Search

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential., (© 2022. The Author(s).)

Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized as indispensable tools for understanding COVID-19, but the true risk of infection to autopsy staff is nevertheless still debated. To clarify the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine points in the PPE of one physician and one assistant after each of 11 full autopsies performed at four centers. Swabs were also obtained from three minimally invasive autopsies (MIAs) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls, and SARS-CoV-2 RNA was detected by real-time RT-PCR. In 9 of 11 full autopsies, PPE samples tested RNA positive through PCR, accounting for 41 of the 198 PPE samples taken (21%). The main contaminated items of the PPE were gloves (64% positive), aprons (50% positive), and the tops of shoes (36% positive) while the fronts of safety goggles, for example, were positive in only 4.5% of the samples, and all the face masks were negative. In MIAs, viral RNA was observed in one sample from a glove but not in other swabs. Infectious virus isolation in cell culture was performed on RNA-positive swabs from the full autopsies. Of all the RNA-positive PPE samples, 21% of the glove samples, taken in 3 of 11 full autopsies, tested positive for infectious virus. In conclusion, PPE was contaminated with viral RNA in 82% of autopsies. In 27% of autopsies, PPE was found to be contaminated even with infectious virus, representing a potential risk of infection to autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore essential to ensure a safe work environment., (© 2022. The Author(s).)

The rapid development of pathology is in contrast to a shortage of qualified staff. The aims of the present study are to compile basic information on the numbers of German physicians in pathology and to compare it with the situation in Europe and overseas. In addition, model calculations will shed light on the effects of part-time working models. Various publicly accessible databases (EuroStat) as well as publications of medical associations and professional associations of European countries and the USA/Canada were examined. In addition, a survey was carried out among the institutes of German universities. Figures from 24 European countries and the USA/Canada were evaluated. With one pathologist per 47,989 inhabitants, the density of pathologists in Germany in relation to the population is the second-lowest in Europe (average: 32,018). Moreover, the proportion of pathologists among the physicians working in Germany is the lowest in Europe and at the same time lower than in the USA and Canada (Germany: 1:200, USA: 1:70, Canada: 1:49). The ratio of pathologists to medical specialists is shifted in the same direction. The survey among university pathologists revealed a relevant increase in the workload over the last 10 years. The majority of institutes can manage this workload only with considerable difficulties. With a ratio between specialists and residents of 1:1, the university institutes show a high commitment in the area of training. The results of this study indicate a shortage of pathologists in Germany that could lead to a bottleneck in large parts of the health system.

Ever declining autopsy rates have been a concern of pathologists as well as clinicians for decades. Notably, in the field of oncology, data on autopsies and discrepancies between clinical and autoptic diagnoses are particularly scarce. In this retrospective study, we show the effect of a simple catalog of measures consisting of a different approach to obtain consent for autopsy, structured conferencing, and systematic teaching of residents, as well as a close collaboration between clinicians and pathologists on the numbers of autopsies, especially of oncological patients. Additionally, postmortem examination protocols from the years 2015 until 2019 were analyzed, regarding rates of discrepancies between clinical and autoptic causes of death in this category of patients. Autopsy numbers could be significantly increased from a minimum in 2014 (60 autopsies) to a maximum in 2018 (142 autopsies) (p < 0.0001). In the 67 autopsies of oncological cases, a high rate of 51% of major discrepancy between clinical and autoptic causes of death could be detected. In contrast to the general reported decline of autopsy rates, we present rising autopsy numbers over the past 5 years with an increasing number of oncological cases who underwent a postmortem examination. The high percentage of major discrepancies between clinical and autopsy diagnosis is in contrast to an expected decrease of major discrepancies in times of precise diagnostic methods and underlines the importance of autopsies to ensure high quality in diagnostics and therapy not only in the field of oncology.

