Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience

Gynecol Oncol. 2020 May;157(2):514-520. doi: 10.1016/j.ygyno.2020.02.006. Epub 2020 Mar 19.

Abstract

Objectives: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of ovarian, fallopian tube (FT), and peritoneal carcinoma (collectively OC). We describe rates of occult neoplasia in the largest single-institution prospective cohort of women undergoing RRSO, including those with mutations in non-BRCA homologous repair (HRR) genes.

Methods: Participants undergoing RRSO enrolled in a prospective tissue bank between 1999 and 2017. Ovaries and FTs were serially sectioned in all cases. Participants had OC susceptibility gene mutations or a family history suggesting OC risk. Analyses were completed in Stata IC 15.1.

Results: Of 644 women, 194 (30.1%) had mutations in BRCA1, 177 (27.5%) BRCA2, 27 (4.2%) other HRR genes, and 15 (2.3%) Lynch Syndrome-associated genes. Seventeen (2.6%) had occult neoplasms at RRSO, 15/17 (88.2%) in the FT. Of BRCA1 carriers, 14/194 (7.2%) had occult neoplasia, 8/194 (4.1%) invasive. One PALB2 and two BRCA2 carriers had intraepithelial FT neoplasms. Occult neoplasm occurred more frequently in BRCA1/2 carriers ≥45 years of age (6.5% vs 2.2%, chi square, p = .04), and 211/371 (56.9%) BRCA1/2 carriers had surgery after guideline-recommended ages. Four in 8 (50%) invasive and 2/9 (22%) intraepithelial neoplasms had positive pelvic washings. None with intraepithelial neoplasms developed recurrence or peritoneal carcinoma.

Conclusions: BRCA1 carriers have the highest risk of occult neoplasia at RRSO, and the frequency increased with age. Women with BRCA1/2 mutations often have RRSO beyond recommended ages. One PALB2 carrier had FT intraepithelial neoplasia, a novel finding. Serial sectioning is critical to identifying occult neoplasia and should be performed for all risk-reducing surgeries.

Keywords: BRCA1; BRCA2; Occult neoplasm; PALB2; Risk-reducing salpingo-oophorectomy; Serial sectioning.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA2 Protein / genetics
  • Cohort Studies
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / pathology
  • Fallopian Tube Neoplasms / prevention & control*
  • Fallopian Tubes / surgery*
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasms, Unknown Primary / diagnosis
  • Neoplasms, Unknown Primary / pathology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / prevention & control*
  • Ovary / surgery*
  • Pedigree
  • Prospective Studies
  • Salpingo-oophorectomy
  • Ubiquitin-Protein Ligases / genetics

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • BRAP protein, human
  • Ubiquitin-Protein Ligases