RESUMO
Various histological subtypes of leukaemia and lymphoma are associated with diagnostic chromosome translocations, and substantial strides have been made in determining the specific oncogenes targetted by those translocations. We report the cloning of a novel fusion oncogene associated with a unique leukaemia/lymphoma syndrome. Patients afflicted with this syndrome present with lymphoblastic lymphoma and a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow, which generally progress to full-blown acute myelogenous leukaemia within a year of diagnosis. A specific chromosome translocation, t(8;13)(p11;q11-12), is found in both lymphoma and myeloid leukaemia cells from these patients, supporting bi-lineage differentiation from a transformed stem cell. We find that the 8p11 translocation breakpoints, in each of four patients, interrupt intron 8 of the fibroblast growth factor receptor 1 gene (FGFR1). These translocations are associated with aberrant transcripts in which four predicted zinc-finger domains, contributed by a novel and widely expressed chromosome-13 gene (ZNF198), are fused to the FGFR1 tyrosine-kinase domain. Transient expression studies show that the ZNF198-FGFR1 fusion transcript directs the synthesis of an approximately 87-kD polypeptide, localizing predominantly to the cytoplasm. Our studies demonstrate an FGFR1 oncogenic role and suggest a tumorigenic mechanism in which ZNF198-FGFR1 activation results from ZNF198 zinc-finger-mediated homodimerization.
Assuntos
Proteínas de Transporte , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 8 , Proteínas de Ligação a DNA/genética , Transtornos Mieloproliferativos/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores Proteína Tirosina Quinases , Receptores de Fatores de Crescimento de Fibroblastos/genética , Translocação Genética , Dedos de Zinco/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Transformação Celular Neoplásica , Humanos , Camundongos , Dados de Sequência Molecular , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Síndrome , Fatores de TranscriçãoRESUMO
When injected into mice, the synthetic double-stranded polynucleotide poly(inosinic) X poly(cytidylic) acid induces high natural killer (NK) cell activity within 4 to 12 hours. Induction of NK activity in mice immunized 2 or 3 days previously, or the addition of NK cells to cultures immunized in vitro 2 or 3 days previously, promotes early termination of the ongoing primary immunoglobulin M antibody response. A target for NK cells is a population of accessory cells that has interacted with antigen and is necessary for sustaining the antibody response. The inference is strong that NK cells induced normally by immunization also terminate the usual antibody response in vivo by elimination of antigen-exposed accessory cells.
Assuntos
Formação de Anticorpos , Células Matadoras Naturais/imunologia , Linfócitos/imunologia , Animais , Células Produtoras de Anticorpos/imunologia , Células Cultivadas , Homeostase , Células Matadoras Naturais/efeitos da radiação , Cooperação Linfocítica , Camundongos , Poli I-C/imunologia , Baço/imunologiaRESUMO
BACKGROUND: Human cancer cell lines grown in the presence of the cytotoxic agent mitoxantrone frequently develop resistance associated with a reduction in intracellular drug accumulation without increased expression of the known drug resistance transporters P-glycoprotein and multidrug resistance protein (also known as multidrug resistance-associated protein). Breast cancer resistance protein (BCRP) is a recently described adenosine triphosphate-binding cassette transporter associated with resistance to mitoxantrone and anthracyclines. This study was undertaken to test the prevalence of BCRP overexpression in cell lines selected for growth in the presence of mitoxantrone. METHODS: Total cellular RNA or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene were analyzed by northern and Southern blot hybridization, respectively. RESULTS: A variety of drug-resistant human cancer cell lines derived by selection with mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins. Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that the BCRP gene was also amplified in these cells. CONCLUSIONS: Overexpression of BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with mitoxantrone, suggesting that BCRP is likely to be a major cellular defense mechanism elicited in response to exposure to this drug. It is likely that BCRP is the putative "mitoxantrone transporter" hypothesized to be present in these cell lines.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Mitoxantrona/farmacologia , Proteínas de Neoplasias/biossíntese , Northern Blotting , Southern Blotting , Neoplasias da Mama/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/metabolismo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/genética , RNA Mensageiro/análise , RNA Neoplásico/análise , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas , Regulação para CimaRESUMO
