Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm with multisystem manifestations, which was initially described as lipoid granulomatosis in 1930 [1,2]. The exact incidence of ECD is unknown; however, more than 1500 cases have been reported [1]. The average age at diagnosis is 56 years, with a higher prevalence among males [3]. The discovery of the BRAF V600E mutation [4] and other alterations in the MAPK-ERK pathway or the PI3K-AKT pathway [5], [6], [7] validates ECD as a clonal neoplastic disorder, leading to the revision of the histiocytosis classification in 2016 [8].

ECD can be asymptomatic or present with various manifestations, which are determined by the extent and distribution of histiocytic infiltration. The most prevalent symptom, observed in 80% to 95% of patients, is pain in the long bones [3,9]. Approximately half of ECD patients exhibit cardiac involvement, which is associated with the BRAF V600E mutation [10]. The diagnosis of ECD presents challenges due to its rarity, necessitating the integration of descriptive pathology together with clinical, radiographic, and molecular features [11].

Herein, we reported a case of ECD with recurrent pericardial effusion as the main symptom, accompanied with widespread infiltration in various organs and tissues, confirmed through cytology analysis of the effusion specimen.