ABSTRACT
B. Clinical Manifestations of CNS Tumors 1. Signs and symptoms of raised intracranial pressure
a. Headache: nocturnal or worse when waking up, may improve over the course of the day, worsen with coughing, Valsalva maneuver, or postural change
b. 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 effect
attributable to tumor, surrounding edema and hemorrhage, and hydrocephalus
2. 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 on
localization of the tumor 3. Pain also may result from local invasion of pain-sensitive
structures, e.g., dura mater, intracranial vasculature, and periosteum
A. Temporal Lobe 1. Dysembryonic neuroepithelial tumor (DNET),
ganglioglioma, pleomorphic xanthoastrocytoma, astrocytoma, oligodendroglioma
B. Pituitary Fossa and Sellar and Suprasellar Regions 1. Pituitary gland tumors: pituitary adenoma, Rathke’s
cyst, granular cell tumors 2. Suprasellar region: germ cell tumors, craniopharyn-
gioma, olfactory neuroblastoma, optic nerve gliomas, colloid cyst, epidermoid cyst, dermoid, lymphoma, hamartoma (hypothalamus), metastasis
3. Clivus: chordoma, osteosarcoma, chondrosarcoma 4. Differential diagnosis should also include nonneoplastic
causes: carotid or cavernous aneurysm or fistula, sarcoidosis, cavernous sinus thrombosis
C. Pineal Region 1. Germ cell tumors (germinoma, teratoma), pineal cell
tumors (pineocytoma, pineoblastoma), meningioma, astrocytoma, pineal cysts, metastasis, lipoma, epidermoid and dermoid cysts (also arachnoid cyst)
2. Germ cell tumors occur in childhood
D. 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, hemangioblastoma
E. Corpus Callosum 1. Lymphoma, glioblastoma multiforme
F. Cerebellopontine Angle 1. Schwannoma (acoustic neuroma), meningioma,
epidermoid, metastasis 2. Rare: paraganglioma, choroid plexus papilloma
G. Foramen Magnum 1. Astrocytoma, meningioma, ependymoma, medullo-
blastoma, metastasis 2. Mostly involving the clivus: chordoma, osteosarcoma,
chondrosarcoma
H. Spinal Cord (discussed below)
A. General Characteristics 1. Derived from neuroglia and progenitor cells (stem cells) 2. Include astrocytomas, oligodendrogliomas, mixed
oligoastrocytomas, pleomorphic xanthoastrocytomas, ependymomas
3. 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) astrocytoma
2) Anaplastic astrocytomas: worse prognosis than
anaplastic oligodendrogliomas 4. Other possible prognostic factors
a. Extent of surgical resection b. Mental status changes at onset c. Short duration of symptoms before diagnosis d. Tumor size
B. Associated Inherited Syndromes 1. Li-Fraumeni syndrome
a. Rare autosomal syndrome associated with familial clustering of soft tissue and bone sarcomas, breast carcinomas, and CNS neoplasms
b. Often diagnosed before age 45 years c. Associated with germline mutation of p53 d. Reported brain tumors include astrocytoma (anaplastic
and glioblastoma multiforme) and diffuse B-cell lymphoma
e. Possible association with Sturge-Weber syndrome (no adequate data)
2. Familial polyposis syndromes a. Turcot’s syndrome: adenomatosis polyposis coli associated
with gliomas and primitive neuroepithelial tumors b. Gardner’s syndrome: osteomas and soft tissue tumors
3. Neurofibromatosis type 1 (NF1) a. Neurocutaneous syndrome associated with low-grade
gliomas (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 schwannomas
b. 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 variable
penetrance b. Associated with Lhermitte-Duclos disease and character-
ized by various mucocutaneous papules, noncutaneous benign hamartomatous tumors, and carcinomas
c. Most common malignant tumors are breast and thyroid carcinomas
C. Astrocytoma Classifications (Table 16-1) 1. WHO classification 2. St. Anne/Mayo grading
D. Diffuse (fibrillary) Astrocytomas 1. Low-grade (WHO grade II) diffuse astrocytomas
a. Associated with mutations of the tumor suppressor gene p53 on chromosome 17p13.1 in two-thirds of cases and
g. Neuroimaging characteristics: T2 hyperintense lesions with little to no enhancement, edema, or hemorrhage
h. Prognosis 1) Survival is variable (at least 3-5 years is expected) 2) Most low-grade astrocytomas undergo malignant
transformation with time 3) Risk factors for malignant transformation: tumor
size, gemistocytic pathology, presentation in first decade or after age 50 years, increased enhancement
2. Anaplastic (WHO grade III) astrocytoma a. Associated with mutations of the tumor suppressor gene
p53 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 hemorrhagic
foci d. Microscopic features
1) Cellular proliferation is more prominent than in lowgrade astrocytomas
2) Often, frequent mitotic figures and endovascular proliferation
3) No necrosis e. Seeding of the neuroaxis by cerebrospinal fluid (CSF)
dissemination and ependymal spread may occur but are rare
overexpression of proto-oncogene encoding plateletderived growth factor (PDGF)
b. Occur typically in either first decade or between third and fourth decades
c. Usually hemispheric location, with predilection for temporal and posterior frontal lobes more than anterior parietal lobe
d. Tends to be infiltrative, with no well-defined borders e. Seizure is common presentation f. Pathology
1) Pattern (from most common to least common): often fibrillary, protoplasmic, gemistocytic astrocytomas
2) Fibrillary astrocytomas (Fig. 16-1) a) Well-differentiated astrocytes with scant cyto-
