Final Diagnosis -- Idiopathic Giant Cell Myocarditis


Contributor's note

Idiopathic giant cell myocarditis was first described in 1905 by Saltykow (1) and has in the past been synonymously referred to as Fiedler's myocarditis. It is a rare and often rapidly fatal form of myocarditis of unknown etiology. The majority of patients present with congestive cardiac failure or conduction disturbances. Post mortem examinations have shown the conduction disturbances to be due to bilateral bundle branch block secondary to involvement of the interventricular septum by the inflammatory process (2). Segmental wall motion disturbances have been demonstrated (2), suggesting that giant cell myocarditis (GCM) can be a focal as well as a diffuse process at specific stages of its evolution. Idiopathic giant cell myocarditis is, for the most part, a disease of young and previously healthy adults with reported mean ages of 37 years (five patients), 48 years (five patients) and 42.6 +/- 12.7 years (sixty three patients), in three different series (2-4). The youngest patient reported was six weeks old (5) and the oldest 88 years old (6). The relative infrequency of reported cases in the elderly may be partially attributable to a more or less fulminant course of disease in this population, as well as to a decreased level of suspicion in these patients who often have other cardiovascular problems, as in this patient.

Many autoimmune disorders have been cited to be associated with GCM, including Hashimoto's thyroiditis, myasthenia gravis, ulcerative colitis, rheumatoid arthritis, pernicious anemia, Takayasu's arteritis and orbital myositis (2,7,8). One recent series reported 19% of sixty three patients to have an associated autoimmune disorder (4). These associations, and the reproducibility of experimental GCM in Lewis rats by autoimmunization with myosin (9), suggest that it is an autoimmune disorder dependent on CD-4 positive T lymphocytes. Further support for an autoimmune etiology is the reported response to immunosuppressive therapy. Although this patient had a history of hypothyroidism, there was no previous diagnosis of Hashimoto's thyroiditis, nor was there available laboratory data to substantiate this. Forthermore, the restrictions imposed on the autopsy prevented post mortem examination of the thyroid gland.

The gross and microscopic features described in this case are quite characteristic of this entity, the only exception being biventricular hypertrophy. Most patients described have cardiomegaly with biventricular dilatation, but in this elderly patient with severe coronary artery disease, there was an element of superimposed hypertrophy.

Several controversial issues have surround this uncommon and poorly understood entity. One such debate is the origin of the giant cells. Earlier authors have suggested a myogenic origin, since the giant cells are often located adjacent to necrotic myocytes and ultrastructural observations have shown them to contain cytoplasmic fibrils interpreted as myofilaments (6,10). However, with the advent of immunohistochemical stains, a monocyte / macrophage lineage of the giant cells, showing positive immunoreactivity with KP-1 (CD68) and an absence of staining with the muscle markers, actin and desmin, has been confirmed (2,7,11). In addition, there is ultrastructural evidence of a histiocytic origin, with abundant sarcoplasmic reticulum and cytoplasmic lysosomal vacuoles in these cells (2). A plausible explanation for the cytoplasmic myofilaments previously described is phagocytic engulfment of damaged myofilaments.

The possible relationship to differentiation of GCM and cardiac sarcoidosis has been yet another point of contention. Some authors do not distinguish between GCM and cardiac sarcoidosis (12,13), buts most recent studies suggest that the former is a distinct and well-defined entity (6,14,15). Suggested histopathological differences between the two include:

