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Description : Check out this medical presentation on Ependymoma (Childhood), which is titled "Pediatric Hematology/Oncology Review Course – Brain Tumors", to know about general CNS tumor epidemiology and etiology, neuroanatomy, general CNS tumor pathophysiology, and specific CNS tumors.

Tags : Ependymoma, Childhood, Brain Tumors, CNS tumor, epidemiology, etiology, neuroanatomy, CNS tumor pathophysiology, CNS tumors

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Slide 1-

“Brain Tumors” Jason Fangusaro, MD
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Topical Structure Suggested by the ABP Copyright © 2019 by ASPHO
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2019 ABP Content Outline: Brain Tumors Domain 9: Solid Tumors General considerations Clinical presentations Diagnostic imaging Pathology Other laboratory tests Brain tumors Medulloblastoma Low-grade glioma (LGG) High-grade glioma (HGG) Ependymoma Central nervous system germ-cell tumors (CNS GCT) Rare brain tumors Late Effects Copyright © 2019 by ASPHO
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Goals/Overview Discuss general CNS tumor epidemiology and etiology Quick neuroanatomy lesson Discuss general CNS tumor pathophysiology Discuss specific CNS tumors LGG, HGG, Medulloblastoma, Ependymoma, CNS GCT and “Other” rare tumors (AT/RT, Choroid Plexus Tumors, Craniopharyngioma) Epidemiology and Risk Assessment (including genetic associations) Diagnosis (imaging, staging, pathology and unique testing) Pathophysiology/biology Management and Treatment Outcomes Late Effects Copyright © 2019 by ASPHO
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My Own Personal Goals Make sure everyone in this room gets the probable 3 brain tumor questions on the test correct! Help you all recognize that Pediatric Neuro-Oncology is clearly the most exciting subspecialty and topic! Copyright © 2019 by ASPHO
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Red Font Red Font is my way of highlighting key points throughout the presentation that I think are: Important to remember/memorize Key concepts that make for good test questions Copyright © 2019 by ASPHO
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Pediatric CNS Tumors: General Overview Copyright © 2019 by ASPHO
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CNS Tumors: General Epidemiology CNS tumor are the most common solid malignancy in children and the second most common malignancy overall after leukemia. Astrocytomas are the most common brain tumor overall (most commonly low-grade) Medulloblastomas are the most common “malignant” brain tumor The incidence rate is overall higher in males than females. Approximately 1.2:1 An estimated 3000-4000 new cases of childhood primary brain and other CNS tumors are diagnosed each year in the US. Overall 5-year survival rate is approximately 70-75% (0-19 y/o). Misleading Copyright © 2019 by ASPHO
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Pediatric CNS Tumor: General Completely different from adult brain tumors. Histologically, biologically, treatment paradigms and outcomes Copyright © 2019 by ASPHO
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Pediatric CNS Tumors: General Etiology Far and away, the etiology is unknow with rare exception: History of ionizing radiation (typically history of CNS radiation for a previous CNS tumor or other oncologic condition, like CNS leukemia) Genetic brain tumor predisposition syndromes Copyright © 2019 by ASPHO
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Brain Tumor Genetic Predisposition Disorders Table 3 Copyright © 2019 by ASPHO
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Neuroanatomy Basics Figure 1 Figure 2 Copyright © 2019 by ASPHO
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CNS Tumors: Localizing Symptoms Based on Anatomy Table 1 Copyright © 2019 by ASPHO 2017 Review Course, Brain Tumors, Kenneth J. Cohen, MBA MD
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CNS Tumors: Symptoms Table 2 Copyright © 2019 by ASPHO
