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CNS tumor
Reviewers: Eman Abdelzaher, M.D., Ph.D., Nat Pernick, M.D. (see Reviewers page)
Revised: 1 May 2013, last major update IN PROGRESS
Copyright: (c) 2005-2013, PathologyOutlines.com, Inc.
Table of contents
General: primary references
CNS cysts: general arachnoid choroid plexus colloid dermoid enterogenous ependymal epidermoid glial meningeal nerve root neuroepithelial pineal Rathke simple synovial syrinx
Tumors: general approach to diagnosis WHO classification
Glial tumors:
Glioma-general post-radiation
Astrocytic tumors / astrocytoma: general WHO grading anaplastic cystic diffuse-general diffuse-fibrillary diffuse-gemistocytic diffuse-protoplasmic glioblastoma glioneuronal tumor gliosarcoma granular cell pilocytic 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: angiocentric glioma 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 inflammatory pseudotumor Langerhans cell histiocytosis leukemia lymphomatoid granulomatosis 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 CNS: general metastatic carcinoma metastatic choriocarcinoma metastatic melanoma paraneoplastic syndromes
Miscellaneous: intraoperative consultation procedures grossing features to report staging autopsy
top
AJCC Cancer Staging Manual (7th ed)
Websites: Atlas Interactif de Neuro-Oncologie
Neuronal tumors
“Ganglion cell tumor” is not a WHO diagnosis
Most common in temporal lobe, but may arise anywhere
May resemble developmental lesions, cortical dysplasia and tuberous sclerosis
Often have better prognosis than gliomas that they resemble
Identify based on (a) neurons with large nuclei, large nucleoli, basophilic Nissl substance, synaptophysin+, neurofilament+, NeuN+, neurofilament+; (b) cells are neoplastic based on abnormal neuronal clustering, loss of orderly distribution, variably sized neurons in different stages of development, cytologic atypia (binucleation, large and bizarre nuclei, hyperchromasia); (c) Ki-67/MIB1+
Note: ganglion cells and neurons frequently cluster; ganglion cell tumors also often display heavy bands of fibrous tissue or perivascular round cells, Rosenthal fibers and granular bodies
Must also evaluate glial component for neoplasia (use GFAP to check for reactive cells, which cluster at margin of neoplasm)
Types of ganglion cell tumors:
(a) Gangliocytoma: ganglion cells and reactive glia
(b) Ganglioglioma: ganglion cells and glial neoplasm, not anaplastic; grade based on grade of glial component, using similar system as astrocytomas
(c) Anaplastic ganglioglioma: ganglion cells and anaplastic glial elements
DD: developmental lesions, cortical dysplasia, tuberous sclerosis; cells from glioblastoma, melanoma and astrocytomas may resemble neurons but lack Nissl substance and stain differently; glial tumors entrapping normal neurons
Benign
< 0.5% of glial neoplasms
Especially common in temporal lobe and floor of third ventricle
Patients present with seizures
More common in children and young adults
May be sellar, associated with pituitary adenomas (Virchows Arch 1994;425:93)
Case reports: 48 year old woman with acromegaly and intrasellar tumor (Archives 2005;129:415)
Gross images: hypothalamic-infundibular tumor has cells rich in Nissl substance (highlighted by cresyl violet)
Micro: abnormal mature ganglion cells (neurons with abundant cytoplasm containing Nissl substance, large nuclei with prominent nucleoli) and reactive glia; often binucleate or multinucleated cells; no glial atypia; glia cluster near margin of neoplasm
Micro images: (1) nerve cells of variable size and shape; (2) mature neurons with prominent nucleoli #1; (4) tumor attached to dura (arrow); (5) synaptophysin+ cytoplasm and cell processes; (6) intrasellar tumor from above case history composed of ganglion cells and adenohypophyseal cells
Positive stains: synaptophysin, neurofilament; GFAP (reactive glia)
EM: mature neurons with abundant endoplasmic reticulum, mitochondria and neurofilaments; secretory granules in neuronal processes
DD: ganglioglioma
References: Korean J Radiology 2001;2:108 (free full text)
Dysplastic gangliocytoma of cerebellum
