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Year : 2011  |  Volume : 54  |  Issue : 3  |  Page : 603-605
Parvovirus B19 presenting with persistent pancytopenia in a patient of T-ALL post induction chemotherapy diagnosed on bone marrow examination

1 Hematopathology Laboratory, Tata Memorial Hospital, Parel, Mumbai, India
2 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, India

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Date of Web Publication20-Sep-2011


Manifestations of parvovirus B19 vary even in the normal host from asymptomatic or subclinical infection to a spectrum of illness with symptoms during viremic and immune complex mediated stage of disease. We report the morphological findings of parvovirus B19 infection (confirmed on serology) in a patient of T-acute lymphoblastic lymphoma (T-ALL) who underwent induction phase of chemotherapy (MCP 842 protocol). Persistent pancytopenia in the bone marrow aspirate with mild increase in blasts was thought to be due to failure to achieve marrow remission. However, giant pronormoblasts with prominent intranuclear inclusions confirmed on trephine biopsy led to the suspicion of parvovirus B19 infection which was later confirmed on serology. This case is presented to report the rarely seen classical morphological feature of parvovirus infection on bone marrow examination which was incidentally the first investigation to diagnose the viremic phase of the infection, indicating that a high index of suspicion needs to be kept in mind while examining bone marrows of susceptible patients.

Keywords: Bone marrow, intranuclear inclusion, pancytopenia, parvovirus B19

How to cite this article:
Gadage VS, Viswanathan S, Kunal S, Subramanian P G, Gujral S. Parvovirus B19 presenting with persistent pancytopenia in a patient of T-ALL post induction chemotherapy diagnosed on bone marrow examination. Indian J Pathol Microbiol 2011;54:603-5

How to cite this URL:
Gadage VS, Viswanathan S, Kunal S, Subramanian P G, Gujral S. Parvovirus B19 presenting with persistent pancytopenia in a patient of T-ALL post induction chemotherapy diagnosed on bone marrow examination. Indian J Pathol Microbiol [serial online] 2011 [cited 2020 Nov 30];54:603-5. Available from: https://www.ijpmonline.org/text.asp?2011/54/3/603/85109

   Introduction Top

Parvovirus B19 infection has a wide variety of disease manifestations in immunocompetent and immunocompromised hosts. The viral replication occurs only in human erythrocyte precursors [1],[2] and it is usually diagnosed by detection of viral deoxyribonucleic acid (DNA) or IgM and IgG antibodies in the serum in clinically suspected cases. [1],[2] Its detection as viral intranuclear inclusions in pronormoblasts on bone marrow trephine sections is very rare and gives an indirect evidence of the infection. [3],[4] We report an unusual case of a parvovirus infection presenting with persistent pancytopenia in a patient of T-cell acute lymphoblastic leukemia (T-ALL) post induction chemotherapy, first diagnosed on bone marrow examination.

   Case Report Top

A 38-year-old man, a known case of T-ALL, was on induction chemotherapy with MCP 841 protocol. He was seronegative for human immunodeficiency virus 1 and 2 (HIV1 and HIV2). His post induction (after 1 month of treatment) complete blood counts revealed hemoglobin (Hb) level of 9.6 g/L, platelet count 900 Χ 10 9 /L and total leukocyte count 0.648 Χ 10 9 /L. Peripheral blood smear showed eosinophilia, (neutrophils 28.2%, lymphocytes 30.7%, monocytes 16.3%, eosinophils 24.8%). Red blood cell (RBC) parameters were as follows: RBC count 3.55 Χ 10 12 /L(low), mean corpuscular volume (MCV) 76 fl, mean corpuscular hemoglobin (MCH) 25.5 pg, mean corpuscular hemoglobin concentration (MCHC) 33.5 g dL and RBC distribution width (RDW) 18.3%. Blood cultures were negative. Bone marrow aspiration and biopsy were performed to evaluate morphological remission status. Bone marrow aspirate showed 7% blasts with maturation arrest in erythroid cell series. On scanner view, few giant pronormoblasts with intranuclear inclusions and cytoplasmic blebs were identified. The bone marrow biopsy was hypocellular and revealed adequate megakaryocytes and myeloid precursors. Few large cells with nucleomegaly, pale chromatin and prominent eosinophilic nucleoli like inclusions were noted. The interesting feature on trephine biopsy was the paucity of erythroid precursors and giant pronormoblasts with prominent inclusions which morphologically resembled parvovirus B19 infection. Serology was advised for confirmation which showed IgM antibodies for parvovirus [40.1 U/ mL; positive value above 17 U/mL by enzyme-linked immunosorbent assay (ELISA), confirming acute parvovirus infection. The patient received intravenous immunoglobulin and re-induction therapy. Post therapy, his hemoglobin rose to 12 mg% and bone marrow was also in remission with maturing erythroid series.

