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Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined. KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-ß1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-ß1 axis.
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Proteína 7 com Repetições F-Box-WD , Linfoma Difuso de Grandes Células B , Mutação , Proteínas Proto-Oncogênicas c-myc , Linfócitos T Reguladores , Humanos , Proteína 7 com Repetições F-Box-WD/metabolismo , Proteína 7 com Repetições F-Box-WD/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Animais , Camundongos , Feminino , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Masculino , Linfócitos T Reguladores/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Receptores Notch/metabolismo , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Transdução de Sinais , Adulto , Progressão da Doença , IdosoRESUMO
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare form of aggressive B-cell lymphoma with limited molecular information reported regarding interferon regulatory factor 4 (IRF4) status. Here, we presented 3 EBV-positive DLBCL cases with IRF4 rearrangement (EBV+DLBCL-IRF4-R) verified by fluorescence in situ hybridization (FISH). Three patients, including 1 male and 2 females (median age: 64 y; range: 45 to 68 y), had normal immune function. During a median follow-up of 12 months (range: 0 to 24 mo), 2 patients succumbed to the disease, and 1 patient achieved complete response. Three tumors were present in the mediastinum, stomach, and thalamus, respectively. All three tumors exhibited DLBCL morphology and were identified as the non-germinal center B-cell subtype, with EBV-encoded small RNA positivity ranging from 70% to 80%. RNA sequencing was able to identify RHOH and IGH as fusion partners of IRF4 in two cases. No MYC and BCL2 rearrangements were detected in 3 cases by FISH and RNA sequencing. Next-generation sequencing revealed a low mutation burden, and only IRF4 was recurrently mutated in two EBV+DLBCL-IRF4-R cases. Using the LymphGen 2.0 classifier, 1 case was classified as the MCD (including MYD88L265P and CD79B mutations) subtype. We report rare EBV+DLBCL-IRF4-R that may enhance our understanding of the diverse spectrum of large B-cell lymphoma.
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Background: CTLA4, an immune checkpoint, plays an important role in tumor immunotherapy. The purpose of this study was to develop a pathomics signature to evaluate CTLA4 expression and predict clinical outcomes in clear cell renal cell carcinoma (ccRCC) patients. Methods: A total of 354 patients from the TCGA-KIRC dataset were enrolled in this study. The patients were stratified into two groups based on the level of CTLA4 expression, and overall survival rates were analyzed between groups. Pathological features were identified using machine learning algorithms, and a gradient boosting machine (GBM) was employed to construct the pathomics signatures for predicting prognosis and CTLA4 expression. The predictive performance of the model was subsequently assessed. Enrichment analysis was performed on diferentially expressed genes related to the pathomics score (PS). Additionally, correlations between PS and TMB, as well as immune infiltration profiles associated with different PS values, were explored. In vitro experiments, CTLA4 knockdown was performed to investigate its impact on cell proliferation, migration, invasion, TGF-ß signaling pathway, and macrophage polarization. Results: High expression of CTLA4 was associated with an unfavorable prognosis in ccRCC patients. The pathomics signature displayed good performance in the validation set (AUC = 0.737; P < 0.001 in the log-rank test). The PS was positively correlated with CTLA4 expression. We next explored the underlying mechanism and found the associations between the pathomics signature and TGF-ß signaling pathways, TMB, and Tregs. Further in vitro experiments demonstrated that CTLA4 knockdown inhibited cell proliferation, migration, invasion, TGF-ß expression, and macrophage M2 polarization. Conclusion: High expression of CTLA4 was found to correlate with poor prognosis in ccRCC patients. The pathomics signature established by our group using machine learning effectively predicted both patient prognosis and CTLA4 expression levels in ccRCC cases.