plasm; atypical and hyperchromatic nuclei; fine, fibrillary processes
b) Microcysts containing mucinous material c) Scant to absent mitotic figures and vascular
proliferation d) Calcification is rare but may occur in up to 10% to
20% of cases 3) Protoplasmic astrocytomas
a) Hypocellular b) Cells with small round nuclei, sparse cytoplasm c) Prominent characteristic microcystic spaces
4) Gemistocytic astrocytomas (Fig. 16-2) a) Large cells with abundant eosinophilic cytoplasm
and eccentrically placed nuclei b) Usually worse prognosis c) Malignant transformation: more often than other
pathologic subtypes
Table 16-1. WHO Classification and St. Anne/Mayo Grading of Astrocytic Tumors
WHO St. Anne/Mayo_______________________________ ________________________________________________________ Designation Classification Grade (based on criteria)* Criteria*
f. Median survival: usual estimate, about 2 to 3 years after presentation
3. 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 symptoms
d. Genetics 1) Secondary glioblastomas (malignant transformation
of 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 the
proto-oncogenes epidermal growth factor receptor (EGFR) and MDM2, loss of tumor suppressor
gene PTEN, LOH at chromosome 10, and mutation involving the RB gene
e. Most common locations: deep white matter and deep gray matter, including thalamus and basal ganglia
f. Macroscopic and neuroimaging features 1) Heterogeneous-appearing mass with foci of necrosis,
hemorrhage, and peritumoral edema (Fig. 16-3) 2) Neuroimaging often confirms the heterogeneous
appearance, with central area of necrosis and a ringenhancing rim
3) Despite the circumscribed gross appearance, the
tumor 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 multifocal
5) 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 symptoms
g. Microscopic features 1) All the features of anaplastic astrocytomas in addition
to 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 tracts
and around the ependyma 2) Atypical: CSF dissemination through neuroaxis
(occurs in 10%-20% of cases), may include pachymeningeal spread
3) Almost never occur: invasion of dura mater and metastasis outside of CNS
4) Meningeal invasion is sometimes called “meningeal gliomatosis,” occurs more frequently with malignant gliomas
i. Treatment 1) Usually includes surgical debulking aimed at relieving
mass 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 multifocal
3) Stereotactic biopsy: reserved for deep and inaccessible
tumors and comorbidities precluding general anesthesia 4) Most effective adjunctive therapy: external beam
radiotherapy 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 hemispheres
b. 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 neurons
c. Treatment 1) Some benefit from chemotherapy (as with PCV or
temozolamide) 2) No role for surgery because of infiltrative nature of
tumor
g. 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 cyst
i. Microscopic features 1) Compact pilocytic arrangements of elongated (some-
times stellate) cells admixed with microcystic areas 2) Classic feature: abundant Rosenthal fibers, may be
slight 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 prognosis
of all primary brain tumors l. Treatment
1) Maximal surgical excision of tumor 2) Surgical excision of the mural nodule may be
3) 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 nodule
f. Optic and hypothalamic gliomas: tend to be solid, pilocytic tumors
adequate and cystic wall need not be removed 3) With increasing thickness or enhancement of nodule
wall, the cystic wall also needs to be removed 4) Nonresectable tumors or recurrence with malignant
transformation may require adjuvant radiotherapy 2. Pleomorphic xanthoastrocytomas (WHO grade II or
III) a. Occur in second or third decade of life (average age at
diagnosis, 26 years) b. Often a history of seizures c. May originate from subpial astrocytes d. Macroscopic features
1) Well-encapsulated tumor frequently containing a mural nodule within a cyst
2) Often located superficially in temporal lobe e. Microsocopic features
1) Large cells with eosinophilic cytoplasm, some containing lipid droplets
2) Nuclear pleomorphism 3) Rare mitoses
f. 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. Treatment
1) Often includes complete resection 2) Radiation and chemotherapy often reserved for
recurrent or malignant tumors h. Postresection survival rates: 81% at 5 years, 70% at
10 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 CSF
outflow and causing hydrocephalus d. Macroscopic features: well-circumscribed, lobulated red
mass (vascular tumor), often calcified and cystic
Large cells with cytoplasmic eosinophilic granular bodies are a characteristic feature of pleomorphic xanthoastrocytoma, which is a low-grade glioma
e. Microscopic features 1) Large, oval cells with abundant eosinophilic cyto-
plasm and large, eccentric nucleus; often surround blood vessels in this vascular tumor
2) Pleomorphism is often present 3) Mitoses and necrosis are unusual
f. Neuroimaging: isointense or hyperintense on T2weighted images; intense, heterogeneous enhancement on T1-weighted imaging with contrast
g. Definitive treatment for symptomatic patients (i.e., hydrocephalus) or extensive tumors: surgical resection
h. Unless symptomatic, patients are only followed with periodic neuroimaging
F. 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 present
