RESUMO
We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a 'Gardos channelopathy'. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.
Assuntos
Anemia Hemolítica Congênita/genética , Canalopatias/genética , Hidropisia Fetal/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Canais Iônicos/genética , Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/cirurgia , Edema/etiologia , Família , Feminino , Hemólise , Humanos , Hidropisia Fetal/cirurgia , Sobrecarga de Ferro , Masculino , Mutação , Mutação de Sentido Incorreto , Gravidez , Estudos Retrospectivos , Esplenectomia/efeitos adversos , TromboseRESUMO
Primary meningeal osteosarcomas are exceedingly rare. We report a case of a 51-year-old man with a chondroblastic osteosarcoma treated with pre-operative embolization, surgical removal, followed by adjuvant chemotherapy and radiation therapy. Patient is alive without any recurrence 43 months after diagnosis.
Assuntos
Neoplasias Meníngeas/patologia , Osteossarcoma/patologia , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Osteossarcoma/terapia , Radioterapia Adjuvante , Tomografia Computadorizada por Raios XRESUMO
A 35-year-old man with a stage I non-seminomatous germ-cell tumor of the right testis was treated with a simple orchidectomy. Sixty-seven months later, the patient who was on clinical follow-up, has presented five bilateral lung nodules on computed-tomography scan. Additional staging showed no other abnormalities. Lung biopsy of two nodules was performed during a videothoracoscopy and the histologic examination revealed a sarcoidosis-like necrotizing granulomatosis. The coexistence of non-caseating granulomas and testis carcinoma showed an increase during the last two decades. The immunopathogenesis of sarcoid formation in malignant tumours is still unknown. During follow-up of patients with testicular carcinomas, the presence of lung nodules requires a histologic examination and sarcoidosis should be considered as differential diagnosis.
Assuntos
Complicações Pós-Operatórias/diagnóstico , Sarcoidose Pulmonar/etiologia , Neoplasias Testiculares/complicações , Adulto , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Masculino , Estadiamento de Neoplasias , Orquiectomia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Sarcoidose Pulmonar/classificação , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgiaRESUMO
Radiation induced gastroparesis as well as the other autonomic nervous system radiation induced neuropathies are poorly described in the literature. A case of gastroparesis associated with phrenic and recurrent laryngeal nerves paralysis was observed in a 69-year old patient. She was already treated two times by rachis radiotherapy in a context of breast cancer with bone metastases. Anatomical and chronological correlation of lesions, concomitant nerve damage in the radiation fields and elimination of the main differential diagnoses allowed us to link this case of gastroparesis with the background of radiotherapy. It confirms the role of vagus nerve lesion in radiation induced gastroparesis. This specific diagnosis led to a successful treatment and a quality of life improvement.
RESUMO
Amyloid arthropathy occurs chiefly as a manifestation of beta(2) microglobulin amyloidosis in patients receiving chronic hemodialysis. AL amyloidosis complicating multiple myeloma is a less common cause. Amyloid arthropathy is exceedingly rare in patients with Waldenström macroglobulinemia. We report a case characterized by lymphoplasmocytoid malignancy with monoclonal IgM production and amyloid arthropathy manifesting as bilateral symmetric polyarthritis. A synovial membrane biopsy established the diagnosis. Chemotherapy was effective in alleviating the joint manifestations. Joint symptoms in patients with monoclonal gammopathies, including those characterized by IgM secretion, should suggest amyloid arthropathy. Treatment of the blood disease may improve the joint symptoms.
Assuntos
Amiloidose/complicações , Artropatias/complicações , Macroglobulinemia de Waldenstrom/complicações , Idoso , Amiloidose/patologia , Artroscopia , Biópsia , Diagnóstico Diferencial , Progressão da Doença , Humanos , Artropatias/patologia , MasculinoRESUMO
A patient meeting published criteria for remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence of non-Hodgkin's malignant lymphoma. Reported cases of RS3PE associated with hematological malignancies and other forms of cancer are reviewed.