Also called Lhermitte-Duclos disease
Rare, <200 cases described
Hamartomatous lesion, not a neoplasm
May present in childhood; slow enlarges and is usually discovered in adults
Due to or associated with PTEN mutation (Am J Hum Genet 2003;73:1191, free full text)
Associated with Cowden’s disease (OMIM #158350, autosomal dominant disorder with trichilemmomas, hamartomas, intestinal polyposis, palmoplantar keratoses, oral papillomas; increased incidence of breast, GU, CNS and thyroid tumors; due to abnormalities in 10q23)
Treatment: complete excision; occasionally recurs late
Case reports: 16 year old girl with headaches and gait disturbance, with Cowden’s disease (Canadian J Neurologic Sciences 2004;31:542)
Gross: grossly thickened cerebellar cortex
Micro: hyperplastic, disordered granular cell neurons that enlarge cerebellum; granular cells may exist in recognizable layer or be large and dysplastic neuronal cell bodies; axonal hypermyelination of molecular layer; often marked reduction in myelination of central white matter of cerebellar folia; no mitotic figures, no necrosis, no endothelial proliferation
Micro images: (1) thick layer of abnormal nerve cells on surface; (2) deformed nerve cells of variable size, usually with little Nissl substance; (3) abnormal enlarged ganglion cells (arrow); (4) large dysplastic nerve cell bodies; (5) neurons are neurofilament+
References: Clin Neurol Neurosurg 2001;103:105, Acta Neurol Scand 2002;105:137
Neoplasm with glial and neuronal components
Uncommon, < 1% of intracranial neoplasms
Occurs anywhere in CNS but most common in temporal lobes and cerebellar hemispheres
Usually age 30 years or less
Associated with epilepsy
Radiologic images: temporal lobe tumor
Treatment: gross total resection; rarely recurs, metastases are extremely rare
Case reports: 30 year old man with spinal tumor, 51 year old man with ganglioglioma containing neurofibrillary tangles, 4 year old boy with seizures (Archives 2003; 127:e387), with pleomorphic xanthoastrocytoma (Archives 2000;124:1707, AJSP 1997;21:763), with dysembryoplastic neuroepithelial tumor (Archives 1999;123:247)
Gross: well demarcated; firm, gray-yellow-brown, may be cystic; usually no hemorrhage or necrosis
Micro: clusters of abnormal ganglion cells and low grade glial neoplasm; often perivascular lymphocytes or microcalcification; variable Rosenthal fibers or eosinophilic granular bodies; rare mitotic figures, neurofibrillary tangles
Micro images: (1) mildly atypical glial cells and neurons #1; #2; #3; #4; (6) variable sized astrocytes and nerve cells and calcification; (7) GFAP+ astrocytes and their processes; (8) nesting pattern with delicate vasculature; (9) various images ; #3 (tumor with neurofibrillary tangles); (12) figure 1: MRI shows temporal lobe mass with cystic component; 2: prominent granular bodies, Rosenthal fibers and microcalcifications; 3: like #2 plus large, binucleated ganglion cells and perivascular cuffing; 4: NSE+
Cytology images: ganglion cell with prominent nucleoli and neoplastic astrocytes #1; #2; #3
Positive stains: GFAP (neoplastic glia), synaptophysin, neurofilament, neuron-specific enolase
DD: gangliocytoma, non-neoplastic brain with synaptophysin+ neurons (AJSP 1998;22:550)
References: eMedicine
Anaplastic ganglioglioma
Due to progression of ganglioglioma
Case reports: dissemination to spinal cord (Surg Neurol 1998;49:445), with sarcomatous component (Neuropathology 2002;22:40), metastases through a ventriculoperitoneal shunt (Pathol Int 1999;49:258), 6 year old girl with mixed ganglion cell tumor-giant cell glioblastoma (Archives 1999;123:342)
Micro: anaplastic glial cells
Positive stains: chromogranin A in ganglion cells, GFAP and vimentin (Acta Neuropathol (Berl) 1992;83:365)
EM: dense core neurosecretory granules and glial filaments
Desmoplastic infantile astrocytoma/ganglioglioma
WHO grade I of IV
First described in 1987 (J Neurosurg 1987;66:58)
Age 18 months and less; uncommon in older children or adults (J Neurooncol 2005 Sep 9 [Epub ahead of print], Neuropathology 2005;25:150)
Associated with hydrocephalus and rapidly increasing head circumference
