RESUMO
Some patients with systemic mastocytosis have concurrent hematological neoplasms, designated in the World Health Organization (WHO) classification as systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD). In this study, we analyzed 29 patients with SM-AHNMD and compared them to 40 patients with pure SM. The AHNMDs were classified as chronic myelomonocytic leukemia (CMML) (n = 10), myelodysplastic syndrome (MDS) (n = 7), myeloproliferative neoplasms (n = 4), B-cell lymphoma/leukemia/plasma cell neoplasms (n = 7), and acute myeloid leukemia (n = 1). Patients with SM-AHNMD were older, more frequently had constitutional symptoms and hematological abnormalities, less often had skin lesions, and had an inferior overall survival compared with pure SM patients (48 months vs. not-reached, P < 0.001). Karyotypic abnormalities were detected in 9/28 (32%) patients with SM-AHNMD but not in pure SM patients (P < 0.001). Combined imaging/ fluorescence-in-situ hybridization performed in four SM-AHNMD cases revealed shared abnormal signals in mast cells and myeloid cells in two patients with SM-CMML and one patient with SM-MDS, but not in the mast cells of a case SM-associated with chronic lymphocytic leukemia with ATM-deletion. Quantitative mutation analysis showed higher levels of mutant KIT D816V in SM-CMML and SM-MDS than in pure SM (P < 0.001). Our data indicate that the SM-AHNMD category in the WHO classification is heterogeneous, including clonally related and unrelated forms of AHNMD. The presentation, treatment, and outcome of patients with SM-AHNMD is often dictated by the type of AHNMD.
Assuntos
Neoplasias Hematológicas/patologia , Leucemia Mieloide Aguda/patologia , Leucemia Mielomonocítica Crônica/patologia , Linfoma de Células B/patologia , Mastócitos/patologia , Mastocitose Sistêmica/patologia , Síndromes Mielodisplásicas/patologia , Cariótipo Anormal , Adulto , Fatores Etários , Idoso , Linhagem da Célula , Células Clonais , Análise Mutacional de DNA , Feminino , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/mortalidade , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Masculino , Mastócitos/metabolismo , Mastocitose Sistêmica/classificação , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/mortalidade , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Proteínas Proto-Oncogênicas c-kit/genética , Taxa de SobrevidaRESUMO
Immunodeficiency-related lymphoproliferative disorders (IR-LPD) may occur in the setting of immunosuppressive therapy with methotrexate and TNF-α antagonists. As far as we are aware, this is the first report of an Epstein-Barr virus-associated B-cell lymphoproliferative disorder, secondary to methotrexate therapy in a patient with mycosis fungoides/Sézary syndrome.
Assuntos
Hospedeiro Imunocomprometido , Transtornos Linfoproliferativos/imunologia , Micose Fungoide/complicações , Síndrome de Sézary/complicações , Neoplasias Cutâneas/complicações , Idoso , Azatioprina/uso terapêutico , Linfócitos B/patologia , Infecções por Vírus Epstein-Barr/complicações , Humanos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/virologia , Masculino , Metotrexato/uso terapêutico , Micose Fungoide/tratamento farmacológico , Prednisona/uso terapêutico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
In the World Health Organization classification, one major and four minor criteria are specified for the diagnosis of systemic mastocytosis. We report our experience using these criteria to diagnose systemic mastocytosis involving bone marrow. A total of 59 patients with clinically suspected systemic mastocytosis underwent comprehensive bone marrow examination, including immunophenotyping by immunohistochemistry and/or flow cytometry and molecular studies for KIT exon 17 mutations. Serum tryptase levels were also assessed. Of these 59, 53 (90%) patients met the diagnostic criteria for systemic mastocytosis. In these patients, multifocal dense infiltrates of mast cells, the major criterion, was observed in 36 (68%) patients. Atypical mast cell morphology was observed in 53 (100%), an aberrant immunophenotype was identified in 50 of 52 (96%), KIT mutation was present in 33 of 44 (75%), and an elevated serum tryptase (>20 ng/ml) was detected in 44 of 52 (85%). In the six patients in which bone marrow examination could not confirm systemic mastocytosis, one had systemic mastocytosis involving spleen, one patient had chronic idiopathic myelofibrosis, and four had no specific diagnosis, but systemic mastocytosis was still considered most likely. Of these six patients, atypical mast cell morphology was identified in five, aberrant immunophenotype in five, KIT mutation in two, and elevated serum tryptase in two. None of these cases met the major criteria. We conclude that the World Health Organization criteria are useful for the diagnosis of systemic mastocytosis in bone marrow specimens. The results also show the relative values of traditional morphologic criteria (ie, major criterion) and the results of ancillary testing (ie, minor criteria). However, as illustrated by the case of splenic systemic mastocytosis as well as the patient with chronic idiopathic myelofibrosis, the current World Health Organization system is neither completely sensitive nor specific for systemic mastocytosis.
Assuntos
Medula Óssea/patologia , Mastócitos/patologia , Mastocitose Sistêmica/classificação , Mastocitose Sistêmica/diagnóstico , Organização Mundial da Saúde , Adulto , Idoso , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Mastocitose Sistêmica/genética , Pessoa de Meia-Idade , Mutação , Fator de Células-Tronco/genética , Triptases/sangueRESUMO
Lymphomatoid papulosis (LyP) is a lymphoproliferative disorder that exists on a spectrum of diseases with cutaneous CD30+ anaplastic large-cell lymphoma (ALCL). Multiple treatment options are available, although none are curative. The typical age of onset for LyP is in the third and fourth decades, but it has been seen occasionally in children. Lymphomatoid papulosis is associated with primary cutaneous ALCL and other lymphoproliferative malignancies, but is rarely associated with extranodal systemic ALCL. A 43-year-old man developed lymphomatoid papulosis lesions at 3 years of age, which persisted into adulthood, and he later developed ALCL of the duodenum. Treatment with standard CHOP (cyclophosphamide/doxorubicin/vincristine/prednisolone) chemotherapy resulted in complete remission of his gastrointestinal lymphoma and temporary improvement of his skin lesions. However, the LyP relapsed and proved refractory to psoralen plus ultraviolet-A phototherapy, and was only temporarily and partially responsive to bexarotene and denileukin diftitox.