5

a. tumor grades (Table 5–1) (Fig. 5–1): all exhibit nuclear atypia; can be cytologically defined as malignant according to MIB-1 antibody labeling of the K_i-67 nuclear antigen, which is a protein of unknown function that is expressed only during mitosis (Box 5.1)

b. genetics (Fig. 5–2)

i.    mutations of the p53 gene, which encodes a cell-cycle regulator that inhibits progression through G1 phase of mitosis; uncommon in primary glioblastoma

ii.   mutations of the MDM2 gene, which encodes a protein that binds p53 protein

(1) mutations may cause overexpression of MDM2 protein, which leads to tumor formation by reducing levels of p53

(2) MDM2 protein also binds mutant p53, thus functional loss of MDM2 may allow abnormally active p53 to cause tumor formation

iii.  mutations of the epidermal growth factor (EGF) receptor gene, which encodes the receptor for EGF and tumor growth factor (TGF)-α

(1) mutations may cause overexpression of mutant EGF receptor that are constitutively active (i.e., do not require ligand binding)

(2) even without mutations, wild-type EGF receptor and related receptors (i.e., fibroblast growth factor receptor, vascular endothelial growth factor receptor) are commonly overexpressed in low-grade astrocytomas

iv.   platelet-derived growth factor-α (PDGF), which is involved in cell proliferation

v.    mutations in the retinoblastoma (RB) factor gene (Box 5.2), which encodes an inhibitory binding protein for transcription factor E2F that promotes proliferation; mutations of RB factor allows inappropriate release of active E2F and progression through G1 phase of mitosis

vi.   mutations of the CDKN2A (Box 5.3), which encode protein kinases that inhibit progression through the cell cycle by affecting the function of RB and p53

(a) the leucine-rich glioma-inactivated (LGI-1) protein (Box 5.4)

(b) PTEN, a tumor suppressor gene

i.    tumors grow along white matter tracts and vasculature, occasionally disseminating into the CSF {seeding}, particularly with tumors in the cerebellum, corpus callosum, or along the ventricles (Box 5.5)

d. epidemiology: accounts for 60% of primary brain tumors in adults; only known risk factor is brain irradiation

e. treatment

Figure 5–3 Juvenile pilocytic astrocytoma exhibits alternating compact and spongy areas that give a “floating” appearance to some of the cells. Multinucleated giant cells are also seen. (From Keating R et al. Tumors of the Pediatric Central Nervous System. Stuttgart, Germany: Georg Thieme; 2001:53, Fig. 5–6c. Reprinted by permission.)

ii.   grade III/anaplastic astrocytoma: surgery + irradiation ± chemotherapy

iii.  grade IV/glioblastoma multiforme: surgery chemotherapy (temozolomide) + irradiation

f. prognosis

i.    grade II/diffuse astrocytoma: 5-year survival

ii.   grade III/anaplastic astrocytoma: 2.5-year survival

iii.  grade IV/glioblastoma multiforme: < 1-year survival

2. Uncommon types of astrocytomas

a. juvenile pilocytic astrocytoma—grade I astrocytoma of the WHO classification

i.    histology: tumor exhibits a dense cellular areas filled with long bipolar astrocytes and numerous Rosenthal fibers, which are interspersed with relatively cell-free regions (Fig. 5–3); also exhibits eosinophilic granular bodies

(1) forms a large cystic mass when located in the cerebellum but a solid tumors when located elsewhere

(2) strongly associated with neurofibromatosis I

ii.   tumor location: cerebellum > hypothalamus, optic nerve

iii.  epidemiology: common only in children

iv.   treatment: surgery is usually curative; tumors in the optic-hypothalamic area respond to chemotherapy with carboplatin and vincristine

b. subependymal giant cell astrocytoma

i.    histology: tumor typically consists of giant astrocytes mixed with differentiated neuron-like cells in a heavily calcified stroma (Fig. 5–4)

(1) no anaplastic potential although exhibits locally invasive growth

(2) typically grow along ependymal surface of lateral ventricles, may block cerebrospinal fluid flow causing hydrocephalus