Murine fibrosarcoma cells were examined for sensitivity to killing by natural killer (NK) and natural cytotoxic lymphocytes from mouse spleens. These tumor cell lines were sensitive to killing by effector cells which were nonadherent to plastic or nylon wool, Thy-1 negative, asialo-GM1 negative, and present in the spleens of beige mice, nude mice, and A/J mice, as well as in the spleens of normal syngeneic and allogeneic control mice. This indicates that the cytotoxic effects were due to natural cytotoxic lymphocytes rather than to NK lymphocytes, T-cells, or macrophages. Although the fibrosarcoma cells were not killed in vitro by endogenous NK cells, these tumor cells were able to "cold target" compete for Yac-1 (an NK-sensitive target) killing and to bind to asialo-GM1-positive, nonadherent spleen lymphocytes in a target cell binding assay. This suggests that the fibrosarcoma cells were recognized by NK cells. In addition, these cell lines were killed in a 4-h NK cytotoxicity assay by polyinosinic-polycytidylic acid-activated effector lymphocytes. The interaction between NK cells and the murine fibrosarcoma cells may have in vivo significance. When syngeneic mice were treated with anti-asialo-GM1 serum to eliminate NK activity and then given i.v. injections of the fibrosarcoma cells, many more lung tumors developed than in control animals. The structural basis for the recognition of the murine fibrosarcoma cells by the NK effector cells is not known. However, laminin may be involved. When the fibrosarcoma cells, which have receptors for the laminin molecule, were preincubated with laminin, they were reduced in their ability to compete for the killing of Yac-1 cells by the NK effectors and had reduced capacity to bind to NK cells in a target cell binding assay.
Assuntos
Fibrossarcoma/imunologia , Gangliosídeo G(M1) , Imunidade Inata , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Animais , Anticorpos Monoclonais , Linhagem Celular , Citotoxicidade Imunológica , Glicoesfingolipídeos/imunologia , Laminina/fisiologia , Camundongos , Poli I-C/imunologia , Receptores Imunológicos/metabolismo , Receptores de LamininaRESUMO
Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post-thymic T cell lymphoma that primarily involves liver and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gammadelta TCL, and plays a role in its pathogenesis.
Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos Par 7 , Leucemia de Células T/genética , Neoplasias Hepáticas/genética , Adolescente , Adulto , Idoso , Bandeamento Cromossômico , Transtornos Cromossômicos , Células Clonais , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Humanos , Imunofenotipagem , Neoplasias Hepáticas/patologia , Masculino , Baço/patologiaRESUMO
A major goal of microarray experiments is to determine which genes are differentially expressed between samples. Differential expression has been assessed by taking ratios of expression levels of different samples at a spot on the array and flagging spots (genes) where the magnitude of the fold difference exceeds some threshold. More recent work has attempted to incorporate the fact that the variability of these ratios is not constant. Most methods are variants of Student's t-test. These variants standardize the ratios by dividing by an estimate of the standard deviation of that ratio; spots with large standardized values are flagged. Estimating these standard deviations requires replication of the measurements, either within a slide or between slides, or the use of a model describing what the standard deviation should be. Starting from considerations of the kinetics driving microarray hybridization, we derive models for the intensity of a replicated spot, when replication is performed within and between arrays. Replication within slides leads to a beta-binomial model, and replication between slides leads to a gamma-Poisson model. These models predict how the variance of a log ratio changes with the total intensity of the signal at the spot, independent of the identity of the gene. Ratios for genes with a small amount of total signal are highly variable, whereas ratios for genes with a large amount of total signal are fairly stable. Log ratios are scaled by the standard deviations given by these functions, giving model-based versions of Studentization. An example is given.
