INTRODUCTION: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis characterized by bone marrow histiocytes and lymphocytes, and long bone sclerosis sparing the epiphysis. Nonosseus disease occurs in the brain, orbit and vessels with typical pulmonary involvement manifesting as diffuse interstitial disease and pleural thickening.
CASE PRESENTATION: A 60-year-old previously healthy man presented in 2002 with intermittent right body spasticity and dysarthria. Brain magnetic resonance imaging (MRI) demonstrated abnormal signals in the pons and midbrain, and enhancing right temporal lesions. Electroencephalogram was negative for seizure activity. No diagnosis was established and there was no improvement after a brief trial of steroids. Chest computed tomography only revealed small noncalcified densities in the left lung (5 mm) and right middle lobe (RML) (3 mm). Positron emission tomography(PET) uptake was positive in the brain lesions only. Bronchoscopy with RML transbronchial biopsies were non-diagnostic, revealing reactive foreign body giant cells. Repeat brain MRIs demonstrated waxing and waning variable regression of the brain lesions. The patient was lost to followup, and re-presented in September 2005 with progressive dyspnea, left-sided weakness, spasticity, and diplopia. His exam was now significant for proptosis, cranial nerve palsies, left hemiparesis, and ataxia. Imaging revealed bilateral pleural effusions and a 7.0 x 4.5 cm soft tissue mass, with infiltration to the RML and right lower lobe (RLL), and a left lung soft tissue lesion. Sclerotic bone lesions were seen in the sternum, vertebral bodies, and humeri. PET scan uptake was present in the pulmonary lesions and brain. Rheumatological studies, HIV testing, and studies for coccidiomycosis, cryptococcus, and histoplasma were negative. Thoracentesis yielded clear, exudative, lymphocytic predominant fluid negative for malignancy and pathogens. Bronchoscopy suggested a stenotic RML orifice. Transbronchial biopsies revealed non-specific inflammation, and poorly defined histiocytes. Cultures were negative. Thorascopic biopsy demonstrated a hard mass in the RML and RLL and thickened pleura. RML biopsies demonstrated chronic fibrosis and foamy histiocytes, which stained positive for CD68. A bone marrow biopsy revealed histiocytes staining positive for CD68 and negative for s-100. Only reactive astrocytes and mild gliosis were seen on temporal lobe brain biopsy. Skeletal surveys showed bilateral long bone sclerosis with sparing of the epiphyses.
DISCUSSIONS: The constellation of findings in this patient was most consistent with Erdheim-Chester Disease (ECD).The differential diagnoses under consideration included necrotizing sarcoid granulomatosis, lymphomatoid granulomatosis, malignancy, and lymphoma. Sarcoidosis was not supported by multiple biopsies, and marrow findings were not representative of lymphoma. The waxing and waning nature of the lesions were inconsistent with malignancy or metastasis. Langerhan's Histiocytosis, Behcet's and Hashimoto's were considered. Rheumatologic studies and biopsies were not supportive of vasculitis. No infection was identified despite numerous cultures of multiple tissues. The diagnosis of ECD was supported by the bone marrow findings of histiocyte clusters positive for CD68 and negative for S-100. ECD was also supported by bilateral long bone sclerosis with eepiphyseal sparing. Other histiocytoses such as eosinophilic granuloma present with lytic bone lesions. Pulmonary nodules and masses in ECD have not been well described, although retroperitoneal soft tissue masses due to fat infiltration by histiocytes have been reported. Pleural thickening and pleural effusions have been described in ECD.
CONCLUSION: ECD should be considered in the differential diagnosis of a patient presenting with pulmonary, neurological, and osseus manifestions of unclear etiology. This rare entity has variable presentations, and requires exclusion of other malignant, infectious, and inflammatory processes. Interstitial lung disease and pleural involvement are most commonly reported, but pulmonary involvement can also include mass lesions.
DISCLOSURE: Joanne Bando, None.