before age 5, 90% before age 20 e. Tumors involving optic nerve alone have a better
prognosis 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 have
NF1 3) Almost all patients with bilateral optic nerve tumors
sparing optic chiasm have NF1 g. Slow-growing tumors; malignant histologic features or
aggressive 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 nerve
i. Symptoms unique to optic nerve gliomas 1) Visual loss, visual field defects, painless proptosis, and
symptoms related to increased intracranial pressure 2) Symptoms of hypothalamic involvement
a) Endocrinopathies: precocious puberty, diabetes insipidus, other related endocrinopathies
b) Gelastic seizures: characterized by involuntary
laughter, more common with hypothalamic hamartomas
c) “Diencephalic syndrome”: emaciation, cachexia and loss of subcutaneous fat, emesis, pallor, hyperactivity, inappropriate behavior, euphoria
j. Treatment 1) Considered for tumors with aggressive behavior, espe-
cially for patients presenting with visual deterioration 2) Radiotherapy considered for patients older than 5
years presenting with tumors in locations other than intraorbital (intracranial locations such as chiasmal or retrochiasmal) and when total resection is not possible
3) Chemotherapy considered for patients younger than 5 years
4) Surgical excision may be limited to biopsy, especially for tumors involving optic chiasm
2. 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 prognosis
d. Symptoms: usually related to ataxia and other cerebellar
features, 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 variable
degrees of enhancement 2) May contain a cystic component (Fig. 16-9) 3) Diffuse pontine gliomas: all are malignant 4) Most gliomas involving cervicomedullary junction are
low-grade gliomas 5) Tumors of midbrain usually have a better prognosis
than those involving medulla or pons 6) Dorsal exophytic tumors tend to have better
prognosis f. Prognosis
1) 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 neurofibromatosis
2) 5-Year survival: 5% to 30% g. Treatment
1) Best: radiotherapy 2) Surgical resection usually involves stereotactic biopsy;
is best performed on focal, cystic, or exophytic tumors
G. 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 resembling
fibroblasts b. Usually present in the first decade
H. Oligodendroglioma 1. From cells of oligodendroglial origin (O2A progenitor
cells)
2. Genetics a. Development of low-grade oligodendrogliomas: associ-
ated with loss of heterozygosity of chromosomes 1p, 19q, and 4q
b. Development of high-grade oligodendrogliomas from the low-grade tumors: associated with loss of heterozygosity of chromosomes 9p and 10q
c. 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 between
third and fifth decades 6. Small earlier peak in childhood between 6 and 12 years;
thalamic location at presentation is common in children
7. Seizures are often the initial presentation in up to 75% of patients because tumor commonly involves cerebral cortex
8. Most common location: frontal lobe, followed by temporal and parietal lobes; rarely brainstem or spinal cord
9. Slow-growing, infiltrative gliomas: may start in subcortical white matter, tend to spread along white matter tracts and corpus callosum
10. Better prognosis than astrocytomas 11. 5-Year survival rate, 75% 12. Mean postoperative survival, 4 to 11 years
13. 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 cytoplasm
and 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 eggs
d. There may be mucin-rich microcystic spaces e. Capillaries interposed between uniform-appearing cells
may form a delicate vascular “chicken-wire” pattern f. Pleomorphism and endothelial hyperplasia (less commonly,
necrosis) indicate high-grade oligodendroglioma 15. Neuroimaging: heterogeneous appearing T2
hyperintense 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 less
favorable prognosis a. Contrast enhancement b. Endothelial proliferation c. Mitotic figures d. More than 5% of MIB-1 staining e. Astrocytic component (with oligoastrocytomas, as
discussed below) 18. Treatment
a. 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 chemotherapy
d. 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 advantage
I. Oligoastrocytoma 1. Composed of different populations of cells, some
resembling astrocytes, some oligodendrocytes, and some indeterminate
2. A common progenitor cell that differentiates into two different cell lines is likely
3. Glial tumors with predominant oligodendrocytic population of cells are often interpreted as oligodendrocytes
4. Increasing proportion of oligodendroglial component generally portends better prognosis (chromosome 1p and 19q deletions signify greater sensitivity of tumor to chemotherapy)
J. Ependymoma 1. Epidemiology
a. 5% to 8% of all primary intracranial tumors b. Age at presentation often in the first decade, with a
second 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%) or
spinal cord (10%) e. 2/3 of intracranial ependymomas occuring in children
are infratentorial and about 1/3 supratentorial f. 2/3 of intracranial ependymomas occur in children (mostly
infratentorial), 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 frequent
than 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, nystagmus
3. Potential for CSF dissemination: because of close contact with CSF, there may be “drop metastasis” in 5% of cases
