Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma.

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24-74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43-79%) and 68% (95%CI, 47-84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45-83%) and 86% (95%CI, 63-95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

GPCR signaling contributes to immune characteristics of microenvironment and process of EBV-induced lymphomagenesis.

Epstein-Barr virus (EBV) is the oncogenic driver of multiple cancers. However, the underlying mechanism of virus-cancer immunological interaction during disease pathogenesis remains largely elusive. Here we reported the first comprehensive proteogenomic characterization of natural killer/T-cell lymphoma (NKTCL), a representative disease model to study EBV-induced lymphomagenesis, incorporating genomic, transcriptomic, and in-depth proteomic data. Our multi-omics analysis of NKTCL revealed that EBV gene pattern correlated with immune-related oncogenic signaling. Single-cell transcriptome further delineated the tumor microenvironment as immune-inflamed, -deficient, and -desert phenotypes, in association with different setpoints of cancer-immunity cycle. EBV interacted with transcriptional factors to provoke GPCR interactome (GPCRome) reprogramming. Enhanced expression of chemokine receptor-1 (CCR1) on malignant and immunosuppressive cells modulated virus-cancer interaction on microenvironment. Therapeutic targeting CCR1 showed promising efficacy with EBV eradication, T-cell activation, and lymphoma cell killing in NKTCL organoid. Collectively, our study identified a previously unknown GPCR-mediated malignant progression and translated sensors of viral molecules into EBV-specific anti-cancer therapeutics.

A cohort autopsy study defines COVID-19 systemic pathogenesis.

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Prognostic and predictive significance of tumor infiltrating lymphocytes for ductal carcinoma in situ.

This study aims to identify the density of TILs in ductal carcinoma in situ (DCIS) in terms of prognostic significance with recurrence and the benefit of whole breast irradiation (WBI). The clinicopathological data of DCIS patients from Jan 2009 to Dec 2016 who received breast-conserving surgery (BCS) were retrospectively reviewed. Cox regression analysis was used to confirm independent prognostic factors of ipsilateral breast tumor recurrence (IBTR). Kaplan-Meier method was utilized to analyze IBTR and values of WBI. Touching-tumor-infiltrating lymphocytes (TILs) were defined by TILs touching or within one lymphocyte cell thickness from the malignant ducts' basement membrane. In total, 129 patients were enrolled in this analysis with 98 patients who received WBI. After a median follow-up of 53.0 months, there were 16 IBTR events with five invasive IBTRs. Univariate and multivariate analyses showed that touching-TILs >5 were an independent prognostic factor for higher IBTR (HR = 6.17, 95%CI 1.95-19.56, p < .01). The whole cohort was classified into two subgroups: dense group (>5 touching-TILs per duct) and sparse group (≤5 touching-TILs per duct). Dense touching-TILs were associated with unfavorable biologic characteristics. The 5-y rate of IBTR between dense and sparse group was 29.0% versus 4.5% (p < .01). For the sparse group, WBI significantly reduced the rate of 5-y-IBTR risk from 13.2% to 1.7% (p = .02), but there was no benefit of WBI in the dense group. Touching-TILs density was heterogeneous in patients with DCIS. Sparse touching-TILs were associated with better prognosis and benefit from WBI. Dense touching-TILs not only were associated with a higher risk of IBTR but also lack of benefit from WBI.

A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes.

Long noncoding RNAs (lncRNAs) play an essential role in tumor progression. Few researches focused on the clinical and biological relevance of lncRNAs in peripheral T cell lymphoma (PTCL). In this research, a novel lncRNA (ENST00000503502) was identified overexpressed in the main subtypes of PTCL, and designated as T cell lymphoma-associated lncRNA1 (TCLlnc1). Serum TCLlnc1 was associated with extranodal involvement, high-risk International Prognostic Index, and poor prognosis of the patients. Both in vitro and in vivo, overexpression of TCLlnc1 promoted T-lymphoma cell proliferation and migration, both of which were counteracted by the knockdown of TCLlnc1 using small interfering RNAs. As the mechanism of action, TCLlnc1 directly interacted with transcription activator heterogeneous nuclear ribonucleoprotein D (HNRNPD) and Y-box binding protein-1 (YBX1) by acting as a modular scaffold. TCLlnc1/HNRNPD/YBX1 complex upregulated transcription of TGFB2 and TGFBR1 genes, activated the tumor growth factor-ß signaling pathway, resulting in lymphoma progression, and might be a potential target in PTCL.

Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma.

BACKGROUND: Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). RESULTS: Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52-79) and 83% (95% CI 68-91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3-4 neutropenia was reported in 171, grade 3-4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. CONCLUSION: CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

COVID-19 and early-stage lung cancer both featuring ground-glass opacities: a propensity score-matched study.

BACKGROUND: Radiological manifestations of coronavirus disease 2019 (COVID-19) featured ground-glass opacities (GGOs), especially in the early stage, which might create confusion in differential diagnosis with early lung cancer. We aimed to specify the radiological characteristics of COVID-19 and early lung cancer and to unveil the discrepancy between them. METHODS: One hundred and fifty-seven COVID-19 patients and 374 early lung cancer patients from four hospitals in China were retrospectively enrolled. Epidemiological, clinical, radiological, and pathological characteristics were compared between the two groups using propensity score-matched (PSM) analysis. RESULTS: COVID-19 patients had more distinct symptoms, tended to be younger (P<0.0001), male (P<0.0001), and had a higher body mass index (P=0.014). After 1:1 PSM, 121 matched pairs were identified. Regarding radiological characteristics, patients with a single lesion accounted for 17% in COVID-19 and 89% in lung cancer (P<0.0001). Most lesions were peripherally found in both groups. Lesions in COVID-19 involved more lobes (median 3.5 vs. 1; P<0.0001) and segments (median 6 vs. 1; P<0.0001) and tended to have multiple types (67%) with patchy form (54%). Early lung cancer was more likely to have a single type (92%) with oval form (66%). Also, COVID-19 and early lung cancer either had some distinctive features on computed tomography (CT) images. CONCLUSIONS: Both COVID-19 and early lung cancers showed GGOs, with similar but independent features. The imaging characteristics should be fully understood and combined with epidemiological history, pathogen detection, laboratory tests, short-term CT reexamination, and pathological results to aid differential diagnosis.

Implications from Broadband Microwave Absorption of Metal-Modified SiC Fiber Mats.

Understanding the physical requirements for a broad bandwidth is vital for the design of high-efficiency microwave absorber. Our recent works on silicon carbide (SiC) fiber mats-based absorbers imply that metal modification (e.g., Fe or Hf) could benefit their bandwidth effectively. For verification, we fabricated a Co/SiC fiber mat via a similar electrospinning process and subsequent pyrolysis at 1400 °C in Ar atmosphere. The results indicate that after Co modification, the SiC fiber mats show elevated permittivity and tangent loss. With a proper amount of Co adding, the mats could exhibit a wide bandwidth of around 8 GHz (ranging from 10 to 18 GHz) for effective absorption (reflection loss (RL) less than -10 dB) at 2.8 mm thickness. This is similar to our previous findings, confirming that metal modification could be an effective approach to extend the bandwidth of SiC mat absorbers. Explanations can be found through theoretical analysis with the quarter wavelength (λ/4) cancellation theory. It suggests that the declining permittivity (with the increase of frequency) is the key to keep the wavelength in material (λm) nearly unchanged within a frequency range. As a result, in this range, λ/4 cancellation could still be satisfied without changing thickness, which could explain the reasons for the broad bandwidth of metal-modified SiC fiber mats. With this model, it is further predicted that the effective absorption bandwidth could be even extended to be around 12 GHz with appropriate tangent loss. It should be emphasized that the implications obtained in this study could also be applicable to other dielectric absorbers. The requirement of permittivity and the proposed approach could serve as guidelines to achieve a wide bandwidth on a dielectric absorber relying on the λ/4 cancellation principle.

Genomic and Transcriptomic Characterization of Natural Killer T Cell Lymphoma.

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

Pretreatment Liver Injury Predicts Poor Prognosis of DLBCL Patients.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphoma, with different clinical manifestation and prognosis. The International Prognostic Index (IPI), an index designed during the prerituximab era for aggressive lymphoma, showed variable values in the prediction of patient clinical outcomes. The aim of this study was to analyze the prognostic value and causes of pretreatment liver injury in 363 de novo DLBCL patients in our institution. Pretreatment liver impairment, commonly detected in lymphoma patients, showed significant association with poor outcomes and increased serum inflammatory cytokines in DLBCL patients but had no relation to hepatitis B virus replication nor lymphomatous hepatic infiltration. Multivariate analysis revealed that liver dysfunction, advanced Ann Arbor stage, and elevated lactate dehydrogenase (LDH) were independent adverse prognostic factors of both PFS and OS. Accordingly, a new liver-IPI prognostic model was designed by adding liver injury as an important factor in determining IPI score. Based on Kaplan-Meier curves for PFS and OS, the liver-IPI showed better stratification in DLBCL patients than either the IPI or the revised IPI in survival prediction.

