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1.
Neuro Oncol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31950179

RESUMO

BACKGROUND: Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm characterized by recurrent alterations in the mitogen-activating protein kinase (MAPK) pathway. The existing literature about the neuro-oncological spectrum of ECD is limited. METHODS: We present retrospective clinical, radiographic, pathologic, molecular, and treatment data from 30 patients with ECD neurohistiocytic involvement treated at a tertiary center. RESULTS: Median age was 52 (range: 7-77) years and 20 (67%) patients were male. Presenting symptoms included ataxia in 19 (63%), dysarthria in 14 (47%), diabetes insipidus in 12 (40%), cognitive impairment in 10 (33%), and bulbar affect in 9 (30%) patients. Neurosurgical biopsy specimens in 8 patients demonstrated varied morphologic findings often uncharacteristic of typical ECD lesions. Molecular analysis revealed mutations in BRAF (18 patients), MAP2K1 (5), RAS isoforms (2), and two fusions involving BRAF and ALK. Conventional therapies (corticosteroids, immunosuppresants, interferon-alpha [IFN-α], cytotoxic chemotherapy) led to partial radiographic response in 8/40 (20%) by MRI with no complete responses, partial metabolic response in 4/16 (25%) and complete metabolic response in 1/16 (6%) by FDG-PET scan. In comparison, targeted (kinase inhibitor) therapies yielded partial radiographic response in 10/27 (37%) and complete radiographic response in 14/27 (52%) by MRI, and partial metabolic response in 6/25 (24%) and complete metabolic response in 17/25 (68%) by FDG-PET scan. CONCLUSIONS: These data highlight underrecognized symptomatology, heterogenous neuropathology, and robust responses to targeted therapies across the mutational spectrum in ECD patients with neurological involvement, particularly when conventional therapies have failed.

2.
Nat Med ; 25(12): 1839-1842, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768065

RESUMO

Histiocytoses are clonal hematopoietic disorders frequently driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not well understood, and clinically meaningful therapeutic targets outside of BRAF and MEK are undefined. In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.


Assuntos
Quinase do Linfoma Anaplásico/genética , Histiocitose/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Adolescente , Adulto , Aminopiridinas/farmacologia , Benzotiazóis/farmacologia , Criança , Pré-Escolar , Feminino , Genoma Humano , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Histiocitose/tratamento farmacológico , Histiocitose/patologia , Humanos , Lactente , Masculino , Mutação , Ácidos Picolínicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Receptores Proteína Tirosina Quinases/genética , Gêmeos Monozigóticos , Sequenciamento Completo do Exoma , Adulto Jovem
4.
Cancer Treat Res ; 176: 99-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30596215

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common types of T-cell lymphoma, representing about 15-20% of cases of peripheral T-cell lymphoma (PTCL). It is characterized by a unique clinical presentation and distinct pathologic and molecular features. Classes of drugs particularly active in AITL are emerging; however, treatment of relapsed and refractory disease remains a challenge. This chapter reviews the epidemiology, clinical presentation, pathogenesis, diagnosis, and treatment of AITL.


Assuntos
Linfadenopatia Imunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/tratamento farmacológico
6.
Hum Pathol ; 74: 5-16, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29337025

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that arises most often in adolescents and young adults. Patients with HSTCL commonly present with B-symptoms and cytopenias, which may suggest a diagnosis of acute leukemia initially. Patients present with extranodal disease involving the spleen, liver and bone marrow; lymphadenopathy is usually absent. The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage, often negative for CD4 and CD8 and positive for T-cell receptor γδ or, less often, αß. Recent studies have identified gene mutations in oncogenic pathways that are likely involved in pathogenesis and may be targets for therapy. Mutations in STAT3 or STAT5B lead to activation of the JAK/STAT pathway, and mutations involving SETD2, IN080 and ARID1 are involved in chromatin modification. Currently, there is no consensus standard of care for HSTCL patients, although several studies support a role for allogeneic hematopoietic stem cell transplant. Although patients with HSTCL are best treated in the context of clinical trials, the rarity of these neoplasms likely necessitates a multi-institutional approach. In this review, we focus on the clinicopathologic and genetic characteristics of HSTCL. We also discuss the differential diagnosis and therapeutic approaches.


