4 INTRACRANIAL TUMORS (ICTS) Primary or MetastaticOccur with equal frequency in adults, but in children primary tumors are far more common.Primary ICTs account for~2% of cancers in adults20% of all cancers in children.In children 70% of ICTs arise in Posterior fossa (infra-tentorial). asIn adults 70% of ICTs arise in Supra-tentorial.Because of its location, a benign ICT may have fatal “malignant” effects.Malignant ICTs spread by:Direct infiltration of adjacent tissuesMay disseminate within the CNS via CSF.Gliomas account for 60% of primary ICTsMeningiomas for 20% & all others 20%.All CNS tumors behave as malignant clinically . Limited spaceLess than 5 years small round cell tumors eg wills, neuroblastoma leukemia's ets between 5 to 14 lymphomas and CNS tumors
6 The unique features of CNS tumors – “ICP” 1. CNS tumors- < 2% of all malignant tumors. 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.
7 Cytologic origin of CNS tumors Neuro-ectodermal – most important are the Gliomas;Mesenchymal – most frequent ones are the Meningiomas;Ectopic tissues – from tissues „displaced” during embryogenesis: Ex., Dermoid cyst;Retained embryonal structures: various cysts – Paraphyseal cyst;Metastases: Lung, Breast, Melanoma, etc. in 50% of cases
9 WHO Grading System (evolves) Low-gradeWHO Grade I i.e., Juvenile Pilocytic AstrocytomaWHO Grade II i.e., Diffuse AstrocytomaHigh-gradeWHO Grade III i.e., Anaplastic AstrocytomaWHO Grade IV i.e., Glioblastoma Multiforme
10 ASTROCYTOMAS Account for ~ 80% of primary ICTS in adults MC in the cerebral hemispheresMC 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 fibrillary background = fingers of astrocytes
11 Low-grade Astrocytomas Pilocytic Astrocytomas:MC in the cerebellum of children & young adults; and less commonly in the optic nerve, hypothalamic region or cerebral hemispheresMorphology: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 prognosisGrow very slowly (some patients have survived for >40 yrs after incomplete resection) & have an Excellent prognosisDD ;- not to confuse with low grade Fibrillary Astrocytoma
16 Gr. II. AstrocytomaHypercellularity + nuclear atypia
17 Low-Grade Astrocytoma (Grade II) CharacteristicsSlow growingRarely spreads to other parts of the CNSBorders not well definedCommon among men and women in their 20s-50sTreatmentTreatment depends on the size and location of the tumor. The doctor will most likely perform a biopsy or surgery to remove the tumor. Partial resections or inoperable tumors may be treated with radiation. Recurring tumors may require additional surgery, radiation and/or chemotherapy.
21 Gr. III. AstrocytomaIncreased cellularity + nuclear atypia+ mitotic figures
22 Anaplastic Astrocytoma (Grade III) Characteristics Grows faster and more aggressively than grade II astrocytomasTumor cells are not uniform in appearanceInvades neighboring tissueCommon among men and women in their 30s-50sMore common in men than womenAccounts for four percent of all brain tumorsTreatmentTreatment depends on the location of the tumor and how far it has progressed. Surgery and radiation therapy, with chemotherapy during or following radiation, are the standard treatments. If surgery is not an option, then the doctor may recommend radiation and/or chemotherapy. Many clinical trials (experimental treatments) using radiation, chemotherapy, or a combination are available for initial and recurrent anaplastic astrocytomas
24 Glioblastoma Multiforme (GBM ) (Grade IV ) Characteristics Most invasive type of glial tumorCommonly spreads to nearby tissueGrows rapidlyMay be composed of several different kinds of cells (i.e., astrocytes, oligodendrocytes)May have evolved from a low-grade astrocytoma or an oligodendroglioma (see below)Common among men and women in their 50s-70sMore common in men than womenAccounts for 23 percent of all primary brain tumors
25 TreatmentStandard treatment is surgery followed by radiation therapy. If surgery is not an option, the doctor may administer radiation therapy. Chemotherapy is sometimes given during or after radiation therapy or if the tumor recurs. Many clinical trials (experimental treatments) using radiation, chemotherapy, or a combination are available for initial and recurrent GBM.
