Cns tumors bikash

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CNS tumours in children a detailed description in a comphensive manner with referrence from standard text books.

CNS tumours in children a detailed description in a comphensive manner with referrence from standard text books.

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  • Less than 5 years small round cell tumors eg wills, neuroblastoma leukemia's ets between 5 to 14 lymphomas and CNS tumors
  • Upto grade 2 surgery is enough after radio therapy must be added
  • Grade + giant cells
  • Easily removed with little neurological complication rarely
  • USAULLY bilaterally

Transcript

  • 1. CCEENNTTRRAALL NNEERRVVOOUUSS SSYYSSTTEEMM TTUUMMOORRSS IINN CCHHIILLDDRREENN DR BIKASH RANJAN PRAHARAJ
  • 2. Percentage Distribution of Childhood Cancers
  • 3. INTRACRANIAL TUMORS (ICTS) Primary or Metastatic Occur with equal frequency in adults, but in children primary tumors are far more common. Primary ICTs account for  ~2% of cancers in adults  20% of all cancers in children. In children 70% of ICTs arise in  Posterior fossa (infra-tentorial). as In adults 70% of ICTs arise in  Supra-tentorial. Cranial exposure to ionizing radiation is a risk factor.
  • 4. Because of its location, a benign ICT may have fatal “malignant” effects. Malignant ICTs spread by:  Direct infiltration of adjacent tissues  May disseminate within the CNS via CSF. Gliomas account for 60% of primary ICTs Meningiomas for 20% & all others 20%. All CNS tumors behave as malignant clinically (Limited space)
  • 5. Cytologic origin of CNS tumors NNeeuurroo--eeccttooddeerrmmaall –– mmoosstt iimmppoorrttaanntt aarree tthhee GGlliioommaass;; MMeesseenncchhyymmaall –– mmoosstt ffrreeqquueenntt oonneess aarree tthhee MMeenniinnggiioommaass;; EEccttooppiicc ttiissssuueess –– ffrroomm ttiissssuueess „„ddiissppllaacceedd”” dduurriinngg eemmbbrryyooggeenneessiiss:: EExx.., DDeerrmmooiidd ccyysstt;; RReettaaiinneedd eemmbbrryyoonnaall ssttrruuccttuurreess:: vvaarriioouuss ccyyssttss –– PPaarraapphhyysseeaall ccyysstt;; MMeettaassttaasseess:: LLuunngg, BBrreeaasstt, MMeellaannoommaa, eettcc.. iinn 550%% ooff ccaasseess
  • 6. Neuro – ecto - dermal tumors Glial cells: astrocytes (A) - Astrocytoma Oligodendroglial cells - Oligodendroglioma Ependymal cells – Ependymoma Neurons - Gangliocytoma
  • 7. CLINICAL PRESENTATION
  • 8. The unique features of CNS tumors – “ICP” 1. They grow in a unique environment: the intracranial space. 2. The intracranial contents - incompressible Brain and blood contained within a rigid unyielding bony structure. 3. Intracranial pathologies (tumors, abscess, hematoma, infarction, edema, etc.) eventually produce life threatening increase of the intracranial-pressure: ICP.
  • 9. Increased Intracranial Pressure (ICP) Headaches, progressively worsening Vomiting (morning) Irritability Papilledema  rare < 2 y/o - head can expand “Double vision” with 6th nerve palsy Head tilt Bulging fontanelle (infant) In a young cchhiilldd wwiitthh ?? bbrraaiinn ttuummoorr:: MMeeaassuurree hheeaadd cciirrccuummffeerreennccee aanndd oobbsseerrvvee ggaaiitt
  • 10. Supratentorial Tumors Signs depend on age and location: Younger child:  Developmental delay or loss of milestones Older child:  Deteriorating school performance  Personality changes
  • 11. Depending on location  Supratentorial tumours: - Motor weakness - Sensory changes - Speech disorders - Seizures - Reflex abnormalities - Hand preference
  • 12.  In midline/infratentorial tumours: - Classical triad of headache, nausea & vomiting and Papilloedema - Blurred vision, nystagmus & diplopia - Disorder of equilibrium, gait & coordination. - Torticolis: in cerebellar tonsil herniation  Diencephlic syndrome: - Failure to thrive - Emaciation & decreased appetite - Euphoric affect
  • 13.  Brain stem tumours: - Gaze palsy - Multiple cranial N palsies - UMN deficits  Optic N pathway tumours: - Visual disturbances like decreased visual acuity, marcus gunn pupil, nystagmus & visual field defects
