Comparative genomic hybridization study of nasal-type NK/T-cell lymphoma

BACKGROUND: Nasal-type NK/T-cell lymphoma is a rare type of non-Hodgkin's lymphoma. The genetic changes associated with pathogenesis have not been well defined. This study investigates the nonrandom genetic alteration of nasal-type NK/T-cell lymphoma. METHODS: Nine cases were studied. Comparative genomic hybridization (CGH) was carried out using fresh tumor tissues of seven nasal-type NK/T-cell lymphomas. To complement the data by CGH, loss of heterozygosity (LOH) of chromosomes 6q, 1p, and 17p using polymorphic markers and p53 gene mutation by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) were analyzed. RESULTS: The DNA copy number changes of seven nasal-type NK/T-cell lymphomas were gains on chromosomes 2q(5), 13q(4), 10q(3), 21q(2), 3q(2), 5q(2), and 17q(2), and losses involving chromosomes 1p(4), 17p(4), 12q(3), 13q(2), and 6q(1). One of six cases informative for at least two markers for chromosome 6q showed LOH at D6S300, D6S1639, D6S261, D6S407, and D6S292. Two cases showing loss of 1p and 17q by CGH revealed LOH at D1S214, D1S503, and D17S559. P53 mutation was detected in exon 8 in one of nine cases. CONCLUSIONS: Frequent DNA losses at 1p, 17p, and 12q and gains at 2q, 13q, and 10q suggested that these regions could be targets for further molecular genetic analysis to investigate tumor suppressor genes or oncogenes associated with tumorigenesis of NK/T-cell lymphoma. Infrequent alteration of 6q contrary to previous studies raises doubt about an implication of 6q loss in the pathogenesis of early-stage NK/T-cell lymphoma. Further studies on more defined cases are required to verify their association.     

Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

Background

Extraosseous plasmacytoma, so called extramedullary plasmacytoma (EMP) is relatively rare in China. The aim was investigate the clinicopathologic features of EMP and the role of Immunophenotype and genotype detection in diagnosis of EMP.

Methods

Thirty-two cases of EMP were investigated retrospectively by histopathology, immunophenotype, genotype and survival analysis.

Results

Clinically, the mean age of the patients was 53.4. Most of the patients received no treatment after the diagnosis was established, and the prognosis was relatively poor. Histologically, in 40% of the cases, the neoplastic cells were grade II or III. The neoplastic cells expressed one or more PC associated antigens. The immunophenotype of EMP and inflammation of sinonasal regions with numerous PC infiltrations were compared and showed some difference in expression of CD45, CD27, CD44v6 and Bcl-2 as well. Ig light chain restriction was detected in 87.5% of the cases.

Conclusions

we described 32 Chinese cases of EMP, compare with that reported in the literature, some differences are presented, including higher percentage of grade II and III cases, clinically inconsistent treatment and management as well as poor outcome of the disease.     

Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with fine needle aspiration cytology findings

BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal tract, skin, testis and salivary gland. Secondary lymph node involvement is rarely encountered until late in the disease course. The fine needle aspiration cytology of NK/T-cell lymphoma with a nodal presentation has not been described before. CASES: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong Kong. Both patients presented with submandibular lymph node enlargement but unremarkable peripheral blood and bone marrow findings. Fine needle aspiration cytology was available in both cases, showing a heterogeneous population of small to medium-sized lymphoid cells, follicular center cells, plasma cells, eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily discernible nuclear atypia with an irregular nuclear outline. Cell block sections revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical study confirmed the presence of CD56-positive lymphoma cells. In situ hybridization for EBV-encoded RNA also revealed positive nuclear signals. Histologic examination of the surgical biopsies showed interfollicular expansion by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor gene rearrangement studies demonstrated a germline pattern, confirming the putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells. CONCLUSION: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable on the basis of fine needle aspiration biopsy alone, especially in view of its distinctive immunophenotype and EBV association. Recognition of the subtle but definite cytologic atypia of malignant lymphoid cells and presence of an appropriate background (including more eosinophils than usual), together with proper application of ancillary techniques, is crucial to arriving at a correct diagnosis.     

