[Sweat gland carcinoma with neuroendocrine differentiation: a clinicopathological analysis of three cases]

Objective: To investigate the clinicopathological features, immunophenotype, and molecular characteristics of sweat gland carcinoma with neuroendocrine differentiation (SCAND). Methods: Three cases of SCAND diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from June 2022 to June 2025 were collected. Hematoxylin-eosin (HE) staining and immunohistochemistry (EnVision method) were performed to characterize morphologic and immunophenotypic features. Next-generation sequencing (NGS) was utilized to explore their molecular pathological characteristics. Results: All three patients were male, aged 67, 63, and 48 years, respectively. The primary tumors presented as solitary nodules or masses located in the lower abdomen, anterior chest wall, or inguinal region, with a maximum diameter of 2.0, 1.3, and 1.8 cm, respectively. Histologically, the tumors were situated primarily within the dermis, invading the epidermis and subcutaneous tissue, with focal mucin production. The tumor cells were arranged in nests, cords, and sieve-like patterns, exhibiting mild to moderate atypia. The nuclei were round to oval with coarsely granular chromatin and relatively inconspicuous nucleoli, accompanied by eosinophilic cytoplasm. Mitotic figures were scarce. All cases were positive for CK7, GATA3, TRPS1, Ber-EP4, epithelial membrane antigen, estrogen receptor, progesterone receptor, and the neuroendocrine markers of synaptophysin and chromogranin A. The tumors were negative for p40 and HER2. The Ki-67 proliferation index ranged from 2% to 30%. Multiple class Ⅲ and Ⅳ variants were identified by NGS analysis in cases 1 and 2. In case 3, a class Ⅱ variant, specifically an SF3B1 missense mutation, was identified along with multiple class Ⅲ and Ⅳ variants. Additionally, multiple germline variants were detected in all three cases, while none of them were classified as pathogenic or likely pathogenic. The patients were followed up for 13, 37 and 155 months, respectively. Metastases were detected 6, 36, and 96 months after diagnosis. Case 2 showed local metastasis, while cases 1 and 3 developed multiple nodal and bone metastases. Conclusions: SCAND is a rare cutaneous adnexal neoplasm characterized by co-expression of sweat gland and neuroendocrine markers. Despite low-grade morphology, it follows a non-indolent clinical course warranting close clinical attention.