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Background@#Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL.@*Methods@#We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients’ overall survival (OS).@*Results@#Of the 86 patients, 71(82.6%) experienced invasion of AS, 22(25.6%) of soft tissue, and 26(30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ2 = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ2 = 4.105, P = 0.043) or brain involvement (Log rank χ2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ2 = 10.390, P = 0.001) or bones (Log rank χ2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466–20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517–24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates.@*Conclusions@#Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.
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BACKGROUND@#Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL.@*METHODS@#We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients' overall survival (OS).@*RESULTS@#Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ = 4.105, P = 0.043) or brain involvement (Log rank χ = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ = 10.390, P = 0.001) or bones (Log rank χ = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466-20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517-24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates.@*CONCLUSIONS@#Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.
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@# 【Objective】To investigate the effects of Epstein-Barr virus（EBV）on proliferation，apoptosis and lipid metabolism of gastric cancer cells，revealing the pathogenesis and development of EBV-associated gastric carcinoma （EBVaGC）.【Methods】EBV-positive cell line AGS-EBV was established by co-culturing AGS and Akata. Then we compared proliferation，apoptosis and lipid metabolism level between AGS and AGS-EBV cells. CCK-8 assays and Annexin V PE/7-AAD assays were performed to determine the proliferation and apoptosis of gastric cancer cells. Oil-Red O staining and three kinds of kits were used to detect lipid contents including lipid droplets，free fatty acid，triacylglycerol and total cholesterol. Key enzymes of lipogenesis were measured by qRT-PCR.【Results】EBV promoted the proliferation of gastric cancer cell line AGS（F = 23.214，P = 0.001；P values of 24 h，48 h，72 h，96 h and 120 h were 0.007， 0.004，＜0.001，＜0.001 and ＜0.001，respectively），inhibited apoptosis（P values of late and total apoptotic rates were 0.032，< 0.001），and increased intracellular lipid droplets，free fatty acids（P < 0.001），triacylglycerol（P = 0.004） and total cholesterol（P < 0.001）probably via lipogenesis. 【Conclusions】EBV promotes proliferation，inhibits apoptosis， and enhances lipid metabolism of gastric cancer cells.
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OBJECTIVE: To establish a method for rapid screening and quantification of 24 anti-inflammatory painkillers illegally added in traditional Chinese medicines and health foods by UPLC-quadrupole/electrostaticfield orbitrap high resolution mass spectrometry. METHODS: The separation was performed on a Thermo Acquity UPLC system with a Hypersil Gold C18 column with gradient elution of acetonitrile and 20 mmol · L-1 ammonium acetate solution. Electrospray ionization of positive and negative ions and one and two high precision full scan were used for the MS detection. The qualitative and quantitative analyses were carried out by accurate and precise parent ion mass and product ion mass information. RESULTS: The limits of detection (S/N ≥ 3) were 10.0-45.0 μg · kg-1. The average recoveries were 79.6%-98.3%. Thirty positive samples were detected among a total of 45 samples, resulting a positive rate of 66.7%. The detected components were paracetamol, diclofenac sodium, indometacin, and ibuprofen. CONCLUSION: The method is simple, highly accurate, sensitive and selective, and can be used in rapid screening and quantitative analysis of illegally added anti-inflammatory painkillers in traditional Chinese medicines and health foods.
