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Silver Spring, MD, United States

Miettinen M.,U.S. National Cancer Institute | Miettinen M.,Joint Pathology Center | Wang Z.-F.,U.S. National Cancer Institute | Sarlomo-Rikala M.,University of Helsinki | And 3 more authors.
American Journal of Surgical Pathology | Year: 2011

Most gastrointestinal stromal tumors (GISTs) are driven by KIT or PDGFRA-activating mutations, but a small subset is associated with loss of function of the succinate dehydrogenase (SDH) complex of mitochondrial inner membrane proteins. This occurs by germline mutations of the SDH subunit genes and hitherto unknown mechanisms. SDH-deficient GISTs especially include pediatric GISTs and those associated with Carney triad (CT) or Carney-Stratakis syndromes (CSSs); the latter 2 also include paraganglioma as a component. SDH-deficient GISTs were identified in this study on the basis of immunohistochemical loss of succinate dehydrogenase subunit B (SDHB), which signals functional loss of the SDH complex. We found 66 SDH-deficient GISTs among 756 gastric GISTs, with an estimated frequency of 7.5% of unselected cases. Nearly, all gastric GISTs in patients <20 years, and a substantial percentage of those in patients <40 years, but only rare GISTs in older adults were SDH deficient. There was a female predominance of over 2:1. Two patients each had either pulmonary chondroma or paraganglioma (CT), but none of the examined cases had SDH germline mutations (CSS) or somatic KIT/PDGFRA or BRAF mutations. SDH-deficient GISTs were often multiple and typically showed plexiform muscularis propria involvement and epithelioid hypercellular morphology. They were consistently KIT-positive and DOG1/Ano 1-positive and almost always smooth muscle actin negative. Tumor size and mitotic activity varied, and the tumors were somewhat unpredictable with low mitotic rates developing metastases. Gastric recurrences occurred in 11 patients, and peritoneal and liver metastases occurred in 8 and 10 patients, respectively. Lymph node metastases were detected in 5 patients, but lymphovascular invasion was present in >50% of cases studied; these 2 were not related to adverse outcome. Seven patients died of disease, but many had long survivals, even with peritoneal or liver metastases. All 378 nongastric GISTs and 34 gastric non-GIST mesenchymal tumors were SDHB positive. SDH-deficient GISTs constitute a small subgroup of gastric GISTs; they usually occur in children and young adults, often have a chronic course similar to that of pediatric and CT GISTs, and have potential association with paraganglioma, necessitating long-term follow-up. © 2011 Lippincott Williams & Wilkins. Source


Smith A.B.,Uniformed Services University of the Health Sciences | Smith A.B.,American Institute for Radiologic Pathology | Smirniotopoulos J.G.,Uniformed Services University of the Health Sciences | Horkanyne-Szakaly I.,Uniformed Services University of the Health Sciences | Horkanyne-Szakaly I.,Joint Pathology Center
Radiographics | Year: 2013

A variety of neoplasms may arise in the ventricular system. Intraventricu-lar neoplasms may be discovered as an incidental finding at cross-sectional imaging or may manifest with varied symptoms depending on their location, including symptoms of increased intracranial pressure. These lesions may arise from various ventricular structures, including the ependymal lining (eg, ependymoma), subependymal layer (eg, subependymoma), or choroid plexus (eg, choroid plexus neoplasms), or they may have a cell of origin that has yet to be determined (eg, chordoid glioma). Other neoplasms involving the ventricular system include central neurocytoma, subependymal giant cell tumor, meningioma, rosette-forming glioneuronal tumor, and metastases. The differential diagnosis for intraventricular neoplasms can be broad, and many of them have similar patterns of signal intensity and contrast enhancement at imaging. However, the location of the lesion in the ventricular system-along with knowledge of the patient's age, gender, and underlying conditions-will help narrow the differential diagnosis. RSNA, 2013. Source


