Corticosteriods: Counteract VASOgenic edema by ↓ permeability of BBB. Control sxs from peritumoral edema or ↑’d ICP (sxs improve w/in hrs, peak effect in 24-72 h, days to ↓ ICP). Steroids ↓ enhance on MRI/CT. Direct transient cytotoxic effect on lymphoma. Before starting, look for infxn/osteoporosis/PUD/DM. Consider drug interactions (esp phenytoin).

Indications: (1) Symptomatic edema/herniation or radiographic mass effect. (2) Clin/radiographic cord compress. (3) Sx recurrence (double dose, slow taper). (4) Perioperatively (biopsy or resection); partic if sig mass effect.

Dexamethasone: Preferred steroid. Less mineralocorticoid activity = less fluid retention. Long half-life (dosed bid-qid for GI tolerance). Typical start: 10 mg × 1 then 4 mg q6h; BID dosing for outpatients.

Long-term side effects: Immunosuppression: ↑ risk of infxn, including PCP/PJP. Cardiovasc: Exac of CHF, HTN, edema. Endocrine: Impaired glucose tolerance, DM, wt gain, adrenal insuff. GI: Peptic ulcer dz, upset stomach/heartburn, constip. Psychiatric: Insomnia, agitation, psychosis. Neurologic: Tremor, myop, hiccups. Skeletal: Osteoporosis, compress fxs, aseptic necrosis. Dermatologic: Skin thin & breakdown, hair thin, flushing, night sweats.

Prophylaxis: PCP/PJP ppx for >6 wk steroids: TMP-SMX SS PO qd or DS qMWF. Consider if on dose equivalent of ≥20 mg prednisone for >4 wks. GI ppx for perioperative/high dose steroids: PPI daily. Stress dose steroids occ required. Calcium + vitamin D may prevent osteoporosis.

Anti-seizure medications: Prophylaxis : No proven benefit of ppx AEDs in brain tumors; often used anyway. Used after craniotomy (limited data); taper after 1 wk. Hemorrhagic tumors/melanoma mets/oligodendrogliomas: may consider ppx AEDs.

Symptomatic Rx: Initiate AEDs after first sz in brain tumor pts. High recurrent sz risk, high mort from status. Monotherapy preferred. If recurrent szs, ↑dose before new AED. Prefer AEDs that don’t induce P450 (if anticipating chemo): LEV, LTG, TOP, GPN, lacosamide; Avoid: PHT, CBZ, PBT.

Surgery: Decompress for mech compress causing acute sxs, Max resection for 1° CNS tumors/solitary mets. Except: Highly chemosensitive (lymphoma, germ cell tumors). Functional mapping & electrocorticography to avoid functional ctx/find sz focus. VP shunt/EVD to manage hydro/↑ ICP. Surgical fixation for spinal instability prior to radiation.

Radiation therapy (XRT): General principles: Tissue dx nearly always required prior to XRT (imaging 10% FPR). Dose measured in gray (Gy), w/units J/kg = SI unit of absorbed dose. Fraction = dose of each Rx. External-beam radiotherapy = photon or proton beams from external source. Brachytherapy = radiation source placed in/near tumor. Small <3 cm lesions can be Rx’d w/single fraction, larger require fractionated Rx (preserve nl tissue). IMRT = intensity modulated RT: computer optimizes configuration of moving apertures to conform dose to targets & spare critical structures. SRS = Stereotactic radiosurgery (SRS): 1-5 fractions of high intensity radiation. Head fixation crit for accuracy—some systems req rigid head frame placed by neurosurg, others frameless. Photon-& proton-based approaches biologically equal affect on tumors. Proton: Only few centers. Generally for pedi cases/difficult anatomy (cav sinus, skull base).

Typical dosing schedule: Whole brain: qd; 3 Gy × 10 (most common), 2.5 Gy × 14, 4 Gy × 5 (leptomeningeal dz). High grade 1° brain (GBM): qd; 2.0 Gy × 30. Intermediate grade 1° brain (meningioma): qd; 1.8 Gy × 28-33. Acute radiation: Emergent XRT generally uses larger fields (exposing more nl tissue). Urgent Rxfor: tumor-related cord compress, new CN palsy, symptomatic brain mets. Usu Rx w/steroids × 8-24 h before XRT.

