Herpes simplex virus type 1 infection associated with atrial myxoma

Abstract

Some findings suggest an infectious factor in cardiac myxoma and certain histopathological features indicate herpes simplex virus type 1 (HSV-1) infection. We hypothesized that HSV-1 may be involved in the pathogenesis of cardiac myxoma. Paraffin-embedded tissue samples from 17 patients with atrial myxoma were investigated for HSV-1 antigen by immunohistochemistry and viral genomic DNA by nested polymerase chain reaction. The histogenesis and oncogenesis of atrial myxoma were assessed by the expression of calretinin, Ki67, and p53 protein, respectively. Autopsy myocardial samples, including endocardium from 12 patients who died by accident or other conditions, were used for comparison. HSV-1 antigen was detected in atrial myxoma from 12 of 17 patients: 8 of these 12 samples were positive also for HSV-1 DNA. No HSV-1 antigen or DNA was found in tissue from the comparison group. Antigens of HSV-2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were not found in atrial myxoma. Calretinin was found in myxoma cells of all 17 cases but Ki67 was present only in smooth muscle cells or infiltrating cells in some cases. p53 was not detectable in any myxoma. Most infiltrating cells were cytotoxic T lymphocytes. These data suggest that HSV-1 infection is associated with some cases of sporadic atrial myxoma and that these may result from a chronic inflammatory lesion of endocardium.

Figure 1.

Histopathology of atrial myxoma. A: H&E staining of a myxoma tissue section showing multinucleate myxomatous cells. B: H&E staining of a myxoma tissue section showing microscopic hemorrhage and angiogenesis. C: Immunohistochemical staining (brown deposits) for calretinin in myxomatous cells in an atrial myxoma tissue section. D: Immunohistochemical staining for numerous CD3-positive cells in a myxoma tissue section. E: Immunohistochemical staining for CD8-positive cells in a myxoma tissue section. F: Immunohistochemical staining for Ki67 expression in smooth muscle cells or possible endothelial cells. Original magnifications: A, C, D, and F, ×200; B, ×100; E, ×400.

Figure 2.

Detection of HSV-1 antigens in atrial myxoma. Immunohistochemical staining of a myxoma tissue section, showing HSV-1 antigens in myxomatous cells (brown deposits), with the antiserum (A) or Mab (C). B: No signal of immunostaining of HSV-1 antigens was found with universal negative control reagents in an adjacent section. D: Immunostaining of HSV-1 antigens in endothelial cells and smooth muscle cells in thick-walled vessels with the Mab (D) or antiserum (F). E: No signal of immunostaining of HSV-1 antigens was found with universal negative control reagents in a consecutive section. Original magnifications: A and B, ×100; C, D, E, and F, ×200.

Figure 3.

Agarose gel electrophoresis of PCR products. HSV-1 (top) and β-globin (bottom) PCR products from atrial myxoma tissue samples or from amniotic embolism were resolved in 2% agarose gel stained with ethidium bromide. Lane 1: 100 bp DNA ladder; lanes 2 to 11: atrial myxoma cases; lanes 12 and 13: amniotic embolism; lane 14: reagent control.