Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma.
BACKGROUND
Patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) resulting from fumarate hydratase (FH) mutations may present with skin, uterine, and renal tumors, with each having unique pathologic features. This study investigated the association between prospectively identified suspicious pathology (SP) and FH mutations when patients were referred for genetic testing.


METHODS
This was an institutional review board-approved cohort study of patients receiving FH testing from 2008 to 2013. SP was defined as a report of HLRCC histologic features identified during a prospective pathologic assessment. The association between SP and FH mutations was analyzed.


RESULTS
FH testing was performed in 29 patients with a median age of 37 years; 15 (52%) were female, and 18 (62%) were white. Pathologists reported SP from kidney tumors (11 of 18), leiomyomas (9 of 15: uterus [n = 8] and bladder [n = 1]), and metastatic tumors (3 of 6) in 23 of 39 associated specimens (59%) from 21 of the 29 patients (72%). Patients with SP were younger (35 vs 51 years; P = .010), and those with kidney tumors more often had stage pT3 or higher renal cell carcinoma than those without SP (100% vs 33%; P = .006). FH mutations were present in 8 patients with SP (38%) and in 1 patient without SP (13%; P = .37); 7 of these patients had kidney cancer (n for SP = 7), all with N1 disease. Analyzing SP by tissue type identified only SP from renal tumors as being significantly associated with positive testing for an FH mutation (P = .013).


CONCLUSIONS
SP from kidney tumors was statistically associated with FH mutations. An expert pathologic assessment of renal tumors will facilitate the clinical identification of HLRCC cases, and this will result in genetic testing and targeted cancer screening for patients and at-risk family members. Cancer 2017;123:2452-58. © 2017 American Cancer Society.
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Ryan P
RP
Kopp
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Kelly L
KL
Stratton
Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Emily
E
Glogowski
Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Kasmintan A
KA
Schrader
Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Rohini
R
Rau-Murthy
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Paul
P
Russo
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Jonathan A
JA
Coleman
Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Kenneth
K
Offit
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005649:Fumarate Hydratase / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D007889:Leiomyoma / Q000235:genetics / Q000473:pathology*; D018231:Leiomyomatosis / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics / Q000473:pathology*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology*
D005649:Fumarate Hydratase
diagnosis; fumarate hydratase; genetic testing; hereditary leiomyomatosis and renal cell carcinoma (HLRCC); histology; pathology; renal cell carcinoma