Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Lab Hematol ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31529774

RESUMO

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma. Three prognostic factors are widely used in DLBCL: International Prognostic Index (IPI), Revised-IPI (R-IPI), and National Comprehensive Cancer Network-IPI (NCCN-IPI). METHOD: We established a prognostic model using peripheral blood absolute lymphocyte/absolute monocyte counts ratio (LMR), hemoglobin, and platelet counts obtained from complete blood cell counts (CBC) data at diagnosis based on 214 cases of DLBCL who received more than one course of R-CHOP therapy at a single institution. RESULTS: The cutoff values for using the receiver operating characteristics (ROC) curve for LMR, hemoglobin, and platelet counts were 1.6, 100 g/L, and 150 × 109 /L, respectively. Stratification was performed using the three factors (LMR < 1.6, hemoglobin < 100 g/L, and platelet counts < 150 × 109 /L). CBC Group 1 (none of the 3 factors) included 92 cases, CBC Group 2 (1 or 2 of these factors) included 108 cases, and CBC Group 3 (all 3 factors) included 11 cases. The 5-year OS rates were 78.2%, 60.9%, and 10.1%, respectively. In multivariate analysis, CBC Group 3 (hazard ratio, 2.9760; 95% confidence interval, 1.2670-6.991; P = .01) were prognostic factors for OS. CBC Group 3 had factors based on which the further stratification of the poor prognosis group into IPI high-risk and R-IPI poor-risk groups (P = .01, <.0001, respectively) was possible. CONCLUSIONS: In DLBCL, combination of three CBC parameters has the potential to be a useful prognostic tool.

2.
Am J Surg Pathol ; 43(7): 869-884, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31116708

RESUMO

Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.

3.
Ann Hematol ; 98(5): 1197-1207, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30729289

RESUMO

The hepatitis C virus (HCV) is a single-stranded RNA virus which is thought to be involved in the onset of B cell lymphoma. HCV-positive diffuse large B cell lymphoma (DLBCL) has been reported to clinically manifest in extranodal lesions (e.g., in the liver, spleen, and stomach). Here, we investigated HCV-positive and -negative primary splenic DLBCL (p-spDLBCL) and non-primary splenic DLBCL (ordinary DLBCL). Furthermore, to examine HCV lymphomagenesis, RNA in situ hybridization (ISH), RT-PCR (reverse-transcription polymerase chain reaction), and NS3 immunostaining of HCV viral nonstructural proteins were performed. HCV-positive p-spDLBCL patients presented fewer B symptoms (asymptomatic) and better performance status, with elevated presence of splenic macronodular lesions and more germinal center B cell (GCB) sub-group cases than HCV-negative p-spDLBCL patients. However, HCV-positive ordinary DLBCL patients were found to have more non-GCB sub-group cases than HCV-negative ordinary DLBCL patients. HCV-positive DLBCL patients showed 20.6% (7/34) NS3 positivity, 16.7% (1/6) HCV-RNA in situ positivity, and 22.2% (2/9) detection of HCV-RNA in tumor tissue by RT-PCR. Splenic samples were found to have a higher frequency of HCV detection than lymph node samples, thus suggesting that HCV may be closely related to lymphomagenesis, especially in splenic lymphoma.


Assuntos
Transformação Celular Viral , Hepacivirus/metabolismo , Hepatite C , Linfoma Difuso de Grandes Células B , RNA Viral/metabolismo , Neoplasias Esplênicas , Proteínas não Estruturais Virais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite C/metabolismo , Hepatite C/patologia , Humanos , Hibridização In Situ , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Esplênicas/metabolismo , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/virologia
4.
Am J Surg Pathol ; 42(11): 1466-1471, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30307409