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<p><b>OBJECTIVE</b>To investigate the molecular genetic abnormalities of N-myc and C-myc, and their clinical pathological implications in pediatric neuroblastic tumors (NTs).</p><p><b>METHODS</b>Abnormalities of N-myc were detected by interphase fluorescence in situ hybridization (FISH) technique in 246 cases of NTs, including neuroblastoma (NB,188 cases), ganglioneuroblastoma (GNB, 52 cases), ganglioneuroma (GN, 6 cases), and their association with the histological typing of the tumors and prognosis was analyzed. Abnormalities of C-myc were detected by FISH in 133 cases of NTs.</p><p><b>RESULTS</b>Of the 246 cases of NTs, N-myc amplification was only found in 27 cases (11.0%, 27/246) of NB, but not in any cases of GNB or GN (P < 0.05). 89.0% (219/246) N-myc non-amplification were found in NTs, and it included N-myc gain in 175 cases (71.1%, 175/246) and normal N-myc in 44 cases (17.9%, 44/246). Univariate analysis indicated significantly (P = 0.012) poorer outcome in patients with N-myc amplification than N-myc non-amplification. However no significant difference was observed between N-myc gain cases and normal N-myc cases (P = 0.057). C-myc gain was found in 74 of 133 cases (55.6%) of NTs; no C-myc amplification or translocation was detected. Forty percent (6/15) of cases with N-myc amplification and 57.6% (68/118) of cases with N-myc non-amplification were accompanied by C-myc gain. The difference between N-myc amplification and non-amplification with C-myc gain was not significant (P > 0.05). Univariate analysis indicated that the outcome difference was not statistically significant between C-myc gain cases and normal C-myc cases (P = 0.357).</p><p><b>CONCLUSIONS</b>The incidence of N-myc amplification only found in NB is low in pediatric NTs in China. Patients with N-myc amplification predict poorer outcome. No amplification or translocation of C-myc is detected in NTs, whereas C-myc gain is relatively common in NTs. There is no obvious association between N-myc amplification and C-myc gain.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Adrenal Gland Neoplasms , Genetics , Pathology , Follow-Up Studies , Ganglioneuroblastoma , Genetics , Pathology , Ganglioneuroma , Genetics , Pathology , Gene Amplification , Genes, myc , In Situ Hybridization, Fluorescence , Mediastinal Neoplasms , Genetics , Pathology , Neuroblastoma , Genetics , Pathology , Survival RateABSTRACT
<p><b>OBJECTIVE</b>To use array-based comparative genomic hybridization (aCGH) technology to study the molecular cytogenetic abnormalities of anaplastic large cell lymphoma (ALCL) at genome level.</p><p><b>METHODS</b>ALK protein expression and molecular genetic abnormalities were detected by immunohistochemistry and fluorescence in situ hybridization, respectively, in 25 cases of ALCL. Any chromosomal gains/losses were detected by aCGH and correlated with ALK status.</p><p><b>RESULTS</b>aCGH showed that chromosomal alterations in all 25 ALCL cases, and the frequency of chromosomal gains was higher than that of the losses. Chromosomal gains at 5p13.2, 3q21.1, 2q21.3, 3p25.1, 14q32.33, and 17q21.2 regions were detected in more than 50% of the ALCL cases; gains at 4q27, 6p22.1, 20p11.21, 2q22.3, 4q35.1, 1p36.22, 8p23.1, 8p12, 11q14.1, 12q13.13, and 19p13.3 regions were detected in 30%-50% of the ALCL cases; chromosomal losses at 3q26.1 and 3q26.31 regions were detected in 36.0% (9/25) and 24.0% (6/25) of the ALCL cases, respectively. Chromosomal gains at 2q21.3, 6p22.1 and 3p25.1 regions showed significant differences between ALK (+) and ALK (-) ALCL groups (P < 0.05).</p><p><b>CONCLUSIONS</b>aCGH demonstrates complex molecular genetic variations in all ALCL cases. Gains at 2q21.3, 6p22.1 and 3p25.1 regions are significantly different between ALK (+) and ALK (-) ALCL groups, suggesting that the pathogenesis of ALK (+) and ALK (-) ALCL may involve different signaling pathway.</p>
Subject(s)
