Neoplasms of the Nervous System and Related Topics

Abstract

B. Clinical Manifestations of CNS Tumors 1. Signs and symptoms of raised intracranial pressurea. Headache: nocturnal or worse when waking up, may improve over the course of the day, worsen with coughing, Valsalva maneuver, or postural changeb. Nausea, vomiting c. Papilledema d. Altered mental status e. False localizing signs (such as cranial nerve [CN] VI palsy) f. Increased intracranial pressure may be due to mass effectattributable to tumor, surrounding edema and hemorrhage, and hydrocephalus2. Focal neurologic dysfunction a. Seizures: most often partial, some with secondary gener-alization, common with temporal lobe tumors b. Focal signs and symptoms are highly dependent onlocalization of the tumor 3. Pain also may result from local invasion of pain-sensitivestructures, e.g., dura mater, intracranial vasculature, and periosteumA. Temporal Lobe 1. Dysembryonic neuroepithelial tumor (DNET),ganglioglioma, pleomorphic xanthoastrocytoma, astrocytoma, oligodendrogliomaB. Pituitary Fossa and Sellar and Suprasellar Regions 1. Pituitary gland tumors: pituitary adenoma, Rathke’scyst, granular cell tumors 2. Suprasellar region: germ cell tumors, craniopharyn-gioma, olfactory neuroblastoma, optic nerve gliomas, colloid cyst, epidermoid cyst, dermoid, lymphoma, hamartoma (hypothalamus), metastasis3. Clivus: chordoma, osteosarcoma, chondrosarcoma 4. Differential diagnosis should also include nonneoplasticcauses: carotid or cavernous aneurysm or fistula, sarcoidosis, cavernous sinus thrombosisC. Pineal Region 1. Germ cell tumors (germinoma, teratoma), pineal celltumors (pineocytoma, pineoblastoma), meningioma, astrocytoma, pineal cysts, metastasis, lipoma, epidermoid and dermoid cysts (also arachnoid cyst)2. Germ cell tumors occur in childhoodD. Intraventricular 1. Lateral ventricles: astrocytoma, central neurocytoma,oligodendroglioma, subependymoma, meningioma, choroid plexus papilloma, subependymal giant cell astrocytoma (most commonly at foramen of Monro)2. Third ventricle: the above plus colloid cyst 3. Fourth ventricle (special considerations): ependymoma,subependymoma, medulloblastoma, exophytic brainstem gliomas, pilocytic cerebellar astrocytoma, hemangioblastomaE. Corpus Callosum 1. Lymphoma, glioblastoma multiformeF. Cerebellopontine Angle 1. Schwannoma (acoustic neuroma), meningioma,epidermoid, metastasis 2. Rare: paraganglioma, choroid plexus papillomaG. Foramen Magnum 1. Astrocytoma, meningioma, ependymoma, medullo-blastoma, metastasis 2. Mostly involving the clivus: chordoma, osteosarcoma,chondrosarcomaH. Spinal Cord (discussed below)A. General Characteristics 1. Derived from neuroglia and progenitor cells (stem cells) 2. Include astrocytomas, oligodendrogliomas, mixedoligoastrocytomas, pleomorphic xanthoastrocytomas, ependymomas3. Prognostic factors for gliomas a. Age at diagnosis b. Karnofsky performance status (KPS) c. Histologic grade provides helpful prognostic information(see classification below) 1) Astrocytomas (from worse to better prognosis):glioblastoma multiforme, anaplastic astrocytoma, low-grade (World Health Organization [WHO] grade II) astrocytoma2) Anaplastic astrocytomas: worse prognosis thananaplastic oligodendrogliomas 4. Other possible prognostic factorsa. Extent of surgical resection b. Mental status changes at onset c. Short duration of symptoms before diagnosis d. Tumor sizeB. Associated Inherited Syndromes 1. Li-Fraumeni syndromea. Rare autosomal syndrome associated with familial clustering of soft tissue and bone sarcomas, breast carcinomas, and CNS neoplasmsb. Often diagnosed before age 45 years c. Associated with germline mutation of p53 d. Reported brain tumors include astrocytoma (anaplasticand glioblastoma multiforme) and diffuse B-cell lymphomae. Possible association with Sturge-Weber syndrome (no adequate data)2. Familial polyposis syndromes a. Turcot’s syndrome: adenomatosis polyposis coli associatedwith gliomas and primitive neuroepithelial tumors b. Gardner’s syndrome: osteomas and soft tissue tumors3. Neurofibromatosis type 1 (NF1) a. Neurocutaneous syndrome associated with low-gradegliomas (including optic gliomas), neurofibromas b. Linked to a mutation of tumor suppressor gene (NF1)on chromosome 17q11.2 (see Chapter 13) 4. Neurofibromatosis type 2 (NF2)a. Neurocutaneous syndrome associated with meningiomas, astrocytomas, and bilateral schwannomasb. Linked to a mutation of tumor suppressor gene (NF2) on chromosome 22q11.2 (see Chapter 13)5. Cowden’s disease (multiple hamartoma syndrome) a. Autosomal dominant inheritance with variablepenetrance b. Associated with Lhermitte-Duclos disease and character-ized by various mucocutaneous papules, noncutaneous benign hamartomatous tumors, and carcinomasc. Most common malignant tumors are breast and thyroid carcinomasC. Astrocytoma Classifications (Table 16-1) 1. WHO classification 2. St. Anne/Mayo gradingD. Diffuse (fibrillary) Astrocytomas 1. Low-grade (WHO grade II) diffuse astrocytomasa. Associated with mutations of the tumor suppressor gene p53 on chromosome 17p13.1 in two-thirds of cases andg. Neuroimaging characteristics: T2 hyperintense lesions with little to no enhancement, edema, or hemorrhageh. Prognosis 1) Survival is variable (at least 3-5 years is expected) 2) Most low-grade astrocytomas undergo malignanttransformation with time 3) Risk factors for malignant transformation: tumorsize, gemistocytic pathology, presentation in first decade or after age 50 years, increased enhancement2. Anaplastic (WHO grade III) astrocytoma a. Associated with mutations of the tumor suppressor genep53 on chromosome 17p13.1 (as with the low-grade astrocytomas), mutation of the retinoblastoma (RB) tumor suppressor gene on chromosome 13q14 in 1/3 of cases, and loss of heterozygosity (LOH) of chromosome 19q (the latter two are involved in transformation from a low-grade to an anaplastic astrocytoma)b. Presentation is often between 40 and 60 years of age (younger patients have longer survival)c. Mascroscopic features 1) Diffusely infiltrating heterogeneous neoplasm 2) Tumor may appear cystic and/or contain hemorrhagicfoci d. Microscopic features1) Cellular proliferation is more prominent than in lowgrade astrocytomas2) Often, frequent mitotic figures and endovascular proliferation3) No necrosis e. Seeding of the neuroaxis by cerebrospinal fluid (CSF)dissemination and ependymal spread may occur but are rareoverexpression of proto-oncogene encoding plateletderived growth factor (PDGF)b. Occur typically in either first decade or between third and fourth decadesc. Usually hemispheric location, with predilection for temporal and posterior frontal lobes more than anterior parietal lobed. Tends to be infiltrative, with no well-defined borders e. Seizure is common presentation f. Pathology1) Pattern (from most common to least common): often fibrillary, protoplasmic, gemistocytic astrocytomas2) Fibrillary astrocytomas (Fig. 16-1) a) Well-differentiated astrocytes with scant cyto-plasm; atypical and hyperchromatic nuclei; fine, fibrillary processesb) Microcysts containing mucinous material c) Scant to absent mitotic figures and vascularproliferation d) Calcification is rare but may occur in up to 10% to20% of cases 3) Protoplasmic astrocytomasa) Hypocellular b) Cells with small round nuclei, sparse cytoplasm c) Prominent characteristic microcystic spaces4) Gemistocytic astrocytomas (Fig. 16-2) a) Large cells with abundant eosinophilic cytoplasmand eccentrically placed nuclei b) Usually worse prognosis c) Malignant transformation: more often than otherpathologic subtypesTable 16-1. WHO Classification and St. Anne/Mayo Grading of Astrocytic TumorsWHO St. Anne/Mayo_______________________________ ________________________________________________________ Designation Classification Grade (based on criteria)* Criteria*f. Median survival: usual estimate, about 2 to 3 years after presentation3. Glioblastoma multiforme a. Most common primary brain tumor, 50% of all gliomas b. Presentation: typically after age 50 c. With the aggressive nature and rapid progression,presenting symptoms include increased intracranial pressure, seizures, and focal neurologic symptomsd. Genetics 1) Secondary glioblastomas (malignant transformationof lower grade glioma to glioblastoma) can be associated with mutation of gene encoding PDGF-α, loss of tumor suppressor gene PTEN (LOH at chromosome 10q)2) Primary (de novo) glioblastomas a) Have no apparent antecedent low-or intermediate-grade tumor history b) Are often