Central Nervous System-tumor

Last revised 28 May 2008

Last major update January 2006

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See also Central nervous system-nontumor (future topic), Pituitary (future topic)

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Table of contents for Central Nervous System-tumor

Primary references

CNS cysts: general, arachnoid, choroid plexus, colloid, dermoid, enterogenous, ependymal, epidermoid, glial, meningeal, neuroepithelial, pineal, simple, syrinx

Tumors: general, approach to diagnosis, WHO classification

 

Glial tumors

Glioma-general, post-radiation

Astrocytic tumors: general, cystic, granular cell, WHO grading, pilocytic, diffuse, protoplasmic, gemistocytic, anaplastic, glioblastoma, gliosarcoma, pleomorphic xanthoastrocytoma, subependymal giant cell

Oligodendroglial tumors: oligodendroglioma, anaplastic oligodendroglioma

Mixed gliomas: oligoastrocytoma and anaplastic oligoastrocytoma

Ependymal tumors: ependymoma, anaplastic ependymoma, myxopapillary ependymoma, subependymoma

Neuroepithelial tumors of uncertain origin: astroblastoma, chordoid glioma, gliomatosis cerebri

Neuronal and mixed neuronal-glial tumors: ganglion cell tumors-general, gangliocytoma, ganglioglioma, desmoplastic infantile astrocytoma/ganglioglioma, dysembryoblastic neuroepithelial tumor, central neurocytoma, cerebellar liponeurocytoma, extraventricular neurocytoma, papillary glioneuronal tumor, paraganglioma

 

Nonglial tumors

Embryonal tumors: ependymoblastoma, medulloblastoma, supratentorial PNET, atypical teratoid/rhabdoid tumor, medullomyoblastoma, medulloepithelioma

Choroid plexus tumors: general, papilloma, carcinoma

Pineal tumors: pineal gland-normal, tumors-general, papillary tumor, pineoblastoma, pineocytoma, pineal parenchymal tumor of intermediate differentiation

Meningeal tumors: meningioma, WHO grading, anaplastic, atypical, chordoid, clear cell, invasive, papillary, rhabdoid, secretory; meningioangiomatosis, hemangiopericytoma, melanocytic tumors / melanoma

Germ cell tumors: general, germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma

Tumors of the sellar region: craniopharyngioma, ganglion cell tumor, pituicytoma, pituitary adenoma, pituitary carcinoma, spindle cell oncocytoma

Lymphoma and other hematopoietic lesions: primary CNS lymphoma, secondary CNS lymphoma, post-transplant lymphoproliferative disorders, anaplastic large cell, angiotropic, diffuse large B cell lymphoma, Erdheim-Chester disease, histiocytic lymphoma/sarcoma, Hodgkin’s, inflammatory pseudotumor, Langerhans cell histiocytosis, leukemia, lymphomatoid granulomatosis, plasma cell granuloma, Rosai-Dorfman

Mesenchymal and other tumors: chondroma, chondrosarcoma, chordoma, epithelioid hemangioendothelioma, fibro-osseous lesions, hemangioblastoma, lipoma, MPNST, neurofibroma, sarcoma, schwannoma, solitary fibrous tumor, textiloma

Metastatic tumors to brain/spinal cord: general, metastatic carcinoma, metastatic choriocarcinoma, metastatic melanoma, paraneoplastic syndromes

Miscellaneous: intraoperative consultation, procedures, grossing, features to report, staging, autopsy

 

Click here for CNS-nontumor (future topic)

 

Primary references

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American Journal of Surgical Pathology (AJSP), January 1999 to January 2006

Archives of Pathology and Laboratory Medicine (Archives), January 1999 to December 2005

Human Pathology, January 1999 to December 2005

Modern Pathology, January 1999 to December 2005

Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004

Websites: Akron Children’s Hospital, Atlas Interactif de Neuro-Oncologie, Virginia Commonwealth University

Journal search terms: brain, CNS, meninges, spinal cord

 

Please refer to these primary references for more detailed discussions and photographs

 

