Nonmelanoma Skin Cancer

A 70-year-old woman presented to our dermatology clinic with an enlarging lesion on the left anterior aspect of the scalp of 4 years’ duration. She had a history of breast carcinoma in the left breast with positive lymph nodes 2 years prior. Physical examination revealed a 2.5-cm pink, pearly, exophytic plaque on the left anterior aspect of the scalp. The lesion was removed with clear margins by excisional surgery.

The Diagnosis: Clear Cell Hidradenoma

Clear cell hidradenoma (CCH) is a variant of nodular hidradenoma that may contain varying quantities of solid and cystic components and comprises approximately one-third of hidradenomas.¹ Clear cell hidradenomas are slow-growing and fairly uncommon adnexal neoplasms derived from either eccrine sweat glands or apocrine glands. Some researchers have regarded hidradenomas as apocrine tumors due to evidence of apocrine decapitation secretion, whereas others note the lack of apocrine and ultrastructural features of immature eccrine glands.² Clear cell hidradenomas typically develop between the fourth and eighth decades of life, usually peaking during the sixth decade.³ Clear cell hidradenomas usually range in size from 5 to 30 mm and frequently present on the scalp, head, chest, and abdomen; rarely, CCHs present on the joint spaces of the shoulders and knees.^3-5 This neoplasm is more common in women than men³ and generally has a flesh-colored, erythematous, red-brown or blue appearance with a tendency to ulcerate and exude a serous discharge (Figure 1).⁵ The clinical differential diagnosis includes metastatic cancer (eg, renal cell carcinoma, keratoacanthoma, trichoblastoma, trichilemmoma) or other benign adnexal neoplasms.

Figure 1. A 2.5-cm pink plaque on the scalp.

Histopathologic examination of a CCH generally reveals an unencapsulated and circumscribed neoplasm in the mid or upper dermis with occasional extensions into the subcutaneous fat (Figure 2). The tumor typically presents with 2 types of cells: (1) round, fusiform, or polygonal cells with vesicular nuclei and eosinophilic cytoplasm, and (2) cells with clear cytoplasm and basophilic, often eccentrically located nuclei.⁶ Ducts are scattered within the neoplasm and are lined by a layer of cuboidal cells that can be highlighted on carcinoembryonic antigen and epithelial membrane antigen immunostaining.⁶ The tumor cells themselves are highlighted on cytokeratin AE1/AE3 staining.

Figure 2. Histopathologic examination revealed an endophytic/exophytic circumscribed neoplasm extending from the epidermis to the mid reticular dermis with several lobules composed of round cells with clear cytoplasm with several scattered ducts (H&E, original magnification ×4).

Malignant transformation rarely is associated with CCH, with de novo clear cell hidradenocarcinoma being more common. Only approximately 6.7% of CCHs have been shown to be malignant, and the malignant tumors feature nuclear atypia, abnormal mitotic figures, necrosis, and infiltration.^1,7 Although CCH is a benign adnexal neoplasm, it has a high recurrence rate (approximately 10%) following excision.⁷ The treatment of choice is complete surgical excision, though Mohs micrographic surgery is advocated, as it promotes thorough examination of the tumor margin to ensure complete tumor removal.8 Our case illustrates the importance of a broad differential diagnosis when treating patients with CCH as well as keeping in mind nonmalignant lesions are far more common than malignant lesions.  

A 70-year-old woman presented to our dermatology clinic with an enlarging lesion on the left anterior aspect of the scalp of 4 years’ duration. She had a history of breast carcinoma in the left breast with positive lymph nodes 2 years prior. Physical examination revealed a 2.5-cm pink, pearly, exophytic plaque on the left anterior aspect of the scalp. The lesion was removed with clear margins by excisional surgery.

The Diagnosis: Clear Cell Hidradenoma

Clear cell hidradenoma (CCH) is a variant of nodular hidradenoma that may contain varying quantities of solid and cystic components and comprises approximately one-third of hidradenomas.¹ Clear cell hidradenomas are slow-growing and fairly uncommon adnexal neoplasms derived from either eccrine sweat glands or apocrine glands. Some researchers have regarded hidradenomas as apocrine tumors due to evidence of apocrine decapitation secretion, whereas others note the lack of apocrine and ultrastructural features of immature eccrine glands.² Clear cell hidradenomas typically develop between the fourth and eighth decades of life, usually peaking during the sixth decade.³ Clear cell hidradenomas usually range in size from 5 to 30 mm and frequently present on the scalp, head, chest, and abdomen; rarely, CCHs present on the joint spaces of the shoulders and knees.^3-5 This neoplasm is more common in women than men³ and generally has a flesh-colored, erythematous, red-brown or blue appearance with a tendency to ulcerate and exude a serous discharge (Figure 1).⁵ The clinical differential diagnosis includes metastatic cancer (eg, renal cell carcinoma, keratoacanthoma, trichoblastoma, trichilemmoma) or other benign adnexal neoplasms.

Figure 1. A 2.5-cm pink plaque on the scalp.

Histopathologic examination of a CCH generally reveals an unencapsulated and circumscribed neoplasm in the mid or upper dermis with occasional extensions into the subcutaneous fat (Figure 2). The tumor typically presents with 2 types of cells: (1) round, fusiform, or polygonal cells with vesicular nuclei and eosinophilic cytoplasm, and (2) cells with clear cytoplasm and basophilic, often eccentrically located nuclei.⁶ Ducts are scattered within the neoplasm and are lined by a layer of cuboidal cells that can be highlighted on carcinoembryonic antigen and epithelial membrane antigen immunostaining.⁶ The tumor cells themselves are highlighted on cytokeratin AE1/AE3 staining.

Figure 2. Histopathologic examination revealed an endophytic/exophytic circumscribed neoplasm extending from the epidermis to the mid reticular dermis with several lobules composed of round cells with clear cytoplasm with several scattered ducts (H&E, original magnification ×4).

Malignant transformation rarely is associated with CCH, with de novo clear cell hidradenocarcinoma being more common. Only approximately 6.7% of CCHs have been shown to be malignant, and the malignant tumors feature nuclear atypia, abnormal mitotic figures, necrosis, and infiltration.^1,7 Although CCH is a benign adnexal neoplasm, it has a high recurrence rate (approximately 10%) following excision.⁷ The treatment of choice is complete surgical excision, though Mohs micrographic surgery is advocated, as it promotes thorough examination of the tumor margin to ensure complete tumor removal.8 Our case illustrates the importance of a broad differential diagnosis when treating patients with CCH as well as keeping in mind nonmalignant lesions are far more common than malignant lesions.  

A 70-year-old woman presented to our dermatology clinic with an enlarging lesion on the left anterior aspect of the scalp of 4 years’ duration. She had a history of breast carcinoma in the left breast with positive lymph nodes 2 years prior. Physical examination revealed a 2.5-cm pink, pearly, exophytic plaque on the left anterior aspect of the scalp. The lesion was removed with clear margins by excisional surgery.

The Diagnosis: Clear Cell Hidradenoma

Clear cell hidradenoma (CCH) is a variant of nodular hidradenoma that may contain varying quantities of solid and cystic components and comprises approximately one-third of hidradenomas.¹ Clear cell hidradenomas are slow-growing and fairly uncommon adnexal neoplasms derived from either eccrine sweat glands or apocrine glands. Some researchers have regarded hidradenomas as apocrine tumors due to evidence of apocrine decapitation secretion, whereas others note the lack of apocrine and ultrastructural features of immature eccrine glands.² Clear cell hidradenomas typically develop between the fourth and eighth decades of life, usually peaking during the sixth decade.³ Clear cell hidradenomas usually range in size from 5 to 30 mm and frequently present on the scalp, head, chest, and abdomen; rarely, CCHs present on the joint spaces of the shoulders and knees.^3-5 This neoplasm is more common in women than men³ and generally has a flesh-colored, erythematous, red-brown or blue appearance with a tendency to ulcerate and exude a serous discharge (Figure 1).⁵ The clinical differential diagnosis includes metastatic cancer (eg, renal cell carcinoma, keratoacanthoma, trichoblastoma, trichilemmoma) or other benign adnexal neoplasms.

Figure 1. A 2.5-cm pink plaque on the scalp.

Histopathologic examination of a CCH generally reveals an unencapsulated and circumscribed neoplasm in the mid or upper dermis with occasional extensions into the subcutaneous fat (Figure 2). The tumor typically presents with 2 types of cells: (1) round, fusiform, or polygonal cells with vesicular nuclei and eosinophilic cytoplasm, and (2) cells with clear cytoplasm and basophilic, often eccentrically located nuclei.⁶ Ducts are scattered within the neoplasm and are lined by a layer of cuboidal cells that can be highlighted on carcinoembryonic antigen and epithelial membrane antigen immunostaining.⁶ The tumor cells themselves are highlighted on cytokeratin AE1/AE3 staining.

Figure 2. Histopathologic examination revealed an endophytic/exophytic circumscribed neoplasm extending from the epidermis to the mid reticular dermis with several lobules composed of round cells with clear cytoplasm with several scattered ducts (H&E, original magnification ×4).

Malignant transformation rarely is associated with CCH, with de novo clear cell hidradenocarcinoma being more common. Only approximately 6.7% of CCHs have been shown to be malignant, and the malignant tumors feature nuclear atypia, abnormal mitotic figures, necrosis, and infiltration.^1,7 Although CCH is a benign adnexal neoplasm, it has a high recurrence rate (approximately 10%) following excision.⁷ The treatment of choice is complete surgical excision, though Mohs micrographic surgery is advocated, as it promotes thorough examination of the tumor margin to ensure complete tumor removal.8 Our case illustrates the importance of a broad differential diagnosis when treating patients with CCH as well as keeping in mind nonmalignant lesions are far more common than malignant lesions.  

Tumor of the follicular infundibulum (TFI) was first described by Mehregan and Butler¹ in a patient with multiple papules. It typically presents as a solitary lesion that mainly affects the face, neck, and upper trunk, and it generally occurs in elderly patients with a female predilection and occasional vulvar involvement. Sometimes TFI may coexist with an unusual trichilemmal tumor or basal cell carcinoma (BCC) with sebaceous or sweat duct differentiation. Other features of TFI include an eosinophilic cuticle, ductal differentiation, coronoid lamellae, and desmoplasia. Interestingly, approximately one-fourth of reported TFIs were found to be associated with other cutaneous lesions, including BCC, actinic keratosis, desmoplastic malignant melanoma, junctional melanocytic nevus, trichilemmoma, and epidermal inclusion cyst.² Eruptive forms of TFI are rare, presenting as macules, smooth or slightly keratotic papules, or depressed lesions with a flesh-colored erythematous or hypopigmented appearance. We report the case of a 49-year-old woman with multiple TFIs and some new features.

Case Report

A 49-year-old woman presented with multiple lesions on the arms, shoulders, trunk, buttocks, and legs of more than 3 years’ duration. According to the patient, multiple small, reddish papules gradually appeared on the arms and legs approximately 3 years prior to presentation and were accompanied by considerable pruritus. She sought medical assistance several times at local clinics. A diagnosis of eczema and prurigo was made and oral antihistamines and topical glucocorticoids were administered for more than 2 years. The pruritus was controlled to some degree but recurred after discontinuation of treatment. Five months later, the lesions flared up suddenly and rapidly to the back and buttocks, just around the skin areas treated with cupping glass, a traditional Chinese therapy, for heat syncope. She reported constant itching that kept her awake at night.

Physical examination revealed hundreds of erythematous maculopapules scattered over the arms, shoulders, trunk, buttocks, and legs. The individual lesions were minimally elevated, irregularly shaped, and slightly scaly, and they were distributed in a relatively symmetrical manner. Some of the lesions coalesced to form small plaques measuring approximately 0.5 to 3 cm in diameter (Figure 1). Interestingly, several annulated lesions with a hypopigmented center and hyperpigmented periphery could be observed at areas treated with cupping glass, showing a typical presentation of the Köbner phenomenon (Figure 2). No obvious association with sun exposure or hair loss was detected. The patient’s medical history was unremarkable and there was no known family history of similar skin lesions.

Figure 1. Erythematous maculopapules scattered over the upper back. Lesions were minimally elevated, irregularly shaped, and slightly scaly, and they were distributed in a relatively symmetrical pattern. Some of the lesions coalesced to form small plaques measuring approximately 0.5 to 3 cm in diameter. Figure 2. Several annulated lesions with a hypopigmented center and hyperpigmented periphery could be observed on the back at areas treated with cupping glass, a typical presentation of the Köbner phenomenon.

The differential diagnosis included lichen planus, prurigo, and adnexal tumors. Histopathologic examination of biopsies from lesions on the back and around the cupping glass areas revealed a benign platelike proliferation of pale-staining epithelial cells in the papillary dermis connected to the overlying epidermis with a moderate lymphatic cell infiltration (Figure 3A). Weigert staining revealed a network of elastic fibers surrounding the base of the tumor (Figure 3B). The pale epithelial cells were positive on periodic acid–Schiff staining (Figure 3C). Immunohistochemical staining revealed that the proliferation was positive for keratin 17 (Figure 3D).

These striking clinical and histological findings suggested the lesions were multiple TFIs. Treatment with tretinoin ointment 0.1% twice daily for 2 months was ineffective. The patient refused treatment with either oral acitretin or dapsone or invasive techniques such as lasers and cryotherapy. She has been on careful follow-up for the last 2 years with new lesions appearing intermittently.