   Discussion Top

Parvovirus B19, transmitted in humans through exposure to infected respiratory droplets or blood products, [1],[2],[5] can propagate only in erythroid progenitor cells. [5] The infection may remain asymptomatic or cause aplastic crisis, pure red cell aplasia (PRCA) and prolonged erythroid suppression in immunodeficient patients as seen in the present case. [2],[6],[7]

In a patient of acute leukemia after 4 weeks of completion of standard induction chemotherapy, the patient shows recovery of neutrophils and platelets along with less than 5% blasts in bone marrow aspirate. The persistent pancytopenia in the present case was thought to be due to failure to achieve bone marrow remission. [9] The marrow revealed normal myelopoesis and megakaryopoiesis and increase in the number of blasts (7%) with maturation arrest in erythropoiesis at pronormoblast phase. In the post-chemotherapy marrow, the erythroid cell series is the first lineage to regenerate, but the maturation arrest in erythropoiesis with giant pronormoblasts prompted a suspicion of parvovirus B19 infection. Both the aspirate and trephine biopsy revealed intranuclear inclusions and central clearing within giant pronormoblasts. [Figure 1] and [Figure 2]. Infected erythroid cells showed marginated chromatin, pseudopod formation and cytoplasmic vacuolation-lantern cells-all of which are typical of cells undergoing apoptosis. [5],[8] By electron microscopy, virus particles are reported to be seen both in the nucleus as well as the in cell membrane of infected cells. [3]
Figure 1: (a) Bone marrow trephine biopsy showing cells with nucleomegaly, pale chromatin and eosinophilic intranuclear inclusions (H and E, x200); (b) high power of the intranuclear inclusion (H and E, x400)

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Figure 2: Bone marrow aspirate showing giant pronormoblasts with multiple intranuclear inclusions and cytoplasmic projections (dog ear) (Wright's stain, x1000)

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The virus can be detected within 5-6 days of infection by DNA polymerase chain reaction (PCR), a sensitive and rapid method. [1],[10] which was negative in the present case, while IgM antibodies which are reported to appear within 2 weeks were detected. In immunocompromised hosts, the infection is known to persist as a result of failure to produce effective neutralizing antibodies. Detection of viral infection can also be performed by in situ hybridization technique or by immunohistochemistry on the bone marrow, [1],[3],[10] which was not done in this patient.

We report here this case to highlight the rarely seen classical morphological appearance of parvovirus on bone marrow aspirates or trephine biopsies and emphasize the role of keeping a high index of suspicion for parvovirus B19 infection as a cause for pancytopenia in patients following induction chemotherapy.

   References Top

1.Brown KE. Chapter 147: Human parvoviruses, including Parvovirus B19 and Human Bocavirus. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Diseases, Mandell, Douglas and Bennett's Principles and Practice of Human Diseases, 7 th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2007. p. 2087-97.  Back to cited text no. 1
2.Mcomish F, Yap PL, Jordan A, Hart H, Cohen BJ, Simmonds P. Detection of parvovirus B19 in donated blood: A model system for screening by polymerase chain reaction. J Clin Microbiol 1993;31:323-8.  Back to cited text no. 2
3.Flora AV, Isescu DN, Melhem MF. Parvovirus B19 infection in immunocompromised host. Arch Pathol Lab Med 2007;131:799-804.  Back to cited text no. 3
4.Crook TW, Rogers BB, McFarlend RD, Kroft SH, Muretto P, Hemandez JA, et al. Unusual bone marrow manifestations of parvovirus B19 infection in immunocompromised patients. Hum Pathol 2000;31:161-8.  Back to cited text no. 4
5.Jessica TS, Brian VR, Joshua H. Clinical presentation of parvovirus B19 infection. Am Fam Physician 2007;75:373-7.  Back to cited text no. 5
6.Azzi A, Ciappi S, Zakyrzewska K, Morfini M, Marianiand G, Mannucci PM. Human parvovirus B 19 infection in haemophiliac: A first infused with two high purity, virally attenuated factor VIII concentrates. Am J Hematol 1992;39:228-30.  Back to cited text no. 6
7.Frickhonfen N, Arnold R, Hertenstein B, Wilesneth M, Young NS. Parvo B19 infection and bone marrow transplantation. Am J Hematol 1992;64:121-4.  Back to cited text no. 7
8.Morita E, Nakashima A, Asao H, Dato H, Sugamura K. human parvovirus b19 Npnstructural protein (NS1) induces cell cycle arrest at G1 phase. J Virol 2003;77:2921-5.  Back to cited text no. 8
9.Rao P, Koduri. A novel cytomorphology of the giant pronormoblasts of parvovirus B19 infection. Am J Haematol 1998;58:95-9.  Back to cited text no. 9
10.McOmish F, Yap PL, Jorden A, Hart H, Cohen BJ, Simmond P. Detection of Parvovirus B19 in donated blood: A model system for screening by polymerase chain reaction. J Clin Microbiol 1993;31:323-8.  Back to cited text no. 10

Correspondence Address:
Seethalakshmi Viswanathan
Department of Pathology, Tata Memorial Hospital, Parel, Mumbai - 400 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.85109

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