Adolescent , Female , Humans , Male , Chromosome Aberrations , Comparative Genomic Hybridization , Methods , Gene Expression Profiling , In Situ Hybridization, Fluorescence , Lymphoma, Large-Cell, Anaplastic , Genetics , Paraffin Embedding , Receptor Protein-Tyrosine Kinases , Genetics , MetabolismABSTRACT
This study was purposed to analyze the relation of N-myc gene copy number with clinical staging, pathological types and tumor biological factors in children with neuroblastoma (NB), and to investigate the influence of chemotherapy on N-myc gene expression and explore the relationship of N-myc gene copies with prognosis of NB children. The newly diagnosed children with NB from 1 March 2007 to 31 January 2011 were enrolled in this study. The treatment was carried out by BCH-NB-2007 based on Hongkong NB-07 protocol, and the patients were follow up to 31 January 2012. The N-myc gene in NB children was detected by FISH. According to number of N-myc gene copies, the NB children were divided into 3 groups. A group (N-myc gene negative) had less than 2 copies, B group (N-myc gene gains) had 3 to 9 copies, and C group (N-myc amplification) had more than 10 copies. The results showed that the N-myc gene expression in 58 cases of NB was observed. There were 36 males and 22 females. NB children aged from 6.5 to 138 months (median age 47.5 months), all patients were followed up for 11 - 57 months with an average of 31.5 months. INSS stages I-IV were 1, 5, 8 and 44 cases, respectively. Twenty-five cases had primary post mediastinal tumor, thirty-three cases had retroperitoneal and pelvic tumor, three of which also companied with post mediastinal tumor. Thirty-five cases had bone metastasis (60.3%), thirty-two cases had bone marrow metastasis (55%). Of the 54 patients with fully known biologic features, seventeen cases had ganglioneuroblastoma, thirty-seven cases had neuroblastoma (15 displayed differentiated, 7 poorly differentiated or undifferentiated, 15 with pathological changes after chemotherapy), four cases had bone marrow metastasis only detected by bone marrow biopsy. Eleven cases had N-myc gene negative, forty-three had N-myc gains, four had N-myc amplification. The average copy number of N-myc gene copies in 58 cases was 5.96 ± 7.81 in which 28 children were non chemotherapy cases, their average copy number was 4.00 ± 1.88, thirty cases out of 58 cases received preoperation chemotherapy (chemotherapy group), and their average copy number was 7.80 ± 10.46, the difference is significant (P = 0.064). The clinic stage, the location of primary tumor, pathological classification, urine VMA and serum neurogenic specific enolase had no effects on the N-myc gene expression, but the serum LDH level had influence (P < 0.01). Single factor Kaplan-Meier analysis showed that the number of N-myc gene copies in NB patients were closely related with the poor prognosis. The more copies of N-myc gene, the more poor prognosis, the difference is statistically significant (P < 0.05). It is concluded that the number of N-myc gene copies correlates with the rapid growth of NB and its poor prognosis, detecting the N-myc amplification can help to estimate the prognosis and decide the program of treatment. Serum LDH, which correlated with the rapid growth of NB, had effect on the N-myc gene expression and is closely related with the poor prognosis of NB.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Gene Amplification , Genes, myc , Neoplasm Staging , Neuroblastoma , Diagnosis , Genetics , Pathology , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To study clinicopathologic and genetic features of anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL).</p><p><b>METHODS</b>Light microscopy, EliVision immunohistocheimical method and fluorescence in-situ hybridization were used to evaluate three ALK + LBCL cases recently diagnosed accompanied with a literature review.