腎神経内分泌腫瘍（RenNET）の分子病理学的洞察：包括的研究

Renal neuroendocrine tumors (RenNETs) are exceptionally rare neoplasms, accounting for less than 1 % of all renal tumors. Their clinicopathologic features, molecular characteristics, and biological behavior remain inadequately understood. This study aims to provide a comprehensive clinicopathologic and molecular analysis of RenNETs to distinguish them from other renal and neuroendocrine tumors.

A total of seven cases of RenNETs diagnosed between January 2017 and June 2023 were retrospectively analyzed. Clinical and pathologic features were reviewed, and immunohistochemical staining was performed. High-throughput next-generation sequencing (NGS) targeting 425 cancer-related genes was conducted on formalin-fixed, paraffin-embedded tumor samples RESULTS: Among the seven cases, six were non-functional RenNETs and one was associated with Cushing syndrome. Histologically, the tumors exhibited trabecular and solid growth patterns, with neuroendocrine features evident in the tumor cells. Immunohistochemically, all cases were positive for synaptophysin, and a subset showed expression of chromogranin A, INSM1, and β-catenin. NGS revealed 57 distinct somatic mutations, with TP53 (57.1 %) and APC (42.9 %) being the most frequently mutated genes. Additional recurrent alterations included POLE, ERCC6, ABCC2, and ALK. MCL1 amplification was observed in two cases, suggesting activation of anti-apoptotic pathways CONCLUSIONS: RenNETs represent a biologically distinct subtype of neuroendocrine tumors, with unique molecular features such as TP53 and APC mutations and frequent alterations in DNA repair pathways. These findings underscore the necessity for molecular profiling in guiding the diagnosis and potential therapeutic strategies for RenNETs. Further studies are warranted to explore the mechanisms underlying their pathogenesis and clinical behavior.