Coming into focus: the nonovarian origins of ovarian cancer

The traditional view of epithelial ovarian cancer asserts that all tumor subtypes share a common origin in the ovarian surface epithelium (OSE) A literature review was carried out to summarize the emerging understanding of extraovarian sources of epithelial ovarian carcinomas. Historically, there were no diagnostic criteria for documenting the origin of ovarian epithelial carcinomas. Moreover, there are no normal epithelial tissues in the ovary with morphologic similarities to these tumors. In fact, no precursor lesions have ever been reproducibly identified in the ovary. However, there is a strong correlation between extrauterine Mullerian tissue and the development of ovarian carcinomas, tumors of low malignant potential, and cystadenomas. The most recent support for this hypothesis comes from the careful analysis of risk-reducing bilateral salpingo-oopherectomy specimens from BRCA1 or BRCA2 mutation carriers. These studies showed that a significant majority of high-grade serous ovarian carcinomas, the most common subtype, arise from the fallopian tube fimbriae rather than the OSE. Mounting evidence indicates that the vast majority of epithelial ovarian carcinomas are not ovarian in origin. Extrauterine Mullerian epithelium from various sites in the reproductive tract likely accounts for the diverse morphology and behavior of these tumors.