</p><p><b>RESULTS</b>All three cases were male adult patients (mean age = 36.3 years) with nodal involvement by lymphoma. Histologic evaluation revealed a diffuse effacement of the nodal architecture by the infiltration of tumor cells. Sinusoidal infiltration was seen. The neoplastic cells were large and exhibited the immunoblastic/plasmablastic morphology. By immunohistochemistry, all the cases showed a cytoplasmic granular staining of ALK. They were positive for CD45, CD138, and epithelial membrane antigen (EMA), but were negative for CD3, CD20, CD79a and CD30. Fluorescence in situ hybridization (FISH) demonstrated the presence of ALK gene translocation in all of the cases.</p><p><b>CONCLUSIONS</b>ALK + LBCL represents a distinct variant of diffuse large B-cell lymphoma, usually involving lymph node of middle-aged men. The tumor has a immunoblastic/plasmablastic morphology along with a distinct immunophenotypic profile and ALK gene rearrangement.</p>
Subject(s)
Adult , Humans , Male , ADP-ribosyl Cyclase 1 , Metabolism , Diagnosis, Differential , Immunohistochemistry , In Situ Hybridization, Fluorescence , Leukocyte Common Antigens , Metabolism , Lymphoma, Large B-Cell, Diffuse , Genetics , Metabolism , Pathology , Lymphoma, Large-Cell, Anaplastic , Metabolism , Pathology , Mucin-1 , Metabolism , Multiple Myeloma , Metabolism , Pathology , Receptor Protein-Tyrosine Kinases , Genetics , Metabolism , Translocation, GeneticABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD).</p><p><b>METHODS</b>Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected.</p><p><b>RESULTS</b>There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene.</p><p><b>CONCLUSIONS</b>ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , CD3 Complex , Metabolism , Epstein-Barr Virus Infections , Pathology , Follow-Up Studies , Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor , Granzymes , Metabolism , Herpesvirus 4, Human , Killer Cells, Natural , Pathology , Lymphoproliferative Disorders , Drug Therapy , Genetics , Metabolism , Pathology , Virology , Poly(A)-Binding Proteins , Metabolism , RNA, Viral , Metabolism , Retrospective Studies , Survival Rate , T-Cell Intracellular Antigen-1 , T-Lymphocytes , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases.</p><p><b>METHODS</b>The clinical data of 66 cases of ALCL was analyzed. The histologic features were reviewed. Immunohistochemical study for CD30, ALK protein, epithelial membrane antigen, CD2, CD3, granzyme B and TIA-1 was carried out. In-situ hybridization for small mRNA of Epstein-Barr virus (EBER) was also performed. The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH). The differences between ALK-positive and ALK-negative cases were statistically analyzed.</p><p><b>RESULTS</b>There were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL. The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL (P < 0.05), with the median age being 18 years and 36 years, respectively. Fever, especially hyperpyrexia, was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients (33 cases versus 4 cases, P < 0.05). The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL (80% versus 71%; 21 months versus 12.5 months, P > 0.05). There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL. Histologically, most cases showed diffuse growth pattern. Nodular pattern was demonstrated in a minority of cases. "Hallmark" cells were seen in most of the ALCL cases. Focal necrosis and myxomatous stroma were identified in a few cases. Most ALK-positive cases belonged to the common variant (35 cases). A small number represented lymphohistiocytic variant (8 cases). Small cell variant and sarcomatoid subtype were found only in few cases (3 cases and 2 cases, respectively).On the other hand, common variant (17 cases) constituted the majority of ALK-negative ALCL. Lymphohistiocytic variant was seen in only 1 case. Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen. ALK-positive ALCL more often expressed epithelial membrane antigen (100% versus 72%; P < 0.05) but less so for T-cell markers (including CD2, CD3, CD43 and CD45RO). Cytotoxic molecules were more commonly expressed in ALK-positive ALCL (P > 0.05). EBER was negative in all cases studied. FISH showed that in ALK-positive ALCL, 1 case had normal ALK gene, 1 had deletion and multicopy and 2 had deletion. On the other hand, 1 case of ALK-negative ALCL had normal ALK gene.