Clinicopathological features of dermal clear cell sarcoma: A series of 13 cases

Dermal clear cell sarcoma (DCCS) is a rare malignant mesenchymal neoplasm. Owing to the overlaps in its morphological and immunophenotypic profiles with a broad spectrum of tumors exhibiting melanocytic differentiation, it is frequently misdiagnosed as other tumor entities in clinical practice. By systematically analyzing the clinicopathological characteristics, immunophenotypic features, and molecular biological properties of DCCS, this study intends to further enhance pathologists' understanding of this disease and provide a valuable reference for its accurate diagnosis.

A retrospective analysis was conducted on the clinicopathological data of 13 patients diagnosed with DCCS at the First Affiliated Hospital of Air Force Medical University from January 2012 to December 2024. The histopathological features, immunophenotypic profiles, and molecular characteristics of tumors were systematically assessed. Furthermore, detailed prognostic information of the patients was collected through telephone follow-up.

Among the 13 patients diagnosed with DCCS, there were 5 males and 8 females, with a mean age of 32.7 years. Tumors were predominantly located in the distal extremities. 3 patients had a prior history of trauma or surgery, while bone destruction was identified in 5 cases via imaging examinations. Grossly, the tumors appeared as grayish-white or white nodules with a hard texture. Microscopically, 2 tumors involved both the dermis and epidermis, while the other 11 were confined to the dermis. Tumor cells were arranged in nests, fascicles, sheets, mainly spindle-shaped or epithelioid in morphology. "Wreath-like" multinucleated giant cells were observed in 3 cases, and collagenous fibrous septa were present in the stroma of all tumors. All tumors showed diffuse expression of S100 or SOX10, and HMB-45, Melan-A, and MITF were positive to varying degrees. EWSR1 (22q12) gene breakage was detected by fluorescence in situ hybridization (FISH) in all 10 tested cases. Among the cases examined by next-generation sequencing (NGS), 2 had the EWSR1::ATF1 fusion gene and 1 had the EWSR1::CREB1 fusion gene.

DCCS is relatively rare in clinical practice. Its pathogenesis may be associated with a prior history of trauma or surgery; however, this potential association requires further validation through the accumulation of additional cases. Given the overlaps in morphological and immunohistochemical features between DCCS and other tumors exhibiting melanocytic differentiation, molecular testing (including the detection of EWSR1 gene rearrangement or specific fusion genes detection) holds significant value for the accurate diagnosis of primary DCCS.