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Introduction Lung ventilation is a standard sign of life in newborns. Post-mortem computed tomography (PMCT) is highly sensitive to the presence of gas in the body including the lungs. Current standard examinations to determine the pulmonary ventilation status in newborns are the flotation test and histology. The purpose of this study was to compare the accuracy of PMCT with the flotation test for determining the lung ventilation status with histological control as reference standard. A cut-off value as CT number in Hounsfield Units (HU) determining lung ventilation of newborns in PMCT should be established. Methods A total of 38 infant lungs were examined of which 21 lungs were from infants deceased shortly after live birth (control group) and 17 lungs belonged to infants where live birth was in question (study group). All lungs were examined using PMCT, flotation test, and histological examination. Results The control group showed an overall mean attenuation ± standard deviation of −219 HU ± 135; the study group of 45 ± 15 HU in histologically nonventilated lungs versus −192 ± 207 HU; (p Conclusion PMCT is equally well suited to determine lung ventilation as the flotation test. It provides additional information regarding pulmonary infiltration, degree of putrefaction, or signs of trauma (fractures, pneumothorax). Histology remains mandatory in ambiguous cases.

There was a clear increase in the influx of refugees in Germany in 2014 and 2015. The majority of them came from countries without regular access to medical care. There are often precarious hygienic conditions during the flight. An above-average prevalence for infectious diseases, such as tuberculosis and blood-borne viral diseases is described for this group of persons. There are no available data on the causes of death and concomitant diseases in this group. In the Institute of Forensic Medicine at the University of Munich autopsies were carried out on a significant number of refugees for the first time. The macromorphological findings during the autopsies and the prosecution files were evaluated. Blood and urine samples were analyzed for alcohol and drugs by chromatography and mass spectrometry. Femoral vein blood samples (whole blood) were analyzed for human immunodeficiency virus (HIV), hepatitis B and C by the polymerase chain reaction (PCR). The formalin-fixed parenchymatous organs were histologically examined and assessed. The statistical evaluation of the obtained data was carried out using SPSS (version 23). A total of 20 deceased refugees were autopsied during the investigation period and the average age was 26 years. The main countries of origin were Syria, Afghanistan and Eritrea. In 14 cases an unnatural death was detected, in 2 a natural death and in 4 cases the cause of death remained unclear. The cases of unnatural death were caused by drowning accidents, suicide, traffic accidents, drug abuse and one homicide and the cases of natural death by pneumonia and heart failure. In three cases an infectious or parasitic accompanying disease was diagnosed (tuberculosis or roundworm disease). In 12 of the deceased there were non-infectious concomitant diseases, 6 of which were psychiatric diseases. According to our knowledge for the first time a professional overview of autopsies of refugees, their causes of death and existing concomitant diseases can be given. The indications for a medicolegal autopsy of this group are no different from the general German population. Striking was the low average age of the deceased and the leading cause of death in this small study was drowning of non-swimmers during the summer. None of the autopsied refugees had a contagious disease which could be transmitted to third parties. Despite the young age more than half of the cases were caused by internal diseases, which were the cause of death in two cases. No particular danger for infection existed for the personnel involved in the autopsies of the subjects.

Fur den Gleitschirm-, Fallschirm- und Drachenflugsport sind keine fliegerarztlichen Tauglichkeitsuntersuchungen vorgeschrieben. Verunglucken Sportler todlich, kann somit vielfach erst bei der rechtsmedizinischen Untersuchung bewertet werden, ob unerkannt gebliebene Vorerkrankungen eine kausale Rolle beim Unfallereignis gespielt haben. Derartige Falle des Munchner Instituts fur Rechtsmedizin uber die Jahre 2005 bis 2015 wurden insbesondere im Hinblick auf flugmedizinische Risikoerkrankungen ausgewertet. Die insgesamt 6 Getoteten in diesem Zeitraum umfassten 3 Gleitschirmflieger, 2 Fallschirmspringer und einen Drachenflieger. Fur einen Todesfall konnte eine beim Sprung aufgetretene, kardial bedingte Handlungsunfahigkeit als Unfallursache nicht ausgeschlossen werden. Die Obduktionsergebnisse bei 4 der 5 ubrigen Getoteten sprachen ebenfalls fur eine zumindest weiterfuhrend klarungsbedurftige flugmedizinische Befundsituation. Bis zur Erarbeitung entsprechender Daten in Studien an groseren Fallkollektiven erscheint fur den begutachtenden Arzt eine kritische Abwagung im Hinblick auf die Kriterien der JAR-FCL beziehungsweise der EU-Verordnung Nr. 1178/2011 (EU-FCL) empfehlenswert.

