RESUMEN
BACKGROUND AND PURPOSE: T2-FLAIR mismatch is a highly specific imaging biomarker of IDH-mutant diffuse astrocytoma in adults. It has however also been described in MYB/MYBL1-altered low grade tumors. Our aim was to assess the diagnostic power of the T2-FLAIR mismatch in IDH-mutant astrocytoma and MYB/MYBL1-altered low-grade tumors in children and correlate this mismatch with histology. MATERIALS AND METHODS: We evaluated MR imaging examinations of all pediatric patients, performed at the Princess Máxima Center for Pediatric Oncology and the University Medical Center Utrecht between January 2012 and January 2023, with the histomolecular diagnosis of IDH-mutant astrocytoma, diffuse astrocytoma MYB/MYBL1-altered, or angiocentric glioma, and the presence of T2-FLAIR mismatch was assessed. Histologically, the presence of microcysts in the tumor (a phenomenon suggested to be correlated with T2-FLAIR mismatch in IDH-mutant astrocytomas in adults) was evaluated. RESULTS: Nineteen pediatric patients were diagnosed with either IDH-mutant astrocytoma (n = 8) or MYB/MYBL1-altered tumor (n = 11: diffuse astrocytoma, MYB- or MYBL1-altered n = 8; or angiocentric glioma n = 3). T2-FLAIR mismatch was present in 11 patients, 3 (38%) in the IDH-mutant group and 8 (73%) in the MYB/MYBL1 group. No correlation was found between T2-FLAIR mismatch and the presence of microcysts or an enlarged intercellular space in either IDH-mutant astrocytoma (P = .38 and P = .56, respectively) or MYB/MYBL1-altered tumors (P = .36 and P = .90, respectively). CONCLUSIONS: In our pediatric population, T2-FLAIR mismatch was more often found in MYB/MYBL1-altered tumors than in IDH-mutant astrocytomas. In contrast to what has been reported for IDH-mutant astrocytomas in adults, no correlation was found with microcystic changes in the tumor tissue. This finding challenges the hypothesis that such microcystic changes and/or enlarged intercellular spaces in the tissue of these tumors are an important part of explaining the occurrence of the T2-FLAIR mismatch.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Proteínas Proto-Oncogénicas c-myb , Humanos , Astrocitoma/diagnóstico por imagen , Astrocitoma/genética , Astrocitoma/patología , Niño , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Masculino , Femenino , Adolescente , Preescolar , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/patología , Imagen por Resonancia Magnética/métodos , Proteínas Proto-Oncogénicas c-myb/genética , Transactivadores/genética , Biomarcadores de Tumor/genética , Isocitrato Deshidrogenasa/genética , Lactante , Mutación , Estudios Retrospectivos , Proteínas Proto-OncogénicasRESUMEN
Central nervous system tumours represent one of the most lethal cancer types, particularly among children1. Primary treatment includes neurosurgical resection of the tumour, in which a delicate balance must be struck between maximizing the extent of resection and minimizing risk of neurological damage and comorbidity2,3. However, surgeons have limited knowledge of the precise tumour type prior to surgery. Current standard practice relies on preoperative imaging and intraoperative histological analysis, but these are not always conclusive and occasionally wrong. Using rapid nanopore sequencing, a sparse methylation profile can be obtained during surgery4. Here we developed Sturgeon, a patient-agnostic transfer-learned neural network, to enable molecular subclassification of central nervous system tumours based on such sparse profiles. Sturgeon delivered an accurate diagnosis within 40 minutes after starting sequencing in 45 out of 50 retrospectively sequenced samples (abstaining from diagnosis of the other 5 samples). Furthermore, we demonstrated its applicability in real time during 25 surgeries, achieving a diagnostic turnaround time of less than 90 min. Of these, 18 (72%) diagnoses were correct and 7 did not reach the required confidence threshold. We conclude that machine-learned diagnosis based on low-cost intraoperative sequencing can assist neurosurgical decision-making, potentially preventing neurological comorbidity and avoiding additional surgeries.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Toma de Decisiones Clínicas , Aprendizaje Profundo , Cuidados Intraoperatorios , Análisis de Secuencia de ADN , Niño , Humanos , Neoplasias del Sistema Nervioso Central/clasificación , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/cirugía , Toma de Decisiones Clínicas/métodos , Aprendizaje Profundo/normas , Cuidados Intraoperatorios/métodos , Metilación , Estudios Retrospectivos , Análisis de Secuencia de ADN/métodos , Factores de TiempoRESUMEN
BACKGROUND: Blueberry muffin is a descriptive term for a neonate with multiple purpuric skin lesions. Many causes are known, amongst them life-threatening diseases like congenital infections or leukemia. Indeterminate cell histiocytosis (ICH) is an exceptionally rare cause of blueberry muffin rash. ICH is a histiocytic disorder which can be limited to the skin or can present with systemic involvement. A mutation that has been described in histiocytic disorders is a MAP2K1 mutation. In ICH, this mutation has previously been described in merely one case. CASE PRESENTATION: A term male neonate was admitted to the neonatology ward directly after birth because of a blueberry muffin rash. ICH was diagnosed on skin biopsy. The lesions resolved spontaneously. The patient is currently 3 years old and has had no cutaneous lesions or systemic involvement so far. This disease course is similar to that of the Hashimoto-Pritzker variant of LCH. CONCLUSIONS: ICH can manifest in neonates as resolving skin lesions. It is limited to the skin in most cases, but systemic development is possible. Therefore, it is essential to confirm the diagnosis with a biopsy before the lesions resolve and to monitor these patients closely with routine follow-up.