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1.
Presse Med ; 48(7-8 Pt 1): 842-849, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447330

RESUMO

Hairy cell leukemia (HCL) is a well-defined entity. Proliferation with hair cells, morphological aspects of hairy cells are easy to identify. Hairy cells express markers CD11c, CD25, CD103 and CD123. In 80% of cases, a BRAFV600E mutation is highlighted. In the absence of a BRAFV600E mutation, the differential diagnosis with other hair cell proliferations can be difficult, especially with the variant form of hairy leukemia, diffuse lymphoma of the red pulp of the spleen or splenic lymphoma of the marginal zone. Purine analogues (PNA) with or without anti-CD20 antibodies remain the first-line reference treatment. In case of relapse or resistance to PNA, BRAF inhibitors, with or without MEK inhibitors, are proposed in patients with the mutation. In the absence of BRAFV600E mutation, moxetumomab-pasudotox represents an interesting alternative. A multidisciplinary discussion is always necessary. In complex cases, expert advice is desirable.


Assuntos
Leucemia de Células Pilosas , Linfócitos B/patologia , Proliferação de Células , Diagnóstico Diferencial , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/epidemiologia , Leucemia de Células Pilosas/patologia , Leucemia de Células Pilosas/terapia , Linfoma de Zona Marginal Tipo Células B/patologia , Fatores de Risco , Baço/patologia , Neoplasias Esplênicas/patologia
2.
Clin Nucl Med ; 44(7): e458-e460, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30985440

RESUMO

Hairy cell leukemia is a rare hematologic malignancy characterized by splenomegaly, pancytopenia, and susceptibility to infections. We report a case of a 66-year-old man, diagnosed with hairy cell leukemia, without severe cytopenias and splenomegaly, but with an extensive pathological retroperitoneal mass and infiltration of the spleen and skeletal involvement. All findings were highly avid on pretreatment F-FDG PET/CT scan. Treatment response evaluation F-FDG PET/CT scan showed normalization of FDG uptake on all previously pathological sites.


Assuntos
Leucemia de Células Pilosas/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Fluordesoxiglucose F18 , Humanos , Leucemia de Células Pilosas/patologia , Masculino , Compostos Radiofarmacêuticos
4.
J Clin Pathol ; 72(6): 406-411, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30872385

RESUMO

AIMS: BRAF V600E detection assists in the diagnosis of hairy cell leukaemia (HCL); however, testing practices vary. We evaluated the clinical utility of 5 BRAF mutation testing strategies for use on bone marrow trephines (BMT). METHODS: 11 HCL, 5 HCL 'mimic', 2 treated HCL and 10 normal BMT specimens were tested for mutant BRAF, comparing Sanger sequencing, pyrosequencing, amplicon-based next generation sequencing (NGS), automated (Idylla) PCR and immunohistochemistry (IHC). RESULTS: PCR and IHC were cheaper and identified V600E in 100 % of HCL cases. Pyrosequencing detected the mutation in 91%, NGS in 55% of cases and Sanger sequencing in 27%. All assays gave wild-type BRAF results in HCL mimics and normal BMT samples. CONCLUSIONS: PCR and IHC were most sensitive and cost-effective, but these have limited scope for multiplexing and are likely to be replaced by NGS gene panels or whole genome sequencing in the medium to long term.


Assuntos
Biomarcadores Tumorais/genética , Medula Óssea/enzimologia , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Imuno-Histoquímica , Leucemia de Células Pilosas/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Reação em Cadeia da Polimerase em Tempo Real , Automação Laboratorial , Biópsia , Medula Óssea/patologia , Exame de Medula Óssea , Análise Custo-Benefício , Análise Mutacional de DNA/economia , Custos de Cuidados de Saúde , Sequenciamento de Nucleotídeos em Larga Escala/economia , Humanos , Imuno-Histoquímica/economia , Leucemia de Células Pilosas/economia , Leucemia de Células Pilosas/enzimologia , Leucemia de Células Pilosas/patologia , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real/economia , Reprodutibilidade dos Testes
6.
Pathol Int ; 69(4): 219-223, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30843305

RESUMO

BRAF mutation detection is worthwhile for the management of patients with some advanced cancers. The tumor samples are sometimes difficult to analyze using DNA-based molecular methods because of poor tumor DNA quality or quantity. Anti-BRAFV600E VE1 immunohistochemistry (IHC) has been proposed as a valuable ancillary tool to analyze some "molecularly challenging" tumor samples. In this technical study, we focused on its application in the field of decalcified tumor samples. We selected four patients with known BRAFV600E-mutated cancer (3 metastatic melanomas and 1 hairy cell leukemia) and paired non-decalcified/decalcified tumor samples. Molecular analyses failed in the four decalcified samples (3 bone metastases and 1 osteo-medullar biopsy) with non-contributive mutation status. Whereas non-decalcified tumor samples were all positive using anti-BRAFV600E VE1 IHC, the four decalcified samples were concluded negative. Because decalcified tumor samples are difficult to analyze from a molecular point of view, it is tempting to use IHC instead of DNA-based methods searching for BRAFV600E mutations in these samples. Nevertheless, the decalcification process may also cause false-negative results using VE1 IHC. Decalcified samples require specific and optimized IHC and molecular protocols and quality controls.