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CNS Tumors: “Localizing” Symptoms Match Game Symptom New onset seizures (rare overall) Left-sided arm weakness Swallowing difficulty/drooling Visual acuity decline Ataxic gait Tumor Location Right motor cortex (cerebrum) Optic pathway Temporal lobe Brainstem Cerebellum Copyright © 2019 by ASPHO
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Low-Grade Glioma Copyright © 2019 by ASPHO
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Low-Grade Glioma: General Low-grade glioma is the most common CNS tumor. This is a broad term encompassing numerous histologies that all fall into World Health Organization (WHO) grade I and II glial tumors (oligodendroglioma, ganglioglioma pleomorphic xanthoastrocytoma, etc.). Pilocytic astrocytoma is the most common LGG. Copyright © 2019 by ASPHO
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Low-Grade Glioma: Epidemiology 40-50% Low Grade Glioma: WHO I/II Figure 4 Copyright © 2019 by ASPHO
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Low-Grade Glioma: Risk Assessment Subependymal Giant Cell Astrocytoma (SEGA) is associated with Tuberous Sclerosis. Historically treated with surgery, but now mtor inhibitors are moving to front-line therapy Increased risk of LGG in children with Neurofibromatosis type-1 (NF1) Need 2 or more of the following to diagnose NF-1 clinically: 6 or more café au lait macules (> 0.5 cm in children) 2 or more cutaneous/subcutaneous neurofibroma or plexiform neurofibroma Axillary or groin freckling Optic pathway glioma 2 or more Lisch nodules Bony dysplasia First-degree relative with NF-1 Copyright © 2019 by ASPHO
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Neurofibromatosis Type-1 and LGG Approximately 15-20% of NF1 patients will develop a CNS low-grade glioma, most commonly in the optic pathway. Biopsy not necessary if classic appearance Often can be asymptomatic and indolent, and may not require treatment. Treatment typically only initiated with visual acuity decline or other neurologic symptoms Chemotherapy is usual first line of therapy in children with NF1-associated LGG that require treatment. Most common chemotherapies are a combination of carboplatin and vincristine or vinblastine alone Avoid radiotherapy as NF1 patients have a high risk of secondary malignancy with ionizing radiation exposure Avoid alkylators in NF1 patients due to the high risk of secondary malignancy Copyright © 2019 by ASPHO
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NF-1 and LGG 14 year-old with NF-1 and Right Optic Glioma Post-Contrast Axial Orbit 3 year-old with NF-1 and Bilateral Optic Gliomas Axial T2/FLAIR Figure 6 Figure 5 Copyright © 2019 by ASPHO
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Diagnosis made by biopsy or resection with a goal of complete resection whenever possible. Exception is in NF1 patients with a classic appearance of a LGG typically within the optic pathway (diagnosis can be made by imaging) Typically does not spread to other parts of CNS, so full staging not necessary unless clinically indicated based on symptoms or a specific histology. If a patient has associated back pain, a spine MRI may be indicated If a patient has a unique histology, a spine MRI may be warranted For example, there is an increased risk of metastases with pilomyxoid astrocytoma Lumbar puncture for CSF cytology is not routinely performed or required for staging. Low-Grade Glioma: Diagnosis and Evaluation Copyright © 2019 by ASPHO
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Low-Grade Glioma: Pathology The most common histology is pilocytic astrocytoma. Characterized by low to moderate cellularity, GFAP+ and dense fibrillary areas Characterized by Rosenthal fibers Astrocytic cytoplasmic inclusions that are typically elongated or “corkscrew” shape and eosinophilic on H and E Figure 7 Copyright © 2019 by ASPHO Republished with permission of American Journal of Neuroradiology, from Neuropathology for the Neuroradiologist: Rosenthal Fibers. F.J. Wippold, A. Perry and J. Lennerz. © May 2006, 27 (5) 958-961; permission conveyed through Copyright Clearance Center, Inc.
