RESUMO
A 63-year-old man with systemic lupus erythematosus developed tubular proteinuria. All subclasses of serum IgG increased, and the largest IgG subclass increase was IgG4. A renal biopsy showed lupus nephritis (Class II) with severe tubulointerstitial nephritis (so-called predominant tubulointerstitial lupus nephritis, an unusual form of lupus nephritis). Immunofluorescence microscopy revealed positive granular staining for IgG, C3 and C1q in the mesangium and peritubular interstitium, and along the tubular basement membranes (TBM). Electron microscopy also showed electron-dense deposits in the mesangium and TBM. Immunophenotyping of interstitial infiltrating cells disclosed a predominance of T cells. CD8-positive cytotoxic T cells infiltrated the peritubular interstitium, and some of these cells infiltrated the tubules. B cell-rich lymphoid follicles were also observed. IgG subclass analyses showed glomerular IgG1, IgG2 and IgG4 deposition, positive staining of IgG4 in the peritubular interstitium and along the TBM, and abundant IgG1-, IgG3- and IgG4-positive plasma cells in the interstitium. The patient responded well to moderate-dose steroid therapy. This is the first report of immunophenotyping of interstitial infiltrates in predominant tubulointerstitial lupus nephritis. The results suggest CD8-positive cytotoxic T cell-mediated tubular injury. Furthermore, immune complexes containing IgG4 might be one of etiologic factors.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Imunoglobulina G/imunologia , Rim/patologia , Nefrite Lúpica/patologia , Nefrite Intersticial/patologia , Biópsia , Linfócitos T CD8-Positivos/patologia , Humanos , Imunoglobulina G/análise , Imuno-Histoquímica , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/imunologiaRESUMO
This study examines the identification of unusual cell populations highly associated with lymphoma cells (UCP-L) in diagnostic biopsy specimens using three-color flow cytometry (3-FCM). Patterns of surface antigen expression were used to compare the morphology of distinct lymphoid cell populations present in biopsy specimens and determine the presence or absence of UCP-L. UCP-L were identified by their larger size as compared to admixed reactive lymphocytes, and the method is based on the concept that neoplastic lymphoma cells are larger than reactive lymphocytes. The comparison of relative cell sizes was determined by overlaying forward scatter histograms by multicolor gating using PAINT-A-GATE software. In order for separate gates to be set on UCP-L and reactive cell populations, UCP-L had to fulfill one or more immunophenotypic criteria. These included: (1) belonging to a subset of B cell antigen-positive cells showing restricted expression of kappa or lambda light chains; (2) belonging to a subset of CD4-positive cells having dim or absent expression of CD45RA; (3) showing alterations in antigen expression (loss, dimmer or brighter); or (4) expressing an immunophenotype that is present on only rare cell populations or is absent from reactive lymph nodes. The immunophenotypic profiles of the respective cell populations were demonstrated by cubic representations to assess more easily the co-expression of three antigens. The common morphology of UCP-L as defined by forward and side scatter grams was consistent with a 'lymphoid appearance' except in several cases of HTLV-I-positive T cell lymphoma and gammadelta T cell lymphoma. The immunophenotypic profiles of UCP-L were confirmed to correspond to the presumptive lymphoma cell population by use of a live gating procedure on the large cells, which eliminated interference by reactive cells or necrotic tissue fragments. Using this method, we identified UCP-L in 208 of 293 (71%) consecutive cases of non-Hodgkin's lymphomas, while no UCP-L were seen in 72 cases of non-specific hyperplasia of lymph nodes. Twenty-seven cases could not properly be examined about the existence of UCP-L because of massive necrosis, extensive fibrosis or strong non-specific staining reactions of unknown cause. When those cases were eliminated from the analysis, 80% of non-Hodgkin's lymphoma were found to contain UCP-L. In B cell lymphoma, the incidence of UCP-L in nodal lymphomas (80%) was much higher than in extranodal lymphomas (47%). Only one of 21 cases of Hodgkin's lymphoma was found to have UCP-L. The 3-FCM procedure was validated by the combined use of immunohistochemistry, morphologic examination, cytogenetic and antigen receptor gene rearrangement analysis by Southern blot hybridization. Our findings indicate that detection of UCP-L by 3-FCM is a reliable method to distinguish non-Hodgkin lymphomas from reactive hyperplasias in the majority of cases, even when the reactive cell population predominates over the malignant cell population.