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Objective: This study aims to determine whether tele-rehabilitation has similar effects to conventional face-to-face physical rehabilitation for diabetic patients with heart failure with preserved ejection fraction (HFpEF). Materials and methods: Demographic, laboratory, diagnostic and rehabilitation information for patients with type 2 diabetes with HFpEF were extracted from disease-specific databases. Outcome measures, including the Short Physical Performance Battery (SPPB), 6-minute walk distance, frailty status, European Quality of Life 5-Dimension 5-Level questionnaire (EQ-5D-5L) and reduction in HbA1c from admission, patients who received tele-rehabilitation therapy were compared to those received face-to-face rehabilitation. Results: In this study, 90 patients with type 2 diabetes and HFpEF using tele-rehabilitation were matched with 90 patients with type 2 diabetes and HFpEF using face-to-face physical rehabilitation. Improvements in the results of the SPPB scores, 6-min walk distance and gait speed and EQ-5D-5L were noted from the follow-up time point 3 months to 6 months in both two groups. There were no significant differences in functional tests and quality of life between the two groups. Conclusion: Our study proved that mobile-based tele-rehabilitation programs are non-inferior to face-to-face physical rehabilitation for diabetes patients after HFpEF. In addition, adherence to the telerehabilitation program showed that the novel technology was accepted well and could be an alternative to the conventional face-to-face rehabilitation program.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Qualidade de Vida , Volume Sistólico , Telerreabilitação , Humanos , Diabetes Mellitus Tipo 2/reabilitação , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/reabilitação , Insuficiência Cardíaca/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-IdadeRESUMO
Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is an extremely rare kidney tumor seen mainly in patients with end-stage renal disease. Currently, there are few reports on this type of tumor. We describe the case of a 58-year-old man who had been receiving peritoneal dialysis for more than nine years due to chronic renal insufficiency and uremia. One year after undergoing left renal clear cell renal cell carcinoma resection, a space-occupying lesion was found in the right kidney for which he underwent right nephrectomy. The histopathology of this tumor showed solid or tubular cell arrangements, with some areas of cyst formation. Vacuoles of varying sizes were present in the cytoplasm, and varying amounts of calcium oxalate crystals were found in the tumor cells or interstitium. The pathological diagnosis was ACD-RCC. Next-generation sequencing detected mutations in the PTCH1, MTOR, FAT1, SOS1, RECQL4, and CDC73 genes in the right renal tumor. This is a rare case of a patient with ACD-RCC in the right kidney and clear cell renal cell carcinoma in the left kidney. The findings suggest that mutations in PTCH1 associated with ACD-RCC may have acted as oncogenic drivers for the development of ACKD-RCC, together with providing insight into mechanisms underlying ACD-RCC development, as well as diagnostic and treatment options.
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CONTEXT.: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes. OBJECTIVE.: To address the concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC. DESIGN.: Clinical factors included age, sex, tumor size, and outcome. Morphologic factors included cell morphology, presence or absence of a nontubulocystic component, and stromal findings. Immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing were performed to explore the protein expression and molecular profiles of the 2 entities. RESULTS.: We evaluated 6 patients with tubulocystic RCC and 10 patients with tubulocystic FH-deficient RCC. Tubulocystic RCC exhibited a small size (<4.0 cm, pT1a), low Ki-67 index (<5%), retained FH, and negative 2SC expression. Tubulocystic FH-deficient RCC had a relatively large size and a high Ki-67 index. Perinucleolar haloes, loss of FH, and 2SC positivity were always observed. Pure tubulocystic architecture was not observed in FH-deficient RCC, because focal nontubulocystic components can always be seen. CONCLUSIONS.: We emphasized multiple sectioning to identify a nontubulocystic architecture to exclude tubulocystic RCC. Moreover, tumor size, FH/2SC staining, and the Ki-67 index can differentiate tubulocystic FH-deficient RCC from tubulocystic RCC. The diagnosis of tubulocystic RCC was not recommended in renal mass biopsy because of the limited tissues sampled.
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Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is rare in adults. The presence of intratumoral T lymphocytes and primitive rounded cells characterized this neoplasm. We report a 24-year-old Chinese man who developed EBV-SMT in the right adrenal gland with hepatitis B infection and autoimmune hemolytic anemia without a history of HIV infection, primary immune deficiency, organ transplantation, or malignant tumor. This patient had an unknown immunodeficient state. EBV-SMTs are commonly located in the liver, lung, and gastrointestinal tract but rarely in the adrenal gland. We reviewed 10 reported literature on EBV-SMT in the adrenal gland. It is imperative to distinguish EBV-SMT from conventional somatic smooth muscle tumors. The discovery of EBV-SMT forces the clinician to conduct a thorough evaluation of immune function and immune status surveillance, and these patients are vulnerable to subsequent malignant tumors.
