tumors of the cns

Central Nervous SystemCentral Nervous System9. 9. TumorsTumors

Central Nervous SystemCentral Nervous System9. 9. TumorsTumors

INTRACRANIAL TUMORS (ICTS)INTRACRANIAL TUMORS (ICTS)

Primary or MetastaticPrimary or MetastaticOccur with Occur with equal frequency in adultsequal frequency in adults, but in , but in children primarychildren primary tumors are far more common.tumors are far more common.Primary ICTs account for Primary ICTs account for – ~2% of cancers in adults~2% of cancers in adults– 20% of all cancers in children.20% of all cancers in children.

In In children 70% of ICTs arise in children 70% of ICTs arise in Posterior fossa (infra- Posterior fossa (infra-tentorial).tentorial). as asIn In adultsadults 70% of ICTs arise in 70% of ICTs arise in Supra-tentorial Supra-tentorial. . Because of its location, a Because of its location, a benign ICTbenign ICT may have fatal may have fatal “malignant” effects“malignant” effects..Malignant ICTs spread by: Malignant ICTs spread by: – Direct infiltration of adjacent tissuesDirect infiltration of adjacent tissues– May disseminate within the CNS via CSF.May disseminate within the CNS via CSF.

GliomasGliomas account for account for 60% of primary ICTs60% of primary ICTsMeningiomas for 20% & all others 20%.Meningiomas for 20% & all others 20%.All CNS tumors behave as malignant clinically . Limited spaceAll CNS tumors behave as malignant clinically . Limited space

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.

Cytologic origin of CNS tumorsCytologic origin of CNS tumors

Neuro-ectodermalNeuro-ectodermal – most important are the – most important are the GliomasGliomas;;

MesenchymalMesenchymal – most frequent ones are the – most frequent ones are the MeningiomasMeningiomas;;

Ectopic tissuesEctopic tissues – from tissues „displaced” during – from tissues „displaced” during embryogenesis: Ex., embryogenesis: Ex., DermoidDermoid cyst; cyst;

Retained embryonal structuresRetained embryonal structures: various cysts – : various cysts – Paraphyseal cystParaphyseal cyst;;

MetastasesMetastases:: Lung, Breast, Melanoma, etc. in 50% Lung, Breast, Melanoma, etc. in 50% of casesof cases

Neuro – ecto - dermal tumorsNeuro – ecto - dermal tumors

Glial cells:Glial cells:

astrocytes (A) - astrocytes (A) - AstrocytomaAstrocytoma

Oligodendroglial cells - Oligodendroglial cells - OligodendrogliomaOligodendroglioma

Ependymal cells – Ependymal cells – EpendymomaEpendymoma

Neurons - Neurons - GangliocytomaGangliocytoma

Incidence of brain tumorsIncidence of brain tumors

Seen in kids with increased cellularity

What is „benign” and „malignant” in case of CNS tumors?

ASTROCYTOMASASTROCYTOMAS

Account for ~ Account for ~ 80% of primary ICTS in adults80% of primary ICTS in adults

MC in the MC in the cerebral hemispherescerebral hemispheres

MC Symptoms: headaches, seizures, focal MC Symptoms: headaches, seizures, focal neurologic deficits ( usually in the anterior or neurologic deficits ( usually in the anterior or middle)middle)

Low-grade AstrocytomasLow-grade Astrocytomas::– Gross: Gross:

Poorly defined gray-white infiltrative tumors.Poorly defined gray-white infiltrative tumors.

– Histology: Histology: HypercellularityHypercellularity; astrocytic nuclei of mild degree of atypia & ; astrocytic nuclei of mild degree of atypia & astrocytic processes astrocytic processes fibrillary background = fingers of fibrillary background = fingers of

astrocytes astrocytes

Low-grade AstrocytomasLow-grade Astrocytomas

Pilocytic AstrocytomasPilocytic Astrocytomas::– MC in the MC in the cerebellum of children & young adultscerebellum of children & young adults; and ; and

less commonly in the less commonly in the optic nerveoptic nerve, hypothalamic , hypothalamic region or cerebral hemispheresregion or cerebral hemispheres

– Morphology:Morphology:Cystic, with a tumor nodule in the wall of the cyst.Cystic, with a tumor nodule in the wall of the cyst.Composed of bipolar astrocytes, with long hair-like Composed of bipolar astrocytes, with long hair-like processes, processes, Rosenthal fibersRosenthal fibers & & Micro-cysts+ Micro-cysts+ calcification = good prognosiscalcification = good prognosis