CNS cysts

Cysts-general

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No solid nodule of tissue

Tumors that commonly are cystic: pilocytic astrocytoma, craniopharyngioma, ganglioglioma, hemangioblastoma, occasionally metastatic carcinoma

Specimen preparation: save portion for EM; fix tissue and then cut sections of cyst wall; submit as many sections as possible to rule out neoplasm

Micro: no solid nodule of tissue; cyst wall may contain astrocytes, Rosenthal fibers, glial fibrils

DD: abscess (granulation tissue and fibrosis, inflammation); tumors with cystic areas (pilocytic astrocytoma: often in cerebellum; hemangioblastoma: vascular, lipid+, factor VIII+, reticulin outlines each cell), meningeal cyst (on spinal surface, syncytial type cells, collagen+), pineal cyst

 

Arachnoid cyst

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Subdural or subarachnoid cyst containing CSF

1% of intracranial masses; protrude towards brain or spinal cord; often in middle fossa near temporal lobe

Congenital lesions that arise from split in leptomeninges, also due to trauma or leptomeningitis

Treatment: surgery if symptomatic

Radiologic images: MRI - spinal cord cyst; CT - left temporal lobe cyst

Gross: variable size, but may be vary large; thin transparent wall with clear, colorless fluid; cyst is distinct from leptomeninges and dura

Gross images: cyst of left temporal lobe

Micro: thinner wall than epidural cyst; lined by connective tissue and meningothelial cells

Micro images: thin cyst wall; meningothelial cells

 

Choroid plexus cyst

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May be present throughout ventricular system, but usually in glomus of lateral ventricles

More frequent in children than adults

Contain CSF

Present in 1-2% of fetuses, <1% associated with trisomy 18

Radiologic images: MR shows small cyst; choroid cyst

Case reports: 53 year old woman with small lesion at foramen of Monro (Am J Neuroradiology 2002; 23:841)

Gross images: cyst at foramen of Monro

Micro: wall composed of connective tissue and epithelial cells

Positive stains: transthyretin

 

Colloid cyst

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Uncommon; probably due to maldevelopment

Usually ages 20-50 years in third ventricle near foramen of Monro

May cause intermittent positional headaches, hydrocephalus and rarely be fatal if it blocks foramen of Monro

May rupture and mimic abscess or ventriculitis unless colloid is identified

Case reports: 36 year old woman with AIDS, headache and nuchal rigidity (Am J Neuroradiology 2000;21:1470)

Gross: up to 3-4 cm; round, unilocular with thin wall; cyst content after fixation is gray with consistency of soft cartilage

Gross images: colloid cyst #1; #2; #3 in third ventricle; #5; obstruction of foramen of Monro by gelatinous cyst

Micro: fibrous wall lined by simple columnar epithelium (also flattened, cuboidal, squamous) with variable cilia or mucin; also colloid or ghost cells

Micro images: lined by cuboidal or columnar epithelium; epithelium with ciliated and goblet cells resting on collagenous tissue; myelin stain

Positive stains: epithelium - keratin, mucin; contents are PAS+ and Alcian blue+

Negative stains: epithelium - GFAP, vimentin, neurofilament

DD: depending on location enterogenous cyst, ependymal cyst, Rathke cleft cyst

References: eMedicine

 

Dermoid cyst

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Uncommon; much less common than epidermoid cyst

Midline cerebellum, fourth ventricle, skull, spinal dura, cauda equina

May involve CNS or meninges

May derive from embryonic inclusions of skin at time of closure of neural groove at 3-5 weeks of gestation

May have sinus tract in nasofrontal or occipital regions

Benign; may rupture and cause chemical meningitis and inflammation resembling abscess

Radiologic images: various images

Gross: well defined, round/oval, opaque or pearly; variable size, variable wall thickness; contains greasy material with variable hair; may have solid components

Gross images: cyst from cerebellum with hair and sebaceous material

Micro: fibrous wall lined by keratinizing squamous epithelium with skin adnexa, cyst contains squames, hair, sebum; hair shafts are highlighted with polarized light; rupture may cause granulomatous inflammation with foreign body giant cell reaction

