A 38-year-old man presents with a 3-month history of focal seizures and headache. MRI brain shows a T2/FLAIR hyperintense, calcified frontal lobe mass with indistinct margins. Histopathology reveals "fried-egg" cells with a "chicken-wire" capillary network. The molecular signature marked **B** in the diagram (1p/19q codeletion) is confirmed on FISH analysis, along with IDH1 R132H positivity. Which of the following best describes the diagnostic and prognostic significance of the molecular signature marked **B**?
A. Represents an astrocytoma IDH-mutant without 1p/19q codeletion, requiring different management and carrying intermediate prognosis
B. Indicates a secondary glioblastoma with IDH mutation and predicts poor prognosis similar to primary glioblastoma (median OS 12–18 months)
C. Confirms EGFR amplification-driven glioblastoma with rapid progression and resistance to standard chemotherapy
D. Defines oligodendroglioma and confers the most favorable prognosis among adult diffuse gliomas, with median overall survival >15 years for grade 2 disease
Explanation
Why option 1 is right
The molecular signature marked B — whole-arm 1p/19q codeletion in the context of IDH mutation — is the obligate defining feature of oligodendroglioma according to WHO 2021 CNS classification. This combination is pathognomonic and confers the most favorable prognosis of all adult diffuse gliomas. Grade 2 oligodendrogliomas with 1p/19q codeletion achieve median overall survival exceeding 15 years, and grade 3 disease achieves 10–15 years — dramatically superior to glioblastoma. The presence of both IDH1 R132H and 1p/19q codeletion in this patient's tumor definitively establishes the diagnosis and excellent long-term outlook (WHO CNS 2021; Cairncross J Clin Oncol RTOG 9802 2013).
Why each distractor is wrong
Option 2: Secondary glioblastoma is a rare entity arising from lower-grade glioma; the presence of 1p/19q codeletion actually excludes glioblastoma diagnosis entirely. Glioblastomas are defined by TP53 and EGFR/PTEN alterations, not 1p/19q loss. Prognosis is vastly superior to glioblastoma (>15 years vs 12–18 months).
Option 3: An IDH-mutant astrocytoma (without 1p/19q codeletion) is a distinct WHO entity with different molecular profile and worse prognosis than oligodendroglioma. The presence of 1p/19q codeletion explicitly rules out astrocytoma diagnosis and defines oligodendroglioma instead.
Option 4: EGFR amplification is the hallmark of glioblastoma, not oligodendroglioma. The molecular signature marked B (1p/19q codeletion) is mutually exclusive with EGFR-amplified glioblastoma and carries a far superior prognosis.
High-YieldNEET PG
Oligodendroglioma = IDH mutant + 1p/19q codeleted = best glioma prognosis (>15 years grade 2); without 1p/19q codeletion, it is astrocytoma IDH-mutant with worse outcome.
WHO CNS 2021; Cairncross J Clin Oncol RTOG 9802 2013
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