PRAME Immunohistochemistry and Molecular Profiling in Undifferentiated Cutaneous Pleomorphic Neoplasms: A Case Series of 8 Tumors.

Authors

Dylan J Parker, Meghana Agni, Jeffrey M Cloutier, Aravindhan Sriharan, Robert E LeBlanc, Shaofeng Yan, Shabnam Momtahen

Published in

Journal of cutaneous pathology. Oct 18, 2026. Epub Oct 18, 2026.

Abstract

Undifferentiated cutaneous pleomorphic neoplasms are diagnostically challenging, as histopathology and immunohistochemistry often fail to identify undifferentiated melanoma in lesions that instead remain classified provisionally as atypical fibroxanthoma (AFX) or pleomorphic dermal sarcoma (PDS). Given the prognostic and therapeutic implications of melanoma, additional ancillary tools may be helpful in selected cases.
We studied eight patients with undifferentiated pleomorphic neoplasms using molecular profiling and PRAME immunohistochemistry, correlating findings with clinical behavior.
Molecular findings varied across the cohort. Two tumors harbored NRAS hotspot mutations and were associated with aggressive clinical courses. In one patient, the tumor showed focal melanoma in situ associated with an undifferentiated intradermal tumor harboring NF1, TERT, and TP53 variants. The remaining tumors lacked melanoma-associated hotspot mutations. Diffuse PRAME expression was seen in three patients with an established diagnosis of melanoma and three patients with AFX/PDS. Two patients with AFX/PDS were negative for PRAME expression.
Molecular profiling may provide supportive diagnostic evidence for melanoma lineage in a subset of undifferentiated cutaneous pleomorphic neoplasms when interpreted in conjunction with morphology, immunohistochemistry, and clinical findings. In contrast, diffuse PRAME expression was observed in a nonspecific fashion both in cases with melanoma driver mutations and molecularly nonspecific cases in this cohort, limiting its utility as a standalone screening test for triaging molecular analysis.

PMID:
42893888
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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