RESUMO

GNA13 is a G protein involved in modulating tumor proliferative capacity, infiltration, metastasis, and migration. Genomic alteration of GNA13 was frequently observed in follicular lymphoma (FL). In this study, we examined 167 cases of FL by immunostaining of GNA13 using tissue microarray to evaluate the clinical significance. There were 26 GNA13-positive cases (15.6%) and 141 GNA13-negative cases (84.4%). GNA13-positive cases had a higher incidence of early progression of disease for which disease progression was recognized within 2 years compared with GNA13-negative cases (P=0.03). There were no significant differences in other clinicopathologic factors including histological grade, BCL2-IGH translocation, immunohistochemical phenotype, and Follicular Lymphoma International Prognostic Index. In addition, overall survival and progression-free survival were poorer in GNA13-positive cases than in GNA13-negative cases (P=0.009 and 0.005, respectively). In multivariate analysis, GNA13 positivity was found to be a poor prognostic factor for overall survival and progression-free survival. Thus, GNA13 protein expression was an independent prognostic factor and may affect disease progression in FL.

5.
Pathol Int ; 68(11): 614-617, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30255584

RESUMO

Langerhans cell sarcoma (LCS) is a very rare histiocytic and dendritic cell neoplasm originating from Langerhans cells. There are case reports of histiocytic and dendritic cell neoplasms synchronously or sequentially observed in patients with malignant lymphoma. We present a case in which LCS and follicular lymphoma (FL) grade 3a were observed within the same lymph node. A 66-year-old male visited our hospital with a general malaise. Pleural effusion and systemic lymph adenopathy were detected. Biopsy of an inguinal lymph node was performed. The lymph node had regions with follicular structure and regions with acidophilic cytoplasm and large proliferating atypical cells. The tumor cells in the regions with follicular structure showed positivity for CD20 and BCL2 consistent with an FL grade 3a diagnosis. The tumor cells in the regions without follicular structure showed positivity for CD1a and S-100 and were consistent with an LCS diagnosis. Both tumor cells showed the positivity of BCL6 split by FISH. PCR detected IgH clonality in DNA collected from each region, and direct sequence analysis of cells from both tumors detected almost identical amino acid sequences. This finding is important for future research on the development of very rare histiocytic and dendritic cell neoplasms.

6.
Cancer Cell ; 34(2): 286-297.e10, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30057145

RESUMO

Adult T cell leukemia/lymphoma (ATLL) is a frequently incurable disease associated with the human lymphotropic virus type I (HTLV-I). RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. HBZ, the only HTLV-I encoded transcription factor that is expressed in all ATLL cases, binds to an ATLL-specific BATF3 super-enhancer and thereby regulates the expression of BATF3 and its downstream targets, including MYC. Inhibitors of bromodomain-and-extra-terminal-domain (BET) chromatin proteins collapsed the transcriptional network directed by HBZ and BATF3, and were consequently toxic for ATLL cell lines, patient samples, and xenografts. Our study demonstrates that the HTLV-I oncogenic retrovirus exploits a regulatory module that can be attacked therapeutically with BET inhibitors.

7.
PLoS One ; 13(4): e0194525, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29641580

RESUMO

Polyploid chromosomes are those with more than two sets of homologous chromosomes. Polyploid chromosomal abnormalities are observed in various malignant tumors. The prognosis in such cases is generally poor. However, there are no studies examining the prognosis of diffuse large B-cell lymphoma (DLBCL) with polyploid chromosomal abnormalities. Therefore, we statistically compared the clinicopathological features between polyploid DLBCL and DLBCL without polyploid abnormalities. Herein, 51 polyploid DLBCL and 53 control (without polyploid chromosomal abnormalities) cases were examined. G-banding method was employed to define polyploidy by cytogenetic analysis. Subsequently, flow cytometric immunophenotyping and immunohistochemical staining were performed. Polyploid DLBCL was defined as DLBCL with either near-tetraploid or greater number of chromosomes, as detected by the G-band. In a survival analysis, a significantly worse overall survival (OS) was observed for polyploid DLBCL (p = 0.04; p = 0.02 in cases who received R-CHOP regimens). In a multivariate analysis of OS, polyploid chromosomal abnormalities were an independent prognostic factor. Our results suggest that polyploid chromosomal abnormalities detected through G-band may represent a new poor prognostic factor for DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Poliploidia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/metabolismo , Aberrações Cromossômicas , Bandeamento Cromossômico , Feminino , Citometria de Fluxo , Herpesvirus Humano 4 , Humanos , Imuno-Histoquímica , Imunofenotipagem , Cariotipagem , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , RNA Viral , Tetraploidia , Resultado do Tratamento , Adulto Jovem
8.
Oncotarget ; 9(2): 1717-1725, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29416725

