Melanoma

Dermoscopy, or the noninvasive in vivo examination of the epidermis and superficial dermis using magnification, facilitates the diagnosis of pigmented and nonpigmented skin lesions.¹ Despite the benefit of dermoscopy in making early and accurate diagnoses of potentially life-limiting skin cancers, only 48% of dermatologists in the United States use dermoscopy in their practices.² The most commonly cited reason for not using dermoscopy is lack of training.

Although the use of dermoscopy is associated with younger age and more recent graduation from residency compared to nonusers, dermatology resident physicians continue to receive limited training in dermoscopy.² In a survey of 139 dermatology chief residents, 48% were not satisfied with the dermoscopy training that they had received during residency. Residents who received bedside instruction in dermoscopy reported greater satisfaction with their dermoscopy training compared to those who did not receive bedside instruction.³ This article provides a brief comparison of standard dermoscopy versus videodermoscopy for the instruction of trainees on common dermatologic diagnoses.

Bedside Dermoscopy

Standard optical dermatoscopes used for patient care and educational purposes typically incorporate 10-fold magnification and permit examination by a single viewer through a lens. With standard dermatoscopes, bedside dermoscopy instruction consists of the independent sequential viewing of skin lesions by instructors and trainees. Trainees must independently search for dermoscopic features noted by the instructor, which may be difficult for novice users. Simultaneous viewing of lesions would allow instructors to clearly indicate in real time pertinent dermoscopic features to their trainees.

Videodermatoscopes facilitate the simultaneous examination of cutaneous lesions by projecting the dermoscopic image onto a digital screen. Furthermore, these devices can incorporate magnifications of up to 200-fold or greater. In recent years, research pertaining to videodermoscopy has focused on the high magnification capabilities of these devices, specifically dermoscopic features that are visualized at magnifications greater than 10-fold, including the light brown nests of basal cell carcinomas that are seen at 50- to 70-fold magnification, twisted red capillary loops seen in active scalp psoriasis at 50-fold magnification, and longitudinal white indentations seen on nail plates affected by onychomycosis at 20-fold magnification.^4-6 The potential value of videodermoscopy in medical education lies not only in the high magnification potential, which may make subtle dermoscopic findings more apparent to novice dermoscopists, but also in the ability to facilitate simultaneous dermoscopic examinations by instructors and trainees.

Educational Applications for Videodermoscopy

To illustrate the educational potential of videodermoscopy, images taken with a standard dermatoscope at 10-fold magnification are presented with videodermoscopic images taken at magnifications ranging from 60- to 185-fold (Figures 1–3). These examples demonstrate the potential for videodermoscopy to facilitate the visualization of subtle dermoscopic features by novice dermoscopists, relating to both the enhanced magnification potential and the potential for simultaneous rather than sequential examination.

Final Thoughts

High-magnification videodermoscopy may be a useful tool to further dermoscopic education. Videodermatoscopes vary in functionality and cost but are available at price points comparable to those of standard optical dermatoscopes. Owners of standard dermatoscopes can approximate some of the benefits of a digital videodermatoscope by using the standard dermatoscope in conjunction with a camera, including those integrated into mobile phones and tablets. By attaching the standard dermatoscope to a camera with a digital display, the digital zoom of the camera can be used to magnify the standard dermoscopic image, enhancing the ability of novice dermoscopists to visualize subtle findings. By presenting this magnified image on a digital display, dermoscopy instructors and trainees would be able to simultaneously view dermoscopic images of lesions, sometimes with magnifications comparable to videodermatoscopes.

In the setting of a dermatology residency program, videodermoscopy can be incorporated into bedside teaching with experienced dermoscopists and for the live presentation of dermoscopic features at departmental grand rounds. By facilitating the simultaneous, high-magnification and live viewing of skin lesions by dermoscopy instructors and trainees, digital videodermoscopy has the potential to address an area of weakness in dermatologic training.

Dermoscopy, or the noninvasive in vivo examination of the epidermis and superficial dermis using magnification, facilitates the diagnosis of pigmented and nonpigmented skin lesions.¹ Despite the benefit of dermoscopy in making early and accurate diagnoses of potentially life-limiting skin cancers, only 48% of dermatologists in the United States use dermoscopy in their practices.² The most commonly cited reason for not using dermoscopy is lack of training.

Although the use of dermoscopy is associated with younger age and more recent graduation from residency compared to nonusers, dermatology resident physicians continue to receive limited training in dermoscopy.² In a survey of 139 dermatology chief residents, 48% were not satisfied with the dermoscopy training that they had received during residency. Residents who received bedside instruction in dermoscopy reported greater satisfaction with their dermoscopy training compared to those who did not receive bedside instruction.³ This article provides a brief comparison of standard dermoscopy versus videodermoscopy for the instruction of trainees on common dermatologic diagnoses.

Bedside Dermoscopy

Standard optical dermatoscopes used for patient care and educational purposes typically incorporate 10-fold magnification and permit examination by a single viewer through a lens. With standard dermatoscopes, bedside dermoscopy instruction consists of the independent sequential viewing of skin lesions by instructors and trainees. Trainees must independently search for dermoscopic features noted by the instructor, which may be difficult for novice users. Simultaneous viewing of lesions would allow instructors to clearly indicate in real time pertinent dermoscopic features to their trainees.

Videodermatoscopes facilitate the simultaneous examination of cutaneous lesions by projecting the dermoscopic image onto a digital screen. Furthermore, these devices can incorporate magnifications of up to 200-fold or greater. In recent years, research pertaining to videodermoscopy has focused on the high magnification capabilities of these devices, specifically dermoscopic features that are visualized at magnifications greater than 10-fold, including the light brown nests of basal cell carcinomas that are seen at 50- to 70-fold magnification, twisted red capillary loops seen in active scalp psoriasis at 50-fold magnification, and longitudinal white indentations seen on nail plates affected by onychomycosis at 20-fold magnification.^4-6 The potential value of videodermoscopy in medical education lies not only in the high magnification potential, which may make subtle dermoscopic findings more apparent to novice dermoscopists, but also in the ability to facilitate simultaneous dermoscopic examinations by instructors and trainees.

Educational Applications for Videodermoscopy

To illustrate the educational potential of videodermoscopy, images taken with a standard dermatoscope at 10-fold magnification are presented with videodermoscopic images taken at magnifications ranging from 60- to 185-fold (Figures 1–3). These examples demonstrate the potential for videodermoscopy to facilitate the visualization of subtle dermoscopic features by novice dermoscopists, relating to both the enhanced magnification potential and the potential for simultaneous rather than sequential examination.

Final Thoughts

High-magnification videodermoscopy may be a useful tool to further dermoscopic education. Videodermatoscopes vary in functionality and cost but are available at price points comparable to those of standard optical dermatoscopes. Owners of standard dermatoscopes can approximate some of the benefits of a digital videodermatoscope by using the standard dermatoscope in conjunction with a camera, including those integrated into mobile phones and tablets. By attaching the standard dermatoscope to a camera with a digital display, the digital zoom of the camera can be used to magnify the standard dermoscopic image, enhancing the ability of novice dermoscopists to visualize subtle findings. By presenting this magnified image on a digital display, dermoscopy instructors and trainees would be able to simultaneously view dermoscopic images of lesions, sometimes with magnifications comparable to videodermatoscopes.

