McCluggage WG, Young RH. Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors

Harvard University, Cambridge, Massachusetts, United States
Seminars in Diagnostic Pathology (Impact Factor: 2.56). 03/2005; 22(1):3-32. DOI: 10.1053/j.semdp.2005.11.002
Source: PubMed


Aspects of immunohistochemistry (IHC), which are useful in the diagnosis of ovarian tumors (mostly neoplasms but also a few tumor-like lesions), are discussed. The topic is first approached by considering the different growth patterns and cell types that may be encountered. Then a few other specific situations in which IHC may assist are reviewed. Selected findings largely, or only, of academic interest are also mentioned. One of the most common situations in which IHC may aid is in the evaluation of tumors with follicles or other patterns which bring a sex cord-stromal tumor into the differential. The distinction between a sex cord tumor and an endometrioid carcinoma with sex-cord-like patterns may be greatly aided by the triad of epithelial membrane antigen (EMA), inhibin, and calretinin, the latter two being typically positive and EMA negative in sex cord tumors, the converse being typical of endometrioid carcinoma. It should be emphasized that granulosa cell tumors may be inhibin negative and, albeit less specific, calretinin is more reliable in evaluating this particular issue. Lack of staining for inhibin and calretinin may also be supportive in leading to consideration of diverse other neoplasms that may form follicles, including metastatic tumors as varied as carcinoid and melanoma. The well-known staining of the latter neoplasm for S-100 protein and HMB-45 may be very helpful in evaluating melanomas with follicular or other unusual patterns, a challenging aspect of ovarian tumor interpretation. The most common monodermal teratoma, struma ovarii, usually has an overt follicular pattern and is easily recognized, but recognition of unusual appearances ranging from oxyphilic to clear cell to various patterns of malignant struma may be greatly aided by a thyroglobulin or TTF 1 stain. IHC for neuroendocrine markers may assist in the diagnosis of primary and metastatic carcinoid tumor. The broad differential diagnosis of glandular neoplasms with an endometrioid-pseudoendometrioid morphology, or mucinous cell type, has been the subject of much exploration in recent years, particularly the distinction between primary and metastatic neoplasms. The well-known CK7 positive, CK20 negative phenotype of primary endometrioid carcinoma, and the converse profile in most metastatic large intestinal adenocarcinomas with a pseudoendometrioid morphology, has been much publicized but albeit an appropriate supportive adjunct in many cases, exceptions from the typical staining pattern may be encountered. It is even less helpful in the case of primary versus metastatic mucinous neoplasia. Evaluation of the expression of mucin gene products has shown mixed, essentially unreliable, results. Experience with other new markers, such as CDX-2, villin, beta catenin, and P504S (racemase), is limited but is in aggregate promising with regard to providing some aid in this area. The rare differential of metastatic cervical adenocarcinoma versus primary ovarian mucinous or endometrioid carcinoma may be aided by strong p16 staining of the former. Staining for alpha-fetoprotein may aid in confirming the diagnosis of endometrioid-like (and hepatoid) variants of yolk sac tumor. Ependymoma of the ovary may also have an endometrioid-like glandular pattern, but positive stains for glial fibrillary acidic protein contrast with the negative results in others neoplasms with a similar pattern. Immunostains may be very helpful in the evaluation of oxyphilic tumors and tumor-like lesions and in some unusual forms of clear cell neoplasia, such as clear cell struma, both subjects being reviewed herein. Immunostains may highlight both the presence and extent of epithelial cells in a variety of circumstances, including microinvasive foci in cases of serous borderline tumors and mucinous carcinomas, and in determining the extent of carcinoma cells and reactive cells within mural nodules of mucinous neoplasms. As in tumor pathology in general, various markers may be crucial in the diagnosis of small round cell tumors of the ovary, and familiar markers of epithelial, lymphoid, leukemic, and melanocytic neoplasms may assist in the analysis of high grade tumors with a poorly differentiated carcinoma, lymphoma-granulocytic sarcoma, malignant melanoma differential. The evaluation of ovarian cystic lesions may be aided by thyroglobulin or TTF 1 (cystic struma), glial fibrillary acid protein (ependymal cysts), and inhibin-calretinin (follicle cysts and unilocular granulosa cell tumors). Stains for trophoblast markers may occasionally aid in the evaluation of germ cell tumors, although routine stains should usually suffice; they may be of academic interest in confirming trophoblastic differentiation in some high grade surface epithelial carcinomas.

