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PURPOSE: To report on a rare case of intermediate uveitis occurring in a patient with common variable immunodeficiency (CVID) and a heterozygous TNFRSF13B variant. METHODS: Observational case report. RESULTS: A 23-year-old male presented with a 3-month history of increasing floaters and blurred vision to both eyes. He had been treated with topical and intravitreal corticosteroids by his local ophthalmologist nine months before. Ocular examination demonstrated bilateral intermediate uveitis with retinal vasculitis. He had been treated with intravenous immunoglobulins during childhood, due to primary humoral immunodeficiency. Systemic work-up for other causes of intermediate uveitis was unremarkable, notably no features of systemic sarcoid-like disease were detected. Initial treatment with mycophenolate mofetil showed insufficient response, and upon switching to adalimumab, clinical remission was achieved. Immunocytometry and genetic work-up revealed a smB+CD21norm subtype of CVID and a heterozygous TNFRSF13B variant. CONCLUSION: This report of CVID-associated intermediate uveitis in a patient with a heterozygous TNFRSF13B variant highlights the potential involvement of the eye within CVID-associated autoimmunity and the role for anti-TNF blockade in this challenging group of patients.
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A 49-year-old patient with a history of lymphoproliferation and autoimmune cytopenias presented with unexplained longitudinal extensive transverse myelitis. Flow cytometry on peripheral blood showed an elevated level of double negative T lymphocytes, a finding typical for autoimmune lymphoproliferative syndrome (ALPS). Inborn error of immunity (IEI) gene panel demonstrated a heterozygous variant in the FAS gene (c.857G > A, p.(Gly286Glu)), formally confirming the diagnosis. Autoimmune neurological conditions in a context of predisposition for infection and lymphoproliferation should raise suspicion of IEI. Specific testing for ALPS should be considered in patients with a history of non-malignant lymphoproliferation, multilineage cytopenias and unexplained autoimmune (neurological) manifestations.
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Síndrome Linfoproliferativo Autoinmune , Mielitis Transversa , Trombocitopenia , Síndrome Linfoproliferativo Autoinmune/complicaciones , Síndrome Linfoproliferativo Autoinmune/diagnóstico , Síndrome Linfoproliferativo Autoinmune/genética , Heterocigoto , Humanos , Mielitis Transversa/diagnóstico por imagen , Fenotipo , Receptor fasRESUMEN
A 61-year-old female presented with pancytopenia with a hemoglobin of 7.6 g/dL, platelet count of 26.000/µL and neutrophil count of 525/µL. Bone marrow aspirate showed moderately cellular marrow with a dysplastic erythroid lineage and poor megakaryo- and granulopoiesis without excessive blast count. Trephine biopsy revealed profoundly hypocellular marrow with rare hematopoietic elements. Conventional karyotyping was normal and next generation sequencing revealed no mutations. These findings were compatible with transfusion dependent, non-severe aplastic anaemia (AA) with grade 3 thrombopenia and neutropenia. However, diagnostic workup including CT thorax revealed unexpected sclerotic bone conversions in the spine. Additional whole body SPECT with 99mTc-HDP showed multiple bone lesions in the cervical, thoracic and lumbar spine. CT guided biopsy of D12 surprisingly revealed normal trilineage hematopoiesis. These results were very discrepant from the profoundly hypocellular marrow from the trephine biopsy. It is known that in AA residual hyperactive foci of hematopoiesis can persist; so called 'hot pockets'. MRI is the preferred imaging technique in AA; in most cases a homogeneous fatty bone marrow is found, though some patients present with a heterogeneous marrow with foci of decreased intensity, corresponding with residual foci of hematopoiesis. Imaging studies with PET-CT and PET-MRI confirm these different patterns with respectively homogeneous hypometabolism and hypometabolism with focal hyperproliferation. However, there is no previous literature on the aspect of this focal hematopoiesis on computed tomography. This is the first description of a 'hot pocket' manifesting as a sclerotic bone lesion on CT.
