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Ovarian Tumors of Low Malignant Potential

Ovarian Tumors of Low Malignant Potential

The Trimbles have provided a useful overview of the major clinical and pathobiologic issues involving ovarian borderline tumors (also termed atypical proliferative tumors or tumors of low malignant potential). The borderline category of ovarian tumors comprises a heterogeneous group of neoplasms that, when subdivided according to histologic appearance and the presence of peritoneal lesions, form distinctive subgroups, each with characteristic pathologic features and a distinctive clinical course. Thus, retrospective reviews of thousands of reported cases have shown that borderline tumors of all types that are confined to the ovaries (ie, lack peritoneal "implants") are associated with virtually 100% survival and an extremely low recurrence rate.[1] Similarly, based on about 500 reported cases in which peritoneal implants were subclassified into invasive and noninvasive types, serous tumors with noninvasive peritoneal implants were associated with a low recurrence rate and a survival rate approaching 100%. In contrast, serous tumors with invasive peritoneal implants, a high proportion of which display a characteristic micropapillary pattern in the ovary and/or in the peritoneum (serous borderline tumor with micropapillary pattern, or noninvasive micropapillary serous carcinoma), have a significantly worse prognosis.[2] Invasive Peritoneal Implants
Investigators generally agree that women with serous borderline tumors with invasive peritoneal implants have a poor prognosis. The mortality rate after a mean of 7.4 years of follow-up is 34%, but many patients die later,some after 10 or 15 years and, rarely, after more than 20 years. Many of these women develop unequivocal evidence of invasive carcinoma. Although not all experts agree, many believe that invasive peritoneal implants are, in fact, invasive low-grade carcinomas from the outset. The Trimbles suggest that these invasive implants reflect "a primary peritoneal carcinoma, rather than a tumor of [low malignant potential]." We certainly agree that these tumors are invasive carcinomas and do not belong in the borderline (ie, low malignant potential) category. A few of them may indeed be independent primary peritoneal carcinomas, but we believe that most serous borderline tumors with invasive implants reflect two other possibilities: Some may be ovarian carcinomas with relatively small or inconspicuous areas of invasion on gross examination and, therefore, were not sampled for histologic assessment; others may be micropapillary serous carcinomas that are often exophytic growths exposed to the peritoneal cavity. These tumors may be either in situ carcinomas that can detach, implant on the peritoneum, and invade, or invasive serous carcinomas whose morphology is not recognized as invasive based on currently applied criteria. Whether the invasive peritoneal implants are primary peritoneal carcinomas or metastatic ovarian carcinomas, they behave as low-grade carcinomas and do not belong in the borderline category. Ovarian Serous Carcinogenesis
Much remains to be learned about the pathogenesis of ovarian cancer. Some investigators have proposed that the serous borderline tumor represents an intermediate step in the transformation of a serous cystadenoma into a serous carcinoma. The Trimbles refer to this as a "faulty premise," as it appears that this is not true in most cases. Most ovarian serous carcinomas are high grade and appear to develop de novo from the ovarian surface epithelium or inclusions of surface epithelium. However, accumulating evidence suggests that typical serous borderline tumors may be a precursor of the micropapillary variant of serous borderline tumors and thus a precursor of low-grade serous carcinomas, most of which display the characteristic micropapillary architecture but also show clear-cut evidence of invasion. Accordingly, there may be two distinct pathways of ovarian serous carcinogenesis: the more common pathway characterized by de novo origin, high-grade morphology, and rapid clinical progression, and the less common pathway characterized by a benign serous tumor origin, slow growth, and development in a stepwise progression from a benign atypical proliferative tumor (serous borderline tumor) to noninvasive carcinoma (micropapillary variant or noninvasive micropapillary carcinoma) to invasive low-grade serous carcinoma (invasive micropapillary serous carcinoma). Mucinous tumors present a somewhat different problem. The majority of so-called mucinous borderline tumors with an unfavorable outcome are associated with the pseudomyxoma peritonei syndrome. Recent studies have shown that nearly all of these tumors are appendiceal mucinous adenomas that have ruptured and seeded the peritoneal cavity, involving the ovaries secondarily and, therefore, no longer considered ovarian tumors. Primary mucinous ovarian tumors arise as cystadenomas that can progress to atypical proliferative tumors and eventually to mucinous carcinoma. The latter, however, are quite uncommon. Mislabeled Category
Our current understanding of the heterogeneity of the borderline category can provide important prognostic information for patients. In our opinion, stage I borderline tumors of all types are clinically benign, and it is inappropriate to label these as "cancer," which the terms "borderline" and "low malignant potential" imply. They are more appropriately categorized as precancerous lesions, and a better name for them might be atypical proliferative tumors. Patients with serous borderline tumors with noninvasive implants should be followed but informed that their risk of developing a serious complication (ie, invasive carcinoma) is very low, although some develop symptoms due to adhesions that may require surgical intervention. The management of patients with invasive implants is problematic at this time because these low-grade carcinomas do not appear to respond to conventional cytotoxic chemotherapy. Limited data suggest that recurrences of micropapillary tumors can be successfully managed surgically (via secondary cytoreduction). Nonetheless, their prognosis, although better than advanced-stage conventional serous carcinomas, is substantially worse than the usual type of serous borderline tumor (atypical proliferative serous tumor), and careful follow- up is necessary.


The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.


1. Seidman JD, Russell P, Kurman RJ: Surface epithelial tumors of the ovary, in Kurman RJ (ed): Blaustein’s Pathology of the Female Genital Tract, 5th ed, pp 791-904. New York, Springer-Verlag, 2002.
2. Seidman JD, Kurman RJ: Ovarian serous borderline tumors: A critical review of the literature with emphasis on prognostic indicators. Hum Pathol 31:539-557, 2000.
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