Cytomorphologic and molecular analyses of fallopian tube fimbrial brushings for diagnosis of serous tubal intraepithelial carcinoma

Cancer Cytopathol. 2019 Mar;127(3):192-201. doi: 10.1002/cncy.22110. Epub 2019 Mar 12.

Abstract

Background: The paradigm shift localizing the origin of ovarian high-grade serous carcinoma (HGSC) to the fallopian tube underscores the rationale for meticulous microscopic examination of salpingectomy specimens. The precursor, termed "serous tubal intraepithelial carcinoma," is often a focal lesion, which poses difficulties for histologic diagnosis.

Methods: The authors describe a method to examine exfoliated epithelial cells from fallopian tube fimbria by gentle brushing, thereby enabling thorough sampling of the mucosal surface. Fimbrial brushings were collected from 20 fresh salpingectomy specimens from 15 patients, including 5 who had pathologically confirmed ovarian HGSC. Samples taken only from tubes that were grossly negative for tumor were processed for Papanicolaou staining, p53 immunocytochemistry, and tumor protein 53 (TP53) mutation analysis.

Results: Cells with malignant cytomorphologic features were identified only in tubal brushings from patients with ovarian HGSC. In all cases, atypical/malignant cells on cytology corresponded to lesions with similar morphology and immunostaining pattern in permanent sections, demonstrating the sensitivity of the technique while providing reassurance that specimen integrity was not disrupted by the procedure. Targeted next-generation sequencing confirmed the presence of TP53 mutations in fimbrial brushings from HGSC, but not in benign samples, and demonstrated concordance with the immunostaining pattern. Identical mutations were observed in matched lesions microdissected from formalin-fixed tissue sections.

Conclusions: The described technique enables cytologic evaluation of the fallopian tube fimbria for a diagnosis of serous tubal intraepithelial carcinoma, serving as a complement to histology while offering distinct advantages with respect to the procurement of cellular material for ancillary testing and research.

Keywords: exfoliative cytology; fallopian tube; ovarian cancer; precursor lesion; tubal brushing.

MeSH terms

  • Carcinoma in Situ / diagnosis*
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Cell Surface Extensions / metabolism
  • Cell Surface Extensions / pathology*
  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / metabolism
  • DNA Mutational Analysis / methods
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Fallopian Tube Neoplasms / diagnosis*
  • Fallopian Tubes / metabolism
  • Fallopian Tubes / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Mutation
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Salpingectomy
  • Sensitivity and Specificity
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53