Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Virus-associated haemophagocytic syndrome with Epstein-Barr virus infection

  • 24 Accesses

  • 8 Citations


The clinical and histological findings of a 10-year-old girl with virus-associated haemophagocytic syndrome are presented. The serum levels of Epstein-Barr viral antigens were elevated. Epstein-Barr virus (EBV) genome was detected by polymerase chain reaction in bone marrow and lymph node specimens. Histologically, haemophagocytic histiocytes were present in bone marrow, and areas of non-suppurative necrosis were present in lymph nodes, where silver grain deposition of the EBV genome was demonstrated by in situ hybridization.

This is a preview of subscription content, log in to check access.


  1. Andreesn R, Osterholz J, Bodemann H, Bross KJ, Costabel U, Lohr GW (1984) Expression of transferrin receptors and intracellular ferritin during terminal differentiation of human monocytes. Blut 49:195–202

  2. Britton S, Andersson-Anvret M, Gergely P, Henle W, Jondal M, Klein G, Sandstedt B, Svedmyr E (1978) Epstein-Barr-virus immunity and tissue distribution in a fatal case of infectious mononucleosis. N Engl J Med 298:89–92

  3. Cheeseman SH, Henle W, Rubin RH, Tolkoff-Rubin NE, Cosimi B, Cantell K, Winkle S, Herrin JT, Black PH, Russell PS, Hirsch MS (1980) Epstein-Barr virus infections in renal transplant recipients. Effects of antithymocyte globulin and interferon. Ann Intern Med 93:39–42

  4. Epstein MA, Achong BG (eds) (1979) The Epstein-Barr virus. Springer, Berlin Heidelberg New York

  5. Esumi N, Ikushima S, Hibi S, Todo S, Imashuku S (1988) High serum ferritin level as a marker of malignant histiocytosis and virus-associated hemophagocytic syndrome. Cancer 61:2071–2076

  6. Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT (1984) Epstein-Barr virus receptor of human lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci USA 81:4510–4514

  7. Frizzera G (1987) The clinico-pathological expressions of Epstein-Barr virus infection in lymphoid tissues. Virchows Arch [B] 53:1–2

  8. Frizzera G, Hanto DW, Gajl-Peczalska KJ, Rosai J, McKenna RW, Sibley RK, Holahan KP, Lindquist LL (1981) Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res 41:4262–4279

  9. Henle W, Henle G (1981) Epstein-Barr virus-specific serology in immunologically compromised individuals. Cancer Res 41:4222–4225

  10. Kikuchi M, Takeshita M, Tashiro K, Mitsui T, Eimoto T, Okamura S (1986) Immunological study of histiocytic necrotizing lymphadenitis. Virchows Arch [A] 409:299–311

  11. Krasznai G, Gyory GY (1968) Hydantoin lymphadenopathy. J Pathol Bacteriol 95:314–319

  12. McClain K (1986) Epstein-Barr virus DNA in lymphocytes of patients with the virus-associated hemophagocytic syndrome. Am J Pediatr Hematol Oncol 8:121–127

  13. McClain K, Gehrz R, Grierson H, Purtilo D, Filipovich A (1988) Virus-associated histiocytic proliferations in children. Frequent association with Epstein-Barr virus and congenital or acquired immunodeficiencies. Am J Pediatr Hematol Oncol 10:196–205

  14. Ohshima K, Kikuchi M, Eguchi F, Masuda Y, Sumiyoshi Y, Mohtai S, Takeshita M, Kimura N (1991) Analysis of Epstein-Barr viral genomes in lymphoid malignancy using Southern blotting, polymerase chain reaction and in situ hybridization. Virchow Archiv [B] (in press)

  15. Provisor AJ, Iacuone JJ, Chilcote RR, Neiburger RG, Crussi FG, Baehner RL (1975) Acquired agammaglobulinemia after a lifethreatening illness with clinical and laboratory features of infectious mononucleosis in three related male children. N Engl J Med 293:62–65

  16. Purtilo DT, Sakamoto K, Saemundsen AK, Sullivan JL, Synnerholm AC, Anvret M, Pritchard J, Sloper C, Sieff C, Pincott J, Pachman L, Rich K, Cruzi F, Cornet JA, Collins R, Barnes N, Knight J, Sandstedt B, Klein G (1981) Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative diseases by clinical, virological, and immunopathological studies. Cancer Res 41:4226–4236

  17. Reisman R, Greco MA (1984) Virus-associated hemophagocytic syndrome due to Epstein-Barr virus. Hum Pathol 15:290–293

  18. Revoltella RP, Vigneti E, Fruscalzo A, Park M, Ragona G, Rocchi G, Calef E (1989) Epstein-Barr virus DNA sequences in precursor monocyte-macrophage cell lines established from the bone marrow of children with maturation defects of haematopoiesis. J Gen Virol 70:1203–1215

  19. Risdall RJ, McKenna RW, Nesbit ME, Krivit W, Balfour HH, Simmons RL (1979) Virus-associated hemophagocytic syndrome. Cancer 44:993–1002

  20. Rosai J (1981) Ackerman's surgical pathology, 6th edn. Mosby, St. Louis, p 1168

  21. Saito I, Servenius B, Compton T, Fox RI (1989) Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren's syndrome. J Exp Med 169:2191–2198

  22. Singer DB (1981) Pathology of neonatal herpes simplex virus infection. In: Rosenberg HS, Bernstein J (eds) Perspectives in pediatric pathology, vol 6. Masson, New York, p 243

  23. Tenner-Racz K, Racz P, Schmidt H, Dietrich M, Kern P, Lovie A, Gartner S, Popovic M (1988) Immunohistochemical, electron microscopic and in situ hybridization evidence for the involvement of lymphatics in the spread of HIV-1. AIDS 1:299–309

  24. Tindle BH (1978) Lymphadenopathy in influenza. In: Coulson WF (ed) Surgical pathology, vol 2. Lippincott, Philadelphia, p 904

  25. Tindle BH, Parker JW, Lukes RJ (1972) “Reed-Sternberg cells” in infectious mononucleosis? Am J Clin Pathol 58:607–617

  26. Virelizier JL, Lenoir G, Griscelli C (1978) Persistent Epstein-Barr virus infection in a child with hypergammaglobulinemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet II:231–234

  27. Worwood M, Hourahane D, Jones BM (1984) Accumulation and release of isoferritins during incubation in vitro of human peripheral blood mononuclear cells. Br J Haematol 56:31–43

Download references

Author information

Correspondence to Kohichi Ohshima.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ohshima, K., Kikuchi, M., Eguchi, F. et al. Virus-associated haemophagocytic syndrome with Epstein-Barr virus infection. Vichows Archiv A Pathol Anat 419, 519–522 (1991). https://doi.org/10.1007/BF01650682

Download citation

Key words

  • Virus-associated haemophagocytic syndrome
  • Epstein-Barr virus
  • In situ
  • Polymerase chain reaction