</p><p><b>CONCLUSIONS</b>While there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL, the clinical features, immunophenotypes and genetic features of both groups vary. These differences are helpful in guiding the differential diagnosis.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Age Factors , Diagnosis, Differential , Follow-Up Studies , Gene Deletion , Ki-1 Antigen , Metabolism , Lymphoma, Large-Cell, Anaplastic , Drug Therapy , Genetics , Metabolism , Pathology , Malignant Hyperthermia , Mucin-1 , Metabolism , Neoplasm Recurrence, Local , Protein-Tyrosine Kinases , Genetics , Metabolism , Receptor Protein-Tyrosine Kinases , Survival RateABSTRACT
<p><b>OBJECTIVE</b>To investigate the molecular genetic features and diagnostic aspects of sporadic Burkitt's lymphoma (BL) in children.</p><p><b>METHODS</b>Tissue microarray was constructed to include 64 cases of pediatric BL and 6 cases of pediatric diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry and fluorescence in-situ hybridization for c-myc, bcl-2, bcl-6, IgH, myc/IgH and bcl-2/IgH gene were performed. Cases of pediatric Burkitt's lymphomas were subclassified into three groups based on their cellular orgins: the germinal center (GC) group, the late-germinal center (late-GC) group and the post-germinal center (post-GC) group.</p><p><b>RESULTS</b>Among 64 Burkitt's lymphomas studied, expression of CD20, CD10, bcl-6, bcl-2 and MUM1 by immunohistochemistry were 100% (64 cases), 98.4% (63 cases), 96.9% (62 cases), 0 (0 cases) and 23.4% (15 cases), respectively. Various gene rearrangements were found involving the c-myc 93.1% (54/58 cases) and IgH 82.8% (48/58 cases). Detailed rearrangements are as follows: 46 cases (85.2%) myc/IgH gene translocation along with c-myc and IgH gene rearrangement; 4 cases (7.4%) c-myc gene rearrangement without IgH and myc/IgH abnormality; 4 cases (7.4%) without c-myc, IgH or myc/IgH gene rearrangement. No case showed bcl-2 gene abnormality (100%). Fifty nine cases showed normal bcl-6 gene status. One case had bcl-6 gene rearrangement and amplification with the pathologic and immunophenotypic characteristics of BL, leading to a revised pathological diagnosis of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (DLBCL/BL). Two cases showed c-myc gene rearrangement. Two cases showed bcl-6 gene amplification and 6 DLBCL cases had a normal status of bcl-2/IgH.</p><p><b>CONCLUSIONS</b>A majority of pediatric sporadic BL arise from the germinal center B cells, most of which have c-myc gene rearrangement. It is useful to distinguish BL and DLBCL by multiple genes detection.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Antigens, CD20 , Metabolism , Burkitt Lymphoma , Genetics , Metabolism , Pathology , Diagnosis, Differential , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Genes, myc , Genetics , Immunoglobulin Heavy Chains , Genetics , Lymphoma, Large B-Cell, Diffuse , Genetics , Metabolism , Pathology , Neprilysin , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Proto-Oncogene Proteins c-bcl-6 , Metabolism , Translocation, GeneticABSTRACT
<p><b>OBJECTIVE</b>To study the role of pathogenic microorganisms commonly associated with chronic eye disease, including Chlamydia psittaci, Chlamydia trachomatis, Chlamydia pneumoniae, herpes simplex virus (HSV) type 1 and type 2, and adenovirus type 8 and type 19, in the development of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese patients.</p><p><b>METHODS</b>Sixty-eight archival cases of primary ocular adnexal lymphoproliferative lesions, including 38 cases of MALT lymphoma, 3 cases of non-MALT lymphoma and 27 cases of chronic inflammation, were enrolled into the study. DNA was extracted from the paraffin-embedded tissue samples. The presence of DNA of C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 were analyzed by multiplex touchdown enzyme time-release polymerase chain reaction (TETR-PCR).