RESUMEN
Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant, pediatric brain tumor typically arising de novo. Inactivation of SMARCB1 is a defining molecular event. We present here a rare case of an adult (35 years) low-grade SMARCB1-deleted brain tumor with transition into prototypical AT/RT over 14 years. Molecular analysis was performed for 3 tumor presentations including copy number analysis, DNA methylation analysis (450k), and whole exome sequencing. We detected the identical somatic SMARCB1 deletion at all 3 time-points. In an unsupervised hierarchical clustering of methylation data together with 127 reference cases comprising 9 brain tumor classes all 3 manifestations clustered with AT/RT. Exome sequencing revealed an increase of mutational burden over time. The acquired mutations and additional copy number changes did not affect known cancer genes. In conclusion, we demonstrate molecular changes associated with histological and clinical transition of a low-grade brain tumor to an adult AT/RT. Our observation of a stable disease course for nearly 10 years in a tumor with SMARCB1 loss and an AT/RT-like DNA methylation profile indicates that caution may be required in the diagnostic interpretation of such findings in adult patients.
Asunto(s)
Neoplasias Encefálicas/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Eliminación de Secuencia/genética , Teratoma/genética , Adulto , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Metilación de ADN/genética , Análisis Mutacional de ADN , Humanos , Estudios Longitudinales , Masculino , Fosfopiruvato Hidratasa/metabolismo , Tumor Rabdoide/diagnóstico por imagen , Tumor Rabdoide/patología , Teratoma/diagnóstico por imagen , Teratoma/patología , Tomógrafos Computarizados por Rayos XRESUMEN
BACKGROUND CONTEXT: 1H magnetic resonance imaging (MRI) of the spine can rule out common causes of low back pain (LBP), such as disc protrusions or nerve root compression; however, no significant causal relation exists between morphology and the extent of symptoms. Functional MRI techniques, such as 23Na, may provide additional information, allowing indirect assessment of vertebral glycosaminoglycan concentrations, decreases in which are associated with early degenerative changes. PURPOSE: To evaluate 23Na-MRI of asymptomatic healthy volunteers and symptomatic patients with LPB and correlate the results to the Pfirrmann classification of MRI disc morphology. STUDY DESIGN: Retrospective cohort study at an academic medical center. PATIENT SAMPLE: Two groups were studied: (1) 55 healthy volunteers (31 men, 24 women; mean age 28.8 years) and (2) 12 patients (6 men, 6 women; mean age: 35.3 years) with a recent history of LBP. METHODS: Lumbar spines of the aforementioned groups were examined on a 3.0 T MRI scanner with morphological 1H and 23Na imaging. Intervertebral disc (IVD) 23Na at each level was normalized (23Nanorm). Distribution and differences between mean 23Nanorm corresponding to each Pfirrmann classification were evaluated in the two study groups (analysis of variance). Linear correlations between 23Nanorm, body mass index (BMI), and age were assessed (Pearson correlation coefficient). Gender-dependent differences were evaluated (paired t test). OUTCOME MEASURES: Physiological measure: IVD 23Nanorm as determined by 23Na-MRI. RESULTS: A normal distribution of 23Nanorm was confirmed for both groups (p=.072 and p=.073, respectively). The mean Pfirrmann score statistically significantly differed between them (p<.0001). 23Nanorm was statistically significantly reduced in degenerated IVDs (Pfirrmann scores 4+5) (p<.0001). No statistically significant differences were seen for the mean 23Nanorm of IVDs with the same Pfirrmann score in healthy volunteers and patients (.469Asunto(s)
Degeneración del Disco Intervertebral/patología
, Disco Intervertebral/anatomía & histología
, Disco Intervertebral/patología
, Dolor de la Región Lumbar/etiología
, Vértebras Lumbares/anatomía & histología
, Vértebras Lumbares/patología
, Imagen por Resonancia Magnética/métodos
, Adulto
, Cationes
, Femenino
, Glicosaminoglicanos/metabolismo
, Voluntarios Sanos
, Humanos
, Disco Intervertebral/metabolismo
, Degeneración del Disco Intervertebral/complicaciones
, Degeneración del Disco Intervertebral/metabolismo
, Vértebras Lumbares/metabolismo
, Masculino
, Persona de Mediana Edad
, Radiculopatía/patología
, Estudios Retrospectivos
, Sodio