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1.
Pediatr Blood Cancer ; 64(7)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27957801

RESUMO

BACKGROUND: Recurrent genomic changes in B-lymphoblastic leukemia (B-ALL) identified by genome-wide single-nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B-lymphoblastic lymphoma (B-LBL), is limited by the low incidence and lack of fresh tissue for genomic testing. PROCEDURE: We used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalin-fixed paraffin-embedded pediatric B-LBL (n = 23) and B-ALL (n = 55). RESULTS: Similar to B-ALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26%) B-LBL cases. Eleven of 23 (48%) B-LBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of B-ALL. IKZF1 and PAX5 deletions were observed in 13 and 17% of B-LBL, respectively, which was similar to the reported frequency in B-ALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22%) B-LBL cases, compared with only 1% in B-ALL samples. None of the B-LBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25% of B-ALL. CONCLUSIONS: Our study demonstrates that the copy number profile of B-LBL is distinct from B-ALL, suggesting possible differences in pathogenesis between these closely related diseases.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Feminino , Formaldeído , Humanos , Leucemia de Células B/genética , Linfoma de Células B/genética , Masculino , Inclusão em Parafina , Fixação de Tecidos
2.
Adv Anat Pathol ; 21(3): 160-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24713985

RESUMO

Burkitt lymphoma (BL) is the most common non-Hodgkin lymphoma in children and adolescents, but at least 30% of cases occur in patients older than 60 years, and the absolute number of BL cases in adults exceeds those in childhood. BL is described as a monomorphic proliferation of medium-sized transformed B cells with round nuclei, clumped chromatin, basophilic cytoplasm, and squared-off cell borders, cytoplasmic vacuoles, medium-sized paracentral nucleoli, and a starry sky pattern. Translocation involving MYC is characteristic but not specific for BL. No single parameter is the gold standard for diagnosis; morphology, cytogenetics, immunophenotype, and gene expression profiles all may contribute to the diagnosis. Although neither EBV nor MYC are sufficient to cause BL there is increasing information from techniques such as complete RNA sequencing that identify essential pathways that are activated in the pathogenesis of BL. These findings suggest novel opportunities for improved therapeutic intervention.


Assuntos
Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Transformação Celular Neoplásica/genética , Genes myc/genética , Translocação Genética , Humanos
3.
Br J Haematol ; 162(6): 792-801, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23889312

RESUMO

The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS-negative Stage III and IV lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non-Hodgkin lymphoma/BFM-95 therapy with high dose MTX in interim maintenance but no IT-MTX in maintenance (Arm B1). Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5-year event-free survival (EFS) for the four arms: Arm A1, 80% [95% confidence interval (CI) 67-89%] and Arm A2, 81% (95% CI 69-89%); Arm B1, 80% (95% CI 68-88%) and Arm B2, 84% (95% CI 72-91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly [5-year EFS of 63% (95% CI 29-85%)]. For CNS-negative patients, there was no difference in outcome based on CNS prophylaxis (IT-MTX versus HD-MTX) or with intensification.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/prevenção & controle , Neoplasias do Sistema Nervoso Central/secundário , Criança , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
4.
Blood ; 117(9): 2596-603, 2011 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-21079154

RESUMO

Dose-intensified treatment strategies for Hodgkin lymphoma (HL) have demonstrated improvements in cure but may increase risk for acute and long-term toxicities, particularly in children. The Children's Oncology Group assessed the feasibility of a dose-intensive regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in children with high-risk HL (stage IIB or IIIB with bulk disease, stage IV). Rapidity of response was assessed after 4 cycles of BEACOPP. Rapid responders received consolidation therapy with guidelines to reduce the risk of sex-specific long-term toxicities of therapy. Females received 4 cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) without involved field radiation therapy (IFRT). Males received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with IFRT. Slow responders received 4 cycles of BEACOPP and IFRT. Ninety-nine patients were enrolled. Myelosuppression was frequent. Rapid response was achieved by 74% of patients. Five-year event-free-survival is 94%, IFRT with median follow-up of 6.3 years. There were no disease progressions on study therapy. Secondary leukemias occurred in 2 patients. Overall survival is 97%. Early intensification followed by less intense response-based therapy for rapidly responding patients is an effective strategy for achieving high event-free survival in children with high-risk HL. This trial is registered at http://www.clinicaltrials.gov as #NCT00004010.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
5.
Br J Haematol ; 159(4): 454-61, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22994934

