Hereditary renal cell carcinoma syndromes (HRCCS) are characterized by the presence of pathogenic germline variants that predispose patients to renal cell carcinomas as well as additional extra-renal manifestations. The importance of identifying HRCCS patients cannot be overemphasized, as patients and their families can begin surveillance for syndrome-associated manifestations once identified. The present study is a retrospective clinical and morphologic review of 60 hereditary renal tumors from 30 HRCCS patients treated at our institution with either Von Hippel-Lindau disease (VHL), Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex (TSC), hereditary leiomyomatosis and renal cell cancer syndrome, or succinate dehydrogenase (SDH) deficiency syndrome. Hereditary renal cell carcinoma syndromes kidney tumors often demonstrate specific morphologic features, characteristic background changes in renal parenchyma, and extra-renal manifestations, which, when recognized by the pathologist, can trigger genetic testing referral for specific familial cancer syndromes. Our study demonstrates the majority of tumors were consistent with the anticipated clinicopathologic profile of renal tumors found within HRCCS patients, although we found some unique characteristics within this cohort including a case of clear cell papillary renal cell carcinoma within a VHL patient, and a unique renal tumor with tubulopapillary features present in a patient with a germline SDHD mutation. Additionally, although the literature reports the presence of epithelioid angiomyolipoma (AML) as a common occurrence in TSC patients, our cohort of 3 patients with AMLs demonstrated only classic features. The findings we describe facilitate pathologist-based recognition of HRCCS and can prompt genetic evaluation for relevant patients.
Medical oncology (Northwood, London, England). 2019 Jul 22*** epublish ***
John M Kennedy, Xiaoming Wang, Komal R Plouffe, Saravana M Dhanasekaran, Khaled Hafez, Ganesh S Palapattu, Tobias Else, Alon Z Weizer, Todd M Morgan, Daniel E Spratt, Matthew S Davenport, Arul M Chinnaiyan, Aaron M Udager, Rohit Mehra
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA., Michigan Center for Translational Pathology, Ann Arbor, MI, USA., Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA., Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA., Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA., Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. .