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This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained. These markers include gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, and GATA3. The first two are cytoplasmic markers that show comparable sensitivities for breast cancer, although relatively few of the published studies have employed the same antibodies against the target molecule, making direct comparisons challenging. GATA3 is a nuclear transcription factor that shows superior sensitivity to GCDFP-15 and mammaglobin. However, the specificity of GATA3 can pose challenges, inasmuch as carcinomas of the bladder and other sites can show significant levels of positivity. Determination of the optimal panel of antibodies employed in a given clinical setting will thus depend on the non-breast tumours included in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Summary Muscle invasive urothelial carcinoma has been treated with cystectomy ± adjuvant therapy. Recently, a bladder-sparing protocol has been offered to selected patients closely followed with surveillance biopsies. In this setting, radiation-induced changes (RAD-Ch) may be very difficult to distinguish from carcinoma in situ, and failing to recognize them may lead to overtreatment. We ascertained the role of immunohistochemistry using cytokeratin (CK) 20, p53, and CD44s in bladder biopsies from 28 patients with a history of bladder radiation and 17 with carcinoma in situ without radiation. Negative or weak multifocal nuclear p53 staining was seen in 24 of 28 RAD-Ch cases, whereas strong and diffuse nuclear p53 staining was found in 8 of 17 carcinoma in situ cases and moderate and focal to multifocal in 3. CK20 showed strong cytoplasmic staining of only umbrella cells in 22 of 28 RAD-Ch cases. In contrast, 11 of 17 carcinomas in situ showed diffuse and strong CK20 positivity and 5 moderate and focal to multifocal positivity. All carcinomas in situ with weak or no p53 showed significant CK20 staining except 1. CD44s displayed diffuse membranous positivity in 7 of 17 RAD-Ch cases and up to mid-third in 8. Only 1 of 17 carcinomas in situ had diffuse membranous CD44s staining. Diffuse and significant CK20 expression was seen in most carcinomas in situ. Strong and diffuse p53 expression was only seen in carcinoma in situ (~50%), whereas diffuse CD44s staining was typically only seen in RAD-Ch. Our data suggest that a CK20- p53- CD44a panel proves to be very helpful (CK20 more reliable than p53 or CD44s) in the diagnosis of RAD-Ch. [ABSTRACT FROM AUTHOR]

Context.--Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. Objective.--To provide updated, practical guidelines for the pathologic diagnosis of MM. Data Sources.--Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. Conclusions.--There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included. [ABSTRACT FROM AUTHOR]

Context.--Numerous immunohistochemical stains have been shown to exhibit exclusive or preferential positivity in breast myoepithelial cells relative to their luminal/epithelial counterparts. These myoepithelial markers provide invaluable assistance in accurately classifying breast proliferations, especially in core biopsies. Although numerous myoepithelial markers are available, they differ in their sensitivity, specificity, and ease of interpretation, which may be attributed, to a large extent, to the variable immunoreactivity of these markers in stromal cells including myofibroblasts, vessels, luminal/epithelial cells, and tumor cells. Objective.--To review commonly used myoepithelial markers in breast pathology and a selection of diagnostic scenarios where they may be useful. Data Sources.--The information outlined in this review article is based on our experiences with routine cases and a review of English-language articles published between 1987 and 2008. Conclusions.--To demonstrate the presence or absence of myoepithelial cells, a panel-based approach of 2 or more markers is recommended. Markers that most effectively combine sensitivity, specificity, and ease of interpretation include smooth muscle myosin heavy chains, calponin, p75, p63, P-cadherin, basal cytokeratins, maspin, and CD10. These markers, however, display varying cross-reactivity patterns and variably reduced expression in the myoepithelial cells bordering in situ carcinomas. The choice of a myoepithelial marker should be dependent on a combination of factors, including published evidence on its diagnostic utility, its availability, performance characteristics that have been achieved in a given laboratory, and the specific diagnostic scenario. When its use is deemed necessary, immunohistochemistry for myoepithelial cells in breast pathology is most effective when conceptualized as supplemental, rather than central to routine morphologic interpretation. [ABSTRACT FROM AUTHOR]