The tumor stroma ratio (TSR) is a promising prognostic biomarker in colon cancer, which could provide additional risk stratification for therapy adaption. The objective of our study was the investigation of the prognostic significance of TSR at different tumor sites in a simple semiautomatic approach with the open-source program ImageJ. We investigated 206 pT3 and pT4 adenocarcinomas of no special type. According to our established thresholds, 31 tumors (15%) were classified as low tumor proportion (TP) (≤ 15% TP), 42 tumors (20%) were classified as high TP (≥ 54% TP), and 133 tumors (65%) were classified as medium TP. High and low TP were associated with an adverse overall survival in comparison to medium TP (p = 0.001 and p = 0.03). Furthermore, the TP was an independent risk factor of occurrence of distant metastasis next to T status, microsatellite status, and tumor budding. The 5-year survival rate was 49% in patients with high TP, 48% in patients with low TP, and 68% in patients with medium TP (p = 0.042, n = 160). Patients with a high TP had less often tumor budding (p = 0.012), lymphovascular invasion (p = 0.049), and less harvested lymph nodes (p = 0.042) in comparison to low TP tumors. The results provide first evidence that a high tumor proportion/low stroma proportion is also associated with an adverse prognosis and that this subgroup might be difficult to identify with other classical histopathologic characteristics that are linked to an adverse prognosis.

Tumor budding is a mostly accepted adverse prognostic factor in colorectal carcinoma. It is on the cusp of a widespread use after agreement was reached recently on uniform assessment criteria. We investigated whether the interobserver variability has a direct influence on the prognostic relevance in pT3/4 colon cancer in the background of different levels of experience of the investigators. In total, six investigators with different levels of experience evaluated tumor budding on H&E slides in 244 cases with primary diagnosed (2002-2011) colon carcinoma (pT3/4, N+/-, M0). High-grade tumor budding/budding grade 3 (defined as majority assessment among the investigators) was significantly associated with an adverse outcome (overall survival p = 0.03, cancer-specific survival p = 0.08) and the occurrence of distant metastasis (p = 0.009). However, a detailed analysis of the rating results of the individual investigators revealed that only ratings of one investigator (advanced resident) were associated with an adverse outcome (p = 0.01 cancer-specific survival, overall survival p = 0.09, distant metastasis p = 0.002). The results of another investigator (consultant) were significantly associated with distant metastasis (p = 0.007). The kappa values among the investigators have a range between 0.077 and 0.357 (median 0.166). Total agreement of all investigators existed in 109 cases (44.7%). Our results demonstrate that the evaluation of tumor budding on H&E slides in pT3/4 colon cancer goes along with a considerable interobserver variability among investigators of different levels of experience. Furthermore, our results reveal that these findings directly influence the prognostic value.

Fibroelastotic changes (FEC) and especially elastotic polyps of the gastrointestinal (GI) tract are considered rare benign lesions. They consist of accumulations of elastic fibers within the mucosal, submucosal, or muscular layer, occurring in all parts of the GI tract and often appearing as polyps, but also as diffuse non-polyp-forming deposits. They have been the subject of only a few studies. To explore the clinical and histopathological features of FEC in the GI tract, a series of 162 elastotic lesions was collected within a 2-year period. The clinical data and endoscopic findings were correlated. FEC appeared as polyp-forming lesions of the large intestine in 23 samples (14 %), all other samples concerning histological findings without an identifiable gross mass. Frequently related findings were postinterventional status (9 %), previous irradiation (7 %), and history of GI lymphoma (4 %). Eight samples (5 %) presented endoscopically with lesions justifying surgical intervention. We identified three different histological patterns of FEC, which we have called fibroelastosis, angioelastosis, and elastofibroma. Consistent with previous studies, CD34 immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an increase of CD34-positive mesenchymal cells in 95 % of immunostained samples, suggesting a potential role for CD34-positive mesenchymal cells in the accumulation of elastic fibers. In conclusion, FEC are more common in the GI tract than previously recognized. They often present as a benign polyp. Many accompany other diseases like ulcers and atrophic gastritis or represent a residual finding after an intervention.