Serous effusion cytology of extranodal natural killer/T-cell lymphoma

X.‐Y. Su, J. Huang, Y. Jiang, Y. Tang, G.‐D. Li and W.‐P. Liu Serous effusion cytology of extranodal natural killer/T‐cell lymphoma Objective: Extranodal natural killer/T‐cell lymphoma, nasal type (ENKTCL‐N), is a rare form of lymphoma that typically occurs at extranodal sites. It is one of the most common extranodal lymphomas in China. Literature on effusions and cytological findings relating to ENKTCL‐N is limited. We studied five consecutive cases of ENKTCL‐N effusions collected over a 3‐year period. The cytomorphological, immunocytochemical and molecular biological features were evaluated with literature review. The purpose of this study is to discuss how to diagnose ENKTCL‐N cytologically in effusions. Methods: Smears and cell block sections were reviewed for each case. Immunocytochemistry was performed on 4‐μm paraffin sections. Antibodies used were as follows: cCD3 (intracytoplasmic CD3), CD45RO, surface CD3, CD20, CD79a, CD56, TIA‐1, granzyme B, CD30, CD99, TdT and Ki‐67. In situ hybridization for EBER1/2 (EBER‐ISH) and T‐cell receptor γ (TCRγ) gene rearrangement were performed for all cases. Results: Large to medium‐sized tumour cells with pleomorphic nuclei and coarse chromatin were found in a necrotic background in all cases. The cytoplasm of the tumour cells was scant to moderately abundant with occasional cytoplasmic projections; in Giemsa‐stained smears, fine granules were present in some tumour cells. Mitotic figures were frequent. The tumour cells were all positive for CD56, granzyme B, TIA‐1 and cCD3, and were negative for surface CD3, CD20 or CD79a, CD99 and TdT. The MIB index was 50–80%. Epstein‐Barr virus‐encoded RNA (EBER) hybridizing signals were detected for most neoplastic cells. The T‐cell receptor gamma gene rearrangement analysis showed germ‐line configuration, except for one case. Conclusions: Effusion cytology may be appropriate for establishing the diagnosis of ENKTCL‐N, particularly for patients in whom tissue biopsy is not possible.     

Treatment of localized extranodal NK/T cell lymphoma,nasal type: a systematic review

Extranodal natural killer/T cell lymphoma (ENKTL), nasal type, presents predominantly as a localized disease involving the nasal cavity and adjacent sites, and the treatment of localized nasal ENKTL is a major issue. However, given its rarity, there is no standard therapy based on randomized controlled trials and therefore a lack of consensus on the treatment of localized nasal ENKTL. Currently recommended treatments are based mainly on the results of phase II studies and retrospective analyses. Because the previous outcomes of anthracycline-containing chemotherapy were poor, non-anthracycline-based chemotherapy regimens, including etoposide and l-asparaginase, have been used mainly for patients with localized nasal ENKTL. Radiotherapy also has been used as a main component of treatment because it can produce a rapid response. Accordingly, the combined approach of non-anthracycline-based chemotherapy with radiotherapy is currently recommended as a first-line treatment for localized nasal ENKTL. This review summarizes the different approaches for the use of non-anthracycline-based chemotherapy with radiotherapy including concurrent, sequential, and sandwich chemoradiotherapy, which have been proposed as a first-line treatment for newly diagnosed patients with localized nasal ENKTL.     

NK/T-cell lymphoma of bilateral adrenal glands in a patient with pyothorax

ABSTRACT: Primary lymphoma of adrenal glands is rare, and non-B-cell lymphoma associated with pyothorax is also very rare. Here we report the first autopsy case of non-B-cell lymphoma in bilateral adrenal glands of a 79-year-old woman with pyothorax who had an aggressive clinical course. Immunohistochemically, tumor cells showed CD3+, CD45RO+, CD5-, CD7-, CD4-, CD8-, CD10-, CD20-, CD30-, CD79a-, CD138-, CD56-, granzyme B-, TIA-1+ and ALK-. In addition, tumor cells were strongly EBER1-positive by in situ hybridization. In genomic DNA of tumor cells, T-cell receptor rearrangements were not detected by southern blotting. We finally diagnosed this case as extranodal NK/T-cell lymphoma (nasal type).Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8050621197741854.     

