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Context.--Identification of the site of origin of carcinoma of unknown primary using immunohistochemistry is a frequent requirement of anatomic pathologists. Diagnostic accuracy is crucial, particularly in the current era of targeted therapies and smaller sample sizes. Objectives.--To provide practical guidance and suggestions for classifying carcinoma of unknown primary using both proven and new antibodies, as well as targeting panels based on integration of morphologic and clinical features. Data Sources.--Literature review, the authors' practice experience, and authors' research. Conclusions.--With well-performed and interpreted immunohistochemistry panels, anatomic pathologists can successfully identify the site of origin of carcinoma of unknown primary. It is crucial to understand not only the diagnostic uses of the many available antibodies but also the potential limits and pitfalls. [ABSTRACT FROM AUTHOR]

The accurate preoperative diagnosis of thyroid cancer continues to be a significant challenge for those individuals who present with nodular thyroid disease, particularly for tumors with indeterminate cytomorphological features by fine needle aspiration biopsy. In an effort to develop improved diagnostic tools, a number of studies have investigated the discriminatory potential of many different RNA and protein molecules. However, no individual thyroid cancer biomarker has been found with sufficient sensitivity and specificity. Therefore, research focus has shifted to panels of multiple markers with the hope of improved performance and robustness. A panel comprised of GAL3, CK19 and HBME1 is by far the most studied to date and offers some improvement over individual marker performance alone. However, relatively few marker panels have been studied and their performances and application as diagnostic tests have not been consistently reported. We present a comprehensive review of molecular marker panel studies for thyroid tumors and current issues and challenges. In the future, studies evaluating larger numbers of biomarkers in large patient cohorts are required for the development and validation of a clinically applicable test. [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]