Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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Multifocal micronodular pneumocyte hyperplasia is a rare pulmonary manifestation of tuberous sclerosis complex (TSC) that is a tumor suppressor gene disorder characterized by many hamartomas. A purported mechanism of hamartomatous proliferation in TSC is constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway dysregulated by a functional loss of TSC genes. Although multifocal micronodular pneumocyte hyperplasia develops locally as self-limited, benign lesions, it is morphologically similar to the preinvasive lesion of pneumocytes that characterize atypical adenomatous hyperplasia or bronchioloalveolar carcinoma. ⋯ Loss of heterozygosity of TSC was found in the preinvasive lesions of pneumocytes, equal to or less than multifocal micronodular pneumocyte hyperplasia. In contrast, phospho-Akt was expressed in the preinvasive lesions of pneumocytes more frequently than multifocal micronodular pneumocyte hyperplasia, but the other mTOR-related proteins were less frequently expressed in the former than in the latter. These outcomes suggest that functional loss of TSCs and consequent hyperphosphorylation of mTOR-related proteins in multifocal micronodular pneumocyte hyperplasia may cause its benign neoplastic proliferation of pneumocytes.
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Autopsy rates have been affected by a number of factors, including technological advances and clinician beliefs of the diminished value of the autopsy. Such factors have resulted in a cultural shift in medicine away from the autopsy. Despite this shift, a number of studies have shown significant differences between antemortem clinical diagnoses and postmortem findings. ⋯ Overall discrepancy rates for the medical intensive care unit, surgery service and nursing home patients were 27.8, 32.7 and 31.3%, respectively (P=0.84). In addition, we found no statistical difference in the complexity of workup in discrepant and nondiscrepant cases in each clinical setting. Our study data refute the hypothesis that the intensity of antemortem diagnostic evaluation correlates with an actual decrease in the rate of major diagnostic discrepancies identified at autopsy.