RESUMO
Imerslund-Gräsbeck syndrome is an autosomal recessive disorder of vitamin B12 malabsorption presenting with megaloblastic anemia and mild proteinuria in childhood. The disorder is caused by biallelic pathogenic variants in the CUBN or AMN genes, which encode proteins involved in B12 absorption. We present the case of a 17-month-old boy with failure to thrive, pancytopenia, and fevers. His megaloblastic anemia was overlooked leading to unnecessary invasive testing. Findings on bone marrow biopsy prompted investigation for genetic disorders of B12 metabolism. Exome sequencing uncovered 1 known pathogenic variant and 1 novel likely pathogenic variant in CUBN, confirming the diagnosis of Imerslund-Gräsbeck syndrome.
Assuntos
Anemia Megaloblástica , Pancitopenia , Deficiência de Vitamina B 12 , Anemia Megaloblástica/genética , Feminino , Humanos , Lactente , Síndromes de Malabsorção , Masculino , Pancitopenia/genética , Proteinúria , Vitamina B 12/metabolismo , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/genéticaRESUMO
Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL). AITL typically presents with lymphadenopathy, fever, rash, hepatosplenomegaly, and rarely polyarthritis. We report the case of a 50-year-old female who presented with lymphadenopathy, rash, and symmetric polyarthritis. She was later diagnosed with AITL and was treated with chemotherapy with resolution of arthritis. AITL should be suspected in paitents presenting with rheumatoid-like arthritis and diffuse lymphadenopathy.
Assuntos
Artrite/complicações , Linfadenopatia Imunoblástica/complicações , Linfoma de Células T/complicações , Linfoma de Células T/diagnóstico , Antineoplásicos/uso terapêutico , Artrite/diagnóstico , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Cartilagem , Diagnóstico Diferencial , Exantema/complicações , Feminino , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Imuno-Histoquímica , Linfadenopatia/complicações , Linfoma de Células T/tratamento farmacológico , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
AIM: To assess the validity and potential clinical utility of evaluating MYC expression by immunohistochemistry (IHC) in mantle cell lymphoma (MCL). METHODS AND RESULTS: MYC IHC was scored on a tissue microarray containing 62 MCLs and 29 controls by two pathologists. Inter-observer correlation was high (intra-class correlation of 0.98). MYC IHC scores correlated with MYC expression (Spearman's rank correlation 0.69, P < 0.0001) and weakly with Ki67 proliferation index (Spearman's rank correlation 0.30, P = 0.03). Six blastic MCLs did not have higher mean MYC IHC scores or MYC mRNA expression than non-blastic MCLs. None of 57 cases assessed, including all of the blastic cases, showed MYC rearrangement by fluorescence in-situ hybridization. Multivariate analysis with backward selection from potential predictors including age, lactate dehydrogenase, leukocyte count, MIPI score, ECOG performance status, blastic morphology and Ki67 index showed that MYC IHC score is an independent predictor of progression-free survival (hazard ratio 2.34, 95% CI 1.42-3.88, P = 0.0009) and overall survival (hazard ratio 1.90, 95% CI 1.05-3.43, P = 0.034). CONCLUSIONS: We show that a new monoclonal anti-MYC antibody can enable accurate and reproducible visual assessment of MYC expression that is independently predictive of clinical outcomes in MCL.
Assuntos
Biomarcadores Tumorais/análise , Linfoma de Célula do Manto/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-myc/análise , RNA Mensageiro/análise , Análise Serial de TecidosRESUMO
OBJECTIVE: Potential vitamin B(12) deficiency is a common clinical diagnostic problem, and many providers have a low threshold for initiating therapy. The goal of this study was to systematically evaluate current practice patterns regarding the laboratory evaluation of suspected vitamin B(12) deficiency. METHODS: This retrospective study reviewed the electronic medical records of 192 patients initiated on intramuscular vitamin B(12) injections. RESULTS: Only 12 patients had objectively documented hematologic responses: decrease of mean corpuscular volume by ≥5 fL with stable or improved hemoglobin. Another 5 patients had equivocal hematologic responses. There was one plausible neurologic response. Thus, only 18 (9.4%) of 192 patients had data supportive of a clinical response. In these 18 patients, the baseline serum B(12) level was ≤107 pg/mL; only 3 patients also had a baseline serum methylmalonic acid level, which was ≥1.29 µmol/L in all 3 patients. CONCLUSIONS: Currently, only a small minority of patients initiated on intramuscular vitamin B(12) supplementation derive any meaningful clinical benefit. Furthermore, current testing recommendations for vitamin B(12) deficiency are usually not followed. Up-front ordering of a diagnostic testing cascade is recommended to improve compliance; an example is presented with decision points chosen to improve specificity for clinically evident vitamin B(12) deficiency without loss of sensitivity. Ultimately, a better understanding of vitamin B(12) physiology is needed to develop and evaluate laboratory tests that more accurately reflect true intracellular vitamin B(12) status.