32 OLIGODENDROGLIOMA Comprise ~ 5 -15% of Gliomas Arise in the cerebral white matterMC in the 4th & 5th decadesGross:Well circumscribed, gelatinous, gray masses, with foci of hemorrhage & calcification.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)( seen in thyroid, CNS, kidneys etc).Grows slowly, presents commonly with seizures, prognosis is better than Astrocytoma, average survival is 5-10 yrs (with modern therapeutic approaches
37 EPENDYMOMAArise from the Ependymal lining of the ventricles or the central canal of the spinal cordArise in theFourth ventricle in children & young adultsSpinal cord in the middle aged.Morphology:Highly cellular, tumor cells have regular nucleiMay exhibit epithelial features with formation of “rosettes” (Flexner…) or “canals”, also perivascular pseudo-rosettes (homer …)Most tumors are well differentiated4th ventricle tumors:May cause hydrocephalus, usually can’t be completely removedCSF dissemination may occurAverage survival is ~ 4 yrs
38 Myxo-papillary Ependymomas Arise in the filum terminale of the spinal cordPrognosis depends on completeness of surgical excision
40 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.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-rosettesHighly malignant, yet radiosensitive & 5-yr survival 75%.
43 Usually Benign slow-growing tumors of adults, F/M 3:2 MENINGIOMASUsually Benign slow-growing tumors of adults, F/M 3:2Originate from meningothelial cells of the arachnoid.Usually solitary ( multiple meningiomas 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).Malignant Meningioma is very rareInfiltrates the underlying brain, shows marked nuclear atypia, mitoses, & foci of necrosis.Other rare sarcomas of meninges include:Hemangiopericytoma, malignant fibrous histiocytoma & Fibrosarcoma.
44 MeningiomaEasily removed with little neurological complication rarely
48 NERVE SHEATH TUMORS 1. Schwannomas: Consist of Benign tumors of Schwann cellsMC in the vestibular branch of the VIII CN at the cerebello-pontine angle (acoustic neuroma) tinnitus & hearing lossAlso involve branches of the trigeminal nerve & dorsal nerve rootsTumors are encapsulated, attached to one side of the nerve; axons do not pass through the tumorConsist ofAntoni -A areas of high cellularityNuclei form palisades “Verocay bodies”Antoni -B myxoid areas
51 SchwannomaAntoni – A hyprecellularAntoni –B Sparsely cellular
52 2. Neurofibromas:Benign tumors composed predominately of Schwann cells, but also containing fibroblasts & perineural cellsMay involve single or multiple dorsal spinal nerve roots (multiple in patients with von Ricklinghausen's disease - NF1)CN involvement is extremely rareMay present asLocalized fusiform enlargement of a nerve orExtensively infiltrate along the nerve “ropy enlargement” of the nerve & it’s branches (plexiform Neurofibroma)Plexiform neurofibromas are usually part of NF1, excision is very difficultHistology:Wavy spindle shaped cells, myxoid collagenous stroma with interspersed nerve fibers
53 Neurofibromatosis - Von Recklinghausen Dominant inheritanceMultiple neurofibromasCentral - CNSperipheral nervesIncreased incidence of:meningiomagliomaschwannoma - bilateral VIII N.Cafe-au-lait (melanosis) in skinElephantiasis: increased connective tissue
54 Von Recklinghausen’s Disease Café-au-lait spotsMultiple neurofibromas
56 METASTATIC ICTS 50% of ICTs. Common Primaries: Sites of metastases: 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 ofBreast & Prostatic carcinomasThoracic spine 60%, Cervical 20% & Lumbar 20%Treatment : Radiotherapy
57 MetastasisTumor material different from brain tissue
59 CHOROID PLEXUS PAPILLOMA MC in children Arising from the lateral ventriclesIn adults they are found MC in the 4th ventriclePresent with HydrocephalusDue 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.