Chemotherapy: General principles: CNS tumors seldom cured by chemo alone. Neoadjuvant chemo = prior to surgery/XRT. Concurrent chemo = during XRT. Adjuvant chemo= after surgery/XRT.

Epid: 1° brain tumors = 2% of cancers = ˜21/100,000 person-yrs; ↑ing. M > F for malignant tumors, opposite for nonmalignant. Non-Hispanic > Hispanic (excl pituitary), Whites > Blacks (excl mening, pituitary, craniopharyngioma) > Asians & Native Americans. Glioma 50% > meningeal 20%-40% > pituitary 10%-20% > cranial & spinal tumors > PCNSL 3%-5%. Very rare to have systemic mets.

Risk factors: ↑ glioma in 1° relatives. HIV/immunosuppressed ↑ 1° CNS lymphoma. Several genetic synd a/w 1° BTs (see Genetic Synd below), prior XRT ↑ meningiomas, astrocytomas, sarcomas.

Classification: WHO system (named for cell of origin). Gliomas most common (glial cells). Gliomas not easily biopsied named for location (brainstem glioma, optic glioma, etc.). Grade based on appearance, & indicates tendency to spread/growth rate/prognosis. Unlike other tumors, not based on lymph node/metastatic spread (Rare for CNS tumors).

High-grade: Glioblastoma (GBM) & anaplastic astrocytoma: (NEJM 2008;359:492; JAMA 2013;310:1842) Diffusely infiltrating, arise from glial cells, typically in white matter.

Epid: Most common brain tumors (80% of malig tumors, 5/100,000 people). Most common in 6-8th decade, ↑ing, unclear why (? improved imaging). Ionizing radiation is only known nongenetic risk factor.

Dx: Presentation: Szs & HA common; also focal defs/confusion/memory loss. Imaging: Heterogeneously/ring enhancing mass w/edema. MRI: Hypointense T1, inc T2 (edema & tumor). CT: Hypodense ± hemorrhage, ± central necrosis (hypodense). Location: Typically found in cerebral hemispheres, brainstem, thalamus. Path: Grade based on most malig portion. AA/WHO III: Increased cellularity, moderate pleomorphism, no necrosis or vascular proliferation. GBM/WHO IV: Hypercellularity, pleomorphism, microvascular prolif, necrosis ± pseudopalisading.

Rx: Surgery → XRT ± TMZ (NEJM 2005;352:987).

Surgery: Dx, improve sxs, max resect improves recurrence & survival (3-4 mo w/surg alone). Radiation: 60 Gy (1.8-2.0 Gy fractions 5 d/wk × 6 wk). Prolongs survival (7-12 mo w/surg + XRT). Recurrence often in XRT field, inc dose no benefit. Brachy/SRS/Proton no benefit. Chemo: (Temozolomide = TMZ = Temodar) GBM Rx (chemorad → adjuvant chemo). Dosing: During RT = 75 mg/m2, after RT = 150-200 mg/m2 × 5 d, q28d × 6-12 cycles. Prolongs survival: 15 mo vs. 12 mo for surg + XRT alone, 2-yr survival 25% vs. 10%, respectively. MGMT (DNA methylation repair enzyme) silencing increases sensitivity to TMZ. Monitor liver function, blood counts, PCP/PJP prophylaxis while on TMZ + XRT. NovoTTF-110A: a portable, battery-operated device for chronic administration of alternating electric fields to region of tumor via surface electrodes. Shown to have comparable outcomes to standard therapy in recurrent GBM with fewer side effects, phase III trial w NovoTTF + TMZ shows improved PFS (7.1 vs. 4 mo), OS (19.6 vs. 16.6 mo), and 2-yr survival (43% vs. 29%) vs. TMZ alone (NCT00916409). Recurrence: Almost
all recur (median = 7-10 mo after XRT + TMZ). 1 mo MRI ↑enhance in 40% = half “pseudoprogression” (vascular permeability from XRT).

