[Inspection of deceased : Issuing a death certificate]. / Prähospitale Leichenschau : Durchführung und das Ausstellen der Todesbescheinigung.

The obligatory post-mortem examination and the issuing of a death certificate are among the more unpopular medical tasks. Nevertheless, the legislature has entrusted the medical profession with a socially important task that should be carried out carefully. The examining physician decides whether the death remains a private matter or whether an official death investigation should first shed light on the circumstances of the death. The post-mortem examination system is the only instrument for the systematic detection of homicide offences. The prerequisite for issuing a death certificate is a carefully conducted external post-mortem examination, which must be carried out in full at least when certifying a natural or unexplained cause of death. In addition, the medical information on the death certificate serves epidemiological and health policy purposes and contains important information on infection control.

Interobserver variability in the application of the novel IASLC/ATS/ERS classification for pulmonary adenocarcinomas.

Recently, a novel classification for pulmonary adenocarcinomas (ADCs) was published, the cornerstone of which is the quantification of growth patterns. Data on reproducibility in the routine diagnostic setting are lacking. 100 constitutive cases of lung ADC resection specimens from our archives were classified independently by five pulmonary pathologists and two residents according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The most frequent predominant pattern in our cohort was solid (37%), followed by acinar (35%), lepidic (20%), papillary (5%) and micropapillary (3%). κ-values for the denomination of the predominant pattern revealed substantial agreement for pulmonary pathologists (κ=0.44-0.72) and fair agreement for residents (κ=0.38-0.47). Interobserver variability was significantly higher in cases with higher slide numbers (p=0.028) and was considerably reduced after training. Intraobserver variability was low (κ=0.79-0.87). Papillary and micropapillary patterns were the most complicated patterns to evaluate, while evaluation of lepidic and solid tumour growth was straightforward. Our data imply that the novel classification of pulmonary ADC is applicable with acceptable interobserver variability if performed by specifically trained pathologists. Additional efforts are needed to harmonise the application of this novel and clinically important classification scheme of pulmonary ADC.

Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival.

In gastrointestinal stromal tumors (GISTs), the occurrence of an epithelioid/mixed phenotype has been correlated to PDGFRA mutations, gastric localization and favorable outcome. On the other hand, the prognostic significance of an epithelioid/mixed growth pattern occasionally observed in GISTs with KIT mutation is unclear. The aim of this study was to evaluate the prognostic significance of an epithelioid/mixed phenotype in correlation to anatomical localization, genotype, and expression of cell-cycle markers in a series of 116 primary GISTs with KIT mutation on a tissue microarray. Independent of their anatomical localization, the majority of KIT-mutated GISTs displayed a pure spindled phenotype (72%), with the remaining tumors showing an epithelioid/mixed growth pattern. In KIT-mutated GISTs from the stomach, the occurrence of an epithelioid/mixed growth pattern was significantly correlated with larger tumor diameters (P=0.005), higher mitotic counts (P=0.0001), high-risk category (P=0.001), higher expression of the G2-phase cell-cycle marker cyclin B1 (P=0.04), higher expression of the G1 to M-phase proliferation marker Ki67 (P=0.02) and a significantly shorter disease-free survival (P=0.003) compared with tumors with pure spindled morphology. In contrast, there were no significant differences between pure spindled and epithelioid/mixed GISTs from the small/large bowel. Our findings indicate that the epithelioid/mixed phenotype in KIT-mutant gastric GISTs represents a secondary tumor growth pattern associated with tumor progression and adverse outcome, probably through accelerated G1/S-phase restriction point passage.

Organ distribution of diclazepam, pyrazolam and 3-fluorophenmetrazine.