In the setting of a dermatology residency program, videodermoscopy can be incorporated into bedside teaching with experienced dermoscopists and for the live presentation of dermoscopic features at departmental grand rounds. By facilitating the simultaneous, high-magnification and live viewing of skin lesions by dermoscopy instructors and trainees, digital videodermoscopy has the potential to address an area of weakness in dermatologic training.

Dermoscopy, or the noninvasive in vivo examination of the epidermis and superficial dermis using magnification, facilitates the diagnosis of pigmented and nonpigmented skin lesions.¹ Despite the benefit of dermoscopy in making early and accurate diagnoses of potentially life-limiting skin cancers, only 48% of dermatologists in the United States use dermoscopy in their practices.² The most commonly cited reason for not using dermoscopy is lack of training.

Although the use of dermoscopy is associated with younger age and more recent graduation from residency compared to nonusers, dermatology resident physicians continue to receive limited training in dermoscopy.² In a survey of 139 dermatology chief residents, 48% were not satisfied with the dermoscopy training that they had received during residency. Residents who received bedside instruction in dermoscopy reported greater satisfaction with their dermoscopy training compared to those who did not receive bedside instruction.³ This article provides a brief comparison of standard dermoscopy versus videodermoscopy for the instruction of trainees on common dermatologic diagnoses.

Bedside Dermoscopy

Standard optical dermatoscopes used for patient care and educational purposes typically incorporate 10-fold magnification and permit examination by a single viewer through a lens. With standard dermatoscopes, bedside dermoscopy instruction consists of the independent sequential viewing of skin lesions by instructors and trainees. Trainees must independently search for dermoscopic features noted by the instructor, which may be difficult for novice users. Simultaneous viewing of lesions would allow instructors to clearly indicate in real time pertinent dermoscopic features to their trainees.

Videodermatoscopes facilitate the simultaneous examination of cutaneous lesions by projecting the dermoscopic image onto a digital screen. Furthermore, these devices can incorporate magnifications of up to 200-fold or greater. In recent years, research pertaining to videodermoscopy has focused on the high magnification capabilities of these devices, specifically dermoscopic features that are visualized at magnifications greater than 10-fold, including the light brown nests of basal cell carcinomas that are seen at 50- to 70-fold magnification, twisted red capillary loops seen in active scalp psoriasis at 50-fold magnification, and longitudinal white indentations seen on nail plates affected by onychomycosis at 20-fold magnification.^4-6 The potential value of videodermoscopy in medical education lies not only in the high magnification potential, which may make subtle dermoscopic findings more apparent to novice dermoscopists, but also in the ability to facilitate simultaneous dermoscopic examinations by instructors and trainees.

Educational Applications for Videodermoscopy

To illustrate the educational potential of videodermoscopy, images taken with a standard dermatoscope at 10-fold magnification are presented with videodermoscopic images taken at magnifications ranging from 60- to 185-fold (Figures 1–3). These examples demonstrate the potential for videodermoscopy to facilitate the visualization of subtle dermoscopic features by novice dermoscopists, relating to both the enhanced magnification potential and the potential for simultaneous rather than sequential examination.

Final Thoughts

High-magnification videodermoscopy may be a useful tool to further dermoscopic education. Videodermatoscopes vary in functionality and cost but are available at price points comparable to those of standard optical dermatoscopes. Owners of standard dermatoscopes can approximate some of the benefits of a digital videodermatoscope by using the standard dermatoscope in conjunction with a camera, including those integrated into mobile phones and tablets. By attaching the standard dermatoscope to a camera with a digital display, the digital zoom of the camera can be used to magnify the standard dermoscopic image, enhancing the ability of novice dermoscopists to visualize subtle findings. By presenting this magnified image on a digital display, dermoscopy instructors and trainees would be able to simultaneously view dermoscopic images of lesions, sometimes with magnifications comparable to videodermatoscopes.

In the setting of a dermatology residency program, videodermoscopy can be incorporated into bedside teaching with experienced dermoscopists and for the live presentation of dermoscopic features at departmental grand rounds. By facilitating the simultaneous, high-magnification and live viewing of skin lesions by dermoscopy instructors and trainees, digital videodermoscopy has the potential to address an area of weakness in dermatologic training.

A new analysis in non-Hispanic whites suggests that rising melanoma rates are real, not attributable to increased levels of detection, and that the burden of the disease could rise significantly in the coming years.

The incidence of melanoma in light-skinned individuals has been rising worldwide in recent years, but it remains unclear whether that trend is due to an increase in the disease, or better screening and diagnosis. The new results are drawn from California, and track incidence and stage at diagnosis of melanoma across different socioeconomic status (SES) groups. Across all groups, the researchers found increases not only in incidence, but also in advanced disease.

copyright Dlumen/Thinkstock

The Stanford Cancer Institute funded the study. Dr. Swetter reported having no financial disclosures.

dermnews@frontlinemedcom.com

A new analysis in non-Hispanic whites suggests that rising melanoma rates are real, not attributable to increased levels of detection, and that the burden of the disease could rise significantly in the coming years.

The incidence of melanoma in light-skinned individuals has been rising worldwide in recent years, but it remains unclear whether that trend is due to an increase in the disease, or better screening and diagnosis. The new results are drawn from California, and track incidence and stage at diagnosis of melanoma across different socioeconomic status (SES) groups. Across all groups, the researchers found increases not only in incidence, but also in advanced disease.

copyright Dlumen/Thinkstock

The Stanford Cancer Institute funded the study. Dr. Swetter reported having no financial disclosures.

dermnews@frontlinemedcom.com

A new analysis in non-Hispanic whites suggests that rising melanoma rates are real, not attributable to increased levels of detection, and that the burden of the disease could rise significantly in the coming years.

The incidence of melanoma in light-skinned individuals has been rising worldwide in recent years, but it remains unclear whether that trend is due to an increase in the disease, or better screening and diagnosis. The new results are drawn from California, and track incidence and stage at diagnosis of melanoma across different socioeconomic status (SES) groups. Across all groups, the researchers found increases not only in incidence, but also in advanced disease.

copyright Dlumen/Thinkstock

The Stanford Cancer Institute funded the study. Dr. Swetter reported having no financial disclosures.

dermnews@frontlinemedcom.com

Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.

The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.

Related: Getting a Better Picture of Skin Cancer

The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.

The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.

A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.

The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.

Related: Immunotherapy in Melanoma

Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.

Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2

Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.

The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.

Related: Getting a Better Picture of Skin Cancer

The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.

The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.

A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.

The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.

Related: Immunotherapy in Melanoma

Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.

Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2

Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.

The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.

Related: Getting a Better Picture of Skin Cancer

The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.

The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.

A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.

The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.

Related: Immunotherapy in Melanoma

Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.

Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2

Skin cancer is diagnosed in approximately 5.4 million individuals annually in the United States, more than the total number of breast, lung, colon, and prostate cancers diagnosed per year.¹ It is estimated that 1 in 5 Americans will develop skin cancer during their lifetime.² The 2 most common forms of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), accounting for 4 million and 1 million cases diagnosed each year, respectively.³ With the increasing incidence of these skin cancers, the use of noninvasive imaging tools for detection and diagnosis has grown.

