Faculty Bibliography

Background: On January 1, 1898, New York City consolidated the five boroughs to create the modern municipal government. This legislation reorganized the borough-based coroner system and death recordkeeping. The previous year, the world-renowned Bellevue Hospital Medical College pathology department lost its morgue in a fire. Among the records saved in the aftermath, recently rediscovered, were log books documenting hundreds of autopsies performed at Bellevue Hospital in 1897. Design: Data from 324 autopsies (n=325, excluding one duplicate entry) performed at Bellevue Hospital between March 16 and December 31, 1897 were collected in a Microsoft Excel 2010 spreadsheet. Each decedent's name, age, race, ethnicity, country of origin, medical division, ward assignment, time of death, time of autopsy, and autopsist(s) were recorded, along with external examination findings, gross findings by organ system, and final anatomic diagnosis. Frequency tables and measures of central tendency were compiled. The final anatomic diagnoses were subcategorized by etiology (chronic disease, malignancy, infectious disease, therapeutic complication, medicolegal, psychiatric). Where possible, patient and physician identifiers were matched to contemporaneous public records, medical journals, and online archives (NYU Health Sciences Library, New York Public Library, National Library of Medicine). Microscope slides and laboratory medicine results were unavailable. Results: Decedents included 222 men, 82 women, and 20 of unknown sex. Age was recorded for 166 adults and 46 children. The adults' average age at death was 42 years (range 19-78 years); children, 17 months (3 days-13 years). The majority (310) were U.S. born, with 11 European-born (Ireland, Germany, Austria, Italy, Sweden), 3 of unknown birthplace. Six U.S.-born were identified as "colored." The combined medical divisions ordered 208 autopsies, and the surgical 21. Other decedents were from the insane pavilion (2), emergency ward (1), prison (1), and found on the street (6). Average turnaround time was 43 hours (1 hour-14 days after death). Thirty-nine autopsies were same-day. Conclusions: The most frequent causes of death in this cohort match those reported by New York State in 1896-8. Average age at death, 42 years, was younger than U.S. life expectancy (46.3 years for men, 48.3 years for women). There was insufficient data to classify decedents' occupations and socioeconomic status. No major diagnostic errors were seen, accounting for changes in nomenclature over time

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

RATIONALE AND OBJECTIVES: This study aimed to differentiate pathologically defined lepidic predominant lesions (LPL) from more invasive adenocarcinomas (INV) using three-dimensional (3D) volumetric density and first-order texture histogram analysis of surgically excised stage 1 lung adenocarcinomas. MATERIALS AND METHODS: This retrospective study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. Sixty-four cases of pathologically proven stage 1 lung adenocarcinoma surgically resected between September 2006 and October 2015, including LPL (n = 43) and INV (n = 21), were evaluated using high-resolution computed tomography. Quantitative measurements included nodule volume, percent solid volume (% solid), and first-order texture histogram analysis including skewness, kurtosis, entropy, and mean nodule attenuation within each histogram quartile. Binomial logistic regression models were used to identify the best set of parameters distinguishing LPL from INV. RESULTS: Univariate analysis of 3D volumetric density and histogram features was statistically significant between LPL and INV groups (P < .05). Accuracy of a binomial logistic model to discriminate LPL from INV based on size and % solid was 85.9%. With optimized probability cutoff, the model achieves 81% sensitivity, 76.7% specificity, and area under the receiver operating characteristic curve of 0.897 (95% confidence interval, 0.821-0.973). An additional model based on size and mean nodule attenuation of the third quartile (Hu_Q3) of the histogram achieved similar accuracy of 81.3% and area under the receiver operating characteristic curve of 0.877 (95% confidence interval, 0.790-0.964). CONCLUSIONS: Both 3D volumetric density and first-order texture analysis of stage 1 lung adenocarcinoma allow differentiation of LPL from more invasive adenocarcinoma with overall accuracy of 85.9%-81.3%, based on multivariate analyses of either size and % solid or size and Hu_Q3, respectively.

Influenza B is a rare cause of myocarditis that is usually caused by histiocytic and mononuclear cellular infiltrates. We describe a 22-year-old female patient presenting with fulminant myopericarditis secondary to influenza B infection that deteriorated to cardiogenic shock. Endomyocardial biopsy results yielded myocardial necrosis through complement-mediated cellular injury without evidence of interstitial infiltrates. The rare cause of this patient's disease, along with the unique pathologic findings, are an important reminder of the diversity of potential findings in myocarditis.