Rare (< 0.1% of CNS tumors) intracranial tumor, exclusively supratentorial, usually frontoparietal
Good prognosis, with only rare craniospinal seeding or metastases (AJSP 2002;26:1515, Mod Path 1997;10:945, Australas Radiol 2005;49:433, Pediatr Blood Cancer 2005;45:986)
Radiologic images: large cerebral masses with both cystlike and solid portions (figures 7-8)
Treatment: complete resection; chemotherapy if infiltrative or progressive; residual disease may not grow and may spontaneously regress (Neurosurgery 2003;53:979)
Case reports: 6 month old boy with progressive lethargy, with melanocytic colonization, mixed with conventional ganglioglioma (Mod Path 2001;14:720)
Gross: large (up to 13 cm), partially cystic, firm, superficial; often involves multiple lobes and is focally attached to overlying dura
Gross images: mass at silver probe; resected mass
Micro: well delineated from normal brain; spindled or enlarged astrocytes and occasional abnormal binucleated ganglion-type cells; prominent desmoplastic stroma; may have primitive and mitotically active cells resembling PNET or medulloblastoma; may have focal Schwann cell differentiation
no/rare mitotic figures (except in undifferentiated areas), no necrosis, no vascular proliferation
Desmoplastic infantile astrocytoma: no neurons identified
Micro images: ganglion-type and glial cells is desmoplastic background; various images #1; #2; with melanocytic colonization
Cytology: low cellularity with dispersed or variably sized clusters of large neuronal cells with abundant granular cytoplasm, eccentric, hyperchromatic nuclei with undulating nuclear membranes and occasional binucleation, prominent nucleoli; also astroglial cells with smaller cytoplasmic rim, nuclear hyperplasia and more prominent irregularities in nuclear membranes; may have prominent degenerative changes, foamy macrophages; no vascular structures (CytoJournal 2005, 2:1, free full text)
Cytology images: cytology and H&E
Positive stains: GFAP (glia), reticulin (invests tumor cells), trichrome (stroma); neurons are synaptophysin+, NeuN+, neurofilament+, neuron specific enolase+
EM: astrocytic tumor cells are partly invested by pericytoplasmic basal lamina
DD: fibrous ganglioglioma
References: Childs Nerv Syst 2003;19:292, Brain Pathol 1993;3:275
Dysembryoplastic neuroepithelial tumor (DNET)
Grade I of IV (benign)
First described by Daumas-Duport in 1988 (Neurosurgery 1988;23:545)
Mixed glioneuronal neoplasm of teenagers/young adults
May arise during embryogenesis
Incidental or associated with chronic complex partial seizures (1-19% of surgical resections for epilepsy)
Either temporal or frontal cortex
Good prognosis after excision with only rare recurrence, even with subtotal excision
Radiologic images: nodular cortical lesion
Treatment: gross total resection usually is curative, usually eliminates or markedly reduces seizures
Case reports: 9 year old boy with headache and occipital mass (Archives 2002;126:991), 31 year old woman with 5 year history of grand mal seizures, with ganglioglioma (Archives 1999;123:247)
Gross: multinodular tumor of cerebral cortex, often in temporal lobe; usually cystic or gelatinous; discrete margin
Drawing: nodular tumor
Micro: bland cells resembling mature oligodendrocytes (Archives 2000;124:123), astrocytes and neurons that appear to float within mucin pools near bundles of axons flanked by oligodendroglia; may be difficult to identify neurons; cells are mature; often accompanied by cortical dysplasia; no/rare mitotic figures
Cytology: floating neurons in clusters or intricate patterns or microcystic; also prominent extracellular mucin; compared to oligodendrogliomas, have larger nuclei, frequent nuclear indentation and multiple small nucleoli (vs. round nuclei with only occasional nucleoli in oligodendrogliomas); also have eosinophilic granular bodies in background (Acta Cytol 2003;47:624), may have bipolar astrocytes, mild nuclear atypia, microcystic change; adjacent cortex may show cortical dysplasia with disturbed lamination and architectural disarray; no/rare necrosis, no/rare endothelial proliferation, uncommon mitotic figures