– Grow very slowly (some patients have survived for Grow very slowly (some patients have survived for >40 yrs after incomplete resection) & have an >40 yrs after incomplete resection) & have an Excellent prognosisExcellent prognosis

– DD ;- not to confuse with low grade Fibrillary DD ;- not to confuse with low grade Fibrillary AstrocytomaAstrocytoma

Grade I. tumor: pilocytic astro~Grade I. tumor: pilocytic astro~

Pilocytic AstrocytomaPilocytic Astrocytoma

Rosenthal fibersRosenthal fibers

Gr. II. AstrocytomaGr. II. Astrocytoma

Gr. II. astrocytomaGr. II. astrocytoma

Gr. III. astrocytomaGr. III. astrocytoma

GGrr. III. Astrocytoma. III. Astrocytoma

Gr. IV. astro ~ = GBMGr. IV. astro ~ = GBM

GBM: necrosis/pseudo-palisadeGBM: necrosis/pseudo-palisade

GBM: pleomorphic cytologyGBM: pleomorphic cytology

Gr. IV. Astro ~ = GBMGr. IV. Astro ~ = GBM

Die directly

OLIGODENDROGLIOMAOLIGODENDROGLIOMAComprise ~ 5 -15% of GliomasComprise ~ 5 -15% of GliomasArise in the Arise in the cerebral white mattercerebral white matter MC in the MC in the 4th & 5th decades4th & 5th decadesGross: Gross: – Well circumscribed, gelatinous, gray masses, with Well circumscribed, gelatinous, gray masses, with foci of foci of

hemorrhage & calcification. hemorrhage & calcification.

Histology: Histology: – Sheets of cells with rounded nuclei surrounded by a halo Sheets of cells with rounded nuclei surrounded by a halo

of clear cytoplasm (of clear cytoplasm (fried egg appearancefried egg appearance). ). – There is often a delicate network of capillaries & There is often a delicate network of capillaries &

scattered foci of calcification (scattered foci of calcification (psammoma bodiespsammoma bodies)( seen )( seen in thyroid, CNS, kidneys etc).in thyroid, CNS, kidneys etc).

Grows slowly, presents commonly with seizures, Grows slowly, presents commonly with seizures, prognosis is better than Astrocytomaprognosis is better than Astrocytoma, average , average survival is 5-10 yrs (with modern therapeutic survival is 5-10 yrs (with modern therapeutic approaches approaches

OligodendrogliomaOligodendroglioma

Oligo-AstrocytomaOligo-Astrocytoma

EPENDYMOMAEPENDYMOMAArise from the Arise from the Ependymal liningEpendymal lining of the ventricles or of the ventricles or the central canal of the spinal cord the central canal of the spinal cord Arise in the Arise in the – Fourth ventricleFourth ventricle in in children & young adultschildren & young adults– Spinal cord in the middle aged.Spinal cord in the middle aged.

Morphology:Morphology:– Highly cellular, tumor cells have regular nucleiHighly cellular, tumor cells have regular nuclei– May exhibit epithelial features with formation of “May exhibit epithelial features with formation of “rosettesrosettes” ”

(Flexner…) or “canals”, also perivascular (Flexner…) or “canals”, also perivascular pseudo-pseudo-rosettes (homer …)rosettes (homer …)

– Most tumors are Most tumors are well differentiatedwell differentiated

4th ventricle tumors: 4th ventricle tumors: – May cause hydrocephalus, usually can’t be completely May cause hydrocephalus, usually can’t be completely

removed removed

CSF dissemination may occur CSF dissemination may occur Average survival is ~ 4 yrs Average survival is ~ 4 yrs

Myxo-papillary EpendymomasMyxo-papillary Ependymomas

– Arise in the Arise in the filum terminalefilum terminale of the spinal cord of the spinal cord– Prognosis depends on completeness of Prognosis depends on completeness of

surgical excisionsurgical excision

EpendymomaEpendymoma

““Rosettes” & perivascular Pseudo-rosettesRosettes” & perivascular Pseudo-rosettes