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Anemia Hemolítica Autoimune , Infecções por Vírus Epstein-Barr , Hepatite B , Tumor de Músculo Liso , Humanos , Masculino , Tumor de Músculo Liso/patologia , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/virologia , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/patologia , Anemia Hemolítica Autoimune/imunologia , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/virologia , Adulto Jovem , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/patologia , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/virologia , Herpesvirus Humano 4/isolamento & purificaçãoRESUMO
Background. Pigmented microcystic chromophobe renal cell carcinoma (RCC) is a subtype of chromophobe RCC. Its distinct histopathologic features are microcystic and microtubular pattern, pigmentation, and microcalcifications. Pigmented microcystic chromophobe RCC has ultrastructure, immunophenotypic structure, and molecular results similar to chromophobe RCC. Methods. We report five tumors of pigmented microcystic chromophobe RCC. Morphological observation and immunohistochemical examination were performed, and clinical and molecular features were analyzed. Results. Microscopically, all five tumors showed brown pigmentation, microcystic, and tubular cystic structures, one tumor presented microscopic calcifications. All tumors were positive for EMA, AE1/AE3, PAX8, KRT7, KIT (CD117), claudin 7, KRT8, and E-cadherin, and three tumors expressed P504S. All tumors were negative for vimentin, CA9, KRT20, TFE3, TFEB, Melan-A, HMB45, FH, SDHB, and GATA3. Ki-67 index varied from less than 1% to 2%. In three tumors, next-generation sequencing of the 688 gene was performed, the results found gene variants with potential clinical significance such as JMJD1C, MYCL, TP53, PI3KCA, KRAS, APC, GLI1, LRRK2, and gene variants with unclear clinical significance such as NTRK1 and RAD50; All patients remained alive over a follow-up period of 8-46 months without tumor recurrence and sarcomatoid transformation. Conclusions. Pigmented microcystic chromophobe RCC has a relatively benign biological behavior, and distant metastases and sarcomatoid transformation are rare. This overview of five additional tumors of pigmented microcystic chromophobe RCC offers further insight into this special subtype of chromophobe RCC.
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Biomarcadores Tumorais , Carcinoma de Células Renais , Imuno-Histoquímica , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , Feminino , Idoso , Prognóstico , Adulto , Rim/patologia , Rim/cirurgiaRESUMO
BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.
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Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Humanos , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
BACKGROUND: The preoperative diagnosis of peritoneal metastasis (PM) in epithelial ovarian cancer (EOC) is challenging and can impact clinical decision-making. PURPOSE: To investigate the performance of T2 -weighted (T2W) MRI-based deep learning (DL) and radiomics methods for PM evaluation in EOC patients. STUDY TYPE: Retrospective. POPULATION: Four hundred seventy-nine patients from five centers, including one training set (N = 297 [mean, 54.87 years]), one internal validation set (N = 75 [mean, 56.67 years]), and two external validation sets (N = 53 [mean, 55.58 years] and N = 54 [mean, 58.22 years]). FIELD STRENGTH/SEQUENCE: 1.5 or 3 T/fat-suppression T2W fast or turbo spin-echo sequence. ASSESSMENT: ResNet-50 was used as the architecture of DL. The largest orthogonal slices of the tumor area, radiomics features, and clinical characteristics were used to construct the DL, radiomics, and clinical models, respectively. The three models were combined using decision-level fusion to create an ensemble model. Diagnostic performances of radiologists and radiology residents with and without model assistance were evaluated. STATISTICAL TESTS: Receiver operating characteristic analysis was used to assess the performances of models. The McNemar test was used to compare sensitivity and specificity. A two-tailed P < 0.05 was considered significant. RESULTS: The ensemble model had the best AUCs, outperforming the DL model (0.844 vs. 0.743, internal validation set; 0.859 vs. 0.737, external validation set I) and clinical model (0.872 vs. 0.730, external validation set II). After model assistance, all readers had significantly improved sensitivity, especially for those with less experience (junior radiologist1, from 0.639 to 0.820; junior radiologist2, from 0.689 to 0.803; resident1, from 0.623 to 0.803; resident2, from 0.541 to 0.738). One resident also had significantly improved specificity (from 0.633 to 0.789). DATA CONCLUSIONS: T2W MRI-based DL and radiomics approaches have the potential to preoperatively predict PM in EOC patients and assist in clinical decision-making. