RESUMEN
BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor prognosis and frequent central nervous system (CNS) relapses under anthracycline-containing chemotherapy. The aim of this study was to determine the prognosis and CNS relapse incidence of CD5+ DLBCL in the rituximab era. PATIENTS AND METHODS: We analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R-chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab. RESULTS: No significant difference was found in clinical background comparisons between the two groups. In the R-chemotherapy group, 60% of the patients were older than 65 years at diagnosis. Both the complete response rate and overall survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003 and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy without rituximab was associated with unfavorable OS. However, the probability of CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83% of patients who experienced CNS relapse had parenchymal disease. CONCLUSIONS: Our results indicate that rituximab improves the OS of patients with CD5+ DLBCL but does not decrease the CNS relapse rate. More effective treatments with CNS prophylaxis are needed for CD5+ DLBCL patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Antígenos CD5/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundario , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Prednisona/administración & dosificación , Inducción de Remisión , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) comprises â¼10% of DLBCLs, and it is associated with poor prognosis. The clinicopathologic characteristics and prognosis of CD5-negative (CD5-) DLBCL and CD5+ DLBCL were compared. PATIENTS AND METHODS: The subjects were 607 DLBCL patients in whom cell surface markers could be analyzed, among 930 consecutive patients registered in the Adult Lymphoma Treatment Study Group between 1998 and 2008. RESULTS: In all, 102 patients (16.8%) had CD5+ DLBCL. Compared with CD5- DLBCL, CD5+ DLBCL was more closely associated with elevated serum lactate dehydrogenase level, advanced stage, poor performance status, extranodal sites, CD10-, BCL-2+, MUM1+, and nongerminal center B-cell type. The 5-year overall survival (OS) rates of CD5+ DLBCL (n = 102) and CD5- DLBCL (n = 505) were 55% and 65%, respectively (P = 0.032), with 5-year progression-free survival (PFS) rates of 52% and 61%, respectively (P = 0.041). In the CD5+ DLBCL patients, the addition of rituximab to chemotherapy significantly improved PFS (4-year PFS, 47.4% versus 62.5%), but not OS (4-year OS, 57.8% versus 63.5%). CONCLUSIONS: For CD5+ DLBCL, the addition of rituximab to chemotherapy significantly improved the PFS, but not OS. Therefore, it is thought that a new treatment strategy is necessary for CD5+ DLBCL.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Antígenos CD5/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: We carried out immunohistochemistry to examine the expression of nm23-H1 in Hodgkin and Reed-Sternberg cells in patients with classical Hodgkin's lymphoma (CHL). PATIENTS AND METHODS: We evaluated 128 patients with CHL [87 patients with nodular sclerosis (NS) and 41 patients with mixed cellularity (MC)] for CD15, CD20, Ki-67, EBER, TIA-1, and nm23-H1 by immunohistochemistry. RESULTS: CD15 was expressed in 79%, CD20 in 11%, Ki-67 in 93%, EBER in 34%, TIA-1 in 11%, and nm23-H1 in 60% of the CHL patients. NS patients showed a significantly higher rate of nm23-H1 expression than MC patients (P < 0.001). The serum nm23-H1 level was significantly higher in patients with positive nm23 expression. Univariate analysis showed that stage IV, poor performance status, low hemoglobin level, low serum albumin level, age of 45 years or older, TIA-1-positive status, and nm23-H1-positive status were associated with significantly shorter progression-free survival. Multivariate analysis with these factors showed TIA-1 and cytoplasmic nm23-H1 expression to be significant and independent prognostic factors. CONCLUSIONS: Our results indicate that nm23-H1 expression is a prognostic factor for CHL and that it is as important as serum nm23-H1, both of which are useful for planning the treatment strategy.
