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2.
Am J Hematol ; 89(11): E193-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25042343

RESUMO

It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts, formerly referred to as refractory anemia with excess blasts in transformation (RAEBT), should be considered AML or myelodysplastic syndrome (MDS) for the purposes of treatment and prognostication. We retrospectively studied 571 de novo AML in patients aged >50 years, including 142 RAEBT and 429 with ≥30% blasts (AML30), as well as 151 patients with 10-19% BM blasts (RAEB2). RAEBT patients were older and had lower white blood count, but higher hemoglobin, platelet count, and karyotype risk scores compared to AML30, while these features were similar to RAEB2. FLT3 and NPM1 mutations and monocytic morphology occurred more commonly in AML30 than in RAEBT. RAEBT patients were treated less often with induction therapy than AML30, whereas allogeneic stem cell transplant frequency was similar. The median and 4-year OS of RAEBT patients were longer than those of AML30 patients (20.5 vs 12.0 months and 28.6% vs 20.4%, respectively, P = 0.003); this difference in OS was manifested in patients in the intermediate UKMRC karyotype risk group, whereas OS of RAEBT patients and AML30 patients in the adverse karyotype risk group were not significantly different. Multivariable analysis showed that RAEBT (P < 0.0001), hemoglobin (P = 0.005), UKMRC karyotype risk group (P = 0.002), normal BM karyotype (P = 0.004), treatment with induction therapy (P < 0.0001), and stem cell transplant (P < 0.0001) were associated with longer OS. Our findings favor considering de novo RAEBT as a favorable prognostic subgroup of AML.


Assuntos
Anemia Refratária com Excesso de Blastos/patologia , Medula Óssea/patologia , Leucemia Mieloide Aguda/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/mortalidade , Anemia Refratária com Excesso de Blastos/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Células , Aberrações Cromossômicas , Metilação de DNA/efeitos dos fármacos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Cariótipo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/genética , Nucleofosmina , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/genética
3.
J Clin Pathol ; 72(7): 453-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31164443

RESUMO

Clonal haematopoiesis (CH) is defined by the presence of acquired mutations and/or cytogenetic abnormalities in haematopoietic cells. By definition, these premalignant clones do not meet criteria for haematopoietic neoplasms listed in the Revised Fourth Edition of the WHO classification. CH is fairly common in elderly individuals and is associated with higher risks for haematological cancers, in particular myelodysplastic syndrome and acute myeloid leukaemia (AML), as well as cardiovascular events. Similar small clones have also been detected during follow-up in patients with AML in morphological remission, in individuals with aplastic anaemia, and in pre-chemotherapy blood samples from patients with other types of cancers. In each of these contexts, the presence of mutations carries different clinical implications, and sometimes demonstrates unique genetic profiles. Emerging research suggests that the number and identity of mutations, the size of the mutant clones and various other factors, including age, immune status and history of exogenous drugs/toxins, are important for disease biology and progression. This review focuses specifically on the subset of CH with gene mutations detected by sequencing, and includes discussions of nomenclature and molecular technologies that detect and quantify gene mutations.


Assuntos
Aberrações Cromossômicas , Hematopoese/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Células Clonais , Humanos , Mutação
4.
Hum Pathol ; 44(2): 255-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22939574