Ex vivo confocal microscopy is a diagnostic imaging tool that can be used in real-time at the bedside to assess freshly excised tissue for malignancies. It images tissue samples with cellular resolution and within minutes of biopsy or excision. Ex vivo confocal microscopy is a versatile tool that can assist in the diagnosis and management of skin malignancies such as melanoma, BCC, and SCC.

Reflectance vs Fluorescence Mode

Excised lesions can be examined in reflectance or fluorescence mode in great detail but with slightly varying nuclear-to-dermis contrasts depending on the chromophore that is targeted. In reflectance mode (reflectance confocal microscopy [RCM]), melanin and keratin act as endogenous chromophores because of their high refractive index relative to water,^4,5 which allows for the visualization of cellular structures of the skin at low power, as well as microscopic substructures such as melanosomes, cytoplasmic granules, and other cellular organelles at high power. Although an exogenous contrast agent is not required, acetic acid has the capability to highlight nuclei, enhancing the tumor cell-to-dermis contrast in RCM.⁶ Acetic acid is clinically used as a predictor for certain skin and mucosal membrane neoplasms that blanch when exposed to the solution. In the case of RCM, acetic acid increases the visibility of nuclei by inducing the compaction of chromatin. For the acetowhitening to be effective, the sample must be soaked in the solution for a specific amount of time, depending on the concentration.⁷ A concentration between 1% and 10% can be used, but the less concentrated the solution, the longer the time of soaking that is required to achieve sufficiently bright nuclei.⁶

The contrast with acetic acid, however, is quite weak when the tissue is imaged en face, or along the horizontal surface of the sample, due to the collagen in the dermal layer, which has a high reflectance index. This issue is rectified when using the confocal microscope in the fluorescence mode with an exogenous fluorescent dye as a nuclear stain. Fluorescence confocal microscopy (FCM), results in a stronger nuclear-to-dermal contrast because of the role of contrast agents.⁸ The 1000-fold increase in contrast between nuclei and dermis is the result of dye agents that preferentially bind to nuclear DNA, of which acridine orange is the most commonly used.^5,8 Basal cell carcinoma and SCC tumor cells can be visualized with FCM because they appear hyperfluorescent when stained with acridine orange.⁹ The acridine orange–stained cells display bright nuclei, while the cytoplasm and collagen remains dark. A positive feature of acridine orange is that it does not alter the tissue sample during freezing or formalin fixation and thus has no effect on subsequent histopathology that may need to be performed on the sample.¹⁰

High-Resolution Images Aid in Diagnosis

After it is harvested, the tissue sample is soaked in a contrast agent or dye, if needed, depending on the confocal mode to be used. The confocal microscope is then used to take a series of high-resolution individual en face images that are then stitched together to create a final mosaic image that can be up to 12×12 mm.^6,11 With a 200-µm depth visibility, confocal microscopy can capture the cellular structures in the epidermis, dermis, and (if compressed enough) subcutaneous fat in just under 3 minutes.¹²

The images produced through confocal microscopy have an excellent correlation to frozen histological sections and can aid in the diagnosis of many epidermal and dermal malignancies including melanoma, BCC, and SCC. New criteria have been established to aid in the interpretation of the confocal images and identify some of the more common skin cancers.^5,12,13 Basal cell carcinoma samples imaged through fluorescence and reflectance in low-power mode display the distinct nodular patterns with well-demarcated edges, as seen on classical histopathology. In the case of FCM, the cells that make up the tumor display hyperfluorescent areas consistent with nucleated cells that are stained with acridine orange. The main features that identify BCC on FCM images include nuclear pleomorphism and crowding, peripheral palisading, clefting of the basaloid islands, increased nucleus-to-cytoplasm ratio, and the presence of a modified dermis surrounding the mass known as the tumoral stroma^5,12 (Figure).

In addition to fluorescence and a well-defined tumor silhouette, SCC under FCM displays keratin pearls composed of keratinized squames, nuclear pleomorphism, and fluorescent scales in the stratum corneum that are a result of keratin formation.^5,13 The extent of differentiation of the SCC lesion also can be determined by assessing if the silhouette is well defined. A well-defined tumor silhouette is consistent with the diagnosis of a well-differentiated SCC, and vice versa.¹³ Ex vivo RCM also has been shown to be useful in diagnosing malignant melanomas, with melanin acting as an endogenous chromophore. Some of the features seen on imaging include a disarranged epithelium, hyperreflective roundish and dendritic pagetoid cells, and large hyperreflective polymorphic cells in the superficial chorion.¹⁴

Comparison to Conventional Histopathology

Ex vivo confocal microscopy in both the reflectance and fluorescence mode has been shown to perform well compared to conventional histopathology in the diagnosis of biopsy specimens. Ex vivo FCM has been shown to have an overall sensitivity of 88% and specificity of 99% in detecting residual BCC at the margins of excised tissue samples and in the fraction of the time it takes to attain similar results with frozen histopathology.⁹ Ex vivo RCM has been shown to have a higher prognostic capability, with 100% sensitivity and specificity in identifying BCC when scanning the tissue samples en face.¹⁵

Qualitatively, the images produced by RCM and FCM are similar to histopathology in overall architecture. Both techniques enhance the contrast between the epithelium and stroma and create images that can be examined in low as well as high resolution. A substantial difference between confocal microscopy and conventional hematoxylin and eosin–stained histopathology is that the confocal microscope produces images in gray scale. One way to alter the black-and-white images to resemble hematoxylin and eosin–stained slides is through the use of digital staining,¹⁶ which could boost clinical acceptance by physicians who are accustomed to the classical pink-purple appearance of pathology slides and could potentially limit the learning curve needed to read the confocal images.

Application in Mohs Micrographic Surgery

An important clinical application of ex vivo FCM imaging that has emerged is the detection of malignant cells at the excision margins during Mohs micrographic surgery. The use of confocal microscopy has the potential to save time by eliminating the need for tissue fixation while still providing good diagnostic accuracy. Implementing FCM as an imaging tool to guide surgical excisions could provide rapid diagnosis of the tissue, expediting excisions and reconstruction or the Mohs procedure while eliminating patient wait time and the need for frozen histopathology. Ex vivo RCM also has been used to establish laser parameters for CO₂ laser ablation of superficial and early nodular BCC lesions.¹⁷ Other potential uses for ex vivo RCM/FCM could include rapid evaluation of tissue during operating room procedures where rapid frozen sections are currently utilized.

Combining In Vivo and Ex Vivo Confocal Microscopy

Many of the diagnostic guidelines created with the use of ex vivo confocal microscopy have been applied to in vivo use, and therefore the use of both modalities is appealing. In vivo confocal microscopy is a noninvasive technique that has been used to map margins of skin tumors such as BCC and lentigo maligna at the bedside.⁵ It also has been shown to help plan both surgical and nonsurgical treatment modalities and reconstruction before the tumor is excised.¹⁸ This technique also can help the patient understand the extent of the excision and any subsequent reconstruction that may be needed.

