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Lymphoid hyperplasia and eosinophilic pneumonia as histologic manifestations of amiodarone-induced lung toxicity.

Amiodarone use is often limited by pulmonary toxicity. Amiodarone lung disease (ALD) classically manifests as organizing pneumonia with intra-alveolar foamy macrophages, but other patterns may also occur. Here we report 2 previously unreported patterns of ALD: lymphoid hyperplasia (LH) and eosinophilic pneumonia (EP). We identified patients with LH or EP as a prominent feature among 75 cases of probable ALD from the authors' teaching files collected from 1997 to 2010. Clinical history and lung wedge biopsies were reviewed. Twelve patients (7 men) met inclusion criteria (median age, 71 y). The exact amiodarone dose was known in all cases (median, 200 mg/d). Treatment duration was known in 10 cases and ranged from 1 to 12 years. Thoracic imaging showed diffuse infiltrates causing concern for a diagnosis of ALD. Histologic review revealed intra-alveolar foamy macrophages in all cases. Eight cases prominently displayed patterns of LH, including diffuse LH (7), follicular bronchiolitis (5), lymphoid interstitial pneumonia (2), and lymphocytic perivascular cuffing (2). Two showed features of acute EP, including diffuse alveolar damage with abundant eosinophils. Two showed features of chronic EP, including interstitial pneumonia with abundant eosinophils, patchy organization, and fibrinous exudates with macrophages and eosinophils. One chronic EP case also showed focal LH. Additional features included intra-alveolar giant cells (6), pleuritis (3), small poorly formed granulomas (3), and thrombi (2). LH and EP are previously unrecognized histopathologic manifestations of ALD, and amiodarone exposure should be included in their differential diagnosis.

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