A 47-year-old white woman who had previously undergone lung transplant presented with a past medical history significant for chronic obstructive pulmonary disease, asthma, and diabetes mellitus. The patient was on multiple medications related to her lung transplant. Her blood smear was referred for pathologist review based on the presence of atypical cytoplasmic inclusions in the neutrophils. The white blood cell count was 2.6 × 103/μL, hemoglobin 9.2 g/dL, mean corpuscular volume 89 fL, and platelets 202 × 103/μL.
Review of the smear revealed mild poikilocytosis of the red blood cells with occasional elliptocytes, acanthocytes, and rare schistocytes with a white blood cell differential of 6% band neutrophils, 80% segmented neutrophils, 2% lymphocytes, 11% monocytes, and 1% basophils. The neutrophils demonstrated toxic granulation, Dohle bodies, and Howell-Jolly body–like inclusions (Figures 1 and 2).
Bain1 in 1989 described detached nuclear fragments within the cytoplasm of neutrophils as a feature of dysplastic granulopoiesis secondary to immunosuppressive or chemotherapeutic drugs. She was the first to compare them with the Howell-Jolly body seen in erythrocytes.
Similar nuclear fragmentation in neutrophils of patients with acquired immunodeficiency syndrome and Mycobacterium avium complex infection was previously noted by Godwin and associates.2 Howell-Jolly body–like inclusions are observed not only in the neutrophils in the peripheral blood smears of patients with acquired immunodeficiency syndrome, but also in the associated Wright-Giemsa–stained bone marrow aspirates, where they can also be seen in myelocytes, metamyelocytes, and band forms. The Howell-Jolly body–like inclusions may also be seen in neutrophils with toxic granulation, vacuolization, or Dohle bodies.3
Slagel and colleagues3 described Howell-Jolly body–like inclusions as separated from the remaining nuclear material. Howell-Jolly body–like inclusions stain negative with the periodic acid–Schiff, Grocott methenamine silver, and Gram stains but positive with the Feulgen reaction.3 Although they have not undergone ultrastructural analysis, because of the positive Feulgen reaction it is believed that they represent nuclear fragments.
The association between acquired immunodeficiency syndrome and these inclusions has not been determined. Of note, all the patients in the study by Slagel and associates3 were on antiviral agents (except one patient with acquired immunodeficiency syndrome with an unknown medication history). Howell-Jolly body–like inclusions have been reported not only in patients infected with human immunodeficiency virus, but also in transplant recipients such as our patient. Our patient's infectious serologic studies were nonreactive for human immunodeficiency virus 1 and human immunodeficiency virus 2 antibodies. Howell-Jolly body–like inclusions do not represent a specific disease entity. However, recognizing them is important so they are not confused with intracytoplasmic infectious agents, Dohle bodies, and inclusions of inherited conditions.3