RESUMO
Myeloproliferative neoplasms arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of myeloproliferative neoplasms is based on hematologic, histopathologic and molecular characteristics including the presence of the BCR-ABL1 and JAK2 V617F. Although thought to be mutually exclusive, a number of cases with co-occurring BCR-ABL1 and JAK2 V617F have been identified. To characterize the clinicopathologic features of myeloproliferative neoplasms with concomitant BCR-ABL1 and JAK2 V617F, and define the frequency of co-occurrence, we conducted a retrospective multi-institutional study. Cases were identified using a search of electronic databases over a decade at six major institutions. Of 1570 patients who were tested for both BCR-ABL1 and JAK2 V617F, six were positive for both. An additional five patients were identified via clinical records providing a total of 11 cases for detailed evaluation. For each case, clinical variables, hematologic and genetic data, and bone marrow histomorphologic features were analyzed. The sequence of identification of the genetic abnormalities varied: five patients were initially diagnosed with a JAK2 V617F+ myeloproliferative neoplasm, one patient initially had BCR-ABL1+ chronic myeloid leukemia, while both alterations were identified simultaneously in five patients. Classification of the BCR-ABL1-negative myeloproliferative neoplasms varied, and in some cases, features only became apparent following tyrosine kinase inhibitor therapy. Seven of the 11 patients showed myelofibrosis, in some cases before identification of the second genetic alteration. Our data, reflecting the largest reported study comprehensively detailing clinicopathologic features and response to therapy, show that the co-occurrence of BCR-ABL1 and JAK2 V617F is rare, with an estimated frequency of 0.4%, and most often reflects two distinct ('composite') myeloproliferative neoplasms. Although uncommon, it is important to be aware of this potentially confounding genetic combination, lest these features be misinterpreted to reflect resistance to therapy or disease progression, considerations that could lead to inappropriate management.
Assuntos
Neoplasias da Medula Óssea/genética , Medula Óssea/patologia , Proteínas de Fusão bcr-abl/genética , Janus Quinase 2/genética , Sistemas Multi-Institucionais , Transtornos Mieloproliferativos/genética , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Medula Óssea/sangue , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias da Medula Óssea/patologia , Progressão da Doença , Inibidores Enzimáticos/uso terapêutico , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/sangue , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/patologia , Mielofibrose Primária/sangue , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Mielofibrose Primária/patologia , Estudos RetrospectivosRESUMO
A 17-year-old girl with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with persistent minimal residual disease (MRD) who underwent standard chemotherapy was found to have a BCR-ABL1-like gene expression pattern. Genome sequencing revealed a JAK2 mutation not previously described in BCP-ALL and a potential therapeutic target. Due to concern for an on-therapy relapse, the JAK2 inhibitor ruxolitinib was incorporated into a modified chemotherapy backbone to achieve complete remission prior to stem cell transplant. Treatment was well tolerated and she had undetectable MRD prior to a matched allogeneic stem cell transplant and remained in remission at day +100.
Assuntos
Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Pirazóis/uso terapêutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mutação/genética , Neoplasia Residual/tratamento farmacológico , Nitrilas , Pirimidinas , Transplante de Células-Tronco , Resultado do TratamentoRESUMO
The distinction between chronic eosinophilic leukemia, not otherwise specified and idiopathic hypereosinophilic syndrome largely relies on clonality assessment. Prior to the advent of next-generation sequencing, clonality was usually determined by cytogenetic analysis. We applied targeted next-generation sequencing panels designed for myeloid neoplasms to bone marrow specimens from a cohort of idiopathic hypereosinophilic syndrome patients (n=51), and assessed the significance of mutations in conjunction with clinicopathological features. The findings were further compared with those of 17 chronic eosinophilic leukemia, not otherwise specified patients defined by their abnormal cytogenetics and/or increased blasts. Mutations were detected in 14/51 idiopathic hypereosinophilic syndrome patients (idiopathic hypereosinophilic syndrome/next-generation sequencing-positive) (28%), involving single gene in 7 and ≥2 in 7 patients. The more frequently mutated genes included ASXL1 (43%), TET2 (36%), EZH2 (29%), SETBP1 (22%), CBL (14%), and NOTCH1 (14%). Idiopathic hypereosinophilic syndrome/next-generation sequencing-positive patients showed a number of clinical features and bone marrow findings resembling chronic eosinophilic leukemia, not otherwise specified. Chronic eosinophilic leukemia, not otherwise specified patients showed a disease-specific survival of 14.4 months, markedly inferior to idiopathic hypereosinophilic syndrome/next-generation sequencing-negative (P<0.001), but not significantly different from idiopathic hypereosinophilic syndrome/next-generation sequencing-positive (P=0.117). These data suggest that targeted next-generation sequencing helps to establish clonality in a subset of patients with hypereosinophilia that would otherwise be classified as idiopathic hypereosinophilic syndrome. In conjunction with other diagnostic features, mutation data can be used to establish a diagnosis of chronic eosinophilic leukemia, not otherwise specified in patients presenting with hypereosinophilia.