DD: cystic teratoma

References: eMedicine

 

Enterogenous cyst

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Also called neurenteric cyst

Rare, benign; probably due to maldevelopment

Usually in spinal cord (lower cervical and upper thoracic) presenting with spinal cord or cranial nerve compression; rarely intracranial

Usually intradural or subdural; intradural cysts are usually attached to spinal cord

Infants, children and adults

Cells resemble bronchial epithelium (Appl Immunohistochem Mol Morphol 2004;12:230)

Treatment: complete excision; occasionally is adherent to adjacent structures

Case reports: 78 year old man with cyst in front of medulla (Am J Neuroradiology 2001;22:496), intramedullary cyst of spinal cord presenting during pregnancy (J Neurol Neurosurg Psychiatry 2001;71:528), 43 year old man with cystic mass at cerebellopontine angle (Archives 2003;127:e45)

Gross: usually 1 cm or less

Micro: columnar epithelium with mucin (usually without cilia), resting on collagen layer; resembles intestinal or respiratory epithelium; goblet cells often present; may have squamous metaplasia

Micro images: (1) single layer of ciliated columnar epithelium; (2) figure 1: MRI shows mass at cerebellopontine angle; 2: cyst lining has single or pseudostratified columnal epithelium with focal squamous metaplasia; 3: cells have prominent apical cilia with basal nuclei but no atypia

Positive stains: Alcian blue, mucicarmine, PAS, EMA, CK5/6 (basal cells), CEA

Negative stains: GFAP, S100, NSE, vimentin

EM: well developed stereocilia, distinct basal cells, thin basement membrane

DD: colloid cyst (in third ventricle), ependymal cyst (abuts onto gliotic neuropil, GFAP+), cystic tumors

 

Ependymal cyst

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Rare; affects brain and spinal cord; usually not midline

Not in communication with ventricle or CSF spaces

Rarely ruptures and causes meningitis

Radiologic images: frontal ependymal cyst

Case reports: 15 year old boy with recurrent, intramedullary cyst at C2-C3 (Neurology India 2003;51:111-free full text)

Gross: resemble arachnoid cyst

Gross images: ependymal cyst

Micro: ciliated columnar cells with underlying fibrosis or fibrillary glia; may have ependymal-like cells or cilia; no mucin production

Micro images: cyst wall is lined by ependymal cells with focal multilayering

Positive stains: GFAP

EM: neuroepithelial origin

 

Epidermoid cyst

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Also called epidermoid or epidermoid tumor

More common than dermoid cyst (1% of intracranial masses)

Occurs at cerebellopontine angle, temporal lobe, spinal dura, pineal gland, sella, brainstem

Rarely undergoes malignant degeneration

Radiologic images: various images

Case reports: 68 year old man with cyst and sudden death (Am J Forensic Med Path 2002;23:368), woman with cerebellopontine angle cyst that degenerated into squamous cell carcinoma (Neurosurg 2002;97:1237)

Gross: well defined round mass has irregularly nodular capsule with pearly discoloration

Micro: fibrous wall lined by keratinizing squamous epithelium; contains squames but no skin adnexae and no hair

Micro images: fibrous wall with focal squamous epithelium but no skin adnexae

Cytology images: superficial squamous cells

Positive stains: CK8, CK20

DD: dermoid cyst, cystic craniopharyngioma (CK8-, CK20-)

References: eMedicine

 

Glial cyst

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Often in pineal gland

May cause hydrocephalus and sudden death

Case reports: 22 year old man with sudden death due to hydrocephalus from pineal gland cyst (J Clin Path 1996;49:267-free full text), 19 year old woman with thalamic glial cyst causing hydrocephalus due to hemorrhage (Neurol Med Chir (Tokyo) 1997;37:284)

Micro: wall lined by gliosis, Rosenthal fibers present, variable hemosiderin; no epithelial lining

Micro images: pineal gland cyst adjacent to midbrain; pineal tissue (left) and glial tissue (right)

Positive stains: GFAP

 

Meningeal cyst

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Also called diverticulum

Overlying hemispheres or in posterior or lateral epidural space in spinal canal

Radiologic images: various images (figures 1-9)

