Fallopian Tube Intraluminal Tumor Spread From Noninvasive Precursor Lesions

Abstract

Pelvic serous carcinoma is usually advanced stage at diagnosis, indicating that abdominal spread occurs early in carcinogenesis. Recent discovery of a precursor sequence in the fallopian tube, culminating in serous tubal intraepithelial carcinoma (STIC), provides an opportunity to study early disease events. This study aims to explore novel metastatic routes in STICs. A BRCA1 mutation carrier (patient A) who presented with a STIC and tubal intraluminal shedding of tumor cells upon prophylactic bilateral salpingo-oophorectomy (PBSO) instigated scrutiny of an additional 23 women who underwent a PBSO and 40 patients with pelvic serous carcinoma involving the tubes. Complete serial sectioning of tubes and ovaries of patient A did not reveal invasive carcinoma, but subsequent staging surgery showed disseminated abdominal disease. STIC, intraluminal tumor cells, and abdominal metastases displayed an identical immunohistochemical profile (p53/WT1/PAX8/PAX2) and TP53 mutation. In 16 serous carcinoma patients (40%) tubal intraluminal tumor cells were found, compared with none in the PBSO group. This is the first description of a STIC, which plausibly metastasized without the presence of invasion through intraluminal shedding of malignant surface epithelial cells in the tube and subsequently spread throughout the peritoneal cavity. These findings warrant a reconsideration of the malignant potential of STICs and indicate that intraluminal shedding could be a risk factor for early intraperitoneal metastasis. Although rare in the absence of invasive cancer, we show that intraluminal shedding of tumor cells in the fallopian tubes from serous carcinoma cases are common and a likely route of abdominal spread.

Opportunistic salpingectomies for the prevention of a high-grade serous carcinoma: a statement by the Kommission Ovar of the AGO

“…The lesion, 'Secretory Cell Outgrowth' (SCOUT) equals a proliferation of secretory cells and is often regarded as a surrogate marker for precursor lesions. Due to their stemcell-like features, these lesions may also have a potential role in the pathogenesis of EOC [6][7][8][9][10][11][12][13][14][15][16][17].…”

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

“…Studies have shown that the STICs in cases of advanced-stage HGSC harbor identical p53 mutations to the disseminated tumor, establishing that they are clonal. 17,18 Comparison of telomere length in matched STIC and ovarian tumor pairs also suggests that the STICs antedate the ovarian tumor. 19 Subsequently, it has been shown that centrosome amplification is present at higher levels in ovarian tumor samples than in paired STICs, 20 also supporting the conclusion that the STICs are the earlier or precursor lesion.…”

Ovarian Cancer Prevention in High-risk Women

“…Scandinavian population based cohort studies have demonstrated a significant decrease in epithelial ovarian cancer following salpingectomy (113, 114). The implementation of opportunistic salpingectomy is feasible amongst women undergoing tubal ligation, hysterectomy or other pelvic surgery (115).…”