Histone methyltransferase KMT2D inhibits ENKTL carcinogenesis by epigenetically activating SGK1 and SOCS1.

BACKGROUND: Epigenetic alteration plays an essential role in the occurrence and development of extranodal natural killer/T cell lymphoma (ENKTL). Histone methyltransferase (HMT) KMT2D is an epigenetic regulator that plays different roles in different tumors, but its role and mechanism in ENKTL are still unclear. METHODS: We performed immunohistochemical staining of 112 ENKTL formalin-fixed paraffin-embedded (FFPE) samples. Then, we constructed KMT2D knockdown cell lines and conducted research on cell biological behavior. Finally, to further investigate KMT2D-mediated downstream genes, ChIP-seq and ChIP -qPCR was performed. RESULTS: The low expression of KMT2D was related to a decreased abundance in histone H3 lysine 4 mono- and trimethylation (H3K4me1/3). In KMT2D knockdown YT and NK-YS cells, cell proliferation was faster (P < 0.05), apoptosis was decreased (P < 0.05), the abundance of S phase cells was increased (P < 0.05), and the level of H3K4me1 was decreased. Notably, ChIP-seq revealed two crucial genes and pathways downregulated by KMT2D. CONCLUSIONS: KMT2D is a tumor suppressor gene that mediates H3K4me1 and influences ENKTL proliferation and apoptosis by regulating the cell cycle. Moreover, in ENKTL, serum- and glucocorticoid-inducible kinase-1 (SGK1) and suppressor of cytokine signaling-1 (SOCS1) are downstream genes of KMT2D.

Identifying CD1c as a potential biomarker by the comprehensive exploration of tumor mutational burden and immune infiltration in diffuse large B cell lymphoma.

Background: Tumor mutational burden (TMB) is a valuable prognostic biomarker. This study explored the predictive value of TMB and the potential association between TMB and immune infiltration in diffuse large B-cell lymphoma (DLBCL). Methods: We downloaded the gene expression profile, somatic mutation, and clinical data of DLBCL patients from The Cancer Genome Atlas (TCGA) database. We classified the samples into high-and low-TMB groups to identify differentially expressed genes (DEGs). Functional enrichment analyses were performed to determine the biological functions of the DEGs. We utilized the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm to estimate the abundance of 22 immune cells, and the significant difference was determined by the Wilcoxon rank-sum test between the high- and low-TMB group. Hub gene had been screened as the prognostic TMB-related immune biomarker by the combination of the Immunology Database and Analysis Portal (ImmPort) database and the univariate Cox analysis from the Gene Expression Omnibus (GEO) database including six DLBCL datasets. Various database applications such as Tumor Immune Estimation Resource (TIMER), CellMiner, konckTF, and Genotype-Tissue Expression (GTEx) verified the functions of the target gene. Wet assay confirmed the target gene expression at RNA and protein levels in DLBCL tissue and cell samples. Results: Single nucleotide polymorphism (SNP) occurred more frequently than insertion and deletion, and C > T was the most common single nucleotide variant (SNV) in DLBCL. Survival analysis showed that the high-TMB group conferred poor survival outcomes. A total of 62 DEGs were obtained, and 13 TMB-related immune genes were identified. Univariate Cox analysis results illustrated that CD1c mutation was associated with lower TMB and manifested a satisfactory clinical prognosis by analysis of large samples from the GEO database. In addition, infiltration levels of immune cells in the high-TMB group were lower. Using the TIMER database, we systematically analyzed that the expression of CD1c was positively correlated with B cells, neutrophils, and dendritic cells and negatively correlated with CD8+ T cells, CD4+ T cells, and macrophages. Drug sensitivity showed a significant positive correlation between CD1c expression level and clinical drug sensitivity from the CellMiner database. CREB1, AHR, and TOX were used to comprehensively explore the regulation of CD1c-related transcription factors and signaling pathways by the KnockTF database. We searched the GETx database to compare the mRNA expression levels of CD1c between DLBCL and normal tissues, and the results suggested a significant difference between them. Moreover, wet experiments were conducted to verify the high expression of CD1c in DLBCL at the RNA and protein levels. Conclusions: Higher TMB correlated with poor survival outcomes and inhibited the immune infiltrates in DLBCL. Our results suggest that CD1c is a TMB-related prognostic biomarker.

