An Alternate Diagnostic Algorithm for the Diagnosis of Intraepithelial Fallopian Tube Lesions

Abstract

Intraepithelial fallopian tube neoplasia is thought to be a precursor lesion to high-grade serous carcinoma of the Müllerian adnexae, particularly in women with BRCA1 or BRCA2 mutations. This association has led to recommendations to assess fallopian tubes for intraepithelial atypia. However, the diagnostic reproducibility of a diagnosis of intraepithelial neoplasia is unclear. In this study, 2 gynecologic pathologists independently evaluated sections of fallopian tubes from a sample of women (N=198, 623 slides) undergoing salpingectomy. A total of 101 (54%) women were undergoing risk-reducing salpingo-oophorectomy. Pathologists were blinded to patient histories and prior diagnoses. Pathologists rendered one of three diagnoses for each slide: “negative for fallopian tube intraepithelial neoplasia (FTIN),” “indeterminate for FTIN,” or “definite for FTIN.” Cases that were considered by histology definite for FTIN or suspicious for FTIN were stained with p53 and Ki67. Pathologists agreed on the diagnosis of “definite for FTIN” 61.5% of the time. There was no agreement on any cases for the diagnosis of “indeterminate for FTIN.” Fifteen “indeterminate for FTIN” and 12 “definite for FTIN” cases were stained with p53 and Ki67. Two of the “indeterminate” cases (13%) had p53-positive foci. Five of the “definite” cases had p53-positive foci. In 3 of the other 8 “definite” cases, there was obvious carcinoma present, but the carcinoma did not stain with p53, suggesting a possible null phenotype. We propose that immunostains should only be used to aid in the diagnosis of FTIN in cases with indeterminate histology. The use of p53 immunohistochemistry in cases that were considered “definite for FTIN” by histology was minimally helpful, and in fact often served to further confuse the diagnosis.

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis

“…These lesions are alternatively described as fallopian tube intraepithelial neoplasia or high-grade tubal intraepithelial lesions, to specifically denote noninvasive lesions. 23…”

Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature

“…Patients with a STIC and a positive cytology were also included to maintain consistency with previous publications on this subject ( 7 ). Serous intraepithelial neoplasia is also known as STIC and was included ( 18 ). Study exclusion criteria for review were missing clinical data (follow-up) and publications restricted to pathological information only.…”

Serous tubal intra‐epithelial carcinoma: what do we really know at this point?

“…Morphological features for diagnosing STIC have been variably applied by pathologists, 6 and studies have shown that establishing a diagnosis using only morphology does not have high interobserver reproducibity. [17][18][19][20] Thus, a diagnostic algorithm that incorporates histological features coupled with immunohistochemical results for p53 and Ki-67 (Figure 3) was previously developed to aid the classification of epithelial atypias of the fallopian tube, which improves the reproducibility of diagnosing STIC 18,19,21 and allows lesions to be categorised as STIC, atypical lesions intermediate between STIC and p53 signature (serous tubal intra-epithelial lesion [STIL]; lesions analogous to STIL have been described by various terms in other publications, such as dysplasia, tubal intra-epithelial lesion in transition and dormant STIC [the designation dormant STIC has been used in other studies to designate lesions with significant atypia and aberrant p53 expression but without a high Ki-67 proliferation index (see below for thresholds separating low from high indices)] and p53 signature (see Pathogenesis section below). As diagnostic criteria for this continuum of atypical lesions have not been standardised, use of such an algorithm will help with communication among pathologists, clinicians and researchers.…”