RESUMO
The patient, a 79-year-old Japanese man, was diagnosed with the chronic phase of chronic myeloid leukemia and begun on nilotinib therapy in April 2011. The therapeutic response was major molecular response in August. About 19 months after the start of nilotinib therapy at 400 mg/day (November 2012), an adenocarcinoma (24 x 20 mm) confined to the head of the pancreas developed. In February 2013, a pancreaticoduodenectomy was performed. The therapy regimen was switched to dasatinib at 100 mg/day, beginning in April. The response was still major molecular response with no recurrence of pancreatic carcinoma in July 2013. There have been 29 reported cases of secondary neoplasms associated with nilotinib therapy. These secondary neoplasms were characterized by relatively frequent occurrence of papilloma (6 cases), gastric cancer (3 cases), fibroma (3 cases), and thyroid neoplasms (2 cases). The present case, however, is the first to be reported as carcinoma of the pancreas. This report describes the case.
Assuntos
Adenocarcinoma/induzido quimicamente , Antineoplásicos/efeitos adversos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Segunda Neoplasia Primária/epidemiologia , Neoplasias Pancreáticas/induzido quimicamente , Pirimidinas/efeitos adversos , Adenocarcinoma/epidemiologia , Adenocarcinoma/cirurgia , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Causalidade , Ensaios Clínicos como Assunto , Dasatinibe/uso terapêutico , Depressão/induzido quimicamente , Substituição de Medicamentos , Fibroma/epidemiologia , Hemangioma , Humanos , Leucemia Mieloide de Fase Crônica/sangue , Neoplasias Hepáticas , Masculino , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/cirurgia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Pancreatite/induzido quimicamente , Papiloma/epidemiologia , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Neoplasias Gástricas/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologiaAssuntos
Neoplasias Encefálicas/genética , Ciclina D1/metabolismo , Linfoma de Células B/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Biópsia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Diagnóstico Diferencial , Evolução Fatal , Citometria de Fluxo , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Translocação GenéticaRESUMO
A 50-year-old woman who presented with a mass in the thyroid gland was diagnosed as having diffuse large B-cell lymphoma (DLBCL) by biopsy in August 2011. The tumor had a complex chromosomal karyotype, including 8q24 (C-MYC) and 18q21(BCL-2), and fluorescence in situ hybridization confirmed split signals of C-MYC and BCL-2. BCL-2/IgH and C-MYC/IgH fusion signals were also observed. Three courses of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) therapy were given, followed by thyroid gland irradiation. She was achieved complete remission (CR). In January 2012, a mass appeared in the right breast, which was diagnosed as relapse by biopsy. CR was achieved again after the 4th course of R-CHOP therapy, and one course of rituximab, etoposide, methylprednisolone, cytarabine, cisplatin (R-ESHAP) therapy was given. Thereafter, CR has been maintained after high-dose chemotherapy and autologous peripheral blood stem cell transplantation. There have been only 3 reported cases of primary thyroid C-MYC and BCL-2 double-hit lymphoma, including the present case; 2 of the cases were cases of DLBCL. R-CHOP therapy, irradiation and autologous peripheral blood stem cell transplantation are expected to be effective for such patients.
RESUMO
A 78-year-old man was diagnosed as having advanced symptomatic IgG multiple myeloma in June 2008. Melphalan-prednisolone therapy was effective, however, relapse occurred in January 2011 after 21 courses of melphalan-prednisolone therapy. Addition of bortezomib and dexamethasone led to partial remission, but the treatment needed to be discontinued due to autonomic dysfunction. Combined therapy with lenalidomide and dexamethasone was started in May 2012, which resulted in partial remission. The patient had a persistently elevated eosinophil count (2,350/µL) and increased serum IL-6 level. Pleuritis carcinomatosa developed in January 2013. Lenalidomide was discontinued, which was followed by rapid improvement of the eosinophilia. The patient died of respiratory failure in March 2013. There have been only five reported cases of eosinophilia caused by lenalidomide used for the treatment of multiple myeloma. In these cases, lenalidomide has been speculated to activate cytotoxic T cells to control the plasmacytoma. It would be of interest, therefore, that eosinophilia could serve as a new indicator.