Assuntos
Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Síndrome Hipereosinofílica/genética , Leucemia/genética , Mutação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Exame de Medula Óssea , Diagnóstico Diferencial , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Síndrome Hipereosinofílica/mortalidade , Síndrome Hipereosinofílica/patologia , Síndrome Hipereosinofílica/terapia , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Cariótipo , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estados Unidos , Adulto JovemRESUMO
Recent studies have shown that immunohistochemical evaluation of MYC protein expression in diffuse large B-cell lymphoma is a useful prognostic tool with high concordance rate among pathologists. Concordance in these studies was assessed among few pathologists from one institution by scoring tissue microarrays. In daily practice, MYC evaluation is performed on entire tumor sections by a diverse group of pathologists. In our study, nine hematopathologists from two institutions scored whole-tissue sections of two sets of cases. The training set included 13 cases of diffuse large B-cell lymphoma and 4 cases of Burkitt lymphoma. The validation set included 18 cases of diffuse large B-cell lymphoma and 1 case of Burkitt lymphoma. MYC positivity was defined as ≥40% of tumor cells demonstrating nuclear staining similar to prior studies. The mean score for each case was used to determine MYC status with discrepant cases defined as having any score causing a different MYC status designation. Discrepant cases from the training set were characterized by staining heterogeneity, extensive necrosis or crush artifact and had mean scores within 15 percentage points of 40%. Cases from the validation set that demonstrated any of these features were scored twice on two different days. Overall concordance was moderate (Kappa score: 0.68, P-value<0.001) with no significant change between the two sets (Kappa scores: 0.69 vs 0.67). Thirty-nine percent of cases were discrepant. The findings indicate that a significant number of diffuse large B-cell lymphomas are inherently difficult to score due to staining heterogeneity. The effect of heterogeneity can be under-represented when concordance is measured among few pathologists scoring tissue microarrays. Careful scoring strategy in our study failed to improve concordance. In the absence of specific instructions on how to deal with heterogeneity, caution is advised when evaluating MYC expression in diffuse large B-cell lymphoma.
Assuntos
Linfoma de Burkitt/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Linfoma de Burkitt/patologia , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/patologia , Reprodutibilidade dos TestesAssuntos
Gangliosidose GM1/sangue , Linfócitos/patologia , Celulite (Flegmão)/complicações , Gangliosidose GM1/complicações , Gangliosidose GM1/genética , Gangliosidose GM1/patologia , Humanos , Lactente , Leucocitose/sangue , Leucocitose/complicações , Leucocitose/patologia , Masculino , Mutação , beta-Galactosidase/genéticaRESUMO
Proliferation rates in diffuse large B-cell lymphoma have been associated with conflicting outcomes in the literature, more often with high proliferation associated with poor prognosis. In most studies, the proliferation rate was estimated by a pathologist using an immunohistochemical stain for the monoclonal antibody Ki-67. We hypothesized that a quantitative image analysis algorithm would give a more accurate estimate of the proliferation rate, leading to better associations with survival. In all, 84 cases of diffuse large B-cell lymphoma were selected according to the World Health Organization criteria. Ki-67 percentage positivity estimated by the pathologist was recorded from the original report. The same slides were then scanned using an Aperio ImageScope, and Ki-67 percentage positivity was calculated using a computer-based quantitative immunohistochemistry nuclear algorithm. In addition, chart review was performed and survival time was recorded. The Ki-67 percentage estimated by the pathologist from the original report versus quantitative image analysis was significantly correlated (P<0.001), but pathologist Ki-67 percentages were significantly higher than quantitative image analysis (P=0.021). There was less agreement at lower Ki-67 percentages. Comparison of Ki-67 percentage positivity versus survival did not show significant association either with pathologist estimate or quantitative image analysis. However, although not significant, there was a trend of worse survival at higher proliferation rates detected by the pathologist but not by quantitative image analysis. Interestingly, our data suggest that the Ki-67 percentage positivity as assessed by the pathologist may be more closely associated with survival outcome than that identified by quantitative image analysis. This may indicate that pathologists are better at selecting appropriate areas of the slide. More cases are needed to assess whether this finding would be statistically significant. Due to the good correlation between pathologist estimate and quantitative image analysis, there is no substantial benefit to using quantitative image analysis at this point of time.