The organ distribution of 3-fluorophenmetrazine (3-FPM), pyrazolam, diclazepam as well as its main metabolites delorazepam, lormetazepam and lorazepam, was investigated. A solid phase extraction (SPE) and a QuEChERS (acronym for quick, easy, cheap, effective, rugged and safe) - approach were used for the extraction of the analytes from human tissues, body fluids and stomach contents. The detection was performed on a liquid chromatography-tandem mass spectrometry system (LCMS/MS). The analytes of interest were detected in all body fluids and tissues. Results showed femoral blood concentrations of 10 µg/L for 3-FPM, 28 µg/L for pyrazolam, 1 µg/L for diclazepam, 100 µg/L for delorazepam, 6 µg/L for lormetazepam, and 22 µg/L for lorazepam. Tissues (muscle, kidney and liver) and bile exhibited higher concentrations of the mentioned analytes than in blood. Additional positive findings in femoral blood were for 2-fluoroamphetamine (2-FA, approx. 89 µg/L), 2-flourometamphetamine (2-FMA, hint), methiopropamine (approx. 2.2 µg/L), amphetamine (approx. 21 µg/L) and caffeine (positive). Delorazepam showed the highest ratio of heart (C) and femoral blood (P) concentration (C/P ratio = 2.5), supported by the concentrations detected in psoas muscle (430 µg/kg) and stomach content (approx. 210 µg/L, absolute 84 µg). The C/P ratio indicates that delorazepam displays susceptibility for post-mortem redistribution (PMR), supported by the findings in muscle tissue. 3-FPM, pyrazolam, diclazepam, lorazepam and lormetazepam did apparently not exhibit any PMR. The cause of death, in conjunction with autopsy findings was concluded as a positional asphyxia promoted by poly-drug intoxication by arising from designer benzodiazepines and the presence of synthetic stimulants.

Broad-based molecular autopsy: a potential tool to investigate the involvement of subtle cardiac conditions in sudden unexpected death in infancy and early childhood.

OBJECTIVES: Sudden unexplained death in children is a tragic and traumatic event, often worsened when the cause of death cannot be determined. This work aimed to investigate the presence of putative pathogenic genetic variants in a broad spectrum of cardiomyopathy, channelopathy and aortic disease associated genes that may have increased these children's vulnerability to sudden cardiac death. DESIGN: We performed molecular autopsy of 41 cases of sudden unexplained death in infants and children through massive parallel sequencing of up to 86 sudden cardiac death-related genes. Multiple in silico analyses were conducted together with a thorough review of the literature in order to prioritise the putative pathogenic variants. RESULTS: A total of 63 variants in 35 cases were validated. The largest proportion of these variants is located within cardiomyopathy genes although this would have been more expected of channelopathy gene variants. Subtle microscopic features of heart tissue may indicate the presence of an early onset cardiomyopathy as a predisposing condition to sudden unexpected death in some individuals. CONCLUSIONS: Next-generation sequencing technologies reveal the existence of a wide spectrum of rare and novel genetic variants in sarcomere genes, compared with that of cardiac ion channels, in sudden unexplained death in infants and children. Our findings encourage further investigation of the role of early onset inherited cardiomyopathies and other diseases involving myocardial dysfunction in these deaths. Early detection of variants in these individuals could help to unmask subtle forms of disease within their relatives, who would eventually benefit from better counselling about their genetic history.

Training increases concordance in classifying pulmonary adenocarcinomas according to the novel IASLC/ATS/ERS classification.

The International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) proposed a classification for lung adenocarcinomas (ADC) based on the predominant growth pattern. This classification has been shown to have prognostic and maybe even predictive impact. However, until now, the reproducibility of this classification has not been sufficiently demonstrated. Digital images of 40 selected ADC cases were shown twice to members of the Pulmonary Pathology Working Group of the German Society of Pathology. Each time a teledialogue-based survey on the classification was performed. Between the voting procedures, salient features of the novel classification were presented and discussed in detail by its members. The mean percentages of consensual votes per pattern ranged between 59.6 and 75 %, with lepidic and solid being the pattern with the most discordant and concordant votes, respectively. The other patterns ranged in between (papillary 65.8 %; acinar 67.8 %; micropapillary 74.2 %). The extent of disagreement decreased after the educational session. This decrease, however, was heterogeneous for the different patterns with acinar being the pattern with the strongest improvement. The overall number of abstentions decreased significantly after the educational session (p < 0.001) as well. The IASLC/ATS/ERS classification of lung ADC can be applied with reasonable consensus even for difficult cases in a nationwide context. The reproducibility evidently improves following educational sessions, even among experienced lung pathologists. Worldwide harmonization is clearly the next step on the way to a clinically meaningful, internationally accepted use of this novel prognostic and potentially predictive tool in lung pathology.