RESUMO
A 90-year-old man presented with subcutaneous ecchymoses. He had been under treatment with dabigatran etexilate methanesulfonate (DEM). Prolonged APTT and decreased PT was developed 2 months after the start of DEM, more prolonged 6 months later. DEM was discontinued, the coagulopathy did not improve. Factor V activity was decreased, along with appearance of coagulation factor V inhibitor (FVI). He did not have antiphospholipid syndrome or malignancy. He was diagnosed as having acquired FVI caused by DEM. Steroid pulse therapy was effective. There have been 74 reported cases of AFVI induced by drug treatment, but none after treatment with DEM.
RESUMO
A 68-year-old woman was diagnosed as having grade 1 follicular lymphoma of the left breast in November 2012. Bone marrow infiltration was noted histologically and confirmed by Southern blot analysis of the IgHJH locus. The clinical stage was IVA, advanced stage. According to the Follicular Lymphoma International Prognostic Index, the patient was classified into the high risk group. The general condition was good and there were no organ symptoms, therefore, the patient was kept under observation without treatment. After one year and 2 months of follow up, The mass was regressed spontaneously. As previous studies have suggested a poor prognosis of patients with an advanced clinical stage of the disease, careful follow-up of our patient is necessary.
RESUMO
A 46-year-old man developed a fever and cough, and computed tomography showed multiple, nodular infiltrative shadows in lungs. He was diagnosed as having intravascular large B-cell lymphoma (IVLBCL). Brain magnetic resonance imaging (MRI, T2W1) showed an abnormal signal area in the pons, which was IVLBCL involvement. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and intrathecal (I.T.) injection of methotrexate, cytarabine and prednisolone were selected. Complete remission (CR) was achieved and pontine involvement disappeared. A total of 8 courses of R-CHOP therapy and 4 courses of I.T. were performed. CR has been maintained for 1 year and 2 months.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Ponte/patologia , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Ciclofosfamida/uso terapêutico , Citarabina/administração & dosagem , Doxorrubicina/uso terapêutico , Humanos , Injeções Espinhais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisona/uso terapêutico , Indução de Remissão , Rituximab , Neoplasias Vasculares , Vincristina/uso terapêuticoRESUMO
The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, <300/µL) and persistent HPV B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.
Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Glucocorticoides/administração & dosagem , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Infecções por Parvoviridae/tratamento farmacológico , Parvovirus B19 Humano/patogenicidade , Prednisolona/administração & dosagem , Aplasia Pura de Série Vermelha/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/imunologia , Anemia Hemolítica Autoimune/virologia , Biomarcadores/sangue , Exame de Medula Óssea , Contagem de Linfócito CD4 , Criança , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/imunologia , Pulsoterapia , Recidiva , Aplasia Pura de Série Vermelha/sangue , Aplasia Pura de Série Vermelha/diagnóstico , Aplasia Pura de Série Vermelha/imunologia , Aplasia Pura de Série Vermelha/virologia , Indução de Remissão , Testes Sorológicos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
The patient was a 52-year old woman with a history of mosquito-bite hypersensitivity since childhood. In July 2011, she developed pyrexia, headaches, and nausea, and Epstein-Barr virus (EBV)-positive aggressive natural killer leukemia (ANKL) was diagnosed on the basis of both a peripheral blood and bone marrow examination. An inguinal lymph node biopsy, on the other hand, revealed EBV-positive cytotoxic T-cell lymphoma plus the presence of a small number of EBV-positive ANKL cells, and a diagnosis of EBV-positive composite lymphoma was made. Both the cytotoxic T-cell lymphoma and ANKL exhibited EBV terminal repeat (Southern blot analysis) monoclonal patterns, and they were almost the same size, approximately 9.0 kb. If it was the identical EBV clone, it is possible that EBV infected progenitor cells common to both NK cells and T cells, that the progenitor cells then differentiated into NK cells and T cells, a chronic active Epstein-Barr virus infection developed, and neoplastic transformation occurred. If it was not the identical EBV clone, fairly similar EBVs must have infected NK cells and T cells separately, and they then underwent neoplastic transformation. Because the mechanism by which EBV infects NK cells or T cells is still unknown, we concluded that this case is also important from the standpoint of elucidating it. We are currently in the process of conducting gene analyses to determine whether the fairly similar EBVs that infected the ANKL and cytotoxic T-cell lymphoma are the identical clone.
