Abstract
The standard for the histopathologic diagnosis of myocarditis has been the Dallas criteria. Recently, immunohistochemical studies that include the specification and quantification of interstitial inflammatory cells have been proposed as the diagnostic approach for myocarditis. Cut-off limits regarding inflammatory cell numbers for the positive diagnosis of myocarditis have been recommended. However, it is unclear whether these can be applied to postmortem tissues or to infants, as they were established from endomyocardial biopsies and for adults. Nevertheless, cut-off limits for the postmortem diagnosis of myocarditis in the first year of life have been proposed. Studies using these cut-off limits identified myocarditis in a high percentage of presumed sudden infant death syndrome (SIDS) cases. These results were re-evaluated by the present study, which examined heart specimens from infants less than 1 year of age. The study had a test group of 92 SIDS cases and a control group of 15. Myocardial tissue was examined from eight standardized locations, stained with hematoxylin-eosin and for three different immunohistochemical reagents (LCA for leukocytes, CD68 for macrophages, CD45-RO for T-lymphocytes). Histopathological assessment of the number of inflammatory cells was carried out on an aggregate of 80 mm2 of myocardial tissue per case. Myocarditis, based on the Dallas criteria, was histologically diagnosed in only two cases. Immunohistochemical quantification revealed elevated cell counts in the SIDS group for LCA and CD45-RO. However, those differences were neither statistically significant nor clinically relevant as the mean cell counts per mm2 were low. The density of inflammatory cells differed considerably from section to section and even within single sections. Therefore the commonly used arithmetic mean value was not diagnostically relevant, suggesting cut-off values based on the arithmetic mean value as recommended in the literature, cannot be regarded as valid. At least in infants, the diagnosis of myocarditis from autopsy tissues still requires application of the Dallas criteria. Immunohistochemical methods cannot replace the conventional diagnosis of myocarditis.
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Angelini A, Calzolari V, Calabrese F, Boffa GM, Maddalena F, Chioin R, Thiene G. Myocarditis mimicking acute myocardial infarction: role of endomyocardial biopsy in the differential diagnosis. Heart. 2000;84:245–50.
Chimenti C, Pieroni M, Maseri A, Frustaci A. Histologic findings in patients with clinical and instrumental diagnosis of sporadic arrhythmogenic right ventricular dysplasia. JACC. 2004;43:2305–13.
Cooper LT. Myocarditis. N Engl J Med. 2009;360:1526–38.
Klein RM, Vester EG, Brehm MU, Dees H, Picard F, Niederacher D, et al. Entzündung des Myokards als Arrhythmietrigger. Z Kardiol. 2000;89:III24–35.
Kühl U, Pauschinger M, Bock T, Klingel K, Schwimmbeck PL, Seeberg B, et al. Parvovirus B19 infection mimicking acute myocardial infarction. Circulation. 2003;108:945–50.
Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006;114:1581–90.
Pankuweit S, Maisch B. Das Herz bei viralen Infektionen. Internist. 2010;51:836–43.
Casali MB, Lazzaro A, Gentile G, Blandino A, Ronchi E, Zoja R. Forensic grading of myocarditis: an experimental contribution to the distinction between lethal myocarditis and incidental myocarditis. Forensic Sci Int. 2012;223:78–86.
Beckwith JB. The sudden infant death syndrome. Curr Probl Pediatr. 1973;3:1–36.
DeSa DJ. Isolated myocarditis in the first year. Arch Dis Child. 1985;60:484–5.
Dettmeyer R, Schlamann M, Madea B. Immunohistochemical techniques improve the diagnosis of myocarditis in cases of suspected sudden infant death syndrome. Forensic Sci Int. 1999;105:83–94.
Dettmeyer R. Plötzlicher Kindstod. Neue Aspekte zur Bedeutung der virusbedingen Herzmuskelentzündung. Aachen: Shaker; 2004.
Dettmeyer R, Baasner A, Haag C, Bruch S, Schlamann M. Immunohistochemical and molecular-pathological diagnosis of myocarditis in cases of suspected sudden infant death syndrome (SIDS)—a multicenter study. Leg Med (Tokyo). 2009;11:124–7.
Krous HF, Ferandos C, Masoumi H, Arnold J, Haas EA, Stanley C, Grossfeld PD. Myocardial inflammation, cellular death, and viral detection in sudden infant death caused by SIDS, suffocation or myocarditis. Pediatr Res. 2009;66:17–21.
Rambaud C, Cieuta C, Canioni D, Rouzioux C, Lavaud J, Hubert P, et al. Cot death and myocarditis. Cardiol Young. 1992;2:266–71.
Rasten-Almquist P, Eksborg S, Rajs J. Myocarditis and sudden infant death syndrome. APMIS. 2002;110:469–80.