4. Myxopapillary ependymomas a. Well-encapsulated, indolent, slow-growing vascular
tumors arising from filum terminale b. Occur most often in adults c. Associated with good prognosis
5. Posterior fossa ependymomas a. Well-demarcated tumors that tend to fill fourth ventricle
and extend through foramen magnum b. Appear as T2 hyperintense masses with heterogeneous
signal that may represent tumor vascularity (or necrosis) c. Often a heterogeneous pattern of enhancement
6. Microscopic features (Fig. 16-11) a. Sheets of uniform cells with round nuclei and variable
cytoplasm 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 vessel
c. Cytologic pleomorphism, necrosis, mitotic figures, and giant cells often signify anaplastic ependymomas
7. 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 to
obtain maximal possible resection b. For low-grade ependymomas of spine parenchyma or
filum terminale (myxopapillary ependymoma): surgical resection is mainstay of treatment, radiation is considered if residual tumor is present postoperatively
c. Extensive craniospinal radiation to entire neuroaxis required for patients presenting with CSF dissemination
d. 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 resections
K. Subependymoma 1. Slow-growing large firm masses most often occurring in
fourth ventricle, arising from medulla or lateral ventricles attached to septum pellucidum
2. Age at presentation: usually between 40 and 60 years 3. Microscopic features (Fig. 16-12): cells with round
nuclei and sparse cytoplasm; admixed with microcystic clusters and foci of calcification on a fibrillary background
4. Neuroimaging characteristics: mildly hyperintense lesions on T2-weighted images often with heterogeneous appearance and little to no enhancement
A. Ganglion Cell Neoplasms 1. Rare, slow-growing, benign well-circumscribed firm
tumors often occurring in temporal lobes, sometimes with cystic or calcified foci
2. Age at presentation: first 3 decades 3. Most common presentation: seizures (often
intractable) 4. Predilection for temporal lobes (followed by frontal and
parietal lobes); much less common, cerebellum and spinal cord
5. Neuroimaging characteristics: classically appear as well-circumscribed cystic mass (hyperintense on T2weighted images) with a mural nodule with variable enhancement
6. Microscopic features a. Presence of both neuronal (ganglion) and glial neoplastic
cells b. Gangliocytoma: tumors with predominance of
neoplastic ganglion cells without an obvious astrocytic component
c. Ganglioglioma: tumors containing neoplastic glial cells that often outnumber ganglion cells
d. 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 those
with anaplastic histopathologic features 8. Prognosis
a. Most carry benign prognosis with total or subtotal resection
b. Anaplastic histopathologic features: less favorable prognosis
B. Central Neurocytomas 1. Neoplasms of neuronal differentiation 2. Rare (about 0.5% of all primary CNS tumors), occur
primarily in young adults between second and fourth decades
3. 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 adults
5. Microscopic features: sheets of uniform cells with round nuclei; immunoreactive for synaptophysin
6. 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, with
long survival rates
C. Dysembryoplastic Neuroepithelial Tumor (DNET) 1. Rare, slow-growing (sometimes cystic) tumors with
predilection for temporal lobes 2. Most common presentation: complex partial seizures
(often intractable) 3. Microscopic features
a. Mucin-rich cellular glial nodules containing masses of oligodendrocyte-like cells
b. Specific glioneuronal elements c. Adjacent foci of cortical dysplasia d. Dystrophic calcification
4. Neuroimaging characteristics: hyperintense on T2weighted images (hypointense on T1-weighted images)
5. Benign prognosis 6. Surgical resection usually reserved for symptomatic
cases (e.g., intractable seizures)
D. Lhermitte-Duclos Disease (dysplastic gangliocytoma of cerebellum)
1. Commonly presents as slow-growing cerebellar mass with increased intracranial pressure
2. Commonly presents in the fourth decade 3. Associated with Cowden’s disease (about 50% of
patients 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 matter
6. Neuroimaging: laminated increased T2 signal without enhancement
E. 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, and
predilection for frontal and parietal areas 3. DIG has male predominance, DIA female
predominance 4. DIG associated with LOH for chromosomes 17p and
10q 5. Good prognosis with surgical resection (adjuvant
therapy often not needed)
A. Medulloblastoma 1. Most common PNET 2. Arises from cerebellar external granular layer precursor
cells 3. Age at presentation: often between 5 and 9 years old,
with second smaller peak between 20 and 24 years 4. 20% of all intracranial tumors in children 5. 75% of tumors arise from midline cerebellum or vermis 6. 25% of tumors arise from cerebellar hemispheres (more
commonly in adults with medulloblastoma) 7. Most common presentation: signs of increased
intracranial pressure such as nausea, vomiting, nocturnal headache, CN VI palsy (“nonlocalizing” sign due to hydrocephalus); common cerebellar findings of ataxia, titubation, and others
8. Early dissemination through CSF and metastasis a. Leptomeningeal metastasis may occur with CSF