Rx after recurrence: Repeat surgery in some cases for cytoreduction, mass effect, histo/molecular update. Anti-angiogenic therapy increasingly important (decreases vessel permeability, MRI enhancement): bevacizumab approved for progression following standard therapy. Also, consider TMZ rechallenge, other cytotoxic chemotherapy.

Prognosis: Age, grade, resection, performance status, IDH mutation, & MGMT status influence survival. Long-standing sxs, no AMS, small size may be a/w longer survival. 90% recur at original site.

Gliomatosis cerebri: (J Neurooncol 2006;76:201) Rare, diffuse neoplastic glial infiltrate (≥3 lobes), monoclonal. Arise de-novo or from pre-existing glial tumor.

Dx: Clinical sxs nonspec: sz, increased ICP, altered mental status, focal defs.

Ddx: MS, CNS vasculitis, leukoencephalopathy, encephalitis, PML, Behçet’s. Can be astrocytic, oligodendroglial or mixed, usu Grade III (anaplastic).

W/U: MRI better than CT, but nonspec: asymmetric/heterogeneous hyperintense T2, nonenhancing (2/3), thickening of corpus callosum, loss of gray-white differentiation.

Rx: No standard Rx. Not amenable to surgery because of extent of spread. WBXRThigh rate of stabilization, impact on survival unclear. Up front chemo benefits some pts, may be preferred: Rxw/TMZ/PCV (procarbazine, CCNU, vincristine).

Prognosis: Median survival = 14.5-18.5 mo (11 mo w/no tx). Better prognosis: Young, high performance status, lower grade, male, oligodendroglial type, 1p/19q codeletion, MGMT methylation. Poor prognosis: ↑gray matter involvement (Neurology 2009;73:445; JNO 2013;112:267).

Low-grade gliomas: (Oncologist 2006;11:681, Oncologist 2014:14:403) 20%-25% of CNS glial tumors, less common than high grade. Median age at dx: 40s for adults, teens for pilocytic astrocytoma.

Dx: Szs common (85%) (vs. 69% in AA, 49% GBM). Imaging: MRI: Usu nonenhancing, little mass effect/edema. Low T1 signal, High T2 signal (best seen on T2). Arise in WM, extend to cortical surface (Exception: Pilocytic astrocytoma). Hypometabolic on PET (unlike oligodendrogliomas). Grade: WHO I: Pilocytic astrocytoma, subependymal giant-cell astrocytoma (SEGA); WHO II: diffuse astrocytoma, PXA (pleomorphic xanthoastrocytoma). New enhancement or↑ MR perfusion may reflect transformation to high grade.

Rx: Optimal Rx unclear. Surgery: Increase data for early resection vs. obs & delay intervention. Surgery for large, symptomatic tumors; Max safe resection appears to improve survival. XRT: Given at dx; ↑ time to progress & ↓ szs but no survival benefit. Typical dose = 45-54 Gy. Obs if small, min. sxs. Chemo options following XRT include TMZ and PCV; PCV shown to improve PFS and OS in LGG when given after XRT (13.3 yrs vs. 7.8 yrs). TMZ often used for better side effect profile. Szs: Mgt difficult, may require surgery.

Prognosis: 1p/19q deletion a/w superior survival, enhanced sensitivity to Rx in low-grade oligodendrogliomas. IDH1/2 mutations a/w prolonged surgical, enhanced sens to treatment (esp TMZ). Most eventually transform to high-grade tumors. Poor prognostic factors (1 point each): Age > 40, astrocytoma, >6 cm, crossing midline, neuro defs prior to surgery:(0-2 = “low risk,” median survival 7.8 yr; 3-5 = “high risk,” median survival 3.2 yr) (JCO 2002;20:2076).

Recurrence: Sometimes difficult to distinguish from radiation necrosis (may require bx). Consider salvage surgery, radiation, chemo.