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Aprendizado Profundo , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias Ovarianas/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Renal cell carcinoma with fibromyomatous stroma (RCC FMS), defined as an "emerging entity" in the 2016 WHO classification and recommended to be a novel entity by GUPS, is represented by tumor cells with clear to mildly eosinophilic cytoplasm displaying elongated and branching tubules and papillae. A fibromyomatous stroma could be observed in these tumors. These tumors are immunopositive for CK7 and featured by ELOC and/or TSC/mTOR gene mutations. In the 2022 WHO classification, ELOC mutated RCC is classified as a molecularly defined RCCs as an individual renal entity. However, there are limited descriptions of TSC/mTOR alterations in RCC FMS. Herein, we reported a case of 28-year-old woman with RCC FMS with intact ELOC and TSC/mTOR genes but ASXL1 mutation. The tumor cells were positive for mTOR expression. This case may indicate that altered mTOR expression, but not limited to mutated TSC/mTOR gene, that participates in the pathogenesis of RCC FMS.
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Carcinoma de Células Renais , Neoplasias Renais , Mutação , Proteínas Repressoras , Serina-Treonina Quinases TOR , Humanos , Feminino , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/genética , Adulto , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Regulação para Cima , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análiseRESUMO
Background: Primary Sjogren Syndrome (pSS) is an autoimmune disease characterized by immune cell infiltration. While the presence of follicular T helper (Tfh) cells in the glandular microenvironment has been observed, their biological functions and clinical significance remain poorly understood. Methods: We enrolled a total of 106 patients with pSS and 46 patients without pSS for this study. Clinical data and labial salivary gland (LSG) biopsies were collected from all participants. Histological staining was performed to assess the distribution of Tfh cells and B cells. Transcriptome analysis using RNA-sequencing (RNA-seq) was conducted on 56 patients with pSS and 26 patients without pSS to uncover the underlying molecular mechanisms of Tfh cells. To categorize patients, we employed the single-sample gene set enrichment analysis (ssGSEA) algorithm, dividing them into low- and high-Tfh groups. We then utilized gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and deconvolution tools to explore functional and immune infiltration differences between the low- and high-Tfh groups. Results: Patients with pSS had a higher positive rate of the antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB and hypergammaglobulinaemia and higher levels of serum IgG compared to the non-pSS. Histopathologic analyses revealed the presence of Tfh cells (CD4+CXCR5+ICOS+) in germinal centers (GC) within the labial glands of pSS patients. GSEA, WGCNA, and correlation analysis indicated that the high-Tfh group was associated with an immune response related to virus-mediated IFN response and metabolic processes, primarily characterized by hypoxia, elevated glycolysis, and oxidative phosphorylation levels. In pSS, most immune cell types exhibited significantly higher infiltration levels in the high-Tfh group compared to the low-Tfh group. Additionally, patients in the Tfh-high group demonstrated a higher positive rate of the ANA, rheumatoid factor (RF), and hypergammaglobulinaemia, as well as higher serum IgG levels. Conclusion: Our study suggests that Tfh cells may play a crucial role in the pathogenesis of pSS and could serve as potential therapeutic targets in pSS patients.
