Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma

Ryan Kopp, Kelly L. Stratton, Emily Glogowski, Kasmintan A. Schrader, Rohini Rau-Murthy, Paul Russo, Jonathan A. Coleman, Kenneth Offit

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - 2017

Fingerprint

Leiomyomatosis
Genetic Testing
Renal Cell Carcinoma
Fumarate Hydratase
Pathology
Kidney
Mutation
Neoplasms
Kidney Neoplasms
Research Ethics Committees
Leiomyoma
Early Detection of Cancer
Uterus

Keywords

  • Diagnosis
  • Fumarate hydratase
  • Genetic testing
  • Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
  • Histology
  • Pathology
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma. / Kopp, Ryan; Stratton, Kelly L.; Glogowski, Emily; Schrader, Kasmintan A.; Rau-Murthy, Rohini; Russo, Paul; Coleman, Jonathan A.; Offit, Kenneth.

In: Cancer, 2017.

Research output: Contribution to journalArticle

Kopp, Ryan ; Stratton, Kelly L. ; Glogowski, Emily ; Schrader, Kasmintan A. ; Rau-Murthy, Rohini ; Russo, Paul ; Coleman, Jonathan A. ; Offit, Kenneth. / Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma. In: Cancer. 2017.
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abstract = "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.",
keywords = "Diagnosis, Fumarate hydratase, Genetic testing, Hereditary leiomyomatosis and renal cell carcinoma (HLRCC), Histology, Pathology, Renal cell carcinoma",
author = "Ryan Kopp and Stratton, {Kelly L.} and Emily Glogowski and Schrader, {Kasmintan A.} and Rohini Rau-Murthy and Paul Russo and Coleman, {Jonathan A.} and Kenneth Offit",
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doi = "10.1002/cncr.30605",
language = "English (US)",
journal = "Cancer",
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TY - JOUR

T1 - Utility of prospective pathologic evaluation to inform clinical genetic testing for hereditary leiomyomatosis and renal cell carcinoma

AU - Kopp, Ryan

AU - Stratton, Kelly L.

AU - Glogowski, Emily

AU - Schrader, Kasmintan A.

AU - Rau-Murthy, Rohini

AU - Russo, Paul

AU - Coleman, Jonathan A.

AU - Offit, Kenneth

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Diagnosis

KW - Fumarate hydratase

KW - Genetic testing

KW - Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)

KW - Histology

KW - Pathology

KW - Renal cell carcinoma

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U2 - 10.1002/cncr.30605

DO - 10.1002/cncr.30605

M3 - Article

JO - Cancer

JF - Cancer

SN - 0008-543X

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