico, such as Ms. Torres) are more likely to present with melanoma on the lower extremities.^4,10 Additionally, Hispanic patients have high rates of head, neck, and mucosal melanomas compared to all other racial and ethnic groups.²

Hispanic patients diagnosed with melanoma are more likely to present with thicker primary tumors, later stages of disease, and distant metastases compared to non-Hispanic white patients, all of which are associated with poor prognosis.^2,4,11 Five-year survival rates for melanoma are lower in Hispanic patients compared to non-Hispanic white patients.¹² Although the Hispanic community is diverse in socioeconomic and immigration status as well as occupation, lack of insurance also may contribute to decreased access to care, delayed diagnosis, and ultimately worse survival.

These disparities have spurred suggestions for increased education about skin cancer and the signs and symptoms of melanoma, encouragement of self-examinations, and routine clinical skin examinations for Hispanic patients by dermatologists and other providers.⁸ There is evidence that knowledge-based interventions, especially when presented in Spanish, produce statistically significant improvements in knowledge of skin cancer risk and sun-protective behavior among Hispanic patients.¹² Similarly, we have observed that the videos shared by Ms. Torres regarding her melanoma diagnosis and the features of melanoma, in which she spoke in Spanish, have compelled many Hispanic patients to examine their own skin and have led to increased concern for skin cancer in this patient population. In our practice, we refer to the increase in spot checks and skin examinations requested by Hispanic patients as “The Dayanara Effect,” and we hypothesize that this same effect may be taking place throughout the dermatology community.

First reported in 1895, nevus sebaceus (NS) is a con genital papillomatous hamartoma most commonly found on the scalp and face. ¹ Lesions typically are yellow-orange plaques and often are hairless. Nevus sebaceus is most prominent in the few first months after birth and again at puberty during development of the sebaceous glands. Development of epithelial hyperplasia, cysts, verrucas, and benign or malignant tumors has been reported. ¹ The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma. Cases of malignancy are rare, and basal cell carcinoma is the predominant form (approximately 2% of cases). Squamous cell carcinoma (SCC) and adnexal carcinoma are reported at even lower rates. ¹ Malignant transformation occurring during childhood is extremely uncommon. According to a PubMed search of articles indexed for MEDLINE using the terms nevus sebaceous, malignancy, and squamous cell carcinoma and narrowing the results to children, there have been only 4 prior reports of SCC developing within an NS in a child. ^2-5 We report a case of SCC arising in an NS in a 13-year-old adolescent girl with perineural invasion.

Case Report

A 13-year-old fair-skinned adolescent girl presented with a hairless 2×2.5-cm yellow plaque at the hairline on the anterior central scalp. The plaque had been present since birth and had progressively developed a superiorly located 3×5-mm erythematous verrucous nodule (Figure 1) with an approximate height of 6 mm over the last year. The nodule was subjected to regular trauma and bled with minimal insult. The patient appeared otherwise healthy, with no history of skin cancer or other chronic medical conditions. There was no evidence of lymphadenopathy on examination, and no other skin abnormalities were noted. There was no reported family history of skin cancer or chronic skin conditions suggestive of increased risk for cancer or other pathologic dermatoses. Differential diagnoses for the plaque and nodule complex included verruca, Spitz nevus, or secondary neoplasm within NS.

Excision was conducted under local anesthesia without complication. An elliptical section of skin measuring 0.8×2.5 cm was excised to a depth of 3 mm. The resulting wound was closed using a complex linear repair. The section was placed in formalin specimen transport medium and sent to Walter Reed National Military Medical Center (Bethesda, Maryland). Microscopic examination of the specimen revealed features typical for NS, including mild verrucous epidermal hyperplasia, sebaceous gland hyperplasia, presence of apocrine glands, and hamartomatous follicular proliferations (Figure 2). An even more papillomatous epidermal proliferation that was comprised of atypical squamous cells was present within the lesion. Similar atypical squamous cells infiltrated the superficial dermis in nests, cords, and single cells (Figure 3A). One focus showed perineural invasion with a small superficial nerve fiber surrounded by SCC (Figure 3B). The tumor was completely excised, with negative surgical margins extending approximately 2 mm. Adjuvant radiation therapy and further specialized Mohs micrographic excision were not performed because of the clear histologic appearance of the carcinoma and strong evidence of complete excision.

