Pulmonary pathology of Erdheim-Chester disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis that may present with pulmonary symptoms. The condition seems to be nonfami lial and typically affects middle-aged adults. Radiographic and pathologic changes in the long bones are diagnostic, but patients often present with e xtraskeletal manifestations. Advanced pulmonary lesions are associated with extensive fibrosis that may lead to cardiorespiratory failure. The clinica l, radiologic, and pathologic features of six patients with ECD with lung i nvolvement are presented. The patients were three men and three women (mean age, 57). Five presented with progressive dyspnea, and one presented with diabetes insipidus. Open-lung biopsies showed histiocytic infiltrates in a lymphangitic pattern with associated fibrosis and lymphoplasmacytic inflamm atory infiltrates. The histiocytes did not stain with periodic acid-Schiff. Immunoperoxidase studies performed on specimens from five of six patients showed that the histiocytes were positive for CD68 and Factor XIIIa and neg ative for CD1a Specimens from two patients exhibited immunoreactivity for S -100 protein. Electron microscopy studies performed on specimens from two p atients showed phagocytic lysosomes but no Birbeck granules. Clinical follo w-up of up to 16 years was available. At the end of that time, five patient s were dead of complications related to their disease; one patient remains alive 4 years after diagnosis but with severe respiratory compromise. ECD i s a rare non-Langerhans' cell histiocytosis that may present as interstitia l lung disease and resemble other pulmonary conditions, particularly usual interstitial pneumonitis and pulmonary Langerhans' cell histiocytosis. Reco gnition of this entity will allow better assessment of its true incidence, therapeutic options, and prognosis.