Assuntos
Antígenos CD , Citometria de Fluxo/métodos , Linfoma/patologia , Antígenos CD/genética , Antígenos CD/imunologia , Biópsia , Southern Blotting , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Linfócitos/patologia , Linfoma de Células B/patologia , Linfoma de Células T/patologia , Células Tumorais CultivadasRESUMO
All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemia (APL), but the effect of cytokines regulating myeloid differentiation on ATRA-induced APL cells is poorly understood. In this study, maturation and proliferation of fresh APL cells were examined when induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors (G-CSF or GM-CSF) in combination with ATRA. APL cells showed a low proliferating activity when induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed increased DNA syntheses, the levels of which were not significantly affected by the combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF potentiated the capability of ATRA-induced cells to reduce nitroblue tetrazolium (NBT), while G-CSF or GM-CSF alone induced no NBT reduction. Furthermore, in several patients examined, APL cells induced by ATRA with G-CSF showed an increased activity of chemotaxis and CD11a expression. These findings suggest that G-CSF or GM-CSF can potentiate differentiation of ATRA-induced APL cells while stimulating their proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a useful adjunct to promote ATRA-induced differentiation of APL.
Assuntos
Medula Óssea/patologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Leucemia Promielocítica Aguda/patologia , Tretinoína/farmacologia , Adolescente , Adulto , Divisão Celular/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Pré-Escolar , Citarabina/uso terapêutico , Interações Medicamentosas , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Tretinoína/uso terapêutico , Células Tumorais CultivadasRESUMO
This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph(+) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. Leukemia(2000) 14, 169-182.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crônica/genética , Linfoma não Hodgkin/genética , Cromossomo Filadélfia , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Primers do DNA , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Nine cases of peripheral T-cell lymphoma were identified in this study showing a distinctive growth pattern with partial distortion of the lymph node structure and prominent infiltration predominantly of marginal zones by medium-sized cells with clear cytoplasm and significant nuclear atypia. In the paracortical T-zone, there was a marked proliferation of high endothelial venules. Plasmocytosis and capsular fibrosis were other distinctive features. On immunohistochemistry, the lymphomas proved to be of T-helper cell origin (CD3+, CD4+, CD5+/-, CD8-, TIA1-) and proliferation was most prominent in the marginal zone of the regressive B-cell follicles. These cases have a characteristic morphology that may be sufficient to differentiate them as a variant from other peripheral T-cell lymphomas of the "not otherwise specified" group and to include them in the list of currently recognized lymphomas. Because of the distinct perifollicular growth pattern and incomplete effacement of the lymph node architecture, the differential diagnosis consists mainly of marginal zone B-cell lymphoma and reactive lesions.
