Egan, A.

Abstract Introduction: Erdheim-Chester disease (ECD) is an exceptionally rare non-Langerhans cell histiocytic malignant disorder but presents a unique diagnostic challenge due to its diverse clinical manifestations from mild symptoms to severe, life-threatening multiorgan disease. Here, we report a case of ECD that presented with pleuro-pulmonary and vascular involvement rather than skeletal lesions. Case description: A 75-year-old man with a history of systemic lupus erythematosus, rheumatoid arthritis, and chronic obstructive pulmonary disease presented with syncope, anorexia, fatigue, and weight loss. He was noted to be in atrial fibrillation. Subsequent imaging studies, including. The CTA of chest and PET-CT scans showed hyperdense wall thickening in multiple arteries and veins, including the pulmonary arteries and veins, aortic arch, thoracic and abdominal aorta, and iliac arteries as well as pulmonary nodules suggestive of a large vessel vasculitis associated with systemic inflammation. The patient underwent a pleural biopsy which only demonstrated nonspecific inflammation. He subsequently underwent surgical wedge biopsy of a superior right lower lobe and multiple pleural biopsies showed atypical histiocytic infiltrate suspicious for a histoplasmic neoplasm with the atypical histiocytes characterized by plump to spindled nuclei with focal emperipolesis. Atypical histiocytes were positive for CD163, factor 13a, cyclin D1 suggestive of ECD. As further testing demonstrated a negative BRAFV600E mutation, the patient was initiated on cobimetinib 40 mg daily. He responded to therapy with subjective and objective improvement. There has been no radiographic evidence of recurrence. Discussion: The diagnosis of ECD relies on clinical presentation, imaging studies, and distinctive pathological findings. Overall, the prognosis depends on the degree of histiocytic damage before initiation of treatment; degree of inflammation; age; digestive tract involvement. A biopsy revealing non-Langerhans cell histiocytosis, supported by immunohistochemistry exams, is essential for confirming the diagnosis. Diagnosing ECD is challenging due to its rarity and multisystem involvement necessitating a multidisciplinary approach. Pulmonary involvement, seen in 43% of cases, often presents with features of interstitial lung disease but does not significantly impact overall prognosis. Recent evidence implicates the BRAFV600E mutation in ECD pathogenesis, suggesting new therapeutic possibilities.