Skip to main content
Top
Published in: Forensic Science, Medicine and Pathology 2/2015

01-06-2015 | Original Article

Immunohistochemical diagnosis of myocarditis on (infantile) autopsy material: Does it improve the diagnosis?

Authors: Sarah Grasmeyer, Burkhard Madea

Published in: Forensic Science, Medicine and Pathology | Issue 2/2015

Login to get access

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.
Literature
1.
go back to reference 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
2.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference 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. 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.
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference Beckwith JB. The sudden infant death syndrome. Curr Probl Pediatr. 1973;3:1–36.PubMed Beckwith JB. The sudden infant death syndrome. Curr Probl Pediatr. 1973;3:1–36.PubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference Dettmeyer R. Plötzlicher Kindstod. Neue Aspekte zur Bedeutung der virusbedingen Herzmuskelentzündung. Aachen: Shaker; 2004. Dettmeyer R. Plötzlicher Kindstod. Neue Aspekte zur Bedeutung der virusbedingen Herzmuskelentzündung. Aachen: Shaker; 2004.
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference Rambaud C, Cieuta C, Canioni D, Rouzioux C, Lavaud J, Hubert P, et al. Cot death and myocarditis. Cardiol Young. 1992;2:266–71.CrossRef Rambaud C, Cieuta C, Canioni D, Rouzioux C, Lavaud J, Hubert P, et al. Cot death and myocarditis. Cardiol Young. 1992;2:266–71.CrossRef
16.
go back to reference Rasten-Almquist P, Eksborg S, Rajs J. Myocarditis and sudden infant death syndrome. APMIS. 2002;110:469–80.CrossRef Rasten-Almquist P, Eksborg S, Rajs J. Myocarditis and sudden infant death syndrome. APMIS. 2002;110:469–80.CrossRef
17.
go back to reference Shatz A, Hiss J, Arensburg B. Myocarditis misdiagnosed as sudden infant death syndrome (SIDS). Med Sci Law. 1997;37:16–8.PubMed Shatz A, Hiss J, Arensburg B. Myocarditis misdiagnosed as sudden infant death syndrome (SIDS). Med Sci Law. 1997;37:16–8.PubMed
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference Byard RW. Sudden death in the young. 3rd ed. Cambridge: University Press; 2010.CrossRef Byard RW. Sudden death in the young. 3rd ed. Cambridge: University Press; 2010.CrossRef
20.
go back to reference Hort W. Pathologie des Endokard, der Kranzarterien und des Myokard. Berlin: Springer; 1999. Hort W. Pathologie des Endokard, der Kranzarterien und des Myokard. Berlin: Springer; 1999.
21.
go back to reference 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, 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.
23.
go back to reference Billingham ME. The diagnostic criteria of myocarditis by endomycardial biopsy. Heart Vessels Suppl. 1985;1:133–7.CrossRefPubMed Billingham ME. The diagnostic criteria of myocarditis by endomycardial biopsy. Heart Vessels Suppl. 1985;1:133–7.CrossRefPubMed
24.
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference Chow LH, Radio SJ, Sears TD, McManus BM. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. JACC. 1989;14:915–20.CrossRefPubMed Chow LH, Radio SJ, Sears TD, McManus BM. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. JACC. 1989;14:915–20.CrossRefPubMed
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference Forcada P, Beigelman R, Milei J. Inapparent myocarditis and sudden death in pediatrics. Diagnosis by immunohistochemical staining. Int J Cardiol. 1996;56:93–7.CrossRefPubMed Forcada P, Beigelman R, Milei J. Inapparent myocarditis and sudden death in pediatrics. Diagnosis by immunohistochemical staining. Int J Cardiol. 1996;56:93–7.CrossRefPubMed
30.
go back to reference Klingel K, Sauter M, Bock CT, Szalay G, Schnorr JJ, Kandolf R. Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol. 2004;193:101–7.CrossRefPubMed Klingel K, Sauter M, Bock CT, Szalay G, Schnorr JJ, Kandolf R. Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol. 2004;193:101–7.CrossRefPubMed
31.
go back to reference Kühl U, Pauschinger M, Schultheiss HP. Neue Konzepte zur Diagnostik der entzündlichen Herzmuskelentzündung. Dtsch Med Wschr. 1997;122:690–8.CrossRefPubMed Kühl U, Pauschinger M, Schultheiss HP. Neue Konzepte zur Diagnostik der entzündlichen Herzmuskelentzündung. Dtsch Med Wschr. 1997;122:690–8.CrossRefPubMed
32.
go back to reference Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113:876–90.CrossRefPubMed Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113:876–90.CrossRefPubMed
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
34.
go back to reference Strauer BE, Kandolf R, Mall G, Maisch B, Mertens T, Figulla HR, et al. Update 2001. Myokarditis-Kardiomyopathie. Med Klin. 2001;96:608–25.CrossRef Strauer BE, Kandolf R, Mall G, Maisch B, Mertens T, Figulla HR, et al. Update 2001. Myokarditis-Kardiomyopathie. Med Klin. 2001;96:608–25.CrossRef
35.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
36.
go back to reference Madea B. Sudden death, especially in infancy–improvement of diagnosis by biochemistry, immunohistochemistry and molecular pathology. Legal Med. 2009;11:36–42.CrossRef Madea B. Sudden death, especially in infancy–improvement of diagnosis by biochemistry, immunohistochemistry and molecular pathology. Legal Med. 2009;11:36–42.CrossRef
37.
go back to reference 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.PubMed 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.PubMed
38.
go back to reference 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.PubMed 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.PubMed
39.
go back to reference 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. 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.
40.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
41.
44.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
45.
go back to reference Kitulwatte ID, Kim PJ, Pollanen MS. Sudden death related myocarditis: a study of 56 cases. Forensic Sci Med Pathol. 2010;6:13–9.CrossRefPubMed Kitulwatte ID, Kim PJ, Pollanen MS. Sudden death related myocarditis: a study of 56 cases. Forensic Sci Med Pathol. 2010;6:13–9.CrossRefPubMed
46.
go back to reference 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. 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.
Metadata
Title
Immunohistochemical diagnosis of myocarditis on (infantile) autopsy material: Does it improve the diagnosis?
Authors
Sarah Grasmeyer
Burkhard Madea
Publication date
01-06-2015
Publisher
Springer US
Published in
Forensic Science, Medicine and Pathology / Issue 2/2015
Print ISSN: 1547-769X
Electronic ISSN: 1556-2891
DOI
https://doi.org/10.1007/s12024-015-9675-7

Other articles of this Issue 2/2015

Forensic Science, Medicine and Pathology 2/2015 Go to the issue