RESUMO

Hepatitis C virus (HCV) is a single-stranded RNA virus that not only affects hepatocytes, by B cells as well. It is thought that HCV is involved in the onset of B-cell lymphoma. The clinicopathological characteristics of HCV-positive diffuse large B-cell lymphoma (DLBCL) and HCV-positive splenic marginal zone lymphoma (SMZL) are known, but there has been no report on HCV-positive follicular lymphoma (FL). In this study, the clinicopathological characteristics of HCV-positive FL were examined in 263 patients with FL who were classified into a HCV-positive group with HCV antibody and negative groups without one. The number of patients with HCV-positive FL and HCV-negative FL was 10 (3.8%) and 253 (96.2%), respectively. The patients with HCV-positive FL commonly had more than one region of lymphadenopathy, Ann Arbor stage III/IV, hemoglobin <120 g/l, elevated lactate dehydrogenase level, and high-risk categorization of Follicular Lymphoma International Prognostic Index (FLIPI) than in patients with HCV-negative FL. Overall survival and progression-free survival were poorer in patients with HCV-positive FL than in those with HCV-negative FL (p < 0.0001 and 0.006, respectively). Also, multivariate analysis revealed that positive HCV antibody was a poor prognostic factor of OS. In conclusion, HCV-positive FL has unique clinical features and may have a great impact on the overall survival of affected patients.

9.
Histopathology ; 72(6): 945-954, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29297942

RESUMO

AIMS: Adult T cell leukaemia/lymphoma (ATLL) is an aggressive malignancy with a poor prognosis. Human leucocyte antigen (HLA) and ß2 microglobulin (ß2M) serve as key molecules in tumour immunity, and their expression is reduced frequently in tumour cells. Programmed cell death (PD)-1/PD-ligand1 (PD-L1) interactions play a role in escape of tumour cells from T cell immunity. Therefore, this study aimed to determine the clinicopathological relevance of HLA and ß2M expressions in ATLL cells and PD-L1 expression in lymphoma or stromal cells and predict the overall survival of patients with ATLL. METHODS AND RESULTS: We analysed a total of 123 biopsy samples from patients newly diagnosed with ATLL by using immunohistochemical analysis. Of the patients enrolled, 91 (74%) were positive for HLA (in cell membrane, 60 patients), 89 (72%) were positive for ß2M (in cell membrane, 54 patients) and 48 (39%) were positive for both HLA and ß2M in the cell membrane (HLAm+ ß2Mm+ ). No significant clinical differences other than prognosis were found between the HLAm+ ß2Mm+ group and the other groups. Immunophenotypical evaluation revealed significantly higher rates of CD30-positive lymphoma cells (P = 0.003) and PD-L1-positive stromal cells in microenvironments (miPD-L1high ) (P = 0.011) of the HLAm+ ß2Mm+ group than in the other groups. The HLAm+ ß2Mm+ group had a significantly better prognosis that the other groups (P = 0.0096), and patients showing HLAm+ ß2Mm+ with miPD-L1high had the most favourable prognosis among all groups. CONCLUSIONS: The membranous expression of HLA and ß2M is likely to reflect the immune response and would be useful to predict prognosis before starting ATLL therapy.


Assuntos
Biomarcadores Tumorais/imunologia , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Antígenos HLA/análise , Antígenos HLA/biossíntese , Humanos , Estimativa de Kaplan-Meier , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Microglobulina beta-2/análise , Microglobulina beta-2/biossíntese
10.
Haematologica ; 103(6): 1018-1028, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29242302

RESUMO

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.

