The Presence of Mucosal Iron in the Fallopian Tube Supports the “Incessant Menstruation Hypothesis” for Ovarian Carcinoma

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The incessant ovulation hypothesis for the etiology of ovarian carcinoma has been accepted for decades, but recent evidence strongly implicates the fallopian tube mucosa as the source of most high-grade “ovarian serous carcinomas.” Menstrual reflux through the tubes, a normal phenomenon, is a putative source of tubal mucosal exposure to carcinogens. We searched for histologic evidence of deposition of iron, a well-recognized carcinogen, in the fallopian tubes in 196 women with advanced-stage high-grade pelvic serous carcinomas in comparison with 370 controls. Tubal hemosiderin and/or pseudoxanthoma cells were found in 20% of the serous carcinoma cases, and an iron stain was positive in 30% of a sample of pigment-negative cases. Controls displayed pigment in 5% (P<0.001). In both cases and controls, pigment was significantly more frequently present in women with endometriosis as compared with those without. We conclude that tubal mucosal iron is present in a significant proportion of women with advanced-stage high-grade pelvic serous carcinoma. As a carcinogen, iron may play a role in the pathogenesis of these tumors. As compared with the incessant ovulation hypothesis, the recently proposed “incessant menstruation hypothesis” may be a better explanation of the well-recognized association of ovarian carcinoma with the length of the reproductive life uninterrupted by pregnancy.

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