Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients.

BACKGROUND: RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. AIM: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC. METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors. CONCLUSION: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.

Cigarette smoking-related OLC1 overexpression associated with poor prognosis in bladder urothelial carcinoma.

AIMS: To explore the clinical significance of OLC1 and cigarette smoking in bladder urothelial carcinoma (UBC). MATERIALS AND METHODS: OLC1 mRNA expression was detected in 106 UBC samples by mRNA array or reverse real-time PCR. OLC1 protein expression in 114 UBC samples was detected by immunohistochemical staining. Wild-type C57BL/6J mice were injected with cigarette smoke condensate (n = 12) or exposed to cigarette smoke (n = 6) to investigate the correlations between cigarette smoking and OLC1 expression using mRNA array. KEY FINDINGS: The mRNA and protein expression of OLC1 were higher in tumor samples (p < 0.01) and significantly correlated with tumor stage (p < 0.05). OLC1 protein expression and smoking history were correlated with disease-free survival (p < 0.05). OLC1 expression was significantly elevated in smoking patients with higher smoking intensity on both mRNA and protein levels (p < 0.05). Cigarette smoke exposure experiments revealed that OLC1 mRNA overexpressed in bladder uroepithelium of mice. SIGNIFICANCE: OLC1 could serve as a potential prognosis biomarker of UBC, especially for smoking patients.

MeIS: DNA methylation-based immune response signatures for thyroid nodule diagnostics.

CONTEXT: Accurately distinguishing between benign thyroid nodules (BTNs) and papillary thyroid cancers (PTCs) with current conventional methods poses a significant challenge. OBJECTIVE: We identify DNA methylation markers of immune response-related genes for distinguishing BTNs and PTCs. METHODS: In this study, we analyzed a public reduced representative bisulfite sequencing (RRBS) dataset and revealed distinct methylation patterns associated with immune signals in PTCs and BTNs. Based on these findings, we developed a diagnostic classifier named as the Methylation-based Immune Response Signature (MeIS), which was composed of fifteen DNA methylation markers associated with immune response-related genes. We validated the MeIS's performance in two independent cohorts: ZS's retrospective cohort (50 PTC and 18 BTN surgery-leftover samples) and ZS's preoperative cohort (31 PTC and 30 BTN fine-needle aspiration (FNA) samples). RESULTS: The MeIS classifier demonstrated significant clinical promise, achieving AUCs of 0.96, 0.98, 0.89 and 0.90 in the training set, validation set, ZS's retrospective cohort, and ZS's preoperative cohort, respectively. For the cytologically indeterminate thyroid nodules, in the ZS's retrospective cohort, MeIS exhibited a sensitivity of 91% and a specificity of 82%; in the ZS's preoperative cohort, MeIS achieved a sensitivity of 84% and a specificity of 74%. Additionally, combining MeIS and BRAFV600E detection improved the detecting performance of cytologically indeterminate thyroid nodules, yielding sensitivities of 98% and 87%, and specificities of 82% and 74% in the ZS's retrospective cohort and ZS's preoperative cohort, respectively. CONCLUSIONS: The fifteen markers we identified can be employed to improve the diagnostic of cytologically indeterminate thyroid nodules.

Recurrent central nervous system Rosai-Dorfman disease with KRAS mutation: a case report.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis of unknown etiology. we report a very rare case of recurrent central nervous system RDD with KRAS gene mutation and review the literature to improve our understanding of this disease. CASE PRESENTATION: A 19-year-old male patient was admitted to our hospital for headache. Cranial magnetic resonance imaging revealed a mass of abnormal signal shadows in the prepontine cistern. The mass was surgically removed and the patient was consequently diagnosed with intracranial Rosai-Dorfman disease. Seven months later, pathological examination confirmed that the RDD had recurred. Next-generation sequencing found KRAS mutation in exon 4 (C.351A > C. P. K117n). CONCLUSION: RDD of the CNS has no distinct clinical manifestations and imaging characteristics, and the final diagnosis should be based on the results of the pathological examination. Although RDD is not currently classified as a neoplastic disorder, some evidence of clonality has changed our understanding of it. Follow up examinations over a long period are necessary to determine the efficacy of treatment.

Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) patients may present with atherosclerotic lesions in their pulmonary arteries, but their clinical characteristics remain unclear. The metabolic pathways associated with the atherosclerotic lesions may explain their occurrence and have implications for interventions, but they have not been investigated. Methods: We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following a detailed pathological examination of the PEA specimen, the patients were divided into those with and without lesions, and age- and sex matching were performed subsequently using propensity score matching (n = 25 each). Metabolomic profiling was used to investigate the metabolites of the proximal lesions in the PEA specimens. Results: In our study population, 27.2% of all PEA specimens were found to contain atherosclerotic lesions. CTEPH patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism and had a longer timespan between embolism and surgery, whereas the classic risk factors of systemic and coronary circulation could not distinguish CTEPH patients with or without atherosclerotic lesions. Metabolomic profiling revealed that the formation of atherosclerotic lesions in CTEPH was closely related to altered glycine, serine, and threonine metabolic axes, possibly involved in cellular senescence, energy metabolism, and a proinflammatory microenvironment. Conclusion: The occurrence of atherosclerotic lesions in the pulmonary arteries of CTEPH was associated with symptomatic thromboembolic history and prolonged disease duration. The results revealed a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH for the first time. This study has characterized the clinical and metabolic profiles of this distinct group of CTEPH patients, providing new insights into disease pathogenesis and potential interventions.

Clinicopathological Correlation of Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Study.

The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Although pulmonary endarterectomy (PEA) is potentially curative, inoperable patients and persistent pulmonary hypertension (PH) following surgery remain a significant problem. In this study, we aim to describe the histopathological characteristics of CTEPH and explore the potential relationship between pulmonary arterial lesions, radiological parameters, and clinical manifestations. Endarterectomized tissues from 81 consecutive patients of CTEPH were carefully collected, sectioned, and examined by experienced pathologists. Pertinent clinical and radiological data were obtained from medical records and operative reports. Neointima, fresh/organized thrombi, recanalized regions, and atherosclerotic lesions were microscopically examined as previously described. Thrombi and atherosclerosis were dominant in UCSD classification level I PEA materials, while recanalized neo-vessels were more frequently observed in UCSD classification level III cases. Degenerative changes of the extracellular matrix were also noticed in the vascular bed. Atherosclerotic lesions were more frequently observed in cases with higher ratio of the pulmonary artery diameter to ascending aorta diameter (PA/AA) reflected by computed tomographic pulmonary arterial scanning. Furthermore, the removal of pulmonary artery complex lesions (with the combination of three to four types of lesions) by PEA was associated with lower postoperative mean pulmonary arterial pressure (mPAP) and decreased incidences of persistent PH. Our study demonstrates that the histopathological features of CTEPH are strongly linked with clinical manifestations and the postoperative outcome after PEA. These data may provide possible evidence for further studies in searching for appropriate causal factors underlying this disease.

MC-ViT: Multi-path cross-scale vision transformer for thymoma histopathology whole slide image typing.

