[Sarcomatoid malignant mesothelioma: a clinicopathologic and immunohistochemical analysis of 22 cases].

OBJECTIVE: To elaborate on the clinical and pathologic features of sarcomatoid malignant mesothelioma (SMM), its diagnostic criteria and differential diagnoses. METHODS: Twenty-two cases of SMM retrieved from in-house and consultation files (between January 2009 to September 2013) were reviewed with emphasis on the clinicopathologic characteristics, immunophenotypes and the prognostic impact. RESULTS: The mean age of the patients was 54 years (ranged from 24-73 years). There was no sexual predilection and the majority of the patients did not have history of asbestos exposure. Overall, 14 tumors developed in the pleura and 8 cases arose from the peritoneal cavity. Clinically, patients presented signs and symptoms in accord with the location of the tumors, notably coughing, shortness of breath, and chest pain for patients with pleural origin, and nausea, abdominal distention and abdominal pain for those with peritoneal primary. In most cases, CT and MRI scan demonstrated lobulated masses (8/11). However, diffuse infiltrative growth patterns were observed exclusively in a minority of pleural cases (3/11). No visceral lesion was observed in any case. Histologically, 19 cases had either fibrosarcomatous or undifferentiated pleomorphic sarcoma-like appearance. Two cases were consistent with desmoplastic mesothelioma. One case contained osteosarcomatous element. All cases expressed pan-cytokeratin (AE1/AE3), and most cases were also positive for D2-40 (15/20). The staining of calretinin (9/21) and WT1 (10/14) was generally weak and focal. They were all negative for TTF-1, napsin A, SP-A, p63 and CD34. Follow-up information (range from 1 to 36 months) was available in 11 cases, 6 of which were alive with unresectable tumor, 1 patient with recurrent disease and 4 patients succumbed to disease. The overall survival was 5 months (mean 8 months). CONCLUSIONS: The diagnosis of SMM is achieved by comprehensive evaluation of medical history, imageological and pathological findings. Since calretinin immunoreactivity is infrequently observed in SMM, application of pan-cytokeratin and D2-40 immunostains offers a reasonable alternative for diagnosis. Diagnosis of SMM can be made by excluding a variety of spindle cell neoplasms with overlapping features, such as sarcomatoid carcinoma, synovial sarcoma, solitary fibrous tumor and fibrous pleuritis.

Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of gliomas and lung cancer brain metastases.

BACKGROUND: Brain malignancies encompass gliomas and brain metastases originating from extracranial tumours including lung cancer. Approximately 50% of patients with lung adenocarcinoma (LUAD) will eventually develop brain metastases. However, the specific characteristics of gliomas and lung-to-brain metastases (LC) are largely unknown. METHODS: We applied single-cell RNA sequencing to profile immune and nonimmune cells in 4 glioma and 10 LC samples. RESULTS: Our analysis revealed that tumour microenvironment (TME) cells are present in heterogeneous subpopulations. LC reprogramed cells into immune suppressed state, including microglia, macrophages, endothelial cells, and CD8+ T cells, with unique cell proportions and gene signatures. Particularly, we identified that a subset of macrophages was associated with poor prognosis. ROS (reactive oxygen species)-producing neutrophils was found to participant in angiogenesis. Furthermore, endothelial cells participated in active communication with fibroblasts. Metastatic epithelial cells exhibited high heterogeneity in chromosomal instability (CIN) and cell population. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogenicity of the tumor microenvironment and tumour cells and it will be crucial for successful immunotherapy development for brain metastasis of lung cancer.

Malignant Gastrointestinal Neuroectodermal Tumor: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 19 Cases.

A malignant gastrointestinal neuroectodermal tumor (GNET) is rare, and it is therefore yet to be completely understood. This study aimed to present the clinicopathologic features of GNET, including treatment information. We included 19 patients with GNET with a mean tumor size of 4.2 cm. The most common site of tumor origin was the small intestine (57.9%), followed by the stomach (15.8%), colon (10.5%), ileocecal junction (5.3%), lower esophagus (5.3%), and anal canal (5.3%). Microscopically, the tumors were composed of epithelioid cells with eosinophilic or clear cytoplasm arranged in nest, sheet-like, papillary, or pseudoalveolar patterns and/or spindle tumor cells with eosinophilic cytoplasm arranged in a fascicular pattern. Immunohistochemically, the tumor cells stained positively for S100 (19/19,100%), SOX10 (14/15, 93.3%), vimentin (17/17, 100%), synaptophysin (Syn) (7/17, 41.2%), CD56 (4/13, 30.8%), CD99 (1/5, 20%), and CD117 (1/15, 6.7%), and negatively for HMB45, Melan A, DOG1, CD34, AE1/AE3, CAM5.2, chromogranin A, smooth muscle actin, and desmin. In total, 14/15 (93.3%) cases showed split Ewing sarcoma breakpoint region 1 gene (EWSR1) signals consistent with a chromosomal translocation involving EWSR1. Within a mean follow-up of 29.7 months (range: 3 to 63 mo), 2/15 (13.3%) patients died of disease, 5 (33.3%) were alive with disease, and 8 (53.3%) had no evidence of disease. Two and 1 patients showed partial response to apatinib and anlotinib, respectively. In conclusion, GNET has distinctive morphologic, immunohistochemical, and molecular genetic features and should be distinguished from other gastrointestinal tract malignancies. Apatinib and anlotinib might be effective for the treatment of advanced GNET and could prolong patient survival.

Changes in the tumor immune microenvironment in resected recurrent soft tissue sarcomas.

