My approach to and thoughts on the typing of ovarian carcinomas

Abstract

Ovarian carcinomas of epithelial type comprise a heterogeneous group of neoplasms, each with a different underlying pathogenesis and natural behaviour. Accurate classification of ovarian carcinomas is important since each type may be associated with a different behaviour, natural history and outcome. Precise classification is also critical to determine whether alternative therapeutic strategies are appropriate for different tumour types. Previous studies have shown significant interobserver variation in the typing of ovarian carcinomas. There are several areas where there are particular difficulties; these include the distinction between high-grade serous and endometrioid adenocarcinomas and the distinction between a true clear cell carcinoma and clear cell areas within other adenocarcinomas. This review details my approach to the typing of ovarian carcinomas. Morphological assessment, which remains the mainstay in diagnosis, can be supplemented by immunohistochemistry which, for example, is useful in the distinction between serous carcinomas (WT1 positive) and other carcinomas (generally WT1 negative). In recent years, there has been emerging new information regarding the major underlying molecular events in several types of ovarian carcinoma. This has resulted in the acceptance that there are two distinct types of ovarian serous carcinoma. These are termed low-grade and high-grade serous carcinoma, but represent two distinct tumour types rather than low-grade and high-grade variants of the same neoplasm. The integration of clinical, morphological and molecular data has resulted in a more precise classification of ovarian carcinomas and has resulted in the proposal for a broad dualistic pathway of ovarian epithelial carcinogenesis with, in general, low-grade type 1 tumours evolving from benign and borderline neoplasms through a well-defined adenoma-carcinoma sequence, and high-grade type 2 neoplasms arising from an, as yet, undefined precursor lesion.Ovarian carcinomas of epithelial type comprise a heterogeneous group of neoplasms. The major types of primary ovarian epithelial malignancy 1 are listed in the box. Each tumour type has a different underlying pathogenesis and natural behaviour. Although, currently, management of ovarian carcinoma is largely dependent on factors such as tumour grade and stage, and not usually on cell type, it is important to accurately type ovarian carcinomas to ascertain whether the various neoplasms have a different behaviour independent of stage and other clinicopathological parameters. Typing is also important since some tumours, such as mucinous and clear cell carcinoma, seem to exhibit a poor response to platinum-based chemotherapy. 2 In fact, tumour type may be a more reliable predictor of response to chemotherapy than tumour grade. 2This review details my thoughts on and approach to the typing of ovarian carcinomas and is meant as a guide to the practising surgical pathologist. Morphology remains the mainstay in diagnosis but immunohistochemistry may be of value as a...

Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR)

“…30 There are five major subtypes of primary ovarian carcinoma, high-grade serous, clear cell, endometrioid, mucinous and lowgrade serous. [31][32][33][34] There are also other uncommon minor subtypes, those listed by the WHO, including malignant Brenner tumour, seromucinous carcinoma and undifferentiated carcinoma. 30 Carcinosarcoma is a mixed epithelial and mesenchymal malignancy but is included in the category of epithelial malignancies in this data set as most are of epithelial origin and histogenesis.…”

“…This is in part because, although clinically often considered as one disease, there is an increasing realisation that the different morphological subtypes of ovarian carcinoma have a different pathogenesis, are associated with distinct molecular alterations and have a different natural history, response to traditional chemotherapy and prognosis. [31][32][33][34] Tumour typing may also be important in identifying or initiating testing for an underlying genetic predisposition; for example, HGSC may be associated with the underlying BRCA1/2 mutation while endometrioid and clear cell carcinomas can occur in patients with Lynch syndrome (LS). 36 The most common ovarian carcinoma is HGSC (approximately 70%) followed by clear cell and endometrioid.…”

“…The current 2014 WHO classification does not include a category of mixed carcinoma, 31 but the prior classification stated that a diagnosis of mixed carcinoma should only be made if the minor component represents 410% of the neoplasm. 31 However, it is recommended that all different Ovary, tube and primary peritoneal data set morphological subtypes in an ovarian carcinoma are documented, even if they comprise o 10% of the neoplasm. As stated, mixed carcinomas in the ovary are uncommon, the most prevalent combination being clear cell and endometrioid (both of these tumour types often arise in endometriosis).…”

Ovarian carcinoma: An overview of current status

“…The aforementioned data succinctly illustrate ovarian carcinoma as one of the most serious gynecologic malignancies, responsible for the highest number of fatality. Different morphological subtypes of ovarian carcinoma possess different pathogenesis with distinct molecular alterations, different natural history, and prognosis [31][32][33] . In India, the ovarian cancer incidence (age-adjusted rate per 100,000) in different population-based cancer registries is reported to range from 1.7 to 15.2 for the year 2012 to 2014.…”

Letter to the editor regarding ‘Roh MH, Lassin Y, Miron A et al. High-grade fimbrial-ovarian carcinomas are unified by p53, PTEN and PAX2 expression‘

“…[2][3][4][5] Global gene expression profiling has highlighted the molecular similarities between tumors diagnosed as high-grade serous carcinoma and high-grade endometrioid carcinoma, 6,7 and WT1 immunostaining profiles of these tumor types are identical (as shown by Roh et al 1 ). 8,9 This has led to increasing recognition that most of those tumors diagnosed as high-grade endometrioid carcinomas in the past are indistinguishable from high-grade serous carcinomas, [10][11][12] completely distinct from the endometrioid carcinomas that meet the WHO criterion, ie, 'closely resemble the common variant of endometrioid carcinoma of the uterine corpus', 13 and are tumors that are typically low-grade and are frequently associated with endometriosis. This simple change in practice results in a highly reproducible classification of ovarian carcinoma based on tumor cell type, 14 with a classification system that reflects the underlying differences in molecular abnormalities, outcomes and response to treatment (reviewed in Gilks and Prat 12 ).…”