Autopsy Findings in 32 Patients with COVID-19: A Single-Institution Experience.

BACKGROUND: A novel coronavirus, SARS-CoV-2, was identified in Wuhan, China in late 2019. This virus rapidly spread around the world causing disease ranging from minimal symptoms to severe pneumonia, which was termed coronavirus disease (i.e., COVID). Postmortem examination is a valuable tool for studying the pathobiology of this new infection. METHODS: We report the clinicopathologic findings from 32 autopsy studies conducted on patients who died of COVID-19 including routine gross and microscopic examination with applicable special and immunohistochemical staining techniques. RESULTS: SARS-CoV-2 infection was confirmed by nasopharyngeal RT-PCR in 31 cases (97%) and by immunohistochemical staining for SARS-CoV-2 spike-protein in the lung in the remaining 1 case (3%). The ethnically diverse cohort consisted of 22 males and 10 females with a mean age of 68 years (range: 30-100). Patients most commonly presented with cough (17 [55%]), shortness of breath (26 [81%]), and a low-grade fever (17 [55%]). Thirty-one (97%) of the patients had at least 1 comorbidity (mean = 4). Twenty-eight patients (88%) had widespread thromboembolic disease, as well as diffuse alveolar damage (30 [94%]), diabetic nephropathy (17 [57%]) and acute tubular injury. Patterns of liver injury were heterogeneous, featuring 10 (36%) with frequent large basophilic structures in sinusoidal endothelium, and increased immunoblast-like cells in lymph nodes. CONCLUSION: This series of autopsies from patients with COVID-19 confirms the observation that the majority of severely affected patients have significant pulmonary pathology. However, many patients also have widespread microscopic thromboses, as well as characteristic findings in the liver and lymph nodes.

Combining a deep learning model with clinical data better predicts hepatocellular carcinoma behavior following surgery.

Hepatocellular carcinoma (HCC) is among the most common cancers worldwide, and tumor recurrence following liver resection or transplantation is one of the highest contributors to mortality in HCC patients after surgery. Using artificial intelligence (AI), we developed an interdisciplinary model to predict HCC recurrence and patient survival following surgery. We collected whole-slide H&E images, clinical variables, and follow-up data from 300 patients with HCC who underwent transplant and 169 patients who underwent resection at the Cleveland Clinic. A deep learning model was trained to predict recurrence-free survival (RFS) and disease-specific survival (DSS) from the H&E-stained slides. Repeated cross-validation splits were used to compute robust C-index estimates, and the results were compared to those obtained by fitting a Cox proportional hazard model using only clinical variables. While the deep learning model alone was predictive of recurrence and survival among patients in both cohorts, integrating the clinical and histologic models significantly increased the C-index in each cohort. In every subgroup analyzed, we found that a combined clinical and deep learning model better predicted post-surgical outcome in HCC patients compared to either approach independently.

Adverse Tissue Reactions to Orise Gel During Endoscopic Mucosal Resection and Dissection.

BACKGROUND: To facilitate endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), submucosal injection of lifting agents (LAs) is frequently used. ORISE™ gel, approved in 2018 by the US Food and Drug Administration (FDA), has been commonly utilized until recently. Its use grew rapidly due to its practical pre-filled syringe, prolonged lift effect, and ideal coloration. However, it has been noted to cause unexpected tissue reactions, described as "giant cell reaction" (GCR), which can obscure both macroscopic and microscopic views, potentially interfering with pathological evaluation. This study aims to describe the adverse effects of ORISE™ gel. METHODS: This retrospective study analyzed pathology specimens from all consecutive patients who received ORISE™ injections for attempted polyp removal and subsequently underwent segmental colon resection at our center between 2019 and 2022. Descriptive analysis was performed. RESULTS: A total of 45 patients were included, with 38% (n=17) being female and a median age of 66 years. The indications for surgery included adenocarcinoma in 14 patients (31%), suspected malignancy in 3 patients (7%) who had benign GCR-induced masses, and other indications in 28 patients, such as large polyps or recurrent polyps after initial endoscopic treatment. Surgical procedures included right hemicolectomy (44%), low anterior resection (13%), left colectomy (11%), sigmoidectomy (7%), and abdominoperineal resection (4%). Histologic evidence of prior LA injection was seen in 31 patients (69%), with 24 of these exhibiting GCR. At final pathology, no residual neoplasm was found in 9 patients (18%), while 14 patients (31%) had adenocarcinoma [T1 (7), T2 (3), T3 (3), T4 (1)]. CONCLUSION: ORISE™ Gel interacts with various tissue layers of the colon, frequently resulting in GCR. This reaction and the potential subsequent mass effect formation can impact decision-making in the management of complex colorectal lesions. Further study into the cause and consequences of LA tissue reactions is warranted.

