Morphological subtypes of ovarian carcinoma: a ... - BPA Pathology

SUBTYPES OF OVARIAN CARCINOMA 427same way as endometrioid carcinomas 20 (see later). Mostprimary ovarian mucinous carcinomas are well or moderatelydifferentiated (grade 1 or 2) and confined to the ovary.Occasionally, especially in the context of a borderline mucinousneoplasm, there is a sharp demarcation between a borderlinearea and a solid cellular area, a so-called mural nodule. 70,71The mural nodules may be benign (either sarcoma-like composedof a mixture of osteoclast-like giant cells, inflammatorycells and mononuclear cells or corresponding to some specificbenign neoplasm such as leiomyoma, rhabdomyoma or haemangioma)or malignant. The malignancy is most commonlyanaplastic carcinoma but may be sarcoma or carcinosarcoma. 70The anaplastic carcinoma may be composed of spindled,pleomorphic or rhabdoid cells. 70 It is likely that some previouslyreported examples of sarcoma-like mural nodulesactually represent anaplastic spindle cell carcinoma and cytokeratinsstains may be useful in confirming this.Immunohistochemistry of primary ovarian mucinouscarcinomasAs discussed, most primary ovarian mucinous carcinomas (andborderline tumours) are of so-called intestinal type. Intestinaltype ovarian mucinous neoplasms are typically diffuselypositive with CK7 but also commonly express, focally ordiffusely, enteric markers such as CK20, CDX2, CEA andCA19.9 and are negative with hormone receptors, CA125 andWT1. 72,73 CA19.9 especially is often diffusely positive andthere may be elevation of the serum level of this marker. 74Serum CA19.9 levels may be extremely high and are of novalue in predicting preoperatively whether an ovarian mucinousneoplasm is benign, borderline or malignant. 74Molecular events in primary ovarian mucinous carcinomasSimilar to low grade serous carcinomas, ovarian mucinoustumours of intestinal type commonly exhibit k-ras mutationsand identical mutations have been demonstrated in benign,borderline and malignant areas within the same neoplasm,suggesting that k-ras mutation is an early event in the evolutionof these tumours. 75–77 Unlike low grade serous carcinomas,b-raf mutations are not a feature of ovarian mucinousneoplasms of intestinal type.Behaviour of primary ovarian mucinous carcinomasAs discussed previously, most primary ovarian mucinous carcinomasof intestinal type are unilateral and stage I. Advancedstage (stage III or IV) primary ovarian mucinous carcinomasare very rare and a secondary should always be excluded. Theprognosis of stage I primary ovarian mucinous carcinoma isrelatively good, although some cases recur, usually in the pelvisor abdomen; recurrence is associated with a poor prognosis. Inone recent population-based study of 31 primary ovarianmucinous carcinomas, eight of 31 recurred. 65 Infiltrative stromalinvasion is associated with a worse prognosis than expansileinvasion. Advanced stage primary ovarian mucinous carcinomashave a dismal prognosis and respond poorly to thetraditional chemotherapeutic agents used to treat ovarian carcinomas.However, it is again stressed that these are extremelyuncommon. Malignant mural nodules are usually associatedwith a poor prognosis, although a recent study has shown thatstage 1A tumours with malignant mural nodules may beassociated with a relatively favourable outcome. 70ENDOMETRIOID ADENOCARCINOMAMost, but not all, ovarian endometrioid adenocarcinomas arelow grade and low stage (usually confined to the ovary, stage I).They are usually unilateral but approximately 10% are bilateral.They often, although not always, arise from endometriosis(especially an endometriotic cyst) or a pre-existing borderlineadenofibroma. 78,79 The prevalence of primary ovarian endometrioidadenocarcinoma is lower in recent than in olderstudies. 7,8 This is almost certainly due to the recognition thatmany neoplasms which were previously diagnosed as highgrade and high stage endometrioid carcinomas are, in fact,serous in type. This is an area where previously there was poorreproducibility amongst pathologists and where WT1 stainingmay be useful (discussed later). With an endometrioid adenocarcinomainvolving the ovary, there is not uncommonly asynchronous endometrioid proliferation, either premalignant ormalignant, within the uterine corpus. 80 If conservative management(unilateral salpingo-oophorectomy) is undertaken for astage I ovarian endometrioid adenocarcinoma, the endometriumshould be sampled to exclude significant pathology here.Diagnosing a low grade endometrioid adenocarcinoma isusually straightforward, although problems may arise in thedistinction between a grade 1 endometrioid adenocarcinomaand a borderline endometrioid adenofibroma. 79 Some lowgrade endometrioid adenocarcinomas exhibit obvious stromalinvasion but in many (probably the majority) the diagnosis ismade on the basis of a back-to-back glandular architecture withexclusion of stroma, similar to the criteria used to diagnose anendometrioid adenocarcinoma of the endometrium (Fig. 7).The presence of glandular confluence and a back-to-backarchitecture with stromal exclusion should result in a diagnosisof endometrioid adenocarcinoma even when the cytologicalfeatures are low grade. The presence of one or more of theimportant triad of adenofibromatous areas, squamous elements(morular or non-morular) and endometriosis may be a usefulpointer towards an endometrioid neoplasm. Unusual morphologicalfeatures occasionally seen in ovarian endometrioidadenocarcinomas, either focally or diffusely, include sexcord-like formations and spindle cell differentiation; thesefeatures also occur more uncommonly in the correspondinguterine neoplasms. 81 The other morphological variants ofuterine endometrioid adenocarcinoma, such as secretory andoxyphilic, may also occur in the ovary. High grade ovarianFig. 7 Low grade endometrioid adenocarcinoma of ovary with back to backglandular arrangement.Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.