Assuntos
Linfonodos/patologia , Linfoma de Células T Periférico/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização In Situ , Linfoma de Células T Periférico/classificação , Linfoma de Células T Periférico/diagnóstico , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Reação em Cadeia da Polimerase , Coloração e Rotulagem , Fatores de TempoRESUMO
At present, there is no case report of HHV8- primary effusion lymphoma (PEL) with t(9;14)(p13;q32) involving both PAX-5 and immunoglobulin heavy chain gene rearrangement, which is a rare translocation in B-cell non-Hodgkin's lymphoma, in an HIV- patient. We examined an HIV-seronegative 63-year-old Japanese man with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma manifesting peritoneal lymphomatous effusion without tumor mass at any body site. The lymphoma cells were examined twice by light microscopy, immunohistochemistry, three-color flow cytometry, cytogenetics, and molecular analyses. The nuclear morphology of lymphoma cells was similar to that of large noncleaved cells, although the lymphoma cell size was a little smaller that of the usual large-cell lymphoma. Immunophenotyping of lymphoma cells in the ascitic fluid revealed a mature peripheral B-cell phenotype (CD5- CD10- CD19+ CD20+ CD22+ Ig G+ lambda+). Cytogenetics showed a clonal population: 45,X,-Y, der(2) t(2;6)(q31;p21.3), t(4;8)(q21;q11.2), der(6) t(2;6)(q31;p21.3) add(6)(q15), t(9;14)(p13;q32.3) [10]/47, idem, +der(6) t(2;6), +16[10]. Southern blot analysis revealed rearranged fragments with a probe for immunoglobulin heavy chain, some of which were a size similar to those with a PAX-5 gene probe. Polymorphism, not rearrangement, of the c-MYC gene, was also found. HHV8 and the Epstein-Barr virus were not detected by polymerase chain reaction. This case is the first report of an HHV8- PEL with t(9;14) involving a PAX-5 gene rearrangement in an HIV-seronegative patient. This primary effusion lymphoma manifested spontaneous regression without any therapy. These findings suggest that there may be an additional subcategory of primary effusion lymphoma that is not associated with HHV8 nor c-MYC(R) but is pathogenetically associated with the PAX-5 gene or hepatitis C virus.
Assuntos
Líquido Ascítico/genética , Linfócitos B/imunologia , Proteínas de Ligação a DNA/genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Herpesvirus Humano 8 , Linfoma/genética , Proteínas Nucleares/genética , Fatores de Transcrição , Líquido Ascítico/imunologia , Líquido Ascítico/patologia , Líquido Ascítico/virologia , Biomarcadores Tumorais/análise , Southern Blotting , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , DNA de Neoplasias/análise , DNA Viral/análise , Proteínas de Ligação a DNA/imunologia , Evolução Fatal , Rearranjo Gênico de Cadeia Pesada de Linfócito B/imunologia , Genes myc/genética , Hepatite C/patologia , Humanos , Técnicas Imunoenzimáticas , Imunofenotipagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Linfoma/imunologia , Linfoma/patologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Regressão Neoplásica Espontânea , Proteínas Nucleares/imunologia , Fator de Transcrição PAX5 , Reação em Cadeia da Polimerase , Tomografia Computadorizada por Raios XRESUMO
Phenotypic characteristics of blasts were studied in a Down's infant with transient abnormal myelopoiesis (TAM). Two major subpopulations were identified: (1) CD33+CD42b+ cells with platelet peroxidase activity, the commitment of which to megakaryocytic lineage was supported by an increased expression of GATA-1 mRNA; (2) CD33+CD34+CD7+CD4+ cells with immature ultrastructure, which could be either immature megakaryocytic or myeloid cells with aberrant differentiation. Mixed colonies containing megakaryocytes and monocyte/macrophages in the peripheral blood suggested the presence of progenitors common to these subpopulations. These results may indicate that subpopulations of blasts with phenotypic diversity could be derived from aberrant common progenitors to megakaryocytic and myeloid lineages in this patient.
Assuntos
Medula Óssea/patologia , Síndrome de Down/patologia , Hematopoese , Células-Tronco Hematopoéticas/patologia , Megacariócitos/patologia , Northern Blotting , Medula Óssea/metabolismo , Proteínas de Ligação a DNA/genética , Síndrome de Down/metabolismo , Fatores de Ligação de DNA Eritroide Específicos , Feminino , Fator de Transcrição GATA1 , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunofenotipagem , Lactente , Macrófagos/patologia , Megacariócitos/metabolismo , RNA Mensageiro/metabolismo , Fatores de Transcrição/genéticaRESUMO
The case of a male infant with marked deposition of glycogen, confined to the heart, is presented. Clinically, prominent cardiomegaly had been evident from immediately after birth until the infant's death due to heart failure. There were no significant clinical manifestations in other organs, including liver and skeletal muscle, during the clinical course. Autopsy revealed abnormal deposition of normally structured glycogen in the heart, but no deposition in the liver, skeletal muscle, or other systemic organs. This unusual pattern of glycogen deposition was also confirmed by measurement of the glycogen content of each organ. This is the first report of glycogen storage disease confined to the heart. Enzymatic analysis revealed no decrease in the activities of acid maltase, amylo-1,6-glucosidase, and phosphorylase in the heart or in the liver or skeletal muscle. However, phosphorylase kinase activity was not detectable in the heart, although high activity levels were observed in the liver and skeletal muscle. In this case the inborn error of metabolism responsible for the isolated deposition of glycogen in heart muscle may have been due to a deficiency of cardiac phosphorylase kinase.
