Polymerase chain reaction amplification of archival material for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis

Mai P. Hoang, D. Brian Dawson, Zora R. Rogers, Richard H. Scheuermann, Beverly Barton Rogers

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Bone marrow hemophagocytosis may occur as an incidental finding, or it may be a manifestation of a systemic and potentially lethal disorder. When systemic, the proliferation is termed hemophagocytic lymphohistiocytosis (HLH), a clinicopathologic entity characterized by a widespread proliferation of benign hemophagocytic histiocytes, fever, pancytopenia, deranged liver function, and frequently coagulopathy and hepatosplenomegaly. A variety of infectious agents, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19), have been associated with HLH, but the relative frequency of each using one technique has not been evaluated. In addition, infectious causes of incidental bone marrow hemophagocytosis, not occurring in the setting of HLH, have not been evaluated. Review of bone marrow reports from bone marrow examinations done between December 1986 and June 1997 showed that 20 children aged 2 months to 15 years had bone marrow examinations that indicated hemophagocytosis. Archival materials from 19 patients were successfully retrieved, and DNA was extracted from archived unstained coverslips with subsequent polymerase chain reaction for EBV, CMV, HHV6, and PVB19 genomic DNA. DNA extracted from 16 bone marrow specimens of age-matched children was used as negative controls. Eleven of the 19 patients fulfilled the clinical and pathological criteria for HLH; the remaining eight patients had isolated hemophagocytosis without a systematic presentation. Viral DNA was detection in 8 of 11 patients with HLH but in none of eight patients with isolated hemophagocytosis. EBV was present in five of the bone marrows, followed in frequency by HHV6, CMV, and PVB19. Infection with more than one agent was present in three patients. Only one control patient was positive for HV6 DNA; the remaining control patients were negative for all viruses. Viral infection, detected by PCR analysis of bone marrow, is a common finding in patients with HLH but not in patients with isolated bone marrow hemophagocytosis. This technique may provide another marker to aid in the diagnosis of HLH and suggests a different cause of hemophagocytosis occurring in patients with and without HLH.

Original languageEnglish (US)
Pages (from-to)1074-1077
Number of pages4
JournalHuman Pathology
Volume29
Issue number10
DOIs
StatePublished - 1998

Fingerprint

Human Herpesvirus 6
Parvovirus
Cytomegalovirus
Human Herpesvirus 4
Hemophagocytic Lymphohistiocytosis
Bone Marrow
Polymerase Chain Reaction
Bone Marrow Examination
DNA
Pancytopenia
Incidental Findings
Histiocytes
Viral DNA
Virus Diseases
Fever

Keywords

  • CMV
  • EBV
  • Hemophagocytic lymphohistiocytosis
  • Hemophagocytosis
  • HHV6
  • Parvovirus B19

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Polymerase chain reaction amplification of archival material for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis. / Hoang, Mai P.; Dawson, D. Brian; Rogers, Zora R.; Scheuermann, Richard H.; Rogers, Beverly Barton.

In: Human Pathology, Vol. 29, No. 10, 1998, p. 1074-1077.

Research output: Contribution to journalArticle

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abstract = "Bone marrow hemophagocytosis may occur as an incidental finding, or it may be a manifestation of a systemic and potentially lethal disorder. When systemic, the proliferation is termed hemophagocytic lymphohistiocytosis (HLH), a clinicopathologic entity characterized by a widespread proliferation of benign hemophagocytic histiocytes, fever, pancytopenia, deranged liver function, and frequently coagulopathy and hepatosplenomegaly. A variety of infectious agents, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19), have been associated with HLH, but the relative frequency of each using one technique has not been evaluated. In addition, infectious causes of incidental bone marrow hemophagocytosis, not occurring in the setting of HLH, have not been evaluated. Review of bone marrow reports from bone marrow examinations done between December 1986 and June 1997 showed that 20 children aged 2 months to 15 years had bone marrow examinations that indicated hemophagocytosis. Archival materials from 19 patients were successfully retrieved, and DNA was extracted from archived unstained coverslips with subsequent polymerase chain reaction for EBV, CMV, HHV6, and PVB19 genomic DNA. DNA extracted from 16 bone marrow specimens of age-matched children was used as negative controls. Eleven of the 19 patients fulfilled the clinical and pathological criteria for HLH; the remaining eight patients had isolated hemophagocytosis without a systematic presentation. Viral DNA was detection in 8 of 11 patients with HLH but in none of eight patients with isolated hemophagocytosis. EBV was present in five of the bone marrows, followed in frequency by HHV6, CMV, and PVB19. Infection with more than one agent was present in three patients. Only one control patient was positive for HV6 DNA; the remaining control patients were negative for all viruses. Viral infection, detected by PCR analysis of bone marrow, is a common finding in patients with HLH but not in patients with isolated bone marrow hemophagocytosis. This technique may provide another marker to aid in the diagnosis of HLH and suggests a different cause of hemophagocytosis occurring in patients with and without HLH.",
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AB - Bone marrow hemophagocytosis may occur as an incidental finding, or it may be a manifestation of a systemic and potentially lethal disorder. When systemic, the proliferation is termed hemophagocytic lymphohistiocytosis (HLH), a clinicopathologic entity characterized by a widespread proliferation of benign hemophagocytic histiocytes, fever, pancytopenia, deranged liver function, and frequently coagulopathy and hepatosplenomegaly. A variety of infectious agents, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19), have been associated with HLH, but the relative frequency of each using one technique has not been evaluated. In addition, infectious causes of incidental bone marrow hemophagocytosis, not occurring in the setting of HLH, have not been evaluated. Review of bone marrow reports from bone marrow examinations done between December 1986 and June 1997 showed that 20 children aged 2 months to 15 years had bone marrow examinations that indicated hemophagocytosis. Archival materials from 19 patients were successfully retrieved, and DNA was extracted from archived unstained coverslips with subsequent polymerase chain reaction for EBV, CMV, HHV6, and PVB19 genomic DNA. DNA extracted from 16 bone marrow specimens of age-matched children was used as negative controls. Eleven of the 19 patients fulfilled the clinical and pathological criteria for HLH; the remaining eight patients had isolated hemophagocytosis without a systematic presentation. Viral DNA was detection in 8 of 11 patients with HLH but in none of eight patients with isolated hemophagocytosis. EBV was present in five of the bone marrows, followed in frequency by HHV6, CMV, and PVB19. Infection with more than one agent was present in three patients. Only one control patient was positive for HV6 DNA; the remaining control patients were negative for all viruses. Viral infection, detected by PCR analysis of bone marrow, is a common finding in patients with HLH but not in patients with isolated bone marrow hemophagocytosis. This technique may provide another marker to aid in the diagnosis of HLH and suggests a different cause of hemophagocytosis occurring in patients with and without HLH.

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