Limitations

Ex vivo confocal microscopy used as a diagnostic tool does have some limitations. Its novelty may require surgeons and pathologists to be trained to interpret the images properly and correlate them to conventional diagnostic guidelines. The imaging also is limited to a depth of approximately 200 µm; however, the sample may be flipped so that the underside can be imaged as well, which increases the depth to approximately 400 µm. The tissue being imaged must be fixed flat, which may alter its shape. Complex tissue samples may be difficult to flatten out completely and therefore may be difficult to image. A special mount may be required for the sample to be fixed in a proper position for imaging.⁶

Final Thoughts

Despite some of these limitations, the need for rapid bedside tissue diagnosis makes ex vivo confocal microscopy an attractive device that can be used as an additional diagnostic tool to histopathology and also has been tested in other disciplines, such as breast cancer pathology. In the future, both in vivo and ex vivo confocal microscopy may be utilized to diagnose cutaneous malignancies, guide surgical excisions, and detect lesion progression, and it may become a basis for rapid diagnosis and detection.¹⁹

Skin cancer is diagnosed in approximately 5.4 million individuals annually in the United States, more than the total number of breast, lung, colon, and prostate cancers diagnosed per year.¹ It is estimated that 1 in 5 Americans will develop skin cancer during their lifetime.² The 2 most common forms of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), accounting for 4 million and 1 million cases diagnosed each year, respectively.³ With the increasing incidence of these skin cancers, the use of noninvasive imaging tools for detection and diagnosis has grown.

Ex vivo confocal microscopy is a diagnostic imaging tool that can be used in real-time at the bedside to assess freshly excised tissue for malignancies. It images tissue samples with cellular resolution and within minutes of biopsy or excision. Ex vivo confocal microscopy is a versatile tool that can assist in the diagnosis and management of skin malignancies such as melanoma, BCC, and SCC.

Reflectance vs Fluorescence Mode

Excised lesions can be examined in reflectance or fluorescence mode in great detail but with slightly varying nuclear-to-dermis contrasts depending on the chromophore that is targeted. In reflectance mode (reflectance confocal microscopy [RCM]), melanin and keratin act as endogenous chromophores because of their high refractive index relative to water,^4,5 which allows for the visualization of cellular structures of the skin at low power, as well as microscopic substructures such as melanosomes, cytoplasmic granules, and other cellular organelles at high power. Although an exogenous contrast agent is not required, acetic acid has the capability to highlight nuclei, enhancing the tumor cell-to-dermis contrast in RCM.⁶ Acetic acid is clinically used as a predictor for certain skin and mucosal membrane neoplasms that blanch when exposed to the solution. In the case of RCM, acetic acid increases the visibility of nuclei by inducing the compaction of chromatin. For the acetowhitening to be effective, the sample must be soaked in the solution for a specific amount of time, depending on the concentration.⁷ A concentration between 1% and 10% can be used, but the less concentrated the solution, the longer the time of soaking that is required to achieve sufficiently bright nuclei.⁶

The contrast with acetic acid, however, is quite weak when the tissue is imaged en face, or along the horizontal surface of the sample, due to the collagen in the dermal layer, which has a high reflectance index. This issue is rectified when using the confocal microscope in the fluorescence mode with an exogenous fluorescent dye as a nuclear stain. Fluorescence confocal microscopy (FCM), results in a stronger nuclear-to-dermal contrast because of the role of contrast agents.⁸ The 1000-fold increase in contrast between nuclei and dermis is the result of dye agents that preferentially bind to nuclear DNA, of which acridine orange is the most commonly used.^5,8 Basal cell carcinoma and SCC tumor cells can be visualized with FCM because they appear hyperfluorescent when stained with acridine orange.⁹ The acridine orange–stained cells display bright nuclei, while the cytoplasm and collagen remains dark. A positive feature of acridine orange is that it does not alter the tissue sample during freezing or formalin fixation and thus has no effect on subsequent histopathology that may need to be performed on the sample.¹⁰

High-Resolution Images Aid in Diagnosis

After it is harvested, the tissue sample is soaked in a contrast agent or dye, if needed, depending on the confocal mode to be used. The confocal microscope is then used to take a series of high-resolution individual en face images that are then stitched together to create a final mosaic image that can be up to 12×12 mm.^6,11 With a 200-µm depth visibility, confocal microscopy can capture the cellular structures in the epidermis, dermis, and (if compressed enough) subcutaneous fat in just under 3 minutes.¹²

The images produced through confocal microscopy have an excellent correlation to frozen histological sections and can aid in the diagnosis of many epidermal and dermal malignancies including melanoma, BCC, and SCC. New criteria have been established to aid in the interpretation of the confocal images and identify some of the more common skin cancers.^5,12,13 Basal cell carcinoma samples imaged through fluorescence and reflectance in low-power mode display the distinct nodular patterns with well-demarcated edges, as seen on classical histopathology. In the case of FCM, the cells that make up the tumor display hyperfluorescent areas consistent with nucleated cells that are stained with acridine orange. The main features that identify BCC on FCM images include nuclear pleomorphism and crowding, peripheral palisading, clefting of the basaloid islands, increased nucleus-to-cytoplasm ratio, and the presence of a modified dermis surrounding the mass known as the tumoral stroma^5,12 (Figure).

In addition to fluorescence and a well-defined tumor silhouette, SCC under FCM displays keratin pearls composed of keratinized squames, nuclear pleomorphism, and fluorescent scales in the stratum corneum that are a result of keratin formation.^5,13 The extent of differentiation of the SCC lesion also can be determined by assessing if the silhouette is well defined. A well-defined tumor silhouette is consistent with the diagnosis of a well-differentiated SCC, and vice versa.¹³ Ex vivo RCM also has been shown to be useful in diagnosing malignant melanomas, with melanin acting as an endogenous chromophore. Some of the features seen on imaging include a disarranged epithelium, hyperreflective roundish and dendritic pagetoid cells, and large hyperreflective polymorphic cells in the superficial chorion.¹⁴

Comparison to Conventional Histopathology

Ex vivo confocal microscopy in both the reflectance and fluorescence mode has been shown to perform well compared to conventional histopathology in the diagnosis of biopsy specimens. Ex vivo FCM has been shown to have an overall sensitivity of 88% and specificity of 99% in detecting residual BCC at the margins of excised tissue samples and in the fraction of the time it takes to attain similar results with frozen histopathology.⁹ Ex vivo RCM has been shown to have a higher prognostic capability, with 100% sensitivity and specificity in identifying BCC when scanning the tissue samples en face.¹⁵

Qualitatively, the images produced by RCM and FCM are similar to histopathology in overall architecture. Both techniques enhance the contrast between the epithelium and stroma and create images that can be examined in low as well as high resolution. A substantial difference between confocal microscopy and conventional hematoxylin and eosin–stained histopathology is that the confocal microscope produces images in gray scale. One way to alter the black-and-white images to resemble hematoxylin and eosin–stained slides is through the use of digital staining,¹⁶ which could boost clinical acceptance by physicians who are accustomed to the classical pink-purple appearance of pathology slides and could potentially limit the learning curve needed to read the confocal images.

Application in Mohs Micrographic Surgery

An important clinical application of ex vivo FCM imaging that has emerged is the detection of malignant cells at the excision margins during Mohs micrographic surgery. The use of confocal microscopy has the potential to save time by eliminating the need for tissue fixation while still providing good diagnostic accuracy. Implementing FCM as an imaging tool to guide surgical excisions could provide rapid diagnosis of the tissue, expediting excisions and reconstruction or the Mohs procedure while eliminating patient wait time and the need for frozen histopathology. Ex vivo RCM also has been used to establish laser parameters for CO₂ laser ablation of superficial and early nodular BCC lesions.¹⁷ Other potential uses for ex vivo RCM/FCM could include rapid evaluation of tissue during operating room procedures where rapid frozen sections are currently utilized.

