Cytomorphologic and molecular characterization of metastatic renal cell carcinoma diagnosed by fine-needle biopsy: a single-institution study.

INTRODUCTION

Renal cell carcinoma (RCC) is a heterogeneous malignancy with variable histology, molecular drivers, and clinical behavior. Fine needle biopsy (FNB) is commonly used to diagnose metastatic RCC (mRCC), yet data describing histologic classification and the feasibility of molecular profiling using FNB material are limited.

MATERIALS AND

METHODS

We retrospectively reviewed 120 FNBs from 104 patients diagnosed with mRCC at a single academic center between 2010 and 2025. Clinical, histologic, and molecular data were collected from cytology reports, surgical specimens, and next-generation sequencing when available.

RESULTS

The cohort included clear cell RCC (n = 75), papillary RCC (type 1, n = 2; type 2, n = 4), unclassified RCC (n = 7), RCC of unknown type (n = 15), and one presumed mRCC. Lymph nodes (n = 45), lung (n = 23), and pancreas (n = 20) were the most frequent metastatic sites sampled. The mean interval from initial RCC diagnosis to FNB-confirmed metastasis was 5.3 years (range 0-35), with 26% of cases presenting with metastasis at initial diagnosis. Progression varied by grade, with grade 4 clear cell RCCs metastasizing rapidly (mean 1.5 years) while lower-grade tumors showed prolonged latency. Next-generation sequencing was performed in 26 cases. VHL was the most frequently altered gene (n = 13), followed by PBRM1 (n = 7), BAP1 (n = 4), and CDKN2A loss (n = 4). Additional notable alterations included NF2, SMAD4, SMARCB1, and FAT3.

CONCLUSIONS

FNB is frequently used as the primary diagnostic modality for mRCC and can provide sufficient material for histologic classification and, in selected cases, molecular profiling. Integration of cytology and genomic data from FNB specimens may aid diagnostic classification in selected cases, particularly when morphology and immunohistochemistry are limited.