Consultation interface between Pathologists and Forensic Science Experts for histopathology examination

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Consultation interface between Pathologists and Forensic Science Experts for histopathology examination V. Cirielli a,b, M. Brunelli c, F. Bortolotti a, Z. De Battisti a, G. Del Balzo a, A. De Salvia a, A. Eccher c, C. Laposata a, C. Ghimenton c, D. Raniero a, E. Vermiglio a, M.Portas a, A. Scarpa c, F.Tagliaro a, S.Turrina a andd.deleo a. a LegalMedicine, Department ofdiagnostics and Public Health, AOUI-Verona b Legal Medicine, Department ofprevention, ULSS 8Berica-Vicenza c Pathology, Department ofdiagnostics and Public Health, AOUI -Verona Background 1/189= <1% 1

Background 428 autopsy cases 8% cause of death determined by only histology Background Background Standards for the Practice of Forensic Pathology Key word 1998: discretion The extent of histopathological of the autopsy tissue is a the discretion of the pathologist 2

National Association of Medical Examiners(NAME) 2005 The forensic pathologist shall perform histological examination in causes of no gross anatomic or toxicological cause of deaths 1) sudden infant deaths 2) unexplained deaths 3) when necessary establish a tissue diagnosis Background Background Debate remains to how much the magnitude of histopathologic examination may be of benefit to medicolegal purposes 3

Objective& Aim We sought to address the question after reviewing consultation cases requested to pathologists from forensics by an AUDIT in a real word setting Material& Methods We reviewed Consultations performed in Anatomic-Pathology from an Hub single center (Verona) based on requests received from Legal-Medicine Institutes (forensic pathologists) January 2015 to August 2018 Audit - Database 4

Results: epidemiology 2015 yr: n. 124 2016 yr: n. 119 2017 yr: n. 134 2018 yr: n. 121 (august) total: 499 forensic autopsies 54 consultations have been performed along three years 54/499= 10.8% Results - Gross analysis was requested in 24/54 (44%) - Histopathology was requested in 31/54 (57%) performed as follows: 1) on single organs primary on lung&heart in 17/54 (31%) 2) whereas multi-organ sampling was performed in 14/54 (26%) 5

Results 3/54 6% infant sudden death(cardiac fibroelastosis, meconium aspiration syndromeaspirazione) 9/54 17% oncologicaltyping(histotype, grading, staging) 42/54 78% no grosscause of deathor needoftissue diagnosis(ruleout malignancy, other ) Results: multiorgan samplings Lungs Heart Liver Kidneys Brain Pancreas Adrenal glands Spleen Thyroid Parathyroid Vessels (Aortic) Bladder Entericsystem Genital tracts 90% 10% main organs minor Bone-marrow sampling was present in only 3/54 (5%) 6

Results - Special stains was needed in 16% of cases (9/54) - Immunohistochemistry was needed in 33% of cases (18/54) - Molecular analysis was needed in 4% of cases (2/54) - Standard methodology was needed in 15% of cases (8/54) Gross re-sampling Case no. 3 7

special stains: Masson trichromic Case no. 3 H&E and need of additional stains deposition of ialine membranes Case no. 16 8

special stains: Alcian-PAS deposition of ialine membranes Case no. 16 oncology suspicious of mesotelioma Case no. 22 9

immunohistochemical analysis calretinin Case no. 22 Case no. 22 Molecular analysis Patient A Patient B cancer no cancer exchange of bioptic material 10

cytogenetic FISH molecular analysis gross re-sampling caroli disease versus colangiocarcinoma 11

gross re-sampling doubled tissue block sampling asbestos fibers research 30 µm thick sections 12

asbestos fibers research Perls stain ICH Numberof cases Calretinin 3 immunohistochemical processes CD1a 1 CD3 6 CD8 2 CD15 2 CD20 8 CD34 1 CD45 2 CD61 1 CD68 6 CD71 1 CD79alfa 2 CD138PROTEIN 3 CDX2 protein 1 CK5 3 CK8/18 2 CK19 2 ChromograninA 1 Deltan-p63 2 EMA 2 - commercially available antibodies - standardization on formalin-fixed and paraffin embedded tissue - automation - robust processes - interpretation Fat VIII 1 GATA-3 1 HCG 1 HMB45 1 Kappa 1 Ki67 3 Lambda 1 MNDA 2 MPO 3 Napsin A 2 P63 2 PAX-5 1 S100 1 Synaptophysin 1 TdT 1 TTF-1 3 annual quality assessment Vimentin 4 Wilms tumor 3 13

Conclusions 1) standard methodologywas changes in 15% of cases primary for gross re-sampling 2) immunohistochamical analysis was needed in 33%of cases to answer medico-legal questions 3) molecular analysis (cytogenetic FISH) in around 4% of cases 4) lack of systemic sampling of bone marrow (absence of information useful for forensics) Conclusion 10.8%of cases usually need an interface between forensic and anatomic pathologists 14