(3) associated with

(a) soft-tissue sarcomas and breast cancer {Li-Fraumeni syndrome}

(b) multiple intestinal polyps {Turcot syndrome}

(c) phakomatoses: tuberous sclerosis, neurofibromatosis-1 (see Chapter 12)

ii.   treatment: observation; surgery if the tumor grows or causes hydrocephalus

B. Oligodendrogliomas

a. cells exhibit “fried egg” artifact and “chicken wire” vasculature after formalin fixation (Fig. 5–5), resembling the non-artifactual appearance of clear cell ependymomas or central neurocytomas

b. 50% of oligodendrogliomas have a mixed histology with pronounced astrocytoma features {oligoastrocytoma} that may ultimately degenerate into a malignant astrocytoma

i.    both oligodendrocyte and astrocyte components show evidence of malignancy in oligoastrocytomas, that is, astrocytes are not simply trapped in an oligodendroglioma

c. frequently are calcified, or have hemorrhagic or cystic components

d. tumor location: often developing at the gray–white junction and growing toward the cortex, particularly in the frontal lobe

2. Tumor grades: histologically defined as low grade or anaplastic by the presence of mitosis, pleomorphism, vascular proliferation, and necrosis, as per astrocytomas; cytologically defined as malignant according to MIB-1 antibody labeling, as per astrocytomas

3. Genetics

a. p53 gene mutations

b. epidermal growth factor, platelet-derived growth factor, and vascular endothelial growth factor overexpression occurs without gene amplification

c. loss of heterogeneity (LOH): low-grade oligodendrogliomas have LOH on chromosomes 1 or 19; high-grade oligodendrogliomas also have LOH on chromosomes 9 or 10 (Box 5.6)

d. mutations in the CDKN2A gene, which encode the p16 protein cycle regulator (Box 5.7)

6. Diagnostic testing: Exhibits heterogeneous densities on neuroimaging, most of which are calcified (“chunky” or “popcorn-like” calcification) (Fig. 5–6)

7. Treatment

a. surgery ± irradiation (may only observe low-grade oligodendrogliomas after surgery)

b. chemotherapy: highly sensitive to PCV treatment (procarbazine, lomustine [CCNU], vincristine) or temozolomide (Temodar), particularly rapidly enlarging tumors with ring enhancement

i.    response to chemotherapy is not related to MIB-1-labeled K_i-67 ratio but it is proportionate to the amount of oligodendroglial-like cells in the tumor

ii.   tumors with LOH 1 or 1 + 19 have greater chemotherapy responsiveness

8. Prognosis: Tumors with LOH 1 or 1 + 19 are associated with longer survival times; tumors with CDKN2A gene deletions are associated with shorter survival times

1. Histology (Fig. 5–7): the MIB-1 antibody labeling of the K_i-67 antigen can provide a cytological definition of malignancy, as with astrocytomas and oligodendrogliomas

a. WHO grade I subtypes

i. meningothelial meningioma—exhibits groups of tumor cells surrounded by thin collagenous septa that are difficult to visualize, giving the impression of a syncytium

ii. fibrous meningioma—appears similar to dense connective tissue

iii. transitional meningioma—exhibits clumps of cells surrounded by whorls of more cells {onion bulbs}; has elements of meningothelial and fibrous subtypes

iv. psammomatous meningioma—exhibits numerous laminated calcifications at the center of onion bulbs {psammoma bodies} that may become confluent and calcified

v. angiomatous meningioma—appears similar to the meningothelial subtype but has a pronounced vascular component

vi. secretory meningioma—focal epithelial differentiation forms a lumen containing accumulation of glucose polymers (i.e., periodic acid Schiff-positive)

vii. lymphocyte-rich meningioma—exhibits chronic inflammatory infiltrates

4. Diagnostic testing: neuroimaging demonstrates dural-based masses with tails (Fig. 5–8)

a. growth may occur entirely along meningeal surface without forming a tumor mass {en plaque meningioma}

E. Pineal Tumors (Box 5.8)

a. specific histology: tumors show lobular aggregates of well-differentiated pinealocytes arranged as rosettes (Fig. 5–9)

Related posts:

Movement Disorders Behavioral Neurology and Psychiatry Diseases of the Muscles Headache and Pain Disorders Diseases of the Nerves Seizures and Epilepsy

Stay updated, free articles. Join our Telegram channel

Join