Assuntos
Perfilação da Expressão Gênica/estatística & dados numéricos , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Análise de Variância , Biologia Computacional , Glioma/genética , Humanos , Modelos Estatísticos , Análise de Regressão , Células Tumorais CultivadasRESUMO
Three patients with T-cell lymphoblastic lymphoma and peripheral blood eosinophilia are reported. At the time of diagnosis, all patients had lymphadenopathy, and one had a mediastinal mass. Lymph node biopsies revealed lymphoblastic lymphoma admixed with a variable number of mature eosinophils. Immunophenotypic studies demonstrated that each lymphoma had an immature T-cell immunophenotype. Bone marrow biopsies were hypercellular with myeloid hyperplasia and eosinophilia but were negative for lymphoma. All patients received multiagent chemotherapy; one patient achieved a complete remission, and two patients had partial remissions. All patients subsequently developed a myeloid malignancy. Two died of acute myeloid leukemia within 18 months of the diagnosis of lymphoblastic lymphoma. The third patient relapsed with a lymphoma that had histologic and immunophenotypic features of both T-cell lymphoblastic lymphoma and granulocytic sarcoma and also developed a poorly defined myeloproliferative disorder. These findings suggest that T-cell lymphoblastic lymphoma associated with eosinophilia may represent a distinct clinico-pathologic entity with a high risk of subsequent myeloid neoplasia.
Assuntos
Eosinofilia/complicações , Leucemia Mieloide/etiologia , Transtornos Mieloproliferativos/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Doença Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Medula Óssea/patologia , Criança , Citogenética , Feminino , Histocitoquímica , Humanos , Imunofenotipagem , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/patologia , Linfonodos/patologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
The clinical and pathological features of acute pancreas allograft rejection and involvement of the graft by posttransplantation lymphoproliferative disorders (PTLD) overlap. Because the treatment is diametrically opposite in these two types of lesions, an accurate diagnosis is essential. The histological features in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4) from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with the material from 14 patients who did not develop PTLD after 12 to 58 months of follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed rejection-related heavy or atypical inflammatory infiltrates. Features typical of rejection included most (>75%) being of mixed small and large, activated-appearing T lymphocytes, a smaller component of mature plasma cells, and variable numbers of eosinophils. Cytologically atypical cells were always a minority (< 10%). The inflammation involved the septal spaces with proportional involvement of the exocrine tissue, veins, ducts, and arteries. The inflammation was particularly targeted against the acini and was associated with acinar cell damage. Features characteristic of PTLD were nodular and expansile infiltrates, composed of a significant proportion of atypical, plasmacytoid B cells (40% to 70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The infiltrates involved the parenchyma randomly with no apparent affinity for the acinar tissue. Extensive infiltration of the peripancreatic soft tissues was common. Arterial walls were not involved in PTLD unless there was concurrent acute vascular rejection. Features identified in both conditions were foci of necrosis and infiltration of venous walls with associated endotheliitis. Samples with concurrent PTLD and acute rejection showed combinations of these features. In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in the samples from patients with PTLD. Based on the assessment of morphological differences and the selective use of relatively simple ancillary techniques, PTLD can be correctly diagnosed even in small tissue samples such as needle biopsy specimens. An early diagnosis will lead to the appropriate treatment.
