The separation of mesothelial hyperplasia from early malignant mesothelioma remains one of the most difficult problems in histopathology. Inconclusive cases are termed "atypical mesothelial hyperplasia" and treated expectantly. A 49 year old male pipeline engineer was diagnosed as having atypical mesothelial hyperplasia in appendiceal serosa by the US-Canadian Mesothelioma Panel. Eight years later, he developed overtly malignant peritoneal and pleural mesothelioma. In hindsight, histological similarities between the diffuse malignant mesothelioma and the atypical mesothelial proliferation suggested malignancy from the outset. The most important of these features were the degree of mesothelial proliferation, micronodularity, architectural complexity, superficial invasion, uniform mild cytological atypia, and the absence of a clinical cause for a benign mesothelial proliferation. Ancillary investigations including immunohistochemistry were of no benefit in determining whether the atypical mesothelial hyperplasia was benign or malignant. Careful histological examination remains the mainstay of the diagnosis of early mesothelioma.
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