oligodendroglioma_idh-mutant_and_1p_19q-codeleted

Oligodendroglioma IDH-mutant and 1p/19q-codeleted


In 2021, the World Health Organization published the fifth edition of the Classification of Tumors of the Central Nervous System. This classification incorporates advances in understanding the molecular pathogenesis of brain tumors with histopathology in order to group tumors into more biologically and molecularly defined entities. The previous broad category of adult-type diffuse gliomas has been consolidated into 3 types: astrocytoma, isocitrate dehydrogenase (IDH) mutant; oligodendroglioma, IDH mutant and 1p/19q codeleted; and glioblastoma, IDH wild type. These major changes are driven by IDH mutation status and include the restriction of the diagnosis of glioblastoma to tumors that are IDH wild type; the reclassification of tumors previously diagnosed as IDH-mutated glioblastomas as astrocytomas IDH mutated, grade 4; and the requirement for the presence of IDH mutations to classify tumors as astrocytomas or oligodendrogliomas 1)

● slow growing tumor that frequently presents with seizures

● occur primarily in adults, predilection for the frontal lobes

● by definition: a diffusely infiltrating glioma with codeletion of BOTH chromosome arms 1p AND 19q, AND mutation of IDH1 OR IDH2

● histology: classic features of “fried egg” cytoplasm (on permanent pathology) & “chicken wire” vas- culature are unreliable. Calcifications are common

● recommended treatment: as for WHO grade II astrocytic tumors


Arise in the frontal lobe in > 50% of cases.

Moderately cellular tumor composed of cells resembling oligodendroglial cells (uni- form, round nuclei).

A diffusely infiltrating glioma with IDH1 or IDH2 mutation and codeletion of chromosome arms 1p & 19q.

Tumors show moderate cellularity. Cells with monotonous round nuclei (often in cellular sheets) with an eccentric rim of eosinophilic cytoplasm lacking obvious cell processes are the most consis- tent features.

73% of tumors have microscopic calcifications.58 Isolated tumor cells consistently penetrate largely intact parenchyma; an associated solid tumor component may or may not be present.59 When a solid portion is present, permanent (paraffin) pathology demonstrates lucent perinuclear halos, giving a “fried egg” appearance (actually an artifact of formalin fixation, which is not present on frozen section and may make diagnosis difficult on frozen). A “chicken-wire” vascular pattern has also been described.60 These features are variable.

Nuclear atypia and an occasional mitotic figure is compatible with the diagnosis.5 Compare to WHO grade III anaplastic oligodendroglioma, IDH-mutant 1p/19q codeleted .

16% of hemispheric ODGs are cystic58 (cysts form from coalescence of microcysts from microhe- morrhages, unlike astrocytomas, which actively secrete fluid).

GFAP staining: Since most ODGs contain microtubules instead of glial filaments,61 ODGs usually do not stain for GFAP, although some do. In mixed gliomas, the astrocytic component may stain for GFAP.

Metastases reportedly occur in 8–14%, mainly as a microscopic finding, but 1% may be a more realistic estimate. Symptomatic spinal metastases (drop mets) are even more uncommon.

Fluorescein-guided stereotactic biopsy increases the likelihood of definitive neuropathological diagnosis, and the number needed to sample can be reduced by 50% in contrast-enhancing lesions 2)

A strong recommendation for close surveillance alone was made for patients with oligodendroglioma, IDH-mutant, 1p/19q codeleted, WHO grade 2 after gross total resection without high-risk features. For oligodendroglioma, WHO grade 2 with any high-risk features, adjuvant RT was conditionally recommended. However, adjuvant RT was strongly recommended for oligodendroglioma, WHO grade 3. A conditional recommendation for close surveillance alone was made for astrocytoma, IDH-mutant, WHO grade 2 after gross total resection without high-risk features. Adjuvant RT was conditionally recommended for astrocytoma, WHO grade 2, with any high-risk features and strongly recommended for astrocytoma, WHO grade 3. Dose recommendations varied based on histology and grade. Given known adverse long-term effects of RT, consideration for advanced techniques such as intensity modulated radiation therapy/volumetric modulated arc therapy or proton therapy were given as strong and conditional recommendations, respectively. Finally, based on expert opinion, the guideline recommends assessment, surveillance, and management for toxicity management 3)

Median survival with ODG, IDH-mutant & 1p/19q codeletion is 8 years. Codeletion of 1p/19q by itself is also associated with longer median survival. compared to 6.4 years with diffuse astrocytoma, IDH mutant. Also, WHO grade II is an independent favorable prognosticator compared to WHO grade III ana- plastic ODG.

A case of an oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and LS with a germline pathogenic PMS2 mutation. To our knowledge, this has only been reported in a few cases in the literature. While the family history is less typical of LS, previous studies have indicated the absence of a significant family history in patient cohorts with PMS2 mutations due to its low penetrance. Notably, only a handful of studies have worked on characterizing PMS2 mutations in LS, and even fewer have looked at these mutations in the context of brain tumor development. This report aims to add to the limited literature on germline PMS2 mutations and oligodendrogliomas. It highlights the importance of genetic testing in neuro-oncology 4).


1)
Berger TR, Wen PY, Lang-Orsini M, Chukwueke UN. World Health Organization 2021 Classification of Central Nervous System Tumors and Implications for Therapy for Adult-Type Gliomas: A Review. JAMA Oncol. 2022 Oct 1;8(10):1493-1501. doi: 10.1001/jamaoncol.2022.2844. PMID: 36006639.
2)
Xu R, Rösler J, Teich W, Radke J, Früh A, Scherschinski L, Onken J, Vajkoczy P, Misch M, Faust K. Correlation of Tumor Pathology with Fluorescein Uptake and MRI Contrast-Enhancement in Stereotactic Biopsies. J Clin Med. 2022 Jun 10;11(12):3330. doi: 10.3390/jcm11123330. PMID: 35743401; PMCID: PMC9225185.
3)
Halasz LM, Attia A, Bradfield L, Brat DJ, Kirkpatrick JP, Laack NN, Lalani N, Lebow ES, Liu AK, Niemeier HM, Palmer JD, Peters KB, Sheehan J, Thomas RP, Vora SA, Wahl DR, Weiss SE, Yeboa DN, Zhong J, Shih HA. Radiation Therapy for IDH-Mutant Grade 2 and Grade 3 Diffuse Glioma: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2022 Sep-Oct;12(5):370-386. doi: 10.1016/j.prro.2022.05.004. Epub 2022 May 31. PMID: 35902341.
4)
Merchant M, Raygada M, Pang Y, Quezado M, Raffeld M, Xi L, Kim J, Tyagi M, Abdullaev Z, Kim O, Sergi Z, Pillai T, Ozer B, Zaghloul K, Heiss JD, Armstrong TS, Gilbert MR, Aldape K, Wu J. Case report: Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, associated with a germline mutation in PMS2. Front Oncol. 2022 Aug 2;12:954879. doi: 10.3389/fonc.2022.954879. PMID: 35982947; PMCID: PMC9379095.
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  • Last modified: 2022/12/20 14:04
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