CNS & pituitary tumors

• Oligodendrocyte-like tumor cells in myxoid stroma
• Located in septum pellucidum, septal nuclei, corpus callosum or periventricular white matter
• PDGFRA p.K385L/I dinucleotide mutation or other mutation in extracellular domain of PDGFRA (Acta Neuropathol 2018;136;339, Brain Pathol 2020;30:479)
• Corresponds to CNS WHO grade 1

• PDGFRA mutation as solitary genetic driver
• PDGFRA alterations localize in Ig-like C2 type domain, especially in the K385 residue, in the extracellular ligand binding domain portion of the receptor tyrosine kinase (Neuro Oncol 2019;21:800, Brain Pathol 2020;30:479)
• Results in substitution from a basic amino acid (lysine) to a hydrophobic amino acid (leucine or isoleucine) (Brain Pathol 2020;30:479)
• Possibly an oncogenic, gain of function mutation causing constitutive activation of the intracellular kinase domain (Brain Pathol 2020;30:479)

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Contributed by Gabrielle Yeaney, M.D.

Contributed by Gabrielle Yeaney, M.D.

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A 25 year old man has a brain mass in the septum pellucidum, which shows T2 hyperintensity on MRI. The man undergoes a biopsy of the mass. The histology of the lesion is shown in the images above. What is the expected pattern of immunoreactivity?

1. GFAP negative, Olig2 negative, NeuN diffusely positive
2. GFAP negative, Olig2 positive, NeuN focally positive
3. GFAP positive, Olig2 positive, NeuN focally positive
4. GFAP positive, Olig2 positive, NeuN negative

C. GFAP positive, Olig2 positive, NeuN focally positive. Myxoid glioneuronal tumors (MGNT) are diffusely positive for Olig2 and GFAP in bland round oligodendrocyte-like cells. NeuN highlights focal neuronal components (also known as floating neurons). Answer D is incorrect because it is the expected pattern of immunoreactivity for most gliomas including pilocytic astrocytoma or oligodendroglioma. Answer A is incorrect because it is possibly a pattern of immunoreactivity for gangliocytoma or possibly central neurocytoma. Answer B is incorrect because it is the expected pattern of immunoreactivity for dysembryoplastic neuroepithelial tumor. GFAP is typically limited to entrapped reactive astrocytes in cortical dysembryoplastic neuroepithelial tumor (DNT), a useful feature to differentiate it from MGNT, which is diffusely positive for GFAP.

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Reference: Myxoid glioneuronal tumor

An 11 year old girl undergoes a brain biopsy that reveals a tumor composed of bland round nuclei with abundant myxoid matrix. Immunohistochemical stains show that the tumor is positive for SOX10, Olig2, GFAP and has occasional scattered synaptophysin positive neurons within the myxoid matrix. Molecular studies reveal PDGFRA p.K385L/I mutation. What is the most common location of this neoplasm?

1. Brain stem
2. Cerebellar
3. Dural / leptomeningeal
4. Intraventricular
5. Superficial cortical

D. Intraventricular. The question describes the morphologic, immunophenotypic and molecular features of myxoid glioneuronal tumor. Myxoid glioneuronal tumor is genetically characterized by dinucleotide mutation at codon 385 of the PDGFRA p.K385L/I dinucleotide mutation or (less commonly) other mutations in the extracellular ligand binding domain of the protein. These tumors occur primarily in or near the intraventricular region including septum pellucidum, septal nuclei, corpus callosum or periventricular white matter. Rosette forming glioneuronal tumors may have similar histology and location but would show different molecular features (FGFR1 mutation, PIK3CA or NF1 mutation). Answers A and B are incorrect because a tumor with this profile (such as pilocytic astrocytoma) would have different molecular features such as KIAA1549::BRAF fusion. Answer C is incorrect because although this may sound morphologically similar to diffuse leptomeningeal glioneuronal tumor (DLGNT), such a tumor would be expected to have 1p deletion and MAPK pathway alteration such as KIAA1549::BRAF fusion. Answer E is incorrect because the superficial cortex would be an unusual location for myxoid glioneuronal tumor.

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Reference: Myxoid glioneuronal tumor