Micro images: (1) variably sized oligodendroglia and neurons with microcyst formation #1; #2; (3) various images #1; #2; #4; figure 1: moderately cellular with uniform glial cells in somewhat linear pattern; 2: linear fascicles of small glial cells tracking along fine capillaries with axonal fibers; 3: occasional freely suspended neurons
Positive stains: glia-GFAP; oligodendroglia-like cells-S100; mucin-Alcian blue; neurons-NeuN, synaptophysin, neurofilament, neuron specific enolase
EM: oligodendroglial-like cells, elongated processes forming a neuropil-like structure and an expanded mucoid extracellular space (Folia Neuropathol 1999;37:167)
DD: oligodendroglioma (not multinodular, no neurons, no mucin, more polymorphic cells, hyperchromasia, perineuronal satellitosis), ganglioneuroma (more pronounced astrocytes, more collagenous stroma, more pleomorphic neurons), glioma (particularly if midline and intraventricular, AJSP 2001;25:494)
Central neurocytoma - CNS Tumor chapter
First described in 1982 (Acta Neuropathol 1982;56:151)
Grows from foramen of Monro or septum pellucidum into lateral or third ventricle; often calcified
Most common neoplasm of septum pellucidum in young adults, but still <1% of all CNS tumors
Often presents with increased intracranial pressure due to obstructive hydrocephalus
Similar tumors within CNS parenchyma are called extraventricular neurocytoma
Rare before age 10 years
Radiologic images: intraventricular tumor
Case reports: Case of the Week #119, 32 year old woman with ventricular tumor, 11 year old girl with headaches, sudden death due to acute hemorrhage (Am J Forensic Med Path 1999;20:180), 19 year old girl with malignant tumor (Pathol Oncol Res 1999;5:155); pigmented tumor due to lipofuscin and neuromelanin (AJSP 1999;23:1136)
Treatment: good prognosis after complete surgical excision or gamma knife radiosurgery (Cancer 2007;110:2276), although up to 1/3 recur or progress (Int J Radiat Oncol Biol Phys 2007;67:1145); recurrence associated with incomplete excision, or the presence of necrosis, mitotic activity / increased proliferation rates or microvascular proliferation (Cancer 2000;89:1111, Clin Neurol Neurosurg 2008;110:129)
Gross: well demarcated from surrounding tissue; gray, friable, may be gritty due to microcalcifications
Gross images: various images; ventricular mass #1; #2
Central neurocytoma - CNS Tumor chapter (continued)
Micro: well developed neuronal features - monotonous bland cells with modest cytoplasm, often empty-appearing “halo” resembling oligodendroglioma, salt and pepper chromatin, embedded in eosinophilic fibrillar matrix with rare Homer Wright rosettes and ganglion cells; usually no infiltrating margin, no/rare necrosis, no endothelial proliferation, no/rare mitotic figures
Cytology: cellular; monotonous round cells with ill-defined cytoplasm, oval nuclei, finely granular chromatin and micronucleoli; background fibrillar matrix; variable histiocytic giant cells with hemosiderin (Acta Cytol 2004;48:194)
Micro images: sheets of non-pleomorphic cells with modest cytoplasm and neuropil #1; #2; #3; #4; #5; #6
case of the week #119 - image #1; #2; #3; #4; #5; #6; #7
Cytology images: monotonous round tumor cells with minimal cytoplasm and fine chromatin, with reactive astrocytes and fibrillar background
Positive stains: synaptophysin, Neu-N (strong, Histopathology 2006;48:438), neuron specific enolase
Negative stains: GFAP (reactive astrocytes are GFAP+), Ki-67 (<2%)
EM: microtubules, 100-200 nm dense core vesicles, clear vesicles, neuritic-type processes; usually no intermediate filaments
DD: glioma (no/few halo cells, no/focal neuronal features, strongly GFAP+), oligodendroglioma (no prominent neuronal features, negative or focal for neuronal markers), clear cell ependymoma (negative for neuronal markers, strongly positive for GFAP, vimentin and EMA)
Also called lipomatous (lipidized) medulloblastoma or lipomedulloblastoma
Rare; first reported in 1978 (Acta Neuropathol (Berl) 1978;41:261)
Grade I to II of IV
Mean age 50 years; almost always in cerebellum