</p><p><b>RESULTS</b>All of the specimens yielded PCR products of over 100 base pairs and were thus suitable for TETR-PCR screening of infectious agents. The prevalence of DNA of C. psittaci, C. trachomatis and adenovirus type 19 were 0 in MALT lymphoma, non-MALT lymphoma and chronic inflammation. There were 2 cases positive for C. pneumoniae DNA, amongst the 38 cases of MALT lymphoma studied (5.3%, 2/38). HSV type 1, HSV type 2 and adenovirus type 8 DNA was found in each of the 3 patients with chronic inflammation.</p><p><b>CONCLUSION</b>The study indicates that C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 probably play little role in the pathogenesis of ocular adnexal MALT lymphoma in Chinese patients.</p>
Subject(s)
Humans , Adenovirus Infections, Human , Virology , Adenoviruses, Human , Genetics , Chlamydia Infections , Microbiology , Chlamydia trachomatis , Genetics , Chlamydophila Infections , Microbiology , Chlamydophila pneumoniae , Genetics , Chlamydophila psittaci , Genetics , DNA, Bacterial , DNA, Viral , Eye Infections , Microbiology , Virology , Eye Neoplasms , Microbiology , Virology , Herpes Simplex , Virology , Herpesvirus 1, Human , Genetics , Herpesvirus 2, Human , Genetics , Lymphoma, B-Cell, Marginal Zone , Microbiology , Virology , Psittacosis , MicrobiologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas.</p><p><b>METHODS</b>Clinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements.</p><p><b>RESULTS</b>Adequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60 (95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23 cases of reactive lymphoid hyperplasia.</p><p><b>CONCLUSION</b>BIOMED-2 assay is highly sensitive and specific for the detection of clonal B cell gene rearrangement using routine paraffin embedded formalin fixed specimens.</p>
Subject(s)
Humans , Antigens, CD20 , Metabolism , CD79 Antigens , Metabolism , DNA, Neoplasm , Genetics , Gene Rearrangement, B-Lymphocyte , Genetics , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Genetics , Gene Rearrangement, B-Lymphocyte, Light Chain , Genetics , Genes, Immunoglobulin , Immunophenotyping , Lymphoma, B-Cell , Genetics , Allergy and Immunology , Pathology , Lymphoma, B-Cell, Marginal Zone , Genetics , Allergy and Immunology , Pathology , Lymphoma, Large B-Cell, Diffuse , Genetics , Allergy and Immunology , Pathology , Paraffin Embedding , Pseudolymphoma , Genetics , Allergy and Immunology , Pathology , Sensitivity and SpecificityABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings, EBV and c-myc gene status of intra-abdominal non-Hodgkin B-cell lymphoma occurring in children.</p><p><b>METHODS</b>Seventy-four cases of pediatric intra-abdominal non-Hodgkin B-cell lymphoma were retrieved from the archival file. The cases were classified according to the 2008 WHO classification. Tissue microarray including tumor tissues from all the 74 cases was produced. Immunohistochemical study (SP method) for CD20, CD3, CD79a, CD10, bcl-6, MUM1, bcl-2, CD43, CD38 and Ki-67 was performed. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) and fluorescence in-situ hybridization for c-myc gene were also carried out.</p><p><b>RESULTS</b>Amongst the 74 cases studied, 65 of them (87.8%) were Burkitt lymphoma (BL), 4 cases (5.4%) were diffuse large B-cell lymphoma (DLBCL) and the remaining 5 cases (6.8%) showed features in-between DLBCL and BL (DLBCL/BL). The patients often presented with abdominal pain, abdominal masses, ileus and intussusception. The ileocecal bowel wall and mesenteric lymph nodes were commonly involved. The lymphoma cells were of high histologic grade and suggested an aggressive clinical behavior. The staining for CD20 and CD79a were positive in all of the cases, while CD3 was negative. The positive rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in BL were 96.9% (63 cases), 95.4% (62 cases), 0 (0 case), 23.1% (15 cases), 