Assuntos
Proliferação de Células , Interpretação de Imagem Assistida por Computador , Imuno-Histoquímica , Antígeno Ki-67/análise , Linfoma Difuso de Grandes Células B/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
Hematopathology fellowship education has grown in complexity as patient-centered treatment plans have come to depend on integration of clinical, morphologic, immunophenotypic, molecular, and cytogenetic variables. This complexity is in competition with the need for timely hematopathology care with stewardship of patient, laboratory, and societal resources. Accreditation Council for Graduate Medical Education Milestones provide a guidance document for hematopathology training, but fellows and their educators are in need of a simple framework that allows assessment and feedback of growth toward independent hematopathology practice. Entrustable professional activities provide one such framework, and herein, we provide proposed Hematopathology Fellowship Entrustable Professional Activities based on review of pertinent guidelines and literature, with multiple rounds of expert and stakeholder input utilizing a modified mini-Delphi approach. Ten core entrustable professional activities deemed essential for graduating hematopathology fellows were developed together with skills and knowledge statements, example scenarios, and corresponding Accreditation Council for Graduate Medical Education Milestones. Application of these entrustable professional activities in program design, fellow evaluation, and decisions regarding level of supervision is discussed with consideration of benefits and barriers to implementation. These entrustable professional activities may be used by hematopathology fellowship directors and faculty to provide fellows with timely constructive feedback, determine entrustment decisions, provide the Clinical Competency Committee with granular data to support Milestone evaluations, and provide insight into areas of potential improvement in fellowship training. Fellows will benefit from a clear roadmap to independent hematopathology practice with concrete and timely feedback.
Assuntos
Leucemia Mieloide/genética , Células-Tronco Neoplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Translocação Genética , Adulto , Medula Óssea/metabolismo , Medula Óssea/patologia , Expressão Gênica , Humanos , Cariótipo , Leucemia Mieloide/complicações , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismoRESUMO
BCR-ABL1-like B-lymphoblastic leukemia/lymphoma (BCR-ABL1-like ALL or Ph-like ALL) is a neoplastic proliferation of lymphoblasts that has a gene expression profile similar to that of B-ALL with t(9;22)(q34.1;q11.2) BCR-ABL1, but lacks that gene fusion. It is associated with poor prognosis and is seen in 10%-20% of pediatric cases and 20%-30% of adult cases of ALL. It is included as a provisional entity in the revised 4th edition of the WHO Classification. A variety of different genetic abnormalities are identified in this entity, but they all converge on pathways that are potentially responsive to the addition of targeted therapy to conventional chemotherapy. Thus, it is important to screen for BCR-ABL1-like ALL, particularly in adults and pediatric patients with high-risk clinical features. Here, we provide a brief overview of the genetic profile and clinical features of BCR-ABL1-like ALL and review laboratory methodologies for routine identification of this genetically heterogeneous entity.
Assuntos
Proteínas de Fusão bcr-abl , Perfilação da Expressão Gênica/métodos , Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Criança , Feminino , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMO
OBJECTIVES: The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology examined the role of molecular genetics in the diagnosis and biology of acute leukemia. METHODS: Acute leukemias were reviewed in two sessions: "Genetic Testing in Diagnosis of Acute Leukemias" (53 cases) and "Genetics Revealing the Biology of Acute Leukemias" (41 cases). RESULTS: Cases included acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemia of ambiguous lineage. Many cases demonstrated genetic alterations of known diagnostic, prognostic, and/or therapeutic significance, while others exhibited alterations that illuminated disease biology. The workshop highlighted the complexity of acute leukemia diagnosis and follow-up, while illustrating advantages and pitfalls of molecular genetic testing. CONCLUSIONS: Our understanding of the molecular genetics of acute leukemias continues to grow rapidly. Awareness of the potential complexity of genetic architecture and environment is critical and emphasizes the importance of integrating clinical information with morphologic, immunophenotypic, and molecular genetic evaluation.
Assuntos
Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Testes Genéticos , Humanos , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Patologia Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
A 15-month-old girl with Miller-Dieker syndrome, a contiguous gene deletion syndrome involving chromosome 17p13.3 and resulting in lissencephaly, was diagnosed with precursor B-cell acute lymphoblastic leukemia. Cytogenetic analysis identified both the previously detected 17p13.3 deletion and additional complex numerical and structural abnormalities, including loss of chromosome 9, isochromosome 9q and interstitial deletion of 20q. This is, to our knowledge, the first report of acute leukemia in the setting of Miller-Dieker syndrome. Herein we review the literature regarding Miller-Dieker syndrome, with particular attention to the presence of several candidate tumor suppressor genes within the deleted material.
