Recent advances in artificial intelligence (AI) have provided novel tools for rapid and precise pathologic diagnosis. The introduction of digital pathology has enabled the acquisition of scanned slide images that are essential for the application of AI. The application of AI for improved pathologic diagnosis includes the error-free detection of potentially negligible lesions, such as a minute focus of metastatic tumor cells in lymph nodes, the accurate diagnosis of potentially controversial histologic findings, such as very well-differentiated carcinomas mimicking normal epithelial tissues, and the pathological subtyping of the cancers. Additionally, the utilization of AI algorithms enables the precise decision of the score of immunohistochemical markers for targeted therapies, such as human epidermal growth factor receptor 2 and programmed death-ligand 1. Studies have revealed that AI assistance can reduce the discordance of interpretation between pathologists and more accurately predict clinical outcomes. Several approaches have been employed to develop novel biomarkers from histologic images using AI. Moreover, AI-assisted analysis of the cancer microenvironment showed that the distribution of tumor-infiltrating lymphocytes was related to the response to the immune checkpoint inhibitor therapy, emphasizing its value as a biomarker. As numerous studies have demonstrated the significance of AI-assisted interpretation and biomarker development, the AI-based approach will advance diagnostic pathology.

Cytologic diagnosis of nuclear protein in testis (NUT) midline carcinoma (NMC) is important due to its aggressive behavior and miserable prognosis. Early diagnosis of NMC can facilitate proper management, and here we report two rare cases of thoracic NMC with cytohistologic correlation. In aspiration cytology, the tumor presented with mixed cohesive clusters and dispersed single cells, diffuse background necrosis and many neutrophils. Most of the tumor cells had scanty cytoplasm and medium-sized irregular nuclei, which had fine to granular nuclear chromatin. Interestingly, a few dyskeratotic cells or squamoid cell clusters were present in each case. Biopsy specimen histology revealed more frequent squamous differentiation, and additional immunohistochemistry tests showed nuclear expression of NUT. Because this tumor has a notorious progression and has been previously underestimated in terms of its prevalence, awareness of characteristic findings and proper ancillary tests should be considered in all suspicious cases.
Biopsy ; Chromatin ; Cytoplasm ; Diagnosis ; Early Diagnosis ; Immunohistochemistry ; Lung ; Necrosis ; Neutrophils ; Nuclear Proteins ; Nuts ; Prevalence ; Prognosis ; Testis

OBJECTIVE: The objective of this study was to determine relationship between alteration of expression of E-cadherin, beta-catenin and tumor progression, clinical stage, lymph node metastasis, age of patients with uterine cervical cancer. METHODS: The authors evaluated the immunohistochemical expression pattern of E-cadherin and beta- catenin in relationship with tumor stage and clinicopathologic parameters in 71 cervical neoplasia including 36 cases of squamous cell carcinoma (SCC), 10 cases of microinvasive SCC, 22 cases of squamous cell carcinoma in situ, and 3 cases of severe dysplasia. RESULTS: There were aberrant expression in 76.1% of E-cadherin (54 of 71) and 74.6% of beta-catenin (53 of 71) in the cervical cancer. There was positive correlation of aberrant expression of E-cadherin with tumor progression and clinical stage (<0.005). There was positive correlation of aberrant expression of beta- catenin with tumor progression and clinical stage (<0.005). CONCLUSION: These results suggest that the degree or the pattern of E-cadherin, beta-catenin, and E-cadherin/beta-catenin complex may be related to histologic grade and clinical stage of uterine cervical cancer.
beta Catenin ; Cadherins ; Carcinoma, Squamous Cell ; Cervix Uteri* ; Female ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Uterine Cervical Neoplasms

Since the early 2000s, there has been a continued interest in lie detection using functional magnetic resonance imaging (fMRI) in neuroscience and forensic sciences, as well as in newly emerging fields including neuroethics and neurolaw. Related fMRI studies have revealed converging evidence that brain regions including the prefrontal cortex, anterior cingulate cortex, parietal cortex, and anterior insula are associated with deceptive behavior. However, fMRI-based lie detection has thus far not been generally accepted as evidence in court, as methodological shortcomings, generalizability issues, and ethical and legal concerns are yet to be resolved. In the present review, we aim to illustrate these achievements and limitations of fMRI-based lie detection.
Brain ; Deception* ; Forensic Sciences ; Gyrus Cinguli ; Lie Detection* ; Magnetic Resonance Imaging* ; Neurosciences* ; Prefrontal Cortex ; Rabeprazole

Purpose: In Alzheimer disease (AD), brain regions such as the cortex and the hippocampus show abundant amyloid load which correlates with cognitive function decline. Prior to the significant development of AD pathophysiology, patients report the manifestation of neuropsychiatric symptoms, indicating a functional interplay between basal ganglia structures and hippocampal regions. Zinc finger and BTB domain-containing protein 16 (ZBTB16) is a transcription factor that controls the expression of downstream genes and the involvement of ZBTB16 in the striatum undergoing pathological aging in AD and the resulting behavioral phenotypes has not yet been explored. Methods: To study molecular alterations in AD pathogenesis, we analyzed the brain from amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice. The molecular changes in the striatal region of the brain were analyzed via the immunoblotting, and the quantitative RNA sequencing. The cognitive impairments of APP/PS1 mice were assessed via 3 behavioral tests: 3-chamber test, Y-maze test, and noble object recognition test. And multielectrode array experiments for the analysis of the neuronal activity of the striatum in APP/PS1 mice was performed. Results: We found that the alteration in ZBTB16 levels that occurred in the early ages of the pathologically aging striatum coalesces with the disruption of transcriptional dysregulation while causing social memory deficits, anxiety-like behavior. The early ZBTB16 knockdown treatment in the striatum of APP/PS1 mice rescued cognition that continued into later age. Conclusions This study demonstrates that perturbation of transcriptional regulation of ZBTB16 during pathological aging may influence cognitive impairments and reveals a potent approach to targeting the transcriptional regulation of the striatum for the treatment of AD.

