RESUMO
Four individuals from two families presented with a multisystemic condition of suspected genetic origin that was diagnosed only after genome analysis. The main phenotypic features were immune system dysregulation (severe immunodeficiency with autoimmunity) and intellectual disability. The four individuals were found to be homozygous for a 4.4 Kb deletion removing exons 20-23 (NM_003291.4) of the TPP2 gene, predicting a frameshift with premature termination of the protein. The deletion was located on a shared chromosome 13 haplotype indicating a Swiss founder mutation. Tripeptidyl peptidase 2 (TPP2) is a protease involved in HLA/antigen complex processing and amino acid homeostasis. Biallelic variants in TPP2 have been described in 10 individuals with variable features including immune deficiency, autoimmune cytopenias, and intellectual disability or chronic sterile brain inflammation mimicking multiple sclerosis. Our observations further delineate this severe condition not yet included in the OMIM catalog. Timely recognition of TPP2 deficiency is crucial since (1) immune surveillance is needed and hematopoietic stem cell transplantation may be necessary, and (2) for provision of genetic counselling. Additionally, enzyme replacement therapy, as already established for TPP1 deficiency, might be an option in the future.
Assuntos
Aminopeptidases/genética , Doenças Autoimunes/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Mutação da Fase de Leitura/genética , Síndromes de Imunodeficiência/genética , Serina Endopeptidases/genética , Adulto , Criança , Pré-Escolar , Éxons/genética , Feminino , Humanos , Masculino , Adulto JovemRESUMO
A 67-year-old woman was referred for staging of a mucosa-associated lymphoid tumor lymphoma involving the left conjunctiva. CT scan had shown paravertebral and pelvic masses, and a breast nodule. FDG PET/CT demonstrated moderately increased uptake in the left ocular conjunctiva and confirmed the paravertebral and pelvic masses and the breast nodule. Moreover, abnormal FDG uptake was shown in 2 breast nodules, the flank, the gluteus maximus, and the gastric cardia. The patient received 6 cycles of rituximab-bendamustine chemotherapy with a complete clinical and metabolic response at the 6-month follow-up PET/CT and remained relapse-free without visual acuity problem after a 36-month follow-up.
Assuntos
Neoplasias da Túnica Conjuntiva/diagnóstico por imagem , Fluordesoxiglucose F18 , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Túnica Conjuntiva/diagnóstico por imagem , Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Imagem Multimodal , Estadiamento de Neoplasias , Resultado do Tratamento , Imagem Corporal TotalRESUMO
Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach.
Assuntos
Amiloidose/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Idoso , Amiloidose/complicações , Amiloidose/mortalidade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Nefropatias/terapia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Indução de Remissão , Taxa de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
Primary indolent leptomeningeal lymphoma is a rare entity, and corresponds in most cases to mucosa-associated lymphoid tissue (MALT) type lymphoma. We are reporting a case of a 75 years old woman, who presented with a 2-year history of behavioral disorder, progressive memory loss and aphasia. Neuroimaging showed a mass infiltrating the frontal circumvolutions and the roof of the orbit. The biopsy revealed an infiltration of the dura by an indolent lymphoma, characteristic of a MALT-type lymphoma. Complete staging work-up did not show any evidence of systemic involvement. A treatment with systemic methotrexate, combined with intrathecal chemotherapy and followed by radiotherapy (30,6 Gy) of the primary site, was conducted. The 3-year follow-up confirms the persistent remission, the patient remaining well and free of symptoms. The review of the literature highlights the importance to recognize the indolent PLML as a distinct clinical entity, which exhibits a rather good prognosis following a relatively non-toxic therapy.