Objectives: Accurate histological typing plays an important role in diagnosing thymoma or thymic carcinoma (TC) and predicting the corresponding prognosis. In this paper, we develop and validate a deep learning-based thymoma typing method for hematoxylin & eosin (H&E)-stained whole slide images (WSIs), which provides useful histopathology information from patients to assist doctors for better diagnosing thymoma or TC. Methods: We propose a multi-path cross-scale vision transformer (MC-ViT), which first uses the cross attentive scale-aware transformer (CAST) to classify the pathological information related to thymoma, and then uses such pathological information priors to assist the WSIs transformer (WT) for thymoma typing. To make full use of the multi-scale (10×, 20×, and 40×) information inherent in a WSI, CAST not only employs parallel multi-path to capture different receptive field features from multi-scale WSI inputs, but also introduces the cross-correlation attention module (CAM) to aggregate multi-scale features to achieve cross-scale spatial information complementarity. After that, WT can effectively convert full-scale WSIs into 1D feature matrices with pathological information labels to improve the efficiency and accuracy of thymoma typing. Results: We construct a large-scale thymoma histopathology WSI (THW) dataset and annotate corresponding pathological information and thymoma typing labels. The proposed MC-ViT achieves the Top-1 accuracy of 0.939 and 0.951 in pathological information classification and thymoma typing, respectively. Moreover, the quantitative and statistical experiments on the THW dataset also demonstrate that our pipeline performs favorably against the existing classical convolutional neural networks, vision transformers, and deep learning-based medical image classification methods. Conclusion: This paper demonstrates that comprehensively utilizing the pathological information contained in multi-scale WSIs is feasible for thymoma typing and achieves clinically acceptable performance. Specifically, the proposed MC-ViT can well predict pathological information classes as well as thymoma types, which show the application potential to the diagnosis of thymoma and TC and may assist doctors in improving diagnosis efficiency and accuracy.

[Myxiod pleomorphic liposarcoma: a clinicopathological and molecular genetic analysis of six cases].

Objective: To investigate the clinicopathologic and molecular genetic characteristics of myxoid pleomorphic liposarcoma (MPLPS). Methods: Six cases of MPLPS diagnosed and consulted in Fujian Provincial Hospital from 2015 to 2021 were collected for histomorphological observation, immunohistochemistry, and fluorescence in situ hybridization (FISH) detection of DDIT3 (CHOP) gene translocation and MDM2/CDK4 gene amplification. Results: There were four males and two females, aged 26-74 years (mean 53.8 years). The tumor size was 3.8-16.0 cm (mean 11.8 cm). All six cases had similar histopathologic features, showing overlapping histologic morphology of myxoid liposarcoma and pleomorphic liposarcoma. Four cases (4/6) were positive for S-100 protein, and the Ki-67 index was 50%-95%. All cases (6/6) were negative for DDIT3 (CHOP) translocation and MDM2/CDK4 amplification by FISH. TP53 (p.R248w) germline mutation was found in one case. Conclusions: MPLPS is a rare subtype of liposarcoma, characterized by overlapping morphology of myxoid liposarcoma and pleomorphic liposarcoma. Genetically, a few of them have TP53 gene germline mutations, but they lack of DDIT3 (CHOP) translocation or MDM2/CDK4 amplification.

Rapid diagnosis of papillary thyroid carcinoma with machine learning and probe electrospray ionization mass spectrometry.

Frozen section examination could provide pathological diagnosis for surgery of thyroid nodules, which is time-consuming, skill- and experience-dependent. This study developed a rapid classification method for thyroid nodules and machine learning. Total 69 tissues were collected including 43 nodules and 26 nodule-adjacent tissues. Intraoperative frozen section was first performed to give accurate diagnosis, and the rest frozen specimen were pretreated for probe electrospray ionization mass measurement. By multivariate analysis of mass scan data, a series compounds were found downregulated in the extraction solution of papillary thyroid carcinoma (PTC), but some were found upregulated by mass spectrometry imaging. m/z 758.5713 ([PC[34:2] + H]+ ), m/z 772.5845 ([PC[32:0] + K]+ ), and m/z 786.6037 ([PC[36:2] + H]+ ) were firstly identified as potential biomarkers for nodular goiter (NG). Machine learning was employed by means of support vector machine (SVM) and random forest (RF) algorithms. For classification of PTC from NG, SVM and RF algorithms exhibited the same performance and the concordance was 94.2% and 94.4% between prediction and pathological diagnosis with positive and negative mass dataset, respectively. For the classification of PTC from PTC adjacent tissues, SVM was better than RF and the concordance was 93.8% and 83.3% with positive and negative mass dataset, respectively. With the identified compounds as training features, the sensitivity and specificity are 87.5% and 88.9% for the test set. The developed method could also correctly predict the malignancy of one medullary thyroid carcinoma and one adenomatous goiter (benign). The diagnosis time is about 10 min for one specimen, and it is very promising for the intraoperative diagnosis of papillary thyroid carcinoma.