Better prognosis than medulloblastoma; prognosis may be poorer if mitotic figures present and >10% MIB1+ cells (Neuropathology 2005;25:77), although even cases with low mitotic index may progress (J Neurooncol 2005;71:53)
Considered a mixed neuronal-glial tumor; lipid is apparently due to tumoral lipidization, not adipose metaplasia (AJSP 2001;25:1551)
Case reports: 53 year old woman, 48 year old man with midline cerebellar mass, 62 year old woman (Neurol India 2003;51:274-free full text), 6 year old girl with high labeling index (Hum Path 2002;33:564), recurrent tumor with leptomeningeal invasion but no other aggressive histologic features (Neurosurgery 2003;53:1425)
Micro: neuronal and glial differentiation with lipomatous areas; partly resembles medulloblastoma but with low mitotic activity and less atypia; no necrosis, no pleomorphism, no vascular hyperplasia
Micro images: oligodendrocyte- and adipocyte-like cells #1; #2; various images #1; #2; #3
Positive stains: lipid, neuronal markers (Neu-N, synaptophysin, MAP2), GFAP
References: Brain Pathol 2004;14:281 (genetic profiles), Ultrastruct Pathol 2003;27:109 (EM)
Neurocytic tumor within brain parenchyma
Median age 34 years, range 5-76 years
Involves cerebrum
Radiology: circumscribed, solitary, 57% cystic
Poor prognostic factors: incomplete excision, atypical features, high cell proliferation rates; also older patient age
Treatment: total excision prevents recurrence
Case reports: 54 year old woman with atypical neurocytoma with oligodendroglia-like spread (Hum Path 2004;35:1156),
Micro: sheets, clusters, ribbons or rosettes of monotonous tumor cells with round and regular vesicular nuclei and distinct nucleoli embedded in matrix of fine neuropil; ganglion cells in 66%
Atypical if necrosis, vascular proliferation, 3+ mitotic figures/10 HPF
Positive stains: synaptophysin (strong), GFAP (46%; also is staining of entrapped astrocytes at periphery)
EM: neuritic-type processes with microtubules, dense core granules
DD: oligodendroglioma (no ganglion cell differentiation, no salt and pepper chromatin, no neuropil islands; usually more infiltrative, synaptophysin-), ependymoma
References: AJSP 2001;25:1252
Not in WHO classification
Cerebral lesion
Apparently good prognosis
Radiology: contrast-enhancing, cystic
Radiologic images: cystic mass of parieto-occipital lobe
Case reports: 18 year old man with large cystic tumor (Archives 2000;124:1820)
Micro: glial and neural components, focally pseudopapillary; no necrosis, no mitotic figures, no vascular proliferation
Micro images: pseudopapillary pattern, GFAP+, synaptophysin+
Positive stains: GFAP, synaptophysin; low MIB1 index
Negative stains: p53
DD: neurocytoma, pilocytic astrocytoma (Rosenthal fibers, eosinophilic granular bodies), gangliogliomas (atypical ganglion cells, gliomatous component, granular bodies, perivascular lymphoid infiltrate, associated with epilepsy and cortical dysplasia)
Grade I (benign), although rarely metastasizes (J Neurosurg 1991;75:320)
Spinal canal (filum terminale); also temporal bone and posterior fossa
Radiologic images: cauda equina tumor
Treatment: surgery
Micro: nests of neuroendocrine cells (Zellballen) with granular cytoplasm and central bland nucleus; nests are separated by fibrovascular stroma with thin walled vessels; may have focal ganglionic differentiation; no vacuoles
Micro images: tumor of filum terminale
Positive stains: neuroendocrine cells - chromogranin, synaptophysin, cytokeratin; sustentacular cells - S100, GFAP (often, Brain Pathol 2005;15:169)
EM: neurosecretory granules
DD: angiomatous meningioma, myxopapillary ependymoma, hemangioblastoma (mixture of capillary and stromal cells with vacuoles), metastatic renal cell carcinoma
References: Histopathology 1997;31:167, Acta Neurochir (Wien) 1999;141:81, Cancer 1986;58:1720
Nonglial tumors
Embryonal tumors
Rare tumor of young children
Micro: highly cellular, numerous multilayer rosettes composed of medium sized, poorly differentiated cells around small cavity; apical surface of internal cell layer forms thickened limiting membrane; cells have round/oval nuclei; high mitotic activity
Micro images: ependymoblastoma
Positive stains: vimentin, S100, rare GFAP
