Abstract

BACKGROUND/OBJECTIVES

Recent advancements in genetic research have significantly enhanced the understanding of renal cell carcinoma (RCC), now recognized as a heterogeneous group with distinct genetic features. This case report is aimed at illustrating its genetic diversity and implications for diagnosis and treatment.

METHODS

A middle-aged man presented with an incidental finding of RCC in the right kidney on computer tomography (CT) performed for a persistent cough. Comprehensive radiological and blood tests were conducted, followed by a total right nephrectomy. Histological examination showed a concurrent appearance of two manifestly different tumors in the kidney. Molecular analyses, including SNP array and next-generation sequencing (NGS), were conducted to identify genetic mutations and assess clonality.

RESULTS

The nephrectomy identified two distinct tumors: a clear cell RCC (ISUP/WHO grade 3, pT1b) and a papillary RCC (ISUP/WHO grade 2, pT1a). Molecular analysis confirmed VHL, TP53, and SETD2 mutations in the clear cell RCC, whereas no mutations were detected in the papillary RCC. The SNP array revealed significant chromosomal differences, suggesting the tumors were not clonally related. Follow-up imaging detected an adrenal metastasis from the clear cell RCC. The metastasis showed a VHL and SETD2 mutation, which undoubtedly proved to be derived from the clear cell RCC.

CONCLUSIONS

This case underscores the genetic heterogeneity of RCC and the importance of molecular profiling in guiding diagnosis and treatment. The distinct genetic profiles of the two tumors suggest they are not clonally related, highlighting the complexity of RCC and the need for individualized therapeutic approaches.

MeSH

Cells, Genetic Heterogeneity, Neoplasms, Nephrectomy, Kidney, Carcinoma, Renal Cell, Neoplasm Metastasis, Diagnosis, Therapeutics, Mutation