Case Presentation

Clinical Presentation

Mr. D, age 59 and previously healthy, began having cognitive problems, including word-finding difficulty and increasing difficulty with crossword puzzles. His cognitive problems worsened slowly over 3 weeks, eventually progressing to aphasia and apraxia. Mr. D had not experienced any preceding trauma, headaches, or seizure-like activity. He was afebrile with no systemic signs of infection.

Diagnostic Testing

On neurologic examination, Mr. D was able to recall only 1 of 3 items at 5 minutes and had word-finding difficulties. No other focal findings were present and his laboratory results were unremarkable. Brain MRI revealed a large heterogeneously enhancing left temporal lesion with mass effect on T1-postcontrast imaging with significant surrounding vasogenic edema on fluid attenuated inversion recovery (FLAIR) imaging. (Figure 1).

Figure 1: Axial MRI at initial presentation. T1 postcontrast imaging (A), fluid-attenuated inversion recovery (FLAIR) imaging (B).

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Figure 1: Axial MRI at initial presentation. T1 postcontrast imaging (A), fluid-attenuated inversion recovery (FLAIR) imaging (B).

Pathology Findings

Mr. D had a craniotomy with gross total resection of the enhancing lesion (Figure 2). The pathology of the lesion demonstrated a highly cellular mass composed of atypical cells with microvascular proliferation and necrosis. Cells were diffusely positive for glial fibrillary acidic protein (GFAP) and vimentin, S100, and focally positive for epithelial membrane antigen (EMA). The tissue was IDH-wild type (IDHwt), positive for MGMT promoter methylation. In regards to additional molecular markers, Mr. D had somatic mutations in STAG2, PTEN, TP53, TERT, and CDK4. He did not consent to testing for germline mutations.

Figure 2: Axial MRI after initial resection. T1 postcontrast imaging (A), fluid-attenuated inversion recovery (FLAIR) imaging (B).

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Figure 2: Axial MRI after initial resection. T1 postcontrast imaging (A), fluid-attenuated inversion recovery (FLAIR) imaging (B).

Follow Up

Although Mr. D received the standard-of-care treatment and had improvement of his neurologic symptoms, 6 months after the initial diagnosis, he began having seizures, progressive aphasia, and worsening right sided weakness. At this time, imaging (Figure 3) revealed an increase in the enhancement and FLAIR signal abnormality.

Figure 3: Axial MRI obtained after Mr. D’s further neurologic decline. T1 postcontrast imaging (A), fluid-attenuated inversion recovery (FLAIR) imaging (B).

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Figure 3: Axial MRI obtained after Mr. D’s further neurologic decline. T1 postcontrast imaging (A), fluid-attenuated inversion recovery (FLAIR) imaging (B).

Challenge Questions

1. What is the most likely diagnosis?

A. Glioblastoma (GBM)

B. Bacterial brain abscess

C. Tumefactive multiple sclerosis

D. Oligodendroglioma

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Question 1: A, The most likely diagnosis is glioblastoma, which are typically hypointense on MRI T1 enhancing heterogeneously postcontrast.

2. Which molecular finding is most likely for Mr. D’s lesion?

A. 1p/19q codeletion

B. H3K27 mutation

C. TERT promoter mutation

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Question 2: C, The most likely molecular finding for the lesion as described above is TERT mutation.

3. Based on mature randomized phase 3 data, which treatment(s) improve overall survival after initial surgery?

A. Combination radiation/temozolomide chemotherapy

B. Observation only

C. Anti-vascular endothelial growth factor (VEGF)-antibody bevacizumab

D. Combination radiation therapy/temozolomide chemotherapy and tumor treating fields

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Question 3: D, Radiation/temozolomide followed by additional temozolomide (A), sometimes referred to as the "Stupp regimen", has been shown to improve survival when compared to radiation alone when studied in a randomized phase 3 trial.  The addition of tumor treating fields has been shown in another phase 3 trial (EF-14) to further improve survival and progression free survival when compared to the Stupp regimen.

4. After seeing Figure 3, what is the cause of Mr. D’s posttreatment decline?

A. Intraparenchymal hemorrhage

B. Treatment effect

C. Tumor progression

D. Brain herniation

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Question 4: C, After seeing Figure 3, tumor progression is the most likely reason for Mr. D's clinical decline.

5. What is the role of surgical resection in tumor recurrence?

A. Never indicated

B. Possibly indicated

C. Always indicated

D. There is no data to support either way

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Question 5: B, Surgical resection for the tumor recurrence is possibly indicated.

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MY and CS report no disclosures. RVL has received honoraria from NewLink Genetics, ReNeuron, Abbvie, and Monteris for consultation, EBSCO and Medlink Neurology for medical editing, and American Physician Network for preparing and presenting board review CME. CMH has received honoraria from Abbvie for consulting.