FH-Deficient Tumor Screening Protocol: A Review of the Institutional Data
Faculty Mentor
Monika Zak
Area of Research
Clinical Genetics and Pathology
Major
Genetic Counseling
Description
INTRODUCTION: Fumarate Hydratase Tumor Predisposition Syndrome (FHTPS) is a hereditary cancer syndrome caused by germline mutations in the Fumarate Hydratase (FH) gene and is characterized by cutaneous and uterine leiomyomas, renal cell carcinoma, and potentially paraganglioma and pheochromocytoma. Germline FH pathogenic variants can cause well-defined morphologic and immunohistochemical changes in uterine leiomyoma that are defined as fumarate hydratase-deficient.
METHOD: A pathology-based approach for screening uterine fibroids to identify women who would benefit from germline testing was implemented at Weill Cornell Medical in 2015. To determine the effectiveness of this screening approach to identify germline FH pathogenic variants in patients, we undertook a retrospective review of patients with uterine leiomyoma with FH-deficient features between 2015–2025. We compared clinical characteristics between FH-deficient and non-deficient uterine fibroid groups and between germline FH wild-type and pathogenic groups. We reviewed rates of genetic services referral, genetic counseling, and genetic testing uptake for patients with FH-deficient uterine fibroid pathology.
RESULTS: Of 227 patients (n = 227) with reviewable clinical data, 210 patients (n = 210) received IHC staining for FH. 98 of 210 patients (43%) were identified with FH-deficient features (FH loss and/or FH-deficient morphology), but only 36 of 98 (36%) completed germline genetic testing. 11 of 36 (30%) of tested patients were discovered to have germline pathogenic FH variants, representing 11% (11 of 98) of the FH-deficient feature cohort identified by pathological screening.
DISCUSSION/CONCLUSION: This data suggests the utility of current screening methods but highlights issues with actualizing pathology data into actionable germline investigation.
FH-Deficient Tumor Screening Protocol: A Review of the Institutional Data
INTRODUCTION: Fumarate Hydratase Tumor Predisposition Syndrome (FHTPS) is a hereditary cancer syndrome caused by germline mutations in the Fumarate Hydratase (FH) gene and is characterized by cutaneous and uterine leiomyomas, renal cell carcinoma, and potentially paraganglioma and pheochromocytoma. Germline FH pathogenic variants can cause well-defined morphologic and immunohistochemical changes in uterine leiomyoma that are defined as fumarate hydratase-deficient.
METHOD: A pathology-based approach for screening uterine fibroids to identify women who would benefit from germline testing was implemented at Weill Cornell Medical in 2015. To determine the effectiveness of this screening approach to identify germline FH pathogenic variants in patients, we undertook a retrospective review of patients with uterine leiomyoma with FH-deficient features between 2015–2025. We compared clinical characteristics between FH-deficient and non-deficient uterine fibroid groups and between germline FH wild-type and pathogenic groups. We reviewed rates of genetic services referral, genetic counseling, and genetic testing uptake for patients with FH-deficient uterine fibroid pathology.
RESULTS: Of 227 patients (n = 227) with reviewable clinical data, 210 patients (n = 210) received IHC staining for FH. 98 of 210 patients (43%) were identified with FH-deficient features (FH loss and/or FH-deficient morphology), but only 36 of 98 (36%) completed germline genetic testing. 11 of 36 (30%) of tested patients were discovered to have germline pathogenic FH variants, representing 11% (11 of 98) of the FH-deficient feature cohort identified by pathological screening.
DISCUSSION/CONCLUSION: This data suggests the utility of current screening methods but highlights issues with actualizing pathology data into actionable germline investigation.