Combining In Vivo and Ex Vivo Confocal Microscopy

Many of the diagnostic guidelines created with the use of ex vivo confocal microscopy have been applied to in vivo use, and therefore the use of both modalities is appealing. In vivo confocal microscopy is a noninvasive technique that has been used to map margins of skin tumors such as BCC and lentigo maligna at the bedside.⁵ It also has been shown to help plan both surgical and nonsurgical treatment modalities and reconstruction before the tumor is excised.¹⁸ This technique also can help the patient understand the extent of the excision and any subsequent reconstruction that may be needed.

Limitations

Ex vivo confocal microscopy used as a diagnostic tool does have some limitations. Its novelty may require surgeons and pathologists to be trained to interpret the images properly and correlate them to conventional diagnostic guidelines. The imaging also is limited to a depth of approximately 200 µm; however, the sample may be flipped so that the underside can be imaged as well, which increases the depth to approximately 400 µm. The tissue being imaged must be fixed flat, which may alter its shape. Complex tissue samples may be difficult to flatten out completely and therefore may be difficult to image. A special mount may be required for the sample to be fixed in a proper position for imaging.⁶

Final Thoughts

Despite some of these limitations, the need for rapid bedside tissue diagnosis makes ex vivo confocal microscopy an attractive device that can be used as an additional diagnostic tool to histopathology and also has been tested in other disciplines, such as breast cancer pathology. In the future, both in vivo and ex vivo confocal microscopy may be utilized to diagnose cutaneous malignancies, guide surgical excisions, and detect lesion progression, and it may become a basis for rapid diagnosis and detection.¹⁹

Skin cancer is diagnosed in approximately 5.4 million individuals annually in the United States, more than the total number of breast, lung, colon, and prostate cancers diagnosed per year.¹ It is estimated that 1 in 5 Americans will develop skin cancer during their lifetime.² The 2 most common forms of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), accounting for 4 million and 1 million cases diagnosed each year, respectively.³ With the increasing incidence of these skin cancers, the use of noninvasive imaging tools for detection and diagnosis has grown.

Ex vivo confocal microscopy is a diagnostic imaging tool that can be used in real-time at the bedside to assess freshly excised tissue for malignancies. It images tissue samples with cellular resolution and within minutes of biopsy or excision. Ex vivo confocal microscopy is a versatile tool that can assist in the diagnosis and management of skin malignancies such as melanoma, BCC, and SCC.

Reflectance vs Fluorescence Mode

Excised lesions can be examined in reflectance or fluorescence mode in great detail but with slightly varying nuclear-to-dermis contrasts depending on the chromophore that is targeted. In reflectance mode (reflectance confocal microscopy [RCM]), melanin and keratin act as endogenous chromophores because of their high refractive index relative to water,^4,5 which allows for the visualization of cellular structures of the skin at low power, as well as microscopic substructures such as melanosomes, cytoplasmic granules, and other cellular organelles at high power. Although an exogenous contrast agent is not required, acetic acid has the capability to highlight nuclei, enhancing the tumor cell-to-dermis contrast in RCM.⁶ Acetic acid is clinically used as a predictor for certain skin and mucosal membrane neoplasms that blanch when exposed to the solution. In the case of RCM, acetic acid increases the visibility of nuclei by inducing the compaction of chromatin. For the acetowhitening to be effective, the sample must be soaked in the solution for a specific amount of time, depending on the concentration.⁷ A concentration between 1% and 10% can be used, but the less concentrated the solution, the longer the time of soaking that is required to achieve sufficiently bright nuclei.⁶

The contrast with acetic acid, however, is quite weak when the tissue is imaged en face, or along the horizontal surface of the sample, due to the collagen in the dermal layer, which has a high reflectance index. This issue is rectified when using the confocal microscope in the fluorescence mode with an exogenous fluorescent dye as a nuclear stain. Fluorescence confocal microscopy (FCM), results in a stronger nuclear-to-dermal contrast because of the role of contrast agents.⁸ The 1000-fold increase in contrast between nuclei and dermis is the result of dye agents that preferentially bind to nuclear DNA, of which acridine orange is the most commonly used.^5,8 Basal cell carcinoma and SCC tumor cells can be visualized with FCM because they appear hyperfluorescent when stained with acridine orange.⁹ The acridine orange–stained cells display bright nuclei, while the cytoplasm and collagen remains dark. A positive feature of acridine orange is that it does not alter the tissue sample during freezing or formalin fixation and thus has no effect on subsequent histopathology that may need to be performed on the sample.¹⁰

High-Resolution Images Aid in Diagnosis

After it is harvested, the tissue sample is soaked in a contrast agent or dye, if needed, depending on the confocal mode to be used. The confocal microscope is then used to take a series of high-resolution individual en face images that are then stitched together to create a final mosaic image that can be up to 12×12 mm.^6,11 With a 200-µm depth visibility, confocal microscopy can capture the cellular structures in the epidermis, dermis, and (if compressed enough) subcutaneous fat in just under 3 minutes.¹²

The images produced through confocal microscopy have an excellent correlation to frozen histological sections and can aid in the diagnosis of many epidermal and dermal malignancies including melanoma, BCC, and SCC. New criteria have been established to aid in the interpretation of the confocal images and identify some of the more common skin cancers.^5,12,13 Basal cell carcinoma samples imaged through fluorescence and reflectance in low-power mode display the distinct nodular patterns with well-demarcated edges, as seen on classical histopathology. In the case of FCM, the cells that make up the tumor display hyperfluorescent areas consistent with nucleated cells that are stained with acridine orange. The main features that identify BCC on FCM images include nuclear pleomorphism and crowding, peripheral palisading, clefting of the basaloid islands, increased nucleus-to-cytoplasm ratio, and the presence of a modified dermis surrounding the mass known as the tumoral stroma^5,12 (Figure).

In addition to fluorescence and a well-defined tumor silhouette, SCC under FCM displays keratin pearls composed of keratinized squames, nuclear pleomorphism, and fluorescent scales in the stratum corneum that are a result of keratin formation.^5,13 The extent of differentiation of the SCC lesion also can be determined by assessing if the silhouette is well defined. A well-defined tumor silhouette is consistent with the diagnosis of a well-differentiated SCC, and vice versa.¹³ Ex vivo RCM also has been shown to be useful in diagnosing malignant melanomas, with melanin acting as an endogenous chromophore. Some of the features seen on imaging include a disarranged epithelium, hyperreflective roundish and dendritic pagetoid cells, and large hyperreflective polymorphic cells in the superficial chorion.¹⁴

Comparison to Conventional Histopathology

Ex vivo confocal microscopy in both the reflectance and fluorescence mode has been shown to perform well compared to conventional histopathology in the diagnosis of biopsy specimens. Ex vivo FCM has been shown to have an overall sensitivity of 88% and specificity of 99% in detecting residual BCC at the margins of excised tissue samples and in the fraction of the time it takes to attain similar results with frozen histopathology.⁹ Ex vivo RCM has been shown to have a higher prognostic capability, with 100% sensitivity and specificity in identifying BCC when scanning the tissue samples en face.¹⁵

Qualitatively, the images produced by RCM and FCM are similar to histopathology in overall architecture. Both techniques enhance the contrast between the epithelium and stroma and create images that can be examined in low as well as high resolution. A substantial difference between confocal microscopy and conventional hematoxylin and eosin–stained histopathology is that the confocal microscope produces images in gray scale. One way to alter the black-and-white images to resemble hematoxylin and eosin–stained slides is through the use of digital staining,¹⁶ which could boost clinical acceptance by physicians who are accustomed to the classical pink-purple appearance of pathology slides and could potentially limit the learning curve needed to read the confocal images.