Assuntos
Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Hemoglobinas/metabolismo , Humanos , Injeções Intramusculares , Masculino , Ácido Metilmalônico/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Vitamina B 12/administração & dosagem , Deficiência de Vitamina B 12/sangue , Adulto JovemRESUMO
Histiocytic sarcoma (HS) is a very rare hematopoietic neoplasm that has been reported in association with other hematological malignancies. Presentation of HS in the central nervous system is even less common. Diagnosis of HS requires the presence of histiocytic markers and the systematic exclusion of markers of other cell lineages. Primary HS central nervous system tumors are aggressive and generally have poor outcomes. There are no standard treatment guidelines due to lack of clinical trials and a limited number of case reports. Here we present a unique case with two primary histiocytic lesions in the brain, refractory to systemic and radiation therapies, that developed after being treated for T-cell acute lymphoblastic leukemia 16 years prior.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/patologia , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Terapia Combinada , Tratamento Farmacológico , Evolução Fatal , Neoplasias Hematológicas/diagnóstico por imagem , Sarcoma Histiocítico/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Radioterapia , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Histiocytic sarcoma (HS) is a rare malignancy of tissue histiocytes with a dismal prognosis. We report a 4-year-old male who developed HS during maintenance chemotherapy for precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Both tumors showed identical clonal immunoglobulin and T-cell receptor gene re-arrangement patterns, as well as homozygous deletion of the CDKN2A gene encoding p16(INK4A). These data suggest a clonal relationship between the two neoplasms despite their distinct lineages. Since CDKN2A deletion predisposes to development of HS in experimental models, the cytogenetic features of the patient's pre-B ALL may have predisposed to this change in lineage.
Assuntos
Genes p16 , Sarcoma Histiocítico/genética , Segunda Neoplasia Primária/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Separação Celular , Pré-Escolar , Inibidor p16 de Quinase Dependente de Ciclina/genética , Citometria de Fluxo , Furanos , Sarcoma Histiocítico/patologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Segunda Neoplasia Primária/patologia , TiofenosRESUMO
We report the case of a patient who presented with a 3-month history of random epistaxis and recent onset of acute hearing loss associated with fever, chills, and myalgias. Pure tone audiometry revealed bilateral sensorineural hearing loss. Complete blood cell count showed an abnormal neutrophil count of 700/uL (normal >1900/microL) and platelet count of 25 x 10(3)/microL (normal >175 x 10(3)/microL). Giemsa-stained peripheral blood smear revealed neutrophilic intracytoplasmic inclusion consistent with anaplasma morulae. Polymerase chain reaction confirmed Anaplasma phagocytophilum. The patient was treated with oral doxycycline, and, after 14 days of treatment, the hearing loss had improved markedly. Therefore, we concluded that the patient's acute transient bilateral sensorineural hearing loss was associated with anaplasmosis.
Assuntos
Anaplasma phagocytophilum , Ehrlichiose/diagnóstico , Perda Auditiva Neurossensorial/microbiologia , Doença Aguda , Antibacterianos/uso terapêutico , Audiometria de Tons Puros , Diagnóstico Diferencial , Ehrlichiose/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A warfarin treated patient unexpectedly presented with an elevated international normalized ratio (INR). Repeat testing in two laboratories gave conflicting results. The chromogenic assay of factor X was used to determine the correct INR result. The patient had laboratory results consistent with a dysfibrinogenemia, which prevented detection of the endpoint with a photo-optical detection system. The chromogenic assay of factor X is recommended for monitoring patients on warfarin when the INR cannot be accurately determined due to interference with the fibrin endpoint in the INR.
