Recommendations for diagnosing STIC: a systematic review and meta-analysis

Abstract

Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0–3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3–4.2) versus 1.7% (95% CI, 0.0–6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.

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

“…In general, diagnosing STIC is challenging with only moderate reproducibility. A recently published systematic review suggests not only the use of the SEE-FIM protocol, but also evaluation by a subspecialized pathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague to secure the diagnosis ( 41 ). Furthermore, there can also be a HGSC unrelated to a STIC diagnosis.…”

Focal Serous Tubal Intra-Epithelial Carcinoma Lesions Are Associated With Global Changes in the Fallopian Tube Epithelia and Stroma

“…Currently, precursor lesions in fallopian tubes removed from women with a genetic predisposition to ovarian cancer are identified by trained pathologists. Since visual morphologic changes in precursor lesions are subtle, interpretations by pathologists are unavoidably subjective ( 9 , 40 ). Yet, it is important to establish the correct diagnosis because women with isolated premalignant lesions in the fallopian tube are at increased risk of developing carcinomatosis, presumably because cancer cells have spread from the precursor lesion to other organs in the peritoneal cavity prior to preventive surgery.…”

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).…”

“…During the last 20 years an accumulation of voluminous data from multiple clinicopathological, immunohistochemical and molecular studies has shed light on this topic, and elucidated serous tubal intraepithelial carcinoma (STIC) of the fallopian tube as being a precursor for the vast majority of high-grade serous carcinomas of the ovary, fallopian tube and peritoneum. [1][2][3][4][5] However, criteria for diagnosing STIC have varied among multiple investigational studies; 6 thus, the uniform use of criteria is needed to facilitate communication among pathologists. This will be necessary in order to more reproducibly diagnose STIC for reporting purposes, as well as to improve accuracy for classification in research studies and determine the natural history of this lesion.…”