Pilocytic astrocytoma: WHO I, 2%-6% of all 1° brain tumors. Earlier age of onset (generally <25 yo). Slow growing, less invasive, more favorable prognosis. Generally arise in cerebellar hemisphere (75%)/near third vent. Other locations: hypothalamus (precocious puberty), optic pathway (assoc c NF1, esp bilat), thalamus, cerebral hemispheres, corpus callosum.

Dx: Radiology: MRI: ↓T1, ↑T2. Well-demarcated (round/oval), vividly enhancing (94%), cystic (68%). ± enhancing mural nodule. Min. peritumoral edema. Mass effect common. Path: Scant extracellular fibrillary matrix, Rosenthal fibers are hallmark.

Prognosis: Surgery: 10 yr OS > 80% w/resection alone. Cerebellar location best prognosis (more amendable to complete resection). XRT: Reserved for inoperable pts or recurrence. Malig degeneration may rarely occur (<5%). Seeding of subarachnoid space uncommon.

Subependymal giant-cell astrocytoma (SEGA): Almost exclusively in association w/tuberous sclerosis (˜10% of pts w/TS). Often present in first 2 decades of life with sz, signs of ↑ICP. Near foramen of Monro (classic)/on ependymal surface of lateral ventricles. MRI: T1 iso, T2 hyper, common enhancement, often calcified. Asymptomatic tumors do not require Rx. Surgical excision for symptomatic tumors, everolimus (mTOR inhibitor) associated with ↓ size, sz freq.

Diffuse astrocytoma: (J Neurooncol 2009;92:253) Most common low-grade glioma, WHO II, med age 30s. Diffuse, widely infiltr, slow growing, initially indolent on serial scans. Often → high grade after ˜5-7 yr of stability, ultimately incurable.

Dx: MRI: ↓T1, ↑T2, nonenhancing (if enhance = more aggressive). Path: ↑’d cellularity, enlarged astrocyte nuclei, no necrosis, mitotic activity, vascular Δs subdivided into fibrillary (deep), protoplasmic, & gemistocytic (cortical).

Rx: Surgery ↑’s survival (when possible) Postop XRT delays recurrence, ?prolong survival. Chemo: (TMZ) response in 50%-60%; 1p/19q deletion & silenced MGMT predictive.

Prognosis: Better if age <40, no enhancement, small tumor, sz at dx, ↓ proliferative index.

Pleomorphic xanthoastrocytoma: Adolescents & young adults (2/3 <18 yo), <1% of all astrocytic tumors, WHO Grade II. BRAF V600 mutation in ˜60%. Uncommon, usu supratentorial, typically adherent to meninges, may be cystic with mural nodule. Often present w/sz. Bizarre histology, can be mistaken for GBM. Favorable prognosis, often curable w/surgical resection, but can recur as GBM.

Brainstem gliomas: (JCO 2006;24:1266). 95% Astrocytomas; oligodendroglioma rare. Low to high grade. 80% pontine—mostly high-grade tumors (WHO III/IV). 20% midbrain, medulla & cervicomedullary junction, mostly low grade. More common in young children. Often present w/hydrocephalus, signs of ↑ICP, cranial nerve abnormalities.

Dx/imaging: MRI prefer’d for dx & f/u. Often can’t bx if intrinsic to brainstem; dx on MRI alone. Ddx: Consider NF1 (only risk factor). Mimics: Brainstem encephalitis (viral/autoimmune), brainstem encephalop (mitochondrial), vasc malformations, MS, hamartomas.

Oligodendroglioma & mixed gliomas: (JCO 2006;24,1246; Oncologist 2009;14:155). Originate from oligodendrocyte. Uncommon: 5%-20% of gliomas, <5% of primary brain tumors. Usu single, sometimes mult lesions. Supratentorial subcortical (superficial, often infiltrate leptomeninges). Rare involve brainstem or cord. Young- & middle-aged adults (median 40-50 yo), less common in children.