  • 14. Suprasellar & 3rd Ventricle region tumours Leads to neuroendocrine disturbances like  DI  Galactorrhoea  Precocious puberty  Delayed puberty  Hypothyroidism Perinaud syndrome: - Tumour of pineal region - C/F : paresis of upward gaze, pupillary dilation, reactive to accommodation,not to light,eyelid retraction
  • 15.  Spinal cord tumours: - long N tract motor &/or sensory deficits - Bowel & bladder deficit - Radicular or back pain
  • 16. Seen in kids with increased cellularity
  • 17. ASTROCYTOMAS Account for ~ 80% of primary ICTS in adults MC in the cerebral hemispheres MC Symptoms: headaches, seizures, focal neurologic deficits ( usually in the anterior or middle) Low-grade Astrocytomas:  Gross: Poorly defined gray-white infiltrative tumors.  Histology: Hypercellularity; astrocytic nuclei of mild degree of atypia & astrocytic processes Þ fibrillary background = fingers of astrocytes
  • 18. Low-grade Astrocytomas Pilocytic Astrocytomas:  MC in the cerebellum of children & young adults; and less commonly in the optic nerve, hypothalamic region or cerebral hemispheres  Morphology: Cystic, with a tumor nodule in the wall of the cyst. Composed of bipolar astrocytes, with long hair-like processes, Rosenthal fibers & Micro-cysts+ calcification = good prognosis  Grow very slowly (some patients have survived for >40 yrs after incomplete resection) & have an Excellent prognosis  DD: not to confuse with low grade Fibrillary Astrocytoma
  • 19. Rosenthal fibers
  • 20. Gr. III. astrocytoma
  • 21. Gr. IV. astro ~ = GBM
  • 22. GBM: necrosis/pseudo-palisade Pseudo pallisding central necrosis with perpendicular cells
  • 23. Adverse prognostic factors in pt with high grade Astrocytoma  Older age  Histologic f/o glioblastoma  Poor karnofsky performance status  Unresectable tumour  Pt with unmethylated MGMT
  • 24. Glioblastoma Cerebri  Highly infiltrating, non enhancing tumour involving more than 2 lobes  Histologically different from Glioblastoma but behave aggressively & has poor outcome  T/t: RT + Temozolamide
  • 25. OLIGODENDROGLIOMA Comprise ~ 5 -15% of Gliomas Arise in the cerebral white matter MC in the 4th & 5th decades Gross:  Well circumscribed, gelatinous, gray masses, with foci of hemorrhage & calcification.
  • 26. Histology:  Sheets of cells with rounded nuclei surrounded by a halo of clear cytoplasm (fried egg appearance).  There is often a delicate network of capillaries & scattered foci of calcification (psammoma bodies) Grows slowly, presents commonly with seizures, prognosis is better than Astrocytoma, average survival is 5-10 yrs (with modern therapeutic approaches)
  • 27. Oligodendroglioma
  • 28. EPENDYMOMA Arise from the Ependymal lining of the ventricles or the central canal of the spinal cord Arise in the  Fourth ventricle in children & young adults  Spinal cord in the middle aged. Morphology:  Highly cellular, tumor cells have regular nuclei  May exhibit epithelial features with formation of “rosettes” (Flexner Landsteiner) also perivascular pseudo-rosettes (homer Wright)  Most tumors are well differentiated
  • 29. 4th ventricle tumors:  May cause hydrocephalus, usually can’t be completely removed CSF dissemination may occur Average survival is ~ 4 yrs
  • 30. Myxo-papillary Ependymomas  Arise in the filum terminale of the spinal cord  Prognosis depends on completeness of surgical excision
  • 31. Ependymoma ““RRoosseetttteess”” && ppeerriivvaassccuullaarr PPsseeuuddoo--rroosseetttteess
  • 32. MEDULLOBLASTOMAS Second MC ICT of childhood (after Astrocytomas). Occurs exclusively in the cerebellum. Derived from fetal external granular layer of cerebellum. Grows rapidly & occludes CSF flow ® hydrocephalus.
  • 33. Seeds through CSF ® implants around the spinal cord & cauda equina (need irradiation of the whole Neuraxis). Histology:  Extremely cellular, anaplastic, small round or carrot-shaped cells with hyperchromatic nuclei, ­ N/C, may form Homer-Wright pseudo-rosettes Highly malignant, yet radiosensitive & 5-yr survival 75%.