Assuntos
Linfoma Composto/patologia , Linfoma Composto/virologia , Infecções por Vírus Epstein-Barr/complicações , Leucemia Linfocítica Granular Grande/patologia , Leucemia Linfocítica Granular Grande/virologia , Linfoma de Células T/patologia , Linfoma de Células T/virologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Citometria de Fluxo , Humanos , Hipersensibilidade/imunologia , Mordeduras e Picadas de Insetos/imunologia , Pessoa de Meia-IdadeRESUMO
The patient was a 73-year-old male who came to our hospital with a chief complaint of pain and swelling of the left side of his jaw. Computed tomography revealed a mass in his left gingiva but no bone destruction. No lesions were observed at any other sites, and an incisional biopsy was performed on the gingival mass on the left side. Histologically, the mass was a diffuse large B-cell lymphoma (DLBCL), and it was CD20-positive, and CD5-negative, CD10-negative, surface immunoglobulin-negative, and Epstein-Barr virus-encoded RNA (EBER)-negative. A serum Human immunodeficiency virus (HIV)-antibody test was negative. A complete remission was achieved after 6 courses of systemic combination chemotherapy, and the complete remission has been maintained for approximately 3 years. According to the literature, primary gingival DLBCL have a high Ki-67-positive rate and many of the cases are stage I and international prognostic index low-risk. However, HIV patients have a high EBER-positive rate and a high risk of developing a CD20-negative, CD138-positive plasmablastic lymphoma, and they have a poor prognosis. By contrast, limited-stage primary gingival lymphomas whose data can be used have been rare in human immunodeficiency virus-negative patients, and only 12 cases, including our own, have ever been reported. Many of the patients have been around 65 years of age, and all of the cases have been CD20-positive, CD138-negative DLBCLs, and the CD5-negative, Epstein-Barr virus-positive rate has been low, with most cases having been non-germinal-center B-cell-like. The prognosis for relapse-free survival has been favorable.
Assuntos
Neoplasias Gengivais/patologia , Linfoma Difuso de Grandes Células B/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gengivais/tratamento farmacológico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , MasculinoRESUMO
The patient was a 72-year-old female with the chief complaint of abdominal fullness. A giant primary myoma of the uterine cervix was suspected, and total hysterectomy was performed. Based on a postoperative histopathological examination of the tumor a diagnosis of diffuse large B-cell lymphoma (DLBCL) was made in the uterus and a mass in the greater omentum was diagnosed as a marginal zone B-cell lymphoma (MZBCL). No flow-cytometry studies or chromosome or gene examinations were performed on a fresh specimen. The results of an examination of a paraffin block histopathology specimen by fluorescence in-situ hybridization (FISH) showed no mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) (18q21.1), B-cell lymphoma 2 (BCL2) (18q21.3), or BCL6 (3q27) split signals in either the uterus or the greater omentum, however, trisomy 18 was detected in approximately 50%-70% of the tumor cells in both the uterus and the greater omentum. Trisomy 18 was present in around 15-33% of the DLBCL cells and MZBCL cells. These findings suggested a strong possibility that the tumor cells in the uterus and greater omentum were the same clone and that transformation from MZBCL to DLBCL had occurred. Since DLBCLs that result from a transformation usually have a worse outcome than de novo DLBCLs, even when a DLBCL seems to have originated in the uterus the surrounding tissue should always be examined, and caution should be exercised in regard to transformation from a low-grade B-cell lymphoma to a DLBCL.
