Document Type
Conference Proceeding
Publication Date
5-3-2024
Abstract
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an exceedingly rare genetic disorder characterized by skin and uterine leiomyomas and an increased risk of renal cell cancer. HLRCC follows an autosomal dominant pattern and is due to inactivating germline and somatic mutations in the gene encoding the fumarate hydratase enzyme (FH) involved in the citric acid cycle. The rarity and wide phenotypic variation in the presentation of HLRCC complicates suspicion and testing for this syndrome. We describe the case of a young woman who presented with pathological fracture secondary to bone metastasis from renal cell carcinoma. The patient presented to the emergency department with complaints of sudden and severe right arm pain. Right humerus radiography revealed permeative, “moth-eaten” lesions of the distal humeral diaphysis. Magnetic resonance imaging of the upper right arm supported suspicion for metastasis given a history of suspected renal cell carcinoma in childhood. The patient underwent successful particle embolization of the metastatic renal cell carcinoma in the distal humerus and follow-up angiogram demonstrated significant reduction of the neovascularity and tumor stain involving the humerus. Chest CT demonstrated gross splenomegaly and enlarged retroperitoneal lymph nodes. Biopsy of the left retroperitoneal lymph nodes revealed high-grade metastatic renal cell carcinoma with features suggestive of fumarate hydratase-deficient hereditary leiomyomatosis renal cell carcinoma. PET/CT revealed additional metastases in the right hepatic lobe. The patient was urged to undergo genetic testing with a multi-gene panel, which confirmed a germline pathologic variant of the fumarate hydratase gene. Additional history revealed the patient was diagnosed with polycystic kidney disease in childhood. At the time, bilateral nephrectomy was recommended due to biopsy suspicious for renal cell carcinoma but was not undertaken. Several years later, the patient developed biopsy-confirmed leiomyomas on the skin of her legs and was advised by her dermatologist, who suspected Reed’s Syndrome (Multiple Cutaneous and Uterine Leiomyomatosis), to undergo genetic evaluation for a variant of the FH gene; however, genetic testing was not undertaken at that time. Due to the rarity of HLRCC, there are currently no established guidelines on the treatment of this type of renal cell cancer. Limited studies, however, have demonstrated immune checkpoint inhibitors and anti-angiogenic molecules have proven beneficial and the patient was recommended to start a combination of immunotherapy and targeted treatment. This case highlights the importance of proceeding with screening of pathologic variants of the fumarate hydratase gene in patients with a history of leiomyomas and atypical renal pathology findings. Early identification can lead to appropriate surveillance for renal cell carcinoma and prevent an aggressive disease course.
Recommended Citation
Navartna N, Batra N, Chisti M. Aggressive renal cell carcinoma in a patient with a rare genetic syndrome. Presented at: American College of Physicians Michigan Chapter and Society of Hospital Medicine Michigan Chapter 2024 Resident and Medical Student Day; 2024 May 3; Troy, MI.
Comments
American College of Physicians Michigan Chapter and Society of Hospital Medicine Michigan Chapter 2024 Resident and Medical Student Day, May 3, 2024, Troy, MI