A Phase II Study of Methotrexate, Etoposide, Dexamethasone and Pegaspargase Sandwiched with Radiotherapy in the Treatment of Newly Diagnosed, Stage IE to IIE Extranodal Natural-Killer/T-Cell Lymphoma, Nasal-Type.

BACKGROUND: A phase II study of methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) sandwiched with radiotherapy for newly diagnosed, stage IE-IIE extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL) was conducted to explore its clinical efficacy and safety, as well as novel serum biomarkers upon anti-metabolic treatment. METHODS: Four cycles of MESA sandwiched with radiotherapy were administered. The primary end point was the overall response rate (ORR). Serum metabolomic profiles were assessed by liquid chromatography-mass spectrometry, with specific metabolites quantified by targeted metabolic analysis. FINDINGS: Forty patients were enrolled and the ORR was 92.1% (95%CI, 83.1%-100.0%). The 2-year progression-free survival (PFS) rate was 89.1% and overall survival (OS) rate was 92.0%. Grade 3/4 non-hematologic and hematologic toxicities were observed in 17 (42.5%) and 26 patients (65·0%) during chemotherapy, and in 9 (22.5%) and 0 (0.0%) patients during radiotherapy, respectively. Fifty-six significantly decreased and 59 increased metabolites were identified in ENKTL, as compared to healthy volunteers. A predictive principal components analysis model of asparaginase-associated metabolites, asparaginase-associated metabolic score (AspM), was established, including alanine, aspartate, glutamate, and succinic acid. Patients with high AspM score displayed superior survival and prognostic significance of AspM was validated in a historical cohort of early and advanced-stage ENKTL treated with asparaginase-based regimens. Multivariate analysis confirmed AspM as a prognostic score independent of PINK and PINK combined with Epstein-Barr virus DNA. INTERPRETATION: MESA sandwiched with radiotherapy is an effective and safe regimen for early-stage ENKTL. AspM score may be a promising prognostic index of serum metabolites in addition to clinical prognostic index in ENKTL.

Linc00152 promotes Cancer Cell Proliferation and Invasion and Predicts Poor Prognosis in Lung adenocarcinoma.

Background: The long non-coding RNA Linc00152 stimulates tumor progression in cancer. However, its clinical significance and biological functions in lung adenocarcinoma remains unknown. We evaluate the expression of Linc00152 in lung adenocarcinoma and its possible correlation with clinicopathologic features and patient survival to reveal its biological effects in cancer progression and prognosis. Methods: Total RNA extraction was performed on 110 pairs of lung adenocarcinoma and adjacent normal tissue samples, and then RT-qPCR was conducted. Chi-square test analysis was used to calculate the correlation between pathological parameters and the Linc00152 mRNA levels. Kaplan-Meier and Cox proportional hazards analyses were used to analyze the overall survival (OS) and disease-free survival (DFS) rates. We also detected the potential functional effects of overexpression and knockdown of Linc00152 in vitro cell proliferation, tumor cell invasion and migration, as well as in vivo nude mouse xenograft and metastasis models. Results: The Linc00152 expression levels were higher in lung adenocarcinoma samples than in the adjacent normal tissues. Linc00152 expression levels tightly correlated with lymph node metastasis station, remote metastasis and TNM staging. The Kaplan-Meier analysis suggested that high Linc00152 expression caused significantly poorer OS and DFS rates, and a multivariate analysis revealed that Linc00152 was an independent risk factor for both DFS and OS. Overexpression of Linc00152 in lung cancer cells stimulated proliferation, tumor cell invasion and migration. Knockdown of Linc00152 inhibited cell growth and cell invasion and migration. Finally, Linc00152 knockdown inhibited lung tumor growth and tumor metastasis in nude mice models. Conclusions: Our study suggests that Linc00152 independently predicts poor prognosis and promotes tumor progression in lung adenocarcinoma. Linc00152 needs to be considered as a potential molecular target in future cancer pharmacology.