Comment

The etiology of TFI still is unknown but may be related to environmental factors or genetic changes. Tumors of the follicular infundibulum generally are classified as solitary, eruptive, associated with other lesions of Cowden disease, associated with a single tumor, or TFI-like epidermal changes.³ The eruptive form has seldom been reported to date. Eruptive TFIs are nonspecific, ranging in number from several to more than 100. Clinical characteristics and distribution of the lesions can vary from patient to patient, but the lesions tend to be quite monomorphous, even in cases with more than 100 lesions.⁴ Histopathologic features usually are typical and distinctive, allowing its definite diagnosis. To confirm the diagnosis, the immunohistochemical profile may be useful to characterize its follicular origin, which is positive for keratin 17. Tumors of the follicular infundibulum usually are benign; however, in one patient with more than 100 lesions, there was documented transformation into BCC.⁵ Due to the potential for malignant transformation as well as its occurrence within the spectrum of lesions associated with Cowden disease,^6,7 long-term supervision of TFI is strongly recommended, as was the case with our patient.

A remarkable feature in our case was the patient’s severe pruritus, as most reported cases have been asymptomatic. The increased association with other cutaneous lesions,² the Köbner phenomenon, and the underlying inflammatory cell infiltration of the tumors in our case strongly suggested that eruptive TFI may represent a kind of cutaneous reaction.

Figure 3. Histopathologically, a benign platelike proliferation of pale-staining keratinocytes and follicular structures could be observed in the papillary dermis connected to the overlying epidermis with a moderate lymphatic cell infiltration (A)(H&E, original magnification ×40). Weigert staining showed a network of black-blue elastic fi-bers at the base of the tumor (B) (original magnification ×200). The pale kerat- inocytes were positive on periodic acid–Schiff staining (C)(original magnification ×100). Immunohis-tochemically, the proliferation of keratinocytes was positive for keratin 17 (D)(diaminobenzidine, original magnification ×100).

Conclusion

The clinical findings of severe pruritus and the Köbner phenomenon in our patient further expand the constellation of the clinical presentation of the eruptive variant of TFI.

Tumor of the follicular infundibulum (TFI) was first described by Mehregan and Butler¹ in a patient with multiple papules. It typically presents as a solitary lesion that mainly affects the face, neck, and upper trunk, and it generally occurs in elderly patients with a female predilection and occasional vulvar involvement. Sometimes TFI may coexist with an unusual trichilemmal tumor or basal cell carcinoma (BCC) with sebaceous or sweat duct differentiation. Other features of TFI include an eosinophilic cuticle, ductal differentiation, coronoid lamellae, and desmoplasia. Interestingly, approximately one-fourth of reported TFIs were found to be associated with other cutaneous lesions, including BCC, actinic keratosis, desmoplastic malignant melanoma, junctional melanocytic nevus, trichilemmoma, and epidermal inclusion cyst.² Eruptive forms of TFI are rare, presenting as macules, smooth or slightly keratotic papules, or depressed lesions with a flesh-colored erythematous or hypopigmented appearance. We report the case of a 49-year-old woman with multiple TFIs and some new features.

Case Report

A 49-year-old woman presented with multiple lesions on the arms, shoulders, trunk, buttocks, and legs of more than 3 years’ duration. According to the patient, multiple small, reddish papules gradually appeared on the arms and legs approximately 3 years prior to presentation and were accompanied by considerable pruritus. She sought medical assistance several times at local clinics. A diagnosis of eczema and prurigo was made and oral antihistamines and topical glucocorticoids were administered for more than 2 years. The pruritus was controlled to some degree but recurred after discontinuation of treatment. Five months later, the lesions flared up suddenly and rapidly to the back and buttocks, just around the skin areas treated with cupping glass, a traditional Chinese therapy, for heat syncope. She reported constant itching that kept her awake at night.

Physical examination revealed hundreds of erythematous maculopapules scattered over the arms, shoulders, trunk, buttocks, and legs. The individual lesions were minimally elevated, irregularly shaped, and slightly scaly, and they were distributed in a relatively symmetrical manner. Some of the lesions coalesced to form small plaques measuring approximately 0.5 to 3 cm in diameter (Figure 1). Interestingly, several annulated lesions with a hypopigmented center and hyperpigmented periphery could be observed at areas treated with cupping glass, showing a typical presentation of the Köbner phenomenon (Figure 2). No obvious association with sun exposure or hair loss was detected. The patient’s medical history was unremarkable and there was no known family history of similar skin lesions.

Figure 1. Erythematous maculopapules scattered over the upper back. Lesions were minimally elevated, irregularly shaped, and slightly scaly, and they were distributed in a relatively symmetrical pattern. Some of the lesions coalesced to form small plaques measuring approximately 0.5 to 3 cm in diameter. Figure 2. Several annulated lesions with a hypopigmented center and hyperpigmented periphery could be observed on the back at areas treated with cupping glass, a typical presentation of the Köbner phenomenon.

The differential diagnosis included lichen planus, prurigo, and adnexal tumors. Histopathologic examination of biopsies from lesions on the back and around the cupping glass areas revealed a benign platelike proliferation of pale-staining epithelial cells in the papillary dermis connected to the overlying epidermis with a moderate lymphatic cell infiltration (Figure 3A). Weigert staining revealed a network of elastic fibers surrounding the base of the tumor (Figure 3B). The pale epithelial cells were positive on periodic acid–Schiff staining (Figure 3C). Immunohistochemical staining revealed that the proliferation was positive for keratin 17 (Figure 3D).

These striking clinical and histological findings suggested the lesions were multiple TFIs. Treatment with tretinoin ointment 0.1% twice daily for 2 months was ineffective. The patient refused treatment with either oral acitretin or dapsone or invasive techniques such as lasers and cryotherapy. She has been on careful follow-up for the last 2 years with new lesions appearing intermittently.

Comment

The etiology of TFI still is unknown but may be related to environmental factors or genetic changes. Tumors of the follicular infundibulum generally are classified as solitary, eruptive, associated with other lesions of Cowden disease, associated with a single tumor, or TFI-like epidermal changes.³ The eruptive form has seldom been reported to date. Eruptive TFIs are nonspecific, ranging in number from several to more than 100. Clinical characteristics and distribution of the lesions can vary from patient to patient, but the lesions tend to be quite monomorphous, even in cases with more than 100 lesions.⁴ Histopathologic features usually are typical and distinctive, allowing its definite diagnosis. To confirm the diagnosis, the immunohistochemical profile may be useful to characterize its follicular origin, which is positive for keratin 17. Tumors of the follicular infundibulum usually are benign; however, in one patient with more than 100 lesions, there was documented transformation into BCC.⁵ Due to the potential for malignant transformation as well as its occurrence within the spectrum of lesions associated with Cowden disease,^6,7 long-term supervision of TFI is strongly recommended, as was the case with our patient.

A remarkable feature in our case was the patient’s severe pruritus, as most reported cases have been asymptomatic. The increased association with other cutaneous lesions,² the Köbner phenomenon, and the underlying inflammatory cell infiltration of the tumors in our case strongly suggested that eruptive TFI may represent a kind of cutaneous reaction.

Figure 3. Histopathologically, a benign platelike proliferation of pale-staining keratinocytes and follicular structures could be observed in the papillary dermis connected to the overlying epidermis with a moderate lymphatic cell infiltration (A)(H&E, original magnification ×40). Weigert staining showed a network of black-blue elastic fi-bers at the base of the tumor (B) (original magnification ×200). The pale kerat- inocytes were positive on periodic acid–Schiff staining (C)(original magnification ×100). Immunohis-tochemically, the proliferation of keratinocytes was positive for keratin 17 (D)(diaminobenzidine, original magnification ×100).

Conclusion

The clinical findings of severe pruritus and the Köbner phenomenon in our patient further expand the constellation of the clinical presentation of the eruptive variant of TFI.

Tumor of the follicular infundibulum (TFI) was first described by Mehregan and Butler¹ in a patient with multiple papules. It typically presents as a solitary lesion that mainly affects the face, neck, and upper trunk, and it generally occurs in elderly patients with a female predilection and occasional vulvar involvement. Sometimes TFI may coexist with an unusual trichilemmal tumor or basal cell carcinoma (BCC) with sebaceous or sweat duct differentiation. Other features of TFI include an eosinophilic cuticle, ductal differentiation, coronoid lamellae, and desmoplasia. Interestingly, approximately one-fourth of reported TFIs were found to be associated with other cutaneous lesions, including BCC, actinic keratosis, desmoplastic malignant melanoma, junctional melanocytic nevus, trichilemmoma, and epidermal inclusion cyst.² Eruptive forms of TFI are rare, presenting as macules, smooth or slightly keratotic papules, or depressed lesions with a flesh-colored erythematous or hypopigmented appearance. We report the case of a 49-year-old woman with multiple TFIs and some new features.

Case Report

A 49-year-old woman presented with multiple lesions on the arms, shoulders, trunk, buttocks, and legs of more than 3 years’ duration. According to the patient, multiple small, reddish papules gradually appeared on the arms and legs approximately 3 years prior to presentation and were accompanied by considerable pruritus. She sought medical assistance several times at local clinics. A diagnosis of eczema and prurigo was made and oral antihistamines and topical glucocorticoids were administered for more than 2 years. The pruritus was controlled to some degree but recurred after discontinuation of treatment. Five months later, the lesions flared up suddenly and rapidly to the back and buttocks, just around the skin areas treated with cupping glass, a traditional Chinese therapy, for heat syncope. She reported constant itching that kept her awake at night.

Physical examination revealed hundreds of erythematous maculopapules scattered over the arms, shoulders, trunk, buttocks, and legs. The individual lesions were minimally elevated, irregularly shaped, and slightly scaly, and they were distributed in a relatively symmetrical manner. Some of the lesions coalesced to form small plaques measuring approximately 0.5 to 3 cm in diameter (Figure 1). Interestingly, several annulated lesions with a hypopigmented center and hyperpigmented periphery could be observed at areas treated with cupping glass, showing a typical presentation of the Köbner phenomenon (Figure 2). No obvious association with sun exposure or hair loss was detected. The patient’s medical history was unremarkable and there was no known family history of similar skin lesions.

Figure 1. Erythematous maculopapules scattered over the upper back. Lesions were minimally elevated, irregularly shaped, and slightly scaly, and they were distributed in a relatively symmetrical pattern. Some of the lesions coalesced to form small plaques measuring approximately 0.5 to 3 cm in diameter. Figure 2. Several annulated lesions with a hypopigmented center and hyperpigmented periphery could be observed on the back at areas treated with cupping glass, a typical presentation of the Köbner phenomenon.

The differential diagnosis included lichen planus, prurigo, and adnexal tumors. Histopathologic examination of biopsies from lesions on the back and around the cupping glass areas revealed a benign platelike proliferation of pale-staining epithelial cells in the papillary dermis connected to the overlying epidermis with a moderate lymphatic cell infiltration (Figure 3A). Weigert staining revealed a network of elastic fibers surrounding the base of the tumor (Figure 3B). The pale epithelial cells were positive on periodic acid–Schiff staining (Figure 3C). Immunohistochemical staining revealed that the proliferation was positive for keratin 17 (Figure 3D).

These striking clinical and histological findings suggested the lesions were multiple TFIs. Treatment with tretinoin ointment 0.1% twice daily for 2 months was ineffective. The patient refused treatment with either oral acitretin or dapsone or invasive techniques such as lasers and cryotherapy. She has been on careful follow-up for the last 2 years with new lesions appearing intermittently.

Comment

The etiology of TFI still is unknown but may be related to environmental factors or genetic changes. Tumors of the follicular infundibulum generally are classified as solitary, eruptive, associated with other lesions of Cowden disease, associated with a single tumor, or TFI-like epidermal changes.³ The eruptive form has seldom been reported to date. Eruptive TFIs are nonspecific, ranging in number from several to more than 100. Clinical characteristics and distribution of the lesions can vary from patient to patient, but the lesions tend to be quite monomorphous, even in cases with more than 100 lesions.⁴ Histopathologic features usually are typical and distinctive, allowing its definite diagnosis. To confirm the diagnosis, the immunohistochemical profile may be useful to characterize its follicular origin, which is positive for keratin 17. Tumors of the follicular infundibulum usually are benign; however, in one patient with more than 100 lesions, there was documented transformation into BCC.⁵ Due to the potential for malignant transformation as well as its occurrence within the spectrum of lesions associated with Cowden disease,^6,7 long-term supervision of TFI is strongly recommended, as was the case with our patient.

A remarkable feature in our case was the patient’s severe pruritus, as most reported cases have been asymptomatic. The increased association with other cutaneous lesions,² the Köbner phenomenon, and the underlying inflammatory cell infiltration of the tumors in our case strongly suggested that eruptive TFI may represent a kind of cutaneous reaction.

Figure 3. Histopathologically, a benign platelike proliferation of pale-staining keratinocytes and follicular structures could be observed in the papillary dermis connected to the overlying epidermis with a moderate lymphatic cell infiltration (A)(H&E, original magnification ×40). Weigert staining showed a network of black-blue elastic fi-bers at the base of the tumor (B) (original magnification ×200). The pale kerat- inocytes were positive on periodic acid–Schiff staining (C)(original magnification ×100). Immunohis-tochemically, the proliferation of keratinocytes was positive for keratin 17 (D)(diaminobenzidine, original magnification ×100).

Conclusion

The clinical findings of severe pruritus and the Köbner phenomenon in our patient further expand the constellation of the clinical presentation of the eruptive variant of TFI.

SAN DIEGO – Histology of basal cell carcinomas removed by Mohs micrographic surgery showed that presurgical biopsies had not revealed all tumor subtypes in 64% of cases, and had underestimated the aggressiveness of the tumors 24% of the time, according to data from a large, multicenter, retrospective study.

“Unfortunately, while cheap and cost-effective, biopsies are a subsample of the full malignancy,” said Dr. Murad Alam, professor of dermatology, otolaryngology, and surgery at Northwestern University in Chicago. “Skin biopsy of basal cell carcinoma [BCC] may fail to detect all BCC subtypes, and as such may underestimate the aggressiveness of an individual BCC tumor.”