MEDULLOBLASTOMASMEDULLOBLASTOMASSecond MC ICT of childhood (after Astrocytomas).Second MC ICT of childhood (after Astrocytomas).Occurs Occurs exclusivelyexclusively in the in the cerebellumcerebellum..Derived from fetal Derived from fetal external granular layer of external granular layer of cerebellum.cerebellum.Grows rapidly & occludes CSF flowGrows rapidly & occludes CSF flow hydrocephalus. hydrocephalus.Seeds through CSFSeeds through CSF implants around the spinal cord implants around the spinal cord & cauda equina (need irradiation of the whole & cauda equina (need irradiation of the whole Neuraxis).Neuraxis).Histology:Histology:– Extremely cellular, anaplastic, small round or Extremely cellular, anaplastic, small round or carrot-shaped carrot-shaped

cellscells with hyperchromatic nuclei, with hyperchromatic nuclei, N/C, may form N/C, may form Homer-Homer-Wright pseudo-rosettesWright pseudo-rosettes

Highly malignantHighly malignant, yet , yet radiosensitiveradiosensitive & 5-yr survival & 5-yr survival 75%.75%.

MedulloblastomaMedulloblastoma

MedulloblastomaMedulloblastomaHomer-Wright pseudo-rosettesHomer-Wright pseudo-rosettes

carrot-shaped cellscarrot-shaped cells

MENINGIOMASMENINGIOMAS

Usually Usually Benign slow-growingBenign slow-growing tumors of adults, F/M 3:2 tumors of adults, F/M 3:2Originate from Originate from meningothelial cellsmeningothelial cells of the arachnoid. of the arachnoid.Usually Usually solitary solitary ( multiple meningiomas ( multiple meningiomas NF2 ) NF2 ) Morphology:Morphology:– Firm rounded masses, adherent to the dura and Firm rounded masses, adherent to the dura and

compressing the underlying brain (no infiltration).compressing the underlying brain (no infiltration).– Histologic variants include: Histologic variants include:

Syncytial, fibroblastic, transitional, Psammomatous & Syncytial, fibroblastic, transitional, Psammomatous & papillary (papillary ( propensity to recur). propensity to recur).

Malignant Meningioma is very rareMalignant Meningioma is very rare– Infiltrates the underlying brain, shows marked nuclear atypia, Infiltrates the underlying brain, shows marked nuclear atypia,

mitoses, & foci of necrosis. mitoses, & foci of necrosis.

Other rare sarcomas of meninges include: Other rare sarcomas of meninges include: – Hemangiopericytoma, malignant fibrous histiocytoma & Hemangiopericytoma, malignant fibrous histiocytoma &

Fibrosarcoma.Fibrosarcoma.

MeningiomaMeningioma

MeningiomaMeningiomaSyncytialSyncytial PsammomatousPsammomatous Epithelial Membrane Antigen

NERVE SHEATH TUMORSNERVE SHEATH TUMORS1. Schwannomas1. Schwannomas::

– Benign Benign tumors of Schwann cellstumors of Schwann cells– MC in the MC in the vestibular branch of the VIII CNvestibular branch of the VIII CN at the cerebello- at the cerebello-

pontine angle (acoustic neuroma) pontine angle (acoustic neuroma) tinnitus & hearing losstinnitus & hearing loss – Also involve branches of the trigeminal nerve & dorsal nerve Also involve branches of the trigeminal nerve & dorsal nerve

roots roots – Tumors are encapsulated, attached to one side of the nerve; Tumors are encapsulated, attached to one side of the nerve;

axons do not pass through the tumoraxons do not pass through the tumor

Consist of Consist of Antoni -AAntoni -A areas of high cellularity areas of high cellularity

– Nuclei form palisades “Verocay bodies” Nuclei form palisades “Verocay bodies”

Antoni -B Antoni -B myxoid areasmyxoid areas

SchwannomaSchwannoma

Antoni – A hyprecellularAntoni – A hyprecellularAntoni –B Sparsely cellularAntoni –B Sparsely cellular

2. Neurofibromas2. Neurofibromas:: – BenignBenign tumors composed predominately of Schwann cells, but also tumors composed predominately of Schwann cells, but also

containing fibroblasts & perineural cells containing fibroblasts & perineural cells – May involve single or multiple dorsal spinal nerve roots (May involve single or multiple dorsal spinal nerve roots (multiplemultiple in in

patients with patients with von Ricklinghausen's disease - NF1von Ricklinghausen's disease - NF1) ) – CN involvement is extremely rare CN involvement is extremely rare – May present as May present as