Negative stains: keratin, neurofilament
EM: poorly differentiated cells with scanty cytoplasmic organelles, cells united by junctional complexes, frequent rudimentary or incomplete cilia, few basal bodies and few short intercellular glial-like filaments
References: Histopathology 1988;12:17, Cancer 1985;55:1536
Major subtype of central primitive neuroectodermal tumor/PNET
Grade IV of IV
Usually cerebellum or roof of fourth ventricle
Children (5-10 years) and adults in 20’s; rarely age 35 or older
20% of brain tumors in children (#2 after pilocytic astrocytoma of cerebellum)
May grow rapidly and cause hydrocephalus, invade subarachnoid space and fourth ventricle early
5% metastasize systemically, commonly to bone
5 year survival is 75% with surgery/radiation
May arise from primitive cells of external granular layer of cerebellum
Large cell variant: also called anaplastic; more aggressive (AJSP 1992;16:687)
Treatment: resection; must also treat entire neuraxis since spreads along CSF pathways (drop metastases to cauda equina are common); tumors are very radiosensitive
Case reports: cartilaginous differentiation (Archives 1989;113:84)
Gross: well circumscribed, gray-pink, soft/friable; involves surface of cerebellar folia and infiltrates leptomeninges
Gross images: cerebellar tumor extending into fourth ventricle
Micro: small round blue cell tumor composed of sheets of undifferentiated cells with minimal cytoplasm, hyperchromatic and anaplastic nuclei, often elongated and carrot-shaped; frequent mitotic figures; similar to pineoblastoma; careful examination reveals fibrillar nature of tumor cells; occasional Homer-Wright rosettes
Micro images: sheets of primitive small blue cells #1; #2; large cell variant #1 with neuronal differentiation; #2; arising on surface of cerebellum; various images
Cytology images: oval blue tumor cells with minimal cytoplasm and indistinct nuclei in fibrillar background with mitotic figure; bone marrow
Positive stains: NSE, synaptophysin, focal GFAP
Molecular: isochromosome (17q) or 17p-; 5-30% overexpress c-myc or N-myc; c-myc overexpression is associated with poor prognosis (Archives 2002;126:540)
Molecular images: i(17)(q10)
EM: neural features
DD: small cell carcinoma, lymphoma (diffusely infiltrates CNS until it mixes with normal and reactive fibrillar cells), peripheral PNET
References: infobiogen-cytogenetics, eMedicine, Mod Path 1990;3:164 (stains)
Desmoplastic medulloblastoma
Grade IV of IV
May be in lateral cerebellum, not midline
More common in young adults than children (mean age 18 years vs. 6.5 years for classic medulloblastoma in one study, Archives 1989;113:1019)
Associated with nevoid basal cell carcinoma syndrome (Cancer 2003;98:618)
Fibrous reaction may be from leptomeningeal cells in arachnoid space
May have better prognosis than classic medulloblastoma
Case reports: 28 year old man with melanotic tumor (Brain Tumor Pathol 2002;19:93)
Gross: firm consistency
Micro: pale areas lack reticulin compared to reticulin-rich areas of high cellularity
Micro images: clear islands of classic medulloblastoma and dark collagen-rich areas with small tumor cells - #1; #2; reticulin stain
DD: small cell carcinoma
Supratentorial primitive neuroectodermal tumor
Rare tumor in intracranial cavity, usually cerebral hemisphere
Appears to be a different clinical entity than medulloblastoma (central PNET, cPNET) due to different location (cerebral hemisphere vs. cerebellum), different frequency (10% of frequency of cPNET), survival rate (worse than cPNET), different molecular genetics (14q-, 19q- and 3q- vs. i(17q) in cPNET; different hypermethylation profiles, Hum Path 2005;36:1265)
Usually children and young adults
Treatment: wide excision, adjuvant chemotherapy and radiotherapy
Case reports: tumor cell differentiation due to valproic acid treatment for seizures (Pediatr Hematol Oncol 2004;21:743), 51 year old woman with occipital lobe tumor showing extensive mature adipose tissue (Archives 2001;125:264)
Gross: deep seated tumor with cystic component
Micro: small blue cell tumor with round, hyperchromatic cells, abundant mitotic figures and fibrosis