associated with amplification of theproto-oncogenes epidermal growth factor receptor (EGFR) and MDM2, loss of tumor suppressorgene PTEN, LOH at chromosome 10, and mutation involving the RB genee. Most common locations: deep white matter and deep gray matter, including thalamus and basal gangliaf. Macroscopic and neuroimaging features 1) Heterogeneous-appearing mass with foci of necrosis,hemorrhage, and peritumoral edema (Fig. 16-3) 2) Neuroimaging often confirms the heterogeneousappearance, with central area of necrosis and a ringenhancing rim3) Despite the circumscribed gross appearance, thetumor is highly infiltrative and may also spread to opposite hemisphere through the corpus callosum (“butterfly gliomas”)4) Glioblastoma multiforme tumors may arise from malignant transformation of separate regions of the tumor and appear multifocal5) Contrast enhancement and vasogenic edema occur from disrupted blood-brain barrier (BBB)6) Treatment with corticosteroids assists in reestablishment of BBB and can yield almost immediate improvement of symptomsg. Microscopic features 1) All the features of anaplastic astrocytomas in additionto prominent endothelial proliferation and/or necrosis, surrounded by pseudopalisading of cells (Fig. 16-4)2) Neovascularization and endothelial hyperplasia may be due to production of angiogenic factors such as vascular endothelial growth factor (VEGF)h. Natural history and spread 1) Typical: spread of tumor along white matter tractsand around the ependyma 2) Atypical: CSF dissemination through neuroaxis(occurs in 10%-20% of cases), may include pachymeningeal spread3) Almost never occur: invasion of dura mater and metastasis outside of CNS4) Meningeal invasion is sometimes called “meningeal gliomatosis,” occurs more frequently with malignant gliomasi. Treatment 1) Usually includes surgical debulking aimed at relievingmass effect and increasing effectiveness of adjunctive therapy (also sometimes to obtain pathology specimen)2) Complete resection is not possible because tumor is diffusely infiltrative and multifocal3) Stereotactic biopsy: reserved for deep and inaccessibletumors and comorbidities precluding general anesthesia 4) Most effective adjunctive therapy: external beamradiotherapy administered to limited field, up to 60 Gy given in conjunction with temozolomide chemotherapy-median survival, about 14 months; 2-year survival, about 27%4. Gliomatosis cerebri (Fig. 16-5) a. Diffuse, infiltrative glial tumor (usually astrocytoma)causing diffuse expansion of a portion of or entire cerebral hemisphere; may spread to one or both cerebral hemispheresb. Microscopic features (Fig. 16-6) 1) Resembles low-grade glioma 2) Mild increase in cellularity and pleomorphism 3) Rare mitotic figures 4) No hemorrhage or necrosis 5) Neoplastic glial cells cluster around neuronsc. Treatment 1) Some benefit from chemotherapy (as with PCV ortemozolamide) 2) No role for surgery because of infiltrative nature oftumorg. Brainstem gliomas: likely to be solid, diffuse fibrillary astrocytomas (rarely pilocytic tumor arising from fourth ventricle with “dorsally exophytic” growth, which may portend better prognosis)h. Macroscopic features: unencapsulated, but well-circumscribed (there may be limited degrees of infiltration) heterogeneous mass; may have a mural nodule associated with a cysti. Microscopic features 1) Compact pilocytic arrangements of elongated (some-times stellate) cells admixed with microcystic areas 2) Classic feature: abundant Rosenthal fibers, may beslight nuclear pleomorphism and rare mitoses j. 5-Year postoperative survival: 85% to 100% (95%-100% for cerebellar pilocytic astrocytomas) k. Cerbellar pilocytic astrocytomas have the best prognosisof all primary brain tumors l. Treatment1) Maximal surgical excision of tumor 2) Surgical excision of the mural nodule may be3) Marginal benefit from radiotherapy d. 2-Year survival after treatment, 5% to 10%E. Circumscribed Astrocytomas 1. Pilocytic astrocytomas (WHO grade I)a. Usually occur in first or second decade of life b. Better prognosis than diffuse astrocytomas c. Common locations: cerebellum (hemispheres > vermis),optic chiasm, hypothalamus, and periventricular area of third and fourth ventricles (Fig. 16-7 A)d. Less common locations: spinal