Micro: lined by fibrous tissue resembling dura, no arachnoid membrane

Micro images: fibrocollagenous layer without arachnoid

References: Neurosurg Focus 2002;13 (spinal extradural meningeal cyst-PDF file, free full text)

 

Neuroepithelial cyst

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Heterogeneous group of lesions with uncertain etiology

Brain and spinal cord, usually older adults

Rarely rupture and cause meningitis; may be associated with seizures or mass effect

Radiologic images: MRI shows large cerebral cyst

Case reports: neuroepithelial cysts of posterior fossa (Can Assoc Radiol J 1996;47:126), causing movement disorders (Can J Neurol Sci 2003;30:393), 4

Treatment: drainage, possibly with placement of drainage device to prevent recurrence

Micro: epithelioid surface with underlying fibrosis or fibrillary glia, but no obvious ventricular or subarachnoid connection

 

Pineal cyst

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May resemble a cystic tumor

Usually incidental finding present in 2-3% of adults, but may hemorrhage

Large cysts may compress aqueduct

Fine needle aspiration may provide rapid diagnosis (Cancer 2005;105:80)

Radiologic images: various images #1; #2

Gross images: pineal cyst

Micro: resemble glial cyst; dense gliosis with Rosenthal fibers; may be pinker than surrounding pineal gland (with dark calcifications); may compress pineal tissue and make it appear hypercellular; no epithelial or mesenchymal features

Cytology: small, uniform polygonal cells

Micro images: cyst is separated from partially calcified normal pineal tissue by thick layer of gliofibrillary tissue with Rosenthal fibers #1; #2

DD: pilocytic astrocytoma; also (by Xray) - germ cell tumor, enterogenous cyst, epidermoid cyst, dermoid cyst

References: Ann Diagn Path 1997;1:11

 

Simple cyst

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Glial cyst in cerebellum

No communication with ventricles

Case reports: 42 year old man (J Neuroradiol 2001;28:209),

Micro: wall lined by gliosis, Rosenthal fibers present, no epithelial lining

Positive stains: GFAP

References: J Neuroradiol 1995;22:48

 

Syrinx

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Defined as a pathological cavity in the brain or spinal cord, especially in syringomyelia

Dissection of white matter of brainstem or spinal cord NOT continuous with ventricle or spinal canal, and not lined by ependymal cells

Usually from spinal cord (in surgical specimens)

Related to trauma, tumors or abnormalities of cranio-cervical junction

Gross images: syrinx in spinal cord

 

 

CNS Tumors

CNS Tumors-general

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13K deaths in US annually (2% of cancer deaths)

Peaks in childhood, then declines to age 25 years, then increases with age

Childhood tumors: 33% in anterior fossa (supratentorial), 67% in posterior fossa (astrocytoma-26%, medulloblastoma/PNET-24%, ependymoma-14%)

Adults: metastases are more common than primary brain tumors but are usually not biopsied; of biopsied tumors, 67% arise in anterior fossa (glioma-33%, meningioma-13%, metastases-12%, pituitary adenoma-5%), 33% in posterior fossa (schwannoma-8%, misc.-33%)

Most common spinal cord tumors are schwannoma, meningioma and ependymoma

Metastasis of primary CNS tumors outside CNS is rare, usually occurs along brain and spinal cord via subarachnoid space or due to surgery related implantation of tumor cells into vessels

Benign appearing tumors may still be infiltrative and difficult to resect

Tumors may arise from neural stem cells, precursors of neurons and glial cells, recently discovered in mature brain

Symptoms: focal deficits, seizures, increased intracranial pressure (due to mass effect, hydrocephalus, cerebral edema), herniation

Intra-axial: within brain and spinal cord

Extra-axial: not within brain and spinal cord (such as meningioma)

Supratentorial: above tentorial membrane - cerebrum

Infratentorial: below tentorial membrane - cerebellum, brainstem or spinal cord

Labeling index/proliferation index: percentage of MIB1+ or PCNA+ nuclei (compared to all nuclei), usually in regions of highest proliferation; useful prognostic indicator (high values associated with poorer prognosis)

 

Tumors-approach to diagnosis

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Factors to consider:

(1) Neoplasm: yes or no?  Yes - hypercellular, composed of atypical fibrillar cells; if no, may be infectious, inflammatory, toxic-metabolic, traumatic, vascular, development or degenerative

(2) Primary or metastatic neoplasm?