Micro images: tumor with adipose tissue; figure 3: round, hyperchromatic cells, abundant mitotic figures (arrows) and fibrosis; 4: CD99+
Positive stains: CD99 (strong membrane staining), focal GFAP
Negative stains: CAM5.2, S100, CD45, synaptophysin (usually)
Molecular: t(11;22)(q24;q12); i(17q) is very rare
EM: neuronal or glial differentiation
DD: central PNET/medulloblastoma (no t(11;22), CD99-, synaptophysin+), small cell meningioma, anaplastic glioma, melanoma, lymphoma, rhabdomyosarcoma, atypical teratoid/rhabdoid tumor
References: eMedicine, J Neurooncol 2002;60:43, Hum Path 2005;36:36 (DLC1 expression)
Atypical teratoid / rhabdoid tumor
Not in WHO classification
Rare; first described in 1987
Infants and young children (mean age 17 months)
Usually posterior fossa or supratentorial
Very aggressive with poor prognosis (mean survival 11 months post-surgery); metastasizes throughout CSF
Radiologic images: various images
Case reports: two infantile cases (Am J Neuroradiol 2004;25:481-free full text), thalamic tumor (Neurol India 2003;51:273-free full text), with ring chromosome 22, 19 year old man with intradural mass at C6-7 (Archives 1999;123:853), with inherited INI1 mutation (Pediatr Blood Cancer 2005 Oct 31 (epub)), monozygotic twins with congenital disseminated malignant rhabdoid tumor in one and a cerebellar tumor resembling medulloblastoma in the other (AJSP 2002;26:266), 12 year old girl with cerebellar tumor with a few rhabdoid cells but different molecular features (Acta Neuropathol (Berl) 2005;110:69)
Micro: large and pleomorphic rhabdoid cells with abundant eosinophilic cytoplasm (pinker than PNET), often filamentous cytoplasmic inclusions and vacuoles; eccentric round nuclei and prominent nucleolus; may have PNET-like areas with small cells; may have mucinous background resembling chordoma; may have epithelioid features with poorly formed glands or Flexner-Wintersteiner rosettes
Cytology: hypercellular; large tissue fragments with papillary appearance of large tumor cells surrounding capillaries; cells are large, round and plasmacytoid or rhabdoid (intermediate size with granular to fibrillary, brightly eosinophilic cytoplasm and variable inclusions; large, eccentric nuclei with single prominent nucleolus); also small, round, primitive, neural type cells with high N/C ratio; also apoptotic bodies, mitotic figures, marked necrosis; variable dystrophic calcification, bizarre, multinucleated giant cells (Cancer 2005;105:65)
Micro images: (1) tumor cells; (2) A: H&E; B: GFAP; C: keratin; D: smooth muscle actin; (3) epithelioid areas, rhabdoid cells and necrosis; (4) various images #1; #6; (10) spinal tumor - figure 1: MRI; 2: tumor infiltrates peripheral nerve roots; 3: rhabdoid tumor cells; 4: EM shows paranuclear whorled arrays of closely packed intermediate filaments
Positive stains: vimentin, EMA, smooth muscle actin; focal GFAP, cytokeratin, neurofilament; variable synaptophysin and chromogranin
Negative stains: INI1 with positive nuclear staining of blood vessels and lymphocytes as positive control (AJSP 2004;28:644, Mod Path 2005;18:951)
Molecular: 22q11.2 deletions involving hSNF5/IN1 gene (similar to choroid plexus tumors, Hum Path 2001;32:156-using FISH, Brain Pathol 2003;13:409)
EM: globular/fibrillar paranuclear inclusions (whorled intermediate filaments)
DD: PNET/medulloblastoma (no rhabdoid cells, no 22q11 deletions, IN1+, Acta Neurochir (Wien) 2003;145:663), composite rhabdoid tumors (with other component, usually INI1+); also ependymoma, choroid plexus carcinoma, occasional germ cell tumors
References: AJSP 1998;22:1083, Brain Pathol 2005;15:23, Atlas of Genetics (all rhabdoid tumors), OMIM 609322
Not in WHO classification; considered a distinct variant of medulloblastoma
Grade IV of IV
Rare midline posterior fossa tumor of children, usually female
Aggressive; survival usually 1 year or less
Treatment: radical surgery and craniospinal radiation
Micro: contains smooth or striated muscle cells and small medulloblastoma-like cells
Micro images: cross striations; medulloblastoma with striated muscle cells