The musculoskeletal system can be involved as an extra-intestinal manifestation of inflammatory bowel disease. Among these, myositis in ulcerative colitis (UC) is very rare. A 14-year-old girl was admitted due to severe shoulder tenderness. She had complained of left jaw pain and swelling for the past 10 days. Inflammatory markers were elevated with no evidence of infectious etiology. Myositis was suspected by shoulder magnetic resonance imaging. Three days after admission, she developed hematochezia. Muscle biopsy and colonoscopy was performed due to worsening left mandibular area pain and persistent hematochezia. Colonoscopy showed consistent findings with UC. She was finally diagnosed with UC with myositis as an extra-intestinal manifestation. She showed a dramatic response to UC treatment. Gastrointestinal symptoms were well-controlled. After 14 months, UC symptoms and muscle pain were aggravated, which were relieved after steroid and cyclosporin treatment. We report a unique case of UC initially presented with myositis, preceding gastrointestinal symptoms.

PURPOSE: Inconsistent findings have been reported regarding the effect of ambient temperature on ischemic stroke. Furthermore, little is known about how underlying disease and low socioeconomic status influence the association. We, therefore, investigated the relationship between ambient temperature and emergency department (ED) visits for ischemic stroke, and aimed to identify susceptible populations. MATERIALS AND METHODS: Using medical claims data, we identified ED visits for ischemic stroke during 2005–2009 in Seoul, Korea. We conducted piecewise linear regression analyses to find optimum ambient temperature thresholds in summer and winter, and estimated the relative risks (RR) and 95% confidence intervals (CI) per a 1℃ increase in temperature above/below the thresholds, adjusting for relative humidity, holidays, day of the week, and air pollutant levels. RESULTS: There were 63564 ED visits for ischemic stroke. In summer, the risk of ED visits for ischemic stroke was not significant, with the threshold at 26.8℃. However, the RRs were 1.055 (95% CI, 1.006–1.106) above 25.0℃ in medical aid beneficiaries and 1.044 (1.007–1.082) above 25.8℃ in patients with diabetes. In winter, the risk of ED visits for ischemic stroke significantly increased as the temperature decreased above the threshold at 7.2℃. This inverse association was significant also in patients with hypertension and diabetes mellitus above threshold temperatures. CONCLUSION: Ambient temperature increases above a threshold were positively associated with ED visits for ischemic stroke in patients with diabetes and medical aid beneficiaries in summer. In winter, temperature, to a point, and ischemic stroke visits were inversely associated.
Cardiovascular Diseases ; Diabetes Mellitus ; Emergency Service, Hospital ; Holidays ; Humans ; Humidity ; Hypertension ; Korea ; Linear Models ; Seoul ; Social Class* ; Stroke*

PURPOSE: The purpose of this study was to compare the clinical and functional outcomes in patients with primary base of tongue (BOT) cancer who received definitive radiotherapy (RT) or surgery followed by radiotherapy (SRT). MATERIALS AND METHODS: Between January 2002 and December 2016, 102 patients with stage I-IVB primary BOT cancer underwent either definitive RT (n=46) or SRT (n=56), and treatment outcomes were compared between two groups. The expression of p16 was also analyzed. RESULTS: The RT group had more patients with advanced T stage (T3-4) disease (58.7% vs. 35.7%, p=0.021) and who received chemotherapy (91.3% vs. 37.5%, p < 0.001) than the SRT group. At a median follow up of 36.9 months (range, 3.3 to 181.5 months), the 5-year overall survival (OS) and disease-free survival (DFS) were 75.5% and 68.7%, respectively. With respect to treatment group, the 5-year OS and DFS in the RT and SRT groups did not differ significantly (OS, 68.7% vs. 80.5%, p=0.601; DFS, 63.1% vs. 73.1%, p=0.653). In multivariate analysis, OS differed significantly according to p16 expression (p16-negative vs. p16-positive; hazard ratio [HR], 0.145; 95% confidence interval [CI], 0.025 to 0.853; p=0.033). Regarding DFS, p16 expression (p16-negative vs. p16-positive; HR, 0.164; 95% CI, 0.045 to 0.598; p=0.006) showed a significant effect in multivariate analysis. Functional defects (late grade ≥ 3 dysphagia or voice alteration) were more frequently reported in the SRT than in the RT group (16.1% vs. 2.2%, p=0.021). CONCLUSION: Despite advanced disease, patients in the RT group showed comparable survival outcomes and better functional preservation than those in the SRT group.
Chemoradiotherapy* ; Deglutition Disorders ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Organ Preservation ; Radiotherapy ; Radiotherapy, Adjuvant* ; Tongue Neoplasms* ; Tongue* ; Treatment Outcome ; Voice

IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.
Aged ; Carcinoma, Adenosquamous ; Fibrosis ; Humans ; Immunoglobulin G ; Lung Diseases ; Lung Diseases, Interstitial ; Lung Neoplasms ; Lung ; Phlebitis ; Plasma Cells ; Respiratory System

BACKGROUND: Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. METHODS: We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients. RESULTS: Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up. CONCLUSIONS: PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.
Adenocarcinoma ; Aspergillosis ; Cough ; Electronic Health Records ; Female ; Fibrosis ; Follow-Up Studies ; Germinal Center ; Humans ; Hyperplasia ; Immunoglobulin G ; Lymphoma ; Macrophages ; Neutrophils ; Pneumonia ; Pseudolymphoma ; Radiography ; Recurrence ; Thorax ; Tuberculosis