11.
J Clin Exp Hematop ; 57(3): 143-146, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29279551

RESUMO

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by human T-cell leukemia virus type 1 infection. Although conjunctival lymphoma is commonly reported with B-cell lymphoma, it rarely occurs in cases of ATLL. A 73-year-old Japanese female patient was admitted to our institution with evidence of abnormal lymphocytes, lymphadenopathy, and lung nodular lesions. Acute type ATLL was diagnosed, and therapy following the mLSG15 protocol was initiated. At the end of the second course, new bone lesions were detected. A modified treatment regimen was scheduled, but was postponed due to the appearance of gastrointestinal symptoms. Close observation resulted in a diagnosis of cytomegalovirus enteritis. One month after the diagnosis, the patient developed pain and discomfort in her left eye, which was determined to be due to a bulbar conjunctival tumor. Pathological findings revealed conjunctival infiltration of ATLL. Mogamulizumab treatment was initiated and was successful in eradicating the conjunctival lesions after the first course. However, at the end of the third course of therapy, pancytopenia was noted. Therefore, mogamulizumab therapy was discontinued, and the patient was on follow-up observation. Although there was no relapse of the conjunctival lesions, the patient died 1 year after the initial diagnosis, following therapy resistance.


Assuntos
Neoplasias da Túnica Conjuntiva/secundário , Leucemia-Linfoma de Células T do Adulto/patologia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Linfócitos/patologia
12.
Oncotarget ; 8(58): 98723-98732, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228722

RESUMO

Histiocytic and dendritic cell neoplasms are rare and poorly studied. We report the clinical characteristics and prognostic factors in such cases in Japan. We investigated the clinical characteristics and survival in 87 adult patients with histiocytic and dendritic cell neoplasms. Fifty patients had histiocytic sarcoma, 12 had Langerhans cell histiocytosis, 11 had follicular dendritic cell sarcoma, 8 had Langerhans cell sarcoma, 6 had interdigitating cell sarcoma and 1 had indeterminate dendritic cell sarcoma. The median follow-up period was 18.0 (range: 9.6-71.8) months, and median overall survival (OS) was 23.5 months. The 2-year OS rate was 49.2%. In the multivariate analysis, elevated lactate dehydrogenase (LDH) (p =.004), ECOG performance status (PS) 2-4 (p =.006), and Ann Arbor stage III-IV (p =.008) affected OS. Stratification by elevated LDH, ECOG PS 2-4, and Ann Arbor stage III-IV allowed classification of patients into low risk, intermediate risk, and high risk groups. The same classification was applicable for HS and non-HS categories. In the rare neoplasms of histiocytic and dendritic cell sarcoma, ECOG PS, Ann Arbor stage, and LDH are important prognostic factors for predicting survival.

13.
Ann Hematol ; 96(12): 2063-2070, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28975390

RESUMO

Follicular lymphoma (FL) is a low-grade lymphoma that is usually characterized by generalized lymphadenopathy. Extranodal invasion by FL generally involves the bone marrow, skin, and duodenum; splenic infiltration often occurs in the advanced stages. However, primary splenic FL is very rare. Hence, few studies have been performed on splenic FL, and its clinicopathological features have not been established. This study aimed to investigate the clinicopathological features of primary splenic FL, as compared to nodal FL. We analyzed 17 patients diagnosed with primary splenic FL and 153 control patients with systemic FL. Hepatitis C virus (HCV)-positive status was significantly more common in patients with splenic FL than in the control patients (p = 0.02). Ann Arbor stage III or IV (p = 0.0003) and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) (p = 0.03) were significantly less common in patients with splenic FL than in the control patients; however, the overall and progression-free survival curves were not significantly different between the groups. Among the 17 patients with splenic FL, the progression-free survival was significantly worse in patients who underwent splenectomy without receiving postoperative chemotherapy than in those who did (p = 0.03). These results suggest that primary splenic FL should be considered different from systemic FL; accordingly, its management should also be conducted differently.