Diffuse pulmonary lymphangiomatosis involving lungs and mediastinal soft tissue.

Diffuse pulmonary lymphangiomatosis (DPL) is rare in adults. It is characterized by abnormal proliferation, dilatation, and thickening of the lymphatic channels in the lungs, pleura, and mediastinal soft tissue. Here, we report a case of DPL in a young adult man with recurrent productive cough. Chest computed tomography (CT) showed bilateral interlobular septal and peribronchovascular thickening and mediastinal soft tissue infiltration. Lung biopsy through video-assisted thoracic surgery demonstrated proliferation and dilatation of irregular lymphatic spaces, lined by flattened endothelial cells that were positive for CD31, D2-40, and factor VIII-related antigen on immunohistochemical staining. After treatment with propranolol for six months, the chest CT showed improved interlobular septal and peribronchovascular thickening and a unilateral pleural effusion, which turned bloody. Radiologic features can suggest the diagnosis of DPL. Surgical biopsy with adequate section size is critical in the diagnosis. Propranolol might be an effective and safe therapeutic option for patients with DPL.

BRAFV600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

BACKGROUND: The BRAFV600E mutation is valuable for the diagnosis, prognosis, and therapy of papillary thyroid cancer (PTC). However, studies related to this mutation have involved only a small number of patients. Therefore, we performed a large-scale analysis from a single institute to evaluate the accuracy of combined fine-needle aspiration (FNA) and BRAFV600E mutation tests for PTC diagnosis. METHODS: A total of 4600 patients with thyroid nodules who underwent both FNA cytology and BRAFV600E mutation analysis on FNA specimens were enrolled. The association between the BRAFV600E mutation and clinicopathological features was analyzed. A separate analysis was performed for the 311 patients who underwent repeated FNA for comparison of cytological evaluation and BRAFV600E mutation results. The diagnostic efficacy of the BRAFV600E mutation test and cytologic diagnoses was evaluated for 516 patients who underwent preoperative FNA tests in comparison with conclusive postoperative histopathologic results. RESULTS: The cytology results of all 4600 FNA samples were categorized according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC) stages I-VI, which accounted for 11.76%, 60.02%, 6.46%, 3.61%, 6.71%, and 11.43% of the samples, respectively. The BRAFV600E mutation was detected in 762 (16.57%) FNA samples, with rates of 1.48%, 0.87%, 20.20%, 3.01%, 66.02%, and 87.81% for TBSRTC I-VI lesions, respectively. Among the 311 repeat FNA cases, 81.0% of the BRAFV600E -positive and 4.3% of the BRAFV600E -negative specimens with an initial indication of cytological non-malignancy were ultimately diagnosed as malignant by repeat FNA (p < 0.001). Among the 516 patients who underwent thyroidectomy, the sensitivity and specificity of the BRAFV600E mutation test alone for PTC diagnosis were 76.71% and 100.0%, respectively, which increased to 96.62% and 88.03%, respectively, when combining the BRAFV600E mutation test with cytology. BRAFV600E mutation was significantly associated with lymph node metastasis (p < 0.001), but not with age, gender, or tumor size. CONCLUSIONS: The BRAFV600E mutation test in FNA samples has potential to reduce false negatives in PTC diagnosis, and therefore plays an important role in the diagnosis of thyroid nodules, especially those with an indeterminate or nondiagnostic cytology, which should be considered for repeat FNA.

