Fumarate Hydratase-Deficient Renal Cell Carcinoma in a Solitary Kidney: Diagnostic Pitfalls and Onco-Nephrology Constraints in an Older Adult With Chronic Kidney Disease
Year: 2026
Type: article
Study design: Case Report
Abstract: Fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) is a rare, aggressive subtype that is recognized as its own distinct entity in the 2022 WHO classification. It is frequently misclassified as papillary renal cell carcinoma (RCC). Older-onset disease and management in patients with a solitary kidney and chronic kidney disease (CKD) are not well characterized. A 76-year-old man with a remote right nephrectomy for clear cell RCC and stage 3b CKD presented with two to three years of progressive fatigue. Imaging of the solitary left kidney showed a 4.5-5.2 cm upper-pole mass with bulky retroperitoneal, mediastinal, and hilar adenopathy with multiple pulmonary nodules. Core biopsy findings were initially read as papillary RCC; however, the extensive metastatic burden appeared disproportionate to the relatively modest renal primary. Re-review demonstrated loss of FH on immunohistochemistry, and tumor sequencing confirmed a pathogenic FH p.G397R missense variant with programmed death-ligand 1 (PD-L1) tumor proportion score 20%, revising the diagnosis to FH-dRCC (cT1bN1M1). Cytoreductive nephrectomy was not pursued because of the patient's solitary-kidney status, baseline CKD, and disease burden. First-line nivolumab plus cabozantinib was selected; therapy was briefly held for immune-related uveitis, then resumed. This case highlights two important issues: metastatic burden disproportionate to primary tumor size - especially in tumors initially labeled papillary RCC - warrants pathology re-review with FH immunohistochemistry; and a solitary kidney with CKD reshapes the surgical and systemic-therapy calculus in FH-dRCC. Onco-nephrology input is valuable when balancing nephrotoxicity, contrast exposure, and disease-directed therapy.
Source: Cureus
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7214067880