Fumarate Hydratase-Deficient Renal Cell Carcinoma in a Solitary Kidney: Diagnostic Pitfalls and Onco-Nephrology Constraints in an Older Adult With Chronic Kidney Disease.
- 1Medical School, Michigan State University College of Osteopathic Medicine, East Lansing, USA.
- 2Department of Internal Medicine, University of Michigan Health-Sparrow Hospital/Michigan State University (MSU), Lansing, USA.
- 3Department of Hematology and Oncology, McLaren Greater Lansing, Lansing, USA.
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.
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BibTeX
@article{sanka2026fumarate,
title = {{Fumarate Hydratase-Deficient Renal Cell Carcinoma in a Solitary Kidney: Diagnostic Pitfalls and Onco-Nephrology Constraints in an Older Adult With Chronic Kidney Disease.}},
author = {Soumith Sanka and Sai Sushrutha Mudupula Vemula and Ankit Kulkarni and Ujwala Koduru and Borys Hrinczenko},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.116800},
url = {https://europepmc.org/article/MED/42927048},
note = {CC BY},
}
RIS
TY - JOUR
TI - Fumarate Hydratase-Deficient Renal Cell Carcinoma in a Solitary Kidney: Diagnostic Pitfalls and Onco-Nephrology Constraints in an Older Adult With Chronic Kidney Disease.
AU - Soumith Sanka
AU - Sai Sushrutha Mudupula Vemula
AU - Ankit Kulkarni
AU - Ujwala Koduru
AU - Borys Hrinczenko
PY - 2026
DA - 2026/09/23
JO - Cureus
DO - 10.7759/cureus.116800
UR - https://europepmc.org/article/MED/42927048
AB - 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.
SN - 2168-8184
ER -