Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants

E. Arbustini, M. Grasso, M. Diegoli, E. Percivalle, P. Grossi, M. Bramerio, C. Campana, C. Goggi, A. Gavazzi, M. Vigano

Research output: Contribution to journalArticle

Abstract

From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21%) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3%): all were from patients with primary HCMV infection (6 of 13; 46%). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.

Original languageEnglish
Pages (from-to)205-213
Number of pages9
JournalAmerican Journal of Clinical Pathology
Volume98
Issue number2
Publication statusPublished - 1992

Fingerprint

Cytomegalovirus Infections
Transplants
Biopsy
Infection
Polymerase Chain Reaction
In Situ Hybridization
Myocarditis
Muscle Cells
Viral Inclusion Bodies
Leukocytes
Endothelial Cells
Cell Count
Immunohistochemistry

Keywords

  • Endomyocardial biopsy
  • Heart transplantation
  • Human cytomegalovirus
  • Immunohistochemical and molecular hybridization study
  • Polymerase chain reaction
  • Primary and recurrent infection

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants. / Arbustini, E.; Grasso, M.; Diegoli, M.; Percivalle, E.; Grossi, P.; Bramerio, M.; Campana, C.; Goggi, C.; Gavazzi, A.; Vigano, M.

In: American Journal of Clinical Pathology, Vol. 98, No. 2, 1992, p. 205-213.

Research output: Contribution to journalArticle

Arbustini, E, Grasso, M, Diegoli, M, Percivalle, E, Grossi, P, Bramerio, M, Campana, C, Goggi, C, Gavazzi, A & Vigano, M 1992, 'Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants', American Journal of Clinical Pathology, vol. 98, no. 2, pp. 205-213.
Arbustini, E. ; Grasso, M. ; Diegoli, M. ; Percivalle, E. ; Grossi, P. ; Bramerio, M. ; Campana, C. ; Goggi, C. ; Gavazzi, A. ; Vigano, M. / Histopathologic and molecular profile of human cytomegalovirus infections in patients with heart transplants. In: American Journal of Clinical Pathology. 1992 ; Vol. 98, No. 2. pp. 205-213.
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abstract = "From November 1985 to December 1990, 2,552 endomyocardial biopsy specimens from 209 heart transplant patients were studied. Forty-four (21{\%}) patients developed 45 episodes of major human cytomegalovirus infection (HCMV). Human cytomegalovirus infection was primary in 13 of 44 patients. Thirty-one patients developed episodes of recurrent major infection. One patient had both primary and recurrent infections. Conventional histopathologic and immunohistochemical study, in situ hybridization, and polymerase chain reaction were used to diagnose HCMV myocardial involvement on corresponding endomyocardial biopsy specimens performed during infection. Conventional morphologic study showed typical viral inclusion bodies in four biopsy specimens. Two cases had myocyte HCMV localization with necrotizing myocarditis, whereas two had endothelial cell involvement without any inflammatory reaction. In these four biopsy specimens, immunohistochemistry showed a higher number of infected cells than that recognized by conventional histopathologic study. In situ hybridization detected infected cells with no evidence of cytopathic effect. Polymerase chain reaction gave HCMV amplification products in two additional biopsy specimens otherwise interpreted as moderate and mild rejection, respectively. Therefore, 6 biopsies showed HCMV myocardial involvement (6 of 45; 13.3{\%}): all were from patients with primary HCMV infection (6 of 13; 46{\%}). None of 32 major recurrent infections showed any myocardial involvement. In conclusion, our study is the first to demonstrate that myocardial HCMV involvement preferentially occurs in primary infection and HCMV endothelial localization can be free from inflammatory reaction, whereas HCMV myocyte localization leads to necrotizing myocarditis. Polymerase chain reaction has a higher diagnostic sensitivity than in situ hybridization. However, polymerase chain reaction findings of HCMV DNA on otherwise negative endomyocardial biopsy specimens remains of questionable significance because polymerase chain reaction-positive biopsy samples do not necessarily indicate tissue infection. It is impossible to determine whether amplified sequences derive from circulating leukocytes or from tissue cells.",
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