The Detrimental Impact of End-Stage Kidney Disease Is Not Reflected in Autopsy Reports.

CONTEXT.­: End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ∼20% to 30%, many die of complications related to this disease. OBJECTIVE.­: To determine the percentage of autopsy cases of decedents with ESKD in which the contribution of ESKD to death is accurately reflected in the final report. DESIGN.­: Autopsy case records were retrospectively reviewed at 4 institutions (Yale New Haven Hospital, University of Chicago Medical Center, University of Illinois at Chicago Hospital, University of Iowa Hospital). Clinical, macroscopic, and microscopic autopsy findings were reviewed, with attention to renal disease findings. RESULTS.­: One hundred sixty decedents with documented ESKD and premortem dialysis who underwent autopsy assessment were identified. ESKD was implicated as a cause of death (CoD) or significant contributing factor in 44 cases (28%), but not in the remaining 116 cases (72%). Cardiovascular disease was the most common CoD in ESKD. There was significant interpathologist variation in the inclusion of ESKD as a CoD across institutions. These rates ranged from 85% correlation (23 of 27 cases), to 13% (4 of 31 and 8 of 62 cases at 2 institutions), and 22.5% (9 of 40 cases) across the 4 participating institutions. CONCLUSIONS.­: The recognition at autopsy of ESKD as a CoD or contributing CoD at autopsy in patients undergoing dialysis remains low (28%). The detrimental impact of ESKD is not reflected in hospital autopsy reports, which carries implications for collection of vital statistics and allocation of research funding for kidney diseases.

Updating Normal Organ Weights Using a Large Current Sample Database.

CONTEXT.­: Organ weights are an essential part of autopsy analysis. Deviations from normal organ weights provide important clues to disease processes. The assessment of normal organ weights depends on reliable reference tables, but most widely available reference tables are based on data that are either decades old or derived from relatively small sample sizes. OBJECTIVE.­: To provide an updated reference table of organ weights based on contemporary sources and a large sample size. DESIGN.­: Organ weights from 4197 carefully screened autopsies performed on adults at the Palm Beach County Medical Examiner's Office in West Palm Beach, Florida, and the Mayo Clinic Hospital in Rochester, Minnesota. RESULTS.­: Height and body weight data in this study reflect the well-recognized increases in both variables, but most particularly in body weight, seen during the last decades. The study data show a strong positive association between organ weight and body weight for the heart, liver, and spleen. There is a similar but weaker association between body weight and the weight of the lungs and kidneys. Brain weight is independent of body weight but shows a strong negative association with age. Even when controlling for body weight, men's organs are heavier, except for the weight of the liver, which is comparable in men and women. These associations are in agreement with the findings of previous studies. The current study suggests that, for some of the commonly weighed organs, there has been an increase in median organ weight when compared with existing references. CONCLUSIONS.­: The tables presented here provide an updated reference that should prove useful to autopsy pathologists in the forensic and hospital settings.

Somatic Mutation of BAP1 Can Lead to Expression Loss in Non-Small Cell Lung Carcinoma: Next Generation Sequencing and IHC Analysis in A Large Single Institute Cohort.

Introduction. As a tumor suppressor, germline and somatic inactivation of BRCA1 associated protein 1 gene (BAP1) is a common finding in mesothelioma, melanocytic tumors, clear cell renal cell carcinoma and several other epithelial, mesenchymal and neural tumors. Incidence of BAP1 genetic alterations and subsequent expression loss has not been well established in non-small cell lung carcinoma (NSCLC) by large-scale studies. Design. After IRB approval, a total of 356 NSCLC cases of our institution between July 2016 and June 2020 were reviewed. The study cohort consisted of 214 (60%) adenocarcinomas, 89 (25%) squamous cell carcinomas, and 53 (15%) diagnosed as "non-small cell lung carcinoma" without specified subtype. All tumors underwent comprehensive target cancer gene next generation sequencing (Oncomine Assay). The protein expression status of BAP1 was subsequently evaluated by immunohistochemistry. Results. BAP1 somatic mutations were detected in 8 NSCLC tumors (incidence: 2.2%). Tumors harboring BAP1 mutations were all diagnosed at advanced stage and carried at least one additional genetic alteration. Immunohistochemically, four tumors showed complete loss of BAP1 protein expression, including two adenocarcinomas which harbored different missense BAP1 mutations and another two with bioinformatically predicated deleterious frameshifting mutations. Conclusion. Compared with known BAP1 loss associated other malignancies, such as mesothelioma, inactivation of BAP1 by somatic mutation is a rare occurrence in NSCLC. BAP1 mutations and loss of expression in NSCLC are accompanied by other complex genetic alternations, suggesting BAP1 mutation maybe a late event NSCLC carcinogenesis.

The curious case of a Klatskin tumor.

Klatskin tumors are the most common type of cholangiocarcinomas. They are perihilar tumors usually found at the bifurcation of right and left hepatic ducts. The absence of early symptoms leads to the diagnosis of most Klatskin tumors at an advanced incurable stage. Despite emerging adjuvant treatment regimens, survival outcomes remain poor. Surgery is currently the standard of care and the only curative treatment modality available. In this manuscript, we share our experience with an asymptomatic patient with elevated liver enzymes, who was found to have a Klatskin tumor, extending into the left hepatic duct. The patient's diagnosis, management, and prognosis are discussed. The case highlights the importance of screening for hepato-biliary malignancies in elderly patients with abnormal liver function markers.

Neurofibromatosis type 1, recurrent pulmonary embolism, and a periampullary carcinoid tumor: is there a link?

Neurofibromatosis type 1 (NF1), a relatively common autosomal dominantly inherited condition with complete penetrance but extremely variable phenotypic expressivity, is caused by mutations in the NF1 gene. The disease is defined clinically by its cutaneous (cafe-au-lait macules, inguinal and axillary freckles) and neural (neurofibromas, plexiform neurofibromas, Lisch spots, optic nerve gliomas) signs, but it can involve many other systems including the gastrointestinal, pulmonary, respiratory, skeletal and vascular systems. Involvement of these other systems can sometimes manifest itself in clinically confusing ways. For example, the literature includes reports of patients with NF1 that has caused pulmonary hypertension, spontaneous hemothorax, and gastrointestinal bleeding. We present the case of a man with NF1 who presented with recurrent unexplained thromboembolic disease and died suddenly in the hospital. In addition to confirming his suspected massive pulmonary thromboembolus (PE), an autopsy revealed an unsuspected periampullary duodenal carcinoid tumor. The potential connections between the patient's NF1, duodenal tumor, and fatal PE are discussed. The case highlights the importance of bearing in mind the protean clinical manifestations of NF1.

The SIM Time Network.

The Sistema Interamericano de Metrologia (SIM) is a regional metrology organization (RMO) whose members are the national metrology institutes (NMIs) located in the 34 nations of the Organization of American States (OAS). The SIM/OAS region extends throughout North, Central, and South America and the Caribbean Islands. About half of the SIM NMIs maintain national standards of time and frequency and must participate in international comparisons in order to establish metrological traceability to the International System (SI) of units. The SIM time network (SIMTN) was developed as a practical, cost effective, and technically sound way to automate these comparisons. The SIMTN continuously compares the time standards of SIM NMIs and produces measurement results in near real-time by utilizing the Internet and the Global Positioning System (GPS). Fifteen SIM NMIs have joined the network as of December 2010. This paper provides a brief overview of SIM and a technical description of the SIMTN. It presents international comparison results and examines the measurement uncertainties. It also discusses the metrological benefits that the network provides to its participants.