Assuntos
Cardiomiopatias/patologia , Doença de Depósito de Glicogênio/patologia , Miocárdio/enzimologia , Fosforilase Quinase/deficiência , Cardiomiopatias/metabolismo , Glucana 1,4-alfa-Glucosidase/análise , Glicogênio/metabolismo , Doença de Depósito de Glicogênio/enzimologia , Doença de Depósito de Glicogênio/metabolismo , Humanos , Recém-Nascido , Fígado/enzimologia , Glicogênio Hepático/metabolismo , Masculino , Músculos/enzimologia , Músculos/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Fosforilase Quinase/análise , Fosforilases/análiseRESUMO
A 72-year-old Japanese man presented with CD4+ T cell receptor (TCR) gammadelta T cell lymphoma involving bilateral cervical lymph nodes. No involvement by tumor was observed in the liver, spleen, nasal cavity, or bone marrow throughout his clinical course. Although the tumor adequately responded to chemotherapy and irradiation, he relapsed with short remission and a slowly aggressive clinical course, and died 24 months after onset. Simultaneous expression of TCR gammadelta with other T-cell antigens on the lymphoma cells was analyzed by 3-color flow cytometry (3-FCM), and showed a unique phenotype CD3+ CD4+ CD8- CD7- CD5+ CD2++ TCR alphabeta (WT31)- betaF1-TCR gammadelta1 (11F2)+ TCR delta1+. Cytogenetic analysis showed 79-81 and structural abnormalities consisting of del(1)(p11) and i(17)(q10). But no abnormality was identified in chromosome 7. DNA analysis revealed gene rearrangements of TCRgamma and delta, while a nongerm line band in TCRbeta was aberrantly seen. These observations suggest a new subtype of gammadelta T-cell lymphoma, which is characterized by CD4 positivity and by a clinical course not as aggressive as other predominant subtypes.
Assuntos
Relação CD4-CD8 , Linfoma de Células T/química , Linfoma de Células T/patologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Idoso , Linfócitos T CD4-Positivos/imunologia , Antígenos CD8/análise , Antígenos CD8/genética , Citometria de Fluxo/métodos , Humanos , Imuno-Histoquímica , Masculino , Metáfase , Fenótipo , Linfócitos T/imunologiaRESUMO
We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
Assuntos
Antígenos CD2/análise , Antígenos CD4/análise , Antígeno CD56/análise , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Cariotipagem , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/secundário , Prednisona/uso terapêutico , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias da Medula Espinal/tratamento farmacológico , Neoplasias da Medula Espinal/secundário , Vincristina/uso terapêuticoRESUMO
A 59-year-old woman who had received cobalt-60 (60Co) interstitial radiation therapy (total 44 Gy) in the right bucco-gingival region for inflammatory pseudotumour was found to have metachronous double malignant neoplasms. Initial osteosarcoma of the right mandibular angle and subsequent squamous cell carcinoma of the right buccal mucosa were identified 28 and 33 years after the radiation, respectively. Since both tumours were located very close to the focus of previous radiation, the therapy was considered to be responsible for their genesis. The patient had systemic metastases of the osteosarcoma.