Assuntos
Edema/complicações , Linfoma não Hodgkin/complicações , Recidiva Local de Neoplasia/complicações , Sinovite/complicações , Idoso , Feminino , HumanosAssuntos
Antivirais/uso terapêutico , Hepatite E/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Ribavirina/uso terapêutico , Adenina/análogos & derivados , Idoso , Alemtuzumab/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Doença Crônica , Progressão da Doença , Hepatite E/complicações , Hepatite E/diagnóstico , Hepatite E/virologia , Vírus da Hepatite E/efeitos dos fármacos , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , PiperidinasRESUMO
OBJECTIVES: We studied the clinical phenotypes and tolerance to treatments in a series of patients affected by both inflammatory joint diseases and mastocytosis. METHODS: This retrospective multicenter study was conducted on behalf of 3 networks focused on mastocytosis, pediatric, and adults' inflammatory joint diseases. Patients who displayed both mastocytosis and inflammatory joint diseases were included. RESULTS: A total of 31 patients were included. They had spondyloarthritis (SpA) (16 patients), rheumatoid arthritis (6 patients), juvenile idiopathic arthritis (2 patients), and undifferentiated arthritis (7 patients). The median ages at diagnosis of arthritis and mastocytosis were 44 and 40.5 years, respectively. Disease-modifying anti-rheumatic drugs (DMARDs) were required in 22 patients, comprising mostly methotrexate (13 patients), salazopyrin (8 patients), anti-tumor-necrosis-factor agents (7 patients), and corticosteroids (9 patients). They were well tolerated. Adverse events occurred in 2/24 patients receiving non-steroidal anti-inflammatory drugs. The prevalence of SpA among the 600 patients included in the mastocytosis cohort was 2.33%, which is significantly higher than the prevalence of SpA in the French population (p < 0.001). CONCLUSIONS: This study suggests that mastocytosis is associated with a higher prevalence of SpA than expected, and that DMARDs, notably anti-TNFα agents, are well tolerated in patients with mastocytosis. Mast cells might be involved in the development of SpA.
Assuntos
Mastocitose/epidemiologia , Mastocitose/patologia , Fenótipo , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/patologia , Adolescente , Adulto , Idoso , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Comorbidade , França , Humanos , Mastócitos/patologia , Mastócitos/fisiologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Adulto JovemAssuntos
Infecções por Actinomycetales/etiologia , Bacteriemia/etiologia , Leucemia Mieloide Aguda/complicações , Micrococcaceae/patogenicidade , Infecções Oportunistas/microbiologia , Infecções por Actinomycetales/microbiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bacteriemia/microbiologia , Cateterismo Venoso Central/efeitos adversos , Contaminação de Equipamentos , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Micrococcaceae/isolamento & purificação , Síndromes Mielodisplásicas/complicações , Tuberculose Pulmonar/complicaçõesAssuntos
Encefalopatias/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Adenina/análogos & derivados , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalopatias/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Piperidinas , Síndrome , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico por imagemAssuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Carcinoma de Mama in situ/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Carcinoma de Mama in situ/diagnóstico por imagem , Carcinoma de Mama in situ/secundário , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/secundário , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
Imatinib is the treatment of choice for FIP1L1/PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P CEL), but its optimal dosing, duration, and possibility of discontinuation are still a matter of debate. A retrospective multicenter study was conducted with 44 F/P CEL patients identified in the French Eosinophil Network and treated with imatinib. The most frequently involved systems were skin (57%), spleen (52%), and lung (45%), and eosinophilic heart disease was observed in 15 patients (34%). Complete hematologic response (CHR) was obtained in all patients, and complete molecular response (CMR) in 95% of patients (average initial imatinib dose, 165 mg/d). For 29 patients the imatinib dose was tapered with a maintenance dose of 58 mg/d (±34 mg/d), allowing sustained CHR and CMR. None of the patients developed resistance during a median follow-up of 52.3 months (range, 1.4-97.4 mo). Imatinib was stopped in 11 patients; 6 of the patients subsequently relapsed, but 5 remained in persistent CHR or CMR (range, 9-88 mo). These results confirm that an initial low-dose regimen of imatinib (100 mg/d) followed by a lower maintenance dose can be efficient for obtaining long-term CHR and CMR. Our data also suggest that imatinib can be stopped in some patients without molecular relapse.
RESUMO
Dehydrated hereditary stomatocytosis is a genetic condition with defective red blood cell membrane properties that causes an imbalance in intracellular cation concentrations. Recently, two missense mutations in the mechanically activated PIEZO1 (FAM38A) ion channel were associated with dehydrated hereditary stomatocytosis. However, it is not known how these mutations affect PIEZO1 function. Here, by combining linkage analysis and whole-exome sequencing in a large pedigree and Sanger sequencing in two additional kindreds and 11 unrelated dehydrated hereditary stomatocytosis cases, we identify three novel missense mutations and one recurrent duplication in PIEZO1, demonstrating that it is the major gene for dehydrated hereditary stomatocytosis. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of PIEZO1. Remarkably, we find that all PIEZO1 mutations give rise to mechanically activated currents that inactivate more slowly than wild-type currents. This gain-of-function PIEZO1 phenotype provides insight that helps to explain the increased permeability of cations in red blood cells of dehydrated hereditary stomatocytosis patients. Our findings also suggest a new role for mechanotransduction in red blood cell biology and pathophysiology.