Application in Mohs Micrographic Surgery

An important clinical application of ex vivo FCM imaging that has emerged is the detection of malignant cells at the excision margins during Mohs micrographic surgery. The use of confocal microscopy has the potential to save time by eliminating the need for tissue fixation while still providing good diagnostic accuracy. Implementing FCM as an imaging tool to guide surgical excisions could provide rapid diagnosis of the tissue, expediting excisions and reconstruction or the Mohs procedure while eliminating patient wait time and the need for frozen histopathology. Ex vivo RCM also has been used to establish laser parameters for CO₂ laser ablation of superficial and early nodular BCC lesions.¹⁷ Other potential uses for ex vivo RCM/FCM could include rapid evaluation of tissue during operating room procedures where rapid frozen sections are currently utilized.

Combining In Vivo and Ex Vivo Confocal Microscopy

Many of the diagnostic guidelines created with the use of ex vivo confocal microscopy have been applied to in vivo use, and therefore the use of both modalities is appealing. In vivo confocal microscopy is a noninvasive technique that has been used to map margins of skin tumors such as BCC and lentigo maligna at the bedside.⁵ It also has been shown to help plan both surgical and nonsurgical treatment modalities and reconstruction before the tumor is excised.¹⁸ This technique also can help the patient understand the extent of the excision and any subsequent reconstruction that may be needed.

Limitations

Ex vivo confocal microscopy used as a diagnostic tool does have some limitations. Its novelty may require surgeons and pathologists to be trained to interpret the images properly and correlate them to conventional diagnostic guidelines. The imaging also is limited to a depth of approximately 200 µm; however, the sample may be flipped so that the underside can be imaged as well, which increases the depth to approximately 400 µm. The tissue being imaged must be fixed flat, which may alter its shape. Complex tissue samples may be difficult to flatten out completely and therefore may be difficult to image. A special mount may be required for the sample to be fixed in a proper position for imaging.⁶

Final Thoughts

Despite some of these limitations, the need for rapid bedside tissue diagnosis makes ex vivo confocal microscopy an attractive device that can be used as an additional diagnostic tool to histopathology and also has been tested in other disciplines, such as breast cancer pathology. In the future, both in vivo and ex vivo confocal microscopy may be utilized to diagnose cutaneous malignancies, guide surgical excisions, and detect lesion progression, and it may become a basis for rapid diagnosis and detection.¹⁹

NEW YORK – If dermatopathologists had a wish list they could give their dermatologist colleagues, what might it include? High up on the list for many, said Robert Phelps, MD, might be to have them share the clinical picture, treat the specimen gently, and give the best landmarks possible.

Speaking at the summer meeting of the American Academy of Dermatology, Dr. Phelps, director of the dermatopathology service at Mount Sinai Medical Center in New York, led off the dermatopathologist-run session – appropriately titled “Help Me Help You” – by asking, “How can the clinician provide the optimal biopsy?”

It’s always helpful to have as much clinical information as possible, said Dr. Phelps, whose discussion focused on tips for neoplastic lesions. This might include prior history of malignancy, autoimmune disease, pathergy, or other relevant medical history, but clinical pictures can also be a big help, although there can be technical and patient privacy issues to overcome, he noted. If, for example, a larger lesion or rash is being biopsied rather than excised, it can be very helpful to see the larger field and full area of distribution of the lesion in question. Submitting multiple specimens for rashes and larger lesions is always a good idea too, he added.

Although curettage can be a great way to biopsy – and perhaps even definitively treat some lesions – problems can arise on the dermatopathologist’s side when melanocytic lesions are curetted for biopsy, according to Dr. Phelps, a practicing dermatologist and a dermatopathologist. “By virtue of the force of the biopsy, the specimen is often fragmented, and histology can be distorted,” he said. One element of that distortion can be that melanocytes can appear to be free floating, which is a problem. “Dyshesion of melanocytes is usually an indication of atypia … It is an important histologic clue as to the possibility of a malignancy supervening.”

These factors can make it tough for a dermatopathologist to make an accurate call. “If there are free-floating melanocytes from a curetted specimen, I can’t rule out invasive melanoma,” explained Dr. Phelps, since he can’t tell if he is seeing true atypia or disruption that’s an artifact of the collection technique.

In this instance, he said, a dermatopathologist would be “obligated to overcall, because one couldn’t really determine the pathology.” The bottom line? “Don’t curette biopsies of melanocytic lesions.”

Another technique that can interfere with the ability to read a tissue specimen accurately is electrodesiccation. Although it’s often performed in conjunction with curettage, electrodesiccation can cause changes in tissue consistent with thermal injury. “Essentially, the tissue has been burned,” Dr. Phelps pointed out. This can result in a characteristic streaming pattern of nuclei, and the dermis can acquire a “peculiar homogenized appearance,” he said.

Although electrodesiccation can be a useful technique to make sure margins are controlled, “when you do this, just be aware that the interpretation is difficult,” he noted. “It’s difficult to tell where the margins are and if they are the appropriate and correct margins,” he said.

When possible, try to avoid squeezing the tumor, Dr. Phelps advised. Excessive pressure on the specimen can distort cell architecture and make pathological diagnosis really challenging, particularly in lymphoid tumors, he said.

“Often, the tumor is not recognizable,” he added. Crush artifact can result in an appearance of small bluish clumps and smearing of collagen fibers. The effect, he said, can be particularly pronounced with small cell carcinoma and lymphoma, and with rapidly proliferating tumors.

Dr. Phelps said that during his training, he was taught not to use forceps to extract a stubborn punch biopsy specimen; rather, he was trained to use a needle to tease out the specimen. Fear of a self-inflicted needle stick with this technique may be a deterrent, he acknowledged. If forceps are used, he suggested being as gentle as possible and using the finest forceps available.

When pathologists receive an intact excised lesion – one not obtained using a Mohs technique, “delineation of the margin is essential,” Dr. Phelps said. Further, accurate mapping is critical to helping the examiner understand the anatomic orientation of the specimen, a key prerequisite that enables accurate communication from the dermatopathologist back to the clinician if there’s a question regarding the need for retreatment, he added.

For an elliptical excision, ideally, both poles of the ellipse would be suture-tagged, and at least one tag is essential, he said. Then superior and inferior borders can be inked with contrasting colors, and the epidermal borders of the lesion should be marked as well. When the specimen is submitted, it should be accompanied by an accurate map that clearly indicates the coding for medial, lateral, inferior, and superior aspects of the specimen. “Always prepare a specimen diagram for oriented specimens,” Dr. Phelps noted.

Don’t forget to make sure that the left-right orientation on the diagram corresponds to the specimen’s orientation on the patient, he added. Some facilities use a clock face system to indicate orientation and positioning, which may be the clearest method of all.

