Erdheim-Chester disease - Clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease

Erdheim-Chester disease is a clinicopathologic entity defined by a characte ristic pattern of symmetric osteosclerosis caused by an infiltrate of monon uclear cells that include prominent numbers of foamy histiocytes. About hal f of patients have extraskeletal manifestations, including involvement of t he hypothalamus/posterior pituitary, orbit, retroperitoneum, skin, lung, an d heart. Pulmonary involvement is an uncommon but important manifestation o f Erdheim-Chester disease because it causes significant morbidity and morta lity. A review of the Mayo Clinic files produced four patients with confirm ed Erdheim-Chester disease in whom lung biopsy had been performed. One addi tional patient was included from the University of Pittsbugh. Four patients were women. The mean age was 53.6 years (range 25-70 years). All patients had bilateral and symmetric sclerotic bone lesions characteristic of Erdhei m-Chester disease, although in three the skeletal abnormalities were discov ered only after lung biopsy. Four patients had dyspnea, and one also had a dry cough. One patient died 17 months after diagnosis. Chest radiographs sh owed diffuse interstitial infiltrates in all patients, with an upper zone p redominance in three. Thoracic computed tomography (CT) scans showed thicke ning of the visceral pleura and interlobular septa with patchy associated f ine reticular and centrilobular opacities and ground glass attenuation. Lun g biopsy specimens showed an infiltrate of foamy histiocytes, lymphocytes, and scattered Touton giant cells with associated fibrosis in a striking lym phatic distribution. The infiltrate involved visceral pleura, interlobular septa, and bronchovascular bundles. Immunohistochemical stains were positiv e for CD68 in all cases and S-100 protein in four cases. Stains for CD1a we re consistently negative. Ultrastructural studies in one case showed no Bir beck granules. Although in bone the histologic features of Erdheim-Chester disease may overlap with Langerhans' cell histiocytosis, its expression in the lung is distinct. Lung involvement in Erdheim-Chester disease has emerg ed as a unique radiographic and histologic entity.