BACKGROUND: Little is known about how the tumor immune microenvironment (TIME) is modulated in recurrent soft tissue sarcomas (STS). METHODS: We evaluated CD8+ T cells, CD20+ B cells, Foxp3+ regulatory T cells (Tregs), and programmed cell death ligand 1 (PD-L1) in 72 paired pre-recurrent (1st resected) versus post-recurrent (2nd resected) STS by immunohistochemistry. Correlations with time to recurrence and prognosis were determined. RESULTS: We found that CD8, PD-L1, CD20, and Foxp3-positive cell counts changed in post-recurrent STS. PD-L1-positive tumor cell and lymphocyte counts increased in post-recurrent STS, whereas CD8+ T cell counts decreased. Changes in CD8+ T cell, CD20+ B cell, and PD-L1+ lymphocyte counts were associated with the time interval between surgeries. At admission, fewer CD8+ T cells were detected in patients with relapse than in newly diagnosed patients. Furthermore, post-recurrent STS with fewer CD8+ T cells compared with pre-recurrent STS were more likely to exhibit re-recurrence. The change in CD8+ T cells was positively associated with overall survival. In multivariate analyses, a decrease in CD8+ T cell counts in post-recurrent STS was an independent unfavorable prognostic factor. CONCLUSIONS: The TIME differs between pre-recurrent STS and post-recurrent STS. The variation in CD8+ T cells and PD-L1 positivity may have essential roles during tumor relapse and provides a basis for determining therapeutic strategies.

Using deep convolutional neural networks for multi-classification of thyroid tumor by histopathology: a large-scale pilot study.

BACKGROUND: To explore whether deep convolutional neural networks (DCNNs) have the potential to improve diagnostic efficiency and increase the level of interobserver agreement in the classification of thyroid nodules in histopathological slides. METHODS: A total of 11,715 fragmented images from 806 patients' original histological images were divided into a training dataset and a test dataset. Inception-ResNet-v2 and VGG-19 were trained using the training dataset and tested using the test dataset to determine the diagnostic efficiencies of different histologic types of thyroid nodules, including normal tissue, adenoma, nodular goiter, papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC). Misdiagnoses were further analyzed. RESULTS: The total 11,715 fragmented images were divided into a training dataset and a test dataset for each pathology type at a ratio of 5:1. Using the test set, VGG-19 yielded a better average diagnostic accuracy than did Inception-ResNet-v2 (97.34% vs. 94.42%, respectively). The VGG-19 model applied to 7 pathology types showed a fragmentation accuracy of 88.33% for normal tissue, 98.57% for ATC, 98.89% for FTC, 100% for MTC, 97.77% for PTC, 100% for nodular goiter and 92.44% for adenoma. It achieved excellent diagnostic efficiencies for all the malignant types. Normal tissue and adenoma were the most challenging histological types to classify. CONCLUSIONS: The DCNN models, especially VGG-19, achieved satisfactory accuracies on the task of differentiating thyroid tumors by histopathology. Analysis of the misdiagnosed cases revealed that normal tissue and adenoma were the most challenging histological types for the DCNN to differentiate, while all the malignant classifications achieved excellent diagnostic efficiencies. The results indicate that DCNN models may have potential for facilitating histopathologic thyroid disease diagnosis.

miR-375 inhibits the invasion and metastasis of colorectal cancer via targeting SP1 and regulating EMT-associated genes.

Accumulating evidence has shown that aberrantly expressed microRNAs (miRNAs) are associated with tumor development and progression. Our previous study found that microRNA-375 (miR-375) was downregulated in colorectal cancer (CRC), but little is known concerning the role of miR-375 and the related mechanism in CRC development. The proliferation, invasion and migration effects were investigated by Cell Counting Kit-8 (CCK-8), colony formation and Transwell assays with or without Matrigel. In addition, candidate target genes were screened and validated by luciferase reporter and western blot assays. In addition, western blot analysis was performed to explore the molecular mechanisms associated with epithelial­mesenchymal transition (EMT). It was found that miR-375 inhibited proliferation, invasion and migration in DLD1 and HCT8 cells. In addition, miR-375 negatively regulated Sp1 transcription factor (SP1) protein by directly binding to the 3'-untranslated region (3'-UTR). Furthermore, it was found that miR-375 regulated matrix metalloproteinase 2 (MMP2) and EMT-associated genes, E-cadherin, vimentin, snail, N-cadherin and ß-catenin. In conclusion, miR-375 inhibited the proliferation, invasion and migration by directly targeting SP1 and regulating MMP2 and EMT-associated genes.

Rosai-Dorfman disease of the pericardium: a case report and review of literature.

Rosai-Dorfman disease (RDD) is an uncommon histiocytic disease of unknown etiology. It typically presents as massive lymphadenopathy with a predilection for the cervical lymph nodes of children and young adults. However, extranodal involvement is not uncommon and may cause confusion with other neoplasms or reactive disease. We describe here a unique case of extranodal RDD manifesting as a pericardial mass in a 69-year-old man. The lesion was detected by computed tomography during a periodic examination of the chest. Subsequently positron emission tomography scan showed mild increase of flurodeoxyglucose uptake. Clinically, it was supposed to be a mesothelioma. Histological examination showed the typical features of RDD confirmed by the staining of S100 protein, which highlighted the emperipolesis of the characteristic histiocytes. To the best of our knowledge, pericardial RDD represents an extremely rare condition and should be included in the differential diagnosis of pericardial neoplasms.