title: Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications.
abstract: 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.
authors.affiliation: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
authors.forename: Elke A
authors.initials: EA
authors.lastname: Jarboe
authors.forename: David
authors.initials: D
authors.lastname: Kindelberger
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
mesh_terms: D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D024522:Genes, BRCA2 / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D019394:Ki-67 Antigen / Q000378:metabolism; D015588:Observer Variation; D011897:Random Allocation; D015203:Reproducibility of Results
chemical_list: D019394:Ki-67 Antigen