Assuntos
Cromossomos Humanos Par 18 , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Omento/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Trissomia , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Idoso , Biomarcadores Tumorais/análise , Biópsia , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma de Zona Marginal Tipo Células B/química , Linfoma de Zona Marginal Tipo Células B/cirurgia , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/cirurgia , Imageamento por Ressonância Magnética , Omento/química , Omento/cirurgia , Neoplasias Peritoneais/química , Neoplasias Peritoneais/cirurgia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Neoplasias Uterinas/química , Neoplasias Uterinas/cirurgiaRESUMO
The patient was a 74-year-old man who was found to have a cutaneous mass on his left shoulder in February 2012. Because the mass bled easily and was tending to grow, total resection of the cutaneous tumor, which measured approximately 5 cm x 3 cm, was performed in July. Histopathological examination revealed a tumor that extended from the dermis to the cutaneous adipose tissue, but no invasion of the epidermis was seen. The tumor cells were plasmacytoid cells ranging in size from small to intermediate, and there was no nuclear irregularity. They had a high nuclear-cytoplasmic ratio, and nucleoli were observed. The tumor cells were CD4-positive, CD56-positive, and CD123-positive, and they were AE1/AE3-negative, CD3-negative, CD20-negative, and myeloperoxidase-negative. (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT), a bone marrow examination, etc., were performed, but no lesions were detected at other sites. Based on the above findings a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN), Stage IEA, was made. Because the patient had limited-stage BPDCN and was elderly, we treated him with a simultaneous combination of low-dose DeVIC (dexamethasone, VP16, ifosfamide, and carboplatin) therapy and local radiation therapy (LRT) and sustained a complete remission for approximately 1 year. Simultaneous combination of non-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and LRT appeared to be useful in the treatment of limited-stage BPDCN even in the elderly.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia Adjuvante , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/efeitos da radiação , Neoplasias Cutâneas/terapia , Idoso , Biomarcadores Tumorais/análise , Biópsia , Carboplatina/administração & dosagem , Células Dendríticas/química , Células Dendríticas/patologia , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Imuno-Histoquímica , Masculino , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Indução de Remissão , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Fatores de Tempo , Resultado do Tratamento , Imagem Corporal TotalRESUMO
A Japanese man aged 30 years old contracted acute hepatitis B in October 2011, and was cured following conservative treatment. Mild hepatosplenomegaly was the only positive finding on computed tomography (CT) and ultrasonography at that time. In May 2012, slight impairment of the liver function was detected again in the patient; an abdominal CT at this time revealed a tumor mass in the right hepatic lobe, so subsegmentectomy of the right hepatic lobe was performed. On the basis of the findings of the resected specimen, primary hepatic circumscribed Burkitt's lymphoma (sporadic form), stage IA, was diagnosed. Multiple cycles of hyper-CVAD/MTX-Ara-C therapy with concomitant rituximab were administered, under which the patient was successfully maintained in complete remission. To date, at least 15 cases of primary hepatic Burkitt's lymphoma have been reported in the literature; all of the 11 patients without concurrent human immunodeficiency virus (HIV) infection had the sporadic form of the disease. Asians were relatively common (7 patients) among these patients, and patients in their childhood or adolescence accounted for a considerable proportion. Therefore, the present case may be regarded as rather typical. The presence of hepatitis virus infection as a background disorder other than HIV is considered to be of profound interest etiologically.
