Mucinous ovarian carcinoma: Slippery business

Unless you are a recent graduate, you learned in medical school that borderline and malignant ovarian mucinous tumors were common, but clinically unpredictable, and often associated with pseudomyxoma peritonei. General pathology textbooks published through the end of the last century and even more recent gynecology textbooks make the same points. These ideas are outmoded. An attack on these received truths began in the primary pathology literature in the late 1980s, but for whatever reason many pathologists, gynecologists, and medical oncologists have failed to get the message. Zaino et al’s paper in this edition of Cancer brings one part of the argument to a wide audience. To summarize, the paper reports that high-stage mucinous tumors involving the ovary frequently represent metastases from extraovarian primary sites, are often misdiagnosed, and behave virulently. The authors accomplished these results with only astute powers of observation and a willingness to ask questions; neither molecular genetic technology nor inflated research funds were required. It is well recognized that secondary involvement of the ovary by metastatic, extraovarian mucinous carcinoma can result in the mistaken clinical, radiological, and pathological impression of a primary ovarian mucinous carcinoma. Primary ovarian mucinous carcinomas are now considered rare in North American populations. In fact, they constitute only approximately 3% of all ovarian carcinomas, whereas metastatic carcinoma to the ovary is substantially more common. At least two-thirds of primary ovarian mucinous carcinomas are confined to the ovary at presentation. Any extraovarian disease is met with skepticism by pathologists who study this entity, such that classification as primary ovarian mucinous carcinoma in this context is either considered a diagnosis of exclusion or is reflexively excluded as a diagnostic possibility. It is also well recognized that secondary involvement of the ovary by metastatic, extraovarian mucinous carcinoma (particularly from the appendix, gallbladder, or pancreas) can result in the mistaken pathological impression of a mucinous borderline tumor or adenoma. The most common type of mucinous borderline tumor, referred to as either an intestinal or gastrointestinal mucinous borderline tumor, is now considered a clinically benign neoplasm, despite its name and reputation, as long as metastasis to ovary (masquerading as mucinous borderline tumor) is excluded. Pseudomyxoma peritonei is currently recognized as a syndrome that is almost always attributable to appendiceal mucinous neoplasms when tumor cells appear highly differentiated. The only primary ovarian tumor that gives rise to this syndrome is the exceptional appendiceal mucinous neoplasm that occurs within an ovarian teratoma. So, what is the gold standard? How do we know when a mucinous tumor in the ovary arose there? In my opinion, the only mucinous tumors that one can be sure arose in the ovary are those that are present in the context of another primary ovarian neoplasm known to frequently harbor mucinous tumors. Examples include mucinous tumors associated with teratoma, Brenner tumor, and Sertoli-Leydig cell tumor. It is also possible that, for example, some mucinous tumors apparently unassociated with teratoma arose in that context, but overgrew and replaced the teratoma. However, mucinous carcinomas associated with these other primary ovarian neoplasms only exceptionally rarely account for clinically aggressive ovarian mucinous tumors. For the remaining cases, pathologists depend primarily on clinical history. When clinical history of a previously diagnosed carcinoma or pancreatic mass, for example, is unknown or unclear, we are left with playing statistical roulette: approximately 90% of unilateral mucinous ovarian tumors measuring more than 12 cm are primary