Staged Excision of Lentigo Maligna of the Head and Neck: Assessing Surgical Excision Margins With Melan A, SOX10, and PRAME Immunohistochemistry

Abstract

Background:Staged excision has emerged as a superior treatment option for lentigo maligna (LM) of the head and neck when compared with conventional wide local excision. Assessing surgical excision margins for remaining LM poses a diagnostic challenge.Objectives:To determine whether immunohistochemical (IHC) staining with SOX10 and preferentially expressed antigen in melanoma (PRAME) aids in diagnosing LM on excision margins compared with conventional hematoxylin and eosin and Melan A IHC staining.Methods:This study included cases of LM of the head and neck treated with staged excision. Histological findings were reviewed according to standard criteria for the diagnosis of LM and compared with the results after IHC staining for Melan A, SOX10, and PRAME.Results:The cohort consisted of 35 sections. Based on hematoxylin and eosin and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 to be consistent with a diagnosis of LM and 9 revealing features of actinic melanocyte hyperplasia. PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of actinic melanocyte hyperplasia (P = 0.009). The presence of melanocyte nests (P = 0.29) and pagetoid spread (P = 0.003) was the most reliable histological findings distinguishing LM from its mimics.Conclusion:SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.

Melanocyte Density in the Diagnosis of Melanoma In Situ in Sun-Damaged Skin

“…42,43 It could be helpful in addition to other IHC stains, such as SOX-10. 44 Hopefully, we can look forward to more articles dealing with this special IHC stain.…”

Double Immunohistochemical Labelling of PRAME and Melan A in Slow Mohs Biopsy Margin Assessment of Lentigo Maligna and Lentigo Maligna Melanoma

“…These markers can potentially facilitate the diagnosis of LM or the assessment of residual LM in surgical margins within the sun-damaged skin setting. Both SOX10 and Melan A can be used to determine a prime parameter; the cellularity or density of melanocytes within slow Mohs sections, which can help facilitate residual LM/LMM identification and by extension, margin clearance [ 7 ].…”

“…This labelling of “all” melanocytes, significantly limits their use in differentiating LM from its mimics [ 8 ]. However, Preferentially expressed Antigen in MElanoma (PRAME), has been the subject of intense study within the last 5 years, having shown promise in this regard [ 7 – 17 ]. Studies have showed differential PRAME expression within benign and malignant melanocytes, showing high expression in a variety of malignant melanocyte populations—in particular, melanoma and in-situ melanomas such as LM/LMM, with contrasting little to no expression in benign entities such as melanocytic nevi [ 8 – 11 ].…”

“…A Key study by Lezcano et al (2018) sought to evaluate the utility of PRAME IHC as a potentially useful adjunct tool for the assessment of melanocytic tumours, showing early yet promising evidence for PRAME IHC as a useful adjunctive tool within both melanoma and margin assessment studies [ 9 ]. Since then, many others have sought to evaluate PRAME using a variety of approaches and subject matter, seeking to further elucidate the strengths, limitations and pitfalls of PRAME IHC focusing on the differentiation of benign and malignant melanocytic entities [ 7 – 18 ].…”

“…Most congruously, some recent studies have explored the potential for PRAME nuclear labelling, to be used in various double-labelling methods, combined with cytoplasmic HMB-45 or Melan A, in order to further enhance the utility of PRAME within melanocytic investigations [ 7 , 8 , 11 – 13 ].…”