Extranodal natural killer/T-cell lymphoma with hepatosplenic involvement: a retrospective study of a consecutive 14-year case series.

Extranodal natural killer/T-cell lymphoma (ENKTL) with hepatosplenic involvement is rare, accounting for approximately 0.2% of ENKTL cases. The clinicopathologic features of ENKTL with hepatosplenic involvement are still poorly understood. Seven cases of ENKTL with hepatosplenic involvement were investigated retrospectively by clinical features, pathology, immunophenotype, genotype, Epstein-Barr virus (EBV) status, and survival analysis. The median age was 36 years; three patients (3/7) had a history of primary nasal ENKTL. Six cases (6/7) presented liver or spleen structures that were replaced by neoplasms, and the neoplastic cells displayed diffuse infiltration; one case (1/7) displayed neoplastic cells scattered in hepatic sinuses and portal areas. The cellular morphology and immunohistochemical features were similar to those of ENKTL involving other sites. Follow-up data were available in five of the seven patients. All five patients received first-line chemotherapy based on L-asparaginase. Three patients died, and two were still alive by the last follow-up. The median overall survival (OS) was 21 months. ENKTL with hepatosplenic involvement is rare, regardless of whether it is initial or secondary. There are two histopathologic patterns of ENKTL with hepatosplenic involvement, and L-asparaginase-based chemotherapy combined with AHSCT might yield good efficacy. Morphological features of ENKTL in the spleen and liver A The architecture of the spleen was affected, and dense infiltration of the neoplastic cells was observed in the left part; B Focal infiltration of the neoplastic cells was located in the red pulp; C Dense infiltration of the neoplastic cells in the liver, accompanied by fatty change of hepatocytes and congestion; D More neoplastic cells accumulated in sinusoidal region.

Prognostic value and computer image analysis of p53 in mantle cell lymphoma.

P53 prognostic cut-off values differ between studies of mantle cell lymphoma (MCL), and its immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation, which might be inaccurate. This study aimed to investigate the optimal cut-off value for p53 in predicting prognosis of patients with MCL and the possible use of computer image analysis to identify the positive rate of p53. We calculated p53 positive rate using QuPath software and compared it with the data obtained by manual counting and semiquantitative estimation. Survival curves were generated by using the Youden index and the Kaplan-Meier method. The chi-squared (χ2) test was used to compare MIPI, Ann Arbor stage, and cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compare manual counting, computer image analysis and semiquantitative estimation, as well as the consistency between different observers. The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) than those with p53 < 20% (P < 0.0001). MCL patients with MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant cell morphology had more p53 ≥ 20%. There was a strong correlation between computer image analysis and manual counting of p53 from the same areas in MCL tissues (Spearman's rho = 0.966, P < 0.0001). The results of computer analysis are completely consistent between observers, and computer image analysis of Ki-67 can predict the prognosis of MCL patients. MCL patients with p53 ≥ 20% had a shorter OS and a tendency for MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant. Computer image analysis could determine the actual positive rate of p53 and Ki-67 and is a more attractive alternative than semiquantitative estimation in MCL.