RESUMO

T-lymphoblastic leukaemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) are neoplasms derived from immature lymphoid cells of T-cell lineage. These neoplasms are biologically similar, but significant differences may exist between the two given their clinical differences. Although ample data regarding the immunophenotypic characterization T-ALL are available, there is a paucity of such data in children and adolescents with T-LBL. We used flow cytometry and/or immunohistochemistry to characterize the immunophenotypic profile of 180 children and adolescents with newly diagnosed T-LBL enrolled in the Children's Oncology Group 5971 study. Multiple T-cell, B-cell, myeloid, and other markers were evaluated. We identified diagnostically useful immunophenotypic features of T-LBL as well as distinct immunophenotypic subgroups, although none of these was statistically related to event-free or overall survival in this retrospective analysis. Further studies of biologically and immunophenotypically distinct subgroups of T-LBL, such as the early T-cell precursor phenotype, are warranted.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Citometria de Fluxo , Humanos , Imunofenotipagem/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Células Precursoras de Linfócitos T/imunologia , Células Precursoras de Linfócitos T/patologia , Estudos Retrospectivos
6.
Pediatr Blood Cancer ; 59(7): 1229-33, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22488718

RESUMO

BACKGROUND: Localized lymphoblastic lymphoma (LL) is rare in pediatric patients. We report the 5-year event-free survival (EFS) and overall survival (OS) for children and adolescents with localized LL treated on a uniform regimen based on Children's Cancer Group (CCG) leukemia therapy (COG A5971). PROCEDURE: From June 2000 to October 2005, the study enrolled 60 patients >12 months old with Murphy stages I or II LL. Central review confirmed 56 eligible patients. Treatment consisted of 24 months of CCG BFM without day 28 intrathecal methotrexate in maintenance therapy or prophylactic cranial radiation. RESULTS: Most patients had pre-B immunophenotype (75%). At a median follow-up of 5.9 years (range 1.4-9.3 years), the 5-year EFS was 90% [95% confidence interval (CI), 78-96%] and the 5-year OS was 96% (95% CI, 84-99%). Stage (I vs. II), immunophenotype, elevated LDH > institutional normal, or primary site did not impact outcome. Five relapses occurred-none in the CNS and none in patients with pre-T lymphoblastic disease. Patients tolerated treatment well with no toxic deaths. CONCLUSION: Outcomes of pediatric patients with localized LL treated with 2 years of intensive acute lymphoblastic leukemia (ALL)-type therapy was excellent and is similar to the outcome for standard risk ALL treated less intensively. CNS prophylaxis was adequate with limited intrathecal methotrexate and no radiation. Future studies should identify biologic prognostic factors or biomarkers for pediatric patients with LL, explore less intensive treatment for patients with localized disease, and explore novel immunophenotype directed therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/uso terapêutico , Daunorrubicina/uso terapêutico , Intervalo Livre de Doença , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisona/uso terapêutico , Recidiva , Vincristina/uso terapêutico
7.
J Pediatr Hematol Oncol ; 34(1): 68-71, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22215099

RESUMO

This study reports 6 cases of primary follicular lymphoma of the testis (PFLT) in children and adolescents correlated with clinical presentation, pathologic features, treatment, and outcome. All 6 patients (age, 3 to 16 y; median, 4 y) had PFLT grade 3 with disease limited to the testis, completely resected and treated with 2 courses of chemotherapy (cyclophosphamide, vincristine, prednisone, doxorubicin). Event-free survival was 100% (follow-up: median, 73 mo; mean, 53 mo; range, 6 to 96 mo). In conclusion, clinical outcome in children and adolescents with PFLT is excellent with treatment including complete surgical resection and 2 courses of cyclophosphamide, vincristine, prednisone, doxorubicin.