Assuntos
Neoplasias Hepáticas/patologia , Linfoma de Células T/patologia , Neoplasias Esplênicas/patologia , Diagnóstico Diferencial , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Linfoma de Células T/diagnóstico , Prognóstico , Baço/patologia , Neoplasias Esplênicas/diagnóstico
7.
Clin Lymphoma Myeloma Leuk ; 17S: S16-S25, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28760297

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal neoplasms characterized by ineffective hematopoiesis. Hypomethylating agent (HMA) therapy is one of the mainstays of MDS therapy. Failure of HMA therapy is related to poor outcome; hence, new therapeutic approaches are warranted in these patients. In MDS, the immune system has a pivotal role in modulation of hematopoiesis and clonal expansion. In neoplastic conditions, immune checkpoint (PD-1 and CTLA4 molecules) hide tumor cells from immune surveillance. Identification of the pattern of expression of these molecules in MDS provides an interesting alternative within clinical trials. MATERIALS AND METHODS: We describe the clinicopathologic correlations by morphology, immunohistochemistry (PD-L1) and flow cytometry immunophenotypic analysis in an MDS patient treated with immune checkpoint PD-1 inhibitor. RESULTS: Bone marrow (BM) morphology, differential counts and aberrant flow markers were assessed before and after anti PD-1 inhibitor therapy. At baseline, BM showed severe trilineage dysplasia with decreased granulopoiesis; after therapy, BM showed normal trilineage hematopoiesis. A decrease in PD-L1 expression, by manual and automatic analysis, was also noted from 15% to 5% after 26 months of treatment. The findings correlated with the recovery of peripheral blood counts and transfusion independency. CONCLUSION: BM morphology and PD-L1 expression by immunohistochemistry can be used to assess treatment response in immune checkpoints therapy.


Assuntos
Antígeno B7-H1/metabolismo , Medula Óssea/patologia , Síndromes Mielodisplásicas/patologia , Receptor de Morte Celular Programada 1/metabolismo , Idoso , Medula Óssea/efeitos dos fármacos , Antígeno CTLA-4/metabolismo , Progressão da Doença , Feminino , Citometria de Fluxo , Hematopoese/efeitos dos fármacos , Humanos , Imunofenotipagem , Masculino , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/metabolismo , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento
8.
Hum Pathol ; 65: 147-156, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28551329

RESUMO

Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of FGFR1 is ZMYM2, and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with FGFR1, and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia or very rarely, with B-lymphoblastic leukemia (B-ALL). In this study, we analyzed the clinicopathological, cytogenetic, and molecular features of 2 new patients with the t(8;22)(p11.2;q11.2)/BCR-FGFR1 who presented with B-ALL. An underlying MPN became apparent when a morphologic remission of B-ALL was achieved after chemotherapy. We subsequently reviewed the literature and identified 18 additional cases reported with B-ALL in a background MPN or with the MPN as a chronic phase. Our data suggest that the t(8;22)(p11.2;q11.2)/BCR-FGFR1 may arise from a myeloid/B progenitor cell. It is important to recognize that neoplasms carrying the t(8;22)/BCR-FGFR1, although rare, can commonly with B lymphoblastic leukemia at the initial diagnosis, which could distract one from recognizing a possible underlying 8p11 myeloproliferative syndrome.


Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 8 , Análise Citogenética , Transtornos Mieloproliferativos/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Células Precursoras de Linfócitos B/patologia , Translocação Genética , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Criança , Bases de Dados Factuais , Diagnóstico Diferencial , Erros de Diagnóstico , Progressão da Doença , Feminino , Fusão Gênica , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/patologia , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Células Precursoras de Linfócitos B/efeitos dos fármacos , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-bcr/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Ann Diagn Pathol ; 26: 16-22, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28038706

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis. In 6 patients, medication history for the immune disorder was available: 6 patients received 6-mercaptopurine or azathioprine, and 2 patients received steroids; no patients received TNF-α inhibitors. In all 7 patients, the histologic, immunophenotypic, and cytogenetic findings were similar to cases of HSTCL that arise in immunocompetent patients. We reviewed the literature and identified 60 patients with immune disorders who subsequently developed HSTCL. These patients were treated with immunosuppressive drugs in 89%, TNF-α inhibitors in 56%, and both therapies in 54%, and 1 (2%) patient was treated with TNF-α inhibitors only. Our cohort and literature review indicates that TNF-α inhibitor therapy is not essential for the development of HSTCL in patients with immunodysregulatory disorders, and implies that immunosuppressive drugs or other factors (eg, genetic predisposition, chronic antigenic stimulation) may be more critical in the pathogenesis in this context. Although these data are observational, they have implications for the use of TNF-α inhibitors in patients with inflammatory bowel disease and other immunodysregulatory disorders.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças do Sistema Imunitário/complicações , Linfoma de Células T/etiologia , Neoplasias Esplênicas/etiologia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Esplênicas/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
10.
J Clin Pathol ; 70(3): 244-249, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27496968

RESUMO

AIMS: Chromosome 11q23 translocations, resulting in MLL (KMT2A) rearrangement, have been well characterised in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). However, little is known of haematopoietic neoplasms associated with 11q23 translocation but without MLL rearrangement (11q23+/MLL-). The aim of this study is to characterise such cases with 11q23+/MLL-. METHODS AND RESULTS: We retrospectively searched our database for cases with haematopoietic malignancies with 11q23+/MLL-. We identified nine patients, two with AML, two with B-lymphoblastic leukaemia (B-ALL); two with T-lymphoblastic leukaemia (T-ALL), two with myelodysplastic syndrome (MDS) and one with chronic myelomonocytic leukaemia (CMML). The translocations included t(X;11)(p11.2;q23), t(2;11)(p21;q23), t(6;11)(q27;q23), t(8;9;11)(q13;q13;q23), t(11;11)(p15;q23), t(11;14)(q23;q24) and t(11;15)(q23;q14). Five of six patients with acute leukaemia had received chemotherapy and detection of 11q23 translocation occurred at time of disease relapse. Both patients with MDS and the patient with CMML had 11q23 translocation detected at time of initial diagnosis, all three patients progressed to AML after >1 year on hypomethylating agent therapy. All patients received risk-adapted therapies, including stem cell transplant in five patients. At the last follow-up, eight patients died with a median overall survival of 14 months. CONCLUSIONS: 11q23+/MLL- occurs rarely, involving different partner chromosomes and showing clinical and pathological features and disease subtypes different from those cases with MLL rearrangement. 11q23+/MLL- appears to be associated with clonal evolution/disease progression in acute leukaemia, a high risk for AML progression in MDS/CMML and a high incidence of disease relapse.


Assuntos
Cromossomos Humanos Par 11/genética , Leucemia/genética , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Pré-Escolar , Feminino , Citometria de Fluxo , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteína de Leucina Linfoide-Mieloide/genética , Estudos Retrospectivos
11.
Am J Surg Pathol ; 41(1): 82-93, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27755009