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Low-Grade Glioma: Molecular Biology Aberrations of the MAPK pathway are the most common abnormality found in low-grade glioma. Copyright © 2019 by ASPHO
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FGFR Ras GDP Ras GTP NF-1 BRAF ERK MEK Transcription and Proliferation MAPK Pathway - Simplified Figure 8 Copyright © 2019 by ASPHO
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BRAF in Pediatric Low-Grade Glioma The most common mechanisms of BRAF activation in LGG is a genetic fusion resulting in loss of the regulatory domain of BRAF. BRAF KIAA1549 fusion results in activation and has been described in the majority (60-80%) of pilocytic astrocytoma specimens examined by multiple investigators Another alternative mechanism is the BRAFV600E mutation. Found in approximately 10-15% of pilocytic astrocytoma Found in other LGG, such as pleomorphic xanthoastrocytoma (~60%) and ganglioglioma (~15-20%) Copyright © 2019 by ASPHO
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Low-Grade Glioma: Management and Treatment If possible, a gross-total resection should be attempted. If achieved, observation alone and surveillance imaging is typically the management of choice If residual disease or unable to resect due to location, chemotherapy is typically the first line, especially in young children. Most common first-line chemotherapy is carboplatin/vincristine, vinblastine alone or combination of thioguanine, procarbazine, CCNU and vincristine (TPCV) Radiation is very effective, but most practitioners would avoid in young children due to the risk of late effects (neurocognitive, endocrine, ototoxicity and secondary malignancy). Remember in patients with NF1, no treatment necessary unless there are neurologic symptoms or functional deficits (vision dysfunction) Also, avoid TPCV (alkylator) and radiation in NF1 patients due to high risk of secondary malignancy Targeted therapies now being tested (MEK inhibitors, BRAF inhibitors) with very promising results in patients with recurrent disease. Copyright © 2019 by ASPHO
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Low-Grade Glioma: Outcomes With a gross-total resection, 5-year overall survival can be > 90-95%. However, depending on location and ability to resect, many patients have multiple progressions and recurrences. On the most recently published CCG/COG (A9952) study comparing carboplatin/vincristine to TPCV, outcomes were as follows for all patients enrolled: 5-year event-free survival = 45 ± 3.2% 5-year overall survival = 86 ± 2.2% Copyright © 2019 by ASPHO
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Low-Grade Glioma: Diencephalic Syndrome Diencephalic syndrome is a rare condition most often caused by a tumor located in the diencephalon, including the hypothalamus and thalamus. This condition is usually found in infants and young children and results in a constellation of symptoms, including: Failure to thrive and emaciation despite a somewhat normal appetite and intake Abnormal eye movements and vision issues Vomiting Hydrocephalus It is most commonly caused by a low-grade astrocytomas, but the exact mechanism is poorly understood. Biopsy is often indicated to confirm diagnosis and treatment is typically low-grade glioma chemotherapy (carboplatin/vincristine or vinblastine, for example). Symptoms improve with chemotherapy Copyright © 2019 by ASPHO
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Low-Grade Glioma: Diencephalic Syndrome Typical Case 2 y/o female presents with 4 months of failure to thrive with no known etiology. Over the last week, she developed some emesis and new nystagmus. MRI is performed revealing a large hypothalamic mass with associated hydrocephalus. Biopsy confirms a pilocytic astrocytoma. Figure 9 Post-contrast Axial T1 Copyright © 2019 by ASPHO
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High-Grade Glioma Copyright © 2019 by ASPHO
