Pulmonary Pathology of Erdheim-Chester Disease

Abstract

Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis that may present with pulmonary symptoms. The condition seems to be nonfamilial and typically affects middle-aged adults. Radiographic and pathologic changes in the long bones are diagnostic, but patients often present with extraskeletal manifestations. Advanced pulmonary lesions are associated with extensive fibrosis that may lead to cardiorespiratory failure. The clinical, radiologic, and pathologic features of six patients with ECD with lung involvement 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 inflammatory 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 negative for CD1a. Specimens from two patients exhibited immunoreactivity for S-100 protein. Electron microscopy studies performed on specimens from two patients showed phagocytic lysosomes but no Birbeck granules. Clinical follow-up of up to 16 years was available. At the end of that time, five patients were dead of complications related to their disease; one patient remains alive 4 years after diagnosis but with severe respiratory compromise. ECD is a rare nonLangerhans' cell histiocytosis that may present as interstitial lung disease and resemble other pulmonary conditions, particularly usual interstitial pneumonitis and pulmonary Langerhans' cell histiocytosis. Recognition of this entity will allow better assessment of its true incidence, therapeutic options, and prognosis.

Erdheim-Chester Disease: Case Report, PCR-Based Analysis of Clonality, and Review of Literature

“…To our best knowledge, CD1a was uniformly negative in all cases of ECD reported to date. In ECD, the lesional cells are usually S-100 negative, although positivity has been described in previous cases in the literature and in different organs in patients with otherwise typical disease (9,11,20). The histiocytes in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) are similar to those seen in ECD, but they frequently contain intact lymphocytes (emperipolesis).…”

“…Orbital disease with exophthalmos and xanthoma-like lesions of the eyelid are also common (5). Pulmonary involvement is rare, but advanced lesions are associated with extensive fibrosis that can lead to cardiorespiratory failure (9,11,23). No effective treatment strategies have been described in the literature thus far.…”

Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163

“…Although the identity of the positive cells as neoplastic or benign was difficult to determine, the expression of factor XIIIa in a subset of the histiocytes is not entirely unexpected as factor XIIIa expression has also been reported in ErdheimChester disease, a rare non-Langerhans' cell histiocytosis. 73 The significance of this finding and its possible role in the histogenesis of HSs is uncertain and requires investigation in a greater number of cases.…”

Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone

“…Review of previous osteoarticular imaging showed classical changes of the disorder. [1][2][3] In view of the symptomatic and functional deterioration, treatment was restarted with prednisolone 40 mg plus cyclophosphamide 100 mg daily, with mesna and oral bisphosphonate prophylaxis. Over the following 6 weeks VC and TLCO improved from 2.1 to 2.8 l, and from 3.04 to 4.02 mmol/kPa/min, respectively (fig 2), with a modest improvement in exertional dyspnoea, energy, appetite and weight.…”

“…1 Symmetrical osteosclerotic lesions in the long bones, sparing the epiphyses, are virtually pathognomonic. [1][2][3] Thoracic computed tomographic (CT) appearances include reticular and centrilobular nodular opacities, scattered ground glass shadowing, and interlobular septal and pleural thickening, often with an upper zone predominance. Adenopathy is uncommon.…”