At 2-week follow-up, the surgical scar on the anterior central forehead was well healed without evidence of SCC recurrence. On physical examination there was neither lymphadenopathy nor signs of neurologic deficit, except for superficial cutaneous hypoesthesia in the immediate area surrounding the healed site. Following discussion with the patient and her parents, it was decided that the patient would obtain baseline laboratory tests, chest radiography, and abdominal ultrasonography, and she would undergo serial follow-up examinations every 3 months for the next 2 years. Annual follow-up was recommended after 2 years, with the caveat to return sooner if recurrence or symptoms were to arise.

Comment

Historically, there has been variability in the histopathologic interpretation of SCC in NS in the literature. Retrospective analysis of the histologic evidence of SCC in the 2 earliest possible cases of pediatric SCC in NS have been questioned due to the lack of clinical data presented and the possibility that the diagnosis of SCC was inaccurate.⁶ Our case was histopathologically interpreted as superficially invasive, well-differentiated SCC arising within an NS; therefore, we classified this case as SCC and took every precaution to ensure the lesion was completely excised, given the potentially invasive nature of SCC.

Our case is unique because it represents SCC in NS with histologic evidence of perineural involvement. Perineural invasion is a major route of tumor spread in SCC and may result in increased occurrence of regional lymph node spread and distant metastases, with path of least resistance or neural cell adhesion as possible spreading methods.^7-9 However, there is a notable amount of prognostic variability based on tumor type, the nerve involved, and degree of involvement.⁹ It is common for cutaneous SCC to occur with invasion of small intradermal nerves, but a poor outcome is less likely in asymptomatic patients who have perineural involvement that was incidentally discovered on histologic examination.¹⁰

In our patient, the entire tumor was completely removed with local excision. Recurrence of the SCC or future symptoms of deep neural invasion were not anticipated given the postoperative evidence of clear margins in the excised skin and subdermal structures as well as the lack of preoperative and postoperative symptoms. Close clinical follow-up was warranted to monitor for early signs of recurrence or neural involvement. We have confidence that the planned follow-up regimen in our patient will reveal any early signs of new occurrence or recurrence.

In the case of recurrence, Mohs micrographic surgery would likely be indicated. We elected not to treat with adjuvant radiotherapy because its benefit in cutaneous SCC with perineural invasion is debatable based on the lack of randomized controlled clinical evidence.^10,11 The patient obtained postoperative baseline complete blood cell count with differential, posterior/anterior and lateral chest radiographs, as well as abdominal ultrasonography. Each returned negative findings of hematologic or distant organ metastases, with subsequent follow-up visits also negative for any new concerning findings.

First reported in 1895, nevus sebaceus (NS) is a con genital papillomatous hamartoma most commonly found on the scalp and face. ¹ Lesions typically are yellow-orange plaques and often are hairless. Nevus sebaceus is most prominent in the few first months after birth and again at puberty during development of the sebaceous glands. Development of epithelial hyperplasia, cysts, verrucas, and benign or malignant tumors has been reported. ¹ The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma. Cases of malignancy are rare, and basal cell carcinoma is the predominant form (approximately 2% of cases). Squamous cell carcinoma (SCC) and adnexal carcinoma are reported at even lower rates. ¹ Malignant transformation occurring during childhood is extremely uncommon. According to a PubMed search of articles indexed for MEDLINE using the terms nevus sebaceous, malignancy, and squamous cell carcinoma and narrowing the results to children, there have been only 4 prior reports of SCC developing within an NS in a child. ^2-5 We report a case of SCC arising in an NS in a 13-year-old adolescent girl with perineural invasion.

Case Report

A 13-year-old fair-skinned adolescent girl presented with a hairless 2×2.5-cm yellow plaque at the hairline on the anterior central scalp. The plaque had been present since birth and had progressively developed a superiorly located 3×5-mm erythematous verrucous nodule (Figure 1) with an approximate height of 6 mm over the last year. The nodule was subjected to regular trauma and bled with minimal insult. The patient appeared otherwise healthy, with no history of skin cancer or other chronic medical conditions. There was no evidence of lymphadenopathy on examination, and no other skin abnormalities were noted. There was no reported family history of skin cancer or chronic skin conditions suggestive of increased risk for cancer or other pathologic dermatoses. Differential diagnoses for the plaque and nodule complex included verruca, Spitz nevus, or secondary neoplasm within NS.