Assuntos
Linfoma Folicular/terapia , Neoplasias Testiculares/terapia , Adolescente , Criança , Pré-Escolar , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia
8.
Br J Haematol ; 148(4): 600-10, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19895612

RESUMO

Burkitt lymphoma (BL), an aggressive B-cell malignancy, is often curable with short intensive treatment regiments. Nearly all BLs contain rearrangements of the MYC/8q24 region; however, recent cytogenetic studies suggest that certain secondary chromosomal aberrations in BL correlate with an adverse prognosis. In this multi-centre study, the frequency and impact on clinical outcome of del(13q) and +7 in addition to MYC rearrangements as detected by fluorescence in situ hybridization (FISH) in children and adolescents with intermediate and high-risk BL registered on Children's Cancer Group study CCG-5961 were investigated. Analysis with 13q14.3 and 13q34 loci specific probes demonstrated deletions of 13q in 38/90 (42%) cases. The loss of either 13q14.3 or 13q34 alone occurred in 14% and 8% respectively, while 20% exhibited loss of both regions. Gain of chromosome 7 was observed in 7/68 (10%) cases and MYC rearrangements were detected in 84/90 (93%). Prognostic analysis controlling for known risk factors demonstrated that patients exhibiting loss of 13q, particularly 13q14.3, had a significant decrease in 5-year overall survival (77% vs. 95%, P = 0.012). These observations indicate that del(13q) occurs in childhood BL at frequencies higher than previously detected by classical cytogenetics and underscores the importance of molecular cytogenetics in risk stratification.


Assuntos
Linfoma de Burkitt/genética , Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento , Adulto Jovem
9.
Pediatr Blood Cancer ; 51(3): 369-74, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18493992

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) makes up 10-20% of pediatric non-Hodgkin lymphoma, and these patients have a significantly better prognosis than adults with DLBCL. The difference in prognosis may be related to clinical, phenotypic, and/or biological differences between adult and pediatric DLBCL. In adult DLBCL, the germinal center (GC) phenotype is associated with a better prognosis than the activated B-cell (ABC) phenotype. However, a high proliferative index and expression of Bcl2 and c-Myc protein have all been associated with worse outcomes. While multiple studies have addressed the phenotype and expression patterns of adult DLBCL, relatively little is known about these biological variables in pediatric DLBCL. The goal of this study was to investigate the proliferative index, the relative frequencies of the GC and non-GC subtypes, and the expression of Bcl2 and c-Myc protein in a cohort of children with DLBCL treated in a uniform manner. PROCEDURE: We performed immunohistochemistry (IHC) for MIB1, CD10, Bcl6, MUM1, Bcl2, and c-Myc on DLBCL tissue from children treated uniformly in the FAB LMB96 trial (SFOP LMB96/CCG5961/UKCCSG/NHL 9600). RESULTS: Compared to published adult DLBCL studies, pediatric DLBCL demonstrated moderate to high proliferation rates (83%), increased c-Myc protein expression (84%), decreased Bcl2 protein expression (28%), and an increased frequency of the GC phenotype (75%). CONCLUSIONS: These findings suggest that there are significant biologic differences between pediatric and adult forms of DLBCL, which may contribute to the superior prognosis seen in the pediatric population relative to adult disease.


Assuntos
Proliferação de Células , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-myc/análise , Adulto , Criança , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/análise
10.
Cancer Genet Cytogenet ; 172(1): 1-11, 2007 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17175373

RESUMO

Among pediatric non-Hodgkin lymphomas, one of the most frequent types is lymphoblastic lymphoma (LBL). Specific chromosome abnormalities are associated with prognosis in childhood acute lymphoblastic leukemia, but have not been evaluated for prognostic value in pediatric LBL. For the Children's Cancer Group protocol CCG-E-08 Etiologic Study of Non-Hodgkin Lymphoma in Childhood, 13 patients were enrolled with cytogenetic analysis of LBL and on treatment protocol CCG-502. Pathology material and karyotypes at initial diagnosis were given central review. The patients were aged 6-13 years (median 9 years), with a male-to-female ratio of 12:1. All patients had advanced disease. Disease relapsed in six patients (event-free survival 54% +/- 14%, median 10.8 years). Chromosome abnormalities were identified in 11 (85%), and translocations at 14q11.2 likely involving the T-cell receptor alpha/delta locus (TCR A/D) occurred in 4 (31%). For patients with relapse, four had translocations t(1;14)(p32;q11.2), t(8;14)(q24.1;q11.2), t(11;14)(p13;q11.2), or t(9;17)(q34;q23), involving breakpoints in the regions of TAL1, MYC, LMO2, and NOTCH1, respectively. Pediatric advanced LBLs have a high frequency of chromosome abnormalities; in this limited study, these often involved translocations at 14q11.2, the site of TCR A/D. Translocations possibly involving TAL1, MYC, LMO2, or NOTCH1 may have contributed to poor outcome. Further studies are warranted in larger cohorts of children and adolescents with LBL to evaluate the prognostic significance.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Criança , Feminino , Humanos , Cariotipagem , Masculino , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Taxa de Sobrevida , Translocação Genética
11.
Cancer Genet Cytogenet ; 171(2): 89-96, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17116485