Assuntos
Hepacivirus , Hepatite C , Linfoma Folicular , Neoplasias Esplênicas , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Hepatite C/sangue , Hepatite C/mortalidade , Hepatite C/terapia , Humanos , Linfoma Folicular/sangue , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Linfoma Folicular/virologia , Masculino , Pessoa de Meia-Idade , Esplenectomia , Neoplasias Esplênicas/sangue , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/terapia , Neoplasias Esplênicas/virologia , Taxa de Sobrevida
14.
Br J Haematol ; 178(5): 719-727, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28493517

RESUMO

Splenic infiltration is often seen in diffuse large B-cell lymphoma (DLBCL). However, primary splenic DLBCL is rare and studies on its clinicopathological features are limited. We assessed 66 cases of primary splenic DLBCL and 309 control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B symptoms, poor performance status and CD5 positivity differed significantly between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL cases were classified histopathologically into two groups [white pulp pattern (n = 46), red pulp pattern (n = 20)]. Survival analysis showed no difference in overall survival between the primary splenic DLBCL and the control group, but the former had a more favourable progression-free survival. In the examination of primary splenic DLBCL, the white pulp pattern was statistically associated with a lower performance status (2-4), and a lower CD5 positivity than the red pulp pattern. In the survival analysis, the red pulp pattern demonstrated poorer overall survival. Multivariate analysis of overall survival in primary splenic DLBCL cases identified CD5 positivity as an indicator of poor prognosis. Classifying primary splenic DLBCL into white and red pulp patterns was useful in terms of clinicopathological features and overall survival.


Assuntos
Linfoma Difuso de Grandes Células B/patologia , Neoplasias Esplênicas/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Antígenos CD5/metabolismo , Estudos de Casos e Controles , Feminino , Anticorpos Anti-Hepatite C/análise , Hepatite C Crônica/complicações , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias Esplênicas/imunologia , Neoplasias Esplênicas/terapia , Neoplasias Esplênicas/virologia
15.
Pathol Int ; 67(1): 17-23, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27868293

RESUMO

Polyploidy, defined as more than two sets of homologous chromosomes, is found in a variety of malignant tumors and is thought to be related to disease pathogenesis. However, there have been no studies that have investigated polyploidy in diffuse large B-cell lymphoma (DLBCL). Here we reviewed clinicopathological features of 16 cases of DLBCL with polypoidy, which was defined as DLBCL with either near-tetraploid or greater number of chromosomes as detected by the G-band method. The frequency of polyploid DLBCL was 2.9 % (16/544), including 15 near-tetraploid and one near-pentaploid case. CD5, CD30 and EBER positive cases were 13 % (2/16), 13 % (2/16) and 6 % (1/16), respectively. Bcl2 positive cases were 75 % (12/16). The numbers of huge and multinucleated cells were higher in polyploid than in non-polyploid DLBCL (P = 0.0029 and P < 0.0001, respectively). Clinical features of polyploid DLBCL included reduced infiltration of extranodal sites (2/15, 13 %) and major lymph node infiltration. Of seven cases that received chemotherapy, six responded to treatment and survived. Our results suggest that polyploid DLBCL represents a clinicopathologically characteristic group of DLBCL. This knowledge can be useful for informing more personalized and targeted management of DLBCL patients.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Poliploidia , Idoso , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização In Situ , Masculino , Pessoa de Meia-Idade
16.
Blood ; 128(10): 1374-81, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27418641