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Síndrome de Sjogren , Transcriptoma , Humanos , Hipergamaglobulinemia , Síndrome de Sjogren/genética , Biologia de Sistemas , Células T Auxiliares Foliculares , Anticorpos Antinucleares , Imunoglobulina GRESUMO
PURPOSE: BRG1-deficient NSCLCs have been more intriguing recently for its highly aggressive clinical behavior and no effective therapies. This study characterized the clinical and pathological features of BRG1-deficient NSCLCs and investigated their response to immunotherapy. METHODS: Forty-seven cases with BRG1-deficient NSCLC were included. Immunohistochemical markers such as BRG1, CK7, TTF-1, NapsinA, P40, HepPar-1, Ki-67, BRM, ARID1A and ARID1B were stained. Additionally, the PD-L1 expression level, overall survival, progression-free survival and disease control rate of patients received immunotherapy were evaluated. RESULTS: This study revealed that: (1) Patients with BRG1-deficient NSCLC have a male predominance (89.4 %), smoker enrichment (76.6 %) and poor prognosis (median OS: 7.0 months for advanced stage). (2) Histologically, BRG1-deficient NSCLCs presented significant morphological diversity and no lepidic pattern. Inflammatory infiltration and tumor necrosis was a prominent feature. Immunohistochemical analyses showed a distinctive uniform immunophenotype (TTF-1-/NapsinA-/CK7+) in 60.9 % (28/46) of cases and HepPar-1 positive in 46.5 % (20/43) of cases. BRM loss or significant reduction coexisted in 11.8 % (4/34) of cases. No case (0/37) showed loss of ARID1A or ARID1B. (3) Eight patients with advanced tumor stage had received immunotherapy and 4 cases achieved a sustainable clinical response with the disease control rate of 50 %. CONCLUSION: BRG1-deficient NSCLC showed diverse histopathological patterns and a unique immunohistochemical phenotype. ICIs-based immunotherapy is a promising therapy needs to be investigated further for BRG1- deficient NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos Retrospectivos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Imunoterapia , Antígeno B7-H1 , Biomarcadores Tumorais/análiseRESUMO
BACKGROUND: Few studies have been conducted to explore the expression of tumor necrosis factor receptor-associated factor 6 in eosinophilic gastroenteritis patients. Therefore, the expression profile of tumor necrosis factor receptor-associated factor 6 in the gastrointestinal tract of eosinophilic gastroenteritis patients and its associations with clinical features were explored in this study. METHODS: Thirty-four eosinophilic gastroenteritis patients who presented in Ruijin Hospital from December 2012 to May 2019 and had accepted gastrointestinal endoscopic examinations were recruited. Medical records and endoscopic biopsies were collected, and the prognosis was followed up by telephone. Healthy persons were selected as the control group. Hematoxylin and eosin and immunohistochemical staining were performed in both eosinophilic gastroenteritis patients and healthy persons. The final results were analyzed by skilled pathologists, and mean optical density values of tumor necrosis factor receptor-associated factor 6 were calculated by Image J software. Final results were analyzed by Statistical Package for the Social Sciences software 22.0. RESULTS: Thirty-four patients (mean age: 25.56 ± 21.14 years, 61.76% males) were recruited for this study. There was no significant difference in tumor necrosis factor receptor-associated factor 6 mean optical density values of gastric tissues in eosinophilic gastroenteritis patients and healthy people (0.22 ± 0.16 vs. 0.14 ± 0.05, P > .05). Eosinophilic gastroenteritis patients had a significantly lower level of intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values than that of healthy people (0.16 ± 0.05 vs. 0.23 ± 0.06, P < .05). Intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values negatively linearly correlated with serum interleukin-10 level (r = -0.618, P = .043 < .05). There were no differences between eosinophilic gastroenteritis patients with or without relapse regarding the expression level of intestinal tumor necrosis factor receptor-associated factor 6 (P = .227 > .05). CONCLUSION: Patients with eosinophilic gastroenteritis might have a deficiency of intestinal tumor necrosis factor receptor-associated factor 6 compared to healthy controls.