Dx: Sz most common presentation (50%), szs eventually occur in 88%. Imaging: Anaplastic often enhance, low grade may not. CT: Well-demarcated hypodense subcortical mass; calcification common; sometimes hemorrhage. MRI: Irregular, ↓ T1, ↑ T2 (edema & infiltrate), 10% hemorrhage, ± patchy enhance; ring enhance uncommon (worse prognosis). Path: Cystic Δ, calcification, necrosis, & hemorrhage. Uniform, closely packed swollen cells. Dark nuclei w/clear halo (“fried egg”). Capillaries in “chicken wire” pattern. Leptomeningeal spread may occur w/tumor progression.

Majority have loss of 1p & 19q = prolonged nat hx, more responsive to chemo.

Rx: Surgery for dx, sx relief & prolonged survival. Adjuvant XRT/chemo for residual tumor/anaplastic tumors. Timing being studied (XRT + chemo vs. chemo + XRT). XRT felt to delay recurrence & prolong survival. Chemosensitive (due at least in part to 1p19q): chemo occasionally given up front to delay XRT. PCV or TMZ effective, response up to 100% in 1p19q compared w/23%-31% in non-1p19q. PCV improves both PFS and OS when combined w/XRT compared to XRT alone (RTOG 9802). Can initially give one PCV or TMZ, then the other following recurrence.

Prognosis: Better survival than astrocytomas. 1p19q codeletion most important prognostic factor. Often indolent course but ultimately fatal. Natural history = progression from low grade to high grade. High grade have much worse prognosis. Rare systemic mets.

Ependymoma: (Curr Opin Neurol 2008;21:754; Curr Neurol Neurosci Rep 2010;10:240) Uncommon primitive glial tumors (<10% of CNS tumors, ˜25% of spinal cord tumors). From ependymal cells lining ventricles. Children (median age 5 yo): 90% intracranial.

Adults: 75% spinal (intramedullary). Infratentorial (fourth ventricle & subarachnoid) > supratent (lateral vent/parenchymal).

P/w: Depends on location. Post fossa = ↑ ICP (HA, n/v). Supratentorial = szs/focal defs. Spinal cord = Paraparesis, sensory level (cervical common, entire cord possible).

Dx: Imaging: Fourth vent tumor w/calcification classic. CT: Hyperdense w/homogeneous enhance, cysts & calcification common. MRI: ↓ T1, ↑ T2, prominent enhancement. Image entire neuraxis to r/o spinal mets. Spinal seeding more common w/infratent tumors (˜10%). Lumbar puncture: w/CSF cytology for metastasis.

Surgical resection for dx & Rx. Path: Grade corr w/prog: Myxopapillary ependymoma, subependymoma (WHO Grade I). Ependymoma (WHO Grade II). Anaplastic ependymoma (WHO Grade III).

Rx/prognosis: Surgery: Gross total resect improves survival, but often complicated. Potentially curative for WHO Grade I tumors. Higher grade, incomplete resection younger age, male, intracranial tumor location, associated with worse clinical outcome.

XRT: Std Rx after resect, 54 Gy improves 5-yr survival 0%-20% → 50%-75% (consider SRS). Chemo: Role unclear, can allow postponing postop radiation in young children, consider platinum-based regimen.

Even w/surgery & radiation, prognosis poor w/˜50% local recurrence.

Meningioma: (Neurosurgery 2005;57:1088; Curr Neurol Neurosci Rep 2013;13:337): Most common benign BT (54%). 36% of all 1° brain tumors. 7.33/100,000 person-yrs; 98% intracranial. F > M (intracranial 2:1; spinal 9:1). Originate in arachnoidal cells. Most slow growing & benign (78%) = WHO Grade I. Atypical (20%-38%, WHO II), malig (1%-3% WHO III; more aggressive; more common in men). Usu single, but can be mult (familial synd/NF2). Risk factors: Radiation, possibly hormone therapy & breast ca. Tumor size may ↑in pregnancy.

P/w: Depends on location. Often szs (30%-40%), HA (dural based), focal defs. Many found incidentally on imaging, population incidence (˜1%) ↑’s w/age. Location: any meningeal tissue, esp dural reflections (60% parasagittal, convexity, tuberculum sella, and sphenoid ridge).