Assuntos
Linfoma de Burkitt/complicações , Hepatite B/complicações , Neoplasias Hepáticas/complicações , Adulto , Biópsia , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/cirurgia , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Indução de Remissão , Tomografia Computadorizada por Raios XRESUMO
An 85-year-old man presented with pain and numbness in the left buttock, and physical examination revealed an approximately 7 cm mass extending from the first to the third sacral vertebrae; biopsy of the mass led to the diagnosis of CD10-negative, BCL6-weakly positive, MUM1-positive, non-germinal center (non-GC) type diffuse large B-cell lymphoma (DLBCL). Furthermore, serological testing showed negative results for Epstein-Barr virus (EBV) infection, and fluorescence in situ hybridization (FISH) revealed a MYC translocation. Radiographs showed no remarkable osteolytic bone destruction, and the patient was staged with Stage IAE. After 8 cycles of rituximab therapy and 6 cycles of CHOP therapy, complete remission has been maintained until now, approximately 1 year after the treatment. Primary sacral lymphoma is very rare, with only 6 reported cases, including the present one. A review of the reported cases revealed that the disease predominantly affects elderly men, is usually non-GC-type DLBCL and stage IAE, measures approximately 2-7 cm in diameter in general, and does not show early recurrence after chemotherapy or chemoradiotherapy. There is no report in the literature yet of primary sacral DLBCL with MYC translocation, and this is the first case report. On the other hand, 35 cases of CD10-negative DLBCL with MYC translocation, including the present one, have been reported, and a review of the reported cases showed that the disease predominantly affects Asians, middle-aged or elderly men, shows positivity for either BCL6 or MUM1 and negativity for EBV, and has a high international prognostic index and poor prognosis.
Assuntos
Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-myc/genética , Sacro , Neoplasias da Coluna Vertebral/genética , Translocação Genética , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biópsia , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Tomografia por Emissão de Pósitrons , Indução de Remissão , Sacro/patologia , Neoplasias da Coluna Vertebral/química , Neoplasias da Coluna Vertebral/tratamento farmacológico , Neoplasias da Coluna Vertebral/patologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Benzoatos/uso terapêutico , Resistência a Medicamentos , Substituição de Medicamentos , Humanos , Hidrazinas/uso terapêutico , Pirazóis/uso terapêutico , Receptores Fc/administração & dosagem , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Trombopoetina/administração & dosagem , Trombopoetina/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Inherited antithrombin (AT) deficiency is associated with a predisposition to familial venous thromboembolic disease. We analyzed the AT gene in three unrelated patients with an AT deficiency who developed thrombosis. MATERIALS AND METHODS: We analyzed the SERPINC1 gene in three patients. Additionally, we expressed the three mutants in the COS-1 cells and compared their secretion rates and levels of AT activity with those of the wild-type (WT). RESULTS: We identified three distinct heterozygous mutations of c.2534C>T: p.56Arginine â Cysteine (R56C), c.13398C>A: p.459Alanine â Aspartic acid (A459D) and c.2703C>G: p.112 Proline â Arginine (P112R). In the in vitro expression experiments, the AT antigen levels in the conditioned media (CM) of the R56C mutant were nearly equal to those of WT. In contrast, the AT antigen levels in the CM of the A459D and P112R mutants were significantly decreased. The AT activity of R56C was decreased in association with a shorter incubation time in a FXa inhibition assay and a thrombin inhibition-based activity test. However, the AT activity of R56C was comparable to that of WT when the incubation time was increased. CONCLUSIONS: We concluded that the R56C mutant is responsible for type II HBS deficiency. We considered that the A459D and P112R mutants can be classified as belonging to the type I AT deficiency.