Asunto(s)
Enfermedad de Hodgkin/enzimología , Enfermedad de Hodgkin/patología , Nucleósido Difosfato Quinasas NM23/biosíntesis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-1/biosíntesis , Masculino , Persona de Mediana Edad , Células de Reed-Sternberg/enzimología , Células de Reed-Sternberg/patología , Tasa de SupervivenciaRESUMEN
AIMS: The Revised European American Lymphoma classification uses the term Hodgkin's-like anaplastic large cell lymphoma (HD-like ALCL) for borderline cases with features of both anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL). The aim of this study was to clarify the association between cytotoxic molecule (CM) expression and clinical outcome in HD-like ALCL. METHODS AND RESULTS: Subjects were 59 patients with HD-like ALCL, defined by nodal presentation without mediastinal bulky lesions, T- or null-cell phenotype, CD30+ anaplastic lymphoma kinase (ALK)- phenotype and by confluent sheets or nodules of large cells mimicking classic Hodgkin and Reed-Sternberg cells. We evaluated the presenting features and prognosis of subjects on categorization into two defined groups, namely CM (TIA1 and/or granzyme B)-positive (n = 21) and CM-negative (n = 38). The series consisted of 18 women and 41 men ranging from 16 to 88 years of age (median 59 years). The CM+ group had poorer disease-specific survival than the CM- group (P = 0.02) despite the absence of differences in other clinical characteristics. Multivariate analysis confirmed that CM expression was an independent prognostic factor, in contrast to phenotypic categorization (T-cell vs. null-cell group), which had no prognostic impact on disease-specific survival. CONCLUSION: CM expression is predictive of prognosis in HD-like ALCL.
Asunto(s)
Granzimas/metabolismo , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/metabolismo , Proteínas de Unión a Poli(A)/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Regulación Neoplásica de la Expresión Génica , Granzimas/genética , Enfermedad de Hodgkin/patología , Humanos , Linfocitos Nulos/patología , Linfoma de Células B Grandes Difuso/genética , Masculino , Persona de Mediana Edad , Fenotipo , Proteínas de Unión a Poli(A)/genética , Valor Predictivo de las Pruebas , Pronóstico , Células de Reed-Sternberg/patología , Análisis de Supervivencia , Antígeno Intracelular 1 de las Células T , Linfocitos T/patologíaAsunto(s)
Biomarcadores de Tumor/metabolismo , Células Asesinas Naturales/patología , Linfoma de Células T/sangre , Proteínas de Unión al GTP Monoméricas/sangre , Nucleósido-Difosfato Quinasa , Linfocitos T/patología , Factores de Transcripción/sangre , Antígenos CD/sangre , Femenino , Humanos , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Nucleósido Difosfato Quinasas NM23 , Pronóstico , Tasa de SupervivenciaRESUMEN
Primary central nervous system lymphoma (PCNSL) is a rare disease, especially among non-AIDS patients. Although almost all PCNSLs belong to the diffuse large B-cell lymphoma (DLBL) category, its clinical course differs from that of other types of DLBL. To elucidate the histogenesis of PCNSL, we analyzed the source of the cells from its variable region (VH) sequences using the polymerase chain reaction (PCR) method to amplify the immunoglobulin heavy chain (IgH) gene of DNA extracted from paraffin sections. Fifteen patients with AIDS-unrelated PCNSL of DLBL type, (7 males and 8 females), were evaluated. Only one case showed positive evidence of EBV infection. The prognosis was very poor with a median survival of 9 months. Analysis of the VH sequences revealed that the VH4 family was used in 4 cases and the VH3 family in 2 cases. The homology with previously published germline sequences was random, ranging from 82.7-93.2%, showing intermediate to high somatic mutations. In 3 of 6 cases, the existence of intraclonal diversity was suspected. These findings suggest that PCNSLs are histogenetically derived from antigen selected B cells in the germinal center (GC) environment.