Assuntos
Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Anormalidades Múltiplas , Aberrações Cromossômicas , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 9/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/terapia , Evolução Fatal , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Isocromossomos , Cariotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Translocação GenéticaRESUMO
INTRODUCTION: Histiocytic sarcoma (HS) is a rare malignant neoplasm that can occur in patients with a history of treatment for hematologic or solid tumors. Because no optimal treatment has been defined and standardized, the treatment modalities used and outcomes reported have been highly variable. In the present study, 3 major institutions explored the clinicopathologic features of de novo and secondary HS. MATERIALS AND METHODS: After institutional review board approval, clinical, histopathologic, and immunophenotypic data were collected from patients with a diagnosis of HS and treated at the University of Alabama at Birmingham, University of New Mexico, or Brooke Army Medical Center from January 1, 2003 to December 31, 2016. RESULTS: The databases revealed 23 unique cases of HS. The mean age was 55.4 years (range, 5-84 years) and the male-to-female ratio was 0.92. The mean follow-up period was 89.82 months (range, 14-172 months). Of the 23 patients with HS, 6 had a history of an unrelated malignancy treated with chemotherapy or radiotherapy, with a mean delay of 42.2 months (range, 12-91 months). The mean overall survival during the study period was 54.1 months. The overall survival of those with de novo HS was 70 months compared with 11.8 months for those with secondary HS, with a mean difference of 58.2 months (95% confidence interval, 26.2-90.2 months; P = .001). CONCLUSION: The shorter overall survival with secondary HS suggests a more aggressive course than that with de novo disease. Larger scale studies are needed to further investigate the biology and genetics of HS.
Assuntos
Sarcoma Histiocítico/mortalidade , Sarcoma Histiocítico/patologia , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Sarcoma Histiocítico/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
The forthcoming update of the World Health Organization (WHO) classification of hematopoietic neoplasms will feature "Myeloid Neoplasms with Germline Predisposition" as a new provisional diagnostic entity. This designation will be applied to some cases of acute myeloid leukemia and myelodysplastic syndrome arising in the setting of constitutional mutations that render patients susceptible to the development of myeloid malignancies. For the diagnostic pathologist, recognizing these cases and confirming the diagnosis will demand a sophisticated grasp of clinical genetics and molecular techniques. This article presents a concise review of this new provisional WHO entity, including strategies for clinical practice.
Assuntos
Mutação em Linhagem Germinativa , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Predisposição Genética para Doença , Testes Genéticos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Organização Mundial da SaúdeRESUMO
CONTEXT: Lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well-defined clinicopathologic entities. However, distinguishing LPL from MZL and from atypical cases of CLL can sometimes be difficult because of overlapping features. Recent studies have identified a recurrent L265P mutation in the MYD88 gene in most cases of LPL. Although this represents a promising diagnostic marker for LPL, the mutation is also reported in rare cases of MZL and CLL (as well as other types of B-cell lymphoma). Detection rates for this mutation have varied depending on the analytic methodology. OBJECTIVE: To assess the diagnostic utility of MYD88 L265P mutation in diagnosing low-grade B-cell lymphomas. DESIGN: We developed a novel pyrosequencing assay for the MYD88 L265P mutation and assessed its diagnostic utility in 317 cases of low-grade B-cell lymphoma (45 LPL [14%], 53 MZL [17%], and 219 CLL [69%]). We incorporated formal clinical and pathologic review of selected cases to ensure the most accurate diagnosis and subclassification. RESULTS: The MYD88 L265P mutation was identified in 43 cases of LPL (96%), including 3 nonimmunoglobulin-M LPL cases. In contrast, the mutation was present in only 2 cases of MZL (4%), and 5 cases of CLL (2%). Thus, pyrosequencing for the MYD88 L265P mutation demonstrates a high clinical sensitivity and specificity to distinguish LPL from MZL and CLL. CONCLUSIONS: This study confirms the strong association of the MYD88 L265P mutation with LPL, as well as the existence of rare cases of small B-cell lymphoma that complicate this association.
Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Fator 88 de Diferenciação Mieloide/genética , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/classificação , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: In 2001, the University of New Mexico Hospitals implemented a rapid screening tool for the triage of suspected hantavirus cardiopulmonary syndrome based on peripheral blood smear morphology. Five criteria guided clinical decisions: thrombocytopenia, hemoconcentration, granulocytic left shift, absence of toxic changes, and more than 10% immunoblasts. Smears meeting four of five criteria were previously shown to have high predictive value for infection. Our retrospective study aimed to determine clinical performance of this test over the past decade. METHODS: Computerized records of 188 smear results were compared with serology. RESULTS: Receiver operator characteristic curve analysis confirmed that the four of five cutoff was the most clinically useful, with sensitivity and specificity of 89% and 93%, respectively. All patients meeting five of five criteria had confirmed infections. Fifteen discordant results were uncovered, explained by positive subsequent tests in the same patient or severe disease without further testing. CONCLUSIONS: Our findings confirm that peripheral smear analysis is clinically useful in this endemic region.
Assuntos
Doenças Endêmicas , Infecções por Hantavirus/epidemiologia , Orthohantavírus/isolamento & purificação , Triagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Coleta de Amostras Sanguíneas , Criança , Pré-Escolar , Feminino , Testes Hematológicos/métodos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome , Adulto JovemRESUMO
CONTEXT: BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells. OBJECTIVE: To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. DESIGN: We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers. RESULTS: BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION. CONCLUSIONS: To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.
Assuntos
Proteínas de Ligação a DNA/genética , Amplificação de Genes , Doença de Hodgkin/genética , Adulto , Idoso , Análise Citogenética , Feminino , Doença de Hodgkin/patologia , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Interfase/genética , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Translocação GenéticaRESUMO
Reactive bone marrow mast cells reliably lack the morphologic, immunophenotypic, and molecular features of systemic mastocytosis (SM). We report two unusual cases of acquired aplastic anemia (AA) in which multifocal aggregates of bone marrow mast cells fulfilled morphologic and immunophenotypic criteria for SM according to the World Health Organization 2008 classification. In the absence of clinical symptoms attributable to SM, the patients were treated with immunosuppressive therapy directed towards AA. Clinical follow-up and subsequent bone marrow examination revealed no evidence of overt SM in either patient. These cases represent, to our knowledge, the first reported instances in which criteria for SM have been fulfilled in the presence of AA. However, given the clinical courses followed by our patients, the incidental identification of mast cell lesions consistent with indolent SM may be of uncertain significance in the setting of AA.
Assuntos
Anemia Aplástica/complicações , Anemia Aplástica/patologia , Mastocitose Sistêmica/classificação , Mastocitose Sistêmica/patologia , Anemia Aplástica/diagnóstico , Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Células da Medula Óssea/patologia , Exame de Medula Óssea , Ciclosporina/uso terapêutico , Humanos , Masculino , Mastócitos/patologia , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/diagnóstico , Pessoa de Meia-Idade , Prednisona/uso terapêuticoRESUMO
Discrete diagnostic subtypes of T lymphoblastic leukemia/lymphoma (T-cell acute lymphoblastic leukemia/lymphoma, T-ALL) have historically not been widely recognized. Recently, a novel subset with distinctive immunophenotypic, molecular, and clinical features has been proposed. Termed early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), these cases seem to correspond to a very early stage of T-cell development. ETP-ALL is associated with a poor prognosis using standard protocols, and patients with ETP-ALL may benefit from intensified, alternative, or targeted therapies. Recognizing ETP-ALL and distinguishing it from other forms of acute leukemia are important elements of an up-to-date diagnostic approach to precursor T-cell neoplasms.
RESUMO
Chronic myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells, which fall into distinct categories based on a number of characteristics including the presence of the BCR-ABL1 gene fusion (chronic myelogenous leukemia) or the JAK2(V617F) mutation (polycythemia vera, primary myelofibrosis, and essential thrombocythemia). One of the criteria in the 2008 World Health Organization Classification divides MPN into different categories based on the presence of an underlying genetic abnormality, however the WHO does not currently address the classification of myeloproliferative neoplasms that have more than one genetic abnormality. The coexistence of a JAK2(V617F) mutation and BCR-ABL1 is rare, and to our knowledge, less than 25 cases have been reported in the literature. Our case series examines the clinical, histopathologic, and genetic features of 3 patients with myeloproliferative neoplasms characterized by concomitant BCR-ABL1 and JAK2(V617F). The implications for diagnosis and treatment of patients with concomitant BCR-ABL1 and JAK2(V617F) are discussed as well as how the BCR-ABL1 and JAK2(V617F)-positive clones may be related to one another.