Dx: Diagnosed by imaging. Biopsy not always required for Rx (XRT vs. surgery). CT: Homog enhancing extra-axial dural-based lesion (“dural tail”); 15%-20% calcified, rare hemorrhage. MRI: ↓ T1, iso-↑ T2, (calcification ↓ T2). Skull lumps over meningioma suggests invas. Path: WHO I = benign (meningothelial/fibrous/transitional/psammomatous/angiomatous/microcystic/secretory/lymphoplasmacyte-rich/metaplastic). WHO II = atypical (choroid/clear cell. ↑’d mitotic activity ≥4 mitoses/10 hpf & ≥3 of: ↑ nuc: cyt ratio/prominent nucleoli/sheet-like growth/foci of necrosis, or brain invasion). WHO III = anaplastic AKA malig (papillary, rhabdoid. ↑ degree of abnormality, larger areas of necrosis, ↑ mitotic activity ≥20 mitoses/10 hpf). Secretory meningiomas a/w ↑ edema.

Ddx: Lymphoma, dural mets, CNS sarcoid, extramedullary hematopoiesis, chloroma.

Rx: (1) Observe: Asymptomatic/incidental meningiomas. (2) Surgery: Symptomatic or growing asymptomatic meningiomas, or young pts. Complete resection curative in 80%. Incomplete resect = 40% recur in 5 yr. Preoperative embolization may improve resection. (3) XRT: Definitive/following surgery. Can stabilize unresectable/recurrent. Recommended postop for atypical/malig/bone invas. Radiosurgery for <3 cm lesions. Definitive XRT similar outcome to surgery. Postop XRT of SimpsonIV/high grade ↓’s recurrence 2-4×. (4) Systemic therapy: Investigational: anti-angiogenic drugs, somatostatin analogs, hormonal receptor antagonists, hydroxyurrea, TMZ.

Prognosis: (1) Degree of resection: OS at 10 yr w/Simpson I-III resection 80%. With Simpson IV risk of death increases by RR 4.2×. (2) Tumor grade: relapse rate for WHO grade I/II/III 7%/40%/80%, median survival >10/11.5/2.7 yrs. (3) Hormone receptor status: 5% median recurrence rate if PR+, 30% if ER+ or PR/ER-.

Hemangiopericytoma: (Am J Clin Oncol 2014;Epub ahead of print) Rare aggressive mesenchymal tumors arising from pericytes surrounding endothelial lining of capillaries and venules. 2.5% of mening tumors, <1% intracranial tumors; avg age 44 yo; M > F. 70% supratent, 15% post fossa, 15% spinal.

Dx: Sxs usu < 1 yr (2/2 rapid growth). CT: Focal hypodensity, heterogeneous enhancement. MRI: Iso-T1 & T2 + flow voids, heterogeneous enhancement, 50% dural tail.

Rx/prognosis: Gross total resection, often challenging 2/2 high vascularity; subtotal resection ↓ OS (111 mo vs. 158 mo). Local recurrence, distant mets common, often late. XRT ↑ local control & OS (123 mo XRT vs. 93 mo).

Hemangioblastoma: Uncommon, aggressive. Well circumscribed, vascular, typical cerebellum/cord. Most in children & young adults. 1%-2.5% of 1° intracranial tumors (7%-10% of post fossa, 4% of cord). 10%-25% occur in VHL (consider VHL if mult hemangioblastomas, early age at dx). ˜50% sporadic have inactivation of VHL tumor suppressor gene (chrom 3p).

P/w: Sx 2/2 compress, ↑ ICP, hemorrhage, paraneoplastic. Spinal lesions freq p/w pain. Paraneoplastic erythrocytosis in 15%-20% from EPO-like factor secreted by tumor.

W/u: MRI w/gado (CT inadequate; bone obscures posterior fossa/spinal canal). If no MRI, CT + conventional angio. Characteristic: Cerebellar cyst w/enhancing mural nodule/homogeneous spinal lesion. Spinal lesions a/w syrinx/cord edema. Genetic screen for VHL if mult hemangioblastomas or single lesion in pt < 50 yo.