Localized fusiform enlargement of a nerve or Localized fusiform enlargement of a nerve or

Extensively infiltrate along the nerve Extensively infiltrate along the nerve “ropy enlargement”“ropy enlargement” of the of the nerve & it’s branches nerve & it’s branches (plexiform Neurofibroma)(plexiform Neurofibroma)

– PlexiformPlexiform neurofibromas are usually part of neurofibromas are usually part of NF1NF1, excision is very , excision is very difficultdifficult

– Histology: Histology:

Wavy spindle shaped cells, myxoid collagenous stroma with Wavy spindle shaped cells, myxoid collagenous stroma with interspersed nerve fibers interspersed nerve fibers

„„Acoustic Neurinoma” Acoustic Neurinoma” (Schwannoma)(Schwannoma)

METASTATIC ICTSMETASTATIC ICTS50% of ICTs. 50% of ICTs. Common Primaries: Common Primaries: – Broncho-genic small cell undifferentiated (oat cell) ca., Broncho-genic small cell undifferentiated (oat cell) ca.,

Breast ca., Malignant melanoma, RCC. & Colon ca.Breast ca., Malignant melanoma, RCC. & Colon ca.

Sites of metastases: Sites of metastases: – Cerebral cortex 80%;Cerebral cortex 80%; – Rest are in the cerebellum & brain stem. Rest are in the cerebellum & brain stem.

50% are multiple50% are multiple; at the ; at the junctionjunction between the between the gray & gray & white matter.white matter.

Vertebral columnVertebral column is a common site for metastases is a common site for metastases of of – BreastBreast & & Prostatic Prostatic carcinomas carcinomas– Thoracic Thoracic spine 60%, Cervical 20% & Lumbar 20%spine 60%, Cervical 20% & Lumbar 20%

Treatment : RadiotherapyTreatment : Radiotherapy

MetastasisMetastasis

CHOROID PLEXUS PAPILLOMACHOROID PLEXUS PAPILLOMA MC in childrenMC in children Arising from the Arising from the lateral lateral ventriclesventriclesIn In adultsadults they are found MC in the they are found MC in the 4th 4th ventricle ventricle Present with Present with HydrocephalusHydrocephalus– Due to either over-production of CSF or to Due to either over-production of CSF or to

obstruction of the ventricular system.obstruction of the ventricular system.

Consist of Consist of papillae with fibrovascular papillae with fibrovascular stalksstalks covered with a cuboidal or columnar covered with a cuboidal or columnar ciliated epithelium, recapitulating the ciliated epithelium, recapitulating the structure of the normal choroid plexus.structure of the normal choroid plexus.

COLLOID CYST OF THE THIRD VENTRICLECOLLOID CYST OF THE THIRD VENTRICLEA A non-neoplastic cysticnon-neoplastic cystic lesion lesionMorphology:Morphology:– Having a thin fibrous capsule, a lining of Having a thin fibrous capsule, a lining of Cuboidal to Cuboidal to

columnarcolumnar epithelium & containing gelatinous epithelium & containing gelatinous Proteinaceous material.Proteinaceous material.

Attached to the roof of the Attached to the roof of the third ventriclethird ventricle at the at the foramina of Munroe & may cause sudden foramina of Munroe & may cause sudden obstruction of the CSF flow obstruction of the CSF flow acute non-acute non-communicating hydrocephaluscommunicating hydrocephalus brain brain herniation & deathherniation & deathSymptoms: headaches (often positional), Symptoms: headaches (often positional), “drop “drop attacksattacks”, incontinence ”, incontinence Goblet cellsGoblet cells are confirmatory are confirmatory

MISCELLANEOUS (MISCELLANEOUS (MIDLINEMIDLINE) TUMORS) TUMORSPinealomasPinealomas: : – True pineocytomas are True pineocytomas are extremely rareextremely rare, may also have , may also have

pineoblastomas pineoblastomas GerminomasGerminomas: : – MC in the pineal & suprasellar regions in MC in the pineal & suprasellar regions in adolescents & adolescents &

young adults young adults – Closely resemble testicular Seminomas & ovarian Closely resemble testicular Seminomas & ovarian

Dysgerminomas Dysgerminomas – Other GCTs (Teratomas & Choriocarcinomas) also occurOther GCTs (Teratomas & Choriocarcinomas) also occur

Not clear how GCTs arise within the CNS Not clear how GCTs arise within the CNS CraniopharyngiomasCraniopharyngiomas: : – Benign cystic tumors of children & adolescentsBenign cystic tumors of children & adolescents– Develop in the Develop in the suprasellar suprasellar region region HypopituitarismHypopituitarism – Originate from remnants of Originate from remnants of Rathke’s pouchRathke’s pouch & contain & contain

squamous & columnar epithelium, squamous & columnar epithelium, calcificationscalcifications are are common.common.

