The Importance of Immunohistochemistry in the Evaluation of Tumor Depth of Primary Cutaneous Melanoma

Abstract

Primary cutaneous melanoma (PCM) is the most aggressive skin malignancy, with an increasing incidence and significant mortality. Tumoral invasion, expressed as Breslow thickness, is routinely assessed on hematoxylin and eosin (HE), although this stain may sometimes underestimate the tumoral depth. The aim of this study was to compare the efficiency of the immunohistochemical (IHC) markers S-100, SOX10, Melan-A, and HMB-45 with HE for the evaluation of the Breslow thickness and staging of PCM. This retrospective study included 46 cases of PCM diagnosed between 2015 and 2022; for each case, the Breslow thickness using HE, S-100, SOX10, Melan-A, and HMB-45 was measured and the appropriate T category was recorded. The highest values of the Breslow thickness were observed for S-100. However, S-100, SOX10, and Melan-A provided statistically significant higher values of the Breslow thickness compared to HE, but no difference was noted between HMB-45 and HE. S-100 was most frequently involved in increasing the T category (26.1%), the majority of cases being upstaged from T1a to T1b. The IHC markers S-100, SOX10, and Melan-A contributed to better evaluation of the melanoma invasion, especially in thin melanomas, but their impact on staging and consecutive treatment remains to be confirmed by future studies.

Insights into Melanoma Clinical Practice: A Perspective for Future Research

“…In contrast, IHC is considered the most easily adopted test, as it overcomes the aforementioned restrictions and limitations [ 25 ]. While the rate of IHC utilization has significantly increased in recent years [ 26 , 27 , 28 ], properly validated and standardized markers for adoption in clinical melanoma practice remain an issue. In this study, more than 80% of the respondents currently requested IHC tests to confirm a melanoma diagnosis.…”

Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management

“…HMB-45 and Melan-A/MART-1 are melanocyte-specific markers with considerable specificity. HMB-45 recognizes gp100, a component of the melanosomal complex, and is highly specific for melanoma [65][66][67]. HMB-45 is particularly useful in distinguishing between a benign and a malignant melanocytic tumor as nevi gradually lose HMB-45 due to their maturation process [67,68].…”

“…Melan-A expression is predominantly localized within the endoplasmic reticulum and melanosomes, thus having higher sensitivity compared to HMB-45. Melan-A is particularly useful in identifying isolated tumoral melanocytes in the dermis, which can reclassify a melanoma initially diagnosed as in situ to an invasive lesion [66,71,72]. Drabeni M. et al reported an increased Breslow thickness in approximately 60% of cases when utilizing Melan-A compared to H&E staining alone [71].…”