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.

Keywords: Breslow thickness; immunohistochemical markers; primary cutaneous melanoma; tumor staging.

Figure 1

Flow chart illustrating the case selection for the study.

Figure 2

(a) Nodular melanoma, stage pT1a, in a 65-year-old male patient. The tumor is in the vertical growth phase; pagetoid spread and non-brisk TILs can be observed. The value of the Breslow thickness measured on HE was <0.8 mm; Clark level of invasion II. (HE, ×5). (b) The value of the Breslow thickness measured on S-100 was 1.0 mm, upstaging the tumor to pT1b. (S-100, ×5); (c) The value of the Breslow thickness measured on SOX10 was 1.0 mm. (SOX10, ×5). (d) The value of the Breslow thickness measured on HMB-45 was 0.9 mm. (HMB-45, ×5). (e) The value of the Breslow thickness measured on Melan-A was 0.9 mm. (Melan-A, ×5). Isolated tumor cells suggesting invasion are highlighted with black arrows (case from the archive of the County Clinical Hospital Mureș).

Figure 2

(a) Nodular melanoma, stage pT1a, in a 65-year-old male patient. The tumor is in the vertical growth phase; pagetoid spread and non-brisk TILs can be observed. The value of the Breslow thickness measured on HE was <0.8 mm; Clark level of invasion II. (HE, ×5). (b) The value of the Breslow thickness measured on S-100 was 1.0 mm, upstaging the tumor to pT1b. (S-100, ×5); (c) The value of the Breslow thickness measured on SOX10 was 1.0 mm. (SOX10, ×5). (d) The value of the Breslow thickness measured on HMB-45 was 0.9 mm. (HMB-45, ×5). (e) The value of the Breslow thickness measured on Melan-A was 0.9 mm. (Melan-A, ×5). Isolated tumor cells suggesting invasion are highlighted with black arrows (case from the archive of the County Clinical Hospital Mureș).