Pulmonary and Ophthalmic Involvement With Erdheim-Chester Disease: A Case Report and Review of the Literature

Archives of Pathology & Laboratory Medicine,  Dec 2004  by Allen, Timothy Craig,  Chevez-Barrios, Patricia,  Shetlar, Debra J,  Cagle, Philip T

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Erdheim-Chester disease is a rare nonfamilial histiocytic disorder of unknown etiology with characteristic long bone findings. The 3-year survival rate for patients with Erdheim-Chester disease is 50%. Approximately 50% of patients have disease involvement in other tissues, including skin, retro-orbital and periorbital tissues, pituitary-hypothalamic axis, heart, kidney, retroperitoneum, breast, skeletal muscle, and sinonasal mucosa; about 20% of patients have lung involvement. Prognosis generally depends on the extent of the extraosseous disease. For patients with lung involvement, gender distribution is equal, but men typically present at an older age than do women. Approximately 80% of patients present with dyspnea, and most patients have diffuse interstitial infiltrates and pleural and/or interlobar septal thickening on chest radiology. Characteristic lung histopathology includes the accumulation of histiocytes with variable amounts of fibrosis and a variable lymphoplasmacytic infiltrate in a lymphangitic distribution, lmmunostains are diagnostically useful, showing immunopositivity for CD68 and factor XIIIa and immunonegativity for CD1a. Birbeck granules are uniformly absent ultrastructurally.

(Arch Pathol Lab Med. 2004;128:1428-1431)

Erdheim-Chester disease is a rare nonfamilial histiocytic disorder first identified by William Chester in 1930 that primarily affects middle-aged and older adults and predominantly involves the long bones of the extremities.1-3 Bone pain is the most common presenting symptom, and characteristic radiographie changes in the long bones-bilateral cortical sclerosis predominantly involving the metaphyses and diaphyses-is considered virtually pathopneomonic.2 The etiology of Erdheim-Chester disease is unknown.4 It is undetermined whether Erdheim-Chester disease is a monoclonal proliferative disorder or whether it is a polyclonal reactive disease.4,5 While Erdheim-Chester disease has been known to occur in patients who also have Langerhans cell histiocytosis, the 2 diseases are generally considered to be separate entities.4 Neither has Erdheim-Chester disease been found to be a lipid storage disease.5 Approximately 50% of patients have disease involvement in other tissues, including skin, retroorbital and periorbital tissues, pituitary-hypothalamic axis, heart, kidney, retroperitoneum, breast, skeletal muscle, sinonasal mucosa, and lung.4 Prognosis generally depends on the extent of the extraosseous disease, with 59% of patients reportedly dying of their disease and 36% dying of the disease at 6 months.2,6

One hundred seventy-six cases of Erdheim-Chester disease have been reported in the literature. One hundred sixty-four cases had been reported as of August 2002,4 and our review of the English-language literature shows 12 additional case reports published between August 2002 and June 2003.7-18 Forty-one (23%) of the 176 cases showed pulmonary involvement. Detailed descriptions of the pulmonary histopathology were present for 23 of the 41 cases with pulmonary involvement (Table). This case report represents the 24th reported case of Erdheim-Chester disease with pulmonary involvement that presents a detailed description of the pulmonary histopathology.

REPORT OF A CASE

A 60-year-old man with no history of smoking and a past medical history of hypertension presented with painless loss of vision in one eye, dyspnea, iron deficiency anemia, decreased renal function, and sclerotic and lytic lesions on long bone x-ray. Prominent slightly elevated yellow plaque lesions were present on all 4 eyelids (Figure 1). Well-circumscribed lesions surrounding the optic nerves of each orbit were identified by magnetic resonance imaging. Left orbital biopsy showed a firm homogeneous yellow mass composed histologically of adipose tissue infiltrated by foamy histiocytes, with areas of fibrosis and a mixed inflammatory infiltrate surrounding the histiocytes (Figure 2). The histiocytes were immunopositive for CD68 and immunonegative for S100. A diagnosis of orbital xanthogranuloma was made, with the diagnosis of Erdheim-Chester disease suggested based on the presence of bilateral orbital masses.

Long bone radiology showed characteristic bilateral distal femoral and proximal tibial osseous involvement by Erdheim-Chester disease. Chest radiography showed bilateral hilar adenopathy and a mediastinal mass, focal pleural thickening, and diffuse bilateral interstitial opacities, predominantly in the upper lobes. Lung biopsies consisting of a left upper-lobe wedge biopsy (measuring 1.4 × 1.2 × 1.0 cm) and a left upper-lobe wedge resection (measuring 9.0 × 1.5 × 1.0 cm) were performed to evaluate the patient's progressive dyspnea. Histologically, the lung parenchyma contained areas of fibrosis and a mixed inflammatory infiltrate, with interspersed histiocytes arranged in a lymphangitic distribution, involving bronchi, bronchioles, interlobar septa, and subpleural parenchyma (Figures 3 and 4). Lung parenchyma adjacent to these areas was relatively normal. The histiocytes were immunopositive for CD68 and factor XIIIa, focally immunopositive for SlOO, and immunonegative for CD1a (Figure 5). A mediastinal mass biopsy showed fibroadipose tissue with fibrosis. The patient's pulmonary condition worsened and he died 5 months after presentation. Autopsy showed widespread visceral involvement of Erdheim-Chester disease, including pericardium, lungs, kidneys, bladder, retroperitoneum, and orbits.