cord (Fig. 16-7 B and C), brainstem, cerebral hemispheres (temporal lobe is most common hemisphere site); tend to occur in older age group (young adults)e. Cerebellar hemisphere tumors: often large cystic, fluidfilled masses appearing hyperintense on T2-weighted images, with strongly (but somewhat heterogeneously) contrast-enhancing mural nodulef. Optic and hypothalamic gliomas: tend to be solid, pilocytic tumorsadequate and cystic wall need not be removed 3) With increasing thickness or enhancement of nodulewall, the cystic wall also needs to be removed 4) Nonresectable tumors or recurrence with malignanttransformation may require adjuvant radiotherapy 2. Pleomorphic xanthoastrocytomas (WHO grade II orIII) a. Occur in second or third decade of life (average age atdiagnosis, 26 years) b. Often a history of seizures c. May originate from subpial astrocytes d. Macroscopic features1) Well-encapsulated tumor frequently containing a mural nodule within a cyst2) Often located superficially in temporal lobe e. Microsocopic features1) Large cells with eosinophilic cytoplasm, some containing lipid droplets2) Nuclear pleomorphism 3) Rare mitosesf. Neuroimaging: well-circumscribed cystic lesions appearing isointense or hypointense to brain parenchyma on T1-weighted and hyperintense on T2-weighted images,often with intense contrast enhancement of nodule g. Treatment1) Often includes complete resection 2) Radiation and chemotherapy often reserved forrecurrent or malignant tumors h. Postresection survival rates: 81% at 5 years, 70% at10 years; relatively benign prognosis 3. Subependymal giant cell astrocytomas (WHO grade I)a. Very slow-growing tumors, always associated with tuberous sclerosis (found in up to 14% of patients with tuberous sclerosis)b. Presentation: usually in first or second decade of life c. Usually originate near foramen of Monro, blocking CSFoutflow and causing hydrocephalus d. Macroscopic features: well-circumscribed, lobulated redmass (vascular tumor), often calcified and cysticLarge cells with cytoplasmic eosinophilic granular bodies are a characteristic feature of pleomorphic xanthoastrocytoma, which is a low-grade gliomae. Microscopic features 1) Large, oval cells with abundant eosinophilic cyto-plasm and large, eccentric nucleus; often surround blood vessels in this vascular tumor2) Pleomorphism is often present 3) Mitoses and necrosis are unusualf. Neuroimaging: isointense or hyperintense on T2weighted images; intense, heterogeneous enhancement on T1-weighted imaging with contrastg. Definitive treatment for symptomatic patients (i.e., hydrocephalus) or extensive tumors: surgical resectionh. Unless symptomatic, patients are only followed with periodic neuroimagingF. Special Considerations 1. Optic gliomas (Fig. 16-8)a. 3% to 5% of all childhood brain tumors b. 2% of gliomas in adults c. Female predominance (female:male = 2:1) d. More common in children: 50% of patients presentbefore age 5, 90% before age 20 e. Tumors involving optic nerve alone have a betterprognosis than those involving optic chiasm (which have better prognosis than hypothalamic gliomas, although aggressive tumors involving optic chiasm may spread to involve hypothalamus)f. Associated with NF1 1) Occur in 1% to 7% of children with NF1 2) As many as 50% of patients with optic gliomas haveNF1 3) Almost all patients with bilateral optic nerve tumorssparing optic chiasm have NF1 g. Slow-growing tumors; malignant histologic features oraggressive behavior are rare (reported in cases of optic chiasm and hypothalamic gliomas)h. Usually pilocytic astrocytomas causing either diffuse expansion without subarachnoid involvement or primary subarachnoid spread with minimal involvement of optic nervei. Symptoms unique to optic nerve gliomas 1) Visual loss, visual field defects, painless proptosis, andsymptoms related to increased intracranial pressure 2) Symptoms of hypothalamic involvementa) Endocrinopathies: precocious puberty, diabetes insipidus, other related endocrinopathiesb) Gelastic seizures: characterized by involuntarylaughter, more common with hypothalamic hamartomasc) “Diencephalic syndrome”: emaciation, cachexia and loss of subcutaneous fat, emesis, pallor, hyperactivity, inappropriate behavior, euphoriaj. Treatment 