Rare case of low-grade extranodal NK/T-cell lymphoma,nasal type,arising in the setting of chronic rhinosinusitis and harboring a novel N-terminal <Emphasis Type="Italic">KIT</Emphasis> mutation

Background

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), is a rare aggressive subtype of non-Hodgkin lymphoma characterized by angioinvasion, angiodestruction, necrosis and strong association with Epstein-Barr virus (EBV). ENKTCL-NT occurs worldwide and is more prevalent in Asian and the Native American populations of Mexico, Central and South America. It represents approximately 10% of all peripheral T-cell lymphomas worldwide. The aim of this report is to present a rare case of ENKTCL-NT with an unusually indolent clinical course and low-grade histopathologic features.

Case presentation

A 71-year-old Asian woman with a long-standing history of seasonal rhinosinusitis presented with persistent nasal congestion, cough, and fever unresponsive to antihistamines and antibiotics. Histopathological evaluation of a polypoid nasal mass revealed an atypical infiltrate with predominantly small lymphoid cells that were CD2+, surface CD3-, cytoplasmic CD3+, CD5(dim)+, CD7(dim)+, cytotoxic markers (granzyme B and perforin)+, EBER+ and CD56-. The Ki-67 proliferative index was very low (<?1%). T-cell receptor gamma gene rearrangement studies were positive for a monoclonal rearrangement, and sequencing studies identified a novel KIT mutation (p. K167 M, c. 500 A?>?T). A diagnosis of low-grade ENKTCL-NT was rendered.

Conclusions

Our case of ENKTCL-NT is unusual due to (1) an indolent clinical course (2) low-grade histopathologic features including a low proliferative index (3) lack of CD56 expression and (4) a novel KIT mutation. This case raises awareness of the existence of a subset of cases of ENKTCL-NT that can potentially be misdiagnosed as a reactive process, particularly in patients with recurrent chronic rhinosinusitis.

     

基于能值分析的中国生态经济系统可持续发展评估

本文基于能值理论全面评估了2006—2016年中国的可持续发展水平,并根据一次能源投入比例的不同将各省份分为4组进行比较分析,讨论一次能源投入水平对省域间可持续发展水平的影响。结果表明: 2006—2016年,随着经济快速增长,一次能源投入比例不断上涨,使得我国整体生态经济系统的环境负荷由2.78升至3.13。同时,受进口增加的影响,能值产出率相对下降,可持续性指标下降至5.40。能值密度变化趋势与一次能源投入比例的变化基本一致,目前大多数省份依旧通过能源消费带动区域经济发展。其中,北京、上海等虽现代化经济高度发达,但环境压力同样高于其他省份,可持续发展水平不容乐观。以江苏为代表的南方省份能源投入较低而能值产出较高,表现出较高的可持续发展活力。因此,提升内陆地区能源利用效率、调整经济发展模式,并适当减缓发展强度,以缓解经济发展与环境保护之间的矛盾,可以令我国稳步实现生态经济的可持续发展。     

Vero细胞微载体不同培养方法的评价

对三种不同培养方法进行细胞生长速度、密度、营养及代谢产物浓度的比较分析,以优化和筛选最佳培养条件与方式。用同体积生物反应罐,基本培养条件相同,采用批培养、再循环培养、灌流培养三种方式进行了Vero细胞微载体（CytodexI）的周期培养。三种培养方法均达到预期效果,最终细胞密度分别为每毫升2.09×10     

Evaluation of texture features at staging liver fibrosis based on phase contrast X-ray imaging

Background

The purpose of this study is to explore the potential of phase contrast imaging to detect fibrotic progress in its early stage; to investigate the feasibility of texture features for quantified diagnosis of liver fibrosis; and to evaluate the performance of back propagation (BP) neural net classifier for characterization and classification of liver fibrosis.