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High-Grade Glioma: General High-grade gliomas are highly aggressive and malignant glial tumors classified as either WHO Grade III (anaplastic astrocytoma) or WHO Grade IV (glioblastoma multiforme). Much more common in adults, however, the biology is distinct between children and adults despite very similar histologic appearance. In pediatrics, high-grade gliomas are much less common than low-grade gliomas. High-grade gliomas are more resistant to therapy with much poorer survival outcomes compared to LGG. Copyright © 2019 by ASPHO
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High-Grade Glioma: Epidemiology Figure 10 Copyright © 2019 by ASPHO
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High-Grade Glioma: Risk Assessment Increased risk in patients with previous exposure to radiotherapy. CNS leukemia or previous CNS tumor Increased risk in patients with Li Fraumeni syndrome (TP53 gene mutation) and Familial Adenomatous Polyposis (APC gene abnormality). Copyright © 2019 by ASPHO
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High-Grade Glioma: Diagnosis and Evaluation Diagnosis is made by biopsy/resection and tissue evaluation. One exception is Diffuse Intrinsic Pontine Glioma (DIPG) which we will discuss separately The goal is a gross total resection, but this is often difficult due to location and the highly infiltrative nature of high-grade glioma. Rarely spreads to other parts of the CNS, but a baseline spinal MRI is typically done by most practitioners, especially if clinically indicated. Lumbar puncture for CSF cytology is not routinely performed or required for staging. Copyright © 2019 by ASPHO
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High-Grade Glioma: Pathology Classically characterized by being highly cellular with numerous mitoses, vascular proliferation, pseudopalisading necrosis and usually GFAP+. Pseudopalisading necrosis is when rapidly proliferating tumor cells are stacked (or palisade) around a central pale area which represents necrotic tissue I do not think you will need to recognize this, but if these key words (in red above) are used to describe a glial tumor, they are trying to get you to recognize a high-grade glioma, specifically a WHO Grade IV glioblastoma multiforme with a very poor survival outcome. Copyright © 2019 by ASPHO
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Diffuse Intrinsic Pontine Glioma (DIPG) Diffusely infiltrative high-grade lesions of the pons. Represents about 10-12% of all pediatric CNS tumors. Can be diagnosed with imaging alone. The classic age is 5-7 years old. If a biopsy is performed, > 80% will have a histone mutation in H3 K27M (described next slide). Complete resection not feasible. Patients most often present with short duration of symptoms (1-2 months) of the classic triad: Cranial nerve symptoms Long-tract signs Ataxia Focal radiotherapy is the only know beneficial therapy. Many children will enroll on clinical trials Mean survival is about 10-12 months with almost all children succumbing to disease within 2 years regardless of therapy. Figure 11 Non-contrast Axial T1 Non-contrast Axial T2/FLAIR Copyright © 2019 by ASPHO
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High-Grade Glioma: Molecular Biology A molecular feature in some pediatric high-grade glioma is H3 K27M mutant. This is a histone mutation that characterizes what are now known as diffuse midline glioma, H3 K27M mutant These are highly infiltrative, WHO Grade IV lesions of the midline, most commonly the pons (DIPG), thalamus or spinal cord Estimated to be present in 80% of classic diffuse intrinsic pontine glioma (DIPG) A less commonly seen histone mutation is H3.3 G34R which is seen in high-grade gliomas in the cerebral hemispheres, often in teenagers and young adults. Copyright © 2019 by ASPHO
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High-Grade Glioma: Treatment The best known therapy is a maximal safe surgical resection followed by a combination of focal radiotherapy and chemotherapy. Historic studies have shown improvement with the addition of chemotherapy to radiotherapy, but many of these studies are questioned and the exact chemotherapy is not agreed upon. Infant (most commonly < 3 y/o) high-grade glioma have unique biology and a more indolent course. Radiation can sometimes be avoided or delayed with the use of chemotherapy in young children Copyright © 2019 by ASPHO
