Patterns of stromal invasion in ovarian serous tumors of low malignant potential (borderline tumors): a reevaluation of the concept of stromal microinvasion.
ABSTRACT Stromal-epithelial patterns of invasion in serous tumors of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas whereas those with either no stromal invasion or stromal microinvasion are classified as serous tumors of low malignant potential (S-LMP). The histologic features of stromal microinvasion in ovarian S-LMP have been addressed in a variety of studies, but controversy persists regarding diagnostic criteria and prognostic significance, particularly in patients with high-stage disease. In addition, a subset of otherwise typical S-LMP has patterns of invasion that are not classic destructive invasion and do not meet the current diagnostic criteria for stromal microinvasion because of either qualitative features or size restrictions. To further evaluate the full histologic spectrum of stromal-epithelial patterns of invasion in otherwise typical S-LMP, we examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO stages II, III, and IV) with stromal-epithelial alterations not meeting criteria for classic destructive invasion. This group of cases included those meeting the definition of microinvasion and a subset that would be excluded based on size measurements or unusual qualitative features, but did not exhibit significant stromal reaction. Five patterns of invasion were identified: individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, inverted macropapillae, and micropapillae. Individual, discrete aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in greatest linear dimension as measured by conventional methods. The number of discrete foci ranged from 1 to greater than 10; in 7 tumors (12%), the invasive foci were diffusely scattered throughout the stroma without discrete aggregates. These stromal-epithelial alterations were associated with disease progression and/or death due to disease in 9 of 50 (18%) patients with follow-up (mean, 92.5 mo) and were covariant with other adverse prognostic features (invasive implants, nodular lymph node aggregates, high stage, and unresectable disease). Disease progression was most strongly linked to the presence of micropapillae, but the majority of patients with adverse outcome had the more common, classic stromal-epithelial patterns associated with microinvasion (ie, individual cells, cell clusters, and simple papillae). Neither size of the largest contiguous aggregate nor extent of stromal involvement correlated with outcome. Classic microinvasion disproportionately occurred in patients presenting during pregnancy (P<0.0001), and was not associated with adverse outcome in that setting, but follow-up was limited. Based on the cumulative outcome data, the presence of stromal-epithelial patterns of invasion distinct from classic destructive invasion in otherwise typical S-LMP stratifies patients at long-term risk for disease progression, but does not warrant a diagnosis of carcinoma or a change in current management schemes. Maintaining classification as a serous tumor of low malignant potential (serous borderline tumor) with stromal invasion seems appropriate even in the presence of diffuse stromal involvement or discrete aggregates measuring greater than 3 (or 5) mm. As the stromal-epithelial alteration featuring micropapillae may represent a comparatively higher-risk lesion with a clinical course analogous to that of low-grade serous carcinoma, pathologists should identify this specific stromal-epithelial pattern in the diagnostic report until sufficient data is acquired to form more definitive conclusions regarding its prognosis.
- SourceAvailable from: Wenxin Zheng[Show abstract] [Hide abstract]
ABSTRACT: Our understanding of the carcinogenesis and histogenesis of ovarian cancer has undergone a paradigm shift in recent years, after accumulating evidence from morphologic and molecular genetic studies. Findings from these studies suggest that both high-grade and low-grade serous ovarian cancers, traditionally believed to start from the ovarian surface, may originate from the distal fallopian tube. This article reviews recent evidence for the tubal origin of serous ovarian cancers, especially the low-grade serous carcinomas.American Journal of Clinical and Experimental Obstetrics and Gynecology. 12/2013; 1(1):31-36.
- [Show abstract] [Hide abstract]
ABSTRACT: Low-grade serous (LGS) ovarian and primary peritoneal cancer is a rare disease with limited therapeutic options. Low response rates are observed with cytotoxic chemotherapy. However, significant responses have been reported in patients treated with bevacizumab. The objective of this study was to determine the response rate to bevacizumab with or without concurrent chemotherapy in patients with recurrent serous borderline or LGS ovarian or primary peritoneal cancer.International Journal of Gynecological Cancer 07/2014; 24(6):1010-1014. · 1.95 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Most of the literature on serous borderline/atypical proliferative serous tumors (SBT/APSTs) shows no effect of microinvasion or lymph node involvement on outcome. This study is a morphologic and immunohistochemical analysis of the cells comprising SBT/APSTs, microinvasion, lymph node involvement, and low-grade serous carcinoma (LGSC) in an attempt to explain this unusual behavior. We found that the cells in microinvasion and in lymph nodes were morphologically similar to the cells in SBT/APSTs but differed significantly from the cells in LGSCs. In addition, one particular population of cells, those with abundant eosinophilic cytoplasm (eosinophilic cells), in SBT/APSTs, microinvasion, and lymph nodes showed a significant loss of expression of ER, PR, and WT-1 compared with the cuboidal/columnar tumor cells, both in cases of microinvasion (P<0.001 for all 3 markers) and lymph node involvement (P<0.001, P=0.02, P=0.002, respectively). There was a significant decrease in the Ki-67 proliferation index for microinvasion (P=0.004) and a decreasing trend for lymph node involvement (nonsignificant) compared with the columnar/cuboidal cells. In addition, cells in these tumors showed morphologic evidence of apoptosis, which was confirmed by immunostaining with M30, a marker of apoptosis. In contrast, LGSCs lacked eosinophilic cells and showed no loss of expression of ER, PR, and WT-1. They also had a significantly higher Ki-67 proliferation index than their associated SBT/APSTs (P=0.029). On the basis of these findings, we propose that the cells comprising microinvasion do not represent an invasive neoplastic process. Instead, in view of the loss of expression of ER, PR, and WT-1, evidence of apoptosis, and decrease in the Ki-67 proliferation index, we postulate that they are senescent and terminally differentiated with a subset of cells undergoing apoptosis, which could explain their lack of an adverse effect on outcome.The American journal of surgical pathology 01/2014; · 4.59 Impact Factor