title: Quantitative diagnosis of lymphocytic myocarditis in forensic medicine.
abstract: The aim of this study was to establish quantitative diagnostic criteria for lymphocytic myocarditis on autopsy samples by using a stereological cell profile counting method. We quantified and compared the presence of lymphocytes and macrophages in myocardial autopsy specimens from 112 deceased individuals who had been diagnosed with myocarditis according to the Dallas criteria and 86 control subjects with morphologically normal hearts. We found the mean number to be 52.7 lymphocyte profiles/mm(2) (range 3.7-946; standard deviation 131) in the myocarditis group and 9.7 (range 2.1-25.9; standard deviation 4.6) in the control group. The cut-off value for the diagnosis of myocarditis was determined by calculating sensitivity plus specificity, which reached the highest combination at 13 lymphocyte profiles/mm(2) (sensitivity 68%; specificity 83%). A considerable proportion of subjects in both the myocarditis and control groups had lymphocyte profile counts below 30/mm(2), representing a diagnostic challenge due to the increased risk of creating false negative or false positive results. We found it practically impossible to obtain a reliable macrophage count. The present data add new important information on lymphocyte counts in inflamed and non-inflamed myocardium. We suggest a cut-off value in the range of 11-16 lymphocyte profiles/mm(2) for a reliable diagnosis of lymphocytic myocarditis from autopsy samples. To evaluate small inflammatory changes at low lymphocyte counts, a multidisciplinary approach should be implemented, in which diagnostic tools are used ancillary to histological examination. We advise against semi-quantification of macrophages based on cell profile counting.
authors.affiliation: Centre for Clinical Research, Vendsyssel Hospital/Department of Clinical Medicine, Aalborg University, Bispensgade 37, 9800 Hjørring, Denmark; Department of Forensic Medicine, Aarhus University, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. Electronic address: tsn@retsmedicin.au.dk.
authors.forename: Trine Skov
authors.initials: TS
authors.lastname: Nielsen
authors.affiliation: Stereology and EM Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Jens Randel
authors.initials: JR
authors.lastname: Nyengaard
authors.affiliation: Department of Mathematical Sciences, Aalborg University, Fredrik Bajers Vej 7, 9220 Aalborg Ø, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Møller
authors.affiliation: Department of Forensic Medicine, Aarhus University, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark; Department of Forensic Medicine, Copenhagen University, Frederik V's Vej 11, 2100 Copenhagen Ø, Denmark.
authors.forename: Jytte
authors.initials: J
authors.lastname: Banner
authors.affiliation: Department of Virology/Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: Lars Peter
authors.initials: LP
authors.lastname: Nielsen
authors.affiliation: Centre for Clinical Research, Vendsyssel Hospital/Department of Clinical Medicine, Aalborg University, Bispensgade 37, 9800 Hjørring, Denmark.
authors.forename: Ulrik Thorngren
authors.initials: UT
authors.lastname: Baandrup
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D049429:Forensic Pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000175:diagnosis*; D009206:Myocardium / Q000473:pathology*; D012680:Sensitivity and Specificity; D055815:Young Adult
keywords: Forensic pathology; Immunohistochemistry; Lymphocytic myocarditis; Quantitative microscopy