©Kelly Nelson/National Cancer Institute

Basal cell carcinoma is the most common skin cancer worldwide, and can broadly be grouped into aggressive and indolent types, Dr. Alam said at the annual meeting of the American Society for Dermatologic Surgery. But tumors often show mixed histology, and cancer treatment needs to target the most aggressive subtype present in the tumor, he added. Results of past studies suggested that biopsies of BCCs could miss tumor subtypes, but the current research is the first large, multicenter study to confirm these findings, he and his associates said.

For the study, the investigators compared biopsy reports and microscopic slides of Mohs micrographic surgery (MMS) specimens from 871 consecutive cases of BCC treated at three hospitals in Illinois from 2013 to 2014. Patients first underwent biopsies, followed by complete excision of their tumors during MMS. Almost 59% of patients were male, and tumors were most commonly removed from the nose or cheek. In all, 78% of biopsies were obtained by the shave technique, but punch and excisional biopsies also were performed, the researchers noted.

Using standard definitions of BCC subtypes, the investigators compared levels of concordance between biopsy and MMS histology findings, Dr. Alam said. They also grouped tumor specimens as high risk (that is, infiltrative, morpheic, micronodular, basosquamous) or low risk (superficial or nodular), and determined whether tumor biopsy and MMS histology yielded the same or discordant risk assessments, he added.

Biopsies identified only 18% of tumors as being of mixed histology, compared with 57% of MMS specimens, said Dr. Alam. Biopsy results matched MMS histologies in only 31% of cases, while in 64% of cases, the MMS specimen yielded more tumor subtypes than the biopsy specimen. The researchers noted that biopsy yielded more subtypes than did MMS in 4% of cases, and that MMS and biopsy subtypes were fully discordant in only four cases.

Dr. Alam and his associates declared no external funding sources or conflicts of interest.

SAN DIEGO – Histology of basal cell carcinomas removed by Mohs micrographic surgery showed that presurgical biopsies had not revealed all tumor subtypes in 64% of cases, and had underestimated the aggressiveness of the tumors 24% of the time, according to data from a large, multicenter, retrospective study.

“Unfortunately, while cheap and cost-effective, biopsies are a subsample of the full malignancy,” said Dr. Murad Alam, professor of dermatology, otolaryngology, and surgery at Northwestern University in Chicago. “Skin biopsy of basal cell carcinoma [BCC] may fail to detect all BCC subtypes, and as such may underestimate the aggressiveness of an individual BCC tumor.”

©Kelly Nelson/National Cancer Institute

Basal cell carcinoma is the most common skin cancer worldwide, and can broadly be grouped into aggressive and indolent types, Dr. Alam said at the annual meeting of the American Society for Dermatologic Surgery. But tumors often show mixed histology, and cancer treatment needs to target the most aggressive subtype present in the tumor, he added. Results of past studies suggested that biopsies of BCCs could miss tumor subtypes, but the current research is the first large, multicenter study to confirm these findings, he and his associates said.

For the study, the investigators compared biopsy reports and microscopic slides of Mohs micrographic surgery (MMS) specimens from 871 consecutive cases of BCC treated at three hospitals in Illinois from 2013 to 2014. Patients first underwent biopsies, followed by complete excision of their tumors during MMS. Almost 59% of patients were male, and tumors were most commonly removed from the nose or cheek. In all, 78% of biopsies were obtained by the shave technique, but punch and excisional biopsies also were performed, the researchers noted.

Using standard definitions of BCC subtypes, the investigators compared levels of concordance between biopsy and MMS histology findings, Dr. Alam said. They also grouped tumor specimens as high risk (that is, infiltrative, morpheic, micronodular, basosquamous) or low risk (superficial or nodular), and determined whether tumor biopsy and MMS histology yielded the same or discordant risk assessments, he added.

Biopsies identified only 18% of tumors as being of mixed histology, compared with 57% of MMS specimens, said Dr. Alam. Biopsy results matched MMS histologies in only 31% of cases, while in 64% of cases, the MMS specimen yielded more tumor subtypes than the biopsy specimen. The researchers noted that biopsy yielded more subtypes than did MMS in 4% of cases, and that MMS and biopsy subtypes were fully discordant in only four cases.

Dr. Alam and his associates declared no external funding sources or conflicts of interest.

SAN DIEGO – Histology of basal cell carcinomas removed by Mohs micrographic surgery showed that presurgical biopsies had not revealed all tumor subtypes in 64% of cases, and had underestimated the aggressiveness of the tumors 24% of the time, according to data from a large, multicenter, retrospective study.

“Unfortunately, while cheap and cost-effective, biopsies are a subsample of the full malignancy,” said Dr. Murad Alam, professor of dermatology, otolaryngology, and surgery at Northwestern University in Chicago. “Skin biopsy of basal cell carcinoma [BCC] may fail to detect all BCC subtypes, and as such may underestimate the aggressiveness of an individual BCC tumor.”

©Kelly Nelson/National Cancer Institute

Basal cell carcinoma is the most common skin cancer worldwide, and can broadly be grouped into aggressive and indolent types, Dr. Alam said at the annual meeting of the American Society for Dermatologic Surgery. But tumors often show mixed histology, and cancer treatment needs to target the most aggressive subtype present in the tumor, he added. Results of past studies suggested that biopsies of BCCs could miss tumor subtypes, but the current research is the first large, multicenter study to confirm these findings, he and his associates said.

For the study, the investigators compared biopsy reports and microscopic slides of Mohs micrographic surgery (MMS) specimens from 871 consecutive cases of BCC treated at three hospitals in Illinois from 2013 to 2014. Patients first underwent biopsies, followed by complete excision of their tumors during MMS. Almost 59% of patients were male, and tumors were most commonly removed from the nose or cheek. In all, 78% of biopsies were obtained by the shave technique, but punch and excisional biopsies also were performed, the researchers noted.

Using standard definitions of BCC subtypes, the investigators compared levels of concordance between biopsy and MMS histology findings, Dr. Alam said. They also grouped tumor specimens as high risk (that is, infiltrative, morpheic, micronodular, basosquamous) or low risk (superficial or nodular), and determined whether tumor biopsy and MMS histology yielded the same or discordant risk assessments, he added.

Biopsies identified only 18% of tumors as being of mixed histology, compared with 57% of MMS specimens, said Dr. Alam. Biopsy results matched MMS histologies in only 31% of cases, while in 64% of cases, the MMS specimen yielded more tumor subtypes than the biopsy specimen. The researchers noted that biopsy yielded more subtypes than did MMS in 4% of cases, and that MMS and biopsy subtypes were fully discordant in only four cases.

Dr. Alam and his associates declared no external funding sources or conflicts of interest.

SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.

Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.

Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.

Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.

Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.

Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.

SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.

Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.

Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.

Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.

Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.

Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.

SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.

Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.

Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.

Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.

Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.

Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.

In a June 29 article published online in Molecular Carcinogenesis, Fenton et al demonstrated that topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse.

Dasatinib is a tyrosine kinase inhibitor currently used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Its mechanism of action is to block the activity of tyrosine kinases by attaching to their adenosine triphosphate–binding site. It can inhibit the activity of the following tyrosine kinases: Src family kinases (SFK), break point cluster region-Abelson (Bcr-Abl), Ephrin type-A receptor 2 (EphA2), platelet-derived growth factor receptor, and mast/stem cell factor receptor (also called CD117 or c-Kit).

Src family kinases are associated with transformation of cells and progression of cancer. Elevated Src family kinases activity is present in the majority of human carcinomas.

Fyn, a nonreceptor tyrosine kinase, is a member of the Src family kinases. Cell growth, cell migration, and protein kinase B (Akt)–mediated inhibition of apoptosis are influenced by Fyn activity. In addition, Fyn activity is overexpressed in cutaneous squamous cell carcinoma.

In conclusion, dasatinib—an Src family kinases inhibitor—was able to inhibit Fyn activity and thereby reduce UV-induced skin carcinogenesis.

What’s the issue?

In 1962, Falkson and Schulz (Br J Dermatol. 1962;74:229-236) noted not only inflammation and subsequent resolution of actinic keratoses after exposure to sunlight in a woman with colon cancer being treated with systemic 5-fluorouracil but also several other patients whose keratoses were seen to disappear during therapy without preceding erythema. Omura and Torre (JAMA. 1969;208:150-151) confirmed these observations in a woman with breast cancer whose actinic keratoses became inflamed after receiving intravenous 5-fluorouracil and subsequently faded. The route of drug administration was modified and 5-fluorouracil was applied topically. Today topical 5-fluorouracil is still used for the treatment of actinic keratoses.

Topical application of nitrogen mustard is used in the treatment of cutaneous T-cell lymphoma. In addition, intralesional administration of systemic antineoplastic agents has been used to treat cutaneous neoplasms: methotrexate for keratoacanthomas and rituximab for primary cutaneous B-cell lymphomas.

The Fenton et al study suggests that topical dasatinib may be a potential therapeutic intervention for the treatment of cutaneous squamous cell carcinoma. The investigators not only demonstrate laboratory data from mouse studies but also provide a potential molecular mechanism for drug-associated tumor suppression. Indeed, dasatinib solution, dasatinib cream, or both may be the next innovative therapy for the suppression of cutaneous squamous cell carcinoma in organ transplant and immunocompromised patients and for the potential management of this skin cancer in immunocompetent individuals. What do you think?

We want to know your views! Tell us what you think.

In a June 29 article published online in Molecular Carcinogenesis, Fenton et al demonstrated that topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse.

Dasatinib is a tyrosine kinase inhibitor currently used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Its mechanism of action is to block the activity of tyrosine kinases by attaching to their adenosine triphosphate–binding site. It can inhibit the activity of the following tyrosine kinases: Src family kinases (SFK), break point cluster region-Abelson (Bcr-Abl), Ephrin type-A receptor 2 (EphA2), platelet-derived growth factor receptor, and mast/stem cell factor receptor (also called CD117 or c-Kit).

Src family kinases are associated with transformation of cells and progression of cancer. Elevated Src family kinases activity is present in the majority of human carcinomas.

Fyn, a nonreceptor tyrosine kinase, is a member of the Src family kinases. Cell growth, cell migration, and protein kinase B (Akt)–mediated inhibition of apoptosis are influenced by Fyn activity. In addition, Fyn activity is overexpressed in cutaneous squamous cell carcinoma.

In conclusion, dasatinib—an Src family kinases inhibitor—was able to inhibit Fyn activity and thereby reduce UV-induced skin carcinogenesis.

What’s the issue?

In 1962, Falkson and Schulz (Br J Dermatol. 1962;74:229-236) noted not only inflammation and subsequent resolution of actinic keratoses after exposure to sunlight in a woman with colon cancer being treated with systemic 5-fluorouracil but also several other patients whose keratoses were seen to disappear during therapy without preceding erythema. Omura and Torre (JAMA. 1969;208:150-151) confirmed these observations in a woman with breast cancer whose actinic keratoses became inflamed after receiving intravenous 5-fluorouracil and subsequently faded. The route of drug administration was modified and 5-fluorouracil was applied topically. Today topical 5-fluorouracil is still used for the treatment of actinic keratoses.

Topical application of nitrogen mustard is used in the treatment of cutaneous T-cell lymphoma. In addition, intralesional administration of systemic antineoplastic agents has been used to treat cutaneous neoplasms: methotrexate for keratoacanthomas and rituximab for primary cutaneous B-cell lymphomas.

The Fenton et al study suggests that topical dasatinib may be a potential therapeutic intervention for the treatment of cutaneous squamous cell carcinoma. The investigators not only demonstrate laboratory data from mouse studies but also provide a potential molecular mechanism for drug-associated tumor suppression. Indeed, dasatinib solution, dasatinib cream, or both may be the next innovative therapy for the suppression of cutaneous squamous cell carcinoma in organ transplant and immunocompromised patients and for the potential management of this skin cancer in immunocompetent individuals. What do you think?

We want to know your views! Tell us what you think.

In a June 29 article published online in Molecular Carcinogenesis, Fenton et al demonstrated that topical dasatinib treatment of UVB-exposed SKH1 hairless mice reduced the total tumor burden (ie, benign tumors, atypical benign tumors, squamous cell carcinomas) per mouse.

Dasatinib is a tyrosine kinase inhibitor currently used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. Its mechanism of action is to block the activity of tyrosine kinases by attaching to their adenosine triphosphate–binding site. It can inhibit the activity of the following tyrosine kinases: Src family kinases (SFK), break point cluster region-Abelson (Bcr-Abl), Ephrin type-A receptor 2 (EphA2), platelet-derived growth factor receptor, and mast/stem cell factor receptor (also called CD117 or c-Kit).

Src family kinases are associated with transformation of cells and progression of cancer. Elevated Src family kinases activity is present in the majority of human carcinomas.

Fyn, a nonreceptor tyrosine kinase, is a member of the Src family kinases. Cell growth, cell migration, and protein kinase B (Akt)–mediated inhibition of apoptosis are influenced by Fyn activity. In addition, Fyn activity is overexpressed in cutaneous squamous cell carcinoma.

In conclusion, dasatinib—an Src family kinases inhibitor—was able to inhibit Fyn activity and thereby reduce UV-induced skin carcinogenesis.

What’s the issue?

In 1962, Falkson and Schulz (Br J Dermatol. 1962;74:229-236) noted not only inflammation and subsequent resolution of actinic keratoses after exposure to sunlight in a woman with colon cancer being treated with systemic 5-fluorouracil but also several other patients whose keratoses were seen to disappear during therapy without preceding erythema. Omura and Torre (JAMA. 1969;208:150-151) confirmed these observations in a woman with breast cancer whose actinic keratoses became inflamed after receiving intravenous 5-fluorouracil and subsequently faded. The route of drug administration was modified and 5-fluorouracil was applied topically. Today topical 5-fluorouracil is still used for the treatment of actinic keratoses.