Assuntos
Rejeição de Enxerto/patologia , Infecções por Herpesviridae/diagnóstico , Herpesvirus Humano 4/isolamento & purificação , Transtornos Linfoproliferativos/diagnóstico , Transplante de Pâncreas , Complicações Pós-Operatórias/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Doença Aguda , Adulto , Diagnóstico Diferencial , Feminino , Seguimentos , Infecções por Herpesviridae/virologia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Transtornos Linfoproliferativos/virologia , Masculino , Pâncreas/patologia , Pâncreas/virologia , Complicações Pós-Operatórias/virologia , RNA Viral/análise , Transplante Homólogo , Infecções Tumorais por Vírus/virologiaRESUMO
We compared conventional cytogenetic findings in mantle cell lymphomas (MCLs) having an absolute peripheral lymphocytosis of more than 10,000/microL (>10 x 10(9)/L) at diagnosis ("leukemic"; n = 30) with those in cases having no or minimal lymphocytosis ("nodal"; n = 19). Only cases positive for t(11;14) were included for study. Forty-six cases (94%) had abnormalities in addition to t(11;14). The most frequent abnormalities involved chromosome 13 (26 cases [53%]), followed by chromosomes 1, 3, 7, 8, 9, 10, 12, 15, 17, and 21 (11-18 cases [22%-37%]). There was no difference in the number of aberrations between the 2 groups. Abnormalities of chromosomes 17, 21, and 22 were more frequent, and breakpoints involving 8q24, 9p22-24, and 16q24 were found exclusively in leukemic MCL. Chromosome 17 aberrations involved were structural (breakpoints involving 17p13, 17p11.2, 17q) in leukemic MCL but were only numeric in nodal MCL. Thus, leukemic MCL differs from nodal MCL in their cytogenetic profiles, which may contribute to the clinical presentation.
Assuntos
Aberrações Cromossômicas , Linfoma de Célula do Manto/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandeamento Cromossômico , Feminino , Humanos , Linfonodos/patologia , Linfocitose/genética , Linfocitose/patologia , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
We report 8 cases of hepatosplenic T-cell lymphoma (HSTCL) involving bone marrow and correlate histologic findings with disease progression. Immunophenotypic analysis demonstrated mature, aberrant gamma/delta T-cell immunophenotypes. Isochromosome 7q was identified in 4 cases; 1 case showed the t(7;14)(q34;q13). Seven of 7 cases tested had monoclonal TCR gamma gene rearrangements. The initial diagnostic bone marrow biopsy specimens were hypercellular with a frequently subtle, predominantly sinusoidal infiltrate of atypical small to medium-sized lymphoid cells. In all cases, aspirate smears at diagnosis and in subsequent specimens contained malignant cells that resembled blasts, some with fine cytoplasmic granules. With progression, the pattern of HSTCL in bone marrow biopsy specimens became increasingly interstitial, and the neoplastic cells became larger. In aspirate smears, the proportion of blasts increased. Seven patients died; 1 was lost to follow-up. Autopsy performed on 1 patient demonstrated malignant cells within vascular channels in all organs sampled, with relatively little tumor formation, resembling intravascular lymphoma at these sites. HSTCL often can be recognized in bone marrow by its unique combination of a sinusoidal pattern in core biopsy specimens and blastic cytology in aspirate smears.
Assuntos
Medula Óssea/patologia , Neoplasias Hepáticas/patologia , Linfoma de Células T/patologia , Neoplasias Esplênicas/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/imunologia , Criança , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 7/genética , DNA de Neoplasias/análise , Feminino , Rearranjo Gênico do Linfócito T/genética , Hepatomegalia/etiologia , Hepatomegalia/patologia , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/imunologia , Esplenomegalia/etiologia , Esplenomegalia/patologia , Resultado do TratamentoRESUMO
We describe a novel 4-color polymerase chain reaction (PCR) assay combined with GeneScan analysis to assess for T-cell receptor gamma chain gene (TCRgamma) rearrangements and evaluate its usefulness in 86 lymphoproliferative lesions. In this assay, each variable region (Vgamma) family primer is 5' end-labeled with a different fluorescent dye, allowing determination of the Vgamma family involved in each TCRgamma rearrangement. PCR products were analyzed by capillary electrophoresis. We detected clonal TCRgamma rearrangements in 60 (98%) of 61 T-cell lymphomas, 2 (15%) of 13 B-cell lymphomas, and 3 (25%) of 12 reactive lesions. These results compared favorably with conventional PCR methods using denaturing gradient gel electrophoresis, which revealed clonal TCRgamma rearrangements in 37 (90%) of 41 T-cell lymphomas, 1 (25%) of 4 B-cell lymphomas, and 2 (25%) of 8 reactive lesions. This 4-color PCR assay is at least equivalent to conventional PCR methods and is convenient, allows accurate size determination of TCRgamma rearrangements, and identifies the specific Vgamma family involved, providing more specific information about TCRgamma rearrangement.