dissemination b. Parenchymal metastasis occurs from spread to Virchow-
Robin spaces c. Thus, magnetic resonance imaging (MRI) of entire
neuroaxis should be part of the work-up 9. Macroscopic features: firm tumors that may contain
foci of hemorrhage, necrosis, calcification (rare), or cysts
10. Microscopic features (Fig. 16-16) a. Densely packed, undifferentiated cells with dark, small
oval nuclei and sparse cytoplasm, abundant mitotic figures and apoptosis among small foci of necrosis
b. Homer Wright rosettes in 40% of cases, represent attempts at neuroblastic differentiation
c. There may be immunoreactivity to synaptophysin 11. Histologic variants
a. Desmoplastic (nodular) variant 1) Characterized by clusters of neoplastic cells contained
within reticulin-rich firbrous septa 2) Often more neuronal differentiation within center of
Medulloblastoma is associated with relatively high incidence of widespread leptomeningeal dissemination. This occasionally occurs with glioblastoma and ependymoma
the “nodules,” which implies better prognosis 3) This variety may be seen more frequently in adults
and those with nevoid basal cell carcinoma syndrome (Gorlin’s syndrome)
b. Melanotic medulloblastoma: contains focal, limited melanin production
c. Medullomyoblastoma: contains striated muscle differentiation, immunoreactive for myoglobin; less favorable prognosis
12. Neuroimaging: hyperintense on T2-weighted images with a heterogeneous signal and enhancement pattern, often filling fourth ventricle and extending to cisterns
13. Treatment a. Often surgical resection for relief of symptoms of hydro-
cephalus and to establish diagnosis: gross total resection when possible
b. Surgical resection is often followed by craniospinal radiotherapy because of early risk of CSF dissemination
14. Prognosis a. 5-Year survival rate, often more than 50% b. Children older than 3 years often have 5-year survival
better than 75% c. Infants and those with disseminated tumor have 5-year
survival rates between 30% and 40% 15. Collin’s law for medulloblastoma
a. Period of risk for recurrence for tumor is patient’s age at diagnosis plus 9 months
b. If no recurrence within period of risk, tumor is cured
B. Ependymoblastoma 1. Large masses 2. Undifferentiated small cells with hyperchromatic nuclei
(“small blue cells,” as with the rest of PNETs)
C. Esthesioblastoma 1. Originates from neuroepithelial cells of upper nasal
cavity 2. Locally invasive tumor
a. Tends to invade skull through the cribriform plate b. May invade subarachnoid space and brain parenchyma
3. Treatment usually involves gross total resection, often followed by adjuvant radiation (external beam radiotherapy) and chemotherapy
4. Good prognosis with complete resection
D. Pinealoblastoma (see below)
E. Retinoblastoma
F. Cerebral Neuroblastoma (referred to as supratentorial PNET)
1. Peak incidence: in first decade of life, usually before age 5
2. Much less common than neuroblastomas arising from sympathetic chain
3. Presentation: often increased intracranial pressure 4. Associated with opsoclonus, myoclonus, and
encephalopathy 5. Predilection for frontal and parietal lobes 6. Macroscopic features
a. Large, heterogeneous-appearing enhancing mass with predilection for deep white matter and periventricular areas of frontal and parietal lobes
b. Also possible: cystic, hemorrhagic, or necrotic regions
c. CSF dissemination may occur 7. Microscopic features
a. Small cells with hyperchromatic nuclei and sparse cytoplasm
b. High mitotic activity, with scattered Homer Wright rosettes representing some neuronal differentiation
8. Poor prognosis
A. Meningioma 1. Most common nonglial primary CNS tumor 2. Most common benign brain tumor 3. Second most common primary brain tumor after
gliomas: 15% to 20% of all primary brain tumors 4. Female:male = 2:1 5. Peak incidence: in fifth to seventh decades, rare in
children 6. 40% to 80% of meningiomas: associated with mutation
involving gene responsible for NF2 on chromosome 22 and a tumor suppressor gene on chromosome 22q
7. Tumors contain hormone receptors (such as progesterone) and tend to grow during pregnancy
8. Well-circumscribed, slow-growing, dural-based benign tumors arising from arachnoid cap cells a. Tend to compress or envelop (not invade) surrounding
nervous tissue b. May infrequently invade the surrounding bone and soft
tissue 9. Almost 90% are asymptomatic 10. Clinical presentation depends on tumor location 11. Predilection (in order of occurrence): parasagittal >
convexity > sphenoid ridge > tuberculum sellae and olfactory groove > falx cerebri > lateral ventricle (other locations such as the optic nerve sheath, spinal, and extradural/extracranial are much less frequent)
12. 1% to 10% of cases may have mulitple meningiomas: consider NF2
13. Parasagittal and falx cerebri meningiomas may present with weakness and seizures, and olfactory groove meningiomas may present with Foster Kennedy syndrome (ipsilateral optic atrophy, contralateral papilledema, anosmia)
14. Macroscopic features: well-circumscribed firm (sometimes soft) tumors with smooth surface (Fig. 16-17 A)
15. Microscopic features (Fig. 16-17) a. WHO classification: typical, atypical, and anaplastic
meningiomas
b. Meningothelial: sheets or lobules of arachnoid epithelioid oval cells appearing to have inclusions (are essentially nuclear membrane invaginations of the cytoplasm)
