Incidental Nonuterine High-grade Serous Carcinomas Arise in the Fallopian Tube in Most Cases

Abstract

Most nonuterine high-grade serous carcinomas (HGSCs) in women with hereditary breast and ovarian cancer syndrome, due to germline BRCA1/2 mutation, arise in the fimbria of the fallopian tube. However, the site of origin of sporadic HGSC, which is usually widely disseminated at presentation, is not well established. We sought to characterize cases of HGSC discovered incidentally in patients not known to be at high risk, in order to determine the site distribution and possible origin of sporadic HGSC. Incidental microscopic, non-mass-forming cases of serous tubal intraepithelial carcinoma or HGSC in salpingo-oophorectomy specimens in which the tubes and ovaries had been extensively examined were identified. No patients were known or suspected BRCA1/2 mutation carriers. Twenty-one cases were identified (mean age: 57 y). Surgery was for benign disease (n=15), uterine endometrioid adenocarcinoma or atypical hyperplasia (n=3), bladder carcinoma (n=1), or ovarian serous borderline tumor (n=2). In 16 of 21 cases, the lesion was confined to the fallopian tube (unilateral in 14 cases, bilateral in 2). There was serous tubal intraepithelial carcinoma in all cases and invasive HGSC into the underlying lamina propria in 8 of these 16 cases; the invasive focus measured 1.3 cm or less in every case. In the remaining 5 cases, there was fallopian tube mucosal and ovarian involvement; in 2 of these cases, there was also microscopic peritoneal involvement. Sporadic cases of nonuterine HGSC arise in the fallopian tube fimbria in a large majority of cases, providing further evidence for the tubal origin of these neoplasms.

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer

“…Thus, more recent evidence supports the idea that most HGSC in both sporadic and hereditary ovarian cancer are of fallopian tubal origin (23,41,42). Despite the fact that an obvious precursor STIC was contiguous with invasive carcinoma, one third of these patients were not associated with STIC in the fallopian tube (41).…”

Primary site assignment in tubo-ovarian high-grade serous carcinoma: Consensus statement on unifying practice worldwide

“…Using an earlier modification of the criteria listed above, in 53 prospectively studied chemo-naive cases of HGSC with unknown genetic status, 83% were classified as tubal, 17% as ovarian and none as peritoneal primaries (3). The protocol we present here has wider application than that recommended in the ICCR dataset, including guidance for cases diagnosed on small samples and following chemotherapy.…”

Role of salpingectomy at the time of urogynecologic surgery

“…In both BRCA mutation carriers and women from the general population, preinvasive changes within the fimbriated end of the fallopian tube appear to be associated with HGSC [20 & ]. Until recently, ovarian cancer was thought to be derived from the ovarian surface epithelium but histological analyses on prophylactic specimens from BRCA carriers have revealed a characteristic preneoplastic alteration at the fimbriated end of the fallopian tubes, also called serous tubal intraepithelial carcinoma (STIC), that is now considered to be the precursor of the most common ovarian cancer subtype, HGSC [21]. Based on this hypothesis, a salpingectomy may remove the actual site of tumorigenesis therefore protecting against HGSC.…”