Purpose: This study aims to report our multicenter experience with diagnosis, management, and prognosis of anorectal gastrointestinal stromal tumors (GIST)., Patients and Methods: We retrospectively reviewed cases treated and/or followed up at our institutions in the period 2000-2011., Results: Fifteen patients were identified (eight men and seven women; mean age, 55 years). Presenting symptoms were rectal/perirectal (eight), rectovaginal space (four), or retrovesical/prostatic (three) mass. Primary surgical treatment was local excision (six), deep anterior resection (eight), and palliative diagnostic excision (one). Tumor mean size was 4.8 cm. All but two cases were high risk (Miettinen and Lasota, Semin Diagn Pathol 23:70-83, 2006). R0 resection was achieved in 46% of cases: one of six local excisions vs. five of seven deep anterior resection (16 vs. 71%, respectively). All three cases who received total mesorectal excision had R0. Non-R0 status was mainly due to opening of tumor capsule at surgery (Rx). Seven of 14 patients (50%) developed ≥1 pelvic local recurrences at a mean period of 48.4 months (mean follow-up, 61.6 months). Only two patients developed distant metastasis (adrenal, liver, and peritoneal). Recurrences developed after Rx (three), R1 (two), and unknown R-status (two). Successful mutational analysis in 13 patients revealed KIT mutations in all (10 exon 11, 2 exon 9, and 1 exon 13)., Conclusion: Our results confirm the high local recurrence rate of anorectal GISTs (50%) which correlates with the common practice of suboptimal oncological primary tumor resection (Rx or R1 = 7/13). This uncommon subset of GISTs needs more standardized oncological surgical approach to minimize the propensity for local disease recurrence.

Purpose: Minimal lymph node involvement is a potential prognostic factor in colorectal cancer. The International Union Against Cancer defined tumour deposits between 0.2 and 2 mm as micrometastases and clusters and single-cell infiltrations below this cutoff as isolated tumour cells. Nevertheless, only a minority of studies discriminated metastatic involvements according to this definition., Methods: In order to investigate the prognostic significance of micrometastases (0.2-2 mm), we performed a retrospective study enrolling 44 routinely diagnosed micrometastatic cases within 15 years which represent about 1% of our cases. These cases have been re-evaluated., Results: Seven of the micrometastatic cases turned out to be macrometastases after step sectioning. Complete follow-up was available in 33 remaining cases. Collections of node-negative and macrometastatic cases served as control groups. The Kaplan-Meier curves of macro- and micrometastatic cases showed a similar adverse course (p = 0.830) especially during the first 40 months. The 5-year-survival rates were 51, 60 and 64 months for macro-, micrometastatic and node-negative cases, respectively. The difference in overall survival, however, reached only a statistical trend and was not significant (p = 0.137). After re-evaluation with step sections and cytokeratin immunohistochemistry out of an initial 91 node-negative cases, 11 (12%) cases were identified with isolated tumour cells and one (1%) case with a micrometastasis., Conclusions: Our data show that micro- and macrometastatic colorectal cancers show very similar survival rates. Therefore, efforts to improve the detection of lymph node micrometastases seem to be justified.

Purpose: The purpose of the present study is to characterise the lymphatic vessel density (LVD) in the T3 colorectal carcinoma and to correlate it with N status, grading and presence of tumour budding., Methods: A total of 56 cases of T3 colorectal carcinoma were retrieved from the pathology's archive of Klinikum Augsburg. All slides were stained immunohistochemically with D2-40 (lymphatic endothelium) and with pancytokeratin to assess the tumour budding. Tumour budding and lymph vessel density were investigated independently by BM and CC. The highest density of lymphatic vessels was counted both in tumour centre (ILVD) and at the periphery of the tumour (PLVD) within an area of 0.24 mm(2)., Results: Due to the strong intra-observer (BM and CC) difference in ILVD and PLVD, all cases were re-evaluated establishing a consensus that has been used for the further analyses. There was a significant difference between PLVD and ILVD (12 ± 4 versus 6 ± 3; P < 0.001). Moreover, we found a non-significant trend towards high PLVD in the cases with nodal metastasis versus the negative one, 13 ± 5/hpf versus 11 ± 4 (P = 0.072). There was no association between tumour budding and ILVD and PLVD (P = 0.249 and 0.38)., Conclusion: Colorectal carcinoma induces lymphangiogenesis. A higher PLVD could increase the capability of cancer cell to invade the lymphatic system. However, the obvious difficulties in immunohistochemical evaluation and the rather small differences between nodal positive and negative cases in T3 colorectal cancer seem to limit the clinical value of LVD evaluation.

