Context: Although much of the pathology literature focuses on differential diagnosis of diffuse malignant mesothelioma from other types of cancer, the primary diagnostic challenge facing the pathologist is often whether a mesothelial proliferation on a pleural biopsy represents a malignancy or a benign reactive hyperplasia.
Design: Based on previous medical publications, extensive personal consultations, and experience on the United States-Canadian Mesothelioma Reference Panel and the International Mesothelioma Panel, salient information was determined about interpretation of benign versus malignant mesothelial proliferations on pleural biopsies.
Results: Differentiation of benign reactive mesothelial hyperplasia from diffuse malignant mesothelioma is often difficult. Benign reactive mesothelial hyperplasia may mimic many features ordinarily associated with malignancy, and diffuse malignant mesothelioma may be cytologically bland. Entrapment of benign reactive mesothelial cells within organizing pleuritis may mimic tissue invasion.
Conclusions: Various histologic clues favor a benign over a malignant mesothelial proliferation and vice versa. Invasion is the most reliable criterion for determining that a mesothelial proliferation is malignant. When there is any doubt that a pleural biopsy represents a malignancy, we recommend a diagnosis of atypical mesothelial proliferation.