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive T-cell lymphoma that can be challenging to diagnose. In particular, distinguishing HSTCL from T-cell large granular lymphocytic (T-LGL) leukemia of γδ T-cell receptor (TCR) type is difficult without examination of a splenectomy specimen. In this study, we systematically assessed a series of HSTCL cases for findings reported in the literature as supporting or not supporting the diagnosis of HSTCL. We also compared HSTCL with a group of cases of T-LGL of γδ TCR type. Criteria assessed in this study included: B-symptoms, massive splenomegaly, lymphadenopathy, extranodal involvement, peripheral lymphocytosis, lymphoma cells that expand bone marrow sinuses, lymphocyte azurophilic granules, immunophenotype, evidence of infection by Epstein-Barr virus, human immunodeficiency virus, or human T-cell leukemia virus type 1, isochromosome 7q, trisomy 8, and TCR gene rearrangement status. On the basis of the data of this study, we conclude that massive splenomegaly, bone marrow sinusoidal expansion by lymphoma cells, and lymphocytes devoid of azurophilic granules were significantly more common in HSTCL patients than in γδ T-LGL patients (P<0.0001), and these features help support the diagnosis of HSTCL.


Assuntos
Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/imunologia , Linfoma de Células T/diagnóstico , Linfoma de Células T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Leucemia Linfocítica Granular Grande/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T gama-delta , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/patologia , Adulto Jovem
12.
J Natl Compr Canc Netw ; 14(8): 939-44, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27496109

RESUMO

T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell transplantation (SCT) is rare and its natural history and clinical outcome have not been well described. We report the clinical, morphologic, immunophenotypic, and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The patient presented with persistent neutropenia and splenomegaly 9 months after SCT when the chimerism study showed a 100% donor pattern. A splenectomy revealed T-LGL leukemia. Flow cytometric analysis showed an aberrant T-cell population positive for CD3, CD5 (dim, subset), CD7, CD8, CD16 (subset), CD57, CD94 (dim, partial), and T-cell receptor (TCR) αß, and negative for CD4, CD26, CD56, and TCRγδ. Molecular studies showed monoclonal TCRß and TCRγ gene rearrangements. Both the immunophenotype and molecular profile of the T-LGL leukemia were different from the pre-SCT PTCL. Sequencing analysis for STAT3 exon 21 did not reveal any mutation in both pre-SCT and post-SCT specimens. The patient did not receive any treatment for T-LGL leukemia; however, his count progressively increased after splenectomy, despite the presence of persistent T-LGL leukemia in the bone marrow. There was no evidence of recurrent PTCL. We propose an algorithm to diagnose this rare post-SCT neoplasm.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/etiologia , Linfoma de Células T Periférico/diagnóstico , Segunda Neoplasia Primária , Doadores de Tecidos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Medula Óssea/patologia , Terapia Combinada , Rearranjo Gênico , Humanos , Imunofenotipagem , Linfonodos/patologia , Linfoma de Células T Periférico/terapia , Masculino , Fenótipo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Linfócitos T/metabolismo , Linfócitos T/patologia , Transplante Homólogo
13.
Hum Pathol ; 50: 109-17, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26997444

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell lymphoma commonly associated with cytopenias. The pathogenesis of cytopenias in patients with HSTCL is not well defined, although the presence of dyspoietic hematopoietic cells and the common association with trisomy 8 raise the possibility of an associated myelodysplastic syndrome (MDS). In 25 bone marrow specimens involved by HSTCL, we systematically assessed for morphologic features of dyspoiesis and correlated the findings with peripheral cytopenia(s), cytogenetic findings, and detection of chromosome 8 by fluorescence in situ hybridization. The median patient age was 33 years. One patient had a history of MDS diagnosed 1 year prior to the diagnosis of HSTCL. Thirteen (54%) patients had anemia less than 100 g/L, 10 (53%) of 19 had neutropenia less than 1.8 × 10(9)/L, and 15 (60%) had thrombocytopenia less than 100 × 10(9)/L. Dyspoietic features were identified in 1 to 3 hematopoietic cell lineages in 20 (80%) of 25 patients. Cytogenetic analysis identified trisomy 8 in 7 cases. Patients with trisomy 8 had a lower platelet count, but trisomy 8 was not associated with cytopenias, dyspoietic features, or cytogenetic abnormalities. Combined morphologic and fluorescence in situ hybridization analysis showed that trisomy 8 was restricted to the lymphoma cells, except in the 1 patient with a history of MDS. In conclusion, dyspoietic changes are common in the bone marrow of patients with HSTCL. These changes are not associated with cytopenias or chromosomal abnormalities, suggesting that dyspoiesis in patients with HSTCL is not a manifestation of a MDS.


