The role of methylation profiling in histologically diagnosed neurocytoma: a case series

Abstract

Purpose To highlight the clinical, neuroradiographic, neuropathologic, and molecular features of histologically identified neurocytoma in a pediatric cohort and highlight the evolving use methylation profiling in providing diagnostic clarity in difficult to diagnosis pediatric brain tumors. Methods Five consecutive children (ages 9–13, 2 girls 3 boys) were histologically diagnosed with neurocytoma at Rady Children’s Hospital San Diego from 2012 to 2018. Clinical and molecular features were analyzed with regards to treatment course and outcome. Results Presenting symptoms included seizures (n = 2), syncope (n = 1), headache (n = 2), visual disturbances (n = 2) and emesis (n = 2). Tumor location included intraventricular (n = 2), intraventricular with parenchymal spread (n = 1), and extraventricular (n = 2). Magnetic resonance imaging demonstrated reduced diffusivity (2/5), signal abnormality on susceptibility-weighted sequences (3/5), and varying degrees of contrast enhancement (4/5). All patients underwent surgical resection alone. Recurrence occurred in four children that were treated with surgery (4/4), adjuvant radiation (2/4), and chemoradiation (1/4). Neuropathologic features included positivity for GFAP (4/5), synaptophysin (4/5), NSE (2/2), NeuN (4/4), and variable Ki-67 (< 1% to 15%). Next generation sequencing (3/5) and microarray (3/5) collectively were abnormal in four of five tumors. Methylation profiling was successfully performed on four of five samples which led to modification of diagnosis in two patients and the others were either unclassifiable or confirmatory with the histologic diagnosis. Mean time to follow up was 77 months (range 44–112 months). Mean progression free survival and overall survival were 24 months (range 6 to 52 months) and 100% respectively. Conclusion Neurocytomas are a rare clinical entity that warrants further investigation into molecular and pathologic prognosticating features. Methylation profiling may aid in differentiation of neurocytoma from other difficult to diagnose tumors who share similar histologic features.

Central neurocytoma—positive and differential diagnosis: An example through a case report

“…And high levels of MIB-1 (cell proliferation marker), which is a monoclonal antibody against Ki-67, are now thought to be consistent with atypical forms and is considered as the best predictor of proliferative potential and recurrence risk with a cut-off value of 2%–3%. 27 – 29 …”

“…And high levels of MIB-1 (cell proliferation marker), which is a monoclonal antibody against Ki-67, are now thought to be consistent with atypical forms and is considered as the best predictor of proliferative potential and recurrence risk with a cut-off value of 2%-3%. [27][28][29] Although CN is graded as one of "WHO 2" tumors according to the latest classification, it is assumed that those with an aggressive behavior and a higher cutoff of MIB-1 labeling indices (LI) of 10% associated with cellular atypia represent much more a "WHO grade 3." 29 Thus, reported relapse rates are highly variable from 22% with a labeling index of MIB less than 2% till 63% when higher than it.…”

Intraventricular central neurocytoma molecularly defined as extraventricular neurocytoma: A case representing the discrepancy between clinicopathological and molecular classifications.

“…Another hypothesis is that CN can present with molecular features of EVN. Next-generation sequencing and methylation pro ling modi ed the histological diagnosis of CN into ganglioglioma in two cases in a certain cohort [5]. Also, methylation pro ling modi ed the histological diagnosis of EVN into diffuse leptomeningeal glioneuronal tumor, rosette-forming glioneuronal tumor, pilocytic astrocytoma, oligodendroglioma, astrocytoma, diffuse midline glioma H3K27M-mutant and glioblastoma in thirteen cases in another cohort [13].…”

“…Although several chromosomal and genetic aberrations have been observed, the distinguishing molecular features of CN have not been well characterized for decades [1]. Recently, methylation pro ling has emerged as a powerful tool in con rming the diagnosis of CN and enabled differentiation from other tumors with similar histological features [5]. Extraventricular neurocytoma (EVN) is a clinicopathological entity that presents similar histopathological features to CN, albeit it arises from extra-ventricular parenchymal tissue [13].…”

Intraventricular central neurocytoma molecularly defined as extraventricular neurocytoma: a case representing the discrepancy between clinicopathological and molecular classifications

“…Although several chromosomal and genetic aberrations have been observed, the distinguishing molecular features of CN have not been well-characterized for decades [ 1 ]. Recently, methylation profiling has emerged as a powerful tool in confirming the diagnosis of CN and enabled differentiation from other tumors with similar histological features [ 8 ]. Extraventricular neurocytoma (EVN) is a clinicopathological entity that presents similar histopathological features to CN, albeit it arises from extra-ventricular parenchymal tissue [ 19 ].…”