Assuntos
Rearranjo Gênico , Linfoma de Células B/genética , Linfoma de Células T/genética , Transtornos Linfoproliferativos/genética , Reação em Cadeia da Polimerase/métodos , Receptores de Antígenos de Linfócitos T gama-delta/genética , Humanos , Células Jurkat , Reação em Cadeia da Polimerase/normas , Sensibilidade e EspecificidadeRESUMO
We describe the clinical, histologic, immunophenotypic, and genotypic features of five cases of histologically discordant lymphomas with B-cell and T-cell components. Three patients presented with B-cell lymphoma; T-cell lymphoma subsequently developed. One patient presented with T-cell lymphoma; B-cell lymphoma subsequently developed. One patient presented with synchronous B-cell and T-cell lymphomas. There were three men and two women. The median age at the initial diagnosis of lymphoma was 66 years. The mean interval between the development of the two lymphomas was 83 months. All patients died of disease. The mean survival was 96 months after the initial diagnosis of lymphoma and 14 months after the diagnosis of the histologically discordant lymphoma. Epstein-Barr virus was found in two cases--the B-cell lymphoma in the patient who presented with synchronous lymphomas, and the subsequent T-cell lymphoma in one of the patients who presented with B-cell lymphoma. Based on the results of immunophenotypic and genotypic analyses, these cases likely represent the occurrence of two distinct lymphoid neoplasms rather than histologic progression of the same neoplastic clone. Furthermore, a subset of these cases are Epstein-Barr virus-associated.
Assuntos
Linfoma de Células B/patologia , Linfoma de Células T/patologia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Medula Óssea/química , Medula Óssea/patologia , Neoplasias da Medula Óssea/química , Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Medula Óssea/patologia , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patologia , Primers do DNA/análise , Primers do DNA/química , Primers do DNA/genética , DNA de Neoplasias/análise , DNA de Neoplasias/química , DNA de Neoplasias/genética , DNA Viral/análise , DNA Viral/química , DNA Viral/genética , Feminino , Genótipo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunofenotipagem , Linfonodos/química , Linfonodos/patologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/virologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/virologia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/virologia , Pele/química , Pele/patologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Baço/química , Baço/patologia , Neoplasias Esplênicas/química , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/patologiaRESUMO
Non-Hodgkin lymphoma arising in the paratesticular organs without testicular involvement is rare. In most previously reported cases, the classification systems that were used are now outdated and/or immunologic studies were not done. We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma arising in the epididymis and the spermatic cord. Patient 1 was a 35-year-old man who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who presented with a right inguinal mass. Orchiectomy performed in both patients revealed a mass confined to the epididymis in patient 1 and to the spermatic cord in patient 2. Histologic examination in both cases revealed diffuse large cell lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent staging studies showed no other site of disease in patient 1 and an isolated mass anterior to the right psoas muscle in patient 2. Malignant lymphoma involving testicular adnexal structures without involvement of the testis is extremely uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases confined to the spermatic cord have been reported previously.
Assuntos
Epididimo/patologia , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Cordão Espermático/patologia , Neoplasias Testiculares/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Epididimo/metabolismo , Epididimo/cirurgia , Humanos , Técnicas Imunoenzimáticas , Linfoma de Células B/metabolismo , Linfoma de Células B/cirurgia , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Cordão Espermático/metabolismo , Cordão Espermático/cirurgia , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/cirurgiaRESUMO
Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults.
