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A deep learning-based image analysis could improve diagnostic accuracy and efficiency in pathology work. Recently, we proposed a deep learning-based detection algorithm for C4d immunostaining in renal allografts. The objective of this study is to assess the diagnostic performance of the algorithm by comparing pathologists’ diagnoses and analyzing the associations of the algorithm with clinical data. C4d immunostaining slides of renal allografts were obtained from two different institutions (100 slides from the Asan Medical Center and 86 slides from the Seoul National University Hospital) and scanned using two different slide scanners. Three pathologists and the algorithm independently evaluated each slide according to the Banff 2017 criteria. Subsequently, they jointly reviewed the results for consensus scoring. The result of the algorithm was compared with that of each pathologist and the consensus diagnosis. Clinicopathological associations of the results of the algorithm with allograft survival, histologic evidence of microvascular inflammation, and serologic results for donor-specific antibodies were also analyzed. As a result, the reproducibility between the pathologists was fair to moderate (kappa 0.36–0.54), which is comparable to that between the algorithm and each pathologist (kappa 0.34–0.51). The C4d scores predicted by the algorithm achieved substantial concordance with the consensus diagnosis (kappa = 0.61), and they were significantly associated with remarkable microvascular inflammation ( P  = 0.001), higher detection rate of donor-specific antibody ( P  = 0.003), and shorter graft survival ( P  < 0.001). In conclusion, the deep learning-based C4d detection algorithm showed a diagnostic performance similar to that of the pathologists.

Antibody-mediated rejection (ABMR) remains a leading cause of kidney allograft failure, yet the mechanistic roles of innate immune cell subsets such as monocytes and natural killer (NK) cells remain incompletely understood. In this retrospective cohort study, we applied OPAL-based multiplex immunofluorescence (mIF) to human kidney allograft biopsies from 38 recipients with biopsy-proven ABMR (n = 19), T-cell-mediated rejection (TCMR, n = 12), or no rejection (NR, n = 7), enabling spatially resolved quantification of immune subsets in situ. Fluorescence thresholds were pathologist-validated, and co-expression phenotypes were defined using standardized segmentation and spectral unmixing. We observed a significantly higher density of CD1 D11c monocyte-derived cells in ABMR versus TCMR ( = 0.011), and of cytotoxic CD3 PAX8 CD16 CD57 NK cells in ABMR versus TCMR ( = 0.008), implicating both subsets in ABMR pathogenesis. Spatial clustering of these populations was evident in ABMR biopsies, suggesting organized immune infiltration. A logistic regression model combining both subsets yielded an area under the ROC curve of 0.79 (95% CI: 0.65-0.93), indicating moderate discriminatory power for ABMR. While Cox regression did not reveal statistically significant associations with graft survival, CD3 PAX8 CD16 CD57 cells showed a trend toward increased risk (HR = 2.73, = 0.09). These findings support a mechanistic role for monocyte and NK cell subsets in ABMR and demonstrate the utility of OPAL mIF for high-resolution immune profiling in human allografts. Our study advances understanding of cellular immune contributors to ABMR and highlights the potential diagnostic value of intragraft mononuclear cell phenotyping.

There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists’ interpretation.

Background Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). Methods We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. Results Forty‐eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty‐nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). Conclusion Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment.

To compare preoperative CT findings before liver transplantation between patients with Alagille syndrome (AGS) and those with end-stage biliary atresia (BA). The institutional review board approved this retrospective study. Eleven children with AGS (median age, 19.0 ± 13.0 months; male to female ratio, 3:8) and 109 children with end-stage BA (median age, 17.9 ± 25.8 months; male to female ratio, 37:72) who underwent abdomen CT as candidates for liver transplant were included. CT images were reviewed focusing on hepatic parenchymal changes, vascular changes, presence of focal lesions, and signs of portal hypertension. Hepatic parenchymal changes were present in 27% (3/11) of AGS patients and 100% (109/109) of end-stage BA patients (P < .001). The hepatic artery diameter was significantly smaller (1.9 mm versus 3.6 mm, P = 008), whereas portal vein diameter was larger (6.8 mm versus 5.0 mm, P < .001) in patients with AGS compared with patients with end-stage BA. No focal lesion was seen in patients with AGS, whereas 44% (48/109) of patients with end-stage BA had intrahepatic biliary cysts (39%, 43/109) and hepatic tumors (8%, 9/109) (P = .008). Splenomegaly was commonly seen in both groups (P = .082), and ascites (9% [1/11] versus 50% [54/109], P = .010) and gastroesophageal varix (0% [0/11] versus 80% [87/109], P < .001) were less common in patients with AGS than in patients with end-stage BA. Fibrotic or cirrhotic changes of the liver, presence of focal lesions, and relevant portal hypertension were less common in patients with AGS than in patients with end-stage BA.

