Case Report: Identification of Multiple TERT and FGFR2 Gene Fusions in a Pineal Region Glioblastoma Case

As an oncogenic somatic variant, telomerase reverse transcriptase promoter (TERTp) mutations are frequently observed in adult glioblastoma (GBM). Alternatively, we report the first case of glioblastoma with TERT amplification accompanied by multiple TERT and FGFR2 gene fusions instead of TERTp mutation. A 55-year-old woman presented with dizziness, headache, and diplopia for three weeks. Magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing lobulated mass centered in the pineal region. Partial tumor resection and ventriculoperitoneal shunt were achieved, and the residual tumor was then treated with standard radiation. The tumor was diagnosed as GBM, IDH-wild type, WHO grade IV, and the Ki67 proliferation index was high (30–40%). Intriguingly, TERT amplification without TERTp mutation was identified via next generation sequencing (NGS). Further analysis revealed multiple TERT (TERT–NUBPL, MARCH6–TERT, and CJD4–TERT) and FGFR2 (CXCL17–FGFR2, SIPA1L3–FGFR2, FGFR2–SIPA1L3, and FGFR2–CEACAM1) gene fusions. After the surgery, the patient’s condition deteriorated rapidly due to the malignant nature of the tumor and she died with an overall survival of 3 months. Our report provides the molecular clue for a novel telomerase activation and maintenance mechanism in GBM.

Long-term survival of a patient with diffuse midline glioma in the pineal region: A case report and literature review

Background: Diffuse midline glioma (DMG) is an invasive astrocytic tumor arisen from midline structures, such as the pons and thalamus. Five cases of DMG in the pineal region have been reported, but the clinical course was poor; there was no case of survival for more than 2 years. Case Description: We report the case of a 12-year-old boy with DMG in the pineal region who is living a normal daily life for more than 6 years following multimodal treatment. He complained of a headache accompanied by vomiting that had gradually worsened 1 month previously, and initial magnetic resonance imaging revealed a pineal tumor. Germinoma was initially suspected; however, a combination of chemotherapy using carboplatin and etoposide was ineffective. The first surgery was performed through the left occipital transtentorial approach (OTA); the diagnosis was DMG. After 60 Gy radiotherapy concomitant with temozolomide (TMZ), the tumor enlarged. Second surgery was performed through bilateral OTAs, and 90% of the tumor was removed. In addition, stereotactic radiotherapy (30 Gy, six fractions) was administered, and the local equivalent dose in 2 Gy/fraction reached 97.5 Gy. Maintenance chemotherapy using TMZ and bevacizumab was continued for 2 years. After finishing chemotherapy, the enhancing lesion enlarged again, and bevacizumab monotherapy was effective. Now, at 6 years after diagnosis, the patient leads an ordinary life as a student. Conclusion: Maximum resection and high-dose radiotherapy followed by bevacizumab may have been effective in the present case.

INNV-26. NCI-CONNECT PROGRAM PROVIDES RESOURCES TO IMPROVE CARE FOR PEOPLE WITH RARE CENTRAL NERVOUS SYSTEM (CNS) TUMORS

The National Cancer Institute Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) program focuses on improving approaches to care and treatment for 12 rare CNS tumors, each with < 2,000 diagnoses per year. To reach this rare population, the primary objective was to develop a website to share educational resources that provide patients direct access to clinical care and trials. METHODS: The NCI-CONNECT website uses the Drupal platform within NCI’s framework and the content is free to syndicate. A multidisciplinary team developed tumor-specific content in English and Spanish, clinical trial information, and survivorship resources using evidence-based sources. The Central Brain Tumor Registry of the United States provided statistics on incidence and prevalence of rare tumors. Population reach was calculated using Adobe Experience Cloud website analytics. NCI-CONNECT referrals and study participation data were collected prospectively. RESULTS: The English website launched in September 2018 and visits have increased 2,384%. The Spanish website launched in March 2020 and visits have increased 1,137%. From April 2020 to March 2021, top website page views by English page views / Spanish page views / people living with this disease include oligodendroglioma (43,859 / 8,241 / 11,757), ependymoma (31,579 / 12,684 / 13,294), meningioma (30,261 / 19,507 / 2,692), medulloblastoma (28,487 / 9,999 / 3,840), diffuse midline gliomas (23,064 / 3,851 / 6,033), and pineal region tumors (19,939 / 9,973 / 1,297). Referral rates and participation have accelerated – 45% of patients visiting the Neuro-Oncology Clinic at NIH have a rare CNS tumor and 409 patients enrolled in an NCI-CONNECT study. CONCLUSION: Patient-focused websites can provide guidance to those affected by rare cancers outside of in-person health care visits. The NCI-CONNECT website is an educational and clinical resource for patients and families affected by rare CNS tumors and was created to raise awareness and improve patient outcomes.

Manajemen Anestesi pada Pasien dengan Tumor Regio Pineal yang Menjalani Kraniotomi Pengangkatan Tumor dengan Posisi Duduk

Incidence of pineal regio tumor is 0.4-1% of intracranial tumors. Its location which is buried between two cerebral hemispheres, close to brainstem and hypothalamus become a difficult challenge for the neurosurgeon. Surgery with supracerebellar approach in sitting position is the best method to access the lesion. Sitting position also facilitates the optimal visual field with minimal retractions. However, for anesthesiologist, sitting position is challenging since it has its own complexities during positioning the patient and the risk of complications. Venous air embolism is one of the main concern and if not detected early and treated appropriately would leads to cardiovascular collapse instantly. This is a case of a 38-year-old male with chief complaint of severe headache and blurred vision started 4 months before admission. The Magnetic Resonance Imaging showed a pineal region tumor with perifocal edema, without midline deviation. The patient underwent craniotomy tumor removal with sitting position. The procedure lasted for 10 hours and uneventful. The principle of ABCDE neuroanesthesia, sitting position and its implications, and difficult tumor location are some anesthesia considerations for this patient. A thorough preoperative evaluation, good communication and coordination between surgery and anesthesia team are needed for a smooth uneventful procedure performed in sitting position.