(3) Glial, neuronal and other primary tumor considerations

(4) Correlate pathologic diagnosis with age, sex, location and imaging characteristics

Multiple lesions are often metastases, melanoma, medulloblastoma (late) or lymphoma

 

Differential diagnosis (adopted from Sternberg):

Fibrillar cells: fibrosis, granuloma, astrocytoma, astroblastoma, ependymoma, glioblastoma, gliosarcoma, ganglion cell tumor, central neurocytoma, pineocytoma, polar spongioblastoma, fibroblastic meningioma, MFH, schwannoma, neurofibroma, Langerhans cell histiocytosis, hemangioblastoma, melanoma

Epithelioid cells: xanthogranuloma or gitter cells, oligodendroglioma, choroid plexus tumor, medulloepithelioma, meningioma, chordoma, paraganglioma, pituitary adenoma, endodermal sinus tumor, embryonal carcinoma, hemangioblastoma, craniopharyngioma, metastatic carcinoma, melanoma

Conspicuously different cells: oligoastrocytoma, glioblastoma or gliosarcoma with epithelial metaplasia, ependymoma, ganglion cell tumor, desmoplastic medulloblastoma, transitional meningioma, germinoma, teratoma, choriocarcinoma, desmoplastic carcinoma, melanoma

 

WHO classification

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Extensively revised in 1993 (1993 classification; reference: Brain Pathol 1993;3:255)

Later revised in 2000 (J Neuropathol Exp Neurol 2002;61:215; WHO book is out of print but US National Cancer Institute has summary); WHO classification and ICD-O codes-PDF File

Neuroepithelial tumors: glial, neuronal, mixed glial-neuronal or nonglial

Glial tumors: astrocytic, oligodendroglial, mixed, ependymal, unknown origin

 

 

Glial tumors

Glioma-general

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Includes astrocytoma, ependymoma, glioblastoma, oligodendroglioma and various subtypes / combinations

“Glioma” may be used for frozen section, but is not a final diagnosis

Important to identify oligodendroglial component, due to effectiveness of chemotherapy for these gliomas

Most common CNS tumor

Presence of thrombosed vessels in tumors may predict postoperative systemic thromboses (J Neurosurg 1998;89:200)

Classification of gliomas:

Benign: does not recur; applies to pilocytic astrocytomas, certain gangliogliomas and ependymomas; may still have poor prognosis due to location that makes it difficult to resect completely

Low grade: may recur as high grade and kill patient

Gliomatosis cerebri: diffuse and extensive involvement of CNS associated rarely with gliomas; MRI and biopsy helpful for diagnosis

Micro: biopsies of tumor epicenter have cellularity greater than surrounding brain; biopsies of margin only are difficult to grade; often contain granular calcifications among hypercellular glia; also microcysts and mitotic figures (depending on tumor grade); may have uneven distribution of cellular density that obscures gray-white junction or spawns secondary structures of Scherer (subpial and perineuronal neoplastic glia)

Positive stains: GFAP

Negative stains: collagen, reticulin, fibronectin

Exceptions:

Oligodendroglioma cells have variable GFAP and are Leu7+ and S100+

Xanthoastrocytomas are reticulin+

DD: gliosis (even distribution of cellular density, contracts instead of expanding near hypercellular glia; usually less pleomorphism, no nuclear hyperchromasia, no nuclear cluster formation, no nuclear molding, no mitotic figures, no calcifications)

 

Post-radiation glioma

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Often 5-25 years after treatment of pituitary adenoma or craniopharyngioma