Rx: Surveillance. Surgery if tumor grows/causes neuro def/hemorrhage; SRS good alternative for smaller unresectable/mult tumors. Preoperative angiogram to identify feeding vessels of highly vascular. Embolization prior to resection of large lesions. Complete surgical resection often possible, ˜25% recur after surgery. Adjuvant XRT if +margins/incomplete resect. Surgery, XRT for recurrent/resistant cases.

Primary central nervous system lymphoma: (Lancet Neurol 2009;8;581; Nat Rev Neurol 2013;9:317) Rare tumor affecting brain, spinal cord & eyes. Intermediatehigh-grade non-Hodgkin lymphoma (most B cell). Responds to steroids, chemo, XRT, but relapse common. 2%-8% have systemic lymphoma (CXR, CT abd/pelvis). Immunocompromise is main risk factor.

Epid: Incidence 0.47/100,000 person-yrs; 2% of intracranial tumors. Any age; most commonly 50-60 s; M > F (slightly).

P/w: Perivent WM, subcort/cortical, leptomeninges/CSF (40%), vitreous (20%). 30%-40% mult. Sxs vary w/location; Typical: focal defs, cognitive dysfunction. Others: HA, sz, personality Δs, lethargy, amnesia, floaters (vitreous); rarely RPD. Uveitis/vitreitis (10% cases); if+, usu precedes CNS tumor allowing early dx.

W/u: Definitive dx by biopsy/CSF/vitreous aspirate. Hold steroids preop (may ↓ bx yield). (1) Imaging: Brain MRI: Iso/↑ T1, ↑ T2, homog enhance, diffusion restriction. HIV-related: MRI mult ring-enhancing ↑ T2. Image spine if clinical suspicion of cord involvement (2) Biopsy: Path similar to systemic lymphoma; perivascular. (3) CSF: ↑ protein, ↑ lymphocytes; serial large vol LPs for dx by cytology. Send flow cytometry & IgH rearrangement. Check CSF EBV if immunocompromised. (4) Ophtho Exam w/slit lamp exam for vitreous involvement. (5) Body imaging (CT chest/abdomen/pelvis or PET/CT) to r/o systemic dz. Consider testicular U/S. (6) Bone marrow biopsy. (7) Laboratory Eval: CBC, CMP, HIV, LDH.

Ddx: glioma, met, sarcoid, vasculitis, MS, CLIPPERS, Langerhans cell histiocytosis; immunocompromised: TB, toxo

Rx: (1) Dramatic temporary response to corticosteroids. (2) No resection—does not improve prognosis, may worsen deficits (3) XRT: High responses & improved survival but short response duration & long-term neurotoxicity. (4) Methotrexatebased chemo (often combined w/other agents, occ followed by XRT) improves chances of durable remission. Investigational use of stem cell transplant.

Prognosis: Performance status, age are prognostic. No Rx ˜4 mo, WBRT 12-18 mo (contraindicated if >age 60 b/c dementia risk), Chemo Rx + WBRT >40 mo.

Numerous types: Craniopharyngioma, pituitary adenoma, meningioma, optic glioma. Visual impairment common presentation: Classic = Optic chiasm compression or invasion → bitemporal hemianopsia. Hormone-related sx also common → endocrine eval (pituitary/hypothalamus compress or involvement → hypopituitarism; pituitary adenoma → ↑ hormone production). Most tumors benign. Disability from proximity to other structures.

Craniopharyngioma: (J Neurooncol 2009;92:283; Horm Res 2008;69:193; Handb Clin Neurol 2014;124:235-253) In children/adol (30%-50%) 0.11/100,000 person-yrs; 0.8% of BTs (1%-4% in children). In adults, peak 50-70 yo. Benign epithelial sellar tumor; often extends into surrounding structures.

P/w: Sxs from compress of optic chiasm, pituitary & 3rd vent. Headache, visual field defects, hormone aberrations (80%-90%), diabetes insipidus, hydro common.

