Metastases from uveal melanoma may lack S100 expression: A clinico-pathologic and immunohistochemical study with emphasis on potential causes and diagnostic implications

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with a high mortality rate due to metastasis, primarily to the liver. The differential diagnosis of metastatic UM, particularly in distinguishing it from cutaneous melanoma (CM), can be challenging due to overlapping histopathological features. This study investigates the immunohistochemical expression of S100 in a cohort of 41 cases, including 13 metastatic UMs, 18 metastatic CMs, and 10 primary UMs. Our results demonstrate a significant lack of S100 immunoreactivity in metastatic UM, with 84.6 % of cases showing negativity, in contrast to the diffuse positivity seen in both primary UM and metastatic CM. This finding suggests that the absence of S100 could serve as a useful marker to differentiate metastatic UM from CM, especially in cases where the primary tumor is unknown. Furthermore, the study highlights the potential diagnostic pitfall of relying solely on S100 expression on small biopsies. The absence of S100 in metastatic UM may reflect a shift in antigenic expression, possibly due to tumor dedifferentiation or clonal selection of S100-negative cells with a higher metastatic potential. Our findings emphasize the importance of employing a comprehensive immunohistochemical panel, including markers such as HMB45, SOX10, and Melan-A, in the accurate diagnosis of metastatic melanomas.