Identification of FCER1G related to Activated Memory CD4+ T Cells Infiltration by Gene Co-expression Network and Construction of a Risk Prediction Module in Diffuse Large B-Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a group of biologically heterogeneous tumors with different prognoses. The tumor microenvironment plays a vital role in the tumorigenesis and development of DLBCL, and activated memory CD4+ T cells are an essential component of immunological cells in the lymphoma microenvironment. So far, there are few reports about activated memory CD4+T cells infiltration and related genes in the DLBCL tumor microenvironment. This study obtained the mRNA expression profile information of the testing GSE87371 dataset and another six validation datasets (GSE53786, GSE181063, GSE10846, GSE32918, GSE32018, GSE9327, GSE3892, TCGA-DLBC) from the GEO and TCGA databases. Weighted Gene Co-expression Network Analysis (WGCNA) screened gene module associated with activated memory CD4+ T cells infiltration. CIBERSORT and TIMER (immune cells infiltrating estimation analysis tools) were used to identify the relationship between activated memory CD4+ T cells and genes associated with immune infiltrating cells in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) built the risk prediction model and verified it using nomogram and Kaplan-Meier analysis. Further functional characterization includes Gene Ontology, KEGG pathway analysis and Gene Set Enrichment Analysis (GSEA) to investigate the role and underlying mechanisms of these genes. These results suggest that the expression of FCER1G can reflect the invasion of activated memory CD4+ T cells in DLBCL, which provides a new idea for studying the tumor microenvironment and may become a potential predictive biomarker for the assessment of DLBCL.

The Role of PD-L1 Expression in Prediction and Stratification of Recurrent or Refractory Extranodal Natural Killer/T-Cell Lymphoma.

Background and Aims: The clinical outcome of relapsed and refractory (RR) extranodal natural killer/T-cell lymphoma (ENKTL) is poor. It is necessary to identify RR patients in ENKTL and find novel therapeutic targets to improve the prognosis of patients with RR ENKTL. Methods: A total of 189 ENKTL patients with effective clinical characteristics were enrolled. Paraffin specimens were collected for PD-L1 expression identification. Kaplan-Meier curve analysis was performed for survival analysis. Whole exome sequencing (WES) was performed for identifying the mutational characterization of RR and effective treatment (ET) patients. Results: Univariate and multivariate Cox proportional hazards regression analysis showed that negative PD-L1 expression (HR = 1.132, 95% CI = 0.739-1.734, P = 0.036) was an independent predictor of poor prognosis in patients with ENKTL. The overall survival (OS) of PD-L1 positive patients was significantly higher than that of PD-L1 negative patients (P = 0.009). Then, we added PD-L1 expression as a risk factor to the model of Prognostic Index of Natural Killer Lymphoma (PINK), and named as PINK+PD-L1. The PINK+PD-L1 model can significantly distinguish RR patients, ET patients, and the whole cohort. Moreover, our data showed that PD-L1 expression was lower than 25% in most RR patients, suggesting that RR subtypes may be associated with low expression of PD-L1 (P = 0.019). According to the whole exome sequencing (WES), we found that the mutation frequencies of JAK-STAT (P = 0.001), PI3K-AKT (P = 0.02) and NF-kappa B (P < 0.001) pathways in RR patients were significantly higher than those in ET patients. Conclusion: Patients tend to show RR when PD-L1 expression is lower than 25%. The model of PINK+PD-L1 can stratify the risk of different groups and predict OS in ENKTL patients. The mutational profile of ENKTL patients with RR is different from that of patients with ET.

Sonographic Features of Pure Mucinous Brelast Carcinoma With Micropapillary Pattern.