Assuntos
Carcinoma de Células Escamosas/etiologia , Radioisótopos de Cobalto/efeitos adversos , Neoplasias Mandibulares/etiologia , Mucosa Bucal/efeitos da radiação , Neoplasias Bucais/etiologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Osteossarcoma/etiologia , Adulto , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Radioisótopos de Cobalto/uso terapêutico , Feminino , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/radioterapia , Humanos , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/patologia , Doenças da Boca/complicações , Doenças da Boca/patologia , Doenças da Boca/radioterapia , Mucosa Bucal/diagnóstico por imagem , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Neoplasias Induzidas por Radiação/diagnóstico por imagem , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/patologia , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/patologia , Tomografia Computadorizada por Raios XRESUMO
Necropsy findings of an acute fatal case of idiopathic interstitial myocarditis were reported. The patient was a 33 year old housewife who had acute cardiac failure on the sixteenth day after the onset of the disease. Necropsy showed important pathological changes confined to the heart. Both ventricles were affected by confluent granulomas with an ill defined patchy appearance. Histologically these lesions consisted of round cells, histiocytes, eosinophils and myogenic giant cells. The findings were compatible with those of interstitial myocarditis associated with a proliferation of giant cells. Both atriums were also affected to a minor extent, detectable only by histological examination. Electron microscopy and cytochemistry showed that most giant cells noted in the lesion showed myofibrils and primary lysosomes in the cytoplasm. Giant cells were positive for myoglobin. Though the macrophage origin of the giant cell in this disorder has been emphasised in a recent report, these cytological results suggest that giant cells observed in the cardiac granulomatous lesions of this case were mainly myogenic in origin.
Assuntos
Granuloma de Células Gigantes/patologia , Miocardite/patologia , Miocárdio/patologia , Doença Aguda , Adulto , Cardiomiopatias/etiologia , Cardiomiopatias/patologia , Feminino , Granuloma de Células Gigantes/etiologia , Humanos , Miocardite/complicações , Miocárdio/ultraestruturaRESUMO
The most frequent nonrandom chromosome rearrangements in B-cell non-Hodgkin lymphoma (NHL) is the t(14;18)(q32;q21) found in follicular lymphomas. The t(14;18) in Hodgkin disease (HD) was rarely observed using cytogenetic techniques. Although Southern blot analysis failed to demonstrate the t(14;18), there have been conflicting reports concerning the occurrence of the translocation using polymerase chain reaction (PCR) methods in HD. In some HD tissues, the translocation might be derived from background lymphocytes rather than Hodgkin and Reed-Sternberg (HRS) cells, because B-cells with t(14;18) are regularly generated in normal individuals. However, the cells bearing the translocation have remained unidentified. We describe a patient with HD who showed t(14;18) in hyperdiploid cells using fluorescence in situ hybridization (FISH) and HRS cells which were strongly positive for BCL2 by immunohistochemistry. These findings suggest that HRS cells may have a t(14;18).
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Doença de Hodgkin/genética , Translocação Genética , Adulto , Aneuploidia , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/análiseRESUMO
Two cases of B-cell diffuse large cell lymphoma associated with the t(3;7)(q27;p12) and BCL-6 rearrangement are described. Cytogenetic studies revealed [case 1] 47,XY,t(3;7)(q27;p12),+12 and [case 2] 45,X,-Y,t(3;7)(q27;p12),del(6)(q21q25),+16,-21. The translocation of each case had a non-random chromosomal change involving a 3q27 locus associated with BCL-6 gene rearrangement identified by Southern blot analysis. Both cases involved multiple lymph nodes and extranodal regions, such as stomach and peritoneal cavity in case 1, extranodal retroperitoneal space, subcutis, probable liver, and colon in case 2. Chemotherapy provided only short survival after onset: 17 and 16 months, respectively. Altered expression of adhesion molecules CD44, CD54 (case 1) and CD11a and CD18 (case 2) may help to explain the poor outcome of these patients.
