[Diagnostic utility of PRAME immunohistochemistry for distinguishing clear cell sarcoma from malignant melanoma]

Objective: To investigate the diagnostic value of PRAME immunohistochemistry in the differential diagnosis between clear cell sarcoma (CCS) of soft tissue and melanoma, and its utility in routine diagnostic practice. Methods: A retrospective analysis was conducted on 25 CCS and 25 site-matched melanoma cases diagnosed at the Fudan University Shanghai Cancer Center from 2021 to 2025. Clinicopathologic data were collected, histologic features were assessed, and PRAME immunohistochemistry was performed. Clinicopathologic differences between the two groups were compared. The sensitivity and specificity of PRAME for differential diagnosis were evaluated. Results: Twenty-five patients with CCS were included, aged 38.0 (31.5, 56.0) years old. Another 25 patients with melanoma were included, aged 61.0 (54.0, 72.0) years old. In each group, 11 male and 14 female patients were included. Tumors were predominantly located in the extremities and trunks in both groups. In primary or recurrent melanomas, epidermal involvement with pagetoid proliferation at the dermoepidermal junction was frequently observed, whereas epidermal involvement was usually absent in CCS. Epithelioid morphology with prominent tumor-infiltrating lymphocytes and scant fibrous collagen septa were more often observed in metastatic melanomas, whereas a mixed epithelioid-spindle pattern, paucity of tumor-infiltrating lymphocytes, and frequent fibrous collagen septa were more commonly observed in CCS. PRAME negativity was observed in 96.0% (24/25) of the CCS cases, with only one case showing 5% nuclear positivity. By contrast, PRAME positivity was observed in 88.0% (22/25) of the melanoma cases, including diffuse nuclear positivity in>50% of tumor cells in 80.0% (20/25) of cases (P<0.001). With the cut-off of >50% positive cells, the sensitivity and specificity of PRAME for the diagnosis of melanoma were 80.0% and 100.0%, respectively. BRAF V600E immunohistochemistry was positive only in melanoma (56.0%, 14/25). All CCS cases were molecularly confirmed to harbor EWSR1 rearrangement.No co-occurrence of EWSR1 rearrangement and BRAF V600E immunohistochemistry positivity was observed in this cohort. Conclusions: Diffuse PRAME nuclear positivity is highly specific for diagnosing melanoma. It is particularly useful in biopsy specimens from recurrent lesions, needle biopsy specimens from metastatic lesions with inconspicuous pigmentation, biopsies of small primary lesions, and ulcerated specimens lacking an epidermal component. Therefore, PRAME immunohistochemistry is especially practical for community-hospital laboratories and interpreting biopsy specimens with limited tissue.