Update on Low Malignant Potential Ovarian Tumors

Introduction

Epithelial tumors of the ovary account for 60% of all ovarian neoplasms and 80% to 90% of ovarian cancers.[1] Low malignant potential (LMP) tumors of the ovary, also referred to as borderline ovarian tumors, represent a subset of epithelial cancers. These tumors are characterized by the absence of ovarian stromal invasion, and yet they retain the ability to metastasize.

A number of clinical features distinguish LMP ovarian tumors from their invasive counterparts; the most notable of these is the far better outcome of patients with LMP tumors. Clinical and molecular studies continue to refine our understanding of these lesions. This article will review the current management of LMP ovarian tumors.

History

In 1929, Taylor first recognized the existence of a group of ovarian cancers that were associated with an improved prognosis; he termed these lesions “semimalignant” tumors.[2] In 1961, the International Federation of Gynecology and Obstetrics (FIGO) proposed a classification of ovarian tumors that included LMP lesions; this designation became effective in 1971[3] and was incorporated into the World Health Organization classification in 1973.[4]

Epidemiology

Low malignant potential ovarian tumors account for approximately 15% of epithelial ovarian cancers.[5] According to American Cancer Society estimates, almost 4,000 LMP tumors are expected to be diagnosed annually in the United States.[6] The average age of women with LMP ovarian tumors is 49 years, with the highest frequency of cases occurring in the 15- to 29-year age group.[7]

As with invasive ovarian cancer, both oral contraceptive use and lactation lower the risk of developing an LMP tumor, and a history of infertility increases the risk.[8,9] Low malignant potential ovarian tumors may occur in infertile women who have used fertility drugs.[9,10] However, only a small number of such cases have been detected, and limited information is available regarding the specific medications used in these cases; therefore, caution is needed when one is extrapolating from these reports.[9]

The occurrence of pregnancy after treatment for an LMP tumor does not appear to worsen prognosis, nor does the detection of an LMP tumor adversely affect an existing pregnancy.[11]

The use of some deodorizing powders has been associated with an increased risk of developing LMP tumors.[12]

Pathology

Primary Lesions

The architecture of LMP ovarian tumors is characterized by solid and cystic areas. Papillary projections often arise within the cystic areas or loculations; surface papillations may also occur. Microscopic features include epithelial proliferation and stratification, nuclear atypia, and mitotic activity, with the sine qua non being the absence of stromal invasion.[1]

Serous and mucinous tumors comprise the vast majority of cases, with endometrioid, clear cell, and Brenner-type tumors also described.[1]

Serous tumors (Figure 1) are bilateral in 25% to 33% of cases. Serous tumors are associated with extraovarian disease much more commonly than are mucinous lesions (30% vs 15%, respectively).

There are two types of mucinous tumors: intestinal and endocervical. The intestinal type has a bilateral incidence of less than 10% but is associated with pseudomyxoma peritonei. The endocervical variant is bilateral in 40% of cases.

Endometrioid LMP tumors can occur in association with hyperplastic or invasive lesions of the endometrium, although extraovarian disease is uncommon. Clear cell and Brenner-type LMP tumors are quite rare.

Low malignant potential ovarian tumors may occur within a background of benign neoplasia and/or in association with areas of invasive disease. Therefore, a thorough sampling of the primary tumor (usually one section for each centimeter of tumor) is critical to the establishment of an accurate diagnosis.

“Microinvasion”—This term has been applied to cases that appear to bridge the definitions of LMP and invasive lesions. Bell and Scully reported a series of cases in which “small foci of stromal invasion,” none larger than 3 mm in greatest dimension, were detected within LMP tumors.[13] Although 2 of the 21 patients studied had advanced disease, all patients who were followed did well.

The authors suggested that the prognosis of cases associated with “microinvasion” is similar to that of other LMP tumors. Although others concur with this finding,[14] the term “microinvasion” should be used with caution until further data are available.

Intraoperative Diagnosis—Intraoperative diagnoses are determined using the well-established technique of frozen section.[15] This technique can accurately identify LMP ovarian tumors. Menzin and colleagues reported that a frozen-section diagnosis of an LMP tumor excluded benign lesions in 94% of cases, although further histologic examination identified foci of invasive disease in 27% of cases.[16]

Pathologists will often use qualifying terms, such as “rule out LMP” and “at least LMP,” in frozen-section reports.[16,17] In the study by Menzin and colleagues, each of the cases that ultimately proved to be benign (6%) were deemed equivocal on frozen-section evaluation.[16] Therefore, a continuing dialog with consultant pathologists is vital for maintaining a clear understanding of clarifying terms that may influence the appropriate application of surgical therapy.

Extraovarian Disease

The peritoneal lesions associated with ovarian LMP tumors are of three types: endosalpingiosis, noninvasive implants, and invasive implants. Endosalpingiosis refers to benign glandular structures similar in appearance to tubal epithelium that can be found on the peritoneum but have also been described at other sites, including lymph nodes.[18] The finding of endosalpingiosis does not appear to hold any prognostic significance and does not signify advanced-stage disease.

Noninvasive implants have the same characteristics as described above for the primary lesions. Invasive implants are distinguished by their irregular borders, as well as by the desmoplastic response of the underlying stroma that is infiltrated by tumor cells.[19]