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High-Grade Glioma: Outcomes Universally poor, with most large series showing 5-year overall survivals of 15-20%. Infants with improved outcomes most likely due to unique biology. Copyright © 2019 by ASPHO
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Medulloblastoma Copyright © 2019 by ASPHO
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Medulloblastoma: General Medulloblastoma is the most common “malignant” brain tumor of childhood. It is a highly aggressive and rapidly growing embryonal tumor. It is located in the posterior fossa (cerebellum) by definition. Copyright © 2019 by ASPHO
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Medulloblastoma: Epidemiology 2nd most common CNS tumor. Most common “malignant” brain tumor in children. More common in males 1.7:1 Figure 12 Copyright © 2019 by ASPHO
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Medulloblastoma: Risk Assessment Increased risk in patients with Gorlin’s syndrome, also known as Nevoid Basal Cell Carcinoma Syndrome. Due to a PTCH gene mutation Increased risk in Familial Adenomatous Polyposis (Gardner’s, Turcot’s) Syndrome. Due to APC gene mutation Copyright © 2019 by ASPHO
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Medulloblastoma: Diagnosis and Evaluation Imaging will reveal a large heterogenous mass in the posterior fossa (cerebellum), often with some contrast enhancement, however, this is not diagnostic. Tissue is needed for diagnosis, and usually a gross total resection is attempted. Approximately 30% of cases will have metastatic spread throughout the CNS, so both a lumbar CSF cytology and spine MRI are needed for staging. Spine MRI should be done before surgery or a minimum of 10-14 days post-operatively to avoid post-operative products confounding MRI interpretation Lumbar CSF sample for cytology should be done a minimum of 10-14 days post-operatively, again to avoid post-operative products confounding interpretation Copyright © 2019 by ASPHO
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Medulloblastoma: Imaging Axial T2 Post-contrast Axial T1 Images reproduced with permission from Medscape Drugs & Diseases (https://emedicine.medscape.com/), Medulloblastoma Imaging, 2015, available at: https://emedicine.medscape.com/article/341527-overview. Copyright © 2019 by ASPHO
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Medulloblastoma: Pathology Highly cellular tumor with prominent mitosis and synaptophysin positive (neuronal component) There are 4 classic histologic patterns recognized Classic Desmoplastic Extremely Nodular d. Anaplastic/Large Cell Figure 14 Copyright © 2019 by ASPHO Gupta T, Sarkar C, Rajshekhar V, Chatterjee S, Shirsat N, Muzumdar D, Pungavkar S, Chinnaswamy G, Jalali R. Indian Society of Neuro-Oncology consensus guidelines for the contemporary management of medulloblastoma. Neurol India [serial online] 2017 [cited 2018 Oct 31];65:315-32. Available from: http://www.neurologyindia.com/
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Medulloblastoma: Molecular Biology Historically, 4 major subgroups accepted: WNT SHH Group 3 Group 4 Treatment paradigms are evolving based on these. WNT has the best prognosis with many series showing 90-100% overall survival. Ongoing COG trial to reduce therapy in these patients Figure 15 Copyright © 2019 by ASPHO Taylor, M.D., Northcott, P.A., Korshunov, A. et al. Acta Neuropathol (2012) 123: 465. https://doi.org/10.1007/s00401-011-0922-z
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Medulloblastoma: Molecular Subgrouping Table 4 Copyright © 2019 by ASPHO
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Medulloblastoma: Historic Risk Groups and Treatment Classification Standard risk > 3 y/o Gross total resection with < 1.5 cm3 residual disease No signs of metastases Not anaplastic histology High Risk > 1.5 cm3 residual tumor Metastases (by lumbar cytology or spine MRI) Diffusely anaplastic histology Infants (usually < 3 y/o) Although the exact cutoff age varies depending upon geography and clinical trial guidelines Treatment Standard Risk Craniospinal Radiotherapy at lower doses (2340 cGy) +/- weekly vincristine and boost to the posterior fossa (5400 cGy) followed by maintenance chemotherapy High Risk Full dose craniospinal radiotherapy (3600 cGy) +/- weekly vincristine and boost to posterior fossa (5400 cGy) followed by maintenance chemotherapy Infants Typically treated with induction chemotherapy followed by high dose chemotherapy with autologous stem cell rescue +/- radiotherapy Copyright © 2019 by ASPHO
