Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome (HLRCC): A Contemporary Review and Practical Discussion of the Differential Diagnosis for HLRCC-Associated Renal Cell Carcinoma

Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is an uncommon disorder with germline-inactivating mutations in the fumarate hydratase ( FH) gene. The kidney cancers that develop in patients with HLRCC are often unilateral and solitary, with a potentially aggressive clinical course; morphologic identification of suspicious cases is of the utmost importance.

To review classic morphologic features of HLRCC-associated renal cell carcinoma, the reported morphologic spectrum of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in diagnosis of these tumors.

University of Michigan cases and review of pertinent literature about HLRCC and the morphologic spectrum of HLRCC-associated renal cell carcinoma.

Histologic features, such as prominent nucleoli with perinucleolar halos and multiple architectural patterns within one tumor, are suggestive of HLRCC-associated renal cell carcinoma. However, the morphologic spectrum is broad. Appropriate use of FH immunohistochemistry and referral to genetic counseling is important for detection of this syndrome.

Archives of pathology & laboratory medicine. 2018 Oct [Epub]

Stephanie L Skala, Saravana M Dhanasekaran, Rohit Mehra

From the Department of Pathology, University of Michigan Medical School, Ann Arbor (Drs Skala and Mehra); the Rogel Cancer Center, Michigan Medicine, Ann Arbor (Dr Mehra); and the Department of Pathology, Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor (Drs Dhanasekaran and Mehra).