Sometimes, it’s difficult for the dermatopathologist to visualize whether the specimen is aligned in true medial-lateral fashion, or along skin tension lines, which tend to run diagonally, so “the more clinical information, the better,” he said. “With good mapping, precise retreatment can be optimal,” he said.

Dr. Phelps reported that he had no relevant conflicts of interest.
 

koakes@frontlinemedcom.com

On Twitter @karioakes

NEW YORK – If dermatopathologists had a wish list they could give their dermatologist colleagues, what might it include? High up on the list for many, said Robert Phelps, MD, might be to have them share the clinical picture, treat the specimen gently, and give the best landmarks possible.

Speaking at the summer meeting of the American Academy of Dermatology, Dr. Phelps, director of the dermatopathology service at Mount Sinai Medical Center in New York, led off the dermatopathologist-run session – appropriately titled “Help Me Help You” – by asking, “How can the clinician provide the optimal biopsy?”

It’s always helpful to have as much clinical information as possible, said Dr. Phelps, whose discussion focused on tips for neoplastic lesions. This might include prior history of malignancy, autoimmune disease, pathergy, or other relevant medical history, but clinical pictures can also be a big help, although there can be technical and patient privacy issues to overcome, he noted. If, for example, a larger lesion or rash is being biopsied rather than excised, it can be very helpful to see the larger field and full area of distribution of the lesion in question. Submitting multiple specimens for rashes and larger lesions is always a good idea too, he added.

Although curettage can be a great way to biopsy – and perhaps even definitively treat some lesions – problems can arise on the dermatopathologist’s side when melanocytic lesions are curetted for biopsy, according to Dr. Phelps, a practicing dermatologist and a dermatopathologist. “By virtue of the force of the biopsy, the specimen is often fragmented, and histology can be distorted,” he said. One element of that distortion can be that melanocytes can appear to be free floating, which is a problem. “Dyshesion of melanocytes is usually an indication of atypia … It is an important histologic clue as to the possibility of a malignancy supervening.”

These factors can make it tough for a dermatopathologist to make an accurate call. “If there are free-floating melanocytes from a curetted specimen, I can’t rule out invasive melanoma,” explained Dr. Phelps, since he can’t tell if he is seeing true atypia or disruption that’s an artifact of the collection technique.

In this instance, he said, a dermatopathologist would be “obligated to overcall, because one couldn’t really determine the pathology.” The bottom line? “Don’t curette biopsies of melanocytic lesions.”

Another technique that can interfere with the ability to read a tissue specimen accurately is electrodesiccation. Although it’s often performed in conjunction with curettage, electrodesiccation can cause changes in tissue consistent with thermal injury. “Essentially, the tissue has been burned,” Dr. Phelps pointed out. This can result in a characteristic streaming pattern of nuclei, and the dermis can acquire a “peculiar homogenized appearance,” he said.

Although electrodesiccation can be a useful technique to make sure margins are controlled, “when you do this, just be aware that the interpretation is difficult,” he noted. “It’s difficult to tell where the margins are and if they are the appropriate and correct margins,” he said.

When possible, try to avoid squeezing the tumor, Dr. Phelps advised. Excessive pressure on the specimen can distort cell architecture and make pathological diagnosis really challenging, particularly in lymphoid tumors, he said.

“Often, the tumor is not recognizable,” he added. Crush artifact can result in an appearance of small bluish clumps and smearing of collagen fibers. The effect, he said, can be particularly pronounced with small cell carcinoma and lymphoma, and with rapidly proliferating tumors.

Dr. Phelps said that during his training, he was taught not to use forceps to extract a stubborn punch biopsy specimen; rather, he was trained to use a needle to tease out the specimen. Fear of a self-inflicted needle stick with this technique may be a deterrent, he acknowledged. If forceps are used, he suggested being as gentle as possible and using the finest forceps available.

When pathologists receive an intact excised lesion – one not obtained using a Mohs technique, “delineation of the margin is essential,” Dr. Phelps said. Further, accurate mapping is critical to helping the examiner understand the anatomic orientation of the specimen, a key prerequisite that enables accurate communication from the dermatopathologist back to the clinician if there’s a question regarding the need for retreatment, he added.

For an elliptical excision, ideally, both poles of the ellipse would be suture-tagged, and at least one tag is essential, he said. Then superior and inferior borders can be inked with contrasting colors, and the epidermal borders of the lesion should be marked as well. When the specimen is submitted, it should be accompanied by an accurate map that clearly indicates the coding for medial, lateral, inferior, and superior aspects of the specimen. “Always prepare a specimen diagram for oriented specimens,” Dr. Phelps noted.

Don’t forget to make sure that the left-right orientation on the diagram corresponds to the specimen’s orientation on the patient, he added. Some facilities use a clock face system to indicate orientation and positioning, which may be the clearest method of all.

Sometimes, it’s difficult for the dermatopathologist to visualize whether the specimen is aligned in true medial-lateral fashion, or along skin tension lines, which tend to run diagonally, so “the more clinical information, the better,” he said. “With good mapping, precise retreatment can be optimal,” he said.

Dr. Phelps reported that he had no relevant conflicts of interest.
 

koakes@frontlinemedcom.com

On Twitter @karioakes

NEW YORK – If dermatopathologists had a wish list they could give their dermatologist colleagues, what might it include? High up on the list for many, said Robert Phelps, MD, might be to have them share the clinical picture, treat the specimen gently, and give the best landmarks possible.

Speaking at the summer meeting of the American Academy of Dermatology, Dr. Phelps, director of the dermatopathology service at Mount Sinai Medical Center in New York, led off the dermatopathologist-run session – appropriately titled “Help Me Help You” – by asking, “How can the clinician provide the optimal biopsy?”

It’s always helpful to have as much clinical information as possible, said Dr. Phelps, whose discussion focused on tips for neoplastic lesions. This might include prior history of malignancy, autoimmune disease, pathergy, or other relevant medical history, but clinical pictures can also be a big help, although there can be technical and patient privacy issues to overcome, he noted. If, for example, a larger lesion or rash is being biopsied rather than excised, it can be very helpful to see the larger field and full area of distribution of the lesion in question. Submitting multiple specimens for rashes and larger lesions is always a good idea too, he added.

Although curettage can be a great way to biopsy – and perhaps even definitively treat some lesions – problems can arise on the dermatopathologist’s side when melanocytic lesions are curetted for biopsy, according to Dr. Phelps, a practicing dermatologist and a dermatopathologist. “By virtue of the force of the biopsy, the specimen is often fragmented, and histology can be distorted,” he said. One element of that distortion can be that melanocytes can appear to be free floating, which is a problem. “Dyshesion of melanocytes is usually an indication of atypia … It is an important histologic clue as to the possibility of a malignancy supervening.”

These factors can make it tough for a dermatopathologist to make an accurate call. “If there are free-floating melanocytes from a curetted specimen, I can’t rule out invasive melanoma,” explained Dr. Phelps, since he can’t tell if he is seeing true atypia or disruption that’s an artifact of the collection technique.

In this instance, he said, a dermatopathologist would be “obligated to overcall, because one couldn’t really determine the pathology.” The bottom line? “Don’t curette biopsies of melanocytic lesions.”

Another technique that can interfere with the ability to read a tissue specimen accurately is electrodesiccation. Although it’s often performed in conjunction with curettage, electrodesiccation can cause changes in tissue consistent with thermal injury. “Essentially, the tissue has been burned,” Dr. Phelps pointed out. This can result in a characteristic streaming pattern of nuclei, and the dermis can acquire a “peculiar homogenized appearance,” he said.

