Primary Renal Well-Differentiated Neuroendocrine Tumor: A Clinicopathologic and Immunohistochemical Analysis of a Case Series With Emphasis on Potential Diagnostic Pitfalls

<i>Introduction</i>. Primary renal well-differentiated neuroendocrine tumor may present a unique diagnostic and therapeutic challenge. In this retrospective study, we offered insights derived from our clinical experience. <i>Methods</i>. A search of our institutional database (1998-2023) was performed to identify primary renal well-differentiated neuroendocrine tumors, followed by comprehensive clinical, histopathological and immunohistochemical analysis, with emphasis on potential diagnostic pitfalls. <i>Results</i>. Five primary renal well-differentiated neuroendocrine tumors were identified, all of which exhibited a combination of nested, trabecular and tubular growth patterns and renal parenchymal infiltration. Two tumors invaded into the renal sinus. The expression of commonly-used neuroendocrine markers was detected in 5 tumors and PAX8 immunostain was negative in all tumors. During a median follow-up of 119 months (range 12-142 months), one patient received adjuvant chemotherapy due to regional lymph node metastasis at the time of diagnosis. The patient was found to haveliver metastasis at 15 months after the surgery by imaging. This tumor harbored <i>BRAF</i> c.1/99T>A, p.V600E and <i>CDKN2A</i> c.35delC, p.S12fs variants. Liver metastasis was identified in another patient 142 months after his initial presentation. No local recurrence or distant metastasis was detected in other patients. <i>Conclustions</i>. Our experience demonstrates that primary renal well-differentiated neuroendocrine tumors may exhibit indolent behavior, even tumors with local invasion. Most patients were managed with surgical resection alone. In daily practice, they may be misdiagnosed as renal cell carcinomas, especially in biopsy specimens, due to their rarity. Our study expands the clinicopathologic characteristics and immunohistochemical features of this rare entity to raise awareness, with emphasis on potential diagnostic pitfalls.