In children, often follows treatment for acute lymphoblastic leukemia

Usually anaplastic astrocytoma or glioblastoma

Case reports: 48 year old woman with gliosarcoma arising from irradiated anaplastic ependymoma (Hum Path 2004;35:512), arising 11 years after prophylactic brain radiation and intrathecal methotrexate for ALL at age 3 years (Childs Nerv Syst 1988;4:296)

References: Tumori 1994;80:220

 

 

Astrocytic tumors

Astrocytic tumors-general

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Most fibrillar of CNS tumors; other fibrillar tumors are tanycytic ependymoma and subependymoma

Low grade astrocytomas resemble gliosis

Affect entire CNS

Usually young adults

Most common primary brain tumor in children

Indicate the grading system used

Brainstem: 20% of primary brain tumors age 20 years and less are astrocytomas; 50% progress to glioblastoma at autopsy

Gross images: mass effect; brainstem glioma #1; #2; infiltrative margin

Micro: hypercellular; nuclei are angular and indent each other; infiltrative margins; often microcystic degeneration (easier to recognize on unfrozen tissue; on frozen section, microcysts contain protein)

Micro images: hypercellular tumor with infiltrative margin (left) vs. normal brain (right)

Positive stains: GFAP (variable)

 

Cystic astrocytoma

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Not a specific subtype, but a group of entities with similar gross features

Usually low grade unless cysts contain necrotic material

Macroscopic cysts are associated with cerebellar pilocytic astrocytoma

DD: hemangioblastoma

 

Granular cell astrocytic neoplasms

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Rare morphologic variant of astrocytoma and glioblastoma (not a separate WHO designation)

A degenerative change (AJSP 1996;20:55), not a distinct genetic subtype (Brain Path 2003;13:185)

More aggressive than non granular cell tumors, usually fatal (AJSP 2002;26:750)

Case reports: granular cell appearance due to Rosenthal fibers (Acta Neuropathol (Berl) 1993;86:100)

Micro: prominent population of atypical granular cells (large, round with eosinophilic, PAS+ granules, eccentric nuclei), often with transition to a classic infiltrating glioma; often lymphocytic infiltrate or macrophages

Positive stains: PAS (diastase resistant), S100, GFAP, intercellular reticulin; CD68, EMA and ubiquitin are due to lysosomes

EM: cytoplasmic granules are lysosomes, some autophagic

DD: neuroendocrine tumors, histiocytic lesions, demyelinating disease, infarctions

References: Semin Diagn Pathol 1999;16:91 (review), Clin Neuropathol 2000;19:170, Neuropathol Exp Neurol 1986;45:447 (granular cell glioblastoma), Hum Path 1993;24:805 (granular cell anaplastic astrocytoma)

 

WHO grading of astrocytomas (2000)

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1: pilocytic - circumscribed, biphasic, bipolar and multipolar cells, Rosenthal fibers, microcysts, granular bodies; no/rare mitotic figures, no/rare vascular proliferation, no/focal necrosis

2: diffuse - moderately hypercellular, monotonous cells, mild nuclear atypia, no/minimal mitotic activity

3: anaplastic - increased cellularity and diffuse infiltration, increased nuclear atypia, increased mitotic activity

4: glioblastoma - vascular proliferation, necrosis, crowded anaplastic cells, marked nuclear atypia, brisk mitotic activity

 

Pilocytic astrocytoma-grade I

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Pilocytic means “hair like”, due to long, bipolar processes

Most common CNS neoplasm of childhood; incidence of 1/100K; peak age 8-13 years

Better prognosis than diffuse types, particularly if resectable (such as cerebellar tumors)

May be multicentric

Usually involves midline structures in posterior fossa including cerebellum; also third ventricle, thalamus, hypothalamus, neurohypophysis

10 year survival is 100% if supratentorial and gross total resection vs. 74% if subtotal resection

Invasion of subarachnoid space and endothelial proliferation are not poor prognostic factors

Treatment: resection; radiation and chemotherapy for tumors of optic pathway and hypothalamic region; rarely recurs or disseminates

Gross: microcystic or macrocystic; may have mural nodule

Gross images: cerebellar tumor #1; #2 (arrow at mural nodule); #4; #5 with hemorrhage; optic nerve tumor