INTRODUCTION: Intravascular lymphoma (IVL) is a rare subtype of large B cell lymphoma (LBCL) in which growth of neoplastic cells occurs within blood vessels. Half of IVL cases are diagnosed on autopsy due to myriad clinical presentations and lack of established diagnostic approaches. We present a case of IVL that manifested as fatal refractory lactic acidosis. CASE PRESENTATION: A 71 year old female with a history of hypertension presented with generalized fatigue, abdominal pain, and unintentional 10lb weight loss over 3 months. Age appropriate cancer screening was negative. An outpatient abdominal CT scan revealed acute right portal vein thrombosis (PVT), and an isolated 1.8cm pancreatic tail lesion with no lymphadenopathy. Initial vital signs were unremarkable and examination with only mild abdominal distention. Workup revealed new mild anemia Hgb 10.7 g/dL, CO2 12mmol/L, anion gap of 20mmol/L, platelets 76,000/uL, and mild elevation of AST 110 U/L and ALT 73 U/L. Venous blood gas showed pH 7.2, PCO2 36mmHg, HCO3 13mmol/L, and lactate 10.5mmol/L. Heparin was initiated for PVT and empiric blood cultures ultimately grew Weisella confusa, an enteric lactobacillus seen in immmuncompromised hosts, with urine culture growing E.coli and E.faecalis. Biopsy of the pancreatic lesion showed high grade LBCL; bone marrow was negative. She received IV fluids, appropriate antiobiotic therapy, and empiric vasopressor therapy to target higher mean arterial pressures but lactatemia persisted. "Tumor lysis labs" such as lactate dehydrogenase and uric acid were markedly elevated. She was intubated for impending respiratory failure and developed progressive multiorgan failure. Her family eventually decided to palliatively withdraw care and the patient expired. DISCUSSION: Lack of signficant tumor burden on imaging confused interpreting this patients refractory lactic acidosis. Autopsy revealed high grade lymphoma involving nearly all organs and vessels. Her lactic acidosis was likely due to a combination of factors including widespread tumor burden, high cell turnover (Fig.1), and tissue infarction by neoplastic thrombi (Fig. 2). CONCLUSIONS: Diagnosis of IVL is elusive and, unfortunately, often post mortem. Clincal presentaion can include rapidly progressive mutliorgan failure. It is important to recognize this high grade lymphoma as a potential cause of refractory lactic acidosis

The purpose of this case study was to raise awareness among forensic pathologists and medicolegal death investigators regarding two unique socioethnic practices and regional customs that have significant forensic implications. We present two cases involving coining (gua sha) and bloodletting (sapi) that represent two forms of traditional customs that involve the use of blunt force and sharp force trauma, respectively. In coining, the skin lesions are produced as a result of dermabrasion with oils and oval objects such as coin. In sapi, multiple superficial linear scrapes are made in the skin as part of a bloodletting ceremony. The identification of these lesions will prevent the interpretation of them as non-voluntary-inflicted trauma.

Hydrophilic polymers are used to coat catheters and other intravascular devices. In general, these polymers have many salutary properties; however, in some instances, fragmentation of hydrophilic polymers coating intravascular devices can occur with fatal consequences. This report details the histopathologic changes in the lung seen following polymer fragmentation and embolization from a central venous catheter. Polymer emboli detected microscopically are intravascular and consist of basophilic, lamellated, and nonrefractile elements. Typically, an inflammatory response is present to a variable degree. Embolization can result in severe tissue injury with ischemia and infarction.

BACKGROUND: Manipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express PD-1 ligand. METHODS: We retrospectively analyzed a cohort of patients (pts) with relapsed metastatic/unresectable sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least four doses of nivolumab; RECIST 1.1 criteria were used for response assessment. RESULTS: Twenty-eight pts with soft tissue (STS, N = 24) or bone sarcoma (N = 4), received IV nivolumab 3 mg/kg every 2 weeks from July 2015. Median age was 57 (24-78), male:female ratio was 14:14; the median number of nivolumab cycles was eight. Eighteen pts concomitantly received pazopanib at 400-800 mg daily. The most common side effect was grade 1-2 LFT elevations; grade 3-4 toxicity occurred in five patients (colitis, LFT elevations, pneumonitis). Twenty-four pts received at least four cycles. We observed three partial responses: one dedifferentiated chondrosarcoma, one epithelioid sarcoma and one maxillary osteosarcoma (last two patients on pazopanib); nine patients had stable disease including three leiomyosarcomas; 12 patients had progression of disease including 4 leiomyosarcoma. Clinical benefit (response + stability) was observed in 50% of the evaluable patients. CONCLUSIONS: These data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and bone sarcoma.