JAM-A overexpression is related to disease progression in diffuse large B-cell lymphoma and downregulated by lenalidomide.

Cancer stem cells play an important role on tumor progression. Biomarkers of stem cell property and their relationship to extranodal involvement of malignant lymphocytes are undefined in diffuse large B-cell lymphoma (DLBCL). Here we showed that junctional adhesion molecule-A (JAM-A) was highly expressed in DLBCL patients with multiple extranodal lesions. JAM-A maintained B-lymphoma cell stemness and was associated with cell invasion and epithelial-to-mesenchymal transition both in vitro and in vivo. As mechanism of action, JAM-A overexpression selectively activated transforming growth factor-ß (TGF-ß)/NODAL signaling, thereby enhanced B-lymphoma cell aggressiveness and induced extranodal involvement to mesoendoderm-derived organs in DLBCL. Lenalidomide downregulated JAM-A and downstream NODAL expression, resulting in inhibition of B-lymphoma cell invasion and epithelial-to-mesenchymal transition. In a murine xenograft model established with subcutaneous injection of JAM-A-overexpressing B-lymphoma cells, lenalidomide retarded tumor growth and prevented cell invasion to mesoendoderm-derived organs, consistent with the downregulation of JAM-A and NODAL expression. Collectively, these findings indicated that JAM-A was related to extranodal involvement in DLBCL through modulating TGF-ß/NODAL signaling. Identified as a biomarker of stem cell property, JAM-A indicated the sensitivity of B-lymphoma cells to lenalidomide. Therapeutic targeting of JAM-A/NODAL axis could thus be a promising clinical strategy to impede tumor progression in DLBCL.

Pulmonary enteric adenocarcinoma with pancreatic metastasis: A case report.

Pulmonary enteric adenocarcinoma is a markedly rare pathological type of lung adenocarcinoma. As the pancreas is a relatively uncommon site for metastasis, the present case is even more unusual. A 62-year-old male was admitted to hospital following the identification of masses in the left chest wall, right abdominal wall and right upper limb, but with no respiratory symptoms. Computed tomography (CT) of the chest revealed a lump in the lung and a mass in the left chest wall, and 18F-fluorodeoxyglucose (18F-FDG) uptake by the lumps was increased. An enhanced abdominal CT revealed a hypodense and homogeneous mass on the head of the pancreas, which was slightly enhanced compared with normal pancreatic tissue. In addition, the 18F-FDG uptake of the lesion was increased and the standardized uptake value (SUV) delayed was not evidently decreased compared with SUVearly. A number of other abnormal metabolic lesions were also identified using positron emission tomography/CT, whereas no abnormal 18F-FDG uptake was identified in the gastrointestinal organ. Furthermore, rectocolonoscopy was performed to exclude diagnosis of metastatic colorectal adenocarcinoma. The hematoxylin- and eosin-stained smears of the masses in the right lung and left chest demonstrated an enteric pattern, which shared morphological and immunohistochemical (IHC) features with those of colorectal adenocarcinoma. The IHC detection revealed that the lesions in the right lung were positive for cytokeratin 7 (CK7), and negative for CK20 and thyroid transcription factor 1 (TTF-1), and the expression of caudal type homeobox 2 (CDX2) was weakly positive; the masses in the left chest wall were positive for CK7, negative for TTF-1, and CK20 and CDX2 were weakly expressed.

Primary tracheal schwannoma treated by surgical resection: a case report.

The rarity and non-specific symptoms of benign primary tracheal tumors always leaded to misdiagnosis and delayed treatment, and also undefined the optimal treatment. In this case, a 45-year-old woman had a history of progressive shortness of breath and dry cough for several years, CT scan revealed an intra-luminal tracheal mass invaded the left side of tracheal wall. After being located by bronchoscope preoperatively, the tumor was removed by surgical resection. The tumor was 1.5 cm in diameter with intact capsule. The pathological result confirmed the diagnosis of schwannoma.

Primary Intestinal Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Comprehensive Clinicopathological Analysis of 55 Cases.