Topical application of nitrogen mustard is used in the treatment of cutaneous T-cell lymphoma. In addition, intralesional administration of systemic antineoplastic agents has been used to treat cutaneous neoplasms: methotrexate for keratoacanthomas and rituximab for primary cutaneous B-cell lymphomas.

The Fenton et al study suggests that topical dasatinib may be a potential therapeutic intervention for the treatment of cutaneous squamous cell carcinoma. The investigators not only demonstrate laboratory data from mouse studies but also provide a potential molecular mechanism for drug-associated tumor suppression. Indeed, dasatinib solution, dasatinib cream, or both may be the next innovative therapy for the suppression of cutaneous squamous cell carcinoma in organ transplant and immunocompromised patients and for the potential management of this skin cancer in immunocompetent individuals. What do you think?

We want to know your views! Tell us what you think.

A 59-year-old white man presented with 2 large erythematous lesions on the right side of the chest wall that had gradually progressed over the last 1.5 years. The patient denied any fever, night sweats, fatigue, unintentional weight loss, or loss of appetite. Physical examination revealed 2 large, well-circumscribed, nearly contiguous, firm, erythematous tumors. One tumor measured 7.5×4.5 cm and the other measured 4×3.5 cm.

The Diagnosis: Cutaneous B-cell Lymphoma

Biopsies from the right side of the chest wall (Figure 1) revealed an atypical dense and diffuse lymphocytic infiltrate throughout the dermis. There was extensive crush artifact throughout the specimen. However, the findings were consistent with cutaneous B-cell lymphoma (CBCL), and the diffuse large B-cell type was favored (Figure 2). Atypical lymphocytes stained positively for antibodies against CD20 (Figure 3), CD79a, and BCL-6, and stained negatively for antibodies against MUM-1 and BCL-2. Although flow cytometry revealed no definitive immunophenotypic lymphoma population, polymerase chain reaction analysis revealed a monoclonal immunoglobulin heavy chain gene rearrangement. Computed tomography (CT) scans of the chest, abdomen, and pelvis were unremarkable. A preliminary diagnosis of primary CBCL (PCBCL) was formulated. Diffuse large B-cell lymphoma (DLBCL) and follicle center lymphoma subtypes were each considered, which triggered further workup to rule out systemic involvement.

Figure 1. Erythematous firm tumors of the right side of the chest wall (A and B).

Figure 2. Atypical lymphocytic infiltrate with background crush artifact (A and B)(both H&E, original magnifications ×20 and ×40).

Figure 3. Atypical lymphocytes stained positively for antibodies against CD20 (original magnification ×40).

Figure 4. A focus of increased radiotracer deposition is seen in the left proximal humerus on positron emission tomography–computed tomography scanning.

A bone marrow biopsy from the posterior iliac crest revealed normocellular bone marrow with normal trilineage hematopoiesis. However, whole-body staging with positron emission tomography (PET)–CT scanning revealed osseous disease in the left proximal humerus (Figure 4) as well as a slightly hypermetabolic right axillary lymph node. Magnetic resonance imaging of the brain showed no evidence of intracranial disease. Because of the apparent systemic involvement, stage IV non-Hodgkin lymphoma (DLBCL) became the new suspected diagnosis. The patient was started on the first of 6 cycles of chemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and the skin lesions quickly dissipated and flattened. A faint pink discoloration remained over a slightly indented area. A repeat PET-CT scan following 4 cycles of R-CHOP chemotherapy also confirmed a complete response to therapy.

In general, CBCL tends to affect adults and presents as relatively firm and plum-colored papules, nodules, tumors, or plaques, which can be either fast or slow growing. Cutaneous B-cell lymphoma may be primary or secondary to systemic involvement. Primary CBCL refers to a group of non-Hodgkin lymphomas that initially present in the skin with no evidence of extracutaneous involvement at the time of diagnosis.^1,2 Secondary CBCL (SCBCL) refers to cutaneous disease that occurs secondary to systemic B-cell lymphoma. Detecting systemic involvement and distinguishing between PCBCL and SCBCL is valuable in determining prognosis and therapeutic options, as subtypes of PCBCL often have an improved prognosis and may be treated with local irradiation.

The initial staging techniques that are preferred for cutaneous lymphomas have been debated.^3-5 For cutaneous lymphomas, except mycosis fungoides and Sézary syndrome, the International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer recommends obtaining a complete blood cell count with differential; complete metabolic studies including lactate dehydrogenase; and imaging studies of the chest, abdomen, and pelvis. Bone marrow biopsies and imaging studies of the neck or whole-body PET-CT scanning also may be useful depending on the clinical scenario.³ Although a more limited workup may be sufficient for PCBCLs such as primary cutaneous marginal zone lymphoma,⁵ a bone marrow biopsy is recommended for cases of primary cutaneous DLBCL (leg type).³ Senff et al⁵ supported the use of a bone marrow biopsy in the evaluation of follicle center lymphomas first presenting in the skin, though this method is controversial. In our patient, the laboratory results; bone marrow biopsy; and CT scan of the chest, abdomen, and pelvis failed to suggest extracutaneous disease, while the PET-CT scan revealed systemic involvement.

The differential diagnosis of CBCL includes cutaneous lymphoid hyperplasia (pseudolymphoma), which may be the result of insults such as arthropod bites, stings, vaccinations, or trauma. The clinical presentation, histology, and results of molecular studies and immunohistochemistry are essential in differentiating benign versus malignant processes.⁶ Lymphomas are expected to be larger and more persistent than benign processes, demonstrating an atypical lymphocytic infiltrate and monoclonality; immunohistochemistry will aid in the distinction between B-cell and T-cell processes and can delineate the type of B-cell lymphoma. Histology for CBCL typically reveals an atypical lymphocytic infiltrate showing a CD20⁺ and CD79a⁺ immunophenotype. Staining for antibodies against BCL-2, BCL-6, CD10, and MUM-1 also plays an important role in the diagnosis of cutaneous lymphoma and determining where the lesion(s) falls within the classification schemes. For example, to differentiate between primary cutaneous lymphoma subtypes, BCL-2 negativity and BCL-6 positivity in the context of a CD20⁺ and CD79a⁺ immunophenotype supports a follicle center lymphoma or a DLBCL (non–leg type). By contrast, CD20, CD79a, BCL-2, and MUM-1 positivity would favor a DLBCL (leg type).⁷

The natural history and therapeutic options differ greatly between subtypes of CBCL. For example, the prognosis of primary cutaneous follicle center lymphoma is generally favorable with a 5-year disease-specific survival rate of roughly 95%, and radiation therapy is recommended as a first-line therapy for localized disease.^2,8 Conversely, primary cutaneous DLBCL (leg type) frequently spreads to extracutaneous sites⁸ and carries a much lower estimated 5-year disease-specific survival rate of 55%.² Chemotherapy with R-CHOP is typically included in initial therapy for primary cutaneous DLBCL (leg type).⁸ The prognosis of systemic B-cell lymphomas also is highly variable and may depend on the type of B-cell lymphoma, the stage of disease at diagnosis, histologic and immunologic characteristics, and the therapy received. Wright et al⁹ reported that patients with systemic germinal center B cell–like DLBCL had a 5-year survival rate of 62%, whereas patients with activated B cell–like variants of DLBCL had a 5-year survival rate of 26%. Expression of CD40 may be a favorable prognostic factor following treatment with systemic chemotherapy in patients with DLBCL,¹⁰ whereas FOXP1 protein overexpression is correlated with poor disease-specific survival in certain DLBCL phenotypes.¹¹

Although it is uncertain whether the cutaneous lesions preceded systemic disease in our patient, the cutaneous lesions could be arbitrarily classified as secondary because extracutaneous disease was discovered within 6 months of the initial diagnosis.¹ However, classifying the CBCL as primary or secondary did not alter the course of treatment in our patient, as the presumed systemic disease necessitated treatment with systemic chemotherapy; both PCBCLs that develop systemic involvement and SCBCLs (primary extracutaneous disease) usually are treated with systemic chemotherapy. Our case highlights the importance of whole-body staging, as PET-CT scanning changed the course of care by detecting osseous involvement, necessitating systemic therapy as opposed to local radiation therapy alone. A multidisciplinary team with a focus on the diagnosis and management of cutaneous lymphomas helped streamline our patient’s laboratory testing and imaging studies, diagnostic and therapeutic decision making, and treatment implementation. Open channels and frequent opportunities for communication among dermatologists, dermatopathologists, medical oncologists, hematopathologists, radiologists, and radiation oncologists are needed to optimize and coordinate care for patients with cutaneous lymphoma who require transdisciplinary care.

Acknowledgement—The authors would like to thank Henry Koon, MD (hematology/oncology), for his input and expertise.

A 59-year-old white man presented with 2 large erythematous lesions on the right side of the chest wall that had gradually progressed over the last 1.5 years. The patient denied any fever, night sweats, fatigue, unintentional weight loss, or loss of appetite. Physical examination revealed 2 large, well-circumscribed, nearly contiguous, firm, erythematous tumors. One tumor measured 7.5×4.5 cm and the other measured 4×3.5 cm.

The Diagnosis: Cutaneous B-cell Lymphoma

Biopsies from the right side of the chest wall (Figure 1) revealed an atypical dense and diffuse lymphocytic infiltrate throughout the dermis. There was extensive crush artifact throughout the specimen. However, the findings were consistent with cutaneous B-cell lymphoma (CBCL), and the diffuse large B-cell type was favored (Figure 2). Atypical lymphocytes stained positively for antibodies against CD20 (Figure 3), CD79a, and BCL-6, and stained negatively for antibodies against MUM-1 and BCL-2. Although flow cytometry revealed no definitive immunophenotypic lymphoma population, polymerase chain reaction analysis revealed a monoclonal immunoglobulin heavy chain gene rearrangement. Computed tomography (CT) scans of the chest, abdomen, and pelvis were unremarkable. A preliminary diagnosis of primary CBCL (PCBCL) was formulated. Diffuse large B-cell lymphoma (DLBCL) and follicle center lymphoma subtypes were each considered, which triggered further workup to rule out systemic involvement.

Figure 1. Erythematous firm tumors of the right side of the chest wall (A and B).

Figure 2. Atypical lymphocytic infiltrate with background crush artifact (A and B)(both H&E, original magnifications ×20 and ×40).

Figure 3. Atypical lymphocytes stained positively for antibodies against CD20 (original magnification ×40).

Figure 4. A focus of increased radiotracer deposition is seen in the left proximal humerus on positron emission tomography–computed tomography scanning.

A bone marrow biopsy from the posterior iliac crest revealed normocellular bone marrow with normal trilineage hematopoiesis. However, whole-body staging with positron emission tomography (PET)–CT scanning revealed osseous disease in the left proximal humerus (Figure 4) as well as a slightly hypermetabolic right axillary lymph node. Magnetic resonance imaging of the brain showed no evidence of intracranial disease. Because of the apparent systemic involvement, stage IV non-Hodgkin lymphoma (DLBCL) became the new suspected diagnosis. The patient was started on the first of 6 cycles of chemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and the skin lesions quickly dissipated and flattened. A faint pink discoloration remained over a slightly indented area. A repeat PET-CT scan following 4 cycles of R-CHOP chemotherapy also confirmed a complete response to therapy.

In general, CBCL tends to affect adults and presents as relatively firm and plum-colored papules, nodules, tumors, or plaques, which can be either fast or slow growing. Cutaneous B-cell lymphoma may be primary or secondary to systemic involvement. Primary CBCL refers to a group of non-Hodgkin lymphomas that initially present in the skin with no evidence of extracutaneous involvement at the time of diagnosis.^1,2 Secondary CBCL (SCBCL) refers to cutaneous disease that occurs secondary to systemic B-cell lymphoma. Detecting systemic involvement and distinguishing between PCBCL and SCBCL is valuable in determining prognosis and therapeutic options, as subtypes of PCBCL often have an improved prognosis and may be treated with local irradiation.

The initial staging techniques that are preferred for cutaneous lymphomas have been debated.^3-5 For cutaneous lymphomas, except mycosis fungoides and Sézary syndrome, the International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer recommends obtaining a complete blood cell count with differential; complete metabolic studies including lactate dehydrogenase; and imaging studies of the chest, abdomen, and pelvis. Bone marrow biopsies and imaging studies of the neck or whole-body PET-CT scanning also may be useful depending on the clinical scenario.³ Although a more limited workup may be sufficient for PCBCLs such as primary cutaneous marginal zone lymphoma,⁵ a bone marrow biopsy is recommended for cases of primary cutaneous DLBCL (leg type).³ Senff et al⁵ supported the use of a bone marrow biopsy in the evaluation of follicle center lymphomas first presenting in the skin, though this method is controversial. In our patient, the laboratory results; bone marrow biopsy; and CT scan of the chest, abdomen, and pelvis failed to suggest extracutaneous disease, while the PET-CT scan revealed systemic involvement.