OBJECTIVE: Previous studies have mostly discussed the clinical manifestations and prognosis of mucinous breast carcinoma with a micropapillary pattern. The purposes of this study were to investigate the sonographic features of pure mucinous breast carcinoma with micropapillary pattern (MUMPC) and to identify the role of ultrasound in the differential diagnosis between MUMPC and conventional pure mucinous breast carcinoma (cPMBC). MATERIALS AND METHODS: We obtained written informed consent from all patients, and the Ethics Committee of West China Hospital approved this retrospective study. The study was conducted between May and August 2020. We enrolled 133 patients with 133 breast lesions confirmed as mucinous breast carcinoma (MBC) histopathologically between January 2014 and January 2020.We retrospectively assessed sonographic features (margin, shape, internal echogenicity, calcification, posterior acoustic feature, invasive growth, blood flow grade, and rate of missed diagnosis) and clinical characteristics (age, tumor size, tumor texture, initial symptom, and lymph node metastasis). Bivariable analyses were performed using SPSS version 19.0. RESULTS: The 133 lesions included 11 MUMPCs, 65 cPMBCs, and 57 mixed MBCs (MMBCs). There were significant differences in margin, shape, calcification, posterior acoustic feature, invasive growth, rate of missed diagnosis, average tumor size, and lymph node metastasis among the three groups (p < 0.05). The subsequent pairwise comparisons showed that there were significant differences in lymph node metastasis, margin, and invasive growth between MUMPC and cPMBC (p < 0.05). In patients aged >45 years, there was a significant difference in tumor size among the three groups (p = 0.045), and paired comparison showed that the average tumor size in the cPMBC group was larger than that in the MMBC group (p = 0.014). CONCLUSION: MUMPC showed a non-circumscribed margin and invasive growth more frequently than cPMBC did. Lymphatic metastasis was more likely to occur in MUMPC than cPMBC. Ultrasound is helpful to distinguish MUMPC from cPMBC.

Comprehensive Flow-Cytometry-Based Immunophenotyping Analysis for Accurate Diagnosis and Management of Extranodal NK/T Cell Lymphoma, Nasal Type.

BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL-N) is an aggressive lymphoma typically diagnosed by examining small biopsy specimens. Flow cytometry is very valuable for the diagnosis and classification of several kinds of hematolymphoid neoplasms but has not been widely used for diagnosing ENKTL-N. METHODS: We systematically investigated the flow cytometry characteristics of 26 solid tissue biopsy specimens of ENKTL-N at initial diagnosis and compared the results with those from reactive NK-cells in the nasal/nasopharyngeal region and peripheral blood. RESULTS: Our study revealed seven flow cytometry (FCM)-based characteristics for distinguishing between the neoplastic cells and reactive NK-cells, including (1) the proportion of NK-cells among total lymphocytes >10%; (2) forward scatter >105 ; (3) mean fluorescence intensity of CD56 > 5,000; (4) aberrant antigen expression or loss; (5) skewed killer cell immunoglobulin-like receptor repertoire; (6) homogenously positive for CD38; and (7) positive for CD30 or CD336. FCM-based immunophenotyping is a potentially feasible and convenient approach for discriminating cellular lineages, evaluating the activation status of NK-cells, and selecting potential therapy targets of ENKTL-N. CONCLUSIONS: Flow cytometry is very valuable for facilitating routine diagnosis, confirming clonality, predicting the cellular lineage, and guiding individual treatment for ENKTL-N. © 2019 International Clinical Cytometry Society.

Somatic mutations in KMT2D and TET2 associated with worse prognosis in Epstein-Barr virus-associated T or natural killer-cell lymphoproliferative disorders.

Limited studies are available on the molecular pathogenesis of Epstein-Barr virus (EBV)-associated T or natural killer (NK) cell lymphoproliferative disorders (EBV+T/NK-LPD). In this retrospective study, we aim to elucidate the mutation profile of EBV+T/NK-LPD using capture-based targeted sequencing with a panel consisting of 64 lymphoma-related genes to identify driver genes associated with the development of EBV+T/NK-LPD. Targeted sequencing of 169 EBV+T/NK-LPD cases was performed using a panel of 64 lymphoma-related genes. Of the 169 EBV+T/NK-LPD cases, 123 had extra-nodal NK/T-cell lymphoma (ENKTL), 12 had aggressive NK-cell leukemia (ANKL) and 34 had EBV+ T-cell lymphoma of childhood (EBV+TL). The mutation profile revealed that all three subtypes of EBV+T/NK-LPDs had high mutation rates in STAT3, KMT2D, DDX3X, NOTCH1 and TET2. Target sequencing revealed that ENKTL, ANKL and EBV+TL were molecularly distinct, the mutation in nasal-ENKTL and extra-nasal-ENKTL are also different. Survival analysis revealed that ENKTL patients with gene mutations or loss of protein expression in either KMT2D or TET2 were significantly correlated with shorter overall survival. And although the EBV+TL and ANKL groups were too small to confirm survival disadvantage, the adverse prognosis trends of KMT2D or TET2 were showed in these two groups. We conclude that EBV+T/NK lymphoproliferative disorders have very distinct molecular profiles. Our findings also suggest the likely involvement of KMT2D and TET2 in the development of ENKTL, and possibly EBV+T/NK-LPDs in general.