Methods

Fibrous mouse liver samples were imaged by X-ray phase contrast imaging, nine texture measures based on gray-level co-occurrence matrix were calculated and the feasibility of texture features in the characterization and discrimination of liver fibrosis at early stages was investigated. Furthermore, 36 or 18 features were applied to the input of BP classifier; the classification performance was evaluated using receiver operating characteristic curve.

Results

The phase contrast images displayed a vary degree of texture pattern from normal to severe fibrosis stages. The BP classifier could distinguish liver fibrosis among normal, mild, moderate and severe stages; the average accuracy was 95.1% for 36 features, and 91.1% for 18 features.

Conclusion

The study shows that early stages of liver fibrosis can be discriminated by the morphological features on the phase contrast images. BP network model based on combination of texture features is demonstrated effective for staging liver fibrosis.

     

Evaluation of selectivity changes in HIC systems using a preferential interaction based analysis

It is well established that salt enhances the interaction between solutes (e.g., proteins, displacers) and the weak hydrophobic ligands in hydrophobic interaction chromatography (HIC) and that various salts (e.g., kosmotropes, chaotropes, and neutral) have different effects on protein retention. In this article, the solute affinity in kosmotropic, chaotropic, and neutral mobile phases are compared and the selectivity of solutes in the presence of these salts is examined. Since solute binding in HIC systems is driven by the release of water molecules, the total number of released water molecules in the presence of various types of salts was calculated using the preferential interaction theory. Chromatographic retention times and selectivity reversals of both proteins and displacers were found to be consistent with the total number of released water molecules. Finally, the solute surface hydrophobicity was also found to have a significant effect on its retention in HIC systems.     

Multiple interspecies transmissions of human and simian T-cell leukemia/lymphoma virus type I sequences

Using two sets of nucleotide sequences of the human and simian T-cell leukemia/lymphoma virus type I (HTLV-I/STLV-I), one consisting of 522 bp of the env gene from 70 viral strains and the other a 140-bp segment from the pol gene of 52 viral strains, I estimated cladograms based on a statistical parsimony procedure that was developed specifically to estimate within-species gene trees. An extension of a nesting procedure is offered for sequence data that forms nested clades used in hypothesis testing. The nested clades were used to test three hypotheses relating to transmission of HTLV/STLV sequences: (1) Have cross-species transmissions occurred and, if so, how many? (2) In what direction have they occurred? (3) What are the geographic relationships of these transmission events? The analyses support a range of 11-16 cross-species transmissions throughout the history of these sequences. Additionally, outgroup weights were assigned to haplotypes using arguments from coalescence theory to infer directionality of transmission events. Conclusions on geographic origins of transmission events and particular viral strains are inconclusive due to small samples and inadequate sampling design. Finally, this approach is compared directly to results obtained from a traditional maximum parsimony approach and found to be superior at establishing relationships and identifying instances of transmission.      

The morphofunctional characteristics of lymphoma NK/LY cells treated with concanavalin A and Vibrio cholerae neuraminidase

Mouse NK/LY lymphoma cells were modified by Con A or Vibrio cholerae neuraminidase (VCN). Severe damage of the modified cells was not revealed by either supravital staining or light microscopy. Ultrastructural signs of metabolic lowering in the Con-A-treated cells were determined. Some increase in electrophoretic mobility of Con-A-modified cells was found, along with its decrease in VCN-modified cells. The decrease in the pool of proliferating cells was determined in both the types of modification, being more evident in the Con-A-modified material. A marked tumorigenic decrease of Con-A-modified cells was fixed.     

Evaluation in rabbits of different anti-SHIV vaccine strategies based on DNA/fowlpox priming and virus-like particle boosting

Two different prime-boost immunization protocols were tested in rabbits and their immune response was evaluated and compared with the final aim of defining a vaccine strategy that might be able to protect non-human primates from infection with the pathogenic simian/human immunodeficiency virus, SHIV(89.6P). The two regimens were based on three priming immunizations with either an expression plasmid plus a fowlpox (FP) recombinant vector or with two FP recombinant vectors, each one expressing either the SIV(mac239) gag/pol or the HIV-1env(89.6P) genes. In both protocols, priming immunizations were followed by two boosts with SHIV-mimicking virus-like particles (VLP). A complete SHIV-specific response was observed in all animals. Interestingly, the DNA vaccine was three to 10 times more efficient than the FP recombinant in inducing an anti-gag humoral response. Real-time PCR confirmed the memory effect on T-cell subsets secreting interleukin-4 and interferon-gamma, as a consequence of stimulation of both arms of the immune system. Although both protocols were almost equally effective in eliciting homologous neutralizing antibodies and highlighted the efficacy of VLP administration for boosting, protocol A seemed to be more effective in promoting a balanced T-cell memory immune response and appears more promising for vaccine purposes.     