RESUMO

Among pediatric non-Hodgkin lymphomas, one of the most distinctive types is anaplastic large cell lymphoma (ALCL). Specific chromosomal abnormalities are associated with prognosis in childhood acute lymphoblastic leukemia, but chromosome abnormalities have not been evaluated for prognostic value in pediatric ALCL. For Children's Cancer Group protocol CCG-E-08 Etiologic Study of Non-Hodgkin Lymphoma in Childhood, three patients were enrolled with cytogenetic analysis of ALCL and simultaneously enrolled on treatment protocol CCG-552. Pathology material and karyotypes at initial diagnosis underwent central review. Demographics included ages of 9, 12, and 14 years, and a male/female ratio of 1:2. All patients had advanced disease (stage III). Disease progressed or relapsed in two patients, and one died. Chromosomal abnormalities, including t(2;5)(p23;q35), the ALK/NPM fusion gene, and complex karyotypes with multiple additional abnormalities, were identified in all three patients. In two patients with progressive disease or relapse, additional chromosomal abnormalities at 1q21 and 10q24, possibly involving MCL1 and HOX11/TCL3, respectively, may have contributed to worse outcome. Pediatric ALCL cases frequently have complex karyotypes and usually involve ALK/NPM translocations in this limited study. Additional chromosome abnormalities may be involved in the pathogenesis of ALCL. Further studies are warranted in larger cohorts of children and adolescents with ALCL.


Assuntos
Aberrações Cromossômicas , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Criança , Feminino , Humanos , Cariotipagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Translocação Genética
12.
J Clin Oncol ; 20(9): 2293-301, 2002 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11981000

RESUMO

PURPOSE: Non-Hodgkin's lymphoma (NHL) arising in bone is a heterogeneous histologic type of NHL that includes large-cell lymphoma, lymphoblastic lymphoma, and small noncleaved-cell lymphoma. NHL arising in bone is well recognized in adults but is less well characterized and infrequent in children and adolescents. PATIENTS AND METHODS: We performed a retrospective review of Children's Cancer Group (CCG) studies treating children and adolescents with NHL over a 20-year period (CCG-551, CCG-501, CCG-502, CCG-503, CCG-552, CCG-5911, and CCG-5941) and determined the response and event-free survival (EFS) rates in 31 patients with NHL arising in bone. RESULTS: The patients ranged in age from 3 to 17 years (median, 11 years; mean, 11 years), and 64.5% were male. All 31 (100%) patients achieved complete response. For 31 patients with NHL arising in bone, the product-limit estimated 5-year EFS was 83.8% +/- 6.7%. EFS in 17 patients with localized disease (Murphy stages I and II) was 94.1% +/- 5.7%, and EFS in 14 patients with disseminated disease (Murphy stage III) was 70.7% +/- 12.4% (log-rank P =.10). EFS in 17 patients treated with chemotherapy and radiation was 70.1% +/- 11.2%, and EFS in 14 patients treated with chemotherapy without radiation was 100% (P =.03). EFS in 26 patients with histology-directed treatment (LSA2-L2 or ADCOMP for lymphoblastic, other therapy for nonlymphoblastic) was 92.2% +/- 5.3%, and in five patients with nonhistology-directed treatment it was 40.0% +/- 21.9% (P <.001). CONCLUSION: NHL arising in bone is a heterogeneous type of NHL that makes up approximately 2.0% of NHL in children and adolescents on CCG studies. Response and survival in this young age group seem superb, with histology-directed treatment protocols without radiation in both localized and disseminated disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
13.
Am J Clin Pathol ; 124(4): 569-75, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16146820

