Case 2 -
Active Lymphocytic Myocarditis
Office of the Chief Medical Examiner
New York, NY
Click on each slide thumbnail image for an enlarged view
This previously healthy 30 year old obese woman presented to the emergency room with shortness of
breath and weakness. She also had nausea, vomiting, diarrhea, right subscalpular pain, and flank pain.
She was febrile and tachycardic. Her oxygen saturation on room air was 99%. Lab results revealed a
white blood cell count of 22,000, and urine analysis was positive for leucocyte esterase and many white
blood cells. She was diagnosed with pyelonephritis and discharged with PO antibiotics.
The next day she presented to the emergency room again with worsening shortness of breath. She was
hypotensive and tachypnic. Her oxygen saturation was 90% on room air. A chest x-ray was normal. EKG
showed ST elevations. Labs revealed a troponin of 119 and CPK of 960. She developed ventricular
tachycardia and ventricular fibrillation, and could not be resuscitated. The case was reported to and
accepted by the Office of Chief Medical Examiner of the City of New York based on the sudden and
unexpected nature of this woman's death.
Case 2 - Figure 1 - H&E stained section of myocardium shows the diffuse nature of the interstitial inflammatory infiltrate.
Case 2 - Figure 2 - H&E stained section of myocardium shows the mainly mononuclear interstitial inflammatory infiltrate and associated myocyte damage.
Case 2 - Figure 3 - H&E stained section of myocardium , shows that the inflammatory infiltrate is mainly composed of lymphocytes with scattered plasma cells, and the occasional neutrophil, with associated myocyte destruction.
Case 2 - Figure 4 - H&E stained section of myocardium, high power, shows that the inflammatory infiltrate is mainly composed of lymphocytes with scattered plasma cells, and the occasional neutrophil, with associated myocyte destruction.
The body is that of a well-developed, 5'6", 239 lb white woman whose appearance is consistent with the
given age of 30 years. There is no skin rash.
The slightly soft heart weighs 450 gm and has a normal distribution of right predominant coronary
arteries without atherosclerotic stenosis of the epicardial vessels. The epicardial surface is
unremarkable. The myocardium is homogenous, dark red, and firm without pallor, hemorrhage, or fibrosis.
The left ventricle wall is 1.2 cm, and the right is 0.3 cm thick. The foramen ovale is closed. The
endocardial surfaces and cardiac valves are unremarkable. There are no congenital anomalies.
The other organ systems are unremarkable. There is no evidence of pyelonephritis.
Multiple sections of myocardium reveal a dense lymphocytic infiltrate with few plasma cells,
macrophages, and neutrophils throughout the heart. Occasional eosinophils are present. The inflammation
is associated with extensive myocyte necrosis of individual and groups of myocytes. Focal interstitial
edema is present.
Histology of the other major organs is unremarkable. In particular, multiple sections of kidney and
bladder reveal no inflamation.
Active Lymphocytic Myocarditis
Myocarditis is a disease of the myocardium characterized by an inflammatory infiltrate associated with
. Etiologies include infectious, hypersensitivity, and immune-related injury.
The incidence of myocarditis is difficult to estimate as the clinical spectrum is wide, ranging from
subclinical, to congestive heart failure, to sudden death. It is estimated that myocarditis is
responsible for approximately 5% of sudden deaths when marked atherosclerotic cardiovascular disease is
Grossly in the active phase of myocarditis, the heart may appear normal or show focal or diffuse areas
of mottling and softening. Mottling refers to areas of pallor alternating with areas of hemorrhage. The
heart may be normal size or enlarged with cardiac chamber dilatation . In those surviving the active
phase, healed myocarditis may result in a normal appearing heart, or there may be areas of fibrosis.
These are usually patchy and in no apparent vascular distribution, unlike a healed ischemic infarct.
Dilated cardiomyopathy may also result from a healed myocarditis.
The Dallas criteria were developed to establish uniform, reproducible criteria for the endomyocardial
biopsy diagnosis of myocarditis. They define idiopathic myocarditis as "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"
. Histologically, active myocarditis is
characterized by an interstitial mononuclear (predominantly lymphocytic) inflammatory infiltrate with
associated myocyte damage. Myocyte damage includes myocytolysis, irregular myocyte contours, and
necrosis/apoptosis. There may be interstitial edema. Giant cell myocarditis is marked by a fulminant
clinical course and the histologic presence of multinucleated giant cells .