O'Malley D.P.,Clarient | Auerbach A.,Joint Pathology Center | Weiss L.M.,Clarient
Archives of Pathology and Laboratory Medicine | Year: 2015

Context. - Diffuse large B-cell lymphoma is the most commonly diagnosed subtype of lymphoma worldwide. The current World Health Organization (WHO) classification includes several subtypes, based on a combination of clinical, immunohistochemical, and genetic differences. Immunohistochemical staining is essential in evaluating diffuse large B-cell lymphoma and many related large Bcell lymphomas and aggressive B-cell lymphomas. Objective. - To address different immunohistochemical features used for identification, subclassification, prognosis and in some cases, therapy, of diffuse large B-cell lymphoma and related lymphomas. Data Sources. - The information outlined in this review article is based on our experiences with routine cases, on the current WHO classification of hematopoietic and lymphoid tumors, and on a review of English-language articles published throughout 2014. Conclusions. - Features and diagnostic criteria of diffuse large B-cell lymphoma, aggressive variants of B-cell lymphomas, including Burkitt lymphoma and "doublehit" lymphomas, are discussed. Identification of cell of origin (germinal center type versus activated B-cell type) is discussed at length. Finally, practical approaches for diagnosis are discussed. Source


Miettinen M.,U.S. National Cancer Institute | Miettinen M.,Joint Pathology Center | Sarlomo-Rikala M.,University of Helsinki | Wang Z.-F.,U.S. National Cancer Institute
American Journal of Surgical Pathology | Year: 2011

Claudin-5 is a tight junction protein expressed in endothelial cells and in some epithelial cells. It has been shown as a marker in canine angiosarcoma; however, data on human mesenchymal tumors are limited. In this study, we examined claudin-5 in selected normal tissues, in 280 benign and malignant vascular tumors, and in 448 other epithelial, mesenchymal, and neuroectodermal tumors. Early human embryos showed limited claudin-5 expression in endothelia of large truncal vessels, in liver sinusoids, and in the epidermis. In adult human tissues, claudin-5 was widely present in the endothelia of vessels of different calibers. However, neovascular capillaries in carcinomas and other tumors were often negative. Claudin-5 was also present in many glandular and ductal epithelia, hair shafts, and glomerular podocytes. Capillary and cavernous hemangiomas and lymphangiomas generally showed endothelial positivity; however, many vessels, especially those with poorly formed lumina, were negative in juvenile capillary hemangiomas, and fewer vessels were highlighted in lobular capillary hemangiomas. Hemangioendotheliomas of retiform, kaposiform, epithelioid, and epithelioid sarcoma-like types showed positivity, the latter in a diffuse cytoplasmic manner. Most angiosarcomas (115 of 119) and Kaposi sarcomas (28 of 29) showed strong labeling, but rare cases only contained positive cytoplasmic dots. Claudin-5 was commonly present in carcinomas (except in sarcomatoid ones), but most tumors showed heterogenous labeling weaker than that in angiosarcomas. Seminomas and renal cell, hepatocellular, and signet ring cell carcinomas were negative. Among non-vascular mesenchymal tumors, biphasic synovial sarcoma was the only tumor to contain claudin-5-positive nonvascular elements. In hemangiopericytomas, glomus tumor, and melanomas, claudin-5 was expressed in endothelial cells only. Claudin-5 is a promising new marker for angiosarcomas and hemangioendotheliomas, but widespread expression in carcinomas and biphasic synovial sarcoma should be considered in the differential diagnosis and addressed with the use of an antibody panel including keratins, especially the more epithelial-specific AE1/AE3 and epithelial membrane antigen. © 2011 Lippincott Williams & Wilkins. Source


Lucas S.,St. Thomas Hospital | Nelson A.M.,Joint Pathology Center
Journal of Pathology | Year: 2015

Infection with the human immunodeficiency virus (HIV) causes systemic T cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Second, it directly damages many tissues - gut, brain, lung - through mononuclear cell infection and activation. Third, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side-effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation. Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source

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