Assuntos
Medula Óssea/patologia , Neoplasias Hepáticas/complicações , Linfoma de Células T/complicações , Síndromes Mielodisplásicas/complicações , Neutropenia/etiologia , Neoplasias Esplênicas/complicações , Trombocitopenia/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Exame de Medula Óssea , Criança , Pré-Escolar , Cromossomos Humanos Par 8/genética , Feminino , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Contagem de Linfócitos , Linfoma de Células T/genética , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Linfoma de Células T/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Neutropenia/sangue , Neutropenia/genética , Neutropenia/mortalidade , Neutropenia/patologia , Neutropenia/terapia , Fenótipo , Contagem de Plaquetas , Prognóstico , Fatores de Risco , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Trombocitopenia/sangue , Trombocitopenia/genética , Trombocitopenia/mortalidade , Trombocitopenia/patologia , Trombocitopenia/terapia , Fatores de Tempo , Trissomia/genética , Adulto Jovem
14.
Am J Surg Pathol ; 40(5): 676-88, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26872013

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed γδ T-cell receptor (TCR) in 20 (74%), αß TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level ≥1.5 mg/dL, αß TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, αß TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL.


Assuntos
Neoplasias Hepáticas , Linfoma de Células T , Neoplasias Esplênicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Exame de Medula Óssea , Criança , Pré-Escolar , Cromossomos Humanos Par 7 , Cromossomos Humanos Par 8/genética , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Hepatomegalia/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Isocromossomos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Modelos de Riscos Proporcionais , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/imunologia , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/patologia , Esplenomegalia/patologia , Terapêutica , Fatores de Tempo
16.
Am J Clin Pathol ; 144(4): 607-19, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26386082

RESUMO

OBJECTIVES: T-cell large granular lymphocytic (T-LGL) leukemia is a rare disorder in which the neoplastic cells usually express the αß T-cell receptor (TCR). To determine the significance of γδ TCR expression in this leukemia, we compared the clinicopathologic, immunophenotypic, and genetic features of patients with T-LGL leukemia expressing γδ TCR or αß TCR. METHODS: We used the World Health Organization classification criteria to confirm the diagnosis. All patients were diagnosed and treated at our institution. RESULTS: We identified 14 patients with γδ T-LGL leukemia, 11 men and three women; six (43%) patients had a history of rheumatoid arthritis, 10 (71%) had neutropenia, four (29%) had thrombocytopenia, and three (21%) had anemia. Eight (67%) of 12 patients had a CD4-/CD8- phenotype, and four (33%) had a CD4-/CD8+ phenotype. The median overall survival was 62 months. Patients with γδ T-LGL leukemia were more likely to have rheumatoid arthritis (P = .04), lower absolute neutrophil count (P = .04), lower platelet count (P = .004), and a higher frequency of the CD4-/CD8- phenotype (P < .0001). However, there was no significant difference in overall survival between the two groups (P = .64). CONCLUSIONS: Although patients with γδ and αß T-LGL leukemia show some different clinical or phenotypic features, overall survival is similar, suggesting that γδ TCR expression does not carry prognostic significance.