1) Considered for tumors with aggressive behavior, espe-cially for patients presenting with visual deterioration 2) Radiotherapy considered for patients older than 5years presenting with tumors in locations other than intraorbital (intracranial locations such as chiasmal or retrochiasmal) and when total resection is not possible3) Chemotherapy considered for patients younger than 5 years4) Surgical excision may be limited to biopsy, especially for tumors involving optic chiasm2. Brainstem gliomas a. Account for 10% to 15% of brain tumors in children(<5% of gliomas in adults) b. Age at diagnosis: often between 5 and 10 years c. Heterogeneous group of neoplasms: all grades of pathol-ogy observed, but most are malignant, with poor prognosisd. Symptoms: usually related to ataxia and other cerebellarfeatures, long tract signs, or cranial nerve deficits e. Neuroimaging (can predict prognosis better than patho-logic features) 1) Lesions appear as a high T2 signal with variabledegrees of enhancement 2) May contain a cystic component (Fig. 16-9) 3) Diffuse pontine gliomas: all are malignant 4) Most gliomas involving cervicomedullary junction arelow-grade gliomas 5) Tumors of midbrain usually have a better prognosisthan those involving medulla or pons 6) Dorsal exophytic tumors tend to have betterprognosis f. Prognosis1) Best for focal lesions, dorsal exophytic tumors, low histologic grade, longer period from onset of symptoms to diagnosis, adult age group, and in context of neurofibromatosis2) 5-Year survival: 5% to 30% g. Treatment1) Best: radiotherapy 2) Surgical resection usually involves stereotactic biopsy;is best performed on focal, cystic, or exophytic tumorsG. Rare Astrocytic Variants 1. Gliosarcomas: high-grade gliomas admixed with sarco-ma (variant of glioblastoma multiforme, with same prognosis)2. Gliofibroma a. Glioma admixed with population of cells resemblingfibroblasts b. Usually present in the first decadeH. Oligodendroglioma 1. From cells of oligodendroglial origin (O2A progenitorcells)2. Genetics a. Development of low-grade oligodendrogliomas: associ-ated with loss of heterozygosity of chromosomes 1p, 19q, and 4qb. Development of high-grade oligodendrogliomas from the low-grade tumors: associated with loss of heterozygosity of chromosomes 9p and 10qc. Both are associated with overexpression of EGFR 3. Account for 5% of all primary brain tumors and 30%of all intracranial gliomas 4. May be a male predominance (male:female = 3:2) 5. More often presents in adults: usually present betweenthird and fifth decades 6. Small earlier peak in childhood between 6 and 12 years;thalamic location at presentation is common in children7. Seizures are often the initial presentation in up to 75% of patients because tumor commonly involves cerebral cortex8. Most common location: frontal lobe, followed by temporal and parietal lobes; rarely brainstem or spinal cord9. Slow-growing, infiltrative gliomas: may start in subcortical white matter, tend to spread along white matter tracts and corpus callosum10. Better prognosis than astrocytomas 11. 5-Year survival rate, 75% 12. Mean postoperative survival, 4 to 11 years13. Macroscopic features: well-circumscribed, unencapsulated mass with cystic degeneration and calcification (necrosis and hemorrhage are rare)14. Microscopic features (Fig. 16-10) a. Variable b. Homogeneously appearing cells with sparse cytoplasmand round, uniform nuclei c. Cells may appear elongated, with a displaced nucleus;because of fixation artifact, there may be artifactual clearing of the cytoplasm, resembling fried eggsd. There may be mucin-rich microcystic spaces e. Capillaries interposed between uniform-appearing cellsmay form a delicate vascular “chicken-wire” pattern f. Pleomorphism and endothelial hyperplasia (less commonly,necrosis) indicate high-grade oligodendroglioma 15. Neuroimaging: heterogeneous appearing T2hyperintense mass often involving cerebral cortex with variable, heterogeneous enhancement pattern, cystic component, and calcification (in up to 90% of cases)16. Classified into high-grade and low-grade tumors 17. Features associated with high-grade tumors and lessfavorable prognosis a. Contrast enhancement b. Endothelial proliferation c. Mitotic figures d. More than 5% of MIB-1 staining