RESUMO

Programmed cell death ligand 1 (PD-L1) is expressed on both tumor and tumor-infiltrating nonmalignant cells in lymphoid malignancies. The programmed cell death 1 (PD-1)/PD-L1 pathway suppresses host antitumor responses, although little is known about the significance of PD-1/PD-L1 expression in the tumor microenvironment. To investigate the clinicopathological impact of PD-L1 expression in adult T-cell leukemia/lymphoma (ATLL), we performed PD-L1 immunostaining in 135 ATLL biopsy samples. We observed 2 main groups: 1 had clear PD-L1 expression in lymphoma cells (nPD-L1(+), 7.4% of patients), and the other showed minimal expression in lymphoma cells (nPD-L1(-), 92.6%). Within the nPD-L1(-) group, 2 subsets emerged: the first displayed abundant PD-L1 expression in nonmalignant stromal cells of the tumor microenvironment (miPD-L1(+), 58.5%) and the second group did not express PD-L1 in any cell (PD-L1(-), 34.1%). nPD-L1(+) ATLL (median survival time [MST] 7.5 months, 95% CI [0.4-22.3]) had inferior overall survival (OS) compared with nPD-L1(-) ATLL (MST 14.5 months, 95% CI [10.1-20.0]) (P = .0085). Among nPD-L1(-) ATLL, miPD-L1(+) ATLL (MST 18.6 months, 95% CI [11.0-38.5]) showed superior OS compared with PD-L1(-) ATLL (MST 10.2 months, 95% CI [8.0-14.7]) (P = .0029). The expression of nPD-L1 and miPD-L1 maintained prognostic value for OS in multivariate analysis (P = .0322 and P = .0014, respectively). This is the first report describing the clinicopathological features and outcomes of PD-L1 expression in ATLL. More detailed studies will disclose clinical and biological significance of PD-L1 expression in ATLL.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Leucemia-Linfoma de Células T do Adulto/patologia , Células Estromais/metabolismo , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Células Estromais/patologia , Taxa de Sobrevida
17.
Clin Cancer Res ; 22(18): 4727-34, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27166394

RESUMO

PURPOSE: The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis. EXPERIMENTAL DESIGN: PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR. RESULTS: Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1(+) TILs as significant predictors of poor survival, together with Masaoka-Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs. CONCLUSIONS: Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727-34. ©2016 AACR.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais , Carcinoma/genética , Carcinoma/mortalidade , Receptor de Morte Celular Programada 1/genética , Neoplasias do Timo/genética , Neoplasias do Timo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Carcinoma/diagnóstico , Carcinoma/terapia , Feminino , Dosagem de Genes , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/terapia
18.
J Pathol ; 238(5): 621-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26847489

RESUMO

Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.


Assuntos
Biomarcadores Tumorais/genética , Mutação da Fase de Leitura , Leucemia-Linfoma de Células T do Adulto/genética , Receptores CCR4/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Receptores CCR4/análise , Fatores de Tempo
19.
Rinsho Ketsueki ; 56(1): 21-4, 2015 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-25745963

RESUMO

A 70-year-old man received a course of therapy that consisted of prednisolone, cyclosporine, and etoposide due to hemophagocytic syndrome which had developed during primary myelofibrosis. He also received micafungin (MCFG) as prophylaxis against a potential fungal infection. We diagnosed febrile neutropenia due to the hemophagocytic syndrome therapy and candidemia because Candida species were detected in blood cultures. He received liposomal amphotericin B (L-AMB) for the candidemia but did not respond to this treatment. Oliguria was diagnosed and renal failure progressed rapidly. We suspected that his renal failure had been induced by the antibiotics. We thus changed the antibiotic regimen but he died of progressive renal failure. We performed renal necropsy and diagnosed acute interstitial tubular nephritis, due to a yeast-like fungus that generally invades the renal tubules. The yeast-like fungus was later identified as Trichosporon asahii, rather than candida, by blood cultures. An immunocompromised host receiving MCFG for acute progressive renal failure requires an appropriate antifungal drug considering the possibility of disseminated Trichosporon.


Assuntos
Túbulos Renais/lesões , Mielofibrose Primária/terapia , Trichosporon , Tricosporonose/complicações , Doença Aguda , Idoso , Anfotericina B/uso terapêutico , Equinocandinas/uso terapêutico , Humanos , Lipopeptídeos/uso terapêutico , Masculino , Micafungina , Neutropenia/diagnóstico , Neutropenia/terapia , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA