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Update on Low Malignant Potential Ovarian Tumors

Update on Low Malignant Potential Ovarian Tumors

ABSTRACT: Low malignant potential (LMP) ovarian tumors represent a small subset of epithelial ovarian cancers that were first identified 70 years ago but were recognized in a systematic way only within the last 30 years. These lesions afflict women at a much younger age than invasive ovarian cancer, behave in a more indolent manner, and have a much more favorable prognosis. The management of women with LMP tumors is primarily surgical; adjuvant therapy plays little role in early disease and its use in advanced disease is not well defined. Ongoing investigations are attempting to define prognostic factors that may assist clinicians in the appropriate application of postoperative therapy. [ONCOLOGY 14(6):897-906; 2000]

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]

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