A case of recurrent epilepsy‐associated rosette‐forming glioneuronal tumor with anaplastic transformation in the absence of therapy

Abstract

Rosette‐forming glioneuronal tumor (RGNT) most commonly occurs adjacent to the fourth ventricle and therefore rarely presents with epilepsy. Recent reports describe RGNT occurrence in other anatomical locations with considerable morphologic and genetic overlap with the epilepsy‐associated dysembryoplastic neuroepithelial tumor (DNET). Examples of RGNT or DNET with anaplastic change are rare, and typically occur in the setting of radiation treatment. We present the case of a 5‐year‐old girl with seizures, who underwent near total resection of a cystic temporal lobe lesion. Pathology showed morphologic and immunohistochemical features of RGNT, albeit with focally overlapping DNET‐like patterns. Resections of residual or recurrent tumor were performed 1 year and 5 years after the initial resection, but no adjuvant radiation or chemotherapy was given. Ten years after the initial resection, surveillance imaging identified new and enhancing nodules, leading to another gross total resection. This specimen showed areas similar to the original tumor, but also high‐grade foci with oligodendroglial morphology, increased cellularity, palisading necrosis, microvascular proliferation, and up to 13 mitotic figures per 10 high power fields. Ancillary studies the status by sequencing showed wild‐type of the isocitrate dehydrogenase 1 (IDH1), IDH2, and human histone 3.3 (H3F3A) genes, and BRAF studies were negative for mutation or rearrangement. Fluorescence in situ hybridization (FISH) showed codeletion of 1p and 19q limited to the high‐grade regions. By immunohistochemistry there was loss of nuclear alpha‐thalassemia mental retardation syndrome, X‐linked (ATRX) expression only in the high‐grade region. Next‐generation sequencing showed an fibroblast growth factor receptor receptor 1 (FGFR1) kinase domain internal tandem duplication in three resection specimens. ATRX mutation in the high‐grade tumor was confirmed by sequencing which showed a frameshift mutation (p.R1427fs), while the apparent 1p/19q‐codeletion by FISH was due to loss of chromosome arm 1p and only partial loss of 19q. Exceptional features of this case include the temporal lobe location, 1p/19q loss by FISH without true whole‐arm codeletion, and anaplastic transformation associated with ATRX mutation without radiation or chemotherapy.

Rosette‐forming glioneuronal tumor of the fourth ventricle; A case report and review of the literature

“…2,4 Cases of RGNT, located in cerebral hemispheres, just like other supratentorial brain tumors, were associated with epileptic seizures. [31][32][33] The histogenesis of RGNT is, to date, unclear. The presumed origin of the RGNT is the pluripotent cells of the subependymal plate (periventricular germinal matrix), which have also been suggested as the site of origin of DNTs of the cerebellum.…”

“… 2 , 4 Cases of RGNT, located in cerebral hemispheres, just like other supratentorial brain tumors, were associated with epileptic seizures. 31 , 32 , 33…”

Pediatric low-grade glioma models: advances and ongoing challenges

“…There are multiple types of FGFR1 alterations described in pLGGs including tyrosine kinase domain duplication ( FGFR1 TKDD), fusions ( FGFR1-TACC1 ), and FGFR1 hotspot mutations (N546K and K656E). FGFR1 TKDD appears to be largely absent in high-grade gliomas (HGG ( 10 ), but it’s been reported in rosette-forming glioneuronal tumor (RGNT), anaplastic PA, glioneuronal tumor with PA and PXA features ( 34 , 35 ). FGFR1 TKDD includes exons 10-18, producing an in-frame fusion and duplicates the entire FGFR1 region encoding tyrosine kinase domain ( 10 , 13 , 36 ).…”

FGFR- gene family alterations in low-grade neuroepithelial tumors

“…Since then, the association of FGFR1-TKDD with anaplastic histologic features has proven to be an exceedingly rare phenomenon. One reported case of a rosette forming glioneuronal tumor (RGNT) having focal DNETlike features exhibited multiple local recurrences over a ten-year period, ultimately demonstrated elevated mitoses and high-grade histology, and was shown to harbor FGFR1-TKDD in addition to a frameshift mutation in ATRX [33]. Additionally, a glioneuronal tumor with features of pilocytic astrocytoma and pleomorphic xanthoastrocytoma also harboring FGFR1-TKDD was reported to demonstrate focally elevated mitotic activity; molecular characterization revealed multiple additional variants of unknown significance [3].…”