Laryngeal Extranodal Nasal-type Natural Killer/T-cell Lymphoma: A Clinicopathologic Study of 31 Cases in China.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL-N) initially presented in larynx is a rare condition without distinctive clinicopathologic features, with a challenging pathologic diagnosis. This study aimed to evaluate the clinicopathologic features and diagnosis of laryngeal ENKTL-N and spread awareness regarding ENKTL-N. A series of 31 cases of laryngeal ENKTL in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 50 years (range, 13 to 77 y) with a male/female ratio of 5.2:1 (26/5). All patients initially presented with hoarseness and/or laryngalgia, and 10 patients (32.3%) experienced B symptoms. The supraglottic region was the most common site of occurrence (58.1%), the glottic area being the rarest site (6.5%). The mucosal squamous epithelium was detected in 26 specimens and pseudoepitheliomatous hyperplasia was observed in 8 cases (8/26, 30.8%). "Keratin-pearls" and a "pseudoinvasive" pattern were observed in 2 cases. Follow-up data were available for 26 patients (83.9%), the median survival duration was 9 months, and the overall survival rate at 5 years was 29.6%. Univariate analysis revealed that patients experiencing B symptoms (P=0.019) and age above 60 years had a significantly low survival (P=0.049) and that combined radiotherapy and chemotherapy prolongs overall survival (P<0.001). Laryngeal ENKTL-N is a rare entity with high aggressiveness and a poor prognosis. Multiple biopsies are usually required owing to secondary infection and massive necrosis. Laryngeal EKTL-N may mimic inflammatory lesions or well-differentiated squamous cell carcinoma. Therefore, clinical vigilance is essential to prevent misdiagnosis or a delayed diagnosis.

Mediastinal myelolipoma/extramedullary hematopoiesis presenting as a mass: rare differential diagnosis among mediastinal tumors.

OBJECTIVES: Mediastinal myelolipoma/extramedullary hematopoiesis presenting as a mass is infrequent and can lead to misdiagnosis. Here we describe a large series aiming to illustrate the clinicopathologic features. METHODS: We retrospectively searched mediastinal tumors and myelolipoma diagnosed at the Department of Pathology, West China Hospital from 2010 to 2015 and collected 14 mediastinal myelolipoma/extramedullary hematopoiesis cases presenting as an encapsulated mass among 1324 mediastinal mass diseases and 252 myelolipomas. RESULTS: There were 8 females and 6 males aged from 35 to 67 years old, most of whom were diagnosed incidentally. Cross-sectional imaging revealed encapsulated masses located in the posterior mediastinum with fat and soft tissue density showing heterogeneous enhancement. Radiologic diagnosis was neurogenic tumor for most cases. All but one patient underwent surgery and postoperative pathologic findings showed fat and hematologic elements. Considering the accompanying hematologic disorders, 5 patients were diagnosed as extramedullary hematopoiesis and the remaining 9 as myelolipoma. The average hematopoietic tissue percentage in extramedullary hematopoiesis was 70%, significantly higher than it was in myelolipoma. Patients showed no sign of recurrence or metastasis apart from the patient with hepatocellular carcinoma. CONCLUSIONS: Mediastinal myelolipoma/extramedullary hematopoiesis is a rare entity of solid tumors in the posterior mediastinum, affecting patients from their third decades, with no sex predilection and lacking unique clinical symptoms, and may be misdiagnosed as a malignant tumor on cross-sectional imaging. The final diagnosis relies on pathologic findings, and the precise classification of myelolipoma or extramedullary hematopoiesis relies on percentage of hematopoietic tissue and accompanying clinical symptoms. Surgery is the recommended treatment.