RESUMO

Elevated T-cell leukemia-1 (TCL1) oncoprotein expression might promote human Burkitt lymphoma (BL) because increased TCL1 causes Burkitt-like lymphomas in TCL1 transgenic mice. Epstein-Barr virus (EBV) infection has been implicated as a cause of increased TCL1 expression in multiple BL cell lines, suggesting a critical connection between EBV and TCL1-induced BL. The TCL1 expression and EBV status of 14 sporadic pediatric BL cases was determined by immunohistochemical staining for TCL1 and in situ hybridization for EBV-encoded RNA (EBER). Our results showed TCL1 protein in 11 cases, predominantly in the nucleus with strong-intensity staining. EBER was positive in 4 cases, with 3 of these cases also TCL1+. In the 10 cases that were EBER-, TCL1 was strongly positive in 8. These data indicate that the TCL1 oncoprotein is expressed strongly in most pediatric BL cases. However, persistent EBV is not essential for increased TCL1 expression, although elevated TCL1 and c-MYC coexpression might cooperate in the development of most pediatric and adult BL cases.


Assuntos
Linfoma de Burkitt/metabolismo , Herpesvirus Humano 4/isolamento & purificação , Tecido Linfoide/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Adolescente , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Criança , Pré-Escolar , Bandeamento Cromossômico , Feminino , Herpesvirus Humano 4/genética , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Cariotipagem , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Masculino , RNA Viral/análise , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo
14.
Am J Clin Pathol ; 121(3): 384-92, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15023043

RESUMO

Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) account for nearly all pediatric nonlymphoblastic B-cell lymphomas. Because clinical behavior, prognosis, and response to therapy might differ, diagnostic accuracy is important. Morphologic examination often is sufficient, but occasionally, diagnostic ancillary studies are required. In adults, immunophenotyping is useful; however, pediatric data are limited. We characterized the immunohistochemical expression of 6 proteins (c-myc, CD10, bcl-6, bcl-2, CD138, and MIB-1) in pediatric BL (33 cases) and DLBCL (20 cases) with classic morphologic features. Significant differences in c-myc (BL, 30/33 [91%] vs DLBCL, 5/20 [25%]; P < .0001), bcl-2 (BL, 1/25 [4%] vs DLBCL, 7/19 [37%]; P < .02), and mean MIB-1 (BL, 99% vs DLBCL, 56%; P < .0001) expression were observed. There were no significant differences for CD10 (100% expression in BL and DLBCL), bcl-6 (BL, 23/33 [70%] vs DLBCL, 15/20 [75%]), or CD138 (no expression). Thus, pediatric BL and DLBCL have distinctive immunohistochemical profiles, and staining for c-myc, MIB-1, and bcl-2 might be useful in morphologically difficult cases.


Assuntos
Biomarcadores Tumorais/análise , Linfoma de Burkitt/diagnóstico , Linfoma de Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adolescente , Linfoma de Burkitt/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Antígeno Ki-67/metabolismo , Linfoma de Células B/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Neprilisina/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo
15.
Am J Clin Pathol ; 118(3): 335-43, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12219775

RESUMO

Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be derivedfrom cells of the dendritic system. Fascin, a 55-kd actin-bundling protein, represents a highly selective marker for dendritic cells of lymphoid tissues and peripheral blood and is involved in the formation of dendritic processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may represent Langerhans cells arrested at an early stage of activation, immunohistochemical expression offascin in epidermal Langerhans cells and in the lesional cells of 34 cases of LCH was evaluated in paraffin sections using an immunoalkaline phosphatase technique. Though epidermal Langerhans cells were nonreactive for fascin, lesional cells in all LCH cases exhibited immunoreactivityforfascin, CD1a, and S-100 protein. Variation in staining intensity was observed in some cases, possibly reflecting differences in cell maturation or activation. Involved tissues included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional cells of LCH for fascin supports their derivation from cells of the dendritic system and represents another alteration in the phenotype of Langerhans cells that is associated with maturation, migration, culture, or clonal expansion.