60 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 & deathSymptoms: headaches (often positional), “drop attacks”, incontinenceGoblet cells are confirmatory
61 MISCELLANEOUS (MIDLINE) TUMORS Pinealomas:True pineocytomas are extremely rare, may also have pineoblastomasGerminomas:MC in the pineal & suprasellar regions in adolescents & young adultsClosely resemble testicular Seminomas & ovarian DysgerminomasOther GCTs (Teratomas & Choriocarcinomas) also occurNot clear how GCTs arise within the CNSCraniopharyngiomas:Benign cystic tumors of children & adolescentsDevelop in the suprasellar region HypopituitarismOriginate from remnants of Rathke’s pouch & contain squamous & columnar epithelium, calcifications are common.
62 CNS LYMPHOMA Primary CNS lymphomas Secondary CNS lymphomas Account for ~1% of ICTsMC CNS neoplasm in AIDS & other immunosuppressed patients often arise deep within the cerebral hemispheres & are commonly bilateralLymphoma cells exhibit an angiocentric distributionUsually are B-cell lymphomas & many appear to be EBV-related.Secondary CNS lymphomasLymphomas arising outside of the CNS rarely involve the brain parenchymaMay involve the meninges, intradural spinal nerve roots & epidural space
63 Phakomatosis (Neurocut. dysplasia) Neurologic abnormalities + defects of skin or retina (ectodermal).Neurofibromatosis (von Recklinghausen)Tuberous SclerosisSturge-Weber Sy (Encephalofacial Angiomatosis)von Hippel-Lindau DiseaseNeurocutaneous Melanosis
64 PHAKOMATOSES NEUROCUTANEOUS SYNDROMES (PHAKOMATOSES) AD Hamartomas & NeoplasmsEsp. involving the nervous system & skinMutations in tumor suppressor genes1. Neurofibromatosis Type 1 (NF1):Neurofibromas, Neurofibro-sarcomasOptic nerve GliomasPigmented cutaneous macules (café au lait spots)Pigmented nodules of iris (Lisch nodules)2. Neurofibromatosis Type 2 (NF2):Bilateral Schwannomas of CN VIIIMultiple meningiomasSpinal cord Ependymomas
66 4. von Hippel-Lindau disease Hemangioblastomas of the cerebellum, retina, brain stem & spinal cordCysts of liver, kidney & pancreas incidence of RCC, may be bilateral~ 10% of Hemangioblastomas polycythemia
67 Peripheral nerve tumors SchwannomaSchwann cellsCompress the nerve trunkEncapsulatedEasily resectable without nerve damageMicroscopic:Antony A and B fibersVerocay bodiesNeurofibromaSchwann cells, neurites, fibroblastsFusiform and involves nerve trunkNot encapsulatedNot resectable without sacrificing nerveMicro- Intermingled cells with wavy nuclei
68 Embryonal tumors (Primitive neuroectodermal tumors) Neuroblastoma - cerebral hemispheres Neuroblastic (neuronal) differentiationMedulloblastoma - cerebellum Neuronal and glial differentiationEpendymoblastoma – ventricles Ependymal differentiationPineoblastoma- pineal region Retinoblastic differentiationAll commonly known as Primitive neuroectodermal tumor (PNET)
69 Histologic patterns: definitions Whorls: onion-skinning pattern of tumor cellsPsammoma bodies: laminated calciumPseudopalisading: lining up of the tumor cells around a central necrotic areaPalisade: lining up of tumor cells around their own cytoplasmic processes. No necrosis.Pseudorosette: tumor cells around blood vessels, cells equidistant from vessel walls.Rosettes: tumor cells around central lumen or fibrillary area of cellular processes
71 Metastatic brain tumors Most common brain tumor in adults.Common primary sites: melanoma, lung, breast, GI tract, kidney.Most are in cerebrum (MCA territory).In gray-white junctions due to rich capillarityDiscrete, globoid, sharply demarcated tumors. Amenable to surgical resection.Single or multiple.Brain edema frequent.