Acute fibrinous and organizing pneumonia complicated with hemophagocytic lymphohistiocytosis caused by chronic active Epstein-Barr virus infection: a case report.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare lung condition that is associated with acute lung injury. Its etiology may be idiopathic or secondary to a series of conditions, including immune-related diseases, unclassified connective tissue diseases, hematopoietic stem cell transplantation, infections, hematological diseases and drug induced lung toxicity. We report for the first time a case of AFOP complicated with hemophagocytic lymphohistiocytosis (HLH) caused by chronic active Epstein-Barr virus (CAEBV) infection. CASE PRESENTATION: A 64-year-old man was admitted with a complaint of fever and dyspnea for 2 weeks. The patient presented with elevated serum aminotransferase levels, splenomegaly, progressive decrease of red blood cells and platelets, hyperferritinemia, hypofibrinogenemia, and elevated of Soluble interleukin-2 receptor (sCD25). His chest computed tomography (CT) scan revealed multiple patchy consolidation in both lungs and multiple lymphadenopathy in the mediastinum and hilum. The serology for antibodies of VCA-IgG was positive, EBV-DNA in peripheral blood was elevated, and EBV nucleic acid was detected in the alveolar lavage fluid. Histopathology of the lung tissue showed a dominant of intra-alveolar fibrin and organizing pneumonia. Hemophagocytic cells was found in the bone marrow smear and biopsy. EBV-DNA was detected in lung tissue and bone marrow using in situ hybridization with an EBV-encoded RNA (EBER) probe. After 50 days of hospitalization, he was improved in lung and hemogram. CONCLUSION: We report a case of AFOP with HLH caused by CAEBV in an immunocompetent adult, suggesting that AFOP may be a rare but serious complication caused by CAEBV, and glucocorticoid therapy may improve short-term prognosis.

Clinicopathologic features and BRAF mutation status of tracheal glomus tumors - Characterization of 4 cases and the distinction from low-grade neuroendocrine tumors.

BACKGROUND: Glomus tumors are uncommon and mostly benign mesenchymal neoplasms of the perivascular family. To date, only a few cases of glomus tumors occurring in the trachea have been reported. Tracheal glomus tumors simulated low-grade neuroendocrine tumors on clinical and histomorphological examination, so the differential diagnosis between these two entities is very necessary. The latest studies showed that BRAF mutation may be associated with a malignant phenotype of glomus tumors. METHODS: We investigated the clinical, histopathologic, immunohistochemical, and BRAF V600E mutation status of four cases of tracheal glomus tumors. RESULTS: The cases showed a female predilection (male:female, 1:3) with a median age of 35.5. All of the cases had the typical morphological characteristics of glomus tumors, such as uniform round tumor cells with nest-like distribution surrounding thin-walled vessels; two of them met the malignant diagnostic criteria based on the 5th edition of WHO classification, including marked nuclear atypia and any level of mitotic activity. Immunohistochemistry showed diffusely positive for vimentin (4/4), α-SMA (4/4) and collagen IV (4/4), variably reactive for synaptophysin (3/4) and SSTR2 (2/2), and negative for AE1/AE3 (0/4) and chromogranin A (0/4). Three tested cases harbored no BRAF V600E mutation. Three follow-up cases were alive and free of disease with an average follow-up of 89.3 months. CONCLUSIONS: Tracheal glomus tumors are rare mesenchymal tumors that have overlapping morphologic and immunohistochemical features with neuroendocrine neoplasms. Our cases highlight the importance of careful histomorphological examination and comprehensive immunohistochemical study in reaching a correct diagnosis of glomus tumors of the trachea. Other than BRAF mutation, malignant glomus tumors may have a complex mutational profile.

Identification of novel ALK fusions using DNA/RNA sequencing in immunohistochemistry / RT-PCR discordant NSCLC patients.