Clinical and pathological characteristic of metastatic malignant mesothelioma initially diagnosed by lymph node biopsy.

BACKGROUND: It is a great challenge for pathologists to initially diagnose metastatic malignant mesothelioma (MM) by the lymph node biopsy without any history of primary MM. Because the onset of MM is hidden and the metastatic MM in lymph node is relatively uncommon. Besides, morphologic and immuohistochemistry features of MM are similar to other tumors. METHODS: In order to improve the initial diagnostic accuracy of metastatic MM from LN biopsy and to reduce or avoid the possibility of missed diagnosis or misdiagnosis, we had collected the clinical and pathological data of the metastatic MM cases in our department, and summarized the characteristics of morphological, immunohistochemical and fluorescence in situ hybridization (FISH) results. RESULTS: Seven patients (4 males and 3 females) with 21-73 year-old had been included in our study. Six cases showed serous cavity effusion, serosal thickening and systemic multiple lymph node enlargement. The "moderate, nice" tumor cells were arranged in variable patterns. Mitosis was hardly to be found and necrosis was absent. Four immunohistochemical staining panels and FISH detection had been used for diagnosis and differential diagnosis of MM. All cases expressed broad-spectrum epithelial markers and at least 2 mesothelial-cell-origin markers. None were positive for specific-tissue-origin markers, and all cases were diagnosed of malignancy according to immunohistochemical markers and detection of pl6 gene deletion. CONCLUSION: It is necessary for us to keep our awareness of metastatic MM in lymph node. Correct diagnosis of MM metastasis by lymph node biopsy were based on detailed understanding of the clinical manifestation and the image data, careful observation of morphologic characteristics, and properly using immunohistochemical markers or FISH detection if necessary for diagnosis and differential diagnosis.

Primary clear cell carcinoma of nasal cavity: a case report and review of literature.

Primary Clear Cell Carcinoma (CCC) of nasal cavity is rare and is often misdiagnosed as a malignant or benign lesion frequently. We reported a case of primary clear cell carcinoma of nasal cavity, with the complaint of epiphora in right eye, nasal obstruction and bleeding. CCC often confused with the metastatic renal clear cell carcinoma (RCC) of the nasal cavity, pathology and immunohistochemistry are the gold standards of Clear Cell Carcinoma could help us to make a definite diagnosis. Surgery, radiotherapy and chemotherapy are the main treatment methods.

Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites.

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (<712 IU/L), chemotherapy or L-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.

HIV-related Burkitt lymphoma with florid granulomatous reaction: an unusual case with good outcome.

Burkitt lymphoma (BL) is a highly aggressive subtype of non-Hodgkin lymphomas (NHL). Lymphoma related granulomatous reaction rarely occurs in sporadic BL. Herein, we describe the first case of HIV related Burkitt lymphoma with florid granulomatous reaction. A 41-year-old HIV-positive Chinese male presented lymphadenopathy in the right cervical region for 3 months. The enlarged lymph node biopsies revealed the presence of prominent granulomas of varying size with Langhans giant cells, leading to the misdiagnosis of tuberculous lymphadenitis in other hospital. Subsequently, the case was sent to us for consultation. The morphology, immunophenotype, special staining, interphase FISH analysis and blood tests confirmed a diagnosis of HIV related Burkitt lymphoma with granulomatous reaction. Without radiotherapy and chemotherapy, the patient was alive and well with no evidence of lymphoma during the observation period of 24 months. The case suggested that lymphoma with florid granulomatous reaction can easily be misdiagnosed as benign lesions since the large number of epithelioid granulomas could obscure the primary lesion. Moreover, the granulomatous reaction may be an indicator for favorable prognosis in HIV related Burkitt lymphoma.