Assuntos
Leucemia de Células Pilosas/diagnóstico , Melanoma/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Substituição de Aminoácidos , Biópsia , Técnica de Descalcificação , Reações Falso-Negativas , Feminino , Humanos , Imuno-Histoquímica , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/patologia , Masculino , Melanoma/genética , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase
11.
Indian J Pathol Microbiol ; 61(4): 532-536, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30303143

RESUMO

Background: BRAFV600E mutation has been reported as a unique genetic lesion of hairy cell leukemia (HCL), a subset of which lacks this lesion and shows adverse outcomes. Aims: To determine the prevalence of BRAFV600E in HCL from our center and derive clinicopathological correlation, if any. Materials and Methods: A 9-year retrospective analysis of 46 consecutive cases of HCL diagnosed on morphology and immunophenotyping was done. Stained smears were used as samples for amplification refractory mutation system polymerase-chain reaction using fluorescent primers for mutation detection. Results: BRAFV600E mutation was detected in 41/46 patients (89.1%) while absent in control samples of chronic lymphocytic leukemia. Cases mimicking HCL-variant clinically or immunophenotypically too showed the presence of this mutation. HCL with mutated BRAF presented at a younger age. No statistical difference in blood counts, tumor load, and immunophenotype patterns existed among BRAF mutated and unmutated group. Nine patients (45%) with mutated BRAF had residual disease following treatment with cladribine. Conclusion: BRAFV600E mutation analysis has a definitive role in the diagnosis of HCL.


Assuntos
Leucemia de Células Pilosas/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Cladribina/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
J Cancer Res Ther ; 14(5): 1130-1134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197362

RESUMO

Hairy cell leukemia (HCL) is a rare, low-grade mature B-cell neoplasm with a characteristic clinical, morphological, immunophenotypic, and more recently described molecular (BRAF p.V600E mutation) profile. It typically affects middle-aged to elderly male who present with pancytopenia and massive splenomegaly. Lymphadenopathy is usually not seen. Atypical presentations such as absence of splenomegaly and presence of lymphadenopathy and leukocytosis, a hypoplastic marrow masquerading as aplastic anemia, pose a diagnostic challenge to both clinician and pathologist. A diligent morphological examination to look for the presence of hairy cells along with flow cytometric immunophenotyping showing consistent bright expression of CD200, in addition to well-described characteristic immunophenotype, helps in correctly diagnosing the case. This can be further confirmed by the consistent presence of V600E point mutation in BRAF gene. The correct identification of HCL in these unusual clinical presentations is of utmost importance owing to a different treatment approach in these cases. We present here four such cases with atypical presentation.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/genética , Leucemia de Células Pilosas/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Biomarcadores Tumorais/imunologia , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/imunologia , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Mutação
17.
Leukemia ; 32(8): 1768-1777, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30030507

RESUMO

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.


Assuntos
Antineoplásicos/uso terapêutico , Toxinas Bacterianas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Exotoxinas/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Indução de Remissão , Taxa de Sobrevida
18.
Mod Pathol ; 31(11): 1717-1732, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29955146

RESUMO

Hairy cell leukemia-variant is rare. Only a small number of cases have been reported in the literature with little cytogenetic or molecular data available. In this study, we describe the clinicopathologic and genetic features of 23 patients with hairy cell leukemia-variant (16 men and 7 women) with a median age of 70 years. Most patients had splenomegaly (90%), leukocytosis (77%), and lymphocytosis (82%); no patients had monocytopenia. Histologically, the bone marrow biopsy specimens showed a mixed pattern of predominantly interstitial and lesser intrasinusoidal infiltration by leukemic cells. In bone marrow aspirate smears most cells had villous cytoplasmic features and a small nucleolus. We describe unusual sites of hairy cell leukemia-variant involvement in 4 patients, including brain, omentum, terminal ileum, and skin at the time of initial presentation. Immunophenotyping showed monotypic B-cells positive for pan B-cell antigens, CD11c, and CD103, and negative for CD25 and annexin A1. Conventional cytogenetic or fluorescence in situ hybridization analysis showed deletions of 17p13/TP53 and 11q22/ATM gene in 5/12 (42%) and 2/9 (22%) cases, respectively. Sequencing of the variable region of IGVH showed mutations (>2% deviation from germline) in 40% of the cases assessed. MAP2K1 mutation (p.C121S) was seen in 1 of 14 (7%) patients tested. No BRAF V600E mutations were detected. The patients were treated in a heterogeneous manner, but most often with therapies designed for classical hairy cell leukemia and the 5-year overall survival was 84%. In summary, hairy cell leukemia-variant exhibits a heterogeneous spectrum of clinical, morphologic, immunophenotypic, and genetic features that may overlap with classic hairy cell leukemia and other hairy cell-like B-cell neoplasms. A subset of patients can have an aggressive clinical course. In our experience MAP2K1 mutations are uncommon in this disease.


Assuntos
Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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