Polymorphous Low-Grade Neuroepithelial Tumor of the Young (PLNTY): Molecular Profiling Confirms Frequent MAPK Pathway Activation

Abstract

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5–52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.

2021 updates to the World Health Organization classification of adult-type and pediatric-type diffuse gliomas: a clinical practice review

“…PLNTY is a new tumor in the updated CNS WHO classification. PLNTY is a diffusely infiltrating glioma that occurs mostly in children and young adults with epilepsy but has been diagnosed in older patients in their fourth or fifth decade (56)(57)(58). PLNTY occur in the cerebral hemispheres and involve cortex and subcortical white matter.…”

“…Microvascular proliferation and necrosis are not seen. Foci of neoplastic neuronal cells may be encountered, and it remains to be determined if PLNTY would be best classified as a glioneuronal tumors (58). The tumor cells are immunoreactive for OLIG2, and show variable immunoreactivity for GFAP.…”

“…PLNTY are MAPK pathway driven tumors (58). BRAF V600E mutations are commonly identified in tumors from older patients while younger patients often have FGFR fusions, most often with FGFR2 or FGFR3 (56,58,60). Mutations in IDH, ATRX and TP53 are not in keeping with the diagnosis of PLNTY.…”

Unusual low-grade neuroepithelial tumour with novel PDGFRA mutation

“…polymorphous low-grade neuroepithelial tumour of the young. 7 Given the novelty in the genetic mutation, the role and significance the PDGFRA p.K385-mutant plays in tumour growth is unknown.…”

Clinical, Radiological, Pathological Features and Seizure Outcome With Surgical Management of Polymorphous Low-Grade Neuroepithelial Tumor of the Young Associated With Epilepsy

“…Polymorphous low-grade neuroepithelial tumor of the young (PLNTY), a rare variant of the low-grade neuroepithelial tumor, was first described in 2017 by Huse et al (1). Till now, only approximately 55 cases of PLNTY have been reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Similar to ganglioglioma (GG), oligodendroglioma, pleomorphic xanthoastrocytoma (PXA), and dysembryoplastic neuroepithelial tumor (DNET), PLNTY was also defined as a member of long-term epilepsy-associated brain tumors (LEATs) or epileptomas (15,16).…”