[Use of recombinant human beta-defensin-3 to evaluate the effect of adhesion of Candida albicans on the surface of soft lining material].

PURPOSE: To evaluate the effectiveness of recombinant human beta-defensin-3 (rHBD3) on reduction of Candida albicans from the surface of soft lining materials. METHODS: Specimens made of soft lining materials, which had been contaminated with C. albicans, were immersed in 25 µg/mL rHBD3 and 5.25% sodium hypochlorite (a positive control) for 5, 10, 30 and 60 min. The results were analyzed statistically with SPSS 10.0 software package. Confocal laser scanning microscopy(CLSM) of biofilm-associated C. albicans were treated with rHBD3 in different times. RESULTS: The results confirmed that an immersion time of 30 min or higher yielded a good disinfection effect, both for the experimental group and the positive control. A large number of pathogenic bacteria were killed and the cells were stained red by SYTO9/PI after 30 min. CONCLUSIONS: It is possible that soft lining materials immersed in rHBD3 solution that possesses antifungal activity may be clinically protective.

[CD16 expression is an independent prognostic factor for extranodal NK/T cell lymphoma of nasal type].

OBJECTIVE: To analyze the clinicopathologic features of extranodal NK/T cell lymphoma, nasal type (ENKTCL-N), to explore the expression of NK cell-associated receptors in ENKTCL-N and the relationship with prognosis, and to establish a prognostic model. METHODS: One hundred and twenty-six cases of ENKTCL-N were selected from the files of the Department of Pathology, West China Hospital of Sichuan University. The relevant clinical and follow-up data were collected, and the histopathology was reviewed. All specimens were stained immunohistochemically for CD16, ICAM-1 and LFA-1. RT-PCR was used to detect the expression of CD94, NKG2 and KIR. The relationship between the prognosis of ENKTCL-N, clinical features, histopathological characteristics and expression of these markers were also analyzed. RESULTS: ENKTCL-N mainly occurred in middle-age and young patients (median age, 41 years). The male to female ratio was 3.2:1. Sites more commonly involved were the nose and upper aerodigestive tract whereas those for the non-nasal type were the skin and gut. Only six cases involved two or more extranodal sites. Most (86.5%, 109/126) of the patients were in clinical stages I/II. The tumors showed predominately medium-sized tumor cells and large-sized tumor cells accounted for only 9.5% (12/126). Coagulative necrosis was present in all cases. The expression rates of CD56, CD16, CD94, LFA-1 and ICAM-1 were 82.6% (95/115), 15.1% (19/126), 55.4% (41/74), 40.5% (51/126) and 0, respectively. The expression rate of NKG2 receptor was 90.5% (67/74) overall. NKG2 receptor expression was independent of CD94. The overall expression rate of KIR receptor was 33.8% (25/74) and KIR receptor restriction was not detected in 20.8% (5/24) of the cases. Follow-up data was available in all patients, with median and average survival time being 15 months and 20.2 months, respectively. Survival analysis showed that prognostic factors included the gender, age, disease type, extranodal involvement, stage, the expression of CD16, LFA-1 and CD94. Cox's proportional hazard regression analysis revealed four factors, age, involved site, stage and CD16 expression, were independent prognostic factors. CONCLUSIONS: The age, disease type, stage and CD16 expression are independent prognostic factors. Establishment of a prognostic model based on the above four factors can be more accurate in the prognostication of ENKTCL-N. The differences in the clinical features, prognosis, and expression of NK cell-associated receptors are obvious between nasal NK-cell lymphoma and non-nasal NK-cell lymphoma.