Assuntos
Deficiência de Antitrombina III/genética , Antitrombina III/genética , Mutação Puntual , Adulto , Idoso , Animais , Antitrombina III/metabolismo , Deficiência de Antitrombina III/sangue , Testes de Coagulação Sanguínea , Células COS , Chlorocebus aethiops , Feminino , Humanos , Japão , Adulto JovemRESUMO
A 65-year-old man was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) with bone marrow (BM) infiltration and myelofibrosis (MF). The BM infiltration and the condition of the MF improved following CHOP therapy (cyclophosphamide hydrate, doxorubicin hydrochloride, vincristine sulfate, and prednisolone). After complete remission was achieved, early central nervous system recurrence was noted, with no evidence of BM infiltration or MF. The lymph nodes and BM were examined for cytokines by immunohistochemical staining with monoclonal murine antibodies. The lymphoma cells were positive only for platelet-derived growth factor (PDGF) and negative for basic fibroblast growth factor, fibronectin, vascular endothelial growth factor, transforming growth factor-ß (TGF-ß), tumor necrosis factor α, interleukin-1ß, and interleukin-6. It was thus inferred that the lymphoma cells producing PDGF caused the MF, and that the absence of MF at relapse may have been attributable to the absence of BM infiltration. There have been seven reported cases of AITL with intercurrent MF, although cytokine data (elevations of blood PDGF and TGFß levels) are available for only one case. The present report is to our knowledge the only report of a case of AITL complicated by MF for which the results of immunohistostaining with anticytokine antibodies are available.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Células T , Proteínas de Neoplasias/biossíntese , Fator de Crescimento Derivado de Plaquetas/biossíntese , Mielofibrose Primária , Idoso , Medula Óssea/metabolismo , Medula Óssea/patologia , Ciclofosfamida/administração & dosagem , Citocinas/metabolismo , Doxorrubicina/administração & dosagem , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/metabolismo , Linfoma de Células T/patologia , Masculino , Prednisona/administração & dosagem , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Vincristina/administração & dosagemRESUMO
A 56-year-old man developed epistaxis, hoarseness, and swelling of a finger in March 2010. On the basis of biopsies of the masses in the pharynx and finger, he was diagnosed with extramedullary plasmablastic plasmacytoma, with somewhat immature CD45(+), MPC-1(-), and CD49e(-). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and VCAP (vincristine, cyclophosphamide, doxorubicin, and prednisolone) therapy was ineffective, but combination therapy with thalidomide and dexamethasone was highly effective. Thalidomide monotherapy successfully maintained partial remission for approximately 7 months. A mass appeared in the right neck in February 2011, and a biopsy confirmed recurrence. Changes to CD45 negativity and MPC-1 partial positivity were seen, while CD49e negativity persisted, suggesting that the plasmablastic plasmacytoma had reverted to a more immature state. Bortezomib therapy was started in March 2011 and was effective. However, during the second round of treatment, the patient developed acute lung injury, which was improved by steroid pulse therapy. After the discontinuation of bortezomib, the extramedullary mass increased rapidly, and the patient died of multiple organ failure. An autopsy showed that plasmablastic plasmacytomas had infiltrated into multiple organs. Extramedullary plasmacytomas and those that revert to an immature state are associated with a poor prognosis, so further treatment improvements are needed in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Plasmocitoma/tratamento farmacológico , Dexametasona/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Plasmocitoma/diagnóstico , Plasmocitoma/patologia , Talidomida/administração & dosagemRESUMO
A 67-year-old man was diagnosed with CD56(+) angioimmunoblastic T cell lymphoma (AITL), which was associated with autoimmune thrombocytopenic purpura (ATP) and autoimmune hemolytic anemia (AIHA) (Evans syndrome). The ATP was refractory to Helicobacter pylori eradication therapy and steroid. Complete remission (CR) of both AITL and AIHA was achieved with THP-COP chemotherapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone), but ATP was not improved promptly. AITL associated with ATP has been reported in only 14 cases. The present case was not related to the serum interleukin-6 levels, suggesting the possibility of an association with other factors. This case is the first report of Evans syndrome associated with AITL. The AITL relapsed 2 months after CR. The AITL tumor were CD56-positive at initial diagnosis and CD56-negative at relapse, and showed complex additional chromosomal abnormalities, and the morphological characteristics of blast cells. CD56(+) AITL are rare, although CD56 expression has not been investigated in many cases ; our observations suggest that CD56 expression and its significance in AITL should be investigated in the future. There has been only one other case of CD56(+) AITL, the patient died 4 months after the diagnosis. Our patient reported showed early relapse, central nervous system infiltration and was refractory to treatment, suggesting that CD56 positivity may be a poor prognostic marker in patients with AITL. [J Clin Exp Hematop 53(1): 37-47, 2013].
Assuntos
Anemia Hemolítica Autoimune/imunologia , Antígeno CD56/imunologia , Linfoma de Células T/imunologia , Trombocitopenia/imunologia , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Antígeno CD56/biossíntese , Humanos , Linfoma de Células T/diagnóstico , Masculino , Trombocitopenia/diagnósticoRESUMO
A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.