Asunto(s)
Neoplasias del Sistema Nervioso Central/genética , Genes de Inmunoglobulinas/genética , Región Variable de Inmunoglobulina/genética , Linfoma de Células B/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Neoplasias del Sistema Nervioso Central/etiología , Neoplasias del Sistema Nervioso Central/patología , Femenino , Expresión Génica , Reordenamiento Génico/genética , Centro Germinal/patología , Humanos , Japón , Linfoma de Células B/etiología , Linfoma de Células B/patología , Linfoma de Células B Grandes Difuso/etiología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Modelos Genéticos , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Blastic natural killer (NK) cell lymphoma/leukemia is a relatively rare NK cell malignancy. We report the second case of blastic NK cell lymphoma arising from the mediastinum with an aggressive clinical course. The patient was a 63-year-old Japanese man with an anterior mediastinum tumor. The biopsy specimen showed diffuse proliferation of tumor cells with frequent mitotic figures and apoptotic bodies. Both angiocentric features and small foci of coagulative necrosis were found in this section. The tumor cells had medium to large nuclei with a fine chromatin pattern, inconspicuous nucleoli and scanty cytoplasm. The nuclear contour was oval to moderately irregular, showing slight pleomorphism as compared with typical lymphoblastic lymphoma. The tumor cells were positive for CD2, CD56 and terminal deoxynucleotidyl transferase, but negative for other T-cell antigens, B-cell antigens and myeloid markers. In situ hybridization for Epstein-Barr virus encoded small ribonucleic acid 1 was negative.
Asunto(s)
ADN Nucleotidilexotransferasa/metabolismo , Células Asesinas Naturales/patología , Leucemia Linfoide/patología , Neoplasias del Mediastino/patología , Apoptosis , Antígenos CD2/metabolismo , Antígeno CD56/metabolismo , Quimioterapia Adyuvante , Resultado Fatal , Citometría de Flujo , Humanos , Inmunohistoquímica , Células Asesinas Naturales/enzimología , Células Asesinas Naturales/metabolismo , Leucemia Linfoide/enzimología , Leucemia Linfoide/metabolismo , Leucemia Linfoide/terapia , Masculino , Neoplasias del Mediastino/enzimología , Neoplasias del Mediastino/metabolismo , Neoplasias del Mediastino/terapia , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non-Hodgkin's lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B-NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10+, CD19+, CD20+, CD45RO-, CD3- and CD56+. On immunohistochemical study, neither bcl-2 nor TIA-1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.
Asunto(s)
Antígeno CD56/metabolismo , Células Asesinas Naturales/metabolismo , Linfoma de Células B/metabolismo , Linfoma no Hodgkin/metabolismo , Adolescente , Secuencia de Bases/genética , Biomarcadores , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Eliminación de Gen , Humanos , Región Variable de Inmunoglobulina/genética , Inmunofenotipificación , Linfoma de Células B/genética , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Linfoma no Hodgkin/genética , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
A 78-year-old Japanese female was admitted to our hospital with dysphagia and weight loss. An oesophageal tumour was demonstrated radiologically and endoscopically, and was diagnosed as oesophageal cancer by biopsy. Histologically, the resected tumour showed poorly differentiated squamous cell carcinoma with prominent lymphoid stroma and was diagnosed as the so-called lymphoepithelioma-like carcinoma (LELC). Epstein-Barr virus in the tumour was negative by polymerase chain reaction and in situ hybridization. Oesophageal LELC is extremely rare. The cases in the literature, as well as the one reported here, presented with gross features of a submucosal tumour-like appearance. Although the differentiation of the tumour cells is often poor, prognosis seems to be better than for other types of oesophageal cancer. Oesophageal LELC has characteristic clinicopathological features and should be classified by criteria independent of other types of tumour.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Anciano , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/virología , Endoscopía Gastrointestinal , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/virología , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , ARN Viral/genética , RadiografíaRESUMEN
We investigated 44 cases of Hodgkin's disease for Epstein-Barr virus genome with EBER-1 in situ hybridization. Twenty of 44 (45.5%) were positive for EBV. Simultaneously, immunoglobulin gene rearrangements were assessed in 32 of these 44 cases with PCR on DNA extracted from Reed-Sternberg cell (RS-cell) -rich areas microdissected from paraffin sections. Clonally rearranged immunoglobulin (IgH) gene was observed in 15 cases (46.9%). EBV-negative cases showed more frequent IgH rearrangement than EBV-positive cases (10 and 5 cases, respectively). In 9 cases, the RS cells were CD20-positive immunohistochemically and these were all EBV negative and the IgH gene was rearranged in all except one. These findings may suggest that EBV infection has occurred before the immunoglobulin gene rearrangement or that EBV infection has influenced the rearrangement of the immunoglobulin gene. The results may also hint towards the obscure B-cell nature of the RS cells.