e. Astrocytic component (with oligoastrocytomas, asdiscussed below) 18. Treatmenta. Gross total resection when possible (because tumor is infiltrative, microscopic infiltrates always remain)b. Primary adjuvant therapy: chemotherapy with alkylating agent such as temozolomide (before development of temozolomide, procarbazine/lomustine/vincristine [PVC] were used)c. Loss of heterozygosity of chromosome 1p or combined loss of heterozygosity of chromosomes 1p and 19q (50%- 80% of cases) portend better prognosis, prolonged survival, and better response to chemotherapyd. Although intermediate-grade oligodendrogliomas are often chemotherapy-responsive (e.g., 1p/19q deleted tumors), radiation (often in combination with chemotherapy) is still the mainstay of treatment to achieve maximal survival advantageI. Oligoastrocytoma 1. Composed of different populations of cells, someresembling astrocytes, some oligodendrocytes, and some indeterminate2. A common progenitor cell that differentiates into two different cell lines is likely3. Glial tumors with predominant oligodendrocytic population of cells are often interpreted as oligodendrocytes4. Increasing proportion of oligodendroglial component generally portends better prognosis (chromosome 1p and 19q deletions signify greater sensitivity of tumor to chemotherapy)J. Ependymoma 1. Epidemiologya. 5% to 8% of all primary intracranial tumors b. Age at presentation often in the first decade, with asecond peak in the fourth decade (prognosis worse for patients younger than 3 years)c. Third most common brain tumor in children d. Location (pediatric population): intracranial (90%) orspinal cord (10%) e. 2/3 of intracranial ependymomas occuring in childrenare infratentorial and about 1/3 supratentorial f. 2/3 of intracranial ependymomas occur in children (mostlyinfratentorial), and more than 90% of spinal cord ependymomas occur in adults (mostly myxopapillary ependymomas)2. Symptoms at presentation (depend largely on tumor location) a. Intracranial tumors often occur on floor (more frequentthan roof or lateral recesses) of fourth ventricle (medul-loblastomas tend to arise most frequently from roof of fourth ventricle)b. May present with obstructive hydrocephalus and associated symptoms of headache, nausea, vomiting, ataxia, vertigo, nystagmus3. Potential for CSF dissemination: because of close contact with CSF, there may be “drop metastasis” in 5% of cases4. Myxopapillary ependymomas a. Well-encapsulated, indolent, slow-growing vasculartumors arising from filum terminale b. Occur most often in adults c. Associated with good prognosis5. Posterior fossa ependymomas a. Well-demarcated tumors that tend to fill fourth ventricleand extend through foramen magnum b. Appear as T2 hyperintense masses with heterogeneoussignal that may represent tumor vascularity (or necrosis) c. Often a heterogeneous pattern of enhancement6. Microscopic features (Fig. 16-11) a. Sheets of uniform cells with round nuclei and variablecytoplasm among perivascular anuclear fibrillary processes: “pseudorosettes” (fine cellular fibrillary processes that radiate toward blood vessel)b. Myxopapillary ependymomas are characterized by sheets of uniform columnar or cuboidal cells admixed with pools of mucin often bordered by tumor cells and containing a central blood vesselc. Cytologic pleomorphism, necrosis, mitotic figures, and giant cells often signify anaplastic ependymomas7. Treatment: surgical resection and/or adjuvant radiotherapy (optimal outcome with doses between 5,000 cGy and 5,500 cGy) a. Higher survival with gross total resection: goal is toobtain maximal possible resection b. For low-grade ependymomas of spine parenchyma orfilum terminale (myxopapillary ependymoma): surgical resection is mainstay of treatment, radiation is considered if residual tumor is present postoperativelyc. Extensive craniospinal radiation to entire neuroaxis required for patients presenting with CSF disseminationd. Response to chemotherapy is suboptimal; this treatment modality is considered for patients with contraindications to radiation (e.g., children younger than 3 years or patients with recurrent disease )8. Prognosis: generally favorable, especially adults with myxopapillary ependymomas (except for 10%-20% of cases that