  1. The absence of well formed granulomata in GCM as opposed to cardiac sarcoidosis.
  2. The lack of involvement of the epicardial fat in GCM, while in most cases of cardiac sarcoidosis, granulomata were seen in the epicardial fat.
  3. The prominent eosinophilia in the inflammatory infiltrate seen in GCM is in general absent in cardiac sarcoidosis.
These findings, in addition to the absence of extracardiac granulomata, are helpful in differentiating these two entities. Infectious granulomatous myocarditis, rheumatic myocarditis and lymphocytic myocarditis are other conditions to be included in the differential diagnosis. Infectious granulomatous myocarditis often has necrotizing (granulomata) and should be excluded with histochemical stains and cultures. Rheumatic myocarditis is characterized by the presence of interstitial Aschoff bodies, typically adjacent to small intramyocardial arteries, and an absence of widespread necrosis. In idiopathic lymphocytic myocarditis there is a paucity of giant cells and absence of large foci of necrosis. The prognosis of GCM is poor, with a reported median survival of 5.5 months from onset of symptoms to death / transplantation (4). Rapid hemodynamic deterioration with rhythm and conduction disturbances is in general the natural history of the disease. Often the diagnosis is only established post mortem, as in this patient's case. Astute clinical suspicion with endomyocardial biopsy is warranted for the premortem diagnosis.

Clinical trials have suggested immunosuppressive therapy with regimens which include cyclosporine, azathioprine or both, may prolong life. Corticosteroids alone have not been therapeutically successful (2,4). The ultimate possibility for long term survival is cardiac transplantation. Noteworthy, however, are thirteen reported cases of recurrent idiopathic giant cell myocarditis in the transplanted heart, some of which were fatal (4).


  1. Saltykow S. Uber diffuse myokarditis. Arch Pathol Lab Med Anat. 1905;182:1.
  2. Cooper LT Jr., Berry GJ, Rizek M, Schroeder JS. Giant cell myocarditis. J Heart Lung Transplant 1995;14:394-401.
  3. Davidoff R, Palacios I, Southern J, Fallon JT, Newell J, Dec GW. Giant cell vs lymphocytic myocarditis: a comparison of their clinical features and long term outcomes. Circulation 1991;83:953-961.
  4. Cooper LT Jr., Berry GJ, Shabetai R. Idiopathic giant cell myocarditis - natural history and treatment. N Engl J Med 1997;336:1860-1866.
  5. Goldberg GM. Myocaditis of giant-cell type in an infant. Am J Clin Pathol 1955;25:510-513.
  6. Davies MJ, Pomerance A, Teare RD. Idiopathic giant cell myocarditis - a distinctive clinico-pathological entity. Br Heart J 1975;37:192-195.
  7. Ariza A, Lopez MD, Mate J, Curos A, Billagrasa M, Navas-Palacios JJ. Giant cell myocarditis: monocytic immunophenotype of giant cells in a case associated with ulcerative colitis. Hum Pathol 1995;26:121-123.
  8. Humbert P, Fivre R, Fellman D, Bassand JP, Dupond JL, France B. Giant cell myocarditis: an autoimmune disease? Am Heart J 1988;115:485-748.
  9. Kodama M, Matsumoto Y, Fujiwara M, Masani F, Izumi T, Shibata A. A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. Clin Immunol Immunopathol 1990;57:250-262.
  10. Pyun KS, Kim YH, Kalzenstein RE, Kikkawa Y. Giant cell myocarditis: light and electron microscopic study. Arch Pathol 1970;90:181-188.
  11. Ren H, Poston RS, Hruban RH, Baumgartner WA, Baughmwn KL, Hutchins GM. Long survival with giant cell myocarditis. Mod Pathol 1993;6:402-407.
  12. Naramoto A, Ishii K, Nakazawa K, Shigematsu H, Takamatsu M. A case of latent cardiac sarcoidosis in reference to differential diagnosis from giant cell myocarditis. Kokyu To Junkan 1990;38:77.
  13. Roberts WC, McAllister HA Jr., Ferrans VJ. Sarcoidosis of the heart - a clinico-pathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 2). Am J Med 1977;63:86.
  14. Tubbs RR, Sheibani K, Hawk WA. Giant cell myocarditis. Arch Pathol Lab Med 1980;104:245.
  15. Litovski S, Burke AP, Virmani R. Giant cell myocarditis: an entity distinct from sarcoidosis characterized by multiphasic myocyte destruction by cytotoxic T cells and histiocytic giant cells. Mod Pathol 1996;9:1126-1134.

Contributed by Shashi Ariyanayagam-Baksh, MBBS


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