January 2009
Written by Peter M. Banks, M.D., Director of Hematopathology, Carolinas Medical Center, Charlotte, North Carolina.

Submitting Physician
Joel Kaplan, M.D., Pediatric Hematology-Oncology, Levine Children's Hospital, Carolinas Medical Center, Charlotte, North Carolina.

Diagnosis
Parvovirus infection of bone marrow, with resultant hypoplastic anemia and leukopenia.

Clinical History
This 19 year old Southeast Asian male developed anemia (hemoglobin 7.4) with reticulocytopenia and leukopenia (WBC 2300/µl) about 3 months after receiving a renal allograft. The absolute reticulocyte count was 5,600/µl with an immature fraction of 0.28. A bone marrow biopsy and aspiration were performed.

Microscopy
Sections of the biopsy reveal a slightly hypocellular marrow (about 50% cellularity), with a normal distribution of megakaryocytes but with almost no recognizable maturing erythroid clusters. At higher magnification one can recognize peculiar large cells with dark basophilic cytoplasm and clearing zones within large, dark nuclei (see Figure 1).

Aspirate smear preparations show the same features, and the abnormal large cells can be seen to possess faint blue inclusions within their nuclei (see Figure 2).

Ancillary Studies
An immunohistochemical (IHC) stain for parvovirus demonstrates a surprising abundance of positive nuclear inclusions (see Figure 3).

Discussion
The human parvovirus B19 is commonly manifest as a febrile exanthem among children and young adults with little morbidity. About 50% of adults in the United States have serologic evidence of past exposure, which confers lifelong immunity. The infection of erythroid precursor cells is usually a subclinical feature of the disease in the normal host, however, it may be life threatening to a fetus with in utero exposure and to individuals with underlying hemoglobinopathy or with compromised immunity due to immunosuppression or immunodeficiency (1).

This patient had no evidence of hemoglobinopathy but was immunosuppressed, having recently received a renal allograft. The diagnosis of parvovirus infection can be established with IHC demonstration of the agent in marrow samplings, as in this case, or with detection of IgM antibodies. There are new quantitative PCR methods for detection circulating virus levels (1).

This patient was treated with immunoglobulin transfusions for one week, with resultant response in reticulocytosis and gradual increase in hemoglobin. There have been cases reported of extremely refractory bone marrow infection successfully treated with marrow allografting (2)!

References

1. Florea AV, Ionescu DN, Melhem MF.
   Parvovirus B19 infection in the immunocompromised host. Arch Pathol Lab Med. 2007; 131: 799-804. (Review). More online »
2. Kaptan K, Beyan C, Ural AU, Ustün C, et al.
   Successful treatment of severe aplastic anemia associated with human parvovirus B19 and Epstein-Barr virus in a healthy subject with allo-BMT. Am J Hematol. 2001; 67: 252-255. More online »

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