Excision was conducted under local anesthesia without complication. An elliptical section of skin measuring 0.8×2.5 cm was excised to a depth of 3 mm. The resulting wound was closed using a complex linear repair. The section was placed in formalin specimen transport medium and sent to Walter Reed National Military Medical Center (Bethesda, Maryland). Microscopic examination of the specimen revealed features typical for NS, including mild verrucous epidermal hyperplasia, sebaceous gland hyperplasia, presence of apocrine glands, and hamartomatous follicular proliferations (Figure 2). An even more papillomatous epidermal proliferation that was comprised of atypical squamous cells was present within the lesion. Similar atypical squamous cells infiltrated the superficial dermis in nests, cords, and single cells (Figure 3A). One focus showed perineural invasion with a small superficial nerve fiber surrounded by SCC (Figure 3B). The tumor was completely excised, with negative surgical margins extending approximately 2 mm. Adjuvant radiation therapy and further specialized Mohs micrographic excision were not performed because of the clear histologic appearance of the carcinoma and strong evidence of complete excision.

At 2-week follow-up, the surgical scar on the anterior central forehead was well healed without evidence of SCC recurrence. On physical examination there was neither lymphadenopathy nor signs of neurologic deficit, except for superficial cutaneous hypoesthesia in the immediate area surrounding the healed site. Following discussion with the patient and her parents, it was decided that the patient would obtain baseline laboratory tests, chest radiography, and abdominal ultrasonography, and she would undergo serial follow-up examinations every 3 months for the next 2 years. Annual follow-up was recommended after 2 years, with the caveat to return sooner if recurrence or symptoms were to arise.

Comment

Historically, there has been variability in the histopathologic interpretation of SCC in NS in the literature. Retrospective analysis of the histologic evidence of SCC in the 2 earliest possible cases of pediatric SCC in NS have been questioned due to the lack of clinical data presented and the possibility that the diagnosis of SCC was inaccurate.⁶ Our case was histopathologically interpreted as superficially invasive, well-differentiated SCC arising within an NS; therefore, we classified this case as SCC and took every precaution to ensure the lesion was completely excised, given the potentially invasive nature of SCC.

Our case is unique because it represents SCC in NS with histologic evidence of perineural involvement. Perineural invasion is a major route of tumor spread in SCC and may result in increased occurrence of regional lymph node spread and distant metastases, with path of least resistance or neural cell adhesion as possible spreading methods.^7-9 However, there is a notable amount of prognostic variability based on tumor type, the nerve involved, and degree of involvement.⁹ It is common for cutaneous SCC to occur with invasion of small intradermal nerves, but a poor outcome is less likely in asymptomatic patients who have perineural involvement that was incidentally discovered on histologic examination.¹⁰

In our patient, the entire tumor was completely removed with local excision. Recurrence of the SCC or future symptoms of deep neural invasion were not anticipated given the postoperative evidence of clear margins in the excised skin and subdermal structures as well as the lack of preoperative and postoperative symptoms. Close clinical follow-up was warranted to monitor for early signs of recurrence or neural involvement. We have confidence that the planned follow-up regimen in our patient will reveal any early signs of new occurrence or recurrence.

In the case of recurrence, Mohs micrographic surgery would likely be indicated. We elected not to treat with adjuvant radiotherapy because its benefit in cutaneous SCC with perineural invasion is debatable based on the lack of randomized controlled clinical evidence.^10,11 The patient obtained postoperative baseline complete blood cell count with differential, posterior/anterior and lateral chest radiographs, as well as abdominal ultrasonography. Each returned negative findings of hematologic or distant organ metastases, with subsequent follow-up visits also negative for any new concerning findings.

First reported in 1895, nevus sebaceus (NS) is a con genital papillomatous hamartoma most commonly found on the scalp and face. ¹ Lesions typically are yellow-orange plaques and often are hairless. Nevus sebaceus is most prominent in the few first months after birth and again at puberty during development of the sebaceous glands. Development of epithelial hyperplasia, cysts, verrucas, and benign or malignant tumors has been reported. ¹ The most common benign tumors are syringocystadenoma papilliferum and trichoblastoma. Cases of malignancy are rare, and basal cell carcinoma is the predominant form (approximately 2% of cases). Squamous cell carcinoma (SCC) and adnexal carcinoma are reported at even lower rates. ¹ Malignant transformation occurring during childhood is extremely uncommon. According to a PubMed search of articles indexed for MEDLINE using the terms nevus sebaceous, malignancy, and squamous cell carcinoma and narrowing the results to children, there have been only 4 prior reports of SCC developing within an NS in a child. ^2-5 We report a case of SCC arising in an NS in a 13-year-old adolescent girl with perineural invasion.