High-grade urothelial carcinoma in urine cytology: different spaces - different faces, highlighting morphologic variance.

INTRODUCTION: The Paris System for Reporting Urinary Cytology (TPS) was first published in 2016 to standardize reporting and placed a specific emphasis on high-grade urothelial carcinoma (HGUC). The urinary tract is anatomically divided into the upper tract (UT) and the lower tract (LT). A major morphologic criterion in TPS for HGUC defines the nuclear-to-cytoplasmic (N/C) ratio as ≥ 0.7. In this study, we evaluated N/C ratios of HGUC arising from UT and LT urine specimens, to ascertain differences due to location. MATERIALS AND METHODS: Digital annotations of whole slide scanned images were performed and enumerated. RESULTS: The cohort consisted of 59 ThinPrep specimens from 52 patients. The majority of the tumors were located in LT (39 of 59, 66.1%). A total of 590 cells were analyzed (10 cells per case). In UT, the average N/C was 0.58 and LT the average was 0.54 (P < 0.001). The average nuclear area for UT was 126.3 and for LT was 158.2 µm2 (P = 0.01). The average cytoplasmic area for UT was 219.1 µm2 and for LT was 296.2 µm2 (P < 0.001). The average cellular circumference for UT was 59.4 µm and for LT was 66.1 µm (P < 0.001). CONCLUSIONS: We found that UT HGUCs have higher N/C ratios, smaller cell circumference, smaller nuclei, and less cytoplasm compared with LT. When UT was divided into renal pelvis and ureter, no statistical difference was identified.

Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value below 0.7 for positive for high-grade urothelial carcinoma and suspicious for high-grade urothelial carcinoma in urine cytology specimens.

BACKGROUND: Urinary cytology is sensitive and specific for diagnosing and screening high-grade urothelial carcinomas (HGUC). The Paris System (TPS) for urinary cytology was introduced in 2016 to standardize reporting. According to TPS diagnostic categories of HGUC and suspicious for HGUC (SHGUC), the average nuclear-to-cytoplasm (N:C) ratio of atypical cells should be ≥0.7. The objective of the current study was to measure the N:C ratio of urine cytology specimens with HGUC and SHGUC diagnoses and biopsy-proven HGUC follow-up. METHODS: A cohort of 64 cases (HGUC, 49 cases; SHGUC, 15 cases) from 57 patients was constructed. Urine cytology slides were scanned into whole-slide digital images. The nuclear and cytoplasmic areas were enumerated by digital image analysis (DIA), and the N:C ratios were measured. RESULTS: In total, 640 cells were analyzed by DIA (HGUC, 490 cells; SHGUC, 150 cells). For HGUC and SHGUC, the average N:C ratios were 0.57 and 0.53, respectively. The maximum average N:C ratio was 0.73 for HGUC and 0.68 for SHGUC. HGUC had higher average N:C ratio (P < .001), higher average nuclear area (P < .001), higher average maximum N:C ratio (P = .005), and higher average maximum nuclear area (P = .006) compared with SHGUC. CONCLUSIONS: The N:C ratios for the HGUC (0.57) and SHGUC (0.53) categories are lower than those previously suggested in TPS. The authors advocate reducing the N:C ratio below the current threshold of 0.7.