Case 5 -
"Borderline" PVB19 Acute Myocarditis
Christina Basso, Istituto di Anatomia Patologica, Padova, Italy
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M.A., Male 33 Year Old
Italian monk was found death in his cell.
Asymptomatic. Healthy past medical history.
No alcohol, smoke and drug addiction.
No 12 lead ECG tracing was available for revision.
Negative family history of sudden death (SD).
Medico-legal autopsy ruled out unnatural and extracardiac causes of death.
Tissues, blood and other fluids for toxicology and molecular pathology were taken before fixing the
tissues and the whole heart in formalin 10%, as suggested by the European guidelines for autopsy
investigation of SD (Basso et al., 2008).
Gross examination of the heart: Heart weight of 360 gr, transverse diameter 10,5 cm, longitudinal
diameter 9 cm. LV wall thickness 10 mm, septal thickness 12 mm, RV free wall 3 mm. Origin and course of
coronary arteries are normal, with a non obstructive eccentric plaque in the left anterior descending
branch. Semilunar and atrioventricular valves are normal.
Histology of the myocardium (fig.2). Rare focal
inflammatory infiltrates >14 cells/mm2, mostly consisting of T-lymphocyte at immunohistochemistry
(CD43 and CD3 positive) were found, in the absence of clear-cut evidence of myocyte necrosis, small
vessel disease, and fibro-fatty replacement (fig.1). Myofibers waviness was an additional finding.
A toxicological panel was negative and drug addiction was rule out.
Molecular analysis revealed the presence of parvovirus B19 (PVB19) DNA in the myocardium, whereas it
was negative on extra cardiac samples (spleen and blood), thus excluding a contamination.
Negative PCR/RT-PCR results were obtained for other cardiotropic virus.
1. The heart is normal at gross examination.
2-5. histological sections of the left ventricular myocardium, showing focal mononuclear infiltrates HE (2,4: x250 (3,5: x320, close –up of 2,4).
A final diagnosis of "borderline" PVB19 acute myocarditis was put forward as possible cause of SD.
Up to 20% of SD among young adults and athletes are the consequence of acute myocarditis (Basso C et
According to the Dallas criteria for diagnosis and classification of myocarditis in endomyocardial
biopsies from affected patients (Aretz HT et al., 1987), myocarditis is diagnosed by traditional
hematoxylin–eosin staining in the setting of an inflammatory infiltrate of the myocardium with necrosis
and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary
artery disease. However, Dallas criteria apply strictly to endomyocardial biopsy in living patients and
their sensitivity has often been questioned. Immunohistochemical techniques allow more sensitive
detection and characterisation of inflammatory infiltrates (Calabrese et al, 2003). The major pending
issue is the differential diagnosis between "physiologic" and "pathologic" inflammatory cell infiltrates
in the myocardium (Basso et al, 2008). The presence of inflammatory cells infiltrates in the
interstitium of "normal" myocardium is still a controversial issue. A cut off of five lymphocytes per
high power field has been proposed for positive inflammatory cell infiltrate. The Marburg group
suggested 14 cells/mm2 at immunohistochemisty as a quantitative criterion for inflammation (Maisch et
al, 1995). In the case herein reported the histopathological findings are scanty and a diagnosis of
"borderline myocarditis" could have been put forward.
Different cardiotropic viruses have long been recognized as the most common infectious cause of
myocarditis. Among the infective agents implicated, the enterovirus and adenovirus are the most
frequents. More recently, several studies revealed a significant prevalence of PVB19 ranging from 2.5%
to 60% (Caforio et al, 2007; Mahrholdt et al., 2006, Bock et al, 2010) also in the immunocompetent adult.
However, the PVB19 was detected also in healthy transplant donors (Donoso Mantke et al., 2005), in
autoptic samples without myocarditis (Schenk et al., 2009), in patients undergoing myocardial biopsy
other reasons (Wang et al., 2004) or cardiac surgery for conditions not associated with viral infections
(Kuethe et al, 2009), possibly as a consequence of previous infection. More recently, Stewart et al
reported that, in series of adult patients with heart failure, PVB19 was associated with a wide spectrum
of clinical presentation and did not support the causative role for PVB19 persistence, advocating against
the use for antiviral therapy for these patients (Stewart et al 2011).
Some authors suggest that PVB19 can cause myocyte damage indirectly. In situ hybridization revealed
that PVB19 could infect endothelial cells of myocardial vessels, inducing endothelial dysfunction and
migration of inflammatory cells into the interstitium with subsequent myocyte damage (Mahrholdt et al.,
2006; Klingel et al., 2002). Alternatively, it has been proposed that myocarditis arises from
immunological cross-reaction to epitopes shared between the virus and the myocardium (Murry, 2001).
Since PVB19 is a frequent and common infection while myocarditis is a rare event, the involvement of
other factors, both host and virus related, should be investigated to address a true causal role of the
The non-availability of ECG tracing does not exclude both conduction system disease such as
ventricular preexcitation and inherited ion channel disorder, such as long QT and short QT syndromes,
Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, which present with
well-defined abnormalities of basal or effort ECG.
In this setting, the availability of ECG tracings may be crucial for the diagnosis and molecular studies
Thus, although PVB19 acute focal myocarditis seems the most reasonable cause of SD in the case herein
reported, due to ventricular arrhythmias, the scanty histologic features in keeping with "borderline"
myocarditis and the debatable significance of PVB19 DNA in the myocardium suggest to put forward a
descriptive diagnosis instead of a definitive one, accordingly to the AECVP guidelines (Basso et al.,
- Aretz HT, Billingham ME, Edwards WD, Factor SM,
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