  • 34. Medulloblastoma
  • 35. Medulloblastoma HHoommeerr--WWrriigghhtt ppsseeuuddoo--rroosseetttteess ccaarrrroott--sshhaappeedd cceellllss
  • 36. MENINGIOMA Usually Benign slow-growing tumors of adults, F/M 3:2 Originate from meningothelial cells of the arachnoid. Usually solitary ( multiple meningiomas Þ NF2 ) Morphology:  Firm rounded masses, adherent to the dura and compressing the underlying brain (no infiltration).  Histologic variants include: Syncytial, fibroblastic, transitional, Psammomatous & papillary (­ propensity to recur).
  • 37. Malignant Meningioma is very rare  Infiltrates the underlying brain, shows marked nuclear atypia, ­ mitoses, & foci of necrosis. Other rare sarcomas of meninges include:  Hemangiopericytoma, malignant fibrous histiocytoma & Fibrosarcoma.
  • 38. Meningioma
  • 39. Meningioma SSyynnccyyttiiaall PPssaammmmoommaattoouuss Epithelial Membrane Antigen
  • 40. NERVE SHEATH TUMORS 1. Schwannomas:  Benign tumors of Schwann cells  MC in the vestibular branch of the VIII CN at the cerebello-pontine angle (acoustic neuroma) ® tinnitus & hearing loss  Also involve branches of the trigeminal nerve & dorsal nerve roots  Tumors are encapsulated, attached to one side of the nerve; axons do not pass through the tumor Consist of Antoni -A areas of high cellularity Antoni -B myxoid areas
  • 41. Schwannoma AAnnttoonnii ––BB SSppaarrsseellyy cceelllluullaarr Antoni –– AA hhyypprreecceelllluullaarr
  • 42. 2. Neurofibromas:  Benign tumors composed predominately of Schwann cells, but also containing fibroblasts & perineural cells  May involve single or multiple dorsal spinal nerve roots (multiple in patients with von Ricklinghausen's disease – NF1)  CN involvement is extremely rare  May present as Localized fusiform enlargement of a nerve or Extensively infiltrate along the nerve ® “ropy enlargement” of the nerve & it’s branches (plexiform Neurofibroma)  Plexiform neurofibromas are usually part of NF1, excision is very difficult  Histology: Wavy spindle shaped cells, myxoid collagenous stroma with interspersed nerve fibers
  • 43. „Acoustic Neurinoma” (Schwannoma)
  • 44. METASTATIC ICTS Very rare in children. Common Primaries:  Broncho-genic small cell undifferentiated (oat cell) ca., Breast ca., Malignant melanoma, RCC. & Colon ca. Sites of metastases:  Cerebral cortex 80%;  Rest are in the cerebellum & brain stem. 50% are multiple; at the junction between the gray & white matter. Vertebral column is a common site for metastases of  Breast & Prostatic carcinomas  Thoracic spine 60%, Cervical 20% & Lumbar 20% Treatment : Radiotherapy
  • 45. CHOROID PLEXUS PAPILLOMA MC in children  Arising from the lateral ventricles In adults they are found MC in the 4th ventricle Present with Hydrocephalus  Due to either over-production of CSF or to obstruction of the ventricular system. Consist of papillae with fibrovascular stalks covered with a cuboidal or columnar ciliated epithelium, recapitulating the structure of the normal choroid plexus.
  • 46. COLLOID CYST OF THE THIRD VENTRICLE A non-neoplastic cystic lesion Morphology:  Having a thin fibrous capsule, a lining of Cuboidal to columnar epithelium & containing gelatinous Proteinaceous material. Attached to the roof of the third ventricle at the foramina of Munroe & may cause sudden obstruction of the CSF flow ® acute non-communicating hydrocephalus ® brain herniation & death Symptoms: headaches (often positional), “drop attacks”, incontinence Goblet cells are confirmatory
  • 47. MISCELLANEOUS (MIDLINE) TUMORS Pinealomas:  True pineocytomas are extremely rare, may also have pineoblastomas Germinomas:  MC in the pineal & suprasellar regions in adolescents & young adults  Closely resemble testicular Seminomas & ovarian Dysgerminomas  Other GCTs (Teratomas & Choriocarcinomas) also occur
  • 48. Craniopharyngioma  Benign cystic tumors of children & adolescents  Develop in the suprasellar region ® Hypopituitarism  Originate from remnants of Rathke’s pouch & contain squamous & columnar epithelium  calcifications are common.
  • 49. CNS LYMPHOMA Primary CNS lymphomas  Account for ~1% of ICTs  MC CNS neoplasm in AIDS & other immunosuppressed patients often arise deep within the cerebral hemispheres & are commonly bilateral  Lymphoma cells exhibit an angiocentric distribution  Usually are B-cell lymphomas & many appear to be EBV-related.