have CSF dissemination)9. Reduced survival has been associated with young age at onset and anaplastic histopathologic features, and higher risk of recurrence with partial resectionsK. Subependymoma 1. Slow-growing large firm masses most often occurring infourth ventricle, arising from medulla or lateral ventricles attached to septum pellucidum2. Age at presentation: usually between 40 and 60 years 3. Microscopic features (Fig. 16-12): cells with roundnuclei and sparse cytoplasm; admixed with microcystic clusters and foci of calcification on a fibrillary background4. Neuroimaging characteristics: mildly hyperintense lesions on T2-weighted images often with heterogeneous appearance and little to no enhancementA. Ganglion Cell Neoplasms 1. Rare, slow-growing, benign well-circumscribed firmtumors often occurring in temporal lobes, sometimes with cystic or calcified foci2. Age at presentation: first 3 decades 3. Most common presentation: seizures (oftenintractable) 4. Predilection for temporal lobes (followed by frontal andparietal lobes); much less common, cerebellum and spinal cord5. Neuroimaging characteristics: classically appear as well-circumscribed cystic mass (hyperintense on T2weighted images) with a mural nodule with variable enhancement6. Microscopic features a. Presence of both neuronal (ganglion) and glial neoplasticcells b. Gangliocytoma: tumors with predominance ofneoplastic ganglion cells without an obvious astrocytic componentc. Ganglioglioma: tumors containing neoplastic glial cells that often outnumber ganglion cellsd. Some neoplastic ganglion cells are binucleated or multinucleated (unfortunately not always present, but quite helpful when present) (Fig. 16-13)7. Treatment a. Resection b. Radiotherapy: reserved for recurrent tumor or thosewith anaplastic histopathologic features 8. Prognosisa. Most carry benign prognosis with total or subtotal resectionb. Anaplastic histopathologic features: less favorable prognosisB. Central Neurocytomas 1. Neoplasms of neuronal differentiation 2. Rare (about 0.5% of all primary CNS tumors), occurprimarily in young adults between second and fourth decades3. Commonly present with symptoms of increased intracranial pressure (most commonly, headaches)4. Most commonly an intraventricular location, often at foramen of Monro: 50% of all intraventricular tumors in adults5. Microscopic features: sheets of uniform cells with round nuclei; immunoreactive for synaptophysin6. Neuroimaging: heterogeneous signal (isointense or hyperintense on T2-weighted images) with heterogeneous enhancement (Fig. 6-14)7. Treatment often involves resection (total, if possible) 8. Benign prognosis with total or subtotal resection, withlong survival ratesC. Dysembryoplastic Neuroepithelial Tumor (DNET) 1. Rare, slow-growing (sometimes cystic) tumors withpredilection for temporal lobes 2. Most common presentation: complex partial seizures(often intractable) 3. Microscopic featuresa. Mucin-rich cellular glial nodules containing masses of oligodendrocyte-like cellsb. Specific glioneuronal elements c. Adjacent foci of cortical dysplasia d. Dystrophic calcification4. Neuroimaging characteristics: hyperintense on T2weighted images (hypointense on T1-weighted images)5. Benign prognosis 6. Surgical resection usually reserved for symptomaticcases (e.g., intractable seizures)D. Lhermitte-Duclos Disease (dysplastic gangliocytoma of cerebellum)1. Commonly presents as slow-growing cerebellar mass with increased intracranial pressure2. Commonly presents in the fourth decade 3. Associated with Cowden’s disease (about 50% ofpatients with dysplastic gangliocytoma have clinical stigmata of Cowden’s disease)4. Macroscopic features: hypertrophied, thickened cerebellar folia (Fig. 16-15)5. Microscopic features a. Enlarged ganglion cells (neurons) replace granule cells,atrophy of granular layer b. Loss of Purkinje cells c. Reduction and cavitation of cerebellar white matter6. Neuroimaging: laminated increased T2 signal without enhancementE. Desmoplastic Infantile Astrocytoma (DIA) and Ganglioma (DIG)1. Rare, often occurring in the first 2 years of life 2. Large, cystic tumors with dural attachments, andpredilection for frontal and parietal areas 3. DIG has male predominance, DIA femalepredominance 4. DIG as