Interpreting MART-1 Immunohistochemistry Frozen Sections

In this interview, Dr Leitenberger discusses his session, “Mohs for Melanoma Immunohistochemistry (IHC) Refresher,” at the 2023 ACMS Annual Meeting. He covered the topic, “Mohs IHC Interpretation.”

Justin Leitenberger, MD, FACMS, is an associate professor, director of dermatologic surgery, and associate program director of the micrographic surgery and dermatologic oncology fellowship at Oregon Health and Science University (OHSU) in Portland, OR. He is also the president of the International Immunosuppression and Transplant Skin Cancer Collaborative.

The Dermatologist: Can you give us a recap of what was covered during your session at the 2023 ACMS Annual Meeting?

Dr Leitenberger: Our session focused on describing the indications for Mohs for melanoma using the MART-1 immunohistochemistry stain. We also reviewed relevant publications describing the ideal technique and use in specialty site melanomas and how to begin and set up immunostaining protocols in a Mohs lab if a lab does not have those protocols already in place. Most surgeons do not perform this technique, yet it is becoming more common and utilized across the country.

The Dermatologist: How should the frozen MART-1 pathology slides be interpreted and classified?

Dr Leitenberger: I shared numerous slides from our own practice throughout our presentation, which reinforced for the audience the positive and negative margin appearance and how they should be classified. The 5 criteria have been published and they are similar to regular dermatopathology criteria for the diagnosis of melanoma in situ. The first criterion is nesting of 3 or more atypical melanocytes. The second is confluence of 10 or greater melanocytes that are in direct contact with the basement membrane. The third is called follicular extension, described as confluent extension beyond the follicular infundibulum. The fourth criterion is pagetosis or pagetoid spread above the mid-epidermis in the presence of increased density of melanocytes and severe melanocytic atypia. And the fifth criterion is severe melanocytic atypia, which is described as large, atypical nuclei or significant pleomorphism of the melanocytes.

The Dermatologist: Can you go over the key points from your session?

Dr Leitenberger: The session really highlighted the technique and how it requires additional time, lab coordination, and multidisciplinary care. We talked about how when using the Mohs technique for melanoma with MART-1 immunostaining, these patients can result with larger surgical defects and then subsequently a more complex reconstruction. We discussed that there is a learning curve for interpreting MART-1 immunostains, and this may be similar to a learning curve seen at the beginning of any type of fellowship. There are data that show a Mohs fellow makes more errors at the beginning of their fellowship, and then that error rate kind of flattens and becomes less frequent with more experience and exposure. And, similarly, we can think of interpreting MART-1s for the first time, there may be a higher rate of misinterpretation of the immunostains and that accuracy likely improves with more exposure and experience.

One of the things that I think is unique in the approach at OHSU is from the beginning of my career for the first 6 years, we did MART-1 immunostaining with an additional final permanent rate margin that was sent to our dermatopathologist. We recently published data looking at our concordance rate from our MART-1 cases that had a final permanent margin and what the dermatopathologist said. We found that there was around a 3% discordance rate and an approximately 97% concordance rate. So, the concordance rate was quite high, but there was a small subset, about 6% within the 97%, that had indeterminate margins. I tell people that about 90% of the time, this can be pretty straightforward, but about 10% of the time, there might be some questionable slides and interpretation that could be missed or could be a false positive that leads you to potentially make a larger incision or excision and larger wounds. There is some caution, I think, in jumping into interpreting IHCs and going without experience and training.

The Dermatologist: What additional tips and insights would you like to share with your colleagues regarding Mohs IHC interpretation?

Dr Leitenberger: I think that this is a quickly growing area of expertise in dermatologic surgery. Like I mentioned, more Mohs surgeons are at fellowship training programs now with this technique. So more and more graduates are going to feel more comfortable using MART-1 IHC. And while this is exciting, there can be some pitfalls with the interpretation of MART-1 staining. I think it is really important to have a good relationship with a dermatopathologist. Sometimes if you have these indeterminate slides or something is not clear-cut on your interpretation, then either thawing that slide or submitting an additional permanent section can improve patient outcomes with additional input. Melanoma care is inherently multidisciplinary and most surgeons can be an integral part of an expert team to provide the best outcome for these patients.

Reference:
Leitenberger J, Mohs for melanoma immunohistochemistry refresher. Presented at: American College of Mohs Surgery (ACMS) Annual Meeting; May 4–7, 2023; Seattle, WA.

Watch Dr Leitenberger's interview video!