The differential diagnosis of CBCL includes cutaneous lymphoid hyperplasia (pseudolymphoma), which may be the result of insults such as arthropod bites, stings, vaccinations, or trauma. The clinical presentation, histology, and results of molecular studies and immunohistochemistry are essential in differentiating benign versus malignant processes.⁶ Lymphomas are expected to be larger and more persistent than benign processes, demonstrating an atypical lymphocytic infiltrate and monoclonality; immunohistochemistry will aid in the distinction between B-cell and T-cell processes and can delineate the type of B-cell lymphoma. Histology for CBCL typically reveals an atypical lymphocytic infiltrate showing a CD20⁺ and CD79a⁺ immunophenotype. Staining for antibodies against BCL-2, BCL-6, CD10, and MUM-1 also plays an important role in the diagnosis of cutaneous lymphoma and determining where the lesion(s) falls within the classification schemes. For example, to differentiate between primary cutaneous lymphoma subtypes, BCL-2 negativity and BCL-6 positivity in the context of a CD20⁺ and CD79a⁺ immunophenotype supports a follicle center lymphoma or a DLBCL (non–leg type). By contrast, CD20, CD79a, BCL-2, and MUM-1 positivity would favor a DLBCL (leg type).⁷

The natural history and therapeutic options differ greatly between subtypes of CBCL. For example, the prognosis of primary cutaneous follicle center lymphoma is generally favorable with a 5-year disease-specific survival rate of roughly 95%, and radiation therapy is recommended as a first-line therapy for localized disease.^2,8 Conversely, primary cutaneous DLBCL (leg type) frequently spreads to extracutaneous sites⁸ and carries a much lower estimated 5-year disease-specific survival rate of 55%.² Chemotherapy with R-CHOP is typically included in initial therapy for primary cutaneous DLBCL (leg type).⁸ The prognosis of systemic B-cell lymphomas also is highly variable and may depend on the type of B-cell lymphoma, the stage of disease at diagnosis, histologic and immunologic characteristics, and the therapy received. Wright et al⁹ reported that patients with systemic germinal center B cell–like DLBCL had a 5-year survival rate of 62%, whereas patients with activated B cell–like variants of DLBCL had a 5-year survival rate of 26%. Expression of CD40 may be a favorable prognostic factor following treatment with systemic chemotherapy in patients with DLBCL,¹⁰ whereas FOXP1 protein overexpression is correlated with poor disease-specific survival in certain DLBCL phenotypes.¹¹

Although it is uncertain whether the cutaneous lesions preceded systemic disease in our patient, the cutaneous lesions could be arbitrarily classified as secondary because extracutaneous disease was discovered within 6 months of the initial diagnosis.¹ However, classifying the CBCL as primary or secondary did not alter the course of treatment in our patient, as the presumed systemic disease necessitated treatment with systemic chemotherapy; both PCBCLs that develop systemic involvement and SCBCLs (primary extracutaneous disease) usually are treated with systemic chemotherapy. Our case highlights the importance of whole-body staging, as PET-CT scanning changed the course of care by detecting osseous involvement, necessitating systemic therapy as opposed to local radiation therapy alone. A multidisciplinary team with a focus on the diagnosis and management of cutaneous lymphomas helped streamline our patient’s laboratory testing and imaging studies, diagnostic and therapeutic decision making, and treatment implementation. Open channels and frequent opportunities for communication among dermatologists, dermatopathologists, medical oncologists, hematopathologists, radiologists, and radiation oncologists are needed to optimize and coordinate care for patients with cutaneous lymphoma who require transdisciplinary care.

Acknowledgement—The authors would like to thank Henry Koon, MD (hematology/oncology), for his input and expertise.

A 59-year-old white man presented with 2 large erythematous lesions on the right side of the chest wall that had gradually progressed over the last 1.5 years. The patient denied any fever, night sweats, fatigue, unintentional weight loss, or loss of appetite. Physical examination revealed 2 large, well-circumscribed, nearly contiguous, firm, erythematous tumors. One tumor measured 7.5×4.5 cm and the other measured 4×3.5 cm.

The Diagnosis: Cutaneous B-cell Lymphoma

Biopsies from the right side of the chest wall (Figure 1) revealed an atypical dense and diffuse lymphocytic infiltrate throughout the dermis. There was extensive crush artifact throughout the specimen. However, the findings were consistent with cutaneous B-cell lymphoma (CBCL), and the diffuse large B-cell type was favored (Figure 2). Atypical lymphocytes stained positively for antibodies against CD20 (Figure 3), CD79a, and BCL-6, and stained negatively for antibodies against MUM-1 and BCL-2. Although flow cytometry revealed no definitive immunophenotypic lymphoma population, polymerase chain reaction analysis revealed a monoclonal immunoglobulin heavy chain gene rearrangement. Computed tomography (CT) scans of the chest, abdomen, and pelvis were unremarkable. A preliminary diagnosis of primary CBCL (PCBCL) was formulated. Diffuse large B-cell lymphoma (DLBCL) and follicle center lymphoma subtypes were each considered, which triggered further workup to rule out systemic involvement.

Figure 1. Erythematous firm tumors of the right side of the chest wall (A and B).

Figure 2. Atypical lymphocytic infiltrate with background crush artifact (A and B)(both H&E, original magnifications ×20 and ×40).

Figure 3. Atypical lymphocytes stained positively for antibodies against CD20 (original magnification ×40).

Figure 4. A focus of increased radiotracer deposition is seen in the left proximal humerus on positron emission tomography–computed tomography scanning.

A bone marrow biopsy from the posterior iliac crest revealed normocellular bone marrow with normal trilineage hematopoiesis. However, whole-body staging with positron emission tomography (PET)–CT scanning revealed osseous disease in the left proximal humerus (Figure 4) as well as a slightly hypermetabolic right axillary lymph node. Magnetic resonance imaging of the brain showed no evidence of intracranial disease. Because of the apparent systemic involvement, stage IV non-Hodgkin lymphoma (DLBCL) became the new suspected diagnosis. The patient was started on the first of 6 cycles of chemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and the skin lesions quickly dissipated and flattened. A faint pink discoloration remained over a slightly indented area. A repeat PET-CT scan following 4 cycles of R-CHOP chemotherapy also confirmed a complete response to therapy.

In general, CBCL tends to affect adults and presents as relatively firm and plum-colored papules, nodules, tumors, or plaques, which can be either fast or slow growing. Cutaneous B-cell lymphoma may be primary or secondary to systemic involvement. Primary CBCL refers to a group of non-Hodgkin lymphomas that initially present in the skin with no evidence of extracutaneous involvement at the time of diagnosis.^1,2 Secondary CBCL (SCBCL) refers to cutaneous disease that occurs secondary to systemic B-cell lymphoma. Detecting systemic involvement and distinguishing between PCBCL and SCBCL is valuable in determining prognosis and therapeutic options, as subtypes of PCBCL often have an improved prognosis and may be treated with local irradiation.

The initial staging techniques that are preferred for cutaneous lymphomas have been debated.^3-5 For cutaneous lymphomas, except mycosis fungoides and Sézary syndrome, the International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer recommends obtaining a complete blood cell count with differential; complete metabolic studies including lactate dehydrogenase; and imaging studies of the chest, abdomen, and pelvis. Bone marrow biopsies and imaging studies of the neck or whole-body PET-CT scanning also may be useful depending on the clinical scenario.³ Although a more limited workup may be sufficient for PCBCLs such as primary cutaneous marginal zone lymphoma,⁵ a bone marrow biopsy is recommended for cases of primary cutaneous DLBCL (leg type).³ Senff et al⁵ supported the use of a bone marrow biopsy in the evaluation of follicle center lymphomas first presenting in the skin, though this method is controversial. In our patient, the laboratory results; bone marrow biopsy; and CT scan of the chest, abdomen, and pelvis failed to suggest extracutaneous disease, while the PET-CT scan revealed systemic involvement.

The differential diagnosis of CBCL includes cutaneous lymphoid hyperplasia (pseudolymphoma), which may be the result of insults such as arthropod bites, stings, vaccinations, or trauma. The clinical presentation, histology, and results of molecular studies and immunohistochemistry are essential in differentiating benign versus malignant processes.⁶ Lymphomas are expected to be larger and more persistent than benign processes, demonstrating an atypical lymphocytic infiltrate and monoclonality; immunohistochemistry will aid in the distinction between B-cell and T-cell processes and can delineate the type of B-cell lymphoma. Histology for CBCL typically reveals an atypical lymphocytic infiltrate showing a CD20⁺ and CD79a⁺ immunophenotype. Staining for antibodies against BCL-2, BCL-6, CD10, and MUM-1 also plays an important role in the diagnosis of cutaneous lymphoma and determining where the lesion(s) falls within the classification schemes. For example, to differentiate between primary cutaneous lymphoma subtypes, BCL-2 negativity and BCL-6 positivity in the context of a CD20⁺ and CD79a⁺ immunophenotype supports a follicle center lymphoma or a DLBCL (non–leg type). By contrast, CD20, CD79a, BCL-2, and MUM-1 positivity would favor a DLBCL (leg type).⁷

The natural history and therapeutic options differ greatly between subtypes of CBCL. For example, the prognosis of primary cutaneous follicle center lymphoma is generally favorable with a 5-year disease-specific survival rate of roughly 95%, and radiation therapy is recommended as a first-line therapy for localized disease.^2,8 Conversely, primary cutaneous DLBCL (leg type) frequently spreads to extracutaneous sites⁸ and carries a much lower estimated 5-year disease-specific survival rate of 55%.² Chemotherapy with R-CHOP is typically included in initial therapy for primary cutaneous DLBCL (leg type).⁸ The prognosis of systemic B-cell lymphomas also is highly variable and may depend on the type of B-cell lymphoma, the stage of disease at diagnosis, histologic and immunologic characteristics, and the therapy received. Wright et al⁹ reported that patients with systemic germinal center B cell–like DLBCL had a 5-year survival rate of 62%, whereas patients with activated B cell–like variants of DLBCL had a 5-year survival rate of 26%. Expression of CD40 may be a favorable prognostic factor following treatment with systemic chemotherapy in patients with DLBCL,¹⁰ whereas FOXP1 protein overexpression is correlated with poor disease-specific survival in certain DLBCL phenotypes.¹¹

Although it is uncertain whether the cutaneous lesions preceded systemic disease in our patient, the cutaneous lesions could be arbitrarily classified as secondary because extracutaneous disease was discovered within 6 months of the initial diagnosis.¹ However, classifying the CBCL as primary or secondary did not alter the course of treatment in our patient, as the presumed systemic disease necessitated treatment with systemic chemotherapy; both PCBCLs that develop systemic involvement and SCBCLs (primary extracutaneous disease) usually are treated with systemic chemotherapy. Our case highlights the importance of whole-body staging, as PET-CT scanning changed the course of care by detecting osseous involvement, necessitating systemic therapy as opposed to local radiation therapy alone. A multidisciplinary team with a focus on the diagnosis and management of cutaneous lymphomas helped streamline our patient’s laboratory testing and imaging studies, diagnostic and therapeutic decision making, and treatment implementation. Open channels and frequent opportunities for communication among dermatologists, dermatopathologists, medical oncologists, hematopathologists, radiologists, and radiation oncologists are needed to optimize and coordinate care for patients with cutaneous lymphoma who require transdisciplinary care.

Acknowledgement—The authors would like to thank Henry Koon, MD (hematology/oncology), for his input and expertise.

As the most common form of cancer in the United States,¹ dermatologists often focus on treating the physical aspects of skin cancer, but it is equally important to consider the consequences that this disease has on a patient’s quality of life (QOL). Health is a dynamic process, encompassing one’s physical, emotional, and psychosocial well-being. There are a number of ways to measure health outcomes including mortality, morbidity, health status, and QOL. In recent years, health-related QOL (HRQOL) outcomes in dermatology have become increasingly important to clinical practice and may become factors in quality measurement or reimbursement.

Understanding a patient’s HRQOL allows health care providers to better evaluate the burden of disease and disability associated with skin cancer and its treatment. Clinical severity is not always able to capture the extent to which a disease affects one’s life.² Furthermore, physician estimation of disease severity is not always consistent with patient-reported outcomes.³ As such, clinical questionnaires may be invaluable tools capable of objectively reporting a patient’s perception of improvement in health, which may affect how a dermatologist approaches treatment, discussion, and maintenance.

Nonmelanoma Skin Cancer

Most nonmelanoma skin cancer (NMSC) occurs in readily visible areas, namely the head and neck. Surgical treatment minimizes recurrence and complication rates. Nonmelanoma skin cancer has a low mortality and a high cure rate if diagnosed early; therefore, it may be difficult to assess treatment efficacy on cure rates alone. The amalgamation of anxiety associated with the diagnosis, aesthetic and functional concerns regarding treatment, and long-term consequences including fear of future skin cancer may have a lasting effect on an individual’s psychosocial relationships and underscores the need for QOL studies.

Most generic QOL and dermatology-specific QOL instruments fail to accurately detect the concerns of patients with NMSC.^4-6 Generic QOL measures used for skin cancer patients report scores of patients that were similar to population norms,⁴ suggesting that these tools may fail to appropriately assess unique QOL concerns among individuals with skin cancer. Furthermore, dermatology-specific instruments have been reported to be insensitive to specific appearance-related concerns of patients with NMSC, likely because skin cancer patients made up a small percentage of the initial population in their design.^4,7 Nevertheless, dermatology-specific instruments may be suitable depending on the objectives of the study.⁸

Recently, skin cancer–specific QOL instruments have been developed to fill the paucity of appropriate tools for this population. These questionnaires include the Facial Skin Cancer Index, Skin Cancer Index, and the Skin Cancer Quality of Life Impact Tool.⁷ The Skin Cancer Index is a 15-item questionnaire validated in patients undergoing Mohs micrographic surgery and has been used to assess behavior modification and risk perceptions in NMSC patients. Importantly, it does ask the patient if he/she is worried about scarring. The Facial Skin Cancer Index and the Skin Cancer Quality of Life Impact Tool do not take into account detailed aesthetic concerns regarding facial disfigurement and scarring or expectations of reconstruction.⁷ It may be prudent to assess these areas with supplemental scales.