  • 50. PCNSL: Pathophysiology Focal Lesion most common presentation: others include diffuse, uveal, leptomeningeal, and intramedullary. Infiltrates normal brain diffusely. Spreads along CSF pathways. Rarely spreads outside the CNS.
  • 51. Secondary CNS lymphomas  Lymphomas arising outside of the CNS rarely involve the brain parenchyma  May involve the meninges, intradural spinal nerve roots & epidural space
  • 52. Leptomeningeal Carcinomatosis Occurs in 5-8% of patients with solid tumors Most common tumors to metastasize to the leptomeninges are small cell carcinoma (9- 18%), and NHL (5-29%) Other tumors include non-small cell lung, breast, melanoma, and G.U.
  • 53. Leptomeningeal Carcinomatosis: Clinical Presentation SYMPTOMS SIGNS Headaches 33% Reflex assymetry(71%) Lower Motor Weakness 38% Weakness 60% Parasthesias 34% Back/Neck Pain 26% Sensory Loss 27% Radicular Pain 33% CN III Paresis 20% Diplopia 20% CN VII Paresis 17% Mental Status change 17%
  • 54. Carcinomatous Meningitis Diagnosis: MRI Cerebral Spinal Fluid Rarely myelography
  • 55. PHAKOMATOSES Neurocutaneous syndromes AD Hamartomas & Neoplasms  Esp. involving the nervous system & skin  Mutations in tumor suppressor genes
  • 56. 1. Neurofibromatosis Type 1 (NF1):  Neurofibromas, Neurofibro-sarcomas  Optic nerve Gliomas  Pigmented cutaneous macules (café au lait spots)  Pigmented nodules of iris (Lisch nodules) 2. Neurofibromatosis Type 2 (NF2):  Bilateral Schwannomas of CN VIII  Multiple meningiomas  Spinal cord Ependymomas
  • 57. 3. Tuberous Sclerosis Hamartomas (“tubers”) in the cerebral cortex, Sub-Ependymal hamartomas (“candle drippings”) & Sub-Ependymal giant cell Astrocytomas Seizures & mental retardation Extra CNS findings:  Kidney (Angiomyolipoma), Heart (Rhabdomyoma MCC in kids, adult = myxomas) , skin (Angiofibroma)
  • 58. Tuberous Sclerosis
  • 59. 4. von Hippel-Lindau disease Hemangioblastomas of the cerebellum, retina, brain stem & spinal cord Cysts of liver, kidney & pancreas ­­ incidence of RCC, may be bilateral ~ 10% of Hemangioblastomas Þ polycythemia Total surgical removal is curative
  • 60. Von Hippel-Lindau disease HHeemmaannggiioobbllaassttoommaass
  • 61. DDIIAAGGNNOOSSIISS
  • 62.  Evaluation on emergency basis  Complete history, physical examination & neurologic assessment with neuroimaging  For primary tumours: MRI with gadolinium contrast is the gold standard.  Low grade glioma: FLAIR MRI  MRI better than CT: Tumor of suprasellar, optic path, infratentorial & pituitary region
  • 63. Specific investigations  Neuroendocrine dysfunction evaluation : in tumor of suprasellar,midline, pituitary & optic chiasmal region  Serum & CSF bHCG and AFP: germ cell T  Lumbar Puncture: - Indication: Medulloblastoma, ependymoma & germ cell tumours - C/I : newly dx hydrocephalous sec. to CSF flow obstruction, tumour causing supratentorial midline shift & infratentorial tumours.
  • 64. MMAANNAAGGEEMMEENNTT  Multimodal i.e. surgery +/- chemoradiation  Symptomatic & definitive  Definitive:- depends on specific tumour type
  • 65. Symptomatic  Glucocoticoids: decrease perilesional edema & improve neurologic function - DDeexxaammeetthhaassoonnee is the DOC bcoz of low mineralcorticoid activity  Seizure: anticonvulsants - leviteracetam, topiramate, lamotrigine, valproic acid & Lacosamide - Phenytoin & carbamazepine should be avoided as they may hamper the action of chemo bcoz they are enzyme inducers.
