Frontiers in oncology · 2026
POU2F3-positive small cell neuroendocrine carcinoma of the urinary tract: a clinicopathological analysis of five cases.
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Chen Linxi, Lu Hongsheng, Cao Xuequan, Gan Hualei, Liu Peng
Аннотация
OBJECTIVE: To investigate the expression of POU2F3 in urinary tract small cell carcinoma (SmCC) and evaluate its diagnostic value.
METHODS: A retrospective analysis was performed on five cases of POU2F3-positive urinary tract SmCC diagnosed between January 2023 and November 2025 in the Departments of Pathology at Taizhou Central Hospital and Fudan University Shanghai Cancer Center. Immunohistochemistry and next-generation sequencing (NGS) were performed, and the clinicopathological and molecular characteristics were analyzed in combination with a literature review.
RESULTS: Five patients were included in the study group. Two female patients aged 67 and 62 years had bladder tumors and presented with gross hematuria; both underwent transurethral resection of bladder tumor. Three male patients aged 69-70 years had tumors located in the ureter (n=2) and renal pelvis (n=1). Histologically, all tumors showed small round blue cells with a high nuclear-to-cytoplasmic ratio, finely granular chromatin, inconspicuous nucleoli, frequent mitoses, and focal coagulative necrosis. Immunohistochemistry demonstrated loss of conventional neuroendocrine markers (CgA and Syn). Aberrant p53 expression was observed in all cases, and RB1 loss in four cases. Epithelial markers showed weak or paranuclear dot-like positivity. All five cases showed diffuse POU2F3 expression. Six conventional bladder SmCC cases positive for CgA and Syn were used as controls and were all negative for POU2F3. NGS performed in one case revealed a TP53 missense mutation (p.V225I). During follow-up, distant metastases occurred in three patients.
CONCLUSION: POU2F3 may serve as a useful marker for identifying urinary tract SmCC with absent or low neuroendocrine marker expression. Its application may improve diagnostic accuracy and facilitate recognition of a potential neuroendocrine-low phenotype.
METHODS: A retrospective analysis was performed on five cases of POU2F3-positive urinary tract SmCC diagnosed between January 2023 and November 2025 in the Departments of Pathology at Taizhou Central Hospital and Fudan University Shanghai Cancer Center. Immunohistochemistry and next-generation sequencing (NGS) were performed, and the clinicopathological and molecular characteristics were analyzed in combination with a literature review.
RESULTS: Five patients were included in the study group. Two female patients aged 67 and 62 years had bladder tumors and presented with gross hematuria; both underwent transurethral resection of bladder tumor. Three male patients aged 69-70 years had tumors located in the ureter (n=2) and renal pelvis (n=1). Histologically, all tumors showed small round blue cells with a high nuclear-to-cytoplasmic ratio, finely granular chromatin, inconspicuous nucleoli, frequent mitoses, and focal coagulative necrosis. Immunohistochemistry demonstrated loss of conventional neuroendocrine markers (CgA and Syn). Aberrant p53 expression was observed in all cases, and RB1 loss in four cases. Epithelial markers showed weak or paranuclear dot-like positivity. All five cases showed diffuse POU2F3 expression. Six conventional bladder SmCC cases positive for CgA and Syn were used as controls and were all negative for POU2F3. NGS performed in one case revealed a TP53 missense mutation (p.V225I). During follow-up, distant metastases occurred in three patients.
CONCLUSION: POU2F3 may serve as a useful marker for identifying urinary tract SmCC with absent or low neuroendocrine marker expression. Its application may improve diagnostic accuracy and facilitate recognition of a potential neuroendocrine-low phenotype.