[Cost-effectiveness analysis on the once-in-a-lifetime cervical cancer screening program for women living in rural and urban areas of China].

OBJECTIVE: To estimate the cost-effectiveness of once-in-a-lifetime cervical cancer screening program and to predict the optimal modality for its operation on women living in rural and urban areas of China, based on Markov modeling and simulation. METHODS: Three modalities including visual inspection with acetic acid plus Lugol's iodine (VIA/VILI), conventional Pap Smear (Pap Smear), and simple HPV DNA testing (careHPV) were hypothesized for the rural cohort, whereas other five modalities including Pap Smear, liquid-based cytology (LBC), simple HPV DNA testing (careHPV), Hybrid Capture 2 HPV DNA testing (HC2), and LBC plus HC2 (LBC + HC2) were tested for the urban cohort. A Markov model was constructed based on the factors as natural history, screening, diagnosis and treatment on cervical cancer using data related to the epidemics and the costs from rural and urban areas of the country. Long-term effectiveness and cost-effectiveness were predicted through simulation of the model. RESULTS: Compared to the non-screening scenario, the amount of life years saved were 277.97 - 2727.53 and 134.02 - 1446.84 years per 100 000 women, respectively, for different cohorts in rural and urban areas. The cost-effectiveness ratios were 1520.99 - 2453.74 and 3847.35 - 44 570.35 RMB per life year saved, respectively, for different cohorts in rural and urban areas. The incremental cost-effective ratio for careHPV starting from 40 years old (careHPV@40) and careHPV from 30 years old (careHPV@30) dominated other strategies for the rural cohort, while careHPV@40, careHPV@30, HC2 from 30 years old (HC2@30), and LBC + HC2 from 30 years old (LBC + HC2@30) were dominant for the urban cohort. CONCLUSION: All eight once-in-a-lifetime cervical cancer screening modalities were cost-effective based on our model. In particular, careHPV screening starting from 40 years old seemed to be the most cost-effective one for women living in both rural and urban areas.

Hydroa vacciniforme-like lymphoma of an adult: a case report with review of the literature.

Hydroa vacciniforme-like lymphoma (HVL) is a rare type of Epstein-Barr virus (EBV)-positive lymphoma of cytotoxic T-cell or natural killer cell origin that mainly affect children, characterized by a vesicopapular skin eruption that clinically resemble hydroa vacciniforme (HV). In current study, we report an adult patient with the tumor. The patient presented similar morphologic, immunophenotypic and genotypic changes of the disease with that occurred in children, whereas clinically, he showed a prolonged clinical course without hepatosplenomegaly or generalized lymphadenopathy. Whether there are some differences in biologic behavior between children and adults still remains unknown and it is necessary to collect more data to observe and to investigate in the future. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7644172219178472.

Aggressive natural killer-cell leukemia with jaundice and spontaneous splenic rupture: a case report and review of the literature.

Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare aggressive form of NK-cell neoplasm. We report an uncommon case of 36-year-old male who showed jaundice and spontaneous splenic rupture. The diagnosis was established by the biopsy of liver and spleen. The monomorphous medium-size neoplastic cells infiltrated into portal areas and sinus of liver as well as the cords and sinus of the spleen. Necrosis, mitotic figures and significant apoptosis could be seen easily. These neoplastic cells demonstrated a typical immunophenotype of CD3ε+, CD56+, CD16+, Granzyme B+, TIA-1+. T-cell receptor γ (TCR-γ) gene rearrangement analysis showed germline configuration and the result of in situ hybridization for Epstein-Barr virus-encoded RNA (EBER-ISH) was positive. The patient has undergone an aggressive clinical course and died of multi-organ function failure 14 days later after admission. To the best of our knowledge, this is the first case of ANKL with spontaneous splenic rupture, and we should pay more attention to recognize it. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2048154883890867.