PURPOSE: To investigate the clinicopathological features, survival and prognostic factors of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type (PI-ENKTCL). METHODS: Clinical and histological characteristics of PI-ENKTCL cases were retrospectively evaluated. Immunohistochemical phenotype and status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. The overall survival and prognostic parameters were also analyzed. RESULTS: Fifty-five (2.7%) cases with PI-ENKTCL were identified out of 2017 archived ENKTCL cases, with a median age of 39 years and a male to female ratio of 2.1:1. The most common symptom was abdominal pain (90.9%), accompanied frequently with fever and less commonly with intestinal perforation or B symptoms. Small intestine (50.9%) was the most common site to be involved. 47.3% and 36.4% cases presented with stage I and II diseases, respectively. Histologically, most cases displayed characteristic morphologic changes of ENKTCL. Cytoplasmic CD3, TIA-1 and CD56 expression was found in 100%, 94.5% and 89.1% of cases, respectively. In situ hybridization detection for EBV demonstrated positive results in all cases. Monoclonal TCR gene rearrangement was found in 52.9% of tested cases. Chemotherapy with a DICE or L-asparaginase/peg-asparginase-containing regimen was most often employed. Both advanced tumor stage and B symptoms were independent inferior prognostic factors (p = 0.001 and p = 0.010). Noticeably, 6 cases demonstrated a CD4-positive phenotype. These cases featured a relatively older median age (58 years), predominance of small/medium-sized neoplastic cells, a higher rate of TCR rearrangement and slightly favorable outcome. CONCLUSION: We reported by far the largest series of PI-ENKTCL, and demonstrated its heterogeneity, aggressive clinical behavior and unsatisfying response to the current therapeutic strategies. Those CD4-positive cases might represent a unique subtype of PI-ENKTCL or distinct entity. Further investigations are required for the better understanding and management of this unusual disease.

Long non-coding RNA Linc00152 is a positive prognostic factor for and demonstrates malignant biological behavior in clear cell renal cell carcinoma.

Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In the present study, we screened the lncRNAs profile in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) database, and got linc00152, a differentially expressed lncRNA that haven't been reported in ccRCC. To further explore its role in ccRCC, the level of Linc00152 was detected in 77 paired ccRCC tissues and renal cancer cell lines by qRT-PCR, and its association with overall survival was assessed by statistical analysis. Linc00152 expression was significantly up-regulated in cancerous tissues and cell lines compared with normal counterparts, and high Linc00152 expression was closely associated with advanced TNM stage. Moreover, Linc00152 was found to be able to serve as an independent predictor of overall survival. Further experiments demonstrated that overexpression of Linc00152 can significantly promote cell proliferation and invasion, inhibit cell cycle arrest in G1 phase and dramatically decrease apoptosis in both 786O and Caki-2 cell lines, whereas the opposite results were observed with attenuated Linc00152 expression. Our data suggest that Linc00152 is a novel molecule involved in ccRCC progression as well as a potential prognostic biomarker and therapeutic target.

Microcystic/Reticular Schwannoma of the Mandible First Case Report and Review of the Literature.

Schwannoma comprises a group of nerve sheath tumors. Morphologic variants of schwannoma have no distinct relationship to clinical behavior, but unawareness of rare variants may lead to diagnostic pitfall and risk of mistreatment. Microcystic/reticular schwannoma is a recently described rare variant of schwannoma. We report a case of a 61-year-old female with a 5.0 cm × 3.5 cm × 3.0 cm mass in the right mandible, which has never been reported to date. Light microscopic evaluation showed that the mass was circumscribed with focal infiltration. Arranged in a prominent microcystic and reticular growth pattern, tumor cells were spindle-shaped with eosinophilic cytoplasm. No evidence of cytologic atypia, mitosis, or necrosis was observed. The stroma of the tumor mainly contained myxoid material with local infiltration of hyalinized collagen. Tumor cells showed diffuse and strong nuclear and cytoplasmic immunoreactivity for S100 protein. Tumor cells were also positive for CD34, CD99, and NSE, but negative for CK, EMA, CK5/6, P63, Calponin, CD10, SMA, Desmin, GFAP, NF, Syn, and CgA. The proliferation marker MIB-1 showed <1% nuclear reaction. Furthermore, we reviewed the clinical and pathological features of 24 previously reported cases of microcystic/reticular schwannoma. Unlike classic schwannoma, the reticular variant showed striking microcystic and reticular architecture microscopically. Recognition of these distinct entities is essential in avoiding misdiagnosis. Unlike classic schwannoma with a complete capsule, some masses were reported to lack encapsulation or contain focal infiltration. Further follow-up of tentative or identified cases is necessary to better understand this schwannoma.