In situ end-labeling (ISEL) of internucleosomal 3' DNA strand breaks and the morphological proof of nuclear chromatin condensation are two widely used methods to investigate and quantify apoptosis. However, it is still unclear whether both processes are linked with each other and if quantifying apoptosis by both methods leads to comparable results. Therefore, internucleosomal DNA fragmentation and chromatin condensation were measured simultaneously on double-fluorescence-labeled sections of 62 testicular tumors (47 nonseminomatous tumors and 15 seminomas) using immunofluorescence microscopy. Different apoptotic indices (AI), based on DNA fragmentation and/or morphological criteria were determined. The AI were quantified. Morphologically obtained AI ranged between 1.99% for non-seminomatous tumors and 0.88% for seminomas. The detection of DNA fragmentation values ranged between 8.15% for non-seminomatous tumors and 2.70% for seminomas. Only about 30% of all apoptotic cells could be detected with the morphological method compared to 80% using ISEL in both tumor entities. Therefore, the equivalence of investigations using different apoptosis detection methods in human testicular cancer seems questionable.

Objective To clarify epithelial cell proliferation and p27Kip1 expression along the stepwise histological changes from endophytic schneiderian papillomas to associated carcinomas. Study Design Retrospective investigation involved surgical specimens from 58 patients. Methods Immunohistochemical assessment involved the nuclear Ki67 antigen expressed in proliferating cells. Further, the cyclin-dependent kinase (cdk) inhibitor p27Kip1 was assessed. Binding of p27Kip1 to the cyclin E-cdk2 complex inhibits this kinase, which results in cell cycle arrest. The expression rates of both proteins were compared between non-papillomatous nasal mucosa, endophytic schneiderian papillomas, carcinoma in situ, and invasive squamous cell carcinomas. Statistics involved the Wilcoxon and Mann-Whitney u tests. Significance was set at P

Aims—To clarify p21waf1/cip1 expression in sinonasal lesions. Methods—Archived surgical specimens from 38 patients were investigated by means of immunohistochemistry. p21waf1/cip1 staining was evaluated in the different layers of the epithelium. In addition, human papillomavirus (HPV) infection and p53 protein overexpression were assessed and correlated with p21waf1/cip1 expression. Results—p21waf1/cip1 staining was negative in non-papillomatous nasal mucosa. HPV infection and p53 protein overexpression were not seen. Sixteen of 20 inverted papillomas showed p21waf1/cip1 expression. HPV infection was found in 16 cases and p53 protein overexpression was present in 13 specimens. Expression of p21waf1/cip1 was restricted to surface cells in five cases, but involved basal/parabasal cells in 11 specimens. Immunoreactivity for p21waf1/cip1 in basal/parabasal cells colocalised with p53 protein overexpression. Enhanced expression rates for p21waf1/cip1 were seen in transitional and squamous epithelium compared with columnar epithelium. p21waf1/cip1 expression involved only surface cells in cylindrical cell papillomas. HPV infection and p53 protein overexpression were detected in all specimens. One of five squamous cell carcinomas showed p21waf1/cip1 expression. HPV infection was seen in two cases, and all carcinomas showed p53 protein overexpression. Conclusions—Expression of p21waf1/cip1 is associated with terminal differentiation in surface cells in inverted papillomas and cylindrical cell papillomas, but not in non-papillomatous nasal mucosa. Overexpression of p53 protein colocalises with p21waf1/cip1 expression in basal/parabasal cells in inverted papillomas but not in cylindrical cell papillomas. Expression of p21waf1/cip1 in squamous cell carcinomas involves a subset of tumours with p53 protein overexpression. Key Words: p21waf1/cip1 • nasal mucosa • sinonasal papillomas • squamous cell carcinomas