Development of a prognostic model based on an immunogenomic landscape analysis of medulloblastoma

Medulloblastoma (MB) is one of the most common central nervous system tumors in children. At present, the vital role of immune abnormalities has been proved in tumorigenesis and progression. However, the immune mechanism in MB is still poorly understood. In the present study, 51 differentially expressed immune-related genes (DE-IRGs) and 226 survival associated immune-related genes (Sur-IRGs) were screened by an integrated analysis of multi-array. Moreover, the potential pathways were enriched by functional analysis, such as ‘cytokine–cytokine receptor interaction’, ‘Ras signaling pathway’, ‘PI3K-Akt signaling pathway’ and ‘pathways in cancer’. Furthermore, 10 core IRGs were identified from DE-IRGs and Sur-IRGs. And the potential regulatory mechanisms of core IRGs were also explored. Additionally, a new prognostic model, including 7 genes (HDGF, CSK, PNOC, S100A13, RORB, FPR1, and ICAM2) based on IRGs, was established by multivariable COX analysis. In summary, our study revealed the underlying immune mechanism of MB. Moreover, we developed a prognostic model associated with clinical characteristics and could reflect the infiltration of immune cells.     

Extranodal natural killer/T-cell lymphoma involving the gastrointestinal tract: analysis of clinical features and outcomes from the Asia Lymphoma study group

Background

The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract.

Patients and methods

Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries.

Results

The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 – 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone.

Conclusion

Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.

     

Heterogeneity of cell population of lymphoma NK/Ly and leukemia L-1210 according to carbohydrate structure of cell surface: immunocytochemical analysis of lectin binding

The heterogeneity of tumor cell populations according to binding of lectins from lentil (LcL), wheat germs (WGA), peanut (PNA) and concanavalin A was investigated on a model of murine Nemeth-Kellner lymphoma (NK/Ly) and leukemia L-1210. Bound lectins were detected by indirect immunochemical method using home obtained polyclonal antilectin antibodies and immunogold silver staining (IGSS) technique. Significant differences in binding of Con A were revealed between NK/Ly (67% Con A+) and L-1210 (7.2% Con A+) cells, while the differences in binding of other lectins with both types of tumor cells were not significant. A relatively high percentage of PNA+ cells was registered that can indicate a high degree of desialization of membrane glycoproteins.     

Evaluation of different culture systems on the in vitro production of bovine embryos

The objective of this study was to determine the development potential and quality of in vitro produced bovine embryos cultured individually or in groups. After IVM and IVF, presumptive zygotes were cultured in groups or individually, either in drops or in the modified "well of the well" (mWOW) system. In Experiment 1, four culture systems were utilized: T1: drop in group (control); T2: mWOW in groups; T3: mWOW individually; and T4: drop individually. Cleavage and blastocyst rates at Days 6, 7 and 8 and total cell number of Day 6 blastocysts were similar (P > 0.05) for all treatments. However, in Day 7 blastocysts, total cell number was lower (P < 0.05) in embryos cultured individually in a small drop than those cultured in the mWOW. In Experiment 2, blastocysts of T1, T2 and T3 were allocated into two groups, control and vitrified. After warming, the vitrified embryos were cultured for 72 h. At 48 h, the development of the Days 6 and 7 embryos was similar (P > 0.05) for all treatments in the control group. For the vitrified embryos, lower hatching rates (P < 0.05) were observed in the T3 group. In conclusion, embryos cultured in groups in the mWOW system had the same blastocyst rates but better quality (measured by their survival after vitrification) than those cultured individually in the mWOW system.