Assuntos
Leucemia Linfocítica Granular Grande/imunologia , Leucemia Linfocítica Granular Grande/patologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etiologia , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Estimativa de Kaplan-Meier , Leucemia Linfocítica Granular Grande/mortalidade , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T alfa-beta , Adulto Jovem
17.
Clin Lymphoma Myeloma Leuk ; 15 Suppl: S85-90, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26297286

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) with specific balanced 5q33 translocations are classified as AML with myelodysplasia-related changes regardless of their morphologic findings or antecedent hematologic disease, but the clinicopathologic features of such cases remain poorly understood. MATERIALS AND METHODS: From > 2000 cases of hematological malignancies seen at our institution between 2000 and 2013, we identified 9 AML patients with 5q33 translocations with variable partner loci, t(v;5q33). RESULTS: The study group included 8 men and 1 woman, with a median age of 64 years (range, 19-87 years). Four patients had an antecedent myeloproliferative neoplasm (MPN). Cytogenetic analysis showed t(v;5q33) as a sole chromosomal abnormality in 4 (44%) patients, t(v;5q33) and del(3)(q21;q26.2) in 1 (11%) patient, and a complex karyotype in 4 (44%) patients. Only 1 patient had morphologic features of myelodysplasia in 2 or more lineages. Follow-up was available for 7 patients and the median overall survival (OS) was 12 months. Patients with a history of MPN had a significantly shorter OS compared with those with de novo AML (11 vs. 20 months; P = .0445). There was no correlation between complex karyotype and OS in this small group of AML patients (P = .5904). CONCLUSION: The t(v;5q33) is a rare cytogenetic aberration in AML. Although associated with a poor outcome, AML with t(v;5q33) usually lacks morphologic evidence of multilineage dysplasia. Patients who have AML with t(v;5q33) after MPN have a worse OS compared with those with de novo AML.


Assuntos
Análise Citogenética/métodos , Leucemia Mieloide Aguda/genética , Transtornos Mieloproliferativos/genética , Translocação Genética/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Adulto Jovem
18.
Br J Haematol ; 171(1): 91-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26123119

RESUMO

Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = <0·001). Expression of TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F.


Assuntos
Regulação da Expressão Gênica , Mutação , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Proteína Supressora de Tumor p53/biossíntese , Adulto , Idoso , Intervalo Livre de Doença , Fibrose , Humanos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Reticulina , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética
19.
J Gastrointest Surg ; 18(10): 1744-51, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25060552

RESUMO

BACKGROUND: Race/ethnicity has long been suspected to affect survival in patients with gastric adenocarcinoma. However, the clinicohistopathological impact of race or ethnicity on early gastric cancer (EGC) is not known. METHODS: From 2000 to 2013, 286 patients underwent gastrectomy and 104 patients had pathological confirmation of EGC. A retrospective analysis of pathological and clinical prognostic indicators was performed. RESULTS: The study population consisted of 38 (37%) Asian Americans and 66 (63%) non-Asian Americans. Of these, 2 (5.3%) Asian Americans and 19 (28.8%) non-Asian Americans had pathological confirmation of lymph node metastasis (LNM) (p = 0.004). Univariate analysis comparing the clinicohistopathological characteristics in each group did not reveal significant difference regarding histotype, tumor size, grade, location, morphology, or lymphovascular invasion, except for the LNM rate and mean body mass index (23.2 versus 26.6, p < 0.001). Multivariate analysis showed that non-Asian race/ethnicity (odds ratio (OR), 9.09; 95% confidence interval (CI), 1.12-71.43; p = 0.038), younger age (OR, 1.11; 95% CI, 1.01-1.12; p = 0.046), and lymphovascular invasion (OR, 13.9; 95% CI, 2.40-79.99; p = 0.003) were significant predictors for LNM. CONCLUSIONS: This study demonstrated that Asian American race in EGC is associated with a significantly decreased rate of LNM in comparison to non-Asian Americans, despite similar histopathological characteristics of each group.


Assuntos
Adenocarcinoma/etnologia , Detecção Precoce de Câncer , Grupos Étnicos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias Gástricas/etnologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida/tendências , Fatores de Tempo
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