Pancytopenia related to acquired sea‐blue histiocytosis during chronic parenteral nutrition
Authors: Marie‐Charlotte Bourrienne, Imen Ben Salah, Emmanuelle de Raucourt, Jérôme Debus, Lore Billiauws, Dominique Cazals‐Hatem, Francisca Joly, Catherine Trichet
Journal: American Journal of Hematology (2023)

Bone marrow smear showing histiocytes (black arrow) containing sea blue granules stained with May-Grünwald Giemsa. A 70-old-year man on long-term parenteral nutrition (PN), with extensive short-bowel intestinal resection, was referred for investigation of pancytopenia. Peripheral blood examination revealed non-regenerative normocytic anemia (8.2 g/dL), thrombocytopenia (100 × 109/L), leukopenia (3.2 × 109/L) without absolute neutropenia (1.9 × 109/L) and normal blood smear. Vitamin B12, folate, and copper deficiencies were ruled out. Bone marrow smears (May-Grünwald Giemsa [MGG] stain) showed normal cellularity with no excess of blast or myeloid dysplasia. Interestingly, a dense infiltration of macrophages loaded with blue cytoplasmic granules was evidenced, so called "Sea-Blue Histiocytes" (Image 1A,B, original magnification X100). Sea-blue histiocytes were heterogeneously distributed with numerous clusters, and estimated at 11% of hematopoietic cells. Cytochemistry confirmed that sea-blue histiocytes were lipid-laden macrophages, positive for periodic acid Schiff stain and Oil-Red-O (Image 1C,D respectively, original magnification X100). There were no clinical and morphological evidence in support of congenital lysosomal storage diseases such as Nieman-Pick or Gaucher disease (no consanguinity, no family history, absence of vacuolated and foamy histiocytes or Gaucher cells on bone marrow smears). No hepatosplenomegaly was found on abdominal computed tomography. The patient was diagnosed with pancytopenia due to sea-blue histiocytes infiltration of the bone marrow associated with long-term PN. Sea-blue histiocytes are macrophages characterized by bright blue coloration on MGG staining than can accumulate in different tissues (spleen, liver, bone marrow, and lymph node).1, 2 They result from an excessive accumulation of lipids that exceeds the lysosomal capacity of macrophages and subsequently leads to incomplete lipid degradation and accumulation of lipopigments in their cytoplasm (ceroid, lipofuscin…).1 Sea-blue histiocytosis has been reported in a wide range of disorders, including inherited storage diseases, acquired disorders associated with increased cell turnover and membrane degradation, and long-term PN.2-5 Intravenous lipid emulsions (ILEs) are an essential part of the macronutrient composition of PN. Long-term use of ILEs has been reported to be frequently associated with liver disease (steatosis, cholestasis, or fibrosis) and splenomegaly.5 In this case, the absence of hepatosplenomegaly does not support systemic sea-blue histiocytosis although biopsy was not performed to confirm this hypothesis. This case illustrates that ILEs can induce pancytopenia associated with sea-blue histiocyte infiltration of the bone marrow. Reducing the lipid content of the diet is currently being evaluated in this patient to improve it. The authors declare no competing financial interests. Requests for data sharing should be sent to [email protected]