c. Fibrous (fibroblastic) 1) Elongated spindle cells with background of collagen
fiber deposition 2) Whorl formation and psammoma bodies are not
characteristic features d. Transitional
1) Features of both the meningothelial and fibrous types 2) Contains abundant whorls and occasional psammoma
bodies e. Psammomatous: transitional meningioma with many
psammoma bodies f. Secretory: meningothelial or transitional meningioma,
characterized by cytoplasmic PAS-positive eosinophilic globules
g. Clear cell meningioma: clusters of elongated cells with increased cytoplasmic glycogen embedded in a matrix of fibrous septa
h. Microcystic meningioma: foamy cells on a microcystic background
i. Anaplastic meningioma: highly cellular, rapidly progressive tumor with excessive mitotic activity, nuclear atypia, and necrosis
16. Neuroimaging characteristics a. Skull plain films: hyperostosis and bony erosion of sur-
rounding bony structures b. MRI of head
1) Lesion is isointense with gray matter on T1-weighted and T2-weighted images (the latter is more variable), enhances strongly, and most have a “dural tail” (Fig. 16-18)
2) Variable degree of peritumoral vasogenic edema noted as increased T2 signal around tumor
17. Metastasis: rare (benign meningiomas may also rarely metastasize)
18. Treatment a. Primary mode is surgical resection b. Asymptomatic tumors or patients with well-controlled
seizures may be observed with serial scans c. Complete resection is not always possible; risk of recur-
rence depends on amount of residual tumor and histologic grade
d. Stereotactic radiosurgery is considered for partially resected tumors, “difficult-to-reach” places such as falx cerebri, and recurrent tumors
e. For tumors not amenable to stereotactic radiation (e.g., too large, odd shape, proximity to optic apparatus), fractionated radiation can be used
f. Chemotherapy (including treatment with sex steroid receptor antagonists) has been disappointing
B. Hemangioblastoma 1. Rare vascular neoplasm (1% of all primary CNS
tumors) 2. Often presents as cystic lesion of cerebellum with an
enhancing nodule
3. Peak incidence: fifth to seventh decades 4. 10% of cases occur in context of von Hippel-Lindau
disease (90% are sporadic) 5. Predilection for cerebellum (may also occur in spinal
cord, in which it tends to cause syringomyelia)
6. Macroscopic features a. 2/3 are cystic with enhancing mural nodule b. 1/3 are solid c. Cystic wall is often lined by nonneoplastic tissue d. Because of the tumor’s vascular nature, it may grossly
appear as a red cystic mass 7. Microscopic features (Fig. 16-19)
a. Numerous fine vascular channels b. In space between vascular structures are interstitial, stromal
cells with hyperchromatic nuclei and abundant cytoplasm filled with lipid and glycogen
8. Neuroimaging (Fig. 16-20) a. Cystic lesions often appear hyperintense on T2-weighted
images (hypointense to brain parenchyma on T1-weighted images), with intensely enhancing mural nodule
b. When tumor involves spinal cord, it almost always is intramedullary, expansile lesion often associated with syrinx
9. Treatment a. Surgical resection may be curative; this is to include
resection of mural nodule (if one is present) b. CSF dissemination may occur postoperatively
C. Hemangiopericytoma 1. Aggressive vascular tumor of undetermined origin, but
believed to be a dural-based sarcoma 2. Is not a variant of meniongiomas, as once believed 3. Macroscopic features: well-circumscribed, encapsulated
mass that may resemble a meningioma but is often vascular
4. Microscopic features (Fig. 16-21 A and B) a. Sheets of uniform cells interspersed within matrix of
small capillaries and larger blood vessels with a branching, “staghorn” appearance and a dense reticulin pattern
b. Increased mitosis, necrosis, or hemorrhage seen in
anaplastic variety 5. Neuroimaging (Fig. 16-21 C): strongly enhancing
masses with hyperintense signal on T2-weighted images, appearing isointense to surrounding cerebral cortex on T1-weighted images, often with flow voids representing large vascular structures
6. Treatment a. Surgical resection b. Limited experience with radiation c. No defined role for chemotherapy
7. Recurrence rate: may be as high as 60% to 80%; may be higher with high-grade histology (rare)
A. Systemic Lymphoma 1. Nervous system is eventually involved in up to 10% of
cases (rarely at onset of presentation) (leukemics have a very high incidence of leptomeningeal involvement [up to 70% of patients], although incidence of symptomatic cases has decreased with prophylactic CNS treatment)
2. Primary lymphoma that most commonly spreads to nervous system: usually non-Hodgkin’s lymphoma
3. Nervous system involvement most commonly includes leptomeningeal spread, presenting with
a. Cranial nerve palsies b. Increased intracranial pressure and associated symptoms c. Spinal root involvement (e.g., polyradiculopathy)
4. Systemic lymphomas that spread to the spine usually have contiguous spread into epidural space
5. CSF examination: often abnormal; first lumbar puncture is diagnostic in up to 80% of cases
B. Primary Central Nervous System Lymphoma (PCNSL)
1. Epidemiology a. Predilection for immunocompromised patients (most
commonly AIDS)
b. Most common brain tumor in setting of AIDS; second most common intracranial lesion in this population
c. Peak incidence: sixth to seventh decades (younger peak with immunocompromised patients)