CNS LYMPHOMACNS LYMPHOMA

PrimaryPrimary CNS lymphomas CNS lymphomas – Account for Account for ~1%~1% of ICTs of ICTs – MC CNS neoplasm in MC CNS neoplasm in AIDSAIDS & other & other

immunosuppressedimmunosuppressed patients often arise deep within patients often arise deep within the the cerebral hemispherescerebral hemispheres & are commonly & are commonly bilateralbilateral

– Lymphoma cells exhibit an angiocentric distribution Lymphoma cells exhibit an angiocentric distribution – Usually are Usually are B-cellB-cell lymphomas & many appear to be lymphomas & many appear to be

EBV-related.EBV-related.

Secondary Secondary CNS lymphomasCNS lymphomas – Lymphomas arising outside of the CNS Lymphomas arising outside of the CNS rarely involve rarely involve

the brain parenchyma the brain parenchyma – May involve the meninges, intradural spinal nerve May involve the meninges, intradural spinal nerve

roots & epidural spaceroots & epidural space

PHAKOMATOSESPHAKOMATOSESNEUROCUTANEOUS SYNDROMESNEUROCUTANEOUS SYNDROMES (PHAKOMATOSES)(PHAKOMATOSES)ADADHamartomas & NeoplasmsHamartomas & Neoplasms– Esp. involving the Esp. involving the nervous system & skinnervous system & skin– Mutations in tumor suppressor genes Mutations in tumor suppressor genes

1.1. Neurofibromatosis Type 1 ( Neurofibromatosis Type 1 (NF1NF1)):: – Neurofibromas, Neurofibro-sarcomasNeurofibromas, Neurofibro-sarcomas– Optic nerve GliomasOptic nerve Gliomas– Pigmented cutaneous macules (café au lait spots) Pigmented cutaneous macules (café au lait spots) – Pigmented nodules of iris (Pigmented nodules of iris (Lisch nodulesLisch nodules))

2.2. Neurofibromatosis Type 2 ( Neurofibromatosis Type 2 (NF2NF2)):: – Bilateral Schwannomas of CN VIIIBilateral Schwannomas of CN VIII– Multiple meningiomas Multiple meningiomas – Spinal cord EpendymomasSpinal cord Ependymomas

3.3. Tuberous SclerosisTuberous Sclerosis

HamartomasHamartomas (“tubers”) in the cerebral (“tubers”) in the cerebral cortex, Sub-Ependymal hamartomas cortex, Sub-Ependymal hamartomas (“candle drippings”) (“candle drippings”) Sub-Ependymal Sub-Ependymal giant cell Astrocytomasgiant cell Astrocytomas

Seizures & mental retardationSeizures & mental retardation

Extra CNSExtra CNS findings: findings: – Kidney (Angiomyolipoma), Heart Kidney (Angiomyolipoma), Heart

(Rhabdomyoma MCC in kids, adult = (Rhabdomyoma MCC in kids, adult = mixomas ), skin (Angiofibroma) mixomas ), skin (Angiofibroma)

Tuberous SclerosisTuberous Sclerosis

4.4. von Hippel-Lindau disease von Hippel-Lindau disease

HemangioblastomasHemangioblastomas of the cerebellum, of the cerebellum, retina, brain stem & spinal cordretina, brain stem & spinal cord

CystsCysts of liver, kidney & pancreas of liver, kidney & pancreas

incidence of incidence of RCCRCC, may be bilateral, may be bilateral

~ 10% of Hemangioblastomas ~ 10% of Hemangioblastomas polycythemiapolycythemia

von Hippel-Lindau diseasevon Hippel-Lindau diseaseHemangioblastomasHemangioblastomas

tumors of the cns

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