Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis

Abstract

Diffuse leptomeningeal glioneuronal tumours (DLGNT) represent rare enigmatic CNS tumours of childhood. Most patients with this disease share common radiological and histopathological features but the clinical course of this disease is variable. A radiological hallmark of this disease is widespread leptomeningeal enhancement that may involve the entire neuroaxis with predilection for the posterior fossa and spine. The classic pathologic features include low- to moderate-density cellular lesions with OLIG2 expression and evidence of ‘oligodendroglioma-like’ appearance. The MAPK/ERK signaling pathway has recently been reported as a potential driver of tumourigenesis in up to 80% of DLGNT with KIAA1549:BRAF fusions being the most common event seen. Until now, limited analysis of the biological drivers of tumourigenesis has been undertaken via targeted profiling, chromosomal analysis and immunohistochemistry. Our study represents the first examples of comprehensive genomic sequencing in DLGNT and shows that it is not only feasible but crucial to our understanding of this rare disease. Moreover, we demonstrate that DLGNT may be more genomically complex than single-event MAPK/ERK signaling pathway tumours.

Cerebrospinal fluid cytology findings in a case of diffuse leptomeningeal glioneuronal tumour

“…5 CSF analysis typically reveals a mild hyperproteinaemia and lymphocyte pleocytosis, and is done to exclude an infectious aetiology; tumour cells are rarely identified. 3,6 To date only two other case reports of DLGNT have described neoplastic cells in the CSF. 5,7 In both, however, the supportive cytology findings emerged later in the disease, subsequent to histopathological diagnosis, and were therefore not critical in guiding work-up.…”

“…This is challenging; tumour material from biopsies is typically sparse and initial biopsies are frequently non‐diagnostic 2 . Cytological diagnosis via cerebrospinal fluid (CSF) is pragmatically more feasible; however, existing cases have largely failed to identify neoplastic cytology 2–4 . We report a case of DLGNT in which CSF analysis determined the diagnosis and guided subsequent work‐up.…”

“…2 Cytological diagnosis via cerebrospinal fluid (CSF) is pragmatically more feasible; however, existing cases have largely failed to identify neoplastic cytology. [2][3][4] We report a case of DLGNT in which CSF analysis determined the diagnosis and guided subsequent work-up.…”

Clinical progression, pathological characteristics, and radiological findings in children with diffuse leptomeningeal glioneuronal tumors: A systematic review

“…Additionally, DLGNTs have been associated with KIAA1549-BRAF gene fusion and 1p deletion or 1p/19q co-deletion (2,3). Given the rarity of this tumor type, its histological, radiological, and clinical features and pattern of progression remain to be fully elucidated (4).…”

“…Although they frequently occur as leptomeningeal tumors (5), some studies have reported DLGNTs without leptomeningeal dissemination, which manifests as intraspinal or intracerebral cystic or solid masses (6)(7)(8). Notably, clinical follow-up is often incomplete, and some patients present with indolent chronic disease while others experience an aggressive clinical course (4). Moreover, the differential diagnosis often includes tuberculous meningitis, cryptococcal neoformans meningitis, and meningeal metastatic tumor.…”