Shatz A, Hiss J, Arensburg B. Myocarditis misdiagnosed as sudden infant death syndrome (SIDS). Med Sci Law. 1997;37:16–8.
Weber MA, Ashworth MT, Risdon RA, Malone M, Burch M, Sebire NJ. Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series. Arch Dis Child. 2008;93:594–8.
Byard RW. Sudden death in the young. 3rd ed. Cambridge: University Press; 2010.
Hort W. Pathologie des Endokard, der Kranzarterien und des Myokard. Berlin: Springer; 1999.
Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ Jr, et al. Myocarditis. A histopathological definition and classification. Am J Cardiovasc Pathol. 1987;1:3–14.
Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol. 1987;18:619–24.
Billingham ME. The diagnostic criteria of myocarditis by endomycardial biopsy. Heart Vessels Suppl. 1985;1:133–7.
Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Circulation. 2006;113:593–5.
Hauck AJ, Kearney DL, Edwards WD. Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error. Mayo Clin Proc. 1989;64:1235–45.
Chow LH, Radio SJ, Sears TD, McManus BM. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. JACC. 1989;14:915–20.
Shanes JG, Ghali J, Billingham ME, Ferrans VJ, Fenoglio JJ, Edwards WD, et al. Interobserver variability in the pathologic interpretation of endomyocardial biopsy results. Circulation. 1987;75:401–5.
Dennert R, Crijns HJ, Heymans S. Acute viral myocarditis. Eur Heart J. 2008;29:2073–82.
Forcada P, Beigelman R, Milei J. Inapparent myocarditis and sudden death in pediatrics. Diagnosis by immunohistochemical staining. Int J Cardiol. 1996;56:93–7.
Klingel K, Sauter M, Bock CT, Szalay G, Schnorr JJ, Kandolf R. Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol. 2004;193:101–7.
Kühl U, Pauschinger M, Schultheiss HP. Neue Konzepte zur Diagnostik der entzündlichen Herzmuskelentzündung. Dtsch Med Wschr. 1997;122:690–8.
Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113:876–90.
Maisch B, Portig I, Ristic A, Hufnagel G, Pankuweit S. Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus. A status report. Herz. 2000;25:200–9.
Strauer BE, Kandolf R, Mall G, Maisch B, Mertens T, Figulla HR, et al. Update 2001. Myokarditis-Kardiomyopathie. Med Klin. 2001;96:608–25.
Dettmeyer R, Baasner A, Schlamann M, Padosch SA, Haag C, Kandolf R, Madea B. Role of virus-induced myocardial affections in sudden infant death syndrome: a prospective postmortem study. Pediatr Res. 2004;55:947–52.
Madea B. Sudden death, especially in infancy–improvement of diagnosis by biochemistry, immunohistochemistry and molecular pathology. Legal Med. 2009;11:36–42.
Edwards WD, Holmes DR Jr, Reeder GS. Diagnosis of active lymphocytic myocarditis by endomyocardial biopsy: quantitative criteria for light microscopy. Mayo Clin Proc. 1982;57:419–25.
Foley DA, Edwards WD. Quantitation of leukocytes in endomyocardial tissue from 100 normal human hearts at autopsy. Implications for diagnosis of myocarditis from biopsy specimens of living patients. Am J Cardiovasc Pathol. 1988;2:145–9.
Rognum TO, Arnestad M, Bajanowski T, Banner J, Blair P, Borthne A, et al. State of the art conference on the stratification of SUDI. Consensus on diagnostic criteria for the exclusion of SIDS. Nordisk Rettsmedisin. 2003;3/4:49–88.
Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T, et al. Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics. 2004;114:234–8.
Baandrup U, Olsen EGJ. Critical analysis of endomyocardial biopsies from patients suspected of having cardiomyopathy. Br Heart J. 1981;45:475–86.
Cunningham KS, Veinot JP, Butany J. An approach to endomyocardial biopsy interpretation. J Clin Pathol. 2006;59:121–9.
Konno S, Sakakibara S. Endo-Myocardial Biopsy. Dis Chest. 1963;44:345–50.
Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Eur Heart J. 2007;28:3076–93.
Kitulwatte ID, Kim PJ, Pollanen MS. Sudden death related myocarditis: a study of 56 cases. Forensic Sci Med Pathol. 2010;6:13–9.
Nielsen TS, Nyengaard JR, Møller J, Banner J, Nielsen LP, Baandrup UT. Quantitative diagnosis of lymphocytic myocarditis in forensic medicine. For Sci Int. 2014;238:9–15.
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Grasmeyer, S., Madea, B. Immunohistochemical diagnosis of myocarditis on (infantile) autopsy material: Does it improve the diagnosis?. Forensic Sci Med Pathol 11, 168–176 (2015). https://doi.org/10.1007/s12024-015-9675-7
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DOI: https://doi.org/10.1007/s12024-015-9675-7