Histology

Borderline ovarian tumors typically exhibit the following histologic features: architectural complexity of glandular structures, epithelial papillae, cellular stratification, and nuclear atypia, and the requirement for diagnosis is two of these three elements.6 The key to differentiating between an invasive ovarian cancer and a borderline neoplasm is the lack of stromal invasion. Since these tumors may be large, careful and thorough sectioning is required. Borderline tumors are most frequently serous followed by mucinous, but they can also occur less often as endometrioid, clear, transitional, or mixed types (Table 11-1).

In addition to the histology, other important factors such as extraovarian disease, microinvasion, and micropapillary pattern may be present, and the prognostic significance of each continues to be investigated (Table 11-2). All these features have been linked to increased recurrence rates.

Borderline tumors can have foci of extraovarian disease (often termed implants rather than metastases), and stage remains the most important prognostic factor in this disease. Noninvasive implants can be differentiated from invasive implants by the sharp delineation from normal tissue, a fibrotic or inflammatory stroma, and continued gland formation. In contrast, the invasive implants tend to have infiltration of normal tissue with edematous or myxoid stroma and form nests surrounded by a cleft. To add to the complexity, any given patient may have a mix of implant types,7-12 although the majority of extraovarian disease remains noninvasive.11,12 In a review of seven published papers comparing invasive with noninvasive implants, Lu and Bell3 found that the relapse rate and death due to tumor were significantly increased in the invasive implants (44% versus 19%, and 32% versus 7%, respectively).

Table 11-1. Borderline Ovarian Tumor Histology3

Histologic Types Percentage

Serous 43-75

Mucinous 23-40

Endometrioid 2-10

Clear cell 0-8

Brenner <1

Mixed 5-10

Data are taken from references 3, 6, 13, 17, and 21.

Table 11-2. Prognostic Features in Borderline Tumors

Clinicopathologic Feature Significance

Micropapillary histology Increased rates of extraovarian disease

Increased recurrence rates and death due to disease

Stage The most important factor in predicting recurrence

Increased recurrence rates and death due to disease

Microinvasion Increased rates of recurrence

Potential increased rates of recurrence with invasive cancer

Increased mortality rates

Decreased disease-free and overall survival

Microinvasion has also elicited some controversy as to whether tumors exhibiting this feature represent a subset of borderline tumors or may represent early serous papillary carcinoma. Buttin and colleagues13 evaluated the impact of microinvasion (defined as invasive foci less than 3 mm in diameter with a total area less than 5% of the tumor) and found that recurrence rates were significantly higher in women with microinvasion compared with rates in women without microinvasion (23% versus 3.5%, P = .023). Hogg and colleagues14 compared serous grade 1 carcinomas with borderline tumors and concluded that borderline tumors with microinvasion represent early carcinomas. This conclusion was based on qualitative histologic similarities between borderline tumors with microinvasion and grade 1 carcinomas and the frequent coexistence of the two entities. Additional support for this supposition may be the fact that borderline tumors may often recur with low-grade serous carcinoma rather than borderline tumors.15 Finally, Longacre and associates,16 in an analysis of 276 patients, and Ren and associates,17 in an analysis of 234 patients, both found that microinvasion was a significant risk factor for decreased survival on multivariate analysis.

Micropapillary architecture within borderline tumors was first described in the 1990s and was added as a subgroup of borderline tumors by the WHO, although debate continues as to whether these tumors should be an entity separate from both borderline and epithelial ovarian carcinoma. These tumors are distinct from the garden variety of borderline tumors in that they have increased cytologic atypia and a papillary proliferation with a hierarchical branching pattern of epithelium. By convention, the micropapillary component must be at least 5 mm.18,19 There continues to be extensive debate among pathologists as to whether tumors with micropapillary architecture should be classified as a separate entity or as a subset of borderline tumors. Regardless of classification, tumors with micropapillary architecture are more often bilateral, have extraovarian disease, and, in turn, more unfavorable outcomes compared with typical borderline tumors.3,7,20 In comparing the typical borderline pattern with the micropapillary pattern in seven published studies, Lu and Bell3 found that both the relapse rate and death due to tumor were significantly increased in the micropapillary type (32% versus 15% and 15% versus 8%, respectively). Since these micropapillary types more often have invasive implants, it is difficult to discern the isolated impact of the micropapillary feature on survival.

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