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Enterite , Masculino , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Prognóstico , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose TumoralRESUMO
PURPOSE: To evaluate the feasibility of using iodine overlay maps reconstructed from dual-energy CT (DECT) to assess thrombus perviousness and investigate its value in predicting outcomes after intravenous thrombolysis in patients with acute ischemic stroke. METHOD: 86 patients with proximal intracranial occlusions of the anterior circulation who underwent intravenous thrombolysis were included in this study. Thrombus iodine concentrations (ICthrombus) and normalized iodine concentrations (NICthrombus) were compared to conventional perviousness parameters (thrombus attenuation increase, TAI; void fraction, ε and CTA-index). The associations between perviousness parameters and outcomes were analyzed by Spearman's correlation and regression analysis. RESULTS: ICthrombus and NICthrombus were significantly correlated with conventional perviousness parameters (P < 0.001). The median ICthrombus was 6.81 (interquartile range [IQR], 4.76-8.73) mg/ml in the favorable functional outcome group, which was higher than 3.52 (IQR, 2.08-6.86) mg/ml in the unfavorable outcome group (P = 0.001). The median NICthrombus was 0.095 (IQR, 0.068-0.116) and 0.054 (IQR, 0.031-0.083) in the favorable and unfavorable outcome groups, respectively (P < 0.001). NICthrombus predicted favorable outcome with a higher area under the curve (AUC) of 0.755 than any conventional perviousness parameter (P < 0.05). In the multivariable regression model, ICthrombus was independently associated with favorable outcome (odds ratio [OR] = 1.472, 95 % CI: 1.154-1.877, P = 0.002) and successful recanalization (OR = 1.356, 95 % CI: 1.093-1.681, P = 0.006). ICthrombus was negatively correlated with the final infarct volume (FIV) (r = -0.262, P = 0.020). Results for NICthrombus were similar. CONCLUSIONS: DECT is of great value in assessing thrombus perviousness. NICthrombus is a meaningful predictor of stroke prognosis and recanalization after intravenous thrombolysis in acute ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , Angiografia por Tomografia Computadorizada/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Resultado do Tratamento , Terapia Trombolítica , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológicoRESUMO
Rearranged renal cell carcinomas (RCC) are rare types of kidney cancer. The clinicopathological features of rearranged RCC require further validation. The pathological diagnosis usually depends on immunohistochemistry and molecular analysis. This study aimed to explore the expression features of anti-TFE3, TFEB, and ALK in different renal entities. In addition, we collected thirty-six TFE3-rearranged RCC, two TFEB-altered RCC, and one ALK-rearranged RCC to explore their clinicopathological features. We observed that TFE3 can sometimes be weakly expressed in non-TFE3-rearranged RCC. TFE3-rearranged RCC usually exhibited strong TFE3 expression. However, clear cell RCC and FH-deficient RCC also displayed strong TFE3 expression. TFEB also can be weakly expressed in clear cell RCC. However, ALK IHC showed a relatively high specificity and was negative for all non-ALK-rearranged RCC. The ALK-rearranged RCC was analyzed using next generation sequencing to explore gene alterations, and we identified a novel gene partner, SLIT1. ALK-rearranged RCC appears to have eosinophilic cytoplasm. Tumor cells with clear cytoplasm may exclude this diagnosis. Psammomatous bodies (22/38) and pattern multiplicity (35/38) were observed in more than half of the patients. In conclusion, weak TFE3 expression did not indicate TFE3 rearrangement. Strong TFE3 expression had a higher value for indicating TFE3-rearranged RCC, although other entities can also exhibit a strong pattern. Young age combined with morphological features (psammomatous calcification and pattern multiplicity) may indicate the diagnosis of rearranged RCC.
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AIMS: Cytokeratin 5 (CK5) is a surrogate maker of progenitor cells and early glandular and myoepithelial cells (MECs) in the breast, and CK5 expression in breast MECs varies from ducts to lobules, and from normal to diseased tissue. However, the mechanisms underlying immunophenotypic alterations of CK5 expression in MECs remain unclear. METHODS: CK5 expression in MECs of 20 normal breast samples, 58 ductal carcinoma in situ (DCIS; including 21 DCIS with extensive lobular involvement), 11 atypical ductal hyperplasia (ADH), 18 non-invasive lobular neoplasia consisting of 11 atypical lobular hyperplasia (ALH) and 7 lobular carcinoma in situ (LCIS), 20 cystic lobules and 10 usual ductal hyperplasia (UDH) involving lobules were observed to evaluate the effects of contact with benign hyperplastic or cancerous luminal cells and pressure of dilated glands on CK5 expression. RESULTS: CK5 expression in normal ductal MECs was exclusively positive, whereas most normal lobular MECs were negative. In DCIS, cancerous ducts were primarily surrounded by CK5-positive MECs (91.0%), as were lobular acini involved by DCIS (89.2%), while the remaining normal acini maintained CK5-negative. CK5-positive MECs were found in 57.5% of acini in ALH and were more prevalent in LCIS (70.7%). CK5 expression was occasionally positive in both cystic lobules (16.7%) and lobules involved by UDH (14.3%), while an increase of CK5-positive MECs was found in ADH (38.2%). CONCLUSIONS: These results suggest that CK5 expression in lobular MECs may be altered by contact with cancerous luminal cells rather than benign hyperplastic luminal cells or pressure from dilated glands.