  • 66.  Venous thromboembolism: - Ass. With 20-30 % patients with high grade glioma & brain metastasis - Anticoagulants should be used prophylactically
  • 67. Astrocytoma: Surgical Treatment Advantages of Large Resection Accurate histological grade  Palliation of mass effect  ? Improved quality of life Decreased dexamethasone requirement ? Impact on overall survival  Retrospective studies say yes  No prospective, randomized trials
  • 68. Radiation Therapy & Chemotherapy Chemotherapy following external beam radiation is advantageous in adults with anaplastic gliomas. Much less benefit is seen in patients with glioblastoma. The few glioblastoma patients who benefit tend to be those that live the longest, suggesting that treatment preferentially benefits patients with favorable prognostic factors (i.e. young age, good P.S., minimal post-op, residual tumor).
  • 69. Glioblastoma  Maximal surgical resection f/b Partial field external beam radiotherapy with concomittant Temozolamide f/b 6-12 months of adjuvant Temozolamide  In c/o recurrence: reoperation, BCNU/ bevacizumab
  • 70. Temozolomide Active metabolite of DTIC Crosses the blood-brain barrier Oral dosing: 200mg or 150mg/m2/x5d q4 weeks Well tolerated: nausea/vomiting, myelosuppression Idiosyncratic myelosuppression
  • 71. Temozolomide Indications:  Relapsed Gr III anaplastic gliomas  Grade IV glioblastoma multiformae Role in initial therapy uncertain:  Probably equivalent to nitrosourea or PCV for high grade gliomas  Role as a radiosensitizer highly questionable (?) effective in oligodendroglioma.
  • 72. Oligodendroglioma: Treatment Complete surgical resection optimal Radiation therapy of questionable benefit Anaplastic oligodendrogliomas are chemosensitive tumors: Active regimens include:  Single agent nitrosoureas  PCV  Temozolomide  Other alkylating agents Chromosomal karyotypes may help predict therapeutic and clinical outcomes.
  • 73. PCNSL: Treatment Surgery For Diagnostic purposes only; extensive resection contraindicated. Histologic diagnosis may be difficult from a stereotactic biopsy.
  • 74. PCNSL: Radiotherapy Historically standard Tx 80% radiographic CR 14-18 month median survival
  • 75. PCNSL: Treatment • PCNSL recurrent after radiation is often chemotherapy sensitive, although few (if any) are cured. • Drugs should possess anti-lymphoma activity and have at least some ability to traverse a partially disrupted, if not intact BBB ••Multiple drugs shown to have anti-PCNSL activity Methotrexate (high-dose) Procarbazine, CCNU, Vincristine BCNU Ara-C Cyclophosphamide, Adriamycin,Vincristine, Prednisone (“CHOP”). Decadron
  • 76. Brain Metastases: Treatment Solitary Metastases Goals: 1. Palliate neurologic symptoms 2. Decrease future neurologic morbitiy 3. Prolong Survival 4. Potentially “cure” selected patients Treatment: 1. Surgery if medically and anatomically indicated.
  • 77. Brain Metastases: Treatment Multiple Metastases Goals: 1. Palliate neurological symptoms 2 Decrease future neurological morbidity 3. Prolong survival in selected patients Treatment: 1. Whole brain XRT 2. Chemotherapy for chemosensitive tumors (i.e. breast cancer, small cell lung carcinoma)
  • 78. Leptomeningeal Carcinomatosis Goals of Treatment: Destroy circulating and perineural neoplastic cells to stabilize or improve neurologic dysfunction. Prolong survival in specific tumor types (lymphoma, leukemia, breast carcinoma).
  • 79. Leptomeningeal Carcinomatosis Radiation Treatment: Involved field for acute cranial or spinal nerve involvement No cranial-spinal Chemotherapy Intra-CSF: Intrventricular vs. Intrathecal (MTX, ara-C, Depocyte, Thiotepa)  Ease of administration  Patient Comfort  Optimal CSF drug distribution Systemic (?)
  • 80. Spinal Cord Compression Treatment: Dexamethasone Surgical Decompression Laminectomy Anterior resection Radiotherapy  treatment of choice.
  • 81. Spinal Cord Compression Indications for Surgical Interventions: Chance of restoring/preserving neurological function (anterior resection)* Initial presentation from an unknown neoplasm. Previously irradiated field. * Vertebral instability. * Progressive neuroloic deteriation during and following XRT. * Intractable pain despite adequate XRT, steroids, and analgesics. * The decision to surgically intervene ultimately depends on an estimate of the morbidity of surgery versus the potential for significant quality survival.
  • 82. Take home points  Brain tumors are second most common  Brain tumour with best prognosis in children is JPA & worst prognosis : Brain stem Gliomas  Over 70% of children diagnosed with cancer can be cured of their disease.  Management is through multimodal approach
  • 83. THANK U