Foamy Macrophages and Blue Histiocytes as Diagnostic Clues to Acid Sphingomyelinase Deficiency

Abstract

We report the case of a 54‐year‐old Spanish male, born to consanguineous parents, with no relevant medical history, who presented with progressive interstitial lung disease, hepatosplenomegaly with portal hypertension, and pruritic cutaneous lesions. Laboratory tests revealed microcytic anaemia (haemoglobin 89 g/L, MCV 79 fL) and thrombocytopenia (platelets 93 ×10⁹/L), with a normal white blood cell count. Viral hepatitis and full autoimmune screenings were negative except for an elevated angiotensin‐converting enzyme (ACE), low‐titre positive anti‐nuclear antibodies (ANA), and polyclonal hypergammaglobulinaemia. Whole‐body CT scan showed splenic lesions and paravertebral masses. Differential diagnoses included systemic autoimmune conditions, connective tissue disorders, sarcoidosis, infections (e.g., Leishmania, tuberculosis), and haematological malignancies, such as lymphoproliferative or myeloproliferative disorders. The peripheral blood smear showed no abnormalities. Bone marrow aspirate was markedly hypercellular, with preserved trilineage haematopoiesis, reversed myeloid–erythroid ratio, and mild dyserythropoiesis (14%). Strikingly, numerous scattered foamy macrophages coexisted with characteristic blue histiocytes—displaying deeply basophilic cytoplasm on May–Grünwald Giemsa stain This case underscores the diagnostic value of bone marrow morphology in patients with cytopenias and systemic findings. The concurrent presence of foamy macrophages and blue histiocytes should raise suspicion for lipid storage diseases, particularly ASMD, and prompt timely metabolic and genetic investigations to establish a final diagnosis and start early treatment.