Abstract Introduction Gaucher disease is an autosomal recessive lysosomal storage disorder caused by GBA1 mutations, resulting in deficient glucocerebrosidase activity and accumulation of glucocerebroside in macrophages. Classic features include hepatosplenomegaly, cytopenias, and skeletal involvement, while pulmonary disease is uncommon and can mimic hematologic malignancy or granulomatous disorders. We present an unusual case of Gaucher disease with diffuse pulmonary nodules and pancytopenia despite negative GBA1 mutation analysis. Case Presentation A 26-year-old male with a history of splenomegaly, thrombocytopenia, and chronic kidney disease presented for evaluation of worsening pancytopenia. He was hemodynamically stable without dyspnea, bleeding, or constitutional symptoms. Laboratory studies revealed platelets 4 K/µL, leukocytes 3.4 K/µL, hemoglobin 11 g/dL, and creatinine 2.7 mg/dL. Chest CT demonstrated diffuse bilateral pulmonary nodules, hazy opacities, and a 3.5 × 1.5 cm left lower-lobe consolidation. Abdominal imaging revealed hepatosplenomegaly and periaortic lymphadenopathy. Bone marrow biopsy showed a mildly hypercellular marrow with myeloid and megakaryocytic hyperplasia but no malignancy or granulomatous disease. Endobronchial ultrasound (EBUS)-guided biopsy of station 11L lymph node showed benign lymphoid tissue without malignancy or granulomatous inflammation. Extensive infectious, autoimmune, and hematologic workup including flow cytometry, cytogenetics, viral serologies, and ANA was negative. Given his occupational mold exposure, fungal etiologies were initially suspected. He received intravenous immunoglobulin and dexamethasone (40 mg daily) with transient improvement in cytopenias. Liver biopsy demonstrated foamy hepatocytes strongly positive for CD68, negative PAS and AFB stains, and absence of malignancy findings consistent with Gaucher cells. However, DNA analysis for common GBA1 mutations was negative, suggesting a rare undetected variant or a Gaucher-like phenocopy. Conclusion This case highlights an atypical presentation of Gaucher disease with pulmonary and hematologic involvement mimicking infection or malignancy. Pulmonary findings result from infiltration of Gaucher cells within alveolar and interstitial spaces, producing nodular and interstitial opacities. Recognition of this pattern is essential in young adults with cytopenias and organomegaly when standard workup is unrevealing. Despite negative GBA1 testing, histopathology confirmed the diagnosis, emphasizing the limitations of routine genetic panels and the potential role of rare variants. Early identification and initiation of ERT can improve hematologic and pulmonary outcomes, underscoring the need for diagnostic vigilance. Learning Objective To recognize Gaucher disease as a potential cause of unexplained pancytopenia and pulmonary nodules, even in the absence of confirmatory GBA1 mutations, and to emphasize the importance of tissue diagnosis and early initiation of enzyme replacement therapy. This abstract is funded by: None
Francos et al. (Fri,) studied this question.