Chickenpox-related pulmonary granulomas in immunocompetent adults: Clinicopathologic and molecular features of an underrated occurrence

Pulmonary granulomas represent a common inflammatory reaction to several lung infective or noninfective diseases. However, little is known about the histology and clinical presentation of chickenpox-related granulomas in immunocompetent subjects. We collected a series of 8 adult patients (mean age, 40 y; range, 33 to 53 y) with several bilateral pulmonary granulomas incidentally discovered after imaging studies. All patients were asymptomatic and had experienced a varicella-zoster virus (VZV) infection as adults but were clinically suspected to have a metastatic neoplasm of unknown origin. Chest computed tomography scan revealed numerous, tiny (few millimeters to 1 cm in size) nodules randomly dispersed through the lungs. Positron emission tomography scan performed in 4 patients was negative. All patients underwent video-assisted thoracoscopic surgical resection and were still alive and well. At histology, granulomas consisted of well-defined, rounded, small nodules centered by a deeply eosinophilic, acellular necrosis rimmed by lamellar dense collagen and a chronic inflammatory infiltrate with or without multinucleated giant cells. Chickenpox-related granulomas were included in the differential diagnosis along with several other granulomatous diseases. Polymerase chain reaction-based molecular analysis for VZV performed on paraffin sections detected VZV DNA in all 8 cases. By contrast, 85 cases of pulmonary granulomas of different etiologies were simultaneously studied by molecular analysis with negative results. Pathologists should be familiar with the peculiar morphologic appearance of chickenpox-related granulomas. A careful search for a history of VZV infection in adulthood and molecular studies may be very helpful in confirming the diagnosis.