Giant lamellar bodies in a case of Mycobacterium avium complex lung disease

Sir, Giant lamellar bodies (GLBs) are rare pulmonary inclusions and are described in certain pulmonary disorders, including sclerosing haemangioma, plasma cell granuloma, alveolar adenoma, alveolar proteinosis and pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. The mechanism of GLB formation remains controversial. It has been suggested that excessive secretion of surfactant together with failure to clear it away may be responsible for GLB formation. However, other evidence suggests reduction of surfactant protein associated with fusion of lamellar bodies to generate giant forms. We report here a case of pulmonary Mycobacterium avium complex (MAC) disease with a unique finding of GLBs in the alveolar spaces, immunohistochemically concentrating on GLBs to determine their derivation. The patient was a 48-year-old man. Chest computed tomography (CT) demonstrated cavity formation in the left upper lobe. Sputum culture was positive for Mycobacterium avium complex. The patient was a steel industry worker who did not have AIDS or known lung disease; therefore, the diagnosis of pulmonary MAC disease was considered. A left upper lobectomy was performed. The surgically resected lung specimen was immediately fixed in 10% phosphate-buffer formalin solution, processed for paraffin-embedding in the usual manner, and stained with H&E, Ziehl–Neelsen stain for myocobacterium and Berlin blue stain for iron. Immunohistochemical staining was performed, especially on lamellar bodies, using the streptavidin–biotin peroxidase complex (SABC) method (LSAB Kit; Dako, USA) with antibodies against surfactant protein A (PE10; Dako; dilution, 1:100), epithelial membrane antigen (EMA; Dako; dilution, 1:50), KL-6 (10 ng/ml concentration from Dr N. Kohno), pancytokeratin (AE1/ AE3; Boehringer-Mannheim, USA; dilution, 1:400), factor VIII-related antigen (factor VIII; Dako; dilution, 1:400), human urinary protein-1 (Hup-1; Dako; dilution, 1:100), and cytokeratins 18 and 19 (ScyTek Laboratories, USA; dilution, 1:30). Antigen retrieval using 0.1% pronase digestion or microwave pretreatment was performed for antibodies against AE1/AE3, factor VIII, CK18 and CK19. Appropriate positive and negative controls were stained in parallel. Staining procedures were performed according to the manufacturers’ instructions. The patient had a long history of dust exposure. Anthracotic deposits were observed around small airways in the resected lung tissue. Then, a large cavity was found surrounded by epithelioid cells and myofibroblasts intermingling with a few multinucleated giant cells. Multinodular specific granulomas were also detected in the adjoining pulmonary field. With Ziehl–Neelsen stain, positive rodshaped bacteria were detected in the necrotic inner surface of the cavity lesion. Berlin blue stain revealed the positivity of brown-black granules in some alveolar macrophages, suggesting the presence of iron-containing granules. Interestingly, clusters of giant lamellar bodies were focally noted only in some pulmonary lobules dissociated within alveolar spaces. They were eosinophilic, concentrically laminated, and some were associated with cholesterol clefts (Fig. 1A, B). Immunohistochemically, GLBs were strongly positive for only PE10 (Fig. 2A, B) but not positive for KL-6, EMA, AE1/AE3, Hup-1, CK18, CK19 and factor VIII. At higher magnification, lamellar positivity of GLBs with PE10 was obvious (Fig. 2B). Surrounding GLBs, type II pneumocytes along the alveolar septa exhibited clearly positive staining for PE10, KL-6 and EMA in linear fashion on the surface and for AE1/AE3, CK18 and CK19 in the cytoplasm. Bronchiolar epithelial cells reacted with KL-6, EMA and cytokeratins. Staining for Hup-1, which is identical to the Clara cell protein, yielded no evidence that Hup-1 was contained in GLBs, although Clara cells were widely positive. Pulmonary diseases caused by MAC have been described in immunocompetent patients and in association with AIDS. Environmental studies have demonstrated MAC in dust, soil, water and animals. Diseases predisposing to respiratory infection with MAC often involve airway damage and/ or poor mucus clearance. In our case, the patient was a steel industry worker and had a long history of dust exposure. Anthracotic deposits were observed around small airways in the resected lung tissue. The gross and histopathological findings for pulmonary diseases caused by MAC have a close similarity to those of tuberculosis, including the presence of acid-fast bacilli. In our case, numerous giant lamellar bodies in alveolar spaces were a unique finding on microscopic examination. In the literature, GLBs have been most frequently noted in sclerosing haemangiomas, with an incidence of 24%, but have also been identified in association with pulmonary alveolar proteinosis, alveolar adenoma, plasma cell granuloma and pulmonary MALT lymphoma. 8 No case of pulmonary MAC disease associated with GLBs has previously been documented. GLBs are eosinophilic, spherical, concentrically laminated structures which are morphologically similar to cytoplasmic lamellar bodies in type II pneumocytes, but the former are much larger than the latter. It has been proposed that excessive formation/secretion of surfactant as well as stasis of its recycling are the main cause of GLBs. However, fusion of lamellar bodies to generate giant forms has been associated with reduction of surfactant, since GLBs were observed as an early alteration of type II pneumocytes in rat lungs treated with bacterial endotoxin as a model of adult respiratory distress syndrome. Since GLBs are rare pulmonary inclusions and have been described only occasionally in case reports, it