Dx: Imaging: Sellar & suprasellar (70%), suprasellar only (20%), intrasellar only (10%). Commonly calcified. CT: Heterogeneous solid, cystic, calcified mass w/heterog enhance. MRI: Heterog mass, iso/↑ T1; ↑T2; solid/cystic rim enhance.

Rx: May need pre-op EVD/shunt of hydro. Peri-operative stress-steroids, thyroid replacement. Surgery: Radical vs. subtotal resection via frontal/transsphenoidal approach. XRT: 54 Gy for subtotal resect. Conventional/intracavitary/fractionated/SRS.

Prognosis: Hypothalamic obesity synd, hypopituitarism, DI are risks of aggressive surgery. Also ↑ cardiovascular, cerebrovascular, respiratory mortality. Subtotal resection + XRT = 80%-95% success.

Pituitary adenoma: (NEJM 2006;355:2558; Curr Opin Neurol 2012;25:751) Most common sella-region tumor. 1% population w/sympt pit ad, 10% at autopsy. Microadenoma <1.0 cm; macro >1.0 cm.

P/w: Many subclinical. (1) Microadenoma: can be symptomatic from overprod of antpituitary hormone. Hyperprolactinemia—galactorrhea & amenorrhea/hypogonadism (52%). Excessive growth hormone—gigantism & acromegaly (27%). ACTH—Cushing synd (20%). TSH-secreting (rare)—hyperthyroidism. (2) Macroadenoma: sxs from compress of pituitary/stalk: Pituitary insufficiency. Mild hyperprolactinemia (disrupted pituitary stalk & lost hypothalamic inhibition). Chiasm compress—visual field defs. Cavernous sinus—oculomotor paresis. Traction on diaphragmata sella—HA.

Imaging: CT: Microadenomas: Low-density mass in brightly enhancing pituitary. Macroadenomas: Isodense, enhance uniformly; more calcification/hemorrhage. MRI: Iso-T1, slight ↑ T2, uniform enhancement.

Rx: Medical—hormone inhibition, esp for prolactinomas (dopamine agonists, cabergoline > bromocriptine); somatostatin analogs for GH-screting adenomas. Surgical—transsphenoidal resection; esp if visual field def. Gross total resect usu not possible. XRT—after subtotal resect. TMZ can be used for pituitary carcinomas. Monitoring—serial visual field testing. Long-term neuroendo f/u, supplementation.

Epid: Very rare; 0.4%-1% of adult CNS tumors, 1%-11% of pedi. Subtypes: (1) Pineal parenchymal tumors/pinealomas (most <10 yo). (2) Germ cell tumors (most 10-14 yo). (3) Less common: Glioma, meningioma, lipoma, metastasis, pineal cyst.

P/w: Sxs from invas/compress/CSF obstruction. Hydro, visual Δ, nausea/vomiting, impaired ambulation. Classic is Parinaud synd (up to 75% = vertical gaze palsy, lightnear pupillary dissociation, retraction convergence). Less common: Cranial neurop, hypothalamic dysfxn, leptomeningeal mets.

Dx: MRI/CT nonspec, don’t correlate w/histology. MRI w/contrast of entire spine, brain. CSF & serum for cytology & tumor markers preoperatively or 10-14 days postop. Biopsy prior to Rx. Open bx affords: visualization, CSF for markers, third ventriculostomy (if needed) vs. Stereotactic bx. Surgery if bx inconclusive/shows benign tumor.

Rx/prognosis: Surgery: Benign, well encapsulated amendable to resection (few) XRT: Many subtypes respond. 5-yr survival 44 → 90% depends on type, age, extent of dz & Rx.

Pineocytomas: Def: Benign tumor of pineal cells. Epid: Adolescence to mid-life, slow growing, <3 cm. Only 1/3 w/hydro. Dx: CT: Isodense; prominent homog enhance, cysts & calcification common. MRI: Sharply demarcated, ↓ T1, ↑T2, variable intensity. Pathology: Similar to nl pineal gland. Rx: Often surgically removed completely. Adjuvant XRT to subtotal resection does not increase survival.