Transitional Cell Metaplasia of Fallopian Tube Fimbriae

Abstract

Germline mutations in the hereditary breast/ovary carcinoma genes BRCA1 or BRCA2 confer increased lifetime risk for ovarian, fallopian tube, and primary peritoneal carcinoma. This risk can be minimized by prophylactic surgery. Risk-reducing salpingo-oophorectomy (RRSO) provides 2 potential benefits: long-term cancer risk reduction and immediate detection of occult early carcinoma, which frequently arises in the tubal fimbriae. Recognition of occult early tubal carcinoma is challenging because it is often microscopic in size and can be confined to the fimbrial epithelium without invasion. Transitional cell metaplasia is a benign epithelial alteration that is a common finding in the serosa of the tube but is underrecognized in the tubal fimbriae, where it may mimic tubal intraepithelial carcinoma. The aim of this study was to define the incidence, morphology, immunophenotype, and distribution of transitional cell metaplasia of the fimbriae in RRSO specimens from 96 women with BRCA germline mutations and to compare these features to those of tubal intraepithelial carcinoma in this cohort. RRSO specimens from an additional 30 women at increased risk for ovarian cancer based on strong family history were also studied, along with RRSO from 1 patient with Lynch syndrome, and 1 patient with PTEN mutation. Transitional cell metaplasia of the fimbriae was present in 26% of all RRSO specimens. It was commonly multifocal (67%), with involvement of the tip, edges, or base of the fimbrial plicae. Average size of a metaplastic focus was 1.3 mm (range: 0.1 to 10 mm). None of the metaplastic foci expressed p53 by immunohistochemistry nor was there increased staining for the proliferation marker MIB-1. Occult early carcinoma was detected in 6/128 RRSO specimens. Median tumor size was 2.7 mm (range: 1 to 11 mm). All expressed p53 and showed markedly increased MIB-1 staining. The key criteria distinguishing transitional cell metaplasia from tubal intraepithelial carcinoma were uniform cell size and shape, normal nucleus:cytoplasm ratios, lack of nuclear atypia, presence of nuclear grooves, lack of mitoses, and absence of p53 expression or increased staining for MIB-1. No particular clinical variables (BRCA 1 vs. BRCA 2 mutation, parity, personal history of breast cancer, prior abdomino-pelvic surgery, or intraoperative findings) or benign pathologic alterations in the RRSO specimens were associated with the presence of transitional cell metaplasia of the fimbriae. None of the patients with this finding developed peritoneal carcinoma during follow-up ranging from 1 month to 9 years. This study demonstrates that transitional cell metaplasia of the fimbriae is a common benign finding in RRSO specimens that should not be confused with the much less common finding of tubal intraepithelial carcinoma.