Human pathology
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Epstein-Barr virus (EBV) is a member of the human herpesvirus family that was initially isolated from a cultured Burkitt lymphoma cell line by Epstein et al in 1964. Subsequent studies have proven that it is the causative agent in most cases of infectious mononucleosis. ⋯ EBV has been linked to many human neoplasms including hematopoietic, epithelial, and mesenchymal tumors. In this review, we will only discuss the EBV-associated lymphoproliferative disorders, dividing them into B-cell, T/NK-cell, and HIV-related lymphoproliferative disorders.
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Pulmonary arterial hypertension is a severe complication of connective tissue diseases. It is currently well established that pulmonary arterial hypertension associated with connective tissue diseases such as systemic sclerosis is frequently less responsive or even refractory to pulmonary vasodilator therapies. In that setting, pulmonary venoocclusive disease is believed to contribute to treatment failures. ⋯ Findings were compared with 29 pulmonary arterial hypertension cases from patients displaying neither connective tissue diseases nor associated conditions. We found that (a) 6 (75%) of 8 patients with pulmonary arterial hypertension associated with connective tissue diseases showed significant obstructive pulmonary vascular lesions predominating in veins/preseptal venules, as compared with 5 (17.2%) of 29 non-connective tissue diseases control pulmonary arterial hypertension; (b) lesions of small muscular arteries were consistently present in pulmonary arterial hypertension associated with connective tissue diseases, showing mostly intimal fibrosis and thrombotic lesions; and (c) 6 of 8 lung samples from patients with pulmonary arterial hypertension associated with connective tissue diseases revealed perivascular inflammatory infiltration. In conclusion, our study highlights the fact that pulmonary arterial hypertension complicating the course of connective tissue diseases may be characterized by a more frequent involvement of pulmonary veins and may thus explain why these patients are less prone to respond to specific pulmonary arterial hypertension treatment as compared with idiopathic pulmonary arterial hypertension.
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In recent years, immunohistochemical staining for KIT (CD117) has become integral to the diagnosis of gastrointestinal stromal tumors (GISTs), nearly 90% of which harbor activating mutations in the KIT receptor tyrosine kinase gene. Approximately 80% of patients with metastatic GIST show at least some clinical response to the targeted small molecule KIT inhibitor imatinib. The response to imatinib is closely correlated with the presence and type of KIT mutation. ⋯ Sunitinib has recently been approved for patients with GIST, principally those who fail imatinib therapy; and additional small molecule inhibitors are in the pipeline. It is becoming evident that alternative approaches to direct KIT inhibition will be required for long-term survival of patients with advanced GISTs. This review examines the role of KIT in the diagnosis and management of patients with GIST.
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Overexpression of aspartyl (asparaginyl) beta-hydroxylase (AAH) has been demonstrated in hepatocellular carcinoma, cholangiocarcinoma, and pancreatic carcinoma. AAH has an important role in regulating cell motility and invasiveness. Humbug is a truncated homolog of AAH, with a role in calcium regulation. ⋯ Correspondingly, reverse transcriptase-polymerase chain reaction studies demonstrated up-regulation of humbug but not AAH in 95% of colon carcinomas relative to adjacent colon cancer-free mucosa (P < .0001). This study demonstrates that high levels of humbug immunoreactivity in colon carcinomas correlate with histologic grade and tumor behavior, suggesting that humbug can serve as a prognostic biomarker of TNM stage II colon cancers. In addition, molecular studies demonstrated that the increased levels of FB50 detected were due to humbug, as opposed to AAH overexpression.