Case Report

A 13-year-old fair-skinned adolescent girl presented with a hairless 2×2.5-cm yellow plaque at the hairline on the anterior central scalp. The plaque had been present since birth and had progressively developed a superiorly located 3×5-mm erythematous verrucous nodule (Figure 1) with an approximate height of 6 mm over the last year. The nodule was subjected to regular trauma and bled with minimal insult. The patient appeared otherwise healthy, with no history of skin cancer or other chronic medical conditions. There was no evidence of lymphadenopathy on examination, and no other skin abnormalities were noted. There was no reported family history of skin cancer or chronic skin conditions suggestive of increased risk for cancer or other pathologic dermatoses. Differential diagnoses for the plaque and nodule complex included verruca, Spitz nevus, or secondary neoplasm within NS.

Excision was conducted under local anesthesia without complication. An elliptical section of skin measuring 0.8×2.5 cm was excised to a depth of 3 mm. The resulting wound was closed using a complex linear repair. The section was placed in formalin specimen transport medium and sent to Walter Reed National Military Medical Center (Bethesda, Maryland). Microscopic examination of the specimen revealed features typical for NS, including mild verrucous epidermal hyperplasia, sebaceous gland hyperplasia, presence of apocrine glands, and hamartomatous follicular proliferations (Figure 2). An even more papillomatous epidermal proliferation that was comprised of atypical squamous cells was present within the lesion. Similar atypical squamous cells infiltrated the superficial dermis in nests, cords, and single cells (Figure 3A). One focus showed perineural invasion with a small superficial nerve fiber surrounded by SCC (Figure 3B). The tumor was completely excised, with negative surgical margins extending approximately 2 mm. Adjuvant radiation therapy and further specialized Mohs micrographic excision were not performed because of the clear histologic appearance of the carcinoma and strong evidence of complete excision.

At 2-week follow-up, the surgical scar on the anterior central forehead was well healed without evidence of SCC recurrence. On physical examination there was neither lymphadenopathy nor signs of neurologic deficit, except for superficial cutaneous hypoesthesia in the immediate area surrounding the healed site. Following discussion with the patient and her parents, it was decided that the patient would obtain baseline laboratory tests, chest radiography, and abdominal ultrasonography, and she would undergo serial follow-up examinations every 3 months for the next 2 years. Annual follow-up was recommended after 2 years, with the caveat to return sooner if recurrence or symptoms were to arise.

Comment

Historically, there has been variability in the histopathologic interpretation of SCC in NS in the literature. Retrospective analysis of the histologic evidence of SCC in the 2 earliest possible cases of pediatric SCC in NS have been questioned due to the lack of clinical data presented and the possibility that the diagnosis of SCC was inaccurate.⁶ Our case was histopathologically interpreted as superficially invasive, well-differentiated SCC arising within an NS; therefore, we classified this case as SCC and took every precaution to ensure the lesion was completely excised, given the potentially invasive nature of SCC.

Our case is unique because it represents SCC in NS with histologic evidence of perineural involvement. Perineural invasion is a major route of tumor spread in SCC and may result in increased occurrence of regional lymph node spread and distant metastases, with path of least resistance or neural cell adhesion as possible spreading methods.^7-9 However, there is a notable amount of prognostic variability based on tumor type, the nerve involved, and degree of involvement.⁹ It is common for cutaneous SCC to occur with invasion of small intradermal nerves, but a poor outcome is less likely in asymptomatic patients who have perineural involvement that was incidentally discovered on histologic examination.¹⁰

In our patient, the entire tumor was completely removed with local excision. Recurrence of the SCC or future symptoms of deep neural invasion were not anticipated given the postoperative evidence of clear margins in the excised skin and subdermal structures as well as the lack of preoperative and postoperative symptoms. Close clinical follow-up was warranted to monitor for early signs of recurrence or neural involvement. We have confidence that the planned follow-up regimen in our patient will reveal any early signs of new occurrence or recurrence.

In the case of recurrence, Mohs micrographic surgery would likely be indicated. We elected not to treat with adjuvant radiotherapy because its benefit in cutaneous SCC with perineural invasion is debatable based on the lack of randomized controlled clinical evidence.^10,11 The patient obtained postoperative baseline complete blood cell count with differential, posterior/anterior and lateral chest radiographs, as well as abdominal ultrasonography. Each returned negative findings of hematologic or distant organ metastases, with subsequent follow-up visits also negative for any new concerning findings.