Serous Tubal Intraepithelial Carcinoma: A Concise Review for the Practicing Pathologist and Clinician

Abstract

Ovarian cancer is the deadliest gynecologic malignancy, accounting for more than 14,000 deaths each year. With no established way to prevent or screen for it, the vast majority of cases are diagnosed as International Federation of Gynecology and Obstetrics (FIGO) stage III or higher. Individuals with germline BRCA mutations are at particularly high risk for epithelial ovarian cancer and have been the subject of many risk-reducing strategies. In the past ten years, studies looking at risk-reducing salpingo-oophorectomy (RRSO) in this population have uncovered an interesting association: up to 8% of women with BRCA1 or BRCA2 mutations who underwent RRSO had an associated serous tubal intraepithelial carcinoma (STIC). The importance of this finding is highlighted by the fact that up to 60% of ovarian cancer patients will also have an associated STIC. These studies have led to a paradigm shift that a subset of epithelial ovarian cancer originates not in the ovarian epithelium, but rather in the distal fallopian tube. In response to this, many providers have changed their practice by expanding the role of routine salpingectomy, hysterectomy, and sterilization procedures. The American College of Obstetricians and Gynecologists (ACOG) has acknowledged opportunistic salpingectomy as a safe strategy to reduce the risk of epithelial ovarian cancer in Committee Opinion #774. It is thus important for pathologists and clinicians to understand the definition of STIC; how it is diagnosed; and, most importantly, its clinical significance.

Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2

“…Several preneoplastic histopathological entities associated with HGSC have been identified in FTE including the p53-signature [30,31], secretory cell outgrowths (SCOUTs) [55], serous tubal intraepithelial lesions (STILs) and serous tubal intraepithelial carcinoma (STIC) [56] and are depicted in Figure 2. Secretory cell outgrowths (SCOUTs) are arrays of >30 cells found in either the proximal or distal tube with absent ciliated differentiation, loss of PAX2 and intact p53 [55].…”

“…Reports on the incidence of STICs in patients with increased hereditary ovarian cancer risk vary widely [56]. The diagnosis of these rare lesions has poor inter/intra-observer reproducibility and is dependent on micro-sectioning technique [25,64].…”

Preneoplastic Lesions Fimbria Early Diagnosis Markers Underlying Timeline Mechanisms at The Origin of Ovarian Cancer in BRAC1/2 Patients: Case Reports Based on Proteogenomic Study

“…In fact PAX8, a Mullerian marker has been found to be expressed in most of the HGSC but not calretinin (mesothelial marker) (Bowtell, 2010;Folkins et al, 2009;Mingels et al, 2014). This view has not been universally accepted, primarily as it con icts with traditional theories of the OC origins coupled with variation in the detection of tubal lesions in association with HGSC, which may, be due to differences in sampling or di culties in diagnostic interpretation (Bachert et al, 2020;Singh et al, 2015). Recently, advanced studies have provided a stepwise progression of FTE to precursor lesions to carcinoma, with the aid of -p53 signature -STIL -STIC HGSC sequence's model (Kobayashi et al, 2017;Wu et al, 2019;Zeppernick et al, 2015).…”

Preneoplastic lesions fimbria pan-proteomic studies establish the fimbriectomy benefit for BRCA1/2 patients and identify early diagnosis markers of HGSC

“…Three main lesions are defined according to the IHC pattern for the two markers and the architectural alterations of the cells. The p53 signature is identified by a small number of epithelial cells (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) with a proliferation activity like the adjacent normal epithelium, but with a p53 staining pattern corresponding to a missense TP53 mutation. STIC (serous tubal intraepithelial carcinoma) involves many cells with architectural and nuclear alterations, TP53 mutations and a high proliferative activity.…”

“…In fact PAX8, a Mullerian marker has been found to be expressed in most HGSC but not calretinin (mesothelial marker) [4,12,13]. This view has not been universally accepted, primarily as it conflicts with traditional theories on the origins of OC, and secondarily owing to variation in the detection of tubal lesions in association with HGSC, which may in turn be due to differences in sampling or difficulties in diagnostic interpretation [14,15]. Recent studies have provided a stepwise progression of FTE to precursor lesions to (which was not certified by peer review) is the author/funder.…”