Anaplastic lymphocyte kinase (ALK) rearrangement, a key oncogenic driver promoting the expression of ALK protein in tumor cells, is found in 2%-7% of patients with nonsmall cell lung cancer (NSCLC). ALK fusion is routinely determined with immunohistochemistry (IHC) or RT-PCR in many laboratories. However, there were discordant cases. In this study, we employed a hybridization-based next-generation sequencing (NGS) of DNA and RNA to explore the underlying mechanisms. FFPE tissues of 302 NSCLC tumors, which had been ALK tested with IHC and RT-PCR, were retrospectively studied, of which 18 were IHC positive, and 14 were RT-PCR positive. This resulted in 4 discordant cases, which were further analyzed with NGS. One sample failed the RNA quality control due to extensive RNA degradation. Three non-EML4-ALK fusions were identified in the 4 cases with DNA sequencing, including a CLTC-ALK fusion (EX31:EX19), a WDPCP-ALK fusion (EX14:EX20), and a novel PLB1-ALK fusion (EX6:EX20). Interestingly, two additional fusions: STRN-ALK fusion (EX3:EX20) and DCTN1-ALK fusion (EX20:EX20), were identified with RNA sequencing. The discordance of IHC/RT-PCR was mainly due to limited coverage of non-EML4-ALK fusions in the RT-PCR assay. NGS-based DNA/RNA sequencing appears to be a promising rescue technique for nonclear-cut IHC/RT-PCR cases and also offers a unique opportunity to identify novel ALK fusions.

Immunohistochemical Assessment of Transthyretin Association with Colorectal Adenocarcinoma.

BACKGROUND: To explore the association of transthyretin (TRR) with colorectal cancer (CRC) development and progression. METHODS: This study was conducted on 12 normal colorectal tissue samples, 15 colorectal adenomas, and 39 colorectal adenocarcinoma tissue specimens. TTR expression was assessed by immunohistochemistry, and the results were correlated to clinicopathological characteristics of CRC patients. RESULTS: TTR staining was detected in 16.7% (2/12) of normal colon tissues, 46.7% (7/15) of colorectal adenomas, and 89.7% (35/39) of colorectal adenocarcinoma tissues. TTR staining scores in normal colon tissues, adenoma, and adenocarcinoma were 0.58, 2.27, and 5.40, respectively. G3 grade adenocarcinoma had a higher TTR staining score compared with G2 and G1 grades (8.40, p = 0.0009). Lower TTR expression was significantly associated with metastasis (p = 0.043). CONCLUSIONS: TTR expression is positively correlated with adenoma to CRC progression. Thus, TTR has the potential to serve as a predictive marker in CRC.

ACOT11 promotes cell proliferation, migration and invasion in lung adenocarcinoma.

BACKGROUND: Lung cancer is one of the most common cancers in the word. However, the underlying mechanism remains largely unknown. ACOT11 encodes enzymes hydrolyzing the fatty acyl-CoA esters into free fatty acids and CoA. Besides from its role in fatty acid metabolism, the other aspects regarding its function in the progression of lung cancer have not been revealed. METHODS: We first explored the clinical profile of ACOT11 in tumor samples. Next, we combined gene knockdown in vitro and in vivo and microarray gene profiling analysis to decipher the unknown regulatory role of ACOT11 in lung cancer carcinoma. Furthermore, we explored the potential molecular mechanisms of ACOT11 with immunoprecipitation. RESULTS: We found high expression of ACOT11 in tumor samples. High expression of ACOT11 showed significantly poor prognosis in lung squamous carcinoma (LUSC) patients. Knocking down of ACOT11 inhibited the cell proliferation, migration as well as invasion in vitro and in vivo. It also promoted the cell apoptosis and cell cycle arrest via multiple signaling pathways. Additionally, ACOT11 could bind with CSE1L, which was proved to be an oncogene in lung cancer and speculated to be a potential target of ACOT11. CONCLUSIONS: The results revealed that ACOT11 regulates proliferation, migration and invasion of lung cancer carcinoma via multiple signaling pathways, indicating its potential value in molecular therapy.

Rule-based automatic diagnosis of thyroid nodules from intraoperative frozen sections using deep learning.