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Medulloblastoma: Historic Risk Stratification Table 5 Copyright © 2019 by ASPHO
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Medulloblastoma: Outcomes Varies depending on age, risk category and now most probably on molecular subtype, though this latter piece is evolving. Standard risk with 5-year overall survivals of about 75-90%. High risk with 5-year overall survivals of about 40-60%. Infant studies also vary, but survival is approximately 50-70%. Remember retrospective analyses of WNT medulloblastoma have shown excellent survivals, greater than 90% at 5 years. Copyright © 2019 by ASPHO
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Ependymoma Copyright © 2019 by ASPHO
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Ependymoma: General Ependymoma is the third most common pediatric CNS tumor. It is a glial tumor with ependymal cell differentiation. Can occur anywhere in CNS, but far and away most commonly associated with a ventricular surface. Most common location is the posterior fossa (cerebellum) followed by the lateral ventricles and then spinal cord. Figure 16 Cerebellum Spinal cord Copyright © 2019 by ASPHO Cancer Research UK / Wikimedia Commons; Original email from CRUK; 12 January 2016; https://commons.wikimedia.org/wiki/File:Diagram_showing_where_the_ventricles_are_in_the_brain_CRUK_387.svg
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Ependymoma: Epidemiology Craniopharyngioma Astrocytoma/Glioma Ependymoma CNS Germ Cell Tumor Medulloblastoma 50-60% 15-20% 8-10% 6-9% Ependymoma Figure 17 Copyright © 2019 by ASPHO
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Ependymoma: Risk Assessment Increased risk in patients with Neurofibromatosis type 2 Copyright © 2019 by ASPHO
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Diagnosis cannot be made on imaging and tissue is required. Goal is a gross total resection. There is a risk of CNS metastases in about 10-15% of patients, and therefore, staging must include lumbar CSF cytology and full spine MRI. Spine MRI should be done before surgery or a minimum of 10-14 days post-operatively to avoid post-operative products confounding MRI interpretation Lumbar CSF sample for cytology should be done a minimum of 10-14 days post-operatively, again to avoid post-operative products confounding interpretation Ependymoma: Diagnosis and Evaluation Copyright © 2019 by ASPHO
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Ependymoma: Imaging Typically a heterogenous mass in the posterior fossa (cerebellum). Often with patchy heterogenous enhancement. Post-contrast Axial T1 Post-contrast Sagittal T1 Figure 18 Copyright © 2019 by ASPHO Ghosal Nandita, Murthy Ganesh, Dadlani Ravi, Hegde. Alangar Sathya, Singh Devendra. CASE REPORT. Recurrent posterior fossa anaplastic ependymoma with prominent chondroid metaplasia: A case report and review of literature. Indian Journal of Pathology and Microbiology. 2010, 53(4):787-789. http://www.ijpmonline.org/. Published October 27, 2010. Accessed November 1, 2018
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Ependymoma: Pathology Moderately cellular and composed of monomorphic cells with round to oval nuclei. A common and key histologic feature is the presence of perivascular pseudorosettes. Can be diffusely anaplastic which is thought to have a worse prognosis. There is a Grade I myxopapillary ependymoma most commonly found in spine and typically treated with resection alone. Figure 19 Copyright © 2019 by ASPHO Republished with permission of American Journal of Neuroradiology, from Neuropathology for the Neuroradiologist: Rosettes and Pseudorosettes. F.J. Wippold and A. Perry. © March 2006, 27 (3) 488-492; permission conveyed through Copyright Clearance Center, Inc.