Assuntos
Linfoma Folicular/patologia , Neoplasias Testiculares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/química , Linfócitos B/patologia , Biomarcadores Tumorais/análise , Criança , Ciclofosfamida/administração & dosagem , DNA de Neoplasias/análise , Doxorrubicina/administração & dosagem , Humanos , Imuno-Histoquímica , Linfoma Folicular/química , Linfoma Folicular/terapia , Masculino , Proteínas de Neoplasias/análise , Orquiectomia , Reação em Cadeia da Polimerase , Prednisona/administração & dosagem , Neoplasias Testiculares/química , Neoplasias Testiculares/terapia , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: Anaplastic large cell Ki-1 lymphoma has been proposed to be a neoplasm of activated lymphocytes, mostly of T-cell origin. CASE: A previously healthy 12-year-old boy presented with a two-month history of a rapidly growing hard palate mass that involved the nasal cartilage and extended to the floor of the right orbit. By light microscopy (LM) the aspirates were very cellular, containing single, pleomorphic cells and occasional cellular aggregates. The cells showed distinct polarity, with the large, anaplastic nucleus at one end and the tapering cytoplasm, including a prominent paranuclear halo (or "hof"), at the other end ("hand mirror" appearance). The cytoplasmic border showed prominent ruffling, concentrated at the two poles of the cells and corresponding to the areas of the protopod and uropod. Immunocytochemically (ICC) the cells were positive for Ki-1, epithelial membrane antigen and UCHL-1, all of which showed both membrane positivity along with Golgi area staining. LCA showed variable membrane staining. Ultrastructurally (electron microscopy [EM]) the polarity was recapitulated, with an eccentric, horseshoe-shaped nucleus partially enclosing a prominent Golgi complex with associated centrosomes and asymmetric plasma membrane ruffling. CONCLUSION: All three levels of examination (LM, ICC and EM) revealed tumor cell features corresponding to the phenotype of the activated lymphocyte. These features are characteristic, thus allowing the diagnosis of Ki-1 anaplastic lymphoma by fine needle aspiration cytology.
Assuntos
Ativação Linfocitária , Linfoma Anaplásico de Células Grandes/imunologia , Linfoma Anaplásico de Células Grandes/patologia , Neoplasias Palatinas/imunologia , Neoplasias Palatinas/patologia , Biópsia por Agulha , Criança , Humanos , Linfoma Anaplásico de Células Grandes/ultraestrutura , Masculino , Neoplasias Palatinas/ultraestrutura , Linfócitos T/imunologiaRESUMO
The clinical features and outcomes of 148 patients with acute myeloid leukemia (AML) and 11q23 chromosomal abnormalities were compared with those of 2640 patients with non-11q23 AML. Patients with t(9;11) ), t(6;11) or other 11q23 balanced translocations (t(11;v)(q23;v)) presented at a younger age and with higher percentage of bone marrow blasts. Unbalanced 11q23 abnormalities were commonly associated with deletions of chromosomes 5q, 7q and/or complex karyotypes. In multivariate analysis, when compared with patients with non-11q23 AML and unfavorable-risk karyotype, there was a significant difference in overall survival (OS) for patients with t(9;11) (P=0.004), whereas there were no differences in OS for patients with t(6;11) (P=0.62), t(11;19) (P=0.20) and unbalanced 11q23 aberrations (P=0.85) or t(11;v)(q23;v) (P=0.59), indicating that t(9;11) has an independent intermediate prognostic significance, with all others being poor prognostic factors for OS; this was further confirmed by comparing them with patients with non-11q23 AML and intermediate-risk karyotype. Using intention-to treat analysis based on donor availability, we also noted that allogeneic stem cell transplant in first remission had a significant benefit toward improving OS (P<0.001) and relapse-free survival (P<0.001) in patients with AML and 11q23 abnormalities.