Progress in pathologyOvarian carcinoma pathology and genetics: recent advances
Section snippets
Serous carcinoma
One of the most important recent observations is the recognition that low-grade serous carcinoma (LGSC) and HGSC are fundamentally different tumor types [23], [24], [25], [26], [27], [28]. The former are associated with a serous borderline component in most cases and are not related to BRCA abnormalities. In contrast, HGSCs are not associated with serous borderline tumors and may arise from the fallopian tube in a significant number of cases [29], [30], [31]. Because of the fundamental
Demographics
These are the most common ovarian carcinomas, and most patients present with high-stage disease; tumor confined to the ovary at diagnosis is distinctly uncommon [32].
Histopathology
The morphologic spectrum within this tumor subtype is wide, but the most distinctive growth pattern consists of highly stratified epithelium with a fenestrated appearance and slit-like spaces. Other patterns include solid or microcystic growth. The tumor cells are typically of intermediate size, with scattered bizarre mononuclear
Demographics
LGSCs are uncommon and account for considerably fewer than 5% of all cases of ovarian carcinoma (Fig. 2). The presence of small foci of LGSC in a borderline tumor is associated with an excellent prognosis. The prognosis for patients with advanced-stage disease is less favorable, although the disease may follow a relatively indolent course, with long periods between recurrences [16].
Histopathology
LGSCs have uniform nuclei and differentiated architecture with papillary growth; numerous psammoma bodies are a
Mucinous carcinoma
The tumor cells of MCs may resemble those of the endocervix, gastric pylorus, or intestine [1], [2]. Most of these tumors show gastrointestinal differentiation and are the focus of this discussion. It should be acknowledged, however, that in higher-grade MCs, distinction between intestinal type and endocervical-like tumors is problematic.
Endometrioid carcinoma
Endometrioid tumors of the ovary closely resemble those encountered more frequently in the endometrium. The practice in some centers of diagnosing any high-grade carcinomas with glandular differentiation as EC is inappropriate because these tumors express WT1 as frequently as HGSC [4], [5] and their mRNA expression profile is also indistinguishable from HGSC [58]. Glandular differentiation is part of the spectrum of serous neoplasia and is not sufficient for a diagnosis of EC.
Clear cell carcinoma
This is the most enigmatic subtype of ovarian carcinoma. The presence of clear cells alone is not sufficient for a diagnosis of CCC because cells with clear cytoplasm can be seen in HGSC and EC [6], [71]. The accurate diagnosis of CCC depends on consideration of the constellation of architectural and cytological findings characteristic of this tumor type.
Brenner/Transitional Carcinoma
Malignant Brenner tumors (carcinoma admixed with a benign and/or borderline Brenner component) are vanishingly rare. Transitional cell carcinomas without a Brenner component vary widely in frequency in different case series [80], [81] and cannot be reproducibly distinguished from HGSCs based on clinical [82] or molecular features [83], [84], [85], [86]. This suggests that transitional cell carcinomas without a benign or borderline Brenner component are best considered a variant of HGSC rather
Mixed epithelial carcinomas
Much of the historical lack of reproducibility in classification of ovarian carcinoma has resided in the group of high-grade tumors variously diagnosed as high-grade serous/endometrioid/clear cell/transitional/undifferentiated carcinoma. If tumors with areas of undifferentiated growth are classified based on the areas showing a recognizable growth pattern, they usually will end up classified as HGSC. As noted previously, most tumors considered in the past to be mixed high-grade
Adenocarcinoma, unclassified type
There remain a small number of ovarian carcinomas that defy subclassification into one of the types described above. These may be undifferentiated tumors, or tumors with overt glandular differentiation but lacking the architectural patterns or cytological features characteristic of the common ovarian carcinoma subtypes. Approximately 2% of ovarian carcinomas fall into this group in our practice, but it can be anticipated that this number will decrease as better molecular tests for cell type
Conclusions
There has been significant progress in the histopathological subclassification of ovarian surface epithelial carcinomas. The 5 main subtypes of ovarian carcinoma (in descending order of frequency: HGSC, CCC, EC, MC, and LGSC, with representative examples shown as Fig. 5) account for 98% of ovarian carcinomas, can be reproducibly diagnosed, and are inherently different diseases, as indicated by differences in risk factors, molecular abnormalities, natural history, and response to chemotherapy
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