The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients. A total of 1190EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions,acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy wasdiagnosed by computed tomography coronary angiography. Clinical information, including thepatients' survival was retrieved by a review of medical records. Eighty-eight patients(75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellularrejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patientsdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesionsfrom transplantation was longer than that of acute cellular rejections. We found a significant associationbetween Quilty lesions and cardiac allograft vasculopathy. No significant relationship wasfound between Quilty lesions and the patients' survival. Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection.

BackgroundThere are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine.Case-diagnosis/treatmentA 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage.ConclusionsThis is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted.

Gastric-type endocervical adenocarcinoma (GEA) is a rare but distinct histological type of gynecological malignancy. This study aimed to conduct a comprehensive analysis of the cytological features of GEA. We reviewed 18 cytological samples obtained from 14 patients with GEA. All cytology slides were prepared using conventional smear and liquid-based preparations. We examined the differences between the cytological features of GEA and usual-type endocervical adenocarcinoma (UEA). The cytological samples of GEA exhibited flat, honeycomb-like cellular sheets (p=0.035), vesicular nuclei (p=0.037) with prominent nucleoli (p=0.037), and vacuolated cytoplasm (p<0.001) more frequently than those of UEA, irrespective of the sampling site and preparation method. UEA showed three-dimensional cellular clusters (p<0.001), peripheral nuclear feathering (p<0.001), and nuclear hyperchromasia (p=0.014) more frequently than GEA. GEA can be identified cytologically based on the presence of flat, honeycomb-like sheets of tumor cells possessing vesicular nuclei, prominent nucleoli, and abundant vacuolated cytoplasm.

The need for instant histological evaluation of fresh tissue, especially in cancer treatment, remains paramount. The conventional frozen section technique has inherent limitations, prompting the exploration of alternative methods. A recently developed confocal laser endomicroscopic system provides real-time imaging of the tissue without the need for glass slide preparation. Herein, we evaluated its applicability in the histologic evaluation of gastric cancer tissues. A confocal laser endomicroscopic system (CLES) with a Lissajous pattern laser scanning, was developed. Fourteen fresh gastric cancer tissues and the same number of normal gastric tissues were obtained from advanced gastric cancer patients. Fluorescein sodium was used for staining. Five pathologists interpreted 100 endomicroscopic images and decided their histologic location and the presence of cancer. Following the review of matched hematoxylin and eosin (H&E) slides, their performance was evaluated with another 100 images. CLES images mirrored gastric tissue histology. Pathologists were able to detect the histologic location of the images with 65.7% accuracy and differentiate cancer tissue from normal with 74.7% accuracy. The sensitivity and specificity of cancer detection were 71.9% and 76.1%. Following the review of matched H&E images, the accuracy of identifying the histologic location was increased to 92.8% (p<0.0001), and that of detecting cancer tissue was also increased to 90.9% (p<0.001). The sensitivity and specificity of cancer detection were enhanced to 89.1% and 93.2% (p<0.0001). High-quality histological images were immediately acquired by the CLES. The operator training enabled the accurate detection of cancer and histologic location raising its potential applicability as a real-time tissue imaging modality.

Hematoxylin and eosin (H&E) staining has been widely used as a fundamental and essential tool for diagnosing diseases and understanding biological phenomena by observing cellular arrangements and tissue morphological changes. However, conventional staining methods commonly involve solution-based, complex, multistep processes that are susceptible to user-handling errors. Moreover, inconsistent staining results owing to staining artifacts pose real challenges for accurate diagnosis. This study introduces a solution-free H&E staining method based on agarose hydrogel patches that is expected to represent a valuable tool to overcome the limitations of the solution-based approach. Using two agarose gel-based hydrogel patches containing hematoxylin and eosin dyes, H&E staining can be performed through serial stamping processes, minimizing color variation from handling errors. This method allows easy adjustments of the staining color by controlling the stamping time, effectively addressing variations in staining results caused by various artifacts, such as tissue processing and thickness. Moreover, the solution-free approach eliminates the need for water, making it applicable even in environmentally limited middle- and low-income countries, while still achieving a staining quality equivalent to that of the conventional method. In summary, this hydrogel-based H&E staining method can be used by researchers and medical professionals in resource-limited settings as a powerful tool to diagnose and understand biological phenomena.