Primary Renal Neuroendocrine Tumors Presenting as a Complex Cystic Mass and Arising in a Horseshoe Kidney: A Report of Two Cases

Primary renal neuroendocrine tumors (PRNETs) are exceptionally rare neoplasms that account for less than 1% of genitourinary neuroendocrine neoplasms and pose considerable diagnostic difficulty because of their non-specific clinicoradiological presentations and diverse histomorphology, which frequently mimics conventional renal epithelial tumors. We describe two adult patients with well-differentiated PRNET managed by partial nephrectomy including a 41-year-old male with a complex bosniak category IV cystic renal lesion, and another 43-year-old female with a tumor arising from the isthmus of a horse-shoe kidney. Both tumors showed organoid, trabecular, nested, tubulocystic, and focal cribriform architecture with low mitotic activity. Case 1 additionally showed focal capsular and perineural invasion despite of low-grade morphology. Tumor cells were diffusely positive for synaptophysin, chromogranin, and CD99, and negative for PAX8, CK7, CK20, WT1, TTF1, and CDX2, with a Ki-67 index below 2% in both. Electron microscopy confirmed dense-core neurosecretory granules, and both patients remain disease-free on radioimaging based follow-up. These cases illustrate that PRNET should be considered whenever a renal mass, including a complex cystic lesion or arising in a congenital anomalous kidney, not confirming thetypical epithelial morphology, and a combined histomorphological, immunohistochemical, and ultrastructural approach with prolonged surveillance is essential for accurate diagnosis and management.