d. Male predominance (male:female = 3:2) 2. Location
a. Predilection for frontal lobes and deep periventricular regions (may access CSF and subarachnoid space)
b. Infratentorially, more often in the cerebellum than brainstem
c. Leptomeningeal involvement is eventually demonstrated in up to 40% of CSF examinations, but primary leptomeningeal lymphoma is less common
3. Association with Epstein-Barr virus (EBV) a. Almost 100% of PCNSLs occurring in setting of AIDS
are EBV-driven b. EBV genome has been found in only 16% of PCNSLs
in immunocompetent patients c. Although EBV may induce B-cell neoplastic transform-
ation in AIDS, it probably has little role in pathogenesis in immunocompetent patients
4. Clinical presentation a. Symptoms at presentation depend mainly on the area
involved b. With predilection for frontal lobes, psychiatric symptoms,
change in personality and behavior, and altered mentation are common
c. Other less common presentations: signs and symptoms of increased intracranial pressure, cranial nerve palsies, seizures, ataxia
5. Ocular involvement is common a. Most patients with ocular involvement also eventually
have cerebral involvement b. Presents as chronic uveitis c. Diagnosis can be confirmed by vitreous biopsy
6. Primary intramedullary spinal cord parenchymal involvement is rare
7. CSF should be tested for cytology, and EBV polymerase chain reaction (PCR), among other tests, to rule out conditions in differential diagnosis
8. Macroscopic features: tumor is usually well-demarcated despite microscopic infiltrative nature
9. Microscopic features (Fig. 16-22) a. Sheets of neoplastic cells often occupy the perivascular
space and tend to penetrate and destroy walls of surrounding small vessels
b. Most tumors are diffuse large B-cell lymphomas, as noted on immunohistochemistry
c. Foci of necrosis tend to be more common with diffuse large B-cell lymphomas; hemorrhagic infarcts may be
seen with rare angiotropic lymphoma 10. Neuroimaging characteristics (Fig. 16-23)
a. Lesions tend to be isointense or hyperintense on T2weighted images
b. Somewhat specific for lymphoma: mirror-image lesions in deep gray matter, including thalamus and basal ganglia
c. Immunocompromised patients: heterogeneously enhancing mass with sometimes hemorrhagic or necrotic foci
d. Immunocompetent patients: enhancement is often intense and homogeneous; ring enhancement is rare
11. Prognosis a. Age and Karnofsky performance score are important
prognostic indicators
b. Median survival is usually only 3 months without treatment
12. Treatment a. Characteristic ring enhancement in setting of AIDS is
more common with toxoplasmosis, and patients traditionally have initially received treatment for toxoplasmosis
b. Nonresponders usually undergo diagnostic work-up, including biopsy
c. With recent advent of functional imaging, hypermetabolic positron emission tomography (PET) or single photon emission computed tomography (SPECT) plus positive EBV PCR are highly suggestive of lymphoma and occasionally preclude need for brain biopsy
d. Corticosteroids 1) Dramatic response 2) Corticosteroids have both cytotoxic effect on lym-
phoma neoplastic cells and act to decrease peritumoral vasogenic edema
3) Withhold corticosteroid therapy until diagnosis is confirmed because of unacceptable rate of false-negative results on biopsy obtained after corticosteroid therapy is initiated
e. Chemotherapy 1) Mainstay of treatment for PCNSL is generally sys-
temic high-dose methotrexate 2) Most effective agents are those with better penetrance
of BBB, such as procarbazine and high-dose methotrexate and cytarabine
3) Elderly patients are prone to neurotoxic effects of radiation, but long-term chemotherapy is also complicated by neurotoxicity, including encephalopathy
4) Cytotoxic effects of chemotherapy makes this treatment less desirable for AIDS-associated lymphoma
5) Despite this, combination of chemotherapy and radiotherapy has been reported to prolong survival in a proportion of AIDS patients to at least 2 years
f. Radiation is usually saved for palliative situations
A. Clinical Presentations 1. Increased intracranial pressure from noncommunicating
hydrocephalus such as headaches, false-localizing signs (CN VI palsy)
2. Local mass effect: compression on midbrain causing upper brainstem signs, including dorsal midbrain syndrome (Parinaud’s syndrome)—loss of upward gaze and convergence, pupillary abnormalities such as nonreac-
tive pupils 3. Extension into thalamus (may cause motor or sensory
deficits) and hypothalamus (may cause diabetes insipidus, precocious puberty)
B. Germ Cell Tumors 1. Common presentations
a. Symptoms of increased intracranial pressure b. Symptoms of direct brainstem and cerebellar
compression c. Endocrine dysfunction
1) Usually secondary to hydrocephalus or hypothalamic involvement
2) Precocious puberty in boys may occur with tumors of syncytiotrophoblastic cells that secrete β-human chorionic gonadotropin (βhCG) (choriocarcinomas and some germinomas)
3) Secondary sexual characteristics are due to excessive androgens secreted by Leydig cells, stimulated by βhCG
2. Germinomas a. Arise from developmental rests of primordial germ cells,
which may occur in gonads, midline structures of CNS, or elsewhere in the body, such as mediastinum
b. Epidemiology 1) Commonly occur in first to third decades (almost
