Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease
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Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease Cristina Basso • Fiorella Calabrese Annalisa Angelini • Elisa Carturan Gaetano Thiene
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Ó Springer Science+Business Media New York 2012
Abstract In the WHO 1996 classification of cardiomyopathies, myocarditis is defined as an ‘‘inflammatory disease of the myocardium associated with cardiac dysfunction’’ and is listed among ‘‘specific cardiomyopathies’’. Myocarditis is diagnosed on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria, and molecular techniques are recommended to identify viral etiology. Infectious, autoimmune, and idiopathic forms of inflammatory cardiomyopathy are recognized that may lead to dilated cardiomyopathy. According to Dallas criteria, myocarditis is diagnosed in the setting of an ‘‘inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes, not typical of ischemic damage associated with coronary artery disease’’. The majority of experts in the field agree that an actual increase in sensitivity of EMB has now been reached by using immunohistochemistry together with histology. A value of [14 leukocytes/mm2 with the presence of T lymphocytes [7 cells/mm2 has been considered a realistic cut off to reach a diagnosis of myocarditis. The development of molecular biological techniques, particularly amplification methods like polymerase chain reaction (PCR) or nestedPCR, allows the detection of low copy viral genomes even from an extremely small amount of tissue such as in EMB This study was supported by the Registry for Cardio-cerebro-vascular Pathology, Veneto Region, Venice, Italy. C. Basso F. Calabrese A. Angelini E. Carturan G. Thiene (&) Pathological Anatomy, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Via A. Gabelli, 61, 35121 Padua, Italy e-mail: [email protected] C. Basso e-mail: [email protected]
specimens. Positive PCR results obtained on EMB should always be accompanied by a parallel investigation on blood samples collected at the time of the EMB. According to the recent Association for European Cardiovascular Pathology guidelines, optimal specimen procurement and triage indicates at least three, preferably four, EMB fragments, each 1–2 mm in size, that should immediately be fixed in 10 % buffered formalin at room temperature for light microscopic examination. In expected focal myocardial lesions, additional sampling is recommended. Moreover, one or two specimens should be snap-frozen in liquid nitrogen and stored at -80 °C or alternatively stored in RNA-later for possible molecular tests or specific stains. A sample of peripheral blood (5–10 ml) in EDTA or citrate from patients with suspected myocarditis allows molecular testing for the same viral genomes sought in the myocardial tissue. Keywords Cardiomyopathy Endomyocardial biopsy Histology Myocarditis Molecular pathology Pathology Viruses
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