Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications

Int J Gynecol Pathol. 2010 Jul;29(4):310-4. doi: 10.1097/PGP.0b013e3181c713a8.


Serous tubal intraepithelial carcinoma (STIC) is detected in between 5% and 7% of women undergoing risk-reduction salpingooophorectomy for mutations in the BRCA1 or 2 genes (BRCA+), and seems to play a role in the pathogenesis of many ovarian and "primary peritoneal" serous carcinomas. The recognition of STIC is germane to the management of BRCA+ women; however, the diagnostic reproducibility of STIC is unknown. Twenty-one cases were selected and classified as STIC or benign, using both hematoxylin and eosin and immunohistochemical stains for p53 and MIB-1. Digital images of 30 hematoxylin and eosin-stained STICs (n=14) or benign tubal epithelium (n=16) were photographed and randomized for blind digital review in a Powerpoint format by 6 experienced gynecologic pathologists and 6 pathology trainees. A generalized kappa statistic for multiple raters was calculated for all groups. For all reviewers, the kappa was 0.333, indicating poor reproducibility; kappa was 0.453 for the experienced gynecologic pathologists (fair-to-good reproducibility), and kappa=0.253 for the pathology residents (poor reproducibility). In the experienced group, 3 of 14 STICs were diagnosed by all 6 reviewers, and 9 of 14 by a majority of the reviewers. These results show that interobserver concordance in the recognition of STIC in high-quality digital images is at best fair-to-good for even experienced gynecologic pathologists, and a proportion cannot be consistently identified even among experienced observers. In view of these findings, a diagnosis of STIC should be corroborated by a second pathologist, if feasible.

Publication types

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

MeSH terms

  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • Fallopian Tube Neoplasms / diagnosis*
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Genes, BRCA1 / physiology*
  • Genes, BRCA2 / physiology*
  • Genes, p53 / physiology
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry / standards
  • Ki-67 Antigen / metabolism
  • Observer Variation
  • Random Allocation
  • Reproducibility of Results


  • Ki-67 Antigen