70.8% (46 cases), 96.9% (63 cases) and 41.5% (27 cases), respectively. Fifty-four cases carried translocation of c-myc gene. As for DLBCL, the positive cases of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER were 3 cases, 2 cases, 3 cases, 2 cases, 2 cases, 2 cases and 0 case, respectively. One of these cases showed c-myc gene translocation. Amongst the 4 cases of DLBCL, 2 of them belonged to germinal center B-cell-like subtype, while the remaining 2 cases were of non-germinal center B-cell-like subtype. The expression rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in DLBCL/BL were 5/5, 4/5, 0, 3/5, 5/5, 3/5 and 0, respectively. Three of the cases were positive for c-myc gene translocation.</p><p><b>CONCLUSIONS</b>The majority of pediatric intra-abdominal non-Hodgkin B-cell lymphoma belonged to BL. They have characteristic clinical presentation and sites of predilection and are often associated with an aggressive clinical behavior. Thorough morphologic assessment, immunohistochemistry and in-situ hybridization play an important role in subtyping this group of lymphoid malignancy.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Antigens, CD20 , Metabolism , Burkitt Lymphoma , Genetics , Metabolism , Pathology , CD79 Antigens , Metabolism , Genes, myc , Intestinal Neoplasms , Genetics , Metabolism , Pathology , Lymphoma, B-Cell , Genetics , Metabolism , Pathology , Lymphoma, Large B-Cell, Diffuse , Genetics , Metabolism , Pathology , Neprilysin , Metabolism , RNA, Viral , Metabolism , Translocation, GeneticABSTRACT
<p><b>OBJECTIVE</b>To investigate clinicopathological and genetic characteristics of primary ocular adnexal lymphoproliferative lesions.</p><p><b>METHODS</b>Clinical, morphological and immunohistochemical features of 37 archival cases of primary ocular adnexal lymphoproliferative lesions were studied including 5 cases of reactive lymphoid hyperplasia and 32 lymphomas retrospectively. Classification of the lymphomas were made according to the WHO classification of tumors of haematopoietic and lymphoid tissues. All cases were studied by interphase fluorescence in situ hybridization (FISH) using dual color break apart probes of IgH, MALT1, bcl-6, c-Myc, bcl-2, CCND1, bcl-10, and FOXP1 for detection of chromosomal aberrations involving IgH, MALT1, bcl-6, c-Myc, bcl-2, cyclinD1, bcl-10 and FOXP1 genes, respectively. FISH with IgH / bcl-2 dual color dual fusion probe was used for detection of t(14;18)(q32;q21)/IgH-bcl-2. CEP18 spectrum orange probe was used for detection of aneuploidy of the chromosome 18.</p><p><b>RESULTS</b>Among 32 cases of lymphomas, 28 cases (87.5%) were extranodal marginal zone B-cell lymphomas of mucosa associated lymphoid tissue (MALT lymphoma), 2 cases were follicular lymphoma (FL) and 2 cases diffuse large B cell lymphoma (DLBCL). Among the 28 cases of MALT lymphoma, chromosomal aberrations were found in 60.7% (17/28) by interphase FISH analysis. One case showed positive IgH break-apart signal with unknown partner. 16 cases showed three copies of different genes, of which, three copies of MALT1, bcl-6, and c-Myc were identified in 7 cases (25%), 12 cases (43%), and 2 cases (8%) of MALT lymphomas, respectively. In addition, 5 cases showed two genes including three copies of bcl-6 and MALT1 in 4 cases, and three copies of bcl-6 together with c-Myc in one case. Furthermore, all cases with three copies of MALT1 had trisomy 18. t(14;18)(q32;q21) was detected in both follicular lymphomas. Of the 2 DLBCL cases, one showed three copies of bcl-6 together with trisomy 18 and the other one showed three copies of bcl-6 together with IgH and c-Myc rearrangements. Chromosomal aberration was not found in all 5 cases of reactive lymphoid hyperplasia.</p><p><b>CONCLUSIONS</b>The most common entity of primary ocular adnexal lymphomas is MALT lymphoma and FISH is helpful for their differential diagnosis and classification. Trisomy 18 and three copies of bcl-6 are common chromosomal aberrations in primary ocular adnexal MALT lymphomas.</p>