Melanoma

Melanoma, the third most common skin cancer, is highly aggressive and can affect young and middle-aged patients. Because the mortality associated with later-stage melanoma is greater, the QOL impact of melanoma differs from NMSC. There are also 3 distinct periods of melanoma HRQOL impact: diagnosis, treatment, and follow-up. Approximately 30% of patients diagnosed with melanoma report high levels of psychological distress.⁹ The psychosocial effects of a melanoma diagnosis are longitudinal, as there is a high survival rate in early disease but also an increased future risk for melanoma, affecting future behaviors and overall QOL. The diagnosis of melanoma also affects family members due to the increased risk among first-degree relatives. After removal of deeper melanoma, the patient remains at risk for disease progression, which can have a profound impact on his/her social and professional activities and overall lifestyle. There may be a role for longitudinal QOL assessments to monitor changes over time and direct ongoing therapy.

The proportion of patients with melanoma who report high levels of impairment in QOL is comparable to that seen in other malignancies.¹⁰ Generic QOL instruments have found that melanoma patients have medium to high levels of distress and substantial improvement in HRQOL has been achieved with cognitive-behavioral intervention.¹¹ Quality-of-life studies also have shown levels of distress are highest at initial diagnosis and immediately following treatment.¹² In a randomized surgical trial, patients with a larger excision margin had poorer mental and physical function scores on assessment.¹³ Skin-specific QOL instruments have been used in studies of patients with melanoma and found that postmelanoma surveillance did not impact QOL. Also, women experienced greater improvements in QOL over time after reporting lower scores immediately postsurgery.¹³

The FACT-melanoma (Functional Assessment of Cancer Therapy) is a melanoma-specific HRQOL assessment that has been used in patients undergoing clinical trials. It has been shown to distinguish between early and advanced-stage (stages III or IV) HRQOL issues.¹⁴ Patients with early-stage melanoma are more concerned with cosmetic outcome, and those with later-stage melanoma are more concerned with morbidity and mortality associated with treatment.

Comment

Choosing the best QOL instrument depends on the specific objectives of the study. Although generic QOL questionnaires have performed poorly in studies of specific skin diseases and even dermatology-specific tools have shown limited responsiveness in skin cancer, a combination of tools may be an effective approach. However, dermatologists must be cautious when administering these valuable tools to ensure that they do not become a burdensome task for the patient.¹⁵ Although no single skin cancer–specific QOL tool is perfect, it is likely that the current questionnaires still allow for aid with appropriate patient management and comparison of treatments.¹⁶

It behooves clinicians to recognize and appreciate the value of QOL instruments as an important adjunct to treatment. These tools have shown QOL to be an independent predictor of survival among many types of cancer patients, including melanoma.¹⁰ Currently, the psychological and emotional needs of skin cancer patients often go overlooked and undetected by conventional methods. Within one’s own practice, introducing QOL assessments can improve patient self-awareness and physician awareness of matters that may have a greater impact on patient health. On a larger scale, introducing patient-reported outcome measures can affect resource allocation by identifying patient populations that may be most impacted and can give a comprehensive method for physicians to gauge treatment efficacy, leading to improved outcomes.

As the most common form of cancer in the United States,¹ dermatologists often focus on treating the physical aspects of skin cancer, but it is equally important to consider the consequences that this disease has on a patient’s quality of life (QOL). Health is a dynamic process, encompassing one’s physical, emotional, and psychosocial well-being. There are a number of ways to measure health outcomes including mortality, morbidity, health status, and QOL. In recent years, health-related QOL (HRQOL) outcomes in dermatology have become increasingly important to clinical practice and may become factors in quality measurement or reimbursement.

Understanding a patient’s HRQOL allows health care providers to better evaluate the burden of disease and disability associated with skin cancer and its treatment. Clinical severity is not always able to capture the extent to which a disease affects one’s life.² Furthermore, physician estimation of disease severity is not always consistent with patient-reported outcomes.³ As such, clinical questionnaires may be invaluable tools capable of objectively reporting a patient’s perception of improvement in health, which may affect how a dermatologist approaches treatment, discussion, and maintenance.

Nonmelanoma Skin Cancer

Most nonmelanoma skin cancer (NMSC) occurs in readily visible areas, namely the head and neck. Surgical treatment minimizes recurrence and complication rates. Nonmelanoma skin cancer has a low mortality and a high cure rate if diagnosed early; therefore, it may be difficult to assess treatment efficacy on cure rates alone. The amalgamation of anxiety associated with the diagnosis, aesthetic and functional concerns regarding treatment, and long-term consequences including fear of future skin cancer may have a lasting effect on an individual’s psychosocial relationships and underscores the need for QOL studies.

Most generic QOL and dermatology-specific QOL instruments fail to accurately detect the concerns of patients with NMSC.^4-6 Generic QOL measures used for skin cancer patients report scores of patients that were similar to population norms,⁴ suggesting that these tools may fail to appropriately assess unique QOL concerns among individuals with skin cancer. Furthermore, dermatology-specific instruments have been reported to be insensitive to specific appearance-related concerns of patients with NMSC, likely because skin cancer patients made up a small percentage of the initial population in their design.^4,7 Nevertheless, dermatology-specific instruments may be suitable depending on the objectives of the study.⁸

Recently, skin cancer–specific QOL instruments have been developed to fill the paucity of appropriate tools for this population. These questionnaires include the Facial Skin Cancer Index, Skin Cancer Index, and the Skin Cancer Quality of Life Impact Tool.⁷ The Skin Cancer Index is a 15-item questionnaire validated in patients undergoing Mohs micrographic surgery and has been used to assess behavior modification and risk perceptions in NMSC patients. Importantly, it does ask the patient if he/she is worried about scarring. The Facial Skin Cancer Index and the Skin Cancer Quality of Life Impact Tool do not take into account detailed aesthetic concerns regarding facial disfigurement and scarring or expectations of reconstruction.⁷ It may be prudent to assess these areas with supplemental scales.

Melanoma

Melanoma, the third most common skin cancer, is highly aggressive and can affect young and middle-aged patients. Because the mortality associated with later-stage melanoma is greater, the QOL impact of melanoma differs from NMSC. There are also 3 distinct periods of melanoma HRQOL impact: diagnosis, treatment, and follow-up. Approximately 30% of patients diagnosed with melanoma report high levels of psychological distress.⁹ The psychosocial effects of a melanoma diagnosis are longitudinal, as there is a high survival rate in early disease but also an increased future risk for melanoma, affecting future behaviors and overall QOL. The diagnosis of melanoma also affects family members due to the increased risk among first-degree relatives. After removal of deeper melanoma, the patient remains at risk for disease progression, which can have a profound impact on his/her social and professional activities and overall lifestyle. There may be a role for longitudinal QOL assessments to monitor changes over time and direct ongoing therapy.

The proportion of patients with melanoma who report high levels of impairment in QOL is comparable to that seen in other malignancies.¹⁰ Generic QOL instruments have found that melanoma patients have medium to high levels of distress and substantial improvement in HRQOL has been achieved with cognitive-behavioral intervention.¹¹ Quality-of-life studies also have shown levels of distress are highest at initial diagnosis and immediately following treatment.¹² In a randomized surgical trial, patients with a larger excision margin had poorer mental and physical function scores on assessment.¹³ Skin-specific QOL instruments have been used in studies of patients with melanoma and found that postmelanoma surveillance did not impact QOL. Also, women experienced greater improvements in QOL over time after reporting lower scores immediately postsurgery.¹³

The FACT-melanoma (Functional Assessment of Cancer Therapy) is a melanoma-specific HRQOL assessment that has been used in patients undergoing clinical trials. It has been shown to distinguish between early and advanced-stage (stages III or IV) HRQOL issues.¹⁴ Patients with early-stage melanoma are more concerned with cosmetic outcome, and those with later-stage melanoma are more concerned with morbidity and mortality associated with treatment.

Comment

Choosing the best QOL instrument depends on the specific objectives of the study. Although generic QOL questionnaires have performed poorly in studies of specific skin diseases and even dermatology-specific tools have shown limited responsiveness in skin cancer, a combination of tools may be an effective approach. However, dermatologists must be cautious when administering these valuable tools to ensure that they do not become a burdensome task for the patient.¹⁵ Although no single skin cancer–specific QOL tool is perfect, it is likely that the current questionnaires still allow for aid with appropriate patient management and comparison of treatments.¹⁶

It behooves clinicians to recognize and appreciate the value of QOL instruments as an important adjunct to treatment. These tools have shown QOL to be an independent predictor of survival among many types of cancer patients, including melanoma.¹⁰ Currently, the psychological and emotional needs of skin cancer patients often go overlooked and undetected by conventional methods. Within one’s own practice, introducing QOL assessments can improve patient self-awareness and physician awareness of matters that may have a greater impact on patient health. On a larger scale, introducing patient-reported outcome measures can affect resource allocation by identifying patient populations that may be most impacted and can give a comprehensive method for physicians to gauge treatment efficacy, leading to improved outcomes.

As the most common form of cancer in the United States,¹ dermatologists often focus on treating the physical aspects of skin cancer, but it is equally important to consider the consequences that this disease has on a patient’s quality of life (QOL). Health is a dynamic process, encompassing one’s physical, emotional, and psychosocial well-being. There are a number of ways to measure health outcomes including mortality, morbidity, health status, and QOL. In recent years, health-related QOL (HRQOL) outcomes in dermatology have become increasingly important to clinical practice and may become factors in quality measurement or reimbursement.

Understanding a patient’s HRQOL allows health care providers to better evaluate the burden of disease and disability associated with skin cancer and its treatment. Clinical severity is not always able to capture the extent to which a disease affects one’s life.² Furthermore, physician estimation of disease severity is not always consistent with patient-reported outcomes.³ As such, clinical questionnaires may be invaluable tools capable of objectively reporting a patient’s perception of improvement in health, which may affect how a dermatologist approaches treatment, discussion, and maintenance.

Nonmelanoma Skin Cancer

Most nonmelanoma skin cancer (NMSC) occurs in readily visible areas, namely the head and neck. Surgical treatment minimizes recurrence and complication rates. Nonmelanoma skin cancer has a low mortality and a high cure rate if diagnosed early; therefore, it may be difficult to assess treatment efficacy on cure rates alone. The amalgamation of anxiety associated with the diagnosis, aesthetic and functional concerns regarding treatment, and long-term consequences including fear of future skin cancer may have a lasting effect on an individual’s psychosocial relationships and underscores the need for QOL studies.

Most generic QOL and dermatology-specific QOL instruments fail to accurately detect the concerns of patients with NMSC.^4-6 Generic QOL measures used for skin cancer patients report scores of patients that were similar to population norms,⁴ suggesting that these tools may fail to appropriately assess unique QOL concerns among individuals with skin cancer. Furthermore, dermatology-specific instruments have been reported to be insensitive to specific appearance-related concerns of patients with NMSC, likely because skin cancer patients made up a small percentage of the initial population in their design.^4,7 Nevertheless, dermatology-specific instruments may be suitable depending on the objectives of the study.⁸

Recently, skin cancer–specific QOL instruments have been developed to fill the paucity of appropriate tools for this population. These questionnaires include the Facial Skin Cancer Index, Skin Cancer Index, and the Skin Cancer Quality of Life Impact Tool.⁷ The Skin Cancer Index is a 15-item questionnaire validated in patients undergoing Mohs micrographic surgery and has been used to assess behavior modification and risk perceptions in NMSC patients. Importantly, it does ask the patient if he/she is worried about scarring. The Facial Skin Cancer Index and the Skin Cancer Quality of Life Impact Tool do not take into account detailed aesthetic concerns regarding facial disfigurement and scarring or expectations of reconstruction.⁷ It may be prudent to assess these areas with supplemental scales.

Melanoma

Melanoma, the third most common skin cancer, is highly aggressive and can affect young and middle-aged patients. Because the mortality associated with later-stage melanoma is greater, the QOL impact of melanoma differs from NMSC. There are also 3 distinct periods of melanoma HRQOL impact: diagnosis, treatment, and follow-up. Approximately 30% of patients diagnosed with melanoma report high levels of psychological distress.⁹ The psychosocial effects of a melanoma diagnosis are longitudinal, as there is a high survival rate in early disease but also an increased future risk for melanoma, affecting future behaviors and overall QOL. The diagnosis of melanoma also affects family members due to the increased risk among first-degree relatives. After removal of deeper melanoma, the patient remains at risk for disease progression, which can have a profound impact on his/her social and professional activities and overall lifestyle. There may be a role for longitudinal QOL assessments to monitor changes over time and direct ongoing therapy.

The proportion of patients with melanoma who report high levels of impairment in QOL is comparable to that seen in other malignancies.¹⁰ Generic QOL instruments have found that melanoma patients have medium to high levels of distress and substantial improvement in HRQOL has been achieved with cognitive-behavioral intervention.¹¹ Quality-of-life studies also have shown levels of distress are highest at initial diagnosis and immediately following treatment.¹² In a randomized surgical trial, patients with a larger excision margin had poorer mental and physical function scores on assessment.¹³ Skin-specific QOL instruments have been used in studies of patients with melanoma and found that postmelanoma surveillance did not impact QOL. Also, women experienced greater improvements in QOL over time after reporting lower scores immediately postsurgery.¹³

The FACT-melanoma (Functional Assessment of Cancer Therapy) is a melanoma-specific HRQOL assessment that has been used in patients undergoing clinical trials. It has been shown to distinguish between early and advanced-stage (stages III or IV) HRQOL issues.¹⁴ Patients with early-stage melanoma are more concerned with cosmetic outcome, and those with later-stage melanoma are more concerned with morbidity and mortality associated with treatment.

