Expression of melanocytic markers in uterine smooth muscle tumours

Uterine smooth muscle tumours (SMTs) conventionally express myogenic markers such as desmin, h-caldesmon and smooth muscle actin by immunohistochemistry. In contrast, the frequency and extent of melanocytic marker (MM) expression, commonly assessed in the differential diagnosis with perivascular epithelioid cell tumours (PEComas), remain poorly defined. This study aimed to evaluate the positivity of MMs and Cathepsin K in a large cohort of SMTs.

In total, 102 tumours were retrospectively identified, including 72 leiomyomas of various subtypes, 4 cases of SMT of uncertain malignant potential and 26 leiomyosarcomas. Immunohistochemistry for HMB-45, Melan-A, PRAME and Cathepsin K was performed on whole-tissue sections and assessed for the presence, extent and intensity of staining. A chi-square test was used to determine statistical significance. Thirty-eight tumours (37.2%) expressed at least one MM (excluding Cathepsin K). PRAME was the most frequently expressed marker (30/102, 29.4%), showing strong nuclear staining in 27 tumours (26%), predominantly in a focal distribution (<50% of cells; 27/30, 90%). HMB-45 was positive in 16/102 tumours (15.6%), with focal expression in all cases (16/16, 100%), and Melan-A was focally positive only in 2/102 tumours (1.9%). Cathepsin K expression was seen in 32/102 tumours (31.4%), being focal in most positive cases (28/32, 87.5%). Co-expression of PRAME and HMB-45 was observed in 10 cases (9.8%), while no SMT demonstrated co-expression of HMB-45 and Melan-A. In 4 of the 7 HMB-45-positive conventional leiomyomas, staining was observed only in the hyalinized areas. There was no significant difference in the frequency of MM staining between benign/uncertain behaviour (leiomyomas/SMTs of uncertain malignant potential) (36.8%) and malignant tumours (leiomyosarcomas) (38.5%; P = 0.88).

We observed that a subset of SMTs may express MMs, typically in a focal and weak pattern. In our series, no SMT showed concurrent positivity for both HMB-45 and Melan-A; therefore, when evaluating a tumour with equivocal morphology that demonstrates dual and/or diffuse expression of these markers, the diagnosis should be carefully reconsidered.