Incidental Serous Tubal Intraepithelial Carcinoma and Non-Neoplastic Conditions of the Fallopian Tubes in Grossly Normal Adnexa: A Clinicopathologic Study of 388 Completely Embedded Cases

Abstract

Serous tubal intraepithelial carcinoma (STIC), the putative precursor of the majority of extrauterine high-grade serous carcinomas, has been reported in both high-risk women (those with a germline BRCA mutation, a personal history of breast carcinoma, and/or family history of breast or ovarian carcinoma) and average risk women from the general population. We reviewed grossly normal adnexal specimens from 388 consecutive, unselected women undergoing surgery, including those with germline BRCA mutation (37 patients), personal history of breast cancer or family history of breast/ovarian cancer (74 patients), endometrial cancer (175 patients), and a variety of other conditions (102 patients). Among 111 high-risk cases and 277 non-high-risk cases, 3 STICs were identified (0.8%), all in non-high-risk women (high risk vs. non-high risk: P=not significant). STIC was found in 2 women with nonserous endometrial carcinoma and 1 with complex atypical endometrial hyperplasia. Salpingoliths (mucosal calcifications), found in 9% of high-risk cases, and fimbrial adenofibromas in 9.9% of high-risk cases, were significantly more common in high-risk as compared with non-high-risk women (1.8% and 2.5%, respectively; P<0.007). Mucinous metaplasia was found in 3.1%, salpingitis isthmica nodosa in 3.4%, hemosiderin or pseudoxanthoma cells in 4.9%, and fibrous luminal nodules in 4.1%. None of these latter features differed significantly in the high-risk versus non-high-risk groups. These findings suggest a possible association between STIC and endometrial hyperplasia and carcinoma, and clarify the frequency of non-neoplastic tubal findings in grossly normal fallopian tubes.

Frequency of “incidental” serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study

“…Coexistence of these two tumor types is considered rare, confirmed in this study where STIC was discovered in only 0.2% of endometrioid neoplasms. However, other studies have suggested an association between STIC and endometrioid neoplasia [16,20]. Moreover, we have identified an association, albeit unclear, between benign proliferations with a "clonal" appearance (stem cell outgrowths (SCOUTs)) in the tube -some with endometrioid histology -and HGSC [21,22].…”

“…Germane to both goals is the prevalence of STICs in women who are not considered at high risk for HGSC. The prevalence has not been established in large studies but at institutions where complete microscopic examination of the distal fallopian tube has been implemented (SEE-FIM protocol), it is estimated that the frequency of STIC in these women is between 0.6 and 1.1% [12][13][14][15][16].…”

Cell Origins of High-Grade Serous Ovarian Cancer

“…Though STICs are associated chiefly with HGSC, they are not exclusive to HGSCs of the ovary, fallopian tube, and peritoneum. STICs are also found in the fallopian tubes of patients with (high-grade) endometrial serous carcinoma (8–23%) [ 47 , 106 , 143 , 144 ], as well as ones from patients with nonserous endometrial carcinoma or endometrial hyperplasia (1.1%) [ 140 ] ( Table 3 ). STICs are also found in the fallopian tubes of 3% (2/64) of women undergoing surgery not related to ovarian, tubal, or peritoneal malignancy [ 101 ].…”

“…Particularly critical, yet unknown, is the clinical significance of STIC in the general population where 85–90% of HGSC cases occur. The information on the prevalence of STICs in the general population is limited, but several studies suggest that it could vary from 0.8–3.1% [ 101 , 140 , 142 ], while the lifetime risk of ovarian cancer is 1.3% (one in 78 women) [ 50 , 162 ]. Like DCIS, most likely, some STICs would possess malignant potential, while more STICs would not.…”

Effect of menopause on hormonal receptors in ampullae of the fallopian tube with a special reference to the p53 signature

“…In the nonprophylactic setting, Morrison et al14 and Gilks et al15 reported respective mean ages of 62.7 and 57 years among patients with STIC. Under non-neoplastic conditions of the FT, the incidence of STIC was also associated with advanced patient age 16. STIC is commonly located in the tubal fimbria and is associated with p53S 17.…”