Abstract
Objective
A precursor lesion for ovarian carcinoma, tubal intraepithelial carcinoma (TIC), has
been identified in BRCA-mutation carriers undergoing prophylactic bilateral salpingo-oophorectomy
(pBSO). Other lesions were also identified in fallopian tubes, but different terminology,
interpretation, and lack of knowledge of normal epithelium, have hampered to unravel
their possible role in carcinogenesis. The aim of this study is to classify tubal
epithelial lesions in BRCA-mutation carriers and controls to enable comparison of
prevalence, area of localization, and possible malignant potential.
Methods
Two hundred twenty-six BRCA1/2-mutation carriers were included; ovaries and fallopian
tubes, embedded completely, were reviewed. Controls included 105 women who underwent
BSO for non-malignant reasons. Tubal epithelial lesions included the following categories:
hyperplasia, minor epithelial atypia, TIC, and invasive carcinoma.
Results
Tubal neoplasia was identified in 7.1% (invasive carcinoma, 0.9%; TIC, 6.2%) of BRCA-mutation
carriers compared to none in controls (p=0.004, Fisher's exact test). Hyperplasia and minor epithelial atypia were identified
in 41.6% BRCA-mutation carriers and compared to 58.1% in controls (p=0.005, Pearson's chi square). Invasive carcinoma and TIC showed preference for the
fimbrial ends (p=0.027, Pearson's chi square), while hyperplasia and minor epithelial atypia displayed
more variation in localization.
Conclusions
Invasive tubal carcinoma and TIC were limited to BRCA-mutation carriers, whereas hyperplasia
and minor epithelial atypia were commonly found in both BRCA-mutation carriers and
controls. It is suggested that hyperplasia and minor atypia represent variations of
normal tubal epithelium instead of premalignant lesions. Furthermore, total salpingectomy
is strongly recommended as most but not all TIC occurred in the fimbriae.
Highlights
- Tubal epithelium was reviewed in the largest cohort to date of both BRCA-mutation carriers and controls.
- Tubal neoplasia was limited to BRCA-mutation carriers, whereas tubal hyperplasia and minor atypia were more often identified in controls.
- Total salpingectomy rather than only fimbriectomy is essential for prophylactic tubal and ovarian cancer prevention.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Gynecologic OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament.in: Atlas of Tumor Pathology. 3rd ed. Fascicle. 23. Armed Forces Institute of Pathology, Washington DC1998
- Expression of differentiation and proliferation related proteins in epithelium of prophylactically removed ovaries from women with a hereditary female adnexal cancer predisposition.Histopathology. 2003; 43: 26-32
- Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes.Cancer. 2000; 89: 383-390
- Histopathologic features of ovaries at increased risk for carcinoma. A case–control analysis.Int J Gynecol Pathol. 1999; 18: 151-157
- Comparison of prophylactic oophorectomy specimens from carriers and noncarriers of a BRCA1 or BRCA2 gene mutation. United Kingdom Coordinating Committee on Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group.J Natl Cancer Inst. 1999; 91: 626-628
- Tubal ligation and risk of ovarian cancer.Lancet. 2001; 358: 844
- Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status.Am J Surg Pathol. 2001; 25: 1283-1289
- Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation.JAMA. 2006; 296: 185-192
- Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers.J Natl Cancer Inst. 2009; 101: 80-87
- Histopathological characteristics of BRCA1- and BRCA2-associated intraperitoneal cancer: a clinic-based study.Fam Cancer. 2003; 2: 73-78
- Dysplastic changes in prophylactically removed fallopian tubes of women predisposed to developing ovarian cancer.J Pathol. 2001; 195: 451-456
- Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers.Gynecol Oncol. 2006; 100: 58-64
- Predictors of occult neoplasia in women undergoing risk-reducing salpingo-oophorectomy.Am J Obstet Gynecol. 2006; 194: 1702-1709
- Outcome of risk-reducing salpingo-oophorectomy in BRCA carriers and women of unknown mutation status.BJOG. 2011; 118: 814-824
- The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome.Am J Surg Pathol. 2006; 30: 230-236
- Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers: experience with a consecutive series of 111 patients using a standardized surgical–pathological protocol.Int J Gynecol Cancer. 2011; 21: 846-851
- Primary fallopian tube malignancies in BRCA-positive women undergoing surgery for ovarian cancer risk reduction.J Clin Oncol. 2007; 25: 3985-3990
- Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship.Am J Surg Pathol. 2007; 31: 161-169
- Serous tubal intraepithelial carcinoma and the dominant ovarian mass: clues to serous tumor origin?.Am J Surg Pathol. 2009; 33: 376-383
- The distal fallopian tube: a new model for pelvic serous carcinogenesis.Curr Opin Obstet Gynecol. 2007; 19: 3-9
- A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations.Gynecol Oncol. 2008; 109: 168-173
- High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression.Mod Pathol. 2010; 23: 1316-1324
- BRCA1/2-related ovarian cancers are of tubal origin: a hypothesis.Gynecol Oncol. 2003; 90: 491
- The molecular pathogenesis of hereditary ovarian carcinoma: alterations in the tubal epithelium of women with BRCA1 and BRCA2 mutations.Cancer. 2010; 116: 5261-5271
- Atypical epithelial proliferation in fallopian tubes in prophylactic salpingo-oophorectomy specimens from BRCA1 and BRCA2 germline mutation carriers.Int J Gynecol Pathol. 2004; 23: 35-40
- Mucosal epithelial proliferation of the fallopian tube: a particular association with ovarian serous tumor of low malignant potential?.Int J Gynecol Pathol. 1995; 14: 107-113
- Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers.Mod Pathol. 2009; 22: 1133-1138
- Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features: a reproducibility study.Am J Surg Pathol. 2011; 35: 1766-1775
- Ovarian cancer and genetic susceptibility in relation to the BRCA1 and BRCA2 genes. Occurrence, clinical importance and intervention.Acta Obstet Gynecol Scand. 2006; 85: 93-105
- Society of Gynecologic Oncologists Clinical Practice Committee statement on prophylactic salpingo-oophorectomy.Gynecol Oncol. 2005; 98: 179-181
- Radical fimbriectomy: a reasonable temporary risk-reducing surgery for selected women with a germ line mutation of BRCA 1 or 2 genes? Rationale and preliminary development.Gynecol Oncol. 2011; 121: 472-476
- Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers?.Am J Obstet Gynecol. 2011; 204: 19.e1-19.e6
- Multistep level sections to detect occult fallopian tube carcinoma in risk-reducing salpingo-oophorectomies from women with BRCA mutations: implications for defining an optimal specimen dissection protocol.Am J Surg Pathol. 2009; 33: 1878-1885
- Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy.J Clin Oncol. 2005; 23: 127-132
- Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up.Br J Cancer. 2004; 90: 1492-1497
Article info
Publication history
Accepted:
June 8,
2012
Received:
April 19,
2012
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