Comment

Choosing the best QOL instrument depends on the specific objectives of the study. Although generic QOL questionnaires have performed poorly in studies of specific skin diseases and even dermatology-specific tools have shown limited responsiveness in skin cancer, a combination of tools may be an effective approach. However, dermatologists must be cautious when administering these valuable tools to ensure that they do not become a burdensome task for the patient.¹⁵ Although no single skin cancer–specific QOL tool is perfect, it is likely that the current questionnaires still allow for aid with appropriate patient management and comparison of treatments.¹⁶

It behooves clinicians to recognize and appreciate the value of QOL instruments as an important adjunct to treatment. These tools have shown QOL to be an independent predictor of survival among many types of cancer patients, including melanoma.¹⁰ Currently, the psychological and emotional needs of skin cancer patients often go overlooked and undetected by conventional methods. Within one’s own practice, introducing QOL assessments can improve patient self-awareness and physician awareness of matters that may have a greater impact on patient health. On a larger scale, introducing patient-reported outcome measures can affect resource allocation by identifying patient populations that may be most impacted and can give a comprehensive method for physicians to gauge treatment efficacy, leading to improved outcomes.

Perianal squamous cell carcinoma in situ (SCCIS) is an intraepidermal neoplasm with human papillomavirus implicated in its etiology.¹ It can present as a raised, scaly, erythematous, fissured, ulcerated, or pigmented lesion; however, perianal SCCIS often is subclinical and therefore requires a high level of suspicion in individuals with risk factors (eg, history of genital or perianal human papillomavirus infection, other sexually transmitted diseases, or cervical dysplasia).² Although relatively rare, perianal SCCIS is believed to be increasing in frequency and has the potential to progress to invasive squamous cell carcinoma.^1,3 The rarity of this neoplasm and its uncertain natural history has made the development of a definitive, evidence-based management strategy difficult and controversial.^1,4,5 We present the case of a 61-year-old woman with perianal SCCIS who was treated with a novel combination of 5-aminolevulinic acid–based photodynamic therapy (ALA-PDT) and topical imiquimod cream 5% following 2 unsuccessful surgical excisions. Using this treatment regimen, the neoplasm resolved completely with no evidence of recurrence at 2 years’ follow-up.

Case Report

A 61-year-old woman was referred to our dermatology clinic for management of persistent SCCIS of the perianal region. A colorectal surgeon performed 2 unsuccessful excisions of the neoplasm at 6 months and 1 month prior to presentation. Biopsy results from the second excision demonstrated persistent perianal SCCIS with positive margins (Figure 1). The patient was referred to our clinic to discuss Mohs micrographic surgery versus nonsurgical treatment options. The patient’s medical history was remarkable for an abnormal Papanicolaou test 10 years prior, which resulted in cervical cryotherapy.

Figure 1. Enlarged and atypical keratinocytes with koilocytosis extending throughout the full thickness of an acanthotic epithelium (H&E, original magnification ×100). Photograph courtesy of Todd Arends, MD, Chesterfield, Missouri.

Figure 2. A 2×1-cm erythematous scaling patch on the right anal verge (A). Clinical resolution of erythema and scaling was achieved following treatment with imiquimod and 5-aminolevulinic acid–based photodynamic therapy (B).

Physical examination revealed a 2×1-cm pink scar with peripheral scaling on the right anal verge (Figure 2A). Potential therapies discussed with the patient included Mohs surgery, ablative laser treatment, and nonsurgical treatment with ALA-PDT in combination with topical imiquimod cream 5%. To avoid further invasive treatments, we decided to administer a 3-week course of topical imiquimod cream 5% applied 3 times weekly to the entire affected area, followed 1 week later with a treatment of ALA-PDT. The incubation time was 6 hours. After completing 4 cycles of this therapeutic regimen, the erythema and scaling resolved (Figure 2B). The patient did not note any remarkable side effects associated with imiquimod but reported progressively resolving pain in the week following each ALA-PDT treatment, with the worst pain occurring during the first 48 hours after treatment. Three posttreatment scout biopsies revealed no evidence of residual perianal SCCIS. Two years after the negative biopsies, ongoing physical examinations demonstrated no evidence of clinical recurrence. Physicians in the dermatology and gynecology departments are following her closely.

Comment

Wide surgical excision is currently recommended as first-line therapy for perianal SCCIS.^1,3,4 Unfortunately, surgical excision has been associated with difficulty in achieving disease-free margins, recurrence rates as high as 31%, and substantial morbidity.^1,4 Other nonsurgical treatment modalities have been investigated for treating this neoplasm to simultaneously reduce recurrence rates while minimizing structural and functional damage to the treatment area, including radiotherapy, imiquimod, laser ablation, and ALA-PDT.^1,3,4,5

In particular, imiquimod and ALA-PDT have shown promise as monotherapies for the treatment of perianal SCCIS, with several case reports describing complete resolution, low rates of recurrence, and preserved structure and function of the surrounding tissue after therapy^1,3,4; however, recurrence of perianal SCCIS is still known to occur after monotherapy with either ALA-PDT or imiquimod.^5,6

In contrast to noninvasive monotherapies, the literature is largely devoid of reports of noninvasive combination treatments used for perianal SCCIS. Our case represents successful use of a combination of imiquimod and ALA-PDT to treat persistent perianal SCCIS.

Conclusion

Although further research is necessary, the therapeutic success presented in our case suggests noninvasive combination therapy with imiquimod and ALA-PDT may represent a viable alternative to both surgical excision and noninvasive monotherapies for the treatment of perianal SCCIS.

Acknowledgement—The authors would like to thank Alejandro Gru, MD, Columbus, Ohio, for his review of the pathology slides for this case.

Perianal squamous cell carcinoma in situ (SCCIS) is an intraepidermal neoplasm with human papillomavirus implicated in its etiology.¹ It can present as a raised, scaly, erythematous, fissured, ulcerated, or pigmented lesion; however, perianal SCCIS often is subclinical and therefore requires a high level of suspicion in individuals with risk factors (eg, history of genital or perianal human papillomavirus infection, other sexually transmitted diseases, or cervical dysplasia).² Although relatively rare, perianal SCCIS is believed to be increasing in frequency and has the potential to progress to invasive squamous cell carcinoma.^1,3 The rarity of this neoplasm and its uncertain natural history has made the development of a definitive, evidence-based management strategy difficult and controversial.^1,4,5 We present the case of a 61-year-old woman with perianal SCCIS who was treated with a novel combination of 5-aminolevulinic acid–based photodynamic therapy (ALA-PDT) and topical imiquimod cream 5% following 2 unsuccessful surgical excisions. Using this treatment regimen, the neoplasm resolved completely with no evidence of recurrence at 2 years’ follow-up.

Case Report

A 61-year-old woman was referred to our dermatology clinic for management of persistent SCCIS of the perianal region. A colorectal surgeon performed 2 unsuccessful excisions of the neoplasm at 6 months and 1 month prior to presentation. Biopsy results from the second excision demonstrated persistent perianal SCCIS with positive margins (Figure 1). The patient was referred to our clinic to discuss Mohs micrographic surgery versus nonsurgical treatment options. The patient’s medical history was remarkable for an abnormal Papanicolaou test 10 years prior, which resulted in cervical cryotherapy.

Figure 1. Enlarged and atypical keratinocytes with koilocytosis extending throughout the full thickness of an acanthotic epithelium (H&E, original magnification ×100). Photograph courtesy of Todd Arends, MD, Chesterfield, Missouri.

Figure 2. A 2×1-cm erythematous scaling patch on the right anal verge (A). Clinical resolution of erythema and scaling was achieved following treatment with imiquimod and 5-aminolevulinic acid–based photodynamic therapy (B).

Physical examination revealed a 2×1-cm pink scar with peripheral scaling on the right anal verge (Figure 2A). Potential therapies discussed with the patient included Mohs surgery, ablative laser treatment, and nonsurgical treatment with ALA-PDT in combination with topical imiquimod cream 5%. To avoid further invasive treatments, we decided to administer a 3-week course of topical imiquimod cream 5% applied 3 times weekly to the entire affected area, followed 1 week later with a treatment of ALA-PDT. The incubation time was 6 hours. After completing 4 cycles of this therapeutic regimen, the erythema and scaling resolved (Figure 2B). The patient did not note any remarkable side effects associated with imiquimod but reported progressively resolving pain in the week following each ALA-PDT treatment, with the worst pain occurring during the first 48 hours after treatment. Three posttreatment scout biopsies revealed no evidence of residual perianal SCCIS. Two years after the negative biopsies, ongoing physical examinations demonstrated no evidence of clinical recurrence. Physicians in the dermatology and gynecology departments are following her closely.

Comment

Wide surgical excision is currently recommended as first-line therapy for perianal SCCIS.^1,3,4 Unfortunately, surgical excision has been associated with difficulty in achieving disease-free margins, recurrence rates as high as 31%, and substantial morbidity.^1,4 Other nonsurgical treatment modalities have been investigated for treating this neoplasm to simultaneously reduce recurrence rates while minimizing structural and functional damage to the treatment area, including radiotherapy, imiquimod, laser ablation, and ALA-PDT.^1,3,4,5

In particular, imiquimod and ALA-PDT have shown promise as monotherapies for the treatment of perianal SCCIS, with several case reports describing complete resolution, low rates of recurrence, and preserved structure and function of the surrounding tissue after therapy^1,3,4; however, recurrence of perianal SCCIS is still known to occur after monotherapy with either ALA-PDT or imiquimod.^5,6

In contrast to noninvasive monotherapies, the literature is largely devoid of reports of noninvasive combination treatments used for perianal SCCIS. Our case represents successful use of a combination of imiquimod and ALA-PDT to treat persistent perianal SCCIS.

Conclusion

Although further research is necessary, the therapeutic success presented in our case suggests noninvasive combination therapy with imiquimod and ALA-PDT may represent a viable alternative to both surgical excision and noninvasive monotherapies for the treatment of perianal SCCIS.

Acknowledgement—The authors would like to thank Alejandro Gru, MD, Columbus, Ohio, for his review of the pathology slides for this case.

Perianal squamous cell carcinoma in situ (SCCIS) is an intraepidermal neoplasm with human papillomavirus implicated in its etiology.¹ It can present as a raised, scaly, erythematous, fissured, ulcerated, or pigmented lesion; however, perianal SCCIS often is subclinical and therefore requires a high level of suspicion in individuals with risk factors (eg, history of genital or perianal human papillomavirus infection, other sexually transmitted diseases, or cervical dysplasia).² Although relatively rare, perianal SCCIS is believed to be increasing in frequency and has the potential to progress to invasive squamous cell carcinoma.^1,3 The rarity of this neoplasm and its uncertain natural history has made the development of a definitive, evidence-based management strategy difficult and controversial.^1,4,5 We present the case of a 61-year-old woman with perianal SCCIS who was treated with a novel combination of 5-aminolevulinic acid–based photodynamic therapy (ALA-PDT) and topical imiquimod cream 5% following 2 unsuccessful surgical excisions. Using this treatment regimen, the neoplasm resolved completely with no evidence of recurrence at 2 years’ follow-up.

Case Report

A 61-year-old woman was referred to our dermatology clinic for management of persistent SCCIS of the perianal region. A colorectal surgeon performed 2 unsuccessful excisions of the neoplasm at 6 months and 1 month prior to presentation. Biopsy results from the second excision demonstrated persistent perianal SCCIS with positive margins (Figure 1). The patient was referred to our clinic to discuss Mohs micrographic surgery versus nonsurgical treatment options. The patient’s medical history was remarkable for an abnormal Papanicolaou test 10 years prior, which resulted in cervical cryotherapy.

Figure 1. Enlarged and atypical keratinocytes with koilocytosis extending throughout the full thickness of an acanthotic epithelium (H&E, original magnification ×100). Photograph courtesy of Todd Arends, MD, Chesterfield, Missouri.

Figure 2. A 2×1-cm erythematous scaling patch on the right anal verge (A). Clinical resolution of erythema and scaling was achieved following treatment with imiquimod and 5-aminolevulinic acid–based photodynamic therapy (B).

Physical examination revealed a 2×1-cm pink scar with peripheral scaling on the right anal verge (Figure 2A). Potential therapies discussed with the patient included Mohs surgery, ablative laser treatment, and nonsurgical treatment with ALA-PDT in combination with topical imiquimod cream 5%. To avoid further invasive treatments, we decided to administer a 3-week course of topical imiquimod cream 5% applied 3 times weekly to the entire affected area, followed 1 week later with a treatment of ALA-PDT. The incubation time was 6 hours. After completing 4 cycles of this therapeutic regimen, the erythema and scaling resolved (Figure 2B). The patient did not note any remarkable side effects associated with imiquimod but reported progressively resolving pain in the week following each ALA-PDT treatment, with the worst pain occurring during the first 48 hours after treatment. Three posttreatment scout biopsies revealed no evidence of residual perianal SCCIS. Two years after the negative biopsies, ongoing physical examinations demonstrated no evidence of clinical recurrence. Physicians in the dermatology and gynecology departments are following her closely.

Comment

Wide surgical excision is currently recommended as first-line therapy for perianal SCCIS.^1,3,4 Unfortunately, surgical excision has been associated with difficulty in achieving disease-free margins, recurrence rates as high as 31%, and substantial morbidity.^1,4 Other nonsurgical treatment modalities have been investigated for treating this neoplasm to simultaneously reduce recurrence rates while minimizing structural and functional damage to the treatment area, including radiotherapy, imiquimod, laser ablation, and ALA-PDT.^1,3,4,5

In particular, imiquimod and ALA-PDT have shown promise as monotherapies for the treatment of perianal SCCIS, with several case reports describing complete resolution, low rates of recurrence, and preserved structure and function of the surrounding tissue after therapy^1,3,4; however, recurrence of perianal SCCIS is still known to occur after monotherapy with either ALA-PDT or imiquimod.^5,6

In contrast to noninvasive monotherapies, the literature is largely devoid of reports of noninvasive combination treatments used for perianal SCCIS. Our case represents successful use of a combination of imiquimod and ALA-PDT to treat persistent perianal SCCIS.