Purpose: Surgery for colorectal liver metastasis facilitates long-term survival, and neoadjuvant chemotherapy improves resectability but may also alter staging accuracy. The aim of this study was to evaluate the effects of neoadjuvant chemotherapy on the efficacy of positron emission tomography (PET), PET-computed tomography (CT), CT and intraoperative ultrasound (IUS) in the detection of liver metastasis., Methods: Between January 2007 and January 2010, 34 patients with resectable colorectal liver metastasis were included in this retrospective analysis. Seventeen patients had received neoadjuvant chemotherapy. PET or PET-CT, CT or magnetic resonance imaging (MRI) and IUS were performed in all patients. Sensitivity, specificity, positive predictive value and negative predictive value were analysed. Histopathological examination of the resected specimens served as standard reference., Results: A total of 109 liver segments were resected, of which 50 showed no metastatic involvement (45.9%). For patients without systemic chemotherapy, sensitivities for PET, CT/MRI and IUS were 92%, 64% and 100% respectively as compared with 63%, 65% and 94% for patients after neoadjuvant chemotherapy in a segment-based analysis. For PET, standardised uptake values were decreased by 3.9 in 10 patients after chemotherapy whereas lesion diameters were similar (3.0 vs. 3.2 cm). Additional metastases were detected by IUS in seven patients resulting in a change of operative procedure in 20.6%., Conclusion: Staging accuracy of colorectal liver metastasis is influenced by neoadjuvant chemotherapy. For PET, decreased tumour metabolism rather than downsizing may account for a drop in sensitivity after neoadjuvant chemotherapy. IUS is critical to avoid incomplete resections.

The frequency and morphological spectrum of gastrointestinal peripheral nerve sheath tumors (PNSTs) from consecutive case material has not been studied in the c-KIT era. We reviewed all mesenchymal gastrointestinal (GI) lesions at our departments according to current diagnostic criteria. PNSTs formed the third commonest group of mesenchymal GI tumors with a lower frequency (< or =5%) compared to gastrointestinal stromal tumors (GISTs; approximately 50%) and smooth muscle neoplasms ( approximately 30%). Granular cell tumors (GCTs; n = 31) and schwannomas (n = 22) were the most common types of PNSTs encountered. Rare tumors included neurofibromatosis 1 (NF1)-associated PNSTs (n = 5) and gastric perineurioma (n = 1). Thirteen schwannomas (including also some recent cases) were initially diagnosed as GIST, leiomyoma, or neurofibroma. Unusual histological variants included sigmoid GCT with prominent lipomatous component (n = 1), reticular-microcystic schwannoma of small (n = 1) and large (n = 1) bowel, NF1-associated gastric schwannoma (the first case to date), and psammomatous melanotic colonic schwannoma unrelated to Carney complex (n = 1). PNSTs coexisted with GIST in four patients (three had definite NF1). In conclusion, PNSTs of the GI tract are rare uniformly benign neoplasms that may show schwannian, perineurial, fibroblastic, or mixed differentiation. Most of them (92%) occurred sporadically unassociated with NF1 or NF2. Gastrointestinal PNSTs are still underrecognized by general pathologists. Awareness of their diverse morphology will help to avoid confusing them with smooth muscle neoplasms and GIST that they may closely mimic.

Multifocal sporadic gastrointestinal stromal tumours (GISTs) may be misinterpreted as recurrent or metastatic disease, leading to inappropriate treatment. As molecular analysis is generally not available in routine practise, histological criteria that would facilitate diagnosis of multiple primary GISTs in routine slides are needed. We studied 14 GISTs (mean size, 2.7 cm) from six men and one woman (mean age, 70 years) applying morphological features and direct sequencing of KIT, PDGFRA, BRAF, and KRAS. Diagnosis was synchronous in five and metachronous in two patients. Paired tumours originated in stomach/small bowel (n = 5), duodenum/jejunum (n = 1), and stomach/oesophagus (n = 1) and revealed spindle (n = 10) and mixed spindle and epithelioid (n = 4) phenotype. Tumours were well circumscribed and have involved the muscularis propria in a pattern typical of primary GISTs. Different somatic KIT mutations were found in tumours from four patients. One patient had a KIT-mutated and a BRAF-mutated (V600E) tumour. Two patients had wild-type tumours. No PDGFRA or KRAS mutations were detected. Our results underscore the molecular heterogeneity of sporadic multifocal GISTs. The characteristic involvement of the muscularis propria and the site-typical morphology and immunophenotype facilitated the diagnosis of primary GISTs in all cases and correlated with molecular findings, emphasising the value of conventional histology in recognising independent primary GISTs.