RESUMO

Kikuchi-Fujimoto lymphadenitis is a self-limited disorder that typically presents in young females as painless cervical lymphadenopathy with fever, anemia, and leukopenia. The clinical manifestations and pathologic findings suggest a viral etiology, yet specific etiologic agents remain unknown. Although there are studies reporting positive associations between Kikuchi-Fujimoto lymphadenitis and parvovirus B19 and herpesviruses, other studies have failed to find an association with these viruses. To our knowledge, this current study is the largest study of Kikuchi-Fujimoto lymphadenitis in Western patients that used polymerase chain reaction testing for 4 different common viral pathogens often implicated as etiologic agents in Kikuchi-Fujimoto lymphadenitis. Archival material from 3 institutions was included, following confirmation of the diagnosis of Kikuchi-Fujimoto lymphadenitis by 2 independent pathologists. Polymerase chain reaction from the paraffin-embedded tissue sections for parvovirus B19, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 was performed. Eighteen cases of Kikuchi-Fujimoto lymphadenitis were analyzed, 12 of which (60%) were cervical lymph nodes. All the cases showed typical geographic necrosis with abundant apoptotic debris, although the degree of necrosis was variable. Polymerase chain reaction revealed a high prevalence of parvovirus B19 in the controls (44%); there were fewer positive cases seen in the Kikuchi-Fujimoto lymphadenitis cases (11%), but this did not reach statistical significance (P = .25).There were no significant differences between cases and controls in the prevalence of Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 (P = .50 for all 3). Polymerase chain reaction failed to reveal a positive association between Kikuchi-Fujimoto lymphadenitis and 4 common suspected viral agents. These findings do not support a role for Epstein-Barr virus, human herpesvirus 6, human herpesvirus 8, or parvovirus B19 in the pathogenesis of Kikuchi-Fujimoto lymphadenitis.


Assuntos
Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 6/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Linfadenite Histiocítica Necrosante/virologia , Parvovirus B19 Humano/isolamento & purificação , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Herpesvirus Humano 8/genética , Linfadenite Histiocítica Necrosante/patologia , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/genética , Reação em Cadeia da Polimerase , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/virologia , Adulto Jovem
5.
Surg Pathol Clin ; 3(4): 907-31, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26839294

RESUMO

Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and monoclonal B-cell lymphocytosis (MBL) are clonal proliferations of small, mature B cells. CLL and SLL are considered neoplastic, although they are indolent and many patients with these lymphomas never require treatment. Most MBL cases share immunophenotypic and genetic features with CLL and SLL but have a small burden of clonal cells. This review focuses on the pathologic features of CLL, SLL, and MBL and their differential diagnoses. Guidelines are provided to separate the entities from one another and to avoid pitfalls in distinguishing these entities from other lymphomas and from reactive lymphoid proliferations.

6.
Surg Pathol Clin ; 3(4): 1035-59, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26839298

RESUMO

Burkitt lymphoma (BL) is an aggressive B-cell neoplasm with an extremely short doubling time that mainly affects children and young adults. Despite having several characteristic features, none is entirely specific for BL and the differential diagnosis may include diffuse large B-cell lymphoma (DLBCL), B lymphoblastic leukemia/lymphoma, and B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL. We outline a practical approach to establish a diagnosis of BL and distinguish it from other high-grade B-cell malignancies. We pay particular attention to B-cell lymphomas with features intermediate between DLBCL and BL, a new diagnostic category in the 2008 World Health Organization classification system that provides a framework for categorizing challenging cases not meeting diagnostic criteria for either "classic" BL or DLBCL.

7.
Hematol Oncol Clin North Am ; 23(4): 791-827, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19577170

RESUMO

Diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphoma (BL) account for the majority of aggressive lymphomas in adults and children. DLBCLs exhibit marked biological heterogeneity and variable clinical presentation and clinical course. Conversely, BL is genetically relatively homogeneous but associated with variable clinicopathological features. In this article, the authors summarize the recent advances pertaining to these B-cell neoplasms, following the latest World Health Organization classification and focusing on changes introduced since the previous edition. These changes include the addition of variants and subgroups of DLBCLs and "borderline" categories for high-grade B-cell neoplasms that show features intermediate between DLBCL and classical Hodgkin lymphoma, or between DLBCL and BL. In particular, the diagnostic and therapeutic problems related to neoplasms with features intermediate between DLBCL and BL will be discussed.


Assuntos
Linfoma de Burkitt/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Antígenos CD20/imunologia , Linfoma de Burkitt/classificação , Linfoma de Burkitt/imunologia , Antígenos CD5/imunologia , Criança , Diagnóstico Diferencial , Humanos , Imunofenotipagem , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/imunologia , Organização Mundial da Saúde
8.
Surg Pathol Clin ; 3(4): xi-xii, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26839305
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