Patterns of Stromal Invasion in Ovarian Serous Tumors of Low Malignant Potential (Borderline Tumors): A Reevaluation of the Concept of Stromal Microinvasion

Stanford University, Palo Alto, California, United States
American Journal of Surgical Pathology (Impact Factor: 5.15). 10/2006; 30(10):1209-21. DOI: 10.1097/01.pas.0000213299.11649.fa
Source: PubMed


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.

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    • "Third, borderline tumors are found associated with the majority of LG-SCs [16]. It is seen that, foci of true early invasion in borderline tumors resemble LG-SCs [15] [17] [18] [19], and, invasive implants mostly associated with micropapillary serous borderline tumors, which has been recently defined as LS-SC [20] [21] [22], are histologically identical to LG-SCs [23] [24]. All these morphological and histological observations support a model wherein LG-SCs evolve from OEIs, via intermediate stages of serous cystadenomas and borderline tumors. "
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    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.
    Full-text · Article · Dec 2013
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    • "A tumor showing a stromal invasion of less than 3-5 mm without a desmoplastic reaction has been designated as a microinvasive tumor.15 Microinvasion is described in the borderline tumor category as one of the associated features while dealing with SBT.26 Microinvasion can be found in otherwise typical SBT and these microinvasive tumors have similar biologic behaviors and prognosis to those of tumors lacking this feature.15-18,26 Accordingly, SBTs with microinvasion should be distinguished from serous carcinoma. "
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    ABSTRACT: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.
    Full-text · Article · Jun 2012
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    • "Stromal invasion by other tumors of other organs is a commonly recognized concept, and has long been important evidence for the definitive diagnosis of malignant tumor [8] [9]. However, stromal invasion of HCC has not been generally known until quite recently. "
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    ABSTRACT: Stromal invasion (invasive growth of tumor tissue into portal tracts and fibrous septa) is now recognized as the most important finding in the diagnosis of the well-differentiated type of early hepatocellular carcinomas (HCCs). In differentiating stromal invasion from pseudoinvasion (benign hepatic tissue in fibrous stroma), the following 5 items are useful: (1) macroscopic or panoramic views of the histological specimen, (2) the amount of fibrous components of stroma, (3) destruction of the structure of portal tracts, (4) loss of reticulin fibers around cancer cells, and (5) cytokeratin 7 immunostaining for ductular proliferation. Knowledge of stromal invasion is also useful for a better understanding of the vasculature (hypovascular HCCs) and histological features (fatty change) of early HCCs. Invasion of preexisting arteries and portal veins causes hypo-vascularity of HCCs. Further, hypovascularity causes fatty change as a hypoxic change of cancer tissues.
    Full-text · Article · Jun 2011
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