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Anemia Aplásica , Neoplasias Óseas , Pancitopenia , Anemia Aplásica/diagnóstico , Anemia Aplásica/patología , Médula Ósea/patología , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/patología , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed. At diagnosis, liquid biopsies showed detectable copy number alterations in 84.2% of HL (88.6% for classical HL) and 74.1% of DLBCL patients. Copy number profiles between liquid-solid pairs were highly concordant within DLBCL (r=0.815±0.043); and, compared to tissue, HL liquid biopsies had abnormalities with higher amplitudes (P=.010), implying that tumor DNA is more abundant in plasma. Additionally, 39.5% of HL and 13.6% of DLBCL cases had a significantly elevated number of plasmatic Epstein-Barr virus DNA fragments, achieving a sensitivity of 100% compared to current standard. Longitudinal analysis determined that, when detectable, copy number patterns were similar across (re)staging moments in refractory/relapsed patients. Moreover, the overall profile anomaly highly correlated with the total metabolic tumor volume (P.
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Ácidos Nucleicos Libres de Células , Infecciones por Virus de Epstein-Barr , Enfermedad de Hodgkin , Linfoma de Células B Grandes Difuso , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/genética , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genéticaRESUMEN
PURPOSE: To investigate the time-dependent changes in (18)F-FDG uptake by the thymus and marrow following combination chemotherapy for lymphoma in a paediatric study population. METHODS: Included in the study were 27 paediatric patients who were in complete metabolic remission after chemotherapy and who underwent off-therapy follow-up with serial whole-body PET-CT scans. A total of 142 PET-CT scans were recorded. (18)F-FDG uptake by the thymus and marrow was assessed both visually and semiquantitatively. Visual uptake was scored on the three-dimensional maximum intensity projection of the whole-body PET image according to a three-point scale. For the semiquantitative assessment, standard uptake values were measured. To find a pattern in the (18)F-FDG uptake by the thymus and marrow a moving average technique was applied. RESULTS: Our time series analysis indicated that the marrow activity was highest at cessation of chemotherapy and declined thereafter. During an off-chemotherapy period of on average 6 months, marrow activity decreased quickly. From 6 months onward, the activity declined more slowly. The posttherapy changes in (18)F-FDG uptake by the thymus were quite different from the changes in uptake by the marrow. The lowest thymic FDG uptake was found at cessation of chemotherapy. Thereafter, thymic activity steadily increased, reached a peak on average 10 months after therapy, and then slowly decreased. CONCLUSION: Knowledge of the time-dependent changes in metabolic activity in the thymus and marrow is important to avoid misinterpretation of increased (18)F-FDG uptake as disease in the off-therapy setting.
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Médula Ósea/metabolismo , Quimioterapia Combinada , Fluorodesoxiglucosa F18/metabolismo , Linfoma/tratamiento farmacológico , Linfoma/metabolismo , Timo/metabolismo , Adolescente , Transporte Biológico , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Niño , Preescolar , Citocinas/metabolismo , Femenino , Hematopoyesis , Humanos , Linfoma/patología , Masculino , Estudios Retrospectivos , Timo/efectos de los fármacos , Timo/patología , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the correlation between the F-18 FDG uptake in the normal testis as assessed by PET-CT and patient age in a pediatric study population. METHODS: The study population consisted of 22 subjects aged between 9 and 17 years. For these subjects 42 PET-CT scans were available for analysis. The testis was identified on the CT images. Mean standard uptake values and testicular volume were calculated based on manually drawn regions-of-interest over the organ. The correlation between mean SUV and age as well as between testicular volume and age was calculated using Pearson's correlation coefficient. RESULTS: A strong and statistically significant positive correlation between F-18 FDG uptake in the testis and age was documented. The correlation coefficient was 0.406 in the analysis based on 42 PET-CT studies (p = 0.005). The correlation between tracer uptake and age was reassessed based on 22 PET-CT studies including the last recorded PET-CT scan per patient. The correlation coefficient was 0.409 (p = 0.05). In addition, based on 22 PET-CT scans, a strong and statistically significant positive correlation between testicular volume and age was documented (r = 0.67, p < 0.001). CONCLUSION: Whereas it was previously shown that in adult men there was a weak but statistically significant negative correlation between F-18 FDG uptake in the normal testis and age, we found a strong and statistically significant positive correlation in children and teenage boys.