Micro: bipolar neoplastic cells with elongated hairlike processes that are arranged in parallel bundles and resemble mats of hair; Rosenthal fibers, often associated with eosinophilic protein droplets (resembling foamy macrophages); may have microscopically infiltrative margin; mural nodule may be highly vascular; often calcifications

Rarely malignant degeneration with hypercellularity, mitotic figures and necrosis

Micro images: bipolar cells with Rosenthal fibers #1; #2; #3; #4; various images #1; #2; various images with case history #1; #2 (with disseminated tumor)

Cytology images: bipolar long astrocytic processes and central Rosenthal fiber

Positive stains: GFAP (strong), PTAH, PAS (protein droplets), alpha-1-antichymotrypsin (protein droplets)

DD: gliosis, hemangioblastoma (cells appear fibrillar on frozen section)

References: Radiographics 2004;24:1693 (review; free full text); Br J Neurosurg 2004;18:613 (adults)

 

Diffuse astrocytoma-grade II

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Fibrillary, protoplasmic and gemistrocytic (see below) subtypes are called diffuse, but fibrillary is more common

80% of adult primary brain tumors; usually cerebrum, but can be anywhere in CNS

Age 40+ years

May become more anaplastic over time

Grade of small biopsies may not be representative

Median survival is 6-8 years, but rarely has rapid progression and death

Treatment: surgery; average survival is 7 years with wide variability

Poor prognostic factors: high Ki-67, p53, brainstem location

Radiology: mass effect, peritumoral edema

Gross images: diffusely infiltrative tumor

Micro: fibrillary cells contain cellular fibrillar processes and nuclei with greater angularity and density than normal CNS, also intracytoplasmic fibrils and longer cell processes than protoplasmic astrocytomas; microcysts are particularly prominent in protoplasmic subtype, may degenerate into macrocysts; margin gradually diminishes in cellularity and intermingles with normal CNS; may form secondary structures of Scherer

Micro images: smear shows neoplastic astrocytes with cytoplasmic glial processes and variable nuclear atypia; well differentiated tumor, HAM56 negative (no macrophages)

Positive stains: PTAH (fibrillary subtype), GFAP (fibrillary and protoplasmic subtypes)

DD: gliosis, oligodendroglioma (round nuclei with perinuclear halos, chicken wire vessels, mineralization, GFAP negative)

 

Protoplasmic astrocytoma-grade II

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Rare; 3-4% of supratentorial brain tumors

Variant of diffuse astrocytoma; WHO considers a variant of grade II astrocytoma

Mean age 21 years, often with long history of seizures before diagnosis, male predominance

Often in temporal and frontal lobes

Thought to derive from process-poor protoplasmic astrocytomas

Generally a benign clinical course after resection

Micro: proliferation of glial cells with few cytoplasmic processes; round/oval nuclei, microcystic background, no/rare mitotic figures; no vascular proliferative changes, no necrosis

Micro images: scant or vacuolated cytoplasm with short processes, vesicular nuclei and prominent nucleoli #1; #2; GFAP+

Positive stains: GFAP (focal/weak or negative)

Negative stains: Ki-67 (<1% staining)

Molecular: no 1p-

DD: microcystic oligodendroglioma (1p-), dysembryoplastic neuroepithelial tumor (associated with cortical dysplasia, usually multifocal or multinodular)

References: Hum Path 2004;35:317, Am J Clin Path 1995;103:705

 

Gemistocytic astrocytoma-grade II

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Variant of diffuse astrocytoma

May be more aggressive than other grade II astrocytomas (J Neurooncol 2005 [Epub ahead of print], J Neurosurg 1991;74:399)

Restrict diagnosis to cases with at least 20% gemistocytic cells

Case history: congenital brain tumor with various images

Gross images: frontal lobe tumor

Micro: conspicuous (20% of more) gemistocytes (plump cells with abundant, hyaline pink cytoplasm and no/minimal blue Nissl substance, hyperchromatic and angular nuclei at border of cell), perivascular lymphocytic cuffs; infiltrative margins; no neoplastic neurons