Assuntos
Actinas/metabolismo , Células Dendríticas/metabolismo , Histiocitose de Células de Langerhans/metabolismo , Indóis/metabolismo , Adolescente , Adulto , Biomarcadores , Criança , Pré-Escolar , Células Dendríticas/patologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Histiocitose de Células de Langerhans/patologia , Humanos , Técnicas Imunoenzimáticas , Lactente , Masculino , Pessoa de Meia-Idade
16.
Clin Lymphoma ; 5(3): 184-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15636694

RESUMO

Approximately 15% of all cases of childhood classical Hodgkin's disease (HD) express CD20, a B-cell marker associated with immunoglobulin heavy chain rearrangements. Immunoglobulin heavy chain rearrangements in Reed-Sternberg cells could be used to assess minimal residual disease (MRD), as was shown with immunoglobulin heavy chain patient-specific primers (PSPs) in non-Hodgkin's lymphoma. The aim of this study was to analyze pediatric HD for future design of immunoglobulin heavy chain PSP for MRD detection. DNA was extracted from paraffin-embedded tissue from unstained slides of 8 pediatric CD20+ nodular sclerosis HD cases and 10 CD20-nodular sclerosis HD cases. Immunoglobulin heavy chain polymerase chain reaction and sequencing were performed on 16 of 18 cases, which had adequate DNA for further analysis. Sequence analysis from 3 cases (19% of HD cases) demonstrated unique V(D)J regions, which could potentially be used to design PSP. Unique PSPs could be used to assess MRD in advanced-stage HD specimens. Future studies should focus on improved detection and analysis of more cases to identify appropriate specimens in assessing clinical implications of MRD detection.


Assuntos
Antígenos CD20/sangue , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Doença de Hodgkin/imunologia , Adolescente , Antígenos CD/análise , Antígenos CD/sangue , Antígenos CD20/análise , Sequência de Bases , Criança , Pré-Escolar , Primers do DNA , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/patologia , Humanos , Masculino , Estadiamento de Neoplasias
17.
Clin Adv Hematol Oncol ; 1(5): 314-7, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-16224429

RESUMO

Paraffin-embedded diagnostic biopsy materials from a large cohort of pediatric and adolescent patients with mature B-cell non-Hodgkin's lymphoma (NHL) treated on the Children's Cancer Group arm of an international cooperative trial were studied to determine their phenotypic features and the feasibility of using targeted bioimmune therapies. There were 345 patients eligible for analysis: 208 with Burkitt's lymphoma (BL), 43 with high-grade B-cell lymphoma, Burkitt-like (HGBL), and 94 with diffuse large B-cell lymphoma (DLBCL). Samples were immunophenotyped centrally using a standard panel that included CD20, CD79a, CD3, and CD45RO. Additional staining with CD22 was performed on a subset of cases. Immunophenotypic studies showed positive staining with CD20 in 100% of cases of BL and HGBL and in 98% of cases with DLBCL. CD22 expression was present in all cases of BL and DLBCL and in 87% of cases HGBL. This study indicates that immune-based therapies such as rituximab and ibritumomab-tiuxetan (anti-CD20) and epratuzumab (anti-CD22) are feasible in pediatric cases of mature B-cell NHLs.


Assuntos
Antígenos de Neoplasias/análise , Sistemas de Liberação de Medicamentos , Linfoma de Células B/patologia , Adolescente , Adulto , Antígenos de Neoplasias/imunologia , Antígenos de Superfície/análise , Antígenos de Superfície/imunologia , Biópsia , Criança , Pré-Escolar , Humanos , Imunofenotipagem , Imunoterapia , Lactente , Linfoma de Células B/tratamento farmacológico
18.
Am J Surg Pathol ; 37(2): 241-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23282971

