Shyu, IreneMirsadraei, LeiliWang, XiaoyanRobila, ValentinaMehra, RohitMcHugh, Jonathan B.Chen, Ying-BeiUdager, Aaron M.Gill, Anthony J.Cheng, LiangAmin, Mahul B.Lin, OscarSmith, Steven Christopher2023-06-262023-06-262018Shyu I, Mirsadraei L, Wang X, et al. Clues to recognition of fumarate hydratase-deficient renal cell carcinoma: Findings from cytologic and limited biopsy samples. Cancer Cytopathol. 2018;126(12):992-1002. doi:10.1002/cncy.22071https://hdl.handle.net/1805/33949Background: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is rare and highly aggressive and is believed to arise mostly in the setting of hereditary leiomyomatosis-RCC syndrome with a germline mutation of FH. Because of the aggressiveness of these tumors and a frequent lack of ascertainable family history, these tumors may first present as metastases and be sampled by cytology. The cytologic findings of FH-deficient RCC have not previously been reported. Methods: Cytologic and limited biopsy samples from patients with FH-deficient RCC were reviewed retrospectively. Results: In total, 24 cytologic and limited biopsy samples from 19 patients (6 women and 13 men; age range, 22-69 years) who had FH-deficient RCC and metastasis at presentation were evaluated. These included 21 cytology samples ranging from malignant effusions (n = 7) to metastases (n = 11), to samples of primary kidney tumors (n = 3). The samples exhibited cells, often in clusters and abortive papillae, with voluminous, finely vacuolated cytoplasm and large, pleomorphic nuclei with prominent, viral inclusion-like nucleoli. A distinctive finding of peripheral cytoplasmic clearing frequently was apparent, and intranuclear cytoplasmic pseudoinclusions were less frequent. Of 7 cell block and biopsy samples, several of which represented sampling from the same patient, all demonstrated tissue fragments that had discernable morphologic patterns associated with FH-deficient RCC, including tubulocystic and intracystic papillary growth. Conclusions: Features characteristic and suggestive of FH-deficient RCC may be identified in cytologic and small biopsy samples. Although the current samples were identified retrospectively in well characterized cases of FH-deficient RCC, the authors argue that, with appropriate clinical correlation, these features are sufficiently distinctive to trigger recognition and confirmatory workup.en-USPublisher PolicyAspiration cytologyFumarate hydratase-deficient renal cell carcinomaHereditary leiomyomatosis-renal cell carcinoma syndromeHereditary neoplasiaRenal cell carcinomaArticle