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Ependymoma: Molecular Biology Although we are learning much more, these biologic subgroups have not yet universally impacted treatment. Table 6 Copyright © 2019 by ASPHO
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Ependymoma: Treatment Maximum surgical resection. Surgical resection has consistently been found to impact outcome Localized tumors are typically treated with resection followed by focal radiotherapy between 5400-5900 cGy. Metastatic tumors often treated with craniospinal radiotherapy 3600 cGy and boost to focal area 5400-5900 cGy. The role of chemotherapy remains uncertain. Chemotherapy alone approaches often used in very young children (typically < 1 y/o) to delay radiation. Copyright © 2019 by ASPHO
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Ependymoma: Outcome 5-year overall survivals are 60-80%, but many patients relapse late and it is a unique CNS tumor where EFS/OS continues to decline far after 5 years. Many patients will develop multiply recurrent tumor over several years and eventually succumb to the disease. Copyright © 2019 by ASPHO
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Central Nervous System Germ Cell Tumors Copyright © 2019 by ASPHO
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CNS Germ Cell Tumors: General Rare pediatric CNS tumor with similar histologic feature to gonadal germ cell tumors. Unique in that diagnosis can sometime be made by circulating tumor markers in the blood and CSF (AFP and Beta-HCG). Classically, there are 2 major categories: Germinoma (aka non-secreting) – better outcome Non-germinomatous Germ Cell Tumor (NGGCT) (aka secreting) – worse outcome Copyright © 2019 by ASPHO
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CNS Germ Cell Tumors: Epidemiology Represent only 2-3% of pediatric CNS tumors. More common in Japan and other Asian countries. Can be up to 10-15% of pediatric brain tumors in these geographic areas Figure 20 Copyright © 2019 by ASPHO
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CNS Germ Cell Tumor: Risk Assessment There is no significant genetic association with CNS GCT that would be commonly known or tested. Copyright © 2019 by ASPHO
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CNS Germ Cell Tumor: Imaging The most important take home point would be that you would see a heterogenous and enhancing mass in one of the two most common locations: Suprasellar/Pituitary Pineal Sometimes both present and it is then called a “doublet” lesion or “bi-focal” lesion Figure 21 Post-contrast Sagittal T1 Phi J, Kim S, Lee J, Park C, Kim I, Ahn H, Shin H, Kim I, Jung H, Kim D, Paek S, Wang K. The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis?. J Neurosurg Pediatrics. 2013; 11:107–114. ©AANS, 2013 Copyright © 2019 by ASPHO
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CNS Germ Cell Tumors: Unique Symptoms *Parinaud’s syndrome is a cluster of abnormalities of eye movement and pupil dysfunction, characterized by: Paralysis of upwards gaze Pseudo-Argyll Robertson pupil (accommodative paresis and pupils become mildly dilated and show light-near dissociation) Convergence-retraction nystagmus (on fast up-gaze, the eyes pull in and the globes retract) Table 7 Copyright © 2019 by ASPHO
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CNS Germ Cell Tumors: Pathology Many tumors are mixed but can contain a variety of germinoma and other malignant germ cell tumor elements. Among the NGGCT group, there are numerous histologic variants, such as endodermal sinus tumor, yolk sac tumor, embryonal carcinoma and teratoma. Copyright © 2019 by ASPHO
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CNS Germ Cell Tumor: Diagnosis and Evaluation Serum and CSF tumor markers should be drawn on every patient at time of diagnosis. If tumor markers in serum or CSF (AFP, Beta-HCG) are elevated enough, a diagnosis of NGGCT may be made without tissue. On a test question, I imagine they would describe a mass in the pineal or suprasellar region with an AFP or Beta-HCG that is very elevated (> 200) in blood or CSF In germinoma, the classical teaching is that these tumor markers are not elevated, though this is controversial. If markers are not diagnostic, a biopsy is necessary for tissue evaluation. Metastases throughout the CNS is possible, so a full spine MRI and lumbar CSF for cytology are necessary. Copyright © 2019 by ASPHO
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CNS Germ Cell Tumor: Treatment Germinoma Neoadjuvant chemotherapy followed by response based XRT Typical chemotherapy: Carbo/Etoposide x 4 cycles Dose of XRT is dependent on response but ranges between 3000-3600 cGy and always includes whole ventricle XRT alone Dose in range of 4000-4500 cGy and includes whole ventricle (not commonly used anymore) NGGCT Neoadjuvant chemotherapy followed by XRT (extent and dose is controversial) In both (germinoma and NGGCT) second-look surgery often advocated after neoadjuvant chemotherapy if residual mass remains prior to radiotherapy to decipher residual mass (scar tissue, malignant tumor, teratoma). Risk of “Growing Teratoma Syndrome” Copyright © 2019 by ASPHO