Assuntos
Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 7/genética , Proteínas de Ligação a DNA/genética , Rearranjo Gênico do Linfócito B , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Translocação Genética , Idoso , Southern Blotting , DNA de Neoplasias/análise , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Cariotipagem , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6RESUMO
A patient with B-cell lineage diffuse large-cell lymphoma carrying the t(3;16)(q27;p11) and BCL-6 rearrangement is described. Cytogenetic studies showed 46,XY,t(3;16)(q27;p11.2)[.11]/46,idem,add(18)(q21)[7]/46,XY[2]. The chromosomal translocation involving the 3q27 locus was associated with the BCL-6 gene rearrangement identified by Southern blot analysis. This case involved systemic lymph nodes, as large as 3 cm in diameter, bilaterally in neck, axilla, and inguinal regions. The patient obtained complete remission with chemotherapy.
Assuntos
Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 3/genética , Proteínas de Ligação a DNA/genética , Rearranjo Gênico do Linfócito B , Linfoma de Células B/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Antígenos CD/análise , Southern Blotting , Humanos , Cariotipagem , Linfonodos/patologia , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Pescoço , Proteínas Proto-Oncogênicas c-bcl-6RESUMO
The t(1;19)(q23;p13) translocation involving the E2A gene on chromosome 19p13.3 is a nonrandom translocation that is often seen in childhood pre-B-cell acute lymphoblastic leukemia (ALL). However, recent studies have demonstrated the presence of immunophenotypic and molecular heterogeneity among patients with the cytogenetically identical chromosome translocation. Here we report a novel pre-B ALL cell line, TS-2, with t(1;19) translocation not involving the E2A gene. The breakpoint of t(1;19) in TS-2 was demonstrated to be at 19p13.3, a region indistinguishable from the locus of the E2A gene, by cytogenetic study and fluorescence in situ hybridization. However, rearrangement of the E2A gene was not detected in TS-2 by Southern blot analysis. Moreover, the expressions of PBX1 or E2A/PBX1 fusion genes were not detected by an extensive study with Northern blot analysis and reverse transcription-polymerase chain reaction. These findings suggest that TS-2 may have a genetic abnormality involving uncharacterized gene(s) at 19p13.3 distinct from the E2A gene and, therefore, may be useful for investigating the heterogeneity of molecular pathogenesis in leukemias with t(1;19)(q23;p13) translocation.
Assuntos
Proteínas E2 de Adenovirus/genética , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Células Tumorais Cultivadas , Northern Blotting , Southern Blotting , Pré-Escolar , Proteínas de Ligação a DNA/genética , Evolução Fatal , Feminino , Citometria de Fluxo , Proteínas de Homeodomínio/genética , Humanos , Cadeias mu de Imunoglobulina/análise , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Proteínas de Fusão Oncogênica/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Proteínas Proto-Oncogênicas/genéticaRESUMO
We report a clinicopathologic feature of primary cutaneous T-cell lymphoma (CTCL) in a five-year-old boy with increasing swelling of his cheek since two years of age. Histologically, an infiltrate of atypical lymphoid cells with mature T-cell phenotype and clonality was prominent from the dermis to the subcutaneous tissue of the cheek. Although little effect was seen with aggressive multidrug-combined chemotherapy, therapy with interferon-alpha and steroids achieved a prolonged remission. This patient may provide important clues to understanding the clinicopathologic feature of rare primary CTCL in young children.
