Citations

Metastatic neuroendocrine tumour (NET) to brain has been reported in 1.5–5% of patients with NETs. Differentiation between intracranial NET metastasis and meningiomas can cause a diagnostic dilemma. We present a symptomatic case of a 66-year-old male with a history of left-sided skull base mass. The diagnosis of a meningioma was made based on the MRI findings and clinical presentation. The patient received radiation and the mass remained stable on serial MRI images at follow-up visits. Five years after his initial presentation, the patient’s mass showed further growth. He also complained of worsening of his recent diagnosis of irritable bowel syndrome and fluctuations in his blood pressure. Surgical resection was performed, and histopathological features were consistent with moderately differentiated neuroendocrine tumour. Further evaluation with 68 Gallium-DOTATATE positron emission-computed tomography (Ga-68 PET/CT) showed metastatic disease involving the bones, lymph nodes, and liver without convincing evidence of the location of primary malignancy within the bowel loops or the pancreas. The patient was started on combination of capecitabine and temozolomide with partial response and significant improvement of his symptoms. This case highlights the clinical and radiological behaviour of intracranial NET that can mimic the diagnosis of meningioma.

Background: Survival of patients with glioblastoma (GBM) increased in the 2000s, most prominently after the addition of temozolomide to the standard-of-care treatment protocol. The reason for subsequent improvements in survival in the late 2000s and early 2010s was less clear, with explanations including the introduction of bevacizumab, better surgical methods, and advances in supportive care. It is uncertain whether the trend of improving population-level survival has continued. Materials and Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program was analyzed comparing survival of adult GBM patients diagnosed in consecutive 3-year periods from 2000 to 2017. Kaplan-Meier survival analysis and Cox proportional hazards models were used. Results: A total of 38,352 patients diagnosed with GBM between 2000 and 2017 met inclusion criteria. Median survival and percent survival to 12 and 24 months all progressively increased between 2000 and 2011. There were no significant differences in survival comparing 2009-2011 with 2012-2014 or 2015-2017. During the 2015-2017 period, median survival was 11 months, with 12 and 24-month survival proportions of 45.7% (95% confidence interval, 44.5-47.0) and 19.0% (95% confidence interval, 18.6-21.2), respectively. Conclusions: After a period of progressive improvement in GBM survival between 2000 and 2011, survival plateaued. Subsequent advances since 2011 have not yet been translated to improved survival on the population-level as of 2017.

Abstract H3 K27M-mutant diffuse gliomas without midline involvement are extremely rare and their clinical behavior remains elusive due to limited reported follow-up data. We describe an H3 K27M-mutant diffuse non-midline glioma patient with extended follow-up. A 34-year-old woman presented with headache, memory loss, periods of changes in taste and smell, and confusion. Imaging studies revealed an 2.3 cm expansile T2/flair hyperintensity with patchy postcontrast enhancement centered in the left amygdala without associated restricted diffusion and no involvement of the midline structures. The tumor was debulked and consisted of a mitotically active infiltrating astrocytic glioma without tumor necrosis or microvascular proliferation, consistent with anaplastic astrocytoma. Targeted 187-gene neuro-oncology NGS testing detected an H3F3A K27M mutation along with a PTPN11 and a PPM1D mutation. FISH 1p/19q-codeletion testing was negative. MGMT promoter was unmethylated. The patient was treated with chemoradiation with temozolomide for 6 weeks followed by 12 cycles of temozolomide. Four years after initial resection, an area of increased post-contrast enhancement indicating tumor recurrence/progression was noted. Partial resection of the recurrent tumor revealed a mitotically active infiltrating astrocytic glioma with tumor necrosis consistent with glioblastoma. Molecular profiling of the recurrent tumor by the neuro-oncology NGS panel detected similar mutational profile (identical H3F3A K27M and PTPN11 mutation; different PPM1D mutation) with an additional SOS1 mutation. The patient completed 4 cycles of Lomustine and although clinically stable, imaging studies showed slight increase in residual tumor size concerning for tumor progression. Lomustine was discontinued, Bevacizumab therapy was initiated and patient was enrolled in clinical trial (NCT02525692). Despite tumor progression, this patient has had a relatively long disease course (5 years) suggesting that H3 K27M-mutant non-midline diffuse gliomas although molecularly similar, may follow a more favorable clinical course than their midline counterparts possibly due to the hemispheric location, which is more amenable for surgical resection.

Abstract BACKGROUND Somatostatin receptor (SSTR) PET/CT is utilized with increasing frequency in the clinical treatment of neuroendocrine tumors. Incidental CNS lesions are commonly noted and presumed to be meningiomas, however 68Gallium (Ga-68)-DOTATATE radionuclide use lacks specificity for meningioma identification. Currently there is no established SSTR-based imaging criteria for classification of incidental CNS lesions. METHODS We retrospectively analyzed patients across clinical and radiological databases at Mayo Clinic who had undergone both Ga-68-DOTATATE PET/CT and brain MR imaging who had an incidental CNS lesion identified with clinical or radiographic prediction of meningioma. Known meningioma diagnoses prior to imaging were excluded. Imaging indication, semi-quantitative measures, and corresponding clinical history were analyzed to identify metrics impacting both the predictive and descriptive utility of SSTR-based imaging as compared to corresponding MRI prediction in incidental CNS lesions. RESULTS Among 59 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (71%). Cases with concordant lesion type prediction of meningioma between imaging modalities (N = 25) displayed a higher median SUV max and Krenning score on Ga-68-DOTATATE PET compared to cases with concordant prediction of other lesions (N=10) or discordant prediction of meningioma (N=24). Ga-68-DOTATATE was more likely to discordantly predict meningioma as compared to the corresponding patient MRI in cases with lower SUV max values. The addition of Qclear technology was significantly associated with diagnostic clarification in cases of imaging discordant tumor type prediction. Prior cranial radiation or use of a somatostatin mimetic did not affect quantitative radiographic measures in lesion characterization, and MRI-based tumor size was similar across groups. CONCLUSION The continued development of SSTR-based imaging biomarker signatures across incidental CNS lesion subtypes will further define the role of this imaging modality in the clinical diagnosis and management of presumed meningiomas.

Abstract Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5–52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.

AbstractThe ability to accurately differentiate treatment-related changes (ie, pseudoprogression and radiation necrosis) from recurrent glioma remains a critical diagnostic problem in neuro-oncology. Because these entities are treated differently and have vastly different outcomes, accurate diagnosis is necessary to provide optimal patient care. In current practice, this diagnostic quandary commonly requires either serial imaging or histopathologic tissue confirmation. In this article, experts in the field debate the utility of 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography (FDG PET) as an imaging tool to distinguish tumor recurrence from treatment-related changes in a patient with glioblastoma and progressive contrast enhancement on magnetic resonance (MR) following chemoradiotherapy.