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CNS Germ Cell Tumor: Outcomes Germinoma Excellent prognosis with > 90% OS at 5 years with either XRT alone or a combination of chemotherapy + XRT NGGCT In patients with a good response to neoadjuvant chemotherapy (complete response or very good partial response), 5-year overall survival is approaching 80-90% There is a group who have poorer responses (less than a very good PR) to chemotherapy and have significantly worse outcomes. Copyright © 2019 by ASPHO
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Other “Rare Tumors:” AT/RT, Choroid Plexus Tumors, Craniopharyngioma Copyright © 2019 by ASPHO
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Atypical Teratoid Rhabdoid Tumor (AT/RT) A rare embryonal tumor typically seen in young children and infants. About 2% of all pediatric CNS tumors Requires full CNS metastatic evaluation, including spine MRI and lumbar CSF cytology. Historically, prognosis was very poor, but with modern multi-modal therapies combining chemotherapy (sometimes autologous stem cell rescue or “sarcoma-like” therapy) +/-radiation, survival has improved. Pathologically identified by loss of INI-1 on immunohistochemistry or more detailed molecular testing. Mutation can be sporadic in tumor or germline Rhabdoid Tumor Predisposition Syndrome is a germline mutation in SMARCB1 and SMARCB4 (INI-1 or hSNF5) associated with increased risk of AT/RT, other rhabdoid tumors (commonly in kidney) and schwannomatosis. It is important to test for this for familial counseling and risk assessment Copyright © 2019 by ASPHO
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Choroid Plexus Tumors Represent about 1-2% of all pediatric brain tumors. 3 varieties: Choroid plexus papilloma (CPP) Atypical choroid plexus papilloma Choroid plexus carcinoma (CPC) Most commonly located in lateral ventricle. Usually presents in younger children/infants with signs of increased intracranial pressure. Goal is a gross total resection when possible which is usually curative for CPP. 5-year OS > 90% Outcomes for CPC are variable despite a variety of multi-modal therapies with chemotherapy and radiotherapy. In CPC, 5-year overall survivals ranges from 20-50% CPC can be associated with Li Fraumeni and TP53 germline mutation Copyright © 2019 by ASPHO
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Craniopharyngioma Rare epithelial tumor of thought to be due to maldevelopmental origin. Represents about 6-9% of all pediatric brain tumors. Often presents with headache, emesis, visual field cut and endocrinopathies. 80-90% will have endocrinopathies at presentation if tested Most common location is suprasellar/pituitary. Imaging usually shows a mixed solid and cystic mass within the suprasellar region. Pathology consists of squamous epithelium lining cystic cavities, often containing calcium and keratin. Treatment is maximum surgical resection. If a gross total resection is not achievable or progressive disease ensues, focal radiotherapy is often used. Although progression-free and overall survivals are good, many patients have numerous morbidities affecting quality of life (endocrinopathies, behavioral issues, visual dysfunction and seizures). Copyright © 2019 by ASPHO
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CNS Tumors: Late Effects Copyright © 2019 by ASPHO
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CNS Tumors: Late Effects of Therapy After CNS radiation, there is an increased risk of a secondary malignant brain tumor, most commonly high-grade glioma and meningioma. This typically occurs 7-10 after radiotherapy treatment Risk is approximately < 5% and is dependent upon radiation dose and age Table 8 Copyright © 2019 by ASPHO
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CNS Tumors: Secondary Malignancy A classic question would typically be something like the following: A 20 y/o male presents to the ER with complaints of headaches, emesis and right sided weakness. He was treated at age 10 with craniospinal radiation and chemotherapy for a diagnosis of medulloblastoma. Imaging reveals a left-sided mass with associated hydrocephalus and mild midline shift. The differential must include a radiation-induced secondary malignancy, like a high-grade glioma or meningioma Latency period of a secondary high-grade lesion is often 7-10 years after radiation Copyright © 2019 by ASPHO
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Thank you and Best of Luck! Please feel free to reach out with specific questions. jfangus@emory.edu BOARDS SMOARDS! Copyright © 2019 by ASPHO