always occur in boys) 2) 2/3 of pineal region germ cell tumors 3) Most common tumor in pineal region 4) Tumors from different sites of origin are identical
histologically c. Occur in midline: most common site is pineal gland,
followed by suprasellar or hypothalamic region d. Diabetes insipidus: common presenting syndrome of
suprasellar and hypothalamic tumors e. Propensity for CSF dissemination f. Survival rate: better than for other germ cell tumors g. CSF: increased placental alkaline phosphatase, and
increased βhCG in 10% of cases (the latter occurs in germinomas with syncytiotrophoblastic cells and portends a slightly worse prognosis)
h. Macroscopic features: soft, well-circumscribed midline masses that may be cystic
i. Microscopic features: sheets of large cells with glycogenrich clear cytoplasm and prominent nucleoli, surrounded by fibrovascular stroma containing abundant reactive T lymphocytes
j. MRI characteristics: isointense to cerebral cortex with strong enhancement (also on contrast-enhanced computed tomography [CT])
k. Sensitive to radiotherapy and chemotherapy: almost 100% curable
3. Teratomas a. Male predominance b. Commonly occur in childhood, as with germinomas c. Well-circumscribed masses (lobulated, cystic) containing
elements from all three embryonic cell lines (endoderm, ectoderm, mesoderm), often nonfunctional, and arranged in a haphazard way
d. Commonly contain neural tissue e. Mature teratomas (predominantly adult tissue) f. Immature teratomas (predominantly embryonic tissue)
4. Other germ cell tumors a. Embryonal carcinoma
1) Poorly differentiated carcinoma composed of sheets of large, pleomorphic, totipotential cells
2) Elevated CSF placental alkaline phosphatase (as well as βhCG and alpha-fetoprotein)
b. Endodermal sinus tumor (yolk sac tumor) 1) Lacy structure, Schiller-Duval bodies, PAS-positive
eosinophilic bodies 2) CSF elevation of alpha-fetoprotein (and placental
alkaline phosphatase) c. Choriocarcinoma
1) Characterized by multinucleate syncytiotrophoblasts (immunoreactive for βhCG), interspersed with mononucleated syncytiotrophoblastic elements and foci of necrosis and hemorrhage: highly vascular
2) CSF elevation of βhCG (predominantly) C. Pineal Cell Tumors 1. Present with increased intracranial pressure or signs of
brainstem compression such as Parinaud’s syndrome 2. Age at presentation usually between third and fourth
decades (younger age at onset of symptoms for pinealoblastomas)
3. 1/3 of cases are pineocytomas, 1/3 are pinealoblastoma, 1/3 are mixed pathology
4. Pineocytoma a. Benign, slow-growing firm tumor composed of mature
pineal cells (small monomorphic cells) arranged in pineocytomatous rosettes, often identical to normal pineal gland histology
b. Resembles pineal cysts on MRI c. CSF dissemination is rare
5. Pinealoblastoma a. A PNET composed of large undifferentiated pineal cells b. More gelatinous than pineocytoma c. Rarely associated with retinoblastoma in children d. CSF dissemination is common
D. Pineal Cysts 1. Benign, nonneoplastic 2. Often found incidentally 3. Usually observed with serial MRI studies
E. Treatment 1. Treatment of hydrocephalus with CSF shunting 2. Diagnostic stereotactic needle biopsy: predisposed to
sampling error but ideal if CSF dissemination 3. Open biopsy or resection using microsurgery 4. Radiotherapy
a. Most effective for germinomas b. Irradiation of entire neuroaxis indicated if CSF
dissemination
A. Clinical Presentation of Pituitary Region Tumors 1. Mass effect and pituitary hormone excess or deficits 2. Extension of tumor to involve cranial nerves occurs
with pituitary apoplexy or aggressive tumors (not slowgrowing pituitary adenomas)
B. Pituitary Apoplexy (Fig. 16-25) 1. May occur from combination of high metabolic
demand of pituitary tumor and marginal blood supply 2. Often presents as sudden onset of headaches, signs of
compression of cranial nerves (ophthalmoplegia, facial pain), cavernous sinus hypertension (proptosis, chemosis), and altered mentation (especially with hydrocephalus)
3. Pituitary apoplexy may occur in normal pituitary gland or Rathke’s cleft cyst
4. Sheehan’s syndrome: development of apoplexy at time of delivery, possibly induced by transient hypotension and hypoperfusion of physiologically hypertrophied (and otherwise normal) pituitary gland (no underlying neoplasm)
C. Functional Classification of Pituitary Adenomas 1. With the pituitary tumors as a whole, pituitary
hormonal deficits are generally more common than hormonal excess
2. Nonfunctional tumors a. More likely to present from mass effect b. May be signs of hypopituitarism: hypothyroidism,
hypogonadism, diabetes insipidus, hyperprolactinemia (with pituitary stalk syndrome discussed below)
3. Functional tumors a. Most common: prolactinomas presenting with gyneco-
mastia, galactorrhea, hypogonadism b. Nonfunctional pituitary tumors or neoplasms of other
origins in this region may cause hyperprolactinemia as result of compression of pituitary stalk and reduction of hypothalamic dopaminergic inhibition of prolactinproducing cells
c. In the latter situation, plasma prolactin level is often less than 150 ng/mL, which is less than level diagnostic of prolactinomas (>200 ng/mL)
d. Other functional tumors present with gigantism and acromegaly (growth hormone excess before or after closure, respectively, of long-bone epiphyses), Cushing’s disease (elevated corticotropin [ACTH]), etc.