Cytokeratin expression and epithelial differentiation in Warthin’s tumour and its metaplastic (infarcted) variant Aims: Warthin’s tumour is characterized by a bilayered columnar epithelium. Transformation into metaplastic (infarcted) Warthin’s tumour includes squamous metaplasia of the epithelium along with regressive changes in the stroma. Misinterpretation of metaplastic Warthin’s tumour for malignancy is a serious diagnostic pitfall. This study assesses the utility of cytokeratin expression in Warthin’s tumour and its metaplastic variant. Methods and results: Twenty-six cases of Warthin’s tumour, among them eight metaplastic Warthin’s tumours, were investigated employing immunohistochemistry. Both Warthin’s tumour and its metaplastic variant regularly expressed cytokeratins (CK) 7, 8, 18, and 19. Staining results with antibodies to CK10, 10/13, 1/2/10/11, and 20 were negative in all specimens. Immunoreactivity for CK 5/14 and 17 was restricted to basal cells in Warthin’s tumour, but involved basal as well as surface cells in metaplastic Warthin’s tumour. Conclusions: Warthin’s tumour and its metaplastic (infarcted) variant both express CK 7, 8, 18, and 19, which are typical for columnar differentiation. Cytokeratins typical of squamous differentiation are absent from Warthin’s tumour and its metaplastic variant, irrespective of the squamous morphology of the epithelium in metaplastic Warthin’s tumour. The expression of CK 5/14 and 17, which are typical of regenerative cells, is restricted to basal cells in Warthin’s tumour, but is expressed also in surface cells in metaplastic Warthin’s tumour.

Cytokeratin (CK) expression was studied in 22 sinonasal inverted papillomas. Columnar (respiratory) epithelium in inverted papillomas abundantly expressed CK7, CK8, CK18, and CK19. Immunoreactivity for CK5/14 and CK17 was found in basal and parabasal/suprabasal cells. Transitional (cuboidal) and squamous epithelium in inverted papillomas comparably expressed CK7, CK8, CK18, and CK19. In addition CK13 was found in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 involved all layers of the epithelium. In nonpapillomatous nasal mucosa adjacent to inverted papillomas, CK expression in columnar (respiratory) epithelium exactly matched the findings in inverted papillomas. Transitional (cuboidal) and squamous epithelium in nonpaillomatous mucosa were negative for CK7, CK8, CK18, and CK19. CK13 was expressed in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 was restricted to basal and parabasal/suprabasal cells. Conclusively, transitional (cuboidal) and squamous epithelium in inverted papillomas but not in the adjacent mucosa coexpress CKs typical for columnar and squamous differentiation.

Primary mediastinal B-cell lymphoma (MBL) is an aggressive Non-Hodgkin's Lymphoma, which has been recognized as a distinct disease entity. We performed a comprehensive molecular cytogenetic study analyzing 43 MBLs. By comparative genomic hybridization (CGH), the most common aberrations were gains of chromosome arms 9p and Xq, which were present in 56% and 40% of cases, respectively. Based on the limited resolution of CGH, this technique may underestimate the real incidence of aberrations. Therefore, we also did an interphase cytogenetic study with eight DNA probes mapping to chromosome regions frequently altered in B-cell lymphomas. With this approach, both 9p and Xq gains were found in more than 70% of cases (75% and 87%, respectively). The findings were compared with results obtained in 308 other B-cell lymphomas. Gains in 9p were identified in only six of the 308 cases, and only one of these lymphomas with 9p gains was not primarily extranodal in origin (P < 10-(20) for CGH data and P < 10-(11) for fluorescence in situ hybridization data). We also present a novel MBL cell line, MedB-1, which carries the genetic aberrations characteristic of this entity.

In order to clarify the availability of DNA suitable for PCR amplification from gastric content three different preparation systems were applied on a cohort of 48 specimens. A fluorescence-based quantification system was applied to investigate the respective DNA concentrations after the extraction process. The Abbott m Sample Preparation System DNA as well as the Qiagen DNA Mini Kit and DNeasy Mericon Food Kit resulted in successful preparation results from all materials. However, the chemistry provided in the specialized DNeasy Mericon Food Kit resulted in the best results from poorly digested material. In contrast, the Abbott magnetic beads system resulted in the highest DNA yields from liquidized gastric content in further stages of digestion. The degree of digestion of stomach content should be considered when the method for DNA preparation is chosen in forensic casework.

During postmortal CT angiography the body is perfused with lipophilic contrast medium soluted in liquid paraffin. The present study investigated, whether molecular pathology investigations on autopsy tissues following this procedure are impaired or not. Heart tissue from fifteen cases following this type of CT scan as well as the same number of control cases matched for age, gender, pathological findings in the heart, time between death and autopsy, as well as fixation time of the samples were analyzed. DNA preparation was carried out employing a commercially available silica-column based system. The extraction results were quantified and real-time PCR was carried out using an assay for a point mutation frequently assessed in clinical pathology. Low and highly variable recovery rates of DNA were observed both in the study group as well as in the control group. The presence of liquid paraffin and lipophilic contrast medium did not interact with tissue fixation and the DNA preparation technique. Further, no differences were seen between the PCR results from the material with or without previous postmortal CT angiography. Hence, molecular pathology applications can be carried out successfully on autopsy tissues regardless of previous CT angiography.