Assuntos
Bochecha/patologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Pré-Escolar , Rearranjo Gênico , Humanos , Imunofenotipagem , Linfoma Cutâneo de Células T/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Although three subtypes of non-Hodgkin's lymphoma (NHL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), are now well recognized as independent categories, their biological behavior has not been fully compared. One of the reasons for this may be that subclassification by histological examination alone is often difficult since they all have a common variant of a "nodular" growth pattern and occasionally show similar cytological morphology. Recently, we reviewed patients with FL, MCL and MZL, who were prospectively diagnosed, using multiparameter analyses with unfixed fresh biopsy materials. Of 407 NHL patients, 101 (24.8%) belonged to these three categories and 80 could be followed; FL (n=27), MCL (n=27) and MZL (n=26). Twenty eight cases with diffuse large B-cell (DL-B) lineage lymphoma were selected as control at random. The frequency of the MCL patients with performance status (PS) 2 to 4 (41%) was significantly higher than MZL patients (4%) [P< 0.001]. The 3 year survival rate with FL, MCL, MZL and DL-B was 71.5%, 57.4%, 93.3% and 53.1%, respectively. The survival rate for MZL was significantly better than both FL (p = 0.048) and MCL (p = 0.0085). Significant differences were also found in the overall survival rates among the four risk groups as defined by the International Index [I2](low, low-intermediate, high-intermediate and high; 97.4%, 79.6%, 39.4% and 18.2%, respectively). A multivariate analysis revealed that the International Index may be a significant predictor for short survival (p=0.0001) in the patients with FL, MCL or MZL. These results suggest that MZL shows an apparently better prognosis than FL and MCL and is found to be a prognostically independent category. In contrast, the clinical outcome in MCL is the worst among the three subtypes and was closer to that of DL-B. The International Index can be applied to a wide spectrum of NHL, including MCL, MZL and FL, to and can predict prognosis in these cases.
Assuntos
Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , Análise de SobrevidaRESUMO
Two kinds of hybridoma clones, one producing monoclonal antibodies against Sertoli cell (TM-1) and the other the basal lamina of the seminiferous tubule (TM-2), were raised by fusion between P3X63Ag8-653 mouse myeloma cells and spleen cells of BALB/c mice (H-2d) immunized with testicular homogenate of the same inbred mice. Immunohistochemically, TM-1 reacted specifically with cytoplasmic component of Sertoli cell and TM-2 with basal lamina of the seminiferous tubule. Using these monoclonal antibodies, spermatogenic disturbance was induced experimentally in BDF1 (H-2b/d) by intratesticular injection of a set of these two antibodies. Single injection of either TM-1 or TM-2 failed to induce the lesion. This fact indicated that TM-1 antibody could reach the Sertoli cell to impair its function, which was otherwise inaccessible without coincidental action of TM-2 antibody. TM-2 antibody appeared to alter the permeability of the basal lamina of the tubule and lower its barrier effect.
Assuntos
Anticorpos Monoclonais/imunologia , Túbulos Seminíferos/imunologia , Células de Sertoli/imunologia , Espermatogênese , Doenças Testiculares/etiologia , Testículo/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Especificidade de Anticorpos , Membrana Basal/imunologia , Complemento C3/análise , Imunização Passiva , Imunoglobulina M/análise , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Orquite/imunologia , Doenças Testiculares/imunologia , Doenças Testiculares/patologiaRESUMO
From studies of binding of 51Cr-labeled T cells to human thyroid monolayers, we have postulated the existence of tissue "homing-like" receptors on thyroid cells in patients with Graves' disease (GD). In this study we have investigated whether the CD44 (Hermes-1) protein, well known as a putative human lymphocyte homing receptor, is expressed on thyroid cells in patients with GD, and if so whether its expression is influenced by interferon-gamma (IFN-gamma). Cell surface CD44, as well as CD54 (ICAM-1), another putative homing receptor, antigens were analyzed by flow cytometry and immunohistochemistry. CD44 and CD54 were both expressed on thyroid cells from untreated patients with GD, which, in the case of CD44, appeared as two peaks. IFN-gamma treatment enhanced the expression of the CD54 protein on Graves' thyroid cells and inhibited the expression of the larger of the two CD44 peaks, but not the other. Only small amounts of CD44 and CD54 were detected on normal thyroid cells, neither of which was affected by IFN-gamma. The CD44 protein was also demonstrated on both GD and normal thyroid cells by immunohistochemistry. These findings suggest that CD44, and possibly CD54, may induce putative adhesion pathways that lead to the homing of lymphocytes to the thyroid in patients who develop Hashimoto's thyroiditis and Graves' disease.