The mechanism by which myocarditis produces myocyte damage is unclear. The role of the immune system,
be it through T-cell dependent mechanisms or soluble mediators, is thought to be important, as are host
and viral genetics
. Direct viral cytotoxicity is thought to be less important.
The major causes of myocarditis are listed in the table below:
From: Winters, G.L, McManus, B.M. Myocarditis. In: Silver, M.D., Gottlieb, A.I., Schoen, F.J. (eds.), Cardiovascular Pathology. Churchill Livingstone, 2001. 257.
They include infectious agents, (particularly
viruses such as enteroviruses), immune-mediated damage (including hypersensitivity), and toxic reactions.
Documentation of a viral etiology is often difficult but can be attempted by immunohistochemistry, in situ hybridization, or polymerase chain reaction. Myocarditis has also been
associated with human immunodeficiency virus , parasitic infections and systemic diseases such as
rheumatoid arthritis and collagen vascular diseases. Hypersensitivity myocarditis is the result of a
drug exposure and is characterized by a predominance of eosinophils in the inflammatory infiltrate and
less myocyte necrosis. Fibrosis is absent .
The differential diagnosis of myocarditis is wide and highly dependent on the composition of the
From: Winters, G.L, McManus, B.M. Myocarditis. In: Silver, M.D., Gottlieb, A.I., Schoen, F.J. (eds.), Cardiovascular Pathology. Churchill Livingstone, 2001. 258.
Distinguishing myocarditis from ischemic damage can be difficult. As
a rule, in myocarditis, the degree of inflammation is greater than the associated myocyte damage. The
presence of many neutrophils should raise the suspicion of ischemic damage, which is far more common than
myocarditis. Myocarditis can be a very focal disease. Therefore, it is essential that the myocardium be
widely sampled to rule out this diagnosis. As routine autopsy practice, we sample at least 10 sections
of myocardium in this setting.
The complete investigation of a sudden death must include a complete autopsy with toxicology and
appropriate histology, as well as a scene investigation and interviews with family and physicians. Cases
of witnessed, instantaneous death without structurally demonstrable cause at autopsy lead to the
compelling conclusion that the decedent had a lethal cardiac arrhythmia. Occasionally the only finding
in such a case with be a small focus of inflammation associated with myocyte destruction. Although such
foci can be found incidentally in traumatic deaths, one must evaluate this finding in the context of the
particular case. Since myocarditis is known to be a focal disease, it is possible that other, more
significant foci are present but unsampled. The significance of such a small focus in and of itself is
unknown. Caution is advisable with its interpretation, but it should be considered a plausible cause of
death in the appropriate setting.
- Aretz, H.T. Myocarditis: The Dallas criteria. Human Pathology. 1987. 18:619-624.
- Olinde, K.D., O=Connell, J.B. Inflammatory heart disease: Pathogenesis, clinical manifestations, and treatment of myocarditis. Ann Rev Med 1994. 45:481-490.
- Winters, G.L, McManus, B.M. Myocarditis. In: Silver, M.D., Gottlieb, A.I., Schoen, F.J. (eds.), Cardiovascular Pathology. Churchill Livingstone, 2001. 256-284.
- Virmani, R. Burke, AP, Farb, A., Smialek, J. Problems in forensic cardiovascular pathology. In: Schoen, F.J., Gimbrone, M.A., Jr. (eds.), Cardiovascular Pathology: Clinicopathologic correlations and pathogenetic mechanisms. Williams and Wilkins, 1995. 173-193.
- Aretz, H.T. Billingham, M.E., Edwards, W.D., et al. Myocarditis: A histopathologic definition and classification. American J. Cardiovasc. Pathol. 1987. 1:3-14.
- Cooper, L.T., Berry, G.J., Shabetai, R. Idiopathic giant cell myocarditis- natural history and treatment. N Engl J. Med. 1997. 336:1860-1866.
- Barry, W.H. Mechanisms of immune-mediated myocyte injury. Circulation. 1994. 89:2421-2432.
- Maisch, B. Ristic, A.D., Hufnagel, G., Pankuweit, S. Pathophysiology of viral myocarditis: the role of humoral immune response. Cardiovascular Pathology. 2002. 11(2}:112-122.
- Klatt, E.C. Cardiovascular Pathology in AIDS. Adv. Cardiol. 2003. 40:23-48.
- Burke, A.P., Saenger, J., Mullick, F., Virmani, R. Hypersensitivity myocarditis. Arch. Pathol. Lab Med. 1991. 115:764-769.