Although electrodesiccation can be a useful technique to make sure margins are controlled, “when you do this, just be aware that the interpretation is difficult,” he noted. “It’s difficult to tell where the margins are and if they are the appropriate and correct margins,” he said.

When possible, try to avoid squeezing the tumor, Dr. Phelps advised. Excessive pressure on the specimen can distort cell architecture and make pathological diagnosis really challenging, particularly in lymphoid tumors, he said.

“Often, the tumor is not recognizable,” he added. Crush artifact can result in an appearance of small bluish clumps and smearing of collagen fibers. The effect, he said, can be particularly pronounced with small cell carcinoma and lymphoma, and with rapidly proliferating tumors.

Dr. Phelps said that during his training, he was taught not to use forceps to extract a stubborn punch biopsy specimen; rather, he was trained to use a needle to tease out the specimen. Fear of a self-inflicted needle stick with this technique may be a deterrent, he acknowledged. If forceps are used, he suggested being as gentle as possible and using the finest forceps available.

When pathologists receive an intact excised lesion – one not obtained using a Mohs technique, “delineation of the margin is essential,” Dr. Phelps said. Further, accurate mapping is critical to helping the examiner understand the anatomic orientation of the specimen, a key prerequisite that enables accurate communication from the dermatopathologist back to the clinician if there’s a question regarding the need for retreatment, he added.

For an elliptical excision, ideally, both poles of the ellipse would be suture-tagged, and at least one tag is essential, he said. Then superior and inferior borders can be inked with contrasting colors, and the epidermal borders of the lesion should be marked as well. When the specimen is submitted, it should be accompanied by an accurate map that clearly indicates the coding for medial, lateral, inferior, and superior aspects of the specimen. “Always prepare a specimen diagram for oriented specimens,” Dr. Phelps noted.

Don’t forget to make sure that the left-right orientation on the diagram corresponds to the specimen’s orientation on the patient, he added. Some facilities use a clock face system to indicate orientation and positioning, which may be the clearest method of all.

Sometimes, it’s difficult for the dermatopathologist to visualize whether the specimen is aligned in true medial-lateral fashion, or along skin tension lines, which tend to run diagonally, so “the more clinical information, the better,” he said. “With good mapping, precise retreatment can be optimal,” he said.

Dr. Phelps reported that he had no relevant conflicts of interest.
 

koakes@frontlinemedcom.com

On Twitter @karioakes

A handheld detector that offers noninvasive real-time imaging can help dermatologic surgeons get a better idea of skin cancer dimensions before committing to surgery, according to researchers from National Skin Centre and Singapore Bioimaging Consortium, both in Singapore, and Technical University of Munich and iThera Medical GmbH, both in Germany.

Current imaging technologies can lead to excessive or incomplete removal of the cancer, the researchers say. The multispectral optoacoustic tomography (MSOT) allows the user to differentiate tissue chromophores (the chromophore is the part of the molecule responsible for its color) and exogenous contrast agents based on their spectral signatures.

The researchers performed MSOT imaging with 2- and 3-dimensional handheld scanners on 21 patients with nonmelanoma skin cancers. All the skin lesions had recognizable images on MSOT with both detectors, visualizing the shape and thickness of the lesions. The 2D and 3D detectors also offered images with well-resolved tissue chromophores. But the volumetric probe gave more accurate tumor dimensions compared with those from histology analysis.

Aggressive types of skin cancers can involve deeper structures, such as predominant deep blood vessels, the researchers note—another reason the MSOT detector could be useful. In one case, the depth of the basal cell carcinoma, which included its underlying vasculature, reached beyond 3 mm, which might have gone undetected by other imaging modalities, they say.

The fact that the device is also noninvasive and offers real-time imaging, the researchers suggest, makes volumetric MSOT “an ideal modality for longitudinal monitoring of skin diseases and treatment responses.”

Source:

Attia ABE, Chuah SY, Razansky D, et al. Photoacoustics. 2017;7:20-26.
doi: 10.1016/j.pacs.2017.05.003.

A handheld detector that offers noninvasive real-time imaging can help dermatologic surgeons get a better idea of skin cancer dimensions before committing to surgery, according to researchers from National Skin Centre and Singapore Bioimaging Consortium, both in Singapore, and Technical University of Munich and iThera Medical GmbH, both in Germany.

Current imaging technologies can lead to excessive or incomplete removal of the cancer, the researchers say. The multispectral optoacoustic tomography (MSOT) allows the user to differentiate tissue chromophores (the chromophore is the part of the molecule responsible for its color) and exogenous contrast agents based on their spectral signatures.

The researchers performed MSOT imaging with 2- and 3-dimensional handheld scanners on 21 patients with nonmelanoma skin cancers. All the skin lesions had recognizable images on MSOT with both detectors, visualizing the shape and thickness of the lesions. The 2D and 3D detectors also offered images with well-resolved tissue chromophores. But the volumetric probe gave more accurate tumor dimensions compared with those from histology analysis.

Aggressive types of skin cancers can involve deeper structures, such as predominant deep blood vessels, the researchers note—another reason the MSOT detector could be useful. In one case, the depth of the basal cell carcinoma, which included its underlying vasculature, reached beyond 3 mm, which might have gone undetected by other imaging modalities, they say.

The fact that the device is also noninvasive and offers real-time imaging, the researchers suggest, makes volumetric MSOT “an ideal modality for longitudinal monitoring of skin diseases and treatment responses.”

Source:

Attia ABE, Chuah SY, Razansky D, et al. Photoacoustics. 2017;7:20-26.
doi: 10.1016/j.pacs.2017.05.003.

A handheld detector that offers noninvasive real-time imaging can help dermatologic surgeons get a better idea of skin cancer dimensions before committing to surgery, according to researchers from National Skin Centre and Singapore Bioimaging Consortium, both in Singapore, and Technical University of Munich and iThera Medical GmbH, both in Germany.

Current imaging technologies can lead to excessive or incomplete removal of the cancer, the researchers say. The multispectral optoacoustic tomography (MSOT) allows the user to differentiate tissue chromophores (the chromophore is the part of the molecule responsible for its color) and exogenous contrast agents based on their spectral signatures.

The researchers performed MSOT imaging with 2- and 3-dimensional handheld scanners on 21 patients with nonmelanoma skin cancers. All the skin lesions had recognizable images on MSOT with both detectors, visualizing the shape and thickness of the lesions. The 2D and 3D detectors also offered images with well-resolved tissue chromophores. But the volumetric probe gave more accurate tumor dimensions compared with those from histology analysis.

Aggressive types of skin cancers can involve deeper structures, such as predominant deep blood vessels, the researchers note—another reason the MSOT detector could be useful. In one case, the depth of the basal cell carcinoma, which included its underlying vasculature, reached beyond 3 mm, which might have gone undetected by other imaging modalities, they say.

The fact that the device is also noninvasive and offers real-time imaging, the researchers suggest, makes volumetric MSOT “an ideal modality for longitudinal monitoring of skin diseases and treatment responses.”

Source:

Attia ABE, Chuah SY, Razansky D, et al. Photoacoustics. 2017;7:20-26.
doi: 10.1016/j.pacs.2017.05.003.