Frozen sections provide a basis for rapid intraoperative diagnosis that can guide surgery, but the diagnoses often challenge pathologists. Here we propose a rule-based system to differentiate thyroid nodules from intraoperative frozen sections using deep learning techniques. The proposed system consists of three components: (1) automatically locating tissue regions in the whole slide images (WSIs), (2) splitting located tissue regions into patches and classifying each patch into predefined categories using convolutional neural networks (CNN), and (3) integrating predictions of all patches to form the final diagnosis with a rule-based system. To be specific, we fine-tune the InceptionV3 model for thyroid patch classification by replacing the last fully connected layer with three outputs representing the patch's probabilities of being benign, uncertain, or malignant. Moreover, we design a rule-based protocol to integrate patches' predictions to form the final diagnosis, which provides interpretability for the proposed system. On 259 testing slides, the system correctly predicts 95.3% (61/64) of benign nodules and 96.7% (148/153) of malignant nodules, and classify 16.2% (42/259) slides as uncertain, including 19 benign and 16 malignant slides, which are a sufficiently small number to be manually examined by pathologists or fully processed through permanent sections. Besides, the system allows the localization of suspicious regions along with the diagnosis. A typical whole slide image, with 80, 000 × 60, 000 pixels, can be diagnosed within 1 min, thus satisfying the time requirement for intraoperative diagnosis. To the best of our knowledge, this is the first study to apply deep learning to diagnose thyroid nodules from intraoperative frozen sections. The code is released at https://github.com/PingjunChen/ThyroidRule.

Clinical, histopathologic, subtype, and immunohistochemical analysis of jaw phosphaturic mesenchymal tumors.

Jaw phosphaturic mesenchymal tumors (PMTs) are a rare neoplasm with uncertain histogenesis. This study aimed to clarify the clinical and pathological features of jaw PMTs.We reviewed the clinical records of 39 patients diagnosed with PMTs in the jaws, and investigated clinical and morphologic characteristics, histologic subtypes, and immunophenotypes of all cases.Microscopic analyses revealed 2 major histologic tumor subtypes: "phosphaturic mesenchymal tumors of mixed epithelial and connective tissue" (PMTMECT), and "phosphaturic mesenchymal tumors of mixed connective tissue" (PMTMCT). PMTMECTs and PMTMCTs accounted for 29 and 10 cases of PMTs, respectively. Most PMTMECT diagnoses were made predominantly in males aged <45 years, and the incidence was similar in both the mandible and maxilla. In contrast, patients with PMTMCTs are predominantly females aged ≥45 years, and all tumors were in the mandible. Histologically, PMTMECT had lower cellularity and a more elongated and spindled mesenchymal component with less elaborate intrinsic microvasculature than PMTMCT. Immunohistochemically, the epithelia of all PMTMECTs was immunoreactive for AE1/AE3. Other immunohistochemical staining of PMTMECTs revealed positive expression of vimentin, SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34 in either one or both components. Immunohistochemical staining of PMTMCTs was diffusely positive for vimentin and a varied ratio of positivity for SATB2, ERG, CD99, Bcl-2, CD56, S-100, D2-40, CD68, SMA, and CD34, but negative for AE1/AE3. Most patients were cured by complete resection, except 2 patients who had repeated recurrences, one of which also had multiple metastasis.Jaw PMT can be divided into 2 major histological subtypes. PMTMECTs are more common than are PMTMCTs, and can transform into malignant PMTMCTs during the progression. PMTMECTs were more commonly observed in males and the incidence was similar in both the maxilla and mandible. PMTMCTs were almost always observed in the mandible of females. Compared with PMTMCTs, PMTMECTs have an admixture of epithelial components with less prominent vasculature and lower cellularity. There were no statistically significant differences in the expression of immunohistochemical markers except AE1/AE3 between PMTMECTs and PMTMCTs. However, immunohistochemical markers have great significance for differentiating other mesenchymal tumors.