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The secondary Müllerian system, field effect, BRCA, and tubal fimbria: our evolving understanding of the origin of tubo-ovarian high-grade serous carcinoma and why assignment of primary site matters

Singh, Naveena1; Gilks, C. Blake2; Wilkinson, Nafisa3; McCluggage, W. Glenn4

Pathology - Journal of the RCPA: August 2015 - Volume 47 - Issue 5 - p 423–431
doi: 10.1097/PAT.0000000000000291

Summary: It has long been held that most epithelial ovarian carcinomas arise from the ovarian surface epithelium. Theories on origin were based on the assumption that there was a common cell of origin for all ovarian carcinoma histotypes, and that these histotypes were closely related and frequently admixed. It is now recognised that the histotypes are distinct diseases. Recent studies on early, organ-confined, non-uterine high-grade serous carcinoma (HGSC) have led to a change in our understanding of their anatomical site of origin. These studies were initially on patients at high risk of developing HGSC but more recently have been extended to cases without family history or genetic markers of increased risk. These have shown that incidental HGSC, when detected before dissemination, is most commonly identified in the tubal fimbria. As a result, we have had to revisit theories on the cell and site of origin of HGSC. This progress in our understanding has necessitated a change in how we handle cases in clinical practice, as it impacts on primary site assignment, which in turn has implications for staging. In this review we will discuss the evolution of our understanding of the cell of origin of HGSC, the evidence for the tubal fimbria as the anatomical site of origin of most non-uterine HGSC, and the clinical implications of these recent developments.

1Departments of Pathology, Barts Health NHS Trust, London, United Kingdom

2Vancouver General Hospital and University of British Columbia, Vancouver, Canada

3St James’ Hospital, Leeds

4Royals Hospitals Trust, Belfast, United Kingdom

Address for correspondence: Dr Naveena Singh, Department of Cellular Pathology, Barts Health NHS Trust, 2nd Floor, 80 Newark Street, London, E1 2ES, United Kingdom. E-mail:

Received 4 May, 2015

Revised 19 May, 2015

Accepted 19 May, 2015

© 2015 Royal College of Pathologists of Australasia
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