Conclusion

Although further research is necessary, the therapeutic success presented in our case suggests noninvasive combination therapy with imiquimod and ALA-PDT may represent a viable alternative to both surgical excision and noninvasive monotherapies for the treatment of perianal SCCIS.

Acknowledgement—The authors would like to thank Alejandro Gru, MD, Columbus, Ohio, for his review of the pathology slides for this case.

Case Report

An 85-year-old woman presented with a painless red plaque on the right bicep of 5 years’ duration. The patient had not seen a physician in the last 63 years and had unsuccessfully attempted to treat the plaque by occlusion with an adhesive bandage. A review of systems was negative for pain, pruritus, bleeding, fever, unexplained weight loss, and night sweats. Physical examination revealed a raised, 2×4×1-cm, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right bicep (Figure 1). Full-body skin examination revealed erythema and swelling of the right wrist and forearm consistent with cellulitis as well as tinea pedis and onychomycosis of the toenails of both feet.

Figure 1. A raised, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right bicep. Figure 2. The tumor was comprised of gland-forming cells and exhibited crowding, pleomorphism, enlarged hyperchromatic nuclei, and mitotic division figures (H&E, original magnification ×100). Figure 3. Mucicarmine staining highlighted sialomucin within the glandular component (original magnification ×400).

Hematoxylin and eosin as well as mucicarmine staining of a shave biopsy from the lesion demonstrated an invasive epithelial neoplasm comprised of squamoid and gland-forming cells broadly attached to the epidermis, which suggested a primary cutaneous origin (Figures 2 and 3). The tumor cells were arranged in infiltrating cords and nests; they exhibited crowding, pleomorphism, enlarged hyperchromatic nuclei, and mitotic division figures. Epithelial mucin (sialomucin) within the glandular component was highlighted on mucicarmine staining. The gland-forming segment of the tumor was strongly positive for cytokeratin (CK) 7. Gastrointestinal tumors were excluded on negative CDX2 and CK20 staining, pulmonary and thyroid tumors were excluded on negative thyroid transcription factor 1 staining, and endometrial and ovarian tumors were excluded with negative estrogen receptor staining. On physical examination the breasts were soft, nontender, and without deformity. A chest radiograph demonstrated normal heart size and pulmonary vasculature with mild bibasilar atelectasis and no areas of consolidation. Given these clinical findings along with a negative history of cancer and negative estrogen receptor staining, breast cancer was excluded from the differential diagnosis, and the diagnosis of cASC was made. The tumor was excised using Mohs micrographic surgery and was free of recurrence at 6- and 12-month follow-up.

Comment

Primary cutaneous adenosquamous carcinoma (cASC) is an aggressive subtype of squamous cell carcinoma that was first described in 1985.¹ It typically presents as an erythematous, indurated, keratotic papule or plaque with a predilection for the face, scalp, and upper extremities of immunocompromised individuals and elderly men.^2,3 Biopsies generally demonstrate a malignant epithelial neoplasm arising from the epidermis and exhibiting squamous and glandular differentiation. The glandular segment usually is indistinguishable from adenocarcinoma and can be highlighted on CK7, carcinoembryonic antigen, mucicarmine, and periodic acid–Schiff staining. The squamous segment typically is indistinguishable from squamous cell carcinoma and shows aberrant keratinization and intercellular bridges. Tumors often are deeply invasive, poorly differentiated, and associated with a desmoplastic stromal reaction. Local recurrence rates are between 22% and 26%,⁴ but metastasis is rare. Surgical excision is the mainstay of therapy. When clear margins cannot be obtained using Mohs micrographic surgery, adjuvant external beam radiation therapy and epidermal growth factor receptor inhibitors can be used to treat locally recurrent cASCs.²

The differential diagnosis for cASC includes cutaneous mucoepidermoid carcinoma, cutaneous acantholytic squamous cell carcinoma, and cutaneous manifestations of metastatic visceral adenosquamous carcinoma. Mucoepidermoid carcinoma sometimes is used interchangeably with cASC in the literature, but it is a different cutaneous neoplasm that forms goblet cells, intermediate cells, and squamous cells. It is considered the cutaneous analogue of salivary gland mucoepidermoid carcinoma and does not exhibit the anaplasia, stromal desmoplasia, and aggressive course of cASC.⁵ The acantholytic subtype of squamous cell carcinoma forms glandlike spaces due to poor adhesion between keratinocytes, but the glandlike spaces do not form mucin or stain positive for CK7 or carcinoembryonic antigen. Adenosquamous carcinomas are well recognized in the lungs, breasts, genitourinary tract, pancreas, and gastroenteric system. Visceral tumor metastasis to the skin should be excluded by appropriate screening.

Conclusion

Although cASCs are not commonly encountered in clinical practice, accurate diagnosis of these lesions is important due to their potentially aggressive behavior. Misdiagnosis and improper treatment could be attributed to lack of awareness of this type of lesion.

Case Report

An 85-year-old woman presented with a painless red plaque on the right bicep of 5 years’ duration. The patient had not seen a physician in the last 63 years and had unsuccessfully attempted to treat the plaque by occlusion with an adhesive bandage. A review of systems was negative for pain, pruritus, bleeding, fever, unexplained weight loss, and night sweats. Physical examination revealed a raised, 2×4×1-cm, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right bicep (Figure 1). Full-body skin examination revealed erythema and swelling of the right wrist and forearm consistent with cellulitis as well as tinea pedis and onychomycosis of the toenails of both feet.

Figure 1. A raised, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right bicep. Figure 2. The tumor was comprised of gland-forming cells and exhibited crowding, pleomorphism, enlarged hyperchromatic nuclei, and mitotic division figures (H&E, original magnification ×100). Figure 3. Mucicarmine staining highlighted sialomucin within the glandular component (original magnification ×400).

Hematoxylin and eosin as well as mucicarmine staining of a shave biopsy from the lesion demonstrated an invasive epithelial neoplasm comprised of squamoid and gland-forming cells broadly attached to the epidermis, which suggested a primary cutaneous origin (Figures 2 and 3). The tumor cells were arranged in infiltrating cords and nests; they exhibited crowding, pleomorphism, enlarged hyperchromatic nuclei, and mitotic division figures. Epithelial mucin (sialomucin) within the glandular component was highlighted on mucicarmine staining. The gland-forming segment of the tumor was strongly positive for cytokeratin (CK) 7. Gastrointestinal tumors were excluded on negative CDX2 and CK20 staining, pulmonary and thyroid tumors were excluded on negative thyroid transcription factor 1 staining, and endometrial and ovarian tumors were excluded with negative estrogen receptor staining. On physical examination the breasts were soft, nontender, and without deformity. A chest radiograph demonstrated normal heart size and pulmonary vasculature with mild bibasilar atelectasis and no areas of consolidation. Given these clinical findings along with a negative history of cancer and negative estrogen receptor staining, breast cancer was excluded from the differential diagnosis, and the diagnosis of cASC was made. The tumor was excised using Mohs micrographic surgery and was free of recurrence at 6- and 12-month follow-up.

Comment

Primary cutaneous adenosquamous carcinoma (cASC) is an aggressive subtype of squamous cell carcinoma that was first described in 1985.¹ It typically presents as an erythematous, indurated, keratotic papule or plaque with a predilection for the face, scalp, and upper extremities of immunocompromised individuals and elderly men.^2,3 Biopsies generally demonstrate a malignant epithelial neoplasm arising from the epidermis and exhibiting squamous and glandular differentiation. The glandular segment usually is indistinguishable from adenocarcinoma and can be highlighted on CK7, carcinoembryonic antigen, mucicarmine, and periodic acid–Schiff staining. The squamous segment typically is indistinguishable from squamous cell carcinoma and shows aberrant keratinization and intercellular bridges. Tumors often are deeply invasive, poorly differentiated, and associated with a desmoplastic stromal reaction. Local recurrence rates are between 22% and 26%,⁴ but metastasis is rare. Surgical excision is the mainstay of therapy. When clear margins cannot be obtained using Mohs micrographic surgery, adjuvant external beam radiation therapy and epidermal growth factor receptor inhibitors can be used to treat locally recurrent cASCs.²

The differential diagnosis for cASC includes cutaneous mucoepidermoid carcinoma, cutaneous acantholytic squamous cell carcinoma, and cutaneous manifestations of metastatic visceral adenosquamous carcinoma. Mucoepidermoid carcinoma sometimes is used interchangeably with cASC in the literature, but it is a different cutaneous neoplasm that forms goblet cells, intermediate cells, and squamous cells. It is considered the cutaneous analogue of salivary gland mucoepidermoid carcinoma and does not exhibit the anaplasia, stromal desmoplasia, and aggressive course of cASC.⁵ The acantholytic subtype of squamous cell carcinoma forms glandlike spaces due to poor adhesion between keratinocytes, but the glandlike spaces do not form mucin or stain positive for CK7 or carcinoembryonic antigen. Adenosquamous carcinomas are well recognized in the lungs, breasts, genitourinary tract, pancreas, and gastroenteric system. Visceral tumor metastasis to the skin should be excluded by appropriate screening.

Conclusion

Although cASCs are not commonly encountered in clinical practice, accurate diagnosis of these lesions is important due to their potentially aggressive behavior. Misdiagnosis and improper treatment could be attributed to lack of awareness of this type of lesion.

Case Report

An 85-year-old woman presented with a painless red plaque on the right bicep of 5 years’ duration. The patient had not seen a physician in the last 63 years and had unsuccessfully attempted to treat the plaque by occlusion with an adhesive bandage. A review of systems was negative for pain, pruritus, bleeding, fever, unexplained weight loss, and night sweats. Physical examination revealed a raised, 2×4×1-cm, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right bicep (Figure 1). Full-body skin examination revealed erythema and swelling of the right wrist and forearm consistent with cellulitis as well as tinea pedis and onychomycosis of the toenails of both feet.

Figure 1. A raised, red, nontender, ulcerated plaque with slight exudate and gelatinous texture on the right bicep. Figure 2. The tumor was comprised of gland-forming cells and exhibited crowding, pleomorphism, enlarged hyperchromatic nuclei, and mitotic division figures (H&E, original magnification ×100). Figure 3. Mucicarmine staining highlighted sialomucin within the glandular component (original magnification ×400).

Hematoxylin and eosin as well as mucicarmine staining of a shave biopsy from the lesion demonstrated an invasive epithelial neoplasm comprised of squamoid and gland-forming cells broadly attached to the epidermis, which suggested a primary cutaneous origin (Figures 2 and 3). The tumor cells were arranged in infiltrating cords and nests; they exhibited crowding, pleomorphism, enlarged hyperchromatic nuclei, and mitotic division figures. Epithelial mucin (sialomucin) within the glandular component was highlighted on mucicarmine staining. The gland-forming segment of the tumor was strongly positive for cytokeratin (CK) 7. Gastrointestinal tumors were excluded on negative CDX2 and CK20 staining, pulmonary and thyroid tumors were excluded on negative thyroid transcription factor 1 staining, and endometrial and ovarian tumors were excluded with negative estrogen receptor staining. On physical examination the breasts were soft, nontender, and without deformity. A chest radiograph demonstrated normal heart size and pulmonary vasculature with mild bibasilar atelectasis and no areas of consolidation. Given these clinical findings along with a negative history of cancer and negative estrogen receptor staining, breast cancer was excluded from the differential diagnosis, and the diagnosis of cASC was made. The tumor was excised using Mohs micrographic surgery and was free of recurrence at 6- and 12-month follow-up.

Comment

Primary cutaneous adenosquamous carcinoma (cASC) is an aggressive subtype of squamous cell carcinoma that was first described in 1985.¹ It typically presents as an erythematous, indurated, keratotic papule or plaque with a predilection for the face, scalp, and upper extremities of immunocompromised individuals and elderly men.^2,3 Biopsies generally demonstrate a malignant epithelial neoplasm arising from the epidermis and exhibiting squamous and glandular differentiation. The glandular segment usually is indistinguishable from adenocarcinoma and can be highlighted on CK7, carcinoembryonic antigen, mucicarmine, and periodic acid–Schiff staining. The squamous segment typically is indistinguishable from squamous cell carcinoma and shows aberrant keratinization and intercellular bridges. Tumors often are deeply invasive, poorly differentiated, and associated with a desmoplastic stromal reaction. Local recurrence rates are between 22% and 26%,⁴ but metastasis is rare. Surgical excision is the mainstay of therapy. When clear margins cannot be obtained using Mohs micrographic surgery, adjuvant external beam radiation therapy and epidermal growth factor receptor inhibitors can be used to treat locally recurrent cASCs.²

The differential diagnosis for cASC includes cutaneous mucoepidermoid carcinoma, cutaneous acantholytic squamous cell carcinoma, and cutaneous manifestations of metastatic visceral adenosquamous carcinoma. Mucoepidermoid carcinoma sometimes is used interchangeably with cASC in the literature, but it is a different cutaneous neoplasm that forms goblet cells, intermediate cells, and squamous cells. It is considered the cutaneous analogue of salivary gland mucoepidermoid carcinoma and does not exhibit the anaplasia, stromal desmoplasia, and aggressive course of cASC.⁵ The acantholytic subtype of squamous cell carcinoma forms glandlike spaces due to poor adhesion between keratinocytes, but the glandlike spaces do not form mucin or stain positive for CK7 or carcinoembryonic antigen. Adenosquamous carcinomas are well recognized in the lungs, breasts, genitourinary tract, pancreas, and gastroenteric system. Visceral tumor metastasis to the skin should be excluded by appropriate screening.

Conclusion

Although cASCs are not commonly encountered in clinical practice, accurate diagnosis of these lesions is important due to their potentially aggressive behavior. Misdiagnosis and improper treatment could be attributed to lack of awareness of this type of lesion.