Assuntos
Anticoagulantes/uso terapêutico , Fator X/metabolismo , Fibrina/química , Coeficiente Internacional Normatizado , Varfarina/uso terapêutico , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Compostos Cromogênicos , Feminino , Fibrinogênio/imunologia , Insuficiência Cardíaca/complicações , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Tempo de Protrombina , Fatores de TempoRESUMO
Myelofibrosis, either primary or resulting from essential thrombocythemia or polycythemia vera, may present with highly variable white blood cell counts, including progressive leukopaenia with its associated risk of infections. Medications have been developed to reduce splenomegaly and other symptoms, but there are no reports of improved white blood cell counts. We report a case of primary myelofibrosis with marked improvement in leukopaenia and reduced recurrent infections, in addition to reduction in spleen size and improvement in disease-associated symptoms, within 20 weeks after using low-dose ruxolitinib. Although reduction of splenomegaly in myelofibrosis patients is the anticipated benefit of ruxolitinib, the drug may also have the potential to improve leukopaenia if used at a low dose.
Assuntos
Infecções/etiologia , Leucopenia/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Baço/efeitos dos fármacos , Esplenomegalia/tratamento farmacológico , Idoso , Feminino , Humanos , Janus Quinases/antagonistas & inibidores , Contagem de Leucócitos , Leucopenia/etiologia , Nitrilas , Tamanho do Órgão/efeitos dos fármacos , Mielofibrose Primária/complicações , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Pirimidinas , Esplenomegalia/etiologiaRESUMO
The vast majority of cases of T cell large granular lymphocyte (T-LGL) leukemia have a CD3+, CD4-, CD8+ phenotype and express the alphabeta T cell receptor. Whether the rare gammadelta variant should be included in the same diagnostic category is currently unclear. Two well-characterized cases of gammadelta T-LGL leukemia were identified by our laboratory in 2007. These two cases and other reports of gammadelta T-LGL leukemia were compared with the common alphabeta variant. Other than more often being negative for both CD4 and CD8 (in about 35% to 40% of cases), the gammadelta variant of T-LGL leukemia is similar to the common alphabeta type in virtually all respects and should be included in the general category of T-LGL leukemia. However, it is important to exclude other more aggressive gammadelta T cell lymphoproliferative disorders.
RESUMO
CONTEXT: Nonsecretory plasma cell myeloma is characterized by an absence of detectable monoclonal protein in both the serum and urine. It is generally reported to comprise approximately 1% to 5% of all cases of plasma cell myeloma and, because of its rarity, requires a high index of suspicion and bone marrow biopsy to establish the diagnosis. OBJECTIVE: Review the diagnostic strategy when nonsecretory plasma cell myeloma is a clinical consideration in light of a relatively new serum free light chain assay. DATA SOURCES: Case study and review of the literature. CONCLUSIONS: Initial data using a recently developed nephelometric serum free light chain assay suggests that only about one fourth of nonsecretory plasma cell myeloma cases may be truly nonsecretory. The definition of nonsecretory plasma cell myeloma should be modified to exclude cases with evidence of clonality using the serum free light chain assay.
Assuntos
Cadeias Leves de Imunoglobulina/sangue , Plasmócitos/patologia , Plasmocitoma/diagnóstico , Agamaglobulinemia/sangue , Agamaglobulinemia/diagnóstico , Células da Medula Óssea/patologia , Humanos , Imunoensaio/métodos , Proteínas do Mieloma/análise , Osteólise/sangue , Osteólise/diagnóstico , Plasmocitoma/sangue , Kit de Reagentes para DiagnósticoRESUMO
Sideroblastic anaemia with ringed sideroblasts and marked thrombocytosis, hereupon referred to as ringed sideroblasts with thrombocytosis (RST), is a provisional entity in the 2001 World Health Organisation classification scheme. This retrospective study identified 16 patients with RST over a 7-year period. Proposed diagnostic criteria include a sustained platelet count > 500 x 10(9)/l, > or = 15% ringed sideroblasts, < 3% bone marrow blasts, and normal conventional cytogenetics. The median age was 76 years with eight males and eight females. With a median follow-up of 41 months, RST patients had a median overall survival of 71 months, comparable with refractory anaemia having ringed sideroblasts, but less favourable than essential thrombocythaemia. Thus far, no patients with RST are known to have died of disease-related causes. Patients with ringed sideroblasts and/or thrombocytosis need to be carefully evaluated for a variety of haematological diseases that may confer significantly different prognoses.