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The last decade has seen great advances in genomic profiling and prognosis-associated factors of clear cell renal cell carcinoma (RCC), the most common entity in kidney cancer. Following VHL, PBRM1, SETD2, BAP1, and KDM5C have been validated as the most common co-occurring gene mutations in clear cell RCC by multicenter studies. However, the morphological features of clear cell RCC with co-occurring gene mutations remain unclear. In this study, we presented 20 clear cell RCCs that underwent next-generation sequencing, of which 1 tumor was reclassified as ELOC-mutated RCC. PBRM1, SETD2, BAP1, and KDM5C were the most common mutations, following VHL. Morphologically, clear cell RCC with PBRM1 or KDM5C mutation usually displayed a low-grade pattern. Cystic changes and hyalinized stroma were often observed. The Ki67 index was <10%. These observations indicated good prognosis. However, mutated SETD2 may increase the malignancy of clear cell RCC with PBRM1 mutation. Two clear cell RCCs with mutated PBRM1 and SETD2 developed local or distant metastases. Clear cell RCC with BAP1 mutations always had high-grade patterns, and rhabdoid differentiation was also observed, indicating that BAP1 mutation was associated with poor outcomes. Papillary architecture was often a feature of BAP1 mutation, which is uncommon in clear cell RCC. PDL1 was positive in only one tumor with BAP1 mutation, and the positivity rate was limited to 5%. B7H3 was negative in all tumors. Morphologic findings in this small cohort may suggest why PBRM1 mutation does not correlate with decreased survival, whereas BAP1 mutation usually predicts poor outcomes.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Proteínas Supressoras de Tumor/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Mutação , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Ubiquitina Tiolesterase/genética , Histona Desmetilases/genéticaRESUMO
AIMS: Indolent natural killer (NK) cell lymphoproliferative disorder of the gastrointestinal (GI) tract (iNKLPD) is a rare, recently recognised neoplasm. Most of the reported tumours are confined to the GI tract, while a small subset of the tumours harbour JAK3 mutations. We collected four cases of iNKLPD with the goal of adding additional information to the current knowledge of this disease regarding the clinicopathological, immunohistochemical and molecular features. METHODS AND RESULTS: Similar features including medium- to large-sized lymphoid cells with variable amounts of pale or slightly eosinophilic cytoplasm, and no evidence of EBER, TCR rearrangement were found in four cases. JAK3 K563_C565del mutation was found in one of three cases that were subjected to targeted next-generation sequencing. Unique findings of our study include one iNKLPD encountered for the first time in nasopharynx, where lesions could be inadvertently diagnosed as extranodal NK/T cell lymphoma, and one iNKLPD located in the gallbladder extended deeply into muscular and adventitial layers. Exceptional CD8-positive expression was observed in one iNKLPD. In addition, positive staining of phospho-STAT5, phospho-STAT3 and phospho-p38 were found in our cases. None of the four patients received therapy for lymphoma, but all had a benign clinical outcome during a follow-up time of 20-99 months. CONCLUSIONS: We present four iNKLPDs with clinical, immunohistochemical and molecular features similar to the reported cases, as well as some unusual characters, which expand our knowledge on this disease, and further support the neoplastic nature of iNKLPDs.
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Linfoma , Transtornos Linfoproliferativos , Células T Matadoras Naturais , Humanos , Trato Gastrointestinal/patologia , Células Matadoras Naturais/patologia , Transtornos Linfoproliferativos/patologia , Linfoma/patologia , Células T Matadoras Naturais/patologiaRESUMO
PURPOSE: We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery. MATERIALS AND METHODS: The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women). RESULTS: In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20). CONCLUSION: ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary What is the context? ⢠The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively. ⢠ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection. ⢠There is little research on ACE2 in humans, especially in the lung tissue. ⢠In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations. What is new? ⢠Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were: ⢠In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing. ⢠Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue. ⢠Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs. What is the impact? ⢠ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension. ⢠A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.