Background Abelson interactor 1 (Abi1) is an important regulator of actin dynamics during cytoskeletal reorganization. In this study, our aim was to investigate the expression of Abi1 in colonic mucosa with and without inflammation, colonic polyps, colorectal carcinomas (CRC) and metastases as well as in CRC cell lines with respect to BRAF/KRAS mutation status and to find out whether introduction of KRAS mutation or stimulation with TNFalpha enhances Abi1 protein expression in CRC cells. Methodology/Principal Findings We immunohistochemically analyzed Abi1 protein expression in 126 tissue specimens from 95 patients and in 5 colorectal carcinoma cell lines with different mutation status by western immunoblotting. We found that Abi1 expression correlated positively with KRAS, but not BRAF mutation status in the examined tissue samples. Furthermore, Abi1 is overexpressed in inflammatory mucosa, sessile serrated polyps and adenomas, tubular adenomas, invasive CRC and CRC metastasis when compared to healthy mucosa and BRAF-mutated as well as KRAS wild-type hyperplastic polyps. Abi1 expression in carcinoma was independent of microsatellite stability of the tumor. Abi1 protein expression correlated with KRAS mutation in the analyzed CRC cell lines, and upregulation of Abi1 could be induced by TNFalpha treatment as well as transfection of wild-type CRC cells with mutant KRAS. The overexpression of Abi1 could be abolished by treatment with the PI3K-inhibitor Wortmannin after KRAS transfection. Conclusions/Significance Our results support a role for Abi1 as a downstream target of inflammatory response and adenomatous change as well as oncogenic KRAS mutation via PI3K, but not BRAF activation. Furthermore, they highlight a possible role for Abi1 as a marker for early KRAS mutation in hyperplastic polyps. Since the protein is a key player in actin dynamics, our data encourages further studies concerning the exact role of Abi1 in actin reorganization upon enhanced KRAS/PI3K signalling during colonic tumorigenesis.

We report the case of a 58-year-old man who presented with a squamous cell carcinoma pT1a G2 of the left vocal cord. Six months after histologically verified complete resection, the patient experienced an endolaryngeal and extralaryngeal local recurrence pT4 pN2b G2. We applied DNA flow cytometry (FCM) and comparative genomic hybridization (CGH) on both primary and recurrent tumor. The primary tumor and the endolaryngeal compartment of the relapse was an aneuploid cell clone with a FCM DNA index of 1.42 and 1.44, respectively. The extralaryngeal compartment showed a shift featuring a DNA index of 2.78. In the primary tumor and in both compartments of the recurrence there was an identical pattern of complex chromosomal imbalances as detected in CGH (CGH karyotype: rev ish enh [8q24.2-q24.3, 10q26.1-q26.3, 11q24-q25, 12q24.2-q23.33,X], dim [4q, 13q14.3-q31], amp[1p36.1-p36.2]). Hence, the recurrence was not associated with further gains and losses of chromosomal material. However, in the anterior part of the recurrence, the aneuploid tumor cell genome had completely doubled, obviously due to endoreduplication. Immunohistochemical analysis of several cell-cycle regulators revealed altered expression of checkpoint proteins, pointing to a complex disturbance in cell-cycle regulation.

To clarify structural changes in the gastric foveolar epithelium in Helicobacter pylori (Hp)-positive gastritis, the expression rates of keratins 8, 18, 19, and 20 were assessed immunohistochemically in normal tissue and chronic gastritis. In normal tissue, keratin 8 was found in 100% of the cells. Staining for keratins 18 and 19 was abundantly positive. Keratin 20 was not expressed in the deep foveolae, but present in the upper foveolae and on the tips. No differences were found between the antrum and the body. In chronic gastritis, both Hp-positive and -negative, keratins 8, 18, and 19 were expressed comparably to normal tissue. Keratin 20 expression in the antrum was significantly lower in Hp-positive compared with Hp-negative gastritis (P < .05) and normal tissue (P < .05). In the body, staining for keratin 20 did not differ significantly between all groups. The difference in keratin 20 expression between the antrum and the body in Hp-positive gastritis was significant (P < .05). After successful eradication, staining for keratin 20 in the antrum normalized within 6 months (P < .05). These findings indicate structural changes in the gastric foveolar epithelium in Hp-positive gastritis. They predominantly include the antral region and show full reversibility after eradication.