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    • "Birefringent crystals of calcium monohydrate are present in most cases. Immunohistochemical staining for thyroglobulin, triiodothyronine, thyroxine can confirm the diagnosis [61]. Malignancy is defined by histological features of tumor, including cellular atypia and hyperplasia, nuclear pleomorphism, high mitotic activity, microinvasion into surrounding vessels and/or ovarian capsule, and discovery of metastasis by imaging [62] [63]. "
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    ABSTRACT: Struma ovarii is an uncommon type of ovarian tumor derived by germinal cells, characterized by the predominance of thyroid tissue (>50%); 90-95% of these formations are benign and mainly affect the left ovary, while in 6% of the cases struma ovarii is bilateral. The malignant transformation is a rare condition that often occurs after 50 years. In most instances, diagnosis of malignant struma ovarii is made postoperatively during histological analysis. This tumor appears to derive by one germinal cell through loss of heterozygosity of the androgen receptor gene and of the X chromosome. Clinical symptoms comprise abdominopelvic mass, lower abdominal pain, abnormal vaginal bleeding, and ascites (the occurrence of this condition has been observed in one-third of the cases). The patients with struma ovarii generally do not manifest symptoms related to thyroid hyperfunction, reported only in 8% of the cases, and due to hyperstimulation of the thyroid by auto-antibodies. Thyroid tissue of the struma ovarii, often embedded in a teratoma, may be papillary, follicular or with mixed pattern and it can include elements of mucinous cystoadenomas, Brenner's tumor or carcinoid or melanomas cells. Here the authors report their experience with an unusual case of Hashimoto thyroiditis onset after laparoscopic removal of struma ovarii.
    No preview · Article · Jan 2015 · Clinical and experimental obstetrics & gynecology
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    • "In this study, we investigated the IHC expression of PAX8 in determining the type and origin of the primary tumors. The utility of IHC in this field has been mentioned in previous studies.[15] "
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    ABSTRACT: Considering the high prevalence of female genital tract neoplasms, non-specific nature of the initial symptoms, higher possibility of metastasis by the time of diagnosis, importance of differentiating metastatic Mullerian tumors or metastatic breast cancer in the female genital tract, especially in the ovary, and lack of diagnostic markers with high sensitivity and specificity, the purpose of the current study was to evaluate the utility of Paired box protein8 (PAX8) expression in Mullerian and non-Mullerian neoplasms. In this descriptive-analytic, cross-sectional study, paraffin-embedded tissues of patients with definitive pathologic diagnosis of Mullerian and non-Mullerian tumors were selected. PAX8 immunohistochemical (IHC) staining was performed for all selected blocks. Immunopositivity of the slides for PAX8 was reviewed. It was defined as the presence of nuclear staining in at least 10% of the tumor cell nuclei. Thirty-seven Mullerian (including 18 ovarian epithelial tumors, 17 endometrial carcinoma and two endocervical adenocarcinoma) and 37 non-Mullerian tumors were studied for PAX8 expression. Twenty-nine of 37 (78.4%) and one of 37 (2.7%) of the Mullerian and non-Mullerian tumors were positive for PAX8, respectively. The sensitivity and specificity of PAX8 by IHC for differentiation of Mullerian from non-Mullerian tumors was 78.4% and 97.3%, respectively. Our findings indicated that PAX8 could be used as a useful IHC marker for diagnosing Mullerian tumors. It has moderate to high sensitivity, but high specificity, for diagnosing carcinomas of Mullerian origin.
    Full-text · Article · Mar 2014
    • "The ovary is characterized by the occurrence of a wide range of neoplasia with an almost bewildering array of morphological features perhaps more so than any other organ. Although, majority of ovarian neoplasms can readily be categorized by standard morphological examination using routine H and E stained sections, significant problems in diagnosis may occur due to neoplasms of similar or even diverse histogenic origins mimicking each other to a greater or lesser extent.[4] In such cases use of IHC plays a significant role in the classification of these tumors. "
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    ABSTRACT: Among cancers of the female genital tract, the incidence of ovarian cancer ranks below only carcinoma of the cervix and the endometrium. Recent years have witnessed significant development in the use of immunohistochemistry in diagnostic ovarian pathology. We received 95 specimens and biopsies of primary ovarian neoplasms and neoplasms metastatic to the ovary in a period of 2 years. Of these 30 cases were of the primary surface epithelial neoplasms and seven of metastatic tumors. The most common tumors metastasizing to the ovary originate from the gastrointestinal tract followed by the endometrium. We used a panel of six markers including cytokeratin-7 (CK7), CK20, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), estrogen receptor (ER) and Wilms' tumor 1 (WT1) to help classify various surface epithelial tumors as well as to differentiate them from tumors metastatic to the ovary. CK7 is the most helpful marker to differentiate primary ovarian carcinoma from metastatic colorectal carcinoma of the ovary. Nearly, 96% of ovarian adenocarcinomas were positive for CK7 in contrast to metastatic colorectal, which showed only 25% positivity. We also found that CK7, CK20 and CEA are useful markers to differentiate primary serous tumors from primary mucinous tumors; however, these are less helpful in differentiating ovarian mucinous adenocarcinomas from colorectal adenocarcinomas metastasizing to the ovaries. WT1 helps in typing primary surface epithelial tumors of the ovary and is also significant in determining whether a serous carcinoma within the ovary is primary or metastatic.
    No preview · Article · Oct 2013 · South Asian Journal of Cancer
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