RESUMEN
BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. METHODS: We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. RESULTS: The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. CONCLUSIONS: Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Imagen por Resonancia Magnética/métodos , Mutación , Neoplasias Neuroepiteliales/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Niño , Metilación de ADN , Femenino , Humanos , Masculino , Neoplasias Neuroepiteliales/genética , Neoplasias Neuroepiteliales/metabolismo , Pronóstico , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Tasa de SupervivenciaRESUMEN
Solid-pseudopapillary neoplasm of the pancreas is a very rare tumor. It most commonly occurs in young women and has unique pathologic features. Previous immunohistochemical studies demonstrated that most solid-pseudopapillary neoplasms were immunoreactive with antibodies directed against vimentin and neuron-specific enolase. Recently, expression of CD10 and CD56 in this tumor has been reported. In this report, we expanded the demographic profile, highlighting 3 cases of solid-pseudopapillary neoplasm of the pancreas that presented in an elderly woman, a young man, and a young woman and further characterized them histologically and immunophenotypically. Grossly, all 3 tumors were well circumscribed and had a variable degree of cystic formation, necrosis, and hemorrhage. Microscopically, these tumors were characterized by a pseudopapillary pattern of epithelioid cells arranged around a delicate fibrovascular core with sheets of bland epithelioid cells filling cystic spaces. Hyaline globules, cholesterol granulomas, and foamy cells were all seen to be common findings. Although these 3 tumors were strongly immunoreactive for vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, neuron-specific enolase, CD10, CD56, and progesterone receptor, they demonstrated only variable "positivity" for epithelial membrane antigen and broad-spectrum cytokeratin, but were being consistently nonreactive for synaptophysin, insulin, glucogon, chromogranin A, and estrogen receptor. Interestingly, 2 of the 3 tumors were S-100 protein and melanin A reactive but were nonreactive for HMB45.