Fumarate Hydratase Mutations and Renal Tumors: When Is Genetic Testing Appropriate?

Patients with kidney tumors with pathology indicating a fumarate hydratase (FH) mutation should be referred for genetic testing, according to an article published in Cancer.¹ Results from these tests can determine whether a patient and/or his or her family members should go on targeted surveillance for recurrent tumors.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary disorder caused by FH mutation in which patients can be diagnosed with leiomyomas or renal tumors recurrently. Early detection of this disorder is critical for avoiding mortality among family members who develop renal cell carcinoma at a young age.

If, however, HLRCC does not manifest as a skin leiomyoma, but as a renal tumor, targeted surveillance for a patient’s family members can be delayed. For this study, researchers determined whether HLRCC suspicious pathology is a marker for FH mutation.

Of 29 included patients with 39 tumor specimens (kidney, leiomyoma, and metastatic) 21 patients and 23 specimens had suspicious pathology. Suspicious pathology of renal tumors only was linked to an FH mutation.

Patients whose specimens had suspicious pathology were young (median age 35 years vs 51 for others) and more often had stage pT3 or worse tumors.

The authors concluded that patients with HLRCC suspicious pathology renal tumors should be referred for genetic testing for an FH mutation.

Reference

1. Kopp RP, Stratton KL, Glogowski E, et al. Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma. Cancer. 2017 Feb 7. doi: 10.1002/cncr.30605 [Epub ahead of print]