Original ArticlesFallopian Tube Intraluminal Tumor Spread From Noninvasive Precursor Lesions A Novel Metastatic Route in Early Pelvic CarcinogenesisBijron, Jonathan G. MD, PhD*; Seldenrijk, Cornelis A. MD, PhD†; Zweemer, Ronald P. MD, PhD‡; Lange, Joost G. MD, PhD§; Verheijen, René H.M. MD, PhD‡; van Diest, Paul J. MD, PhD*Author Information Departments of *Pathology ‡Gynaecological Oncology, Division of Woman and Baby, University Medical Center Utrecht, Utrecht Departments of †Pathology §Gynaecology, St Antonius Hospital, Nieuwegein, the Netherlands Conflicts of Interest and Source of Funding: Research support was received from University Medical Center Utrecht. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Paul J. van Diest, MD, PhD, Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands (e-mail: [email protected]). The American Journal of Surgical Pathology: August 2013 - Volume 37 - Issue 8 - p 1123-1130 doi: 10.1097/PAS.0b013e318282da7f Buy Metrics 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. © 2013 by Lippincott Williams & Wilkins.