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.

The significance of focally enhanced gastritis in haematopoietic stem cell transplant recipients.

AIMS: The histological diagnosis of acute gastric graft-versus-host-disease (aGVHD) in patients with a history of haematopoietic stem cell transplant (HSCT) is based on the presence of epithelial cell apoptosis and karyorrhectic debris. There is, however, limited information on the histological findings in patients who develop symptoms several months after transplant. Focally enhanced gastritis (FEG), defined by the presence of focal periglandular lymphohistiocytic inflammation with neutrophilic or lymphocytic intra-epithelial infiltration of gastric glands, has been described in patients with inflammatory bowel disease and in HSCT patients. The pattern closely resembles the focal periductal inflammation and lymphocytic exocytosis seen in chronic GVHD of the salivary gland. We sought to evaluate the significance of FEG in HSCT patients. METHODS AND RESULTS: Gastric biopsies from 151 HSCT patients who underwent endoscopies for GVHD-like symptoms were identified. Time from transplant to biopsy, presence of extra-gastric GVHD, medications and outcome were noted. Thirty-five biopsies showed FEG and 21 showed aGVHD; the remainder were either normal or showed non-specific changes. Twenty-one (60%) FEG patients had concurrent histologically proven extra-gastric GVHD. The time to biopsy in FEG patients was significantly longer than in aGVHD patients (162 versus 57 days, P < 0.01). Prior or subsequent gastric biopsies of 14 patients in the FEG cohort were also evaluated and, of these, six showed aGVHD while one showed persistent FEG. CONCLUSIONS: These findings suggest that FEG probably represents a form of late-occurring GVHD. This histological pattern should not be overlooked when identified in gastric biopsies from HSCT patients.

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.

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.

COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City.

SARS-CoV-2, the etiologic agent of COVID-19, is a global pandemic with substantial mortality dominated by acute respiratory distress syndrome. We systematically evaluated lungs of 68 autopsies from 3 institutions in heavily hit areas (2 USA, 1 Italy). Detailed evaluation of several compartments (airways, alveolar walls, airspaces, and vasculature) was performed to determine the range of histologic features. The cohort consisted of 47 males and 21 females with a median age of 73 years (range 30-96). Co-morbidities were present in most patients with 60% reporting at least three conditions. Tracheobronchitis was frequently present, independent from intubation or superimposed pneumonia. Diffuse alveolar damage (DAD) was seen in 87% of cases. Later phases of DAD were less frequent and correlated with longer duration of disease. Large vessel thrombi were seen in 42% of cases but platelet (CD61 positive) and/or fibrin microthrombi were present at least focally in 84%. Ultrastructurally, small vessels showed basal membrane reduplication and significant endothelial swelling with cytoplasmic vacuolization. In a subset of cases, virus was detected using different tools (immunohistochemistry for SARS-CoV-2 viral spike protein, RNA in situ hybridization, lung viral culture, and electron microscopy). Virus was seen in airway epithelium and type 2 pneumocytes. IHC or in situ detection, as well as viable form (lung culture positive) was associated with the presence of hyaline membranes, usually within 2 weeks but up to 4 weeks after initial diagnosis. COVID-19 pneumonia is a heterogeneous disease (tracheobronchitis, DAD, and vascular injury), but with consistent features in three centers. The pulmonary vasculature, with capillary microthrombi and inflammation, as well as macrothrombi, is commonly involved. Viral infection in areas of ongoing active injury contributes to persistent and temporally heterogeneous lung damage.

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.