RESUMO

Human herpesvirus-8 (HHV8)-positive effusion-based lymphomas have been termed primary effusion lymphoma (PEL) in the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Kaposi sarcoma herpesvirus (KSHV)/HHV8-negative effusion-based lymphomas (KSHV/HHV8-negative EBLs) resembling PELs have been reported in the literature and in many cases have been (mis)classified as PEL-like lymphomas. Herein, we present a series of cases and a review of KSHV/HHV8-negative EBLs. This lymphoma, although cytomorphologically resembling PEL, is a distinct entity with characteristic clinical and pathologic features. Patients are older, generally human immunodeficiency virus negative and not immunosuppressed, frequently hepatitis C positive compared with the population baseline, and often have an underlying medical condition leading to fluid overload. The lymphoma cells express pan-B-cell antigens in 86.7%, and CD20 is expressed in 71.1% of the cases. The lymphoma is often of germinal center B or mixed germinal center B/activated B-cell signature with the Hans classifier, and Epstein-Barr virus is positive in nearly 30% of cases. Rare T-cell lymphomas were also reported. Clinical outcomes and response to therapy, including isolated aspiration, are relatively favorable compared with cases of PEL. We suggest that HHV8-negative effusion-based lymphoma is a distinct entity associated with fluid overload states.


Assuntos
Herpesvirus Humano 8/isolamento & purificação , Linfoma de Efusão Primária/patologia , Sarcoma de Kaposi/patologia , Desequilíbrio Hidroeletrolítico/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/metabolismo , Biomarcadores Tumorais/metabolismo , Evolução Fatal , Feminino , Humanos , Linfoma de Efusão Primária/complicações , Linfoma de Efusão Primária/metabolismo , Linfoma de Efusão Primária/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/metabolismo , Resultado do Tratamento , Desequilíbrio Hidroeletrolítico/complicações , Desequilíbrio Hidroeletrolítico/metabolismo
19.
Pediatr Dev Pathol ; 10(5): 403-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17929987

RESUMO

We report the case of an 18-year-old female initially diagnosed with CD5-negative diffuse large B-cell lymphoma in an inguinal lymph node in 1999 who subsequently relapsed with classic-morphology mantle cell lymphoma with involvement of the bone marrow, gastrointestinal tract, and spleen in 2004. Both the 1999 and 2004 lesions were retrospectively positive for Cyclin D1 by immunohistochemistry and positive for t(11:14)(q13;q32) by fluorescence in situ hybridization, and both lesions had identical B-cell receptor gene rearrangements by polymerase chain reaction. This case of a CD5-negative large cell or pleomorphic blastoid variant of mantle cell lymphoma arising in an 18-year-old represents a very early incidence for this type of lymphoma, which is usually not seen in younger patients.


Assuntos
Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclina D1/biossíntese , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Rearranjo Gênico do Linfócito B , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/patologia , Translocação Genética
20.
Br J Haematol ; 138(4): 506-12, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17659054

RESUMO

Immunophenotypic analysis can identify protein epitopes in non-Hodgkin lymphomas (NHL) that may respond to targeted immunotherapies, such as anti-CD20 and anti-CD52. Recent studies suggest additional targets may provide therapeutic benefits in NHL. This study evaluated protein expression of CD25, CD52, CD74 and CD80 in paediatric NHL to determine possible targets for immune-based therapeutic approaches. Patient samples were derived from paediatric NHL clinical trials sponsored by the Children's Cancer Group (CCG, now the Children's Oncology Group, COG) and included Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), disseminated T- and B-cell lymphoblastic lymphoma (T-LBL and B-LBL) and anaplastic large cell (ALCL). Immunophenotypic studies were performed on formalin-fixed, paraffin-embedded diagnostic tissues. CD25 was expressed in 8% of T-LBL and 75% of ALCL cases, but not in BL, DLBCL, or B-LBL. CD52 was expressed in 99% of cases of paediatric NHL of all subtypes. CD74 was expressed in 100% of B-LBL, BL and DLBCL, but was absent in ALCL and T-LBL. CD80 was expressed in 12% of B-LBL, 6% of BL and 10% of DLBCL cases studied, but was not detected in T-cell NHL. These expression patterns suggest that CD25, CD52 and CD74 may represent potential new therapeutic targets in paediatric NHL.


Assuntos
Antígenos CD/análise , Linfoma não Hodgkin/imunologia , Antígenos de Diferenciação de Linfócitos B/análise , Antígenos de Neoplasias/análise , Antígeno B7-1/análise , Antígeno CD52 , Criança , Glicoproteínas/análise , Antígenos de Histocompatibilidade Classe II/análise , Humanos , Imunofenotipagem , Imunoterapia , Subunidade alfa de Receptor de Interleucina-2/análise , Linfoma não Hodgkin/terapia
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