Positive stains (muscle markers): PTAH, desmin, muscle-specific actin; synaptophysin stains neuroectodermal cells
Molecular: alterations in #17 or c-myc amplification
EM: sarcomeres and myofibrils; myoid cells resemble fetal rhabdomyoma (Neurol India 1999;47:178-free full text, Cancer 1984;54:323)
References: Cancer 2004;101:1445
Not in WHO classification
Grade IV of IV
Rare; children age 6 years and less; often in eye
Median survival of 5 months
Case reports: 2 year old girl with lesions in 4th ventricle and left cerebellar hemisphere (Case of Week #218), 3 year old boy with cerebral tumor (Neurol India 2003;51:546-free full text), 3 month old boy with long survival (Clin Neuropathol 2002;21:197)
Micro: tubular and papillary epithelial growth pattern; cells have dense and pink material on apical surface; foci of neuroblastic differentiation present; resembles embryonic neural tube
Micro images: epithelial architecture recapitulates early neuroectoderm #1; #2; highly cellular with tubules and papillae lined by columnar cells
DD: metastatic carcinoma, choroid plexus carcinoma
References: J Neurosurg 1996;84:430
Choroid plexus tumors
Uncommon (0.4 to 0.6% of intracranial neoplasms)
Usually children
Occurs in any portion of choroid plexus, but usually as papillary neoplasms of lateral ventricle of children and fourth ventricle of adults
In preliminary study, Kir7.1 and stanniocalcin-1 may be sensitive/specific choroid plexus tumor markers (AJSP 2006;30:66)
Grade I of IV - benign
Rare (<1% of intracranial neoplasms), slow growing tumor commonly in ventricular system and associated with hydrocephalus due to excess production of CSF or direct tumor obstruction of CSF flow
Often causes developmental delay, behavioral problems or epilepsy in children
85% occur at age 10 years or less; often present at birth
Needle biopsy not recommended since histologically resembles normal choroid plexus
10-30% become histologically malignant
High survival unless becomes malignant (then 5 year survival is 26%), although histology does not predict behavior
Radiologic images: various images
Treatment: surgical excision, possibly radiation therapy if incomplete excision
Case reports: case with rhinorrhea as only symptom, 49 year old woman with oncocytic tumor (Archives 2004;128:1448)
Gross: larger than normal choroid plexus; lobulated encapsulated mass
Gross images: fourth ventricle tumor; lobulated vascular mass
Micro: resembles normal choroid plexus with single layer of epithelial cells overlying a fibrovascular core; epithelial cells are more crowded and piled up than normal; mild atypia; may be pigmented, oncocytic, osteogenic, adenomatous, acinar, mucus secreting, tubular; may have vascular stalk that provides mobility within ventricular system
Micro images: (1) papillary architecture at low power; (2) cuboidal / columnar cells overlying fibrovascular core #1; #3; (5) various images #1-pigmented tumor; #3; (8) anaplastic choroid plexus papilloma; (9) oncocytic tumor; (10) cuboidal/columnar cells overlying fibrovascular core; (11) glandular differentiation; (12) CK7+; (13f) atypical features
Cytology images: papillary fronds of choroid plexus tumor with focal calcification
Positive stains: CAM 5.2 (94%), transthyretin (89%), vimentin, S100 (54%); mucin stains, CK7 (usually); focal GFAP (up to 70%), EMA (11-71%); occasionally synaptophysin; fibrovascular core is positive for type IV collagen, reticulin and laminin
Negative stains: p53 (usually), CK20 (usually), BerEP4
DD: papillary ependymoma (more than one layer of cells), metastatic thyroid, breast, kidney or ovarian carcinoma (necrosis and anaplasia present), myxopapillary ependymoma (different location), papillary meningioma (solid and syncytial foci of whorled cells, no mucin)
References: eMedicine, Mod Path 2000;13:638 (CK7/CK20)
WHO grade III of IV
Extremely rare
Resembles metastatic carcinoma but usually occurs in children
Associated with germline p53 mutations (Eur J Cancer 2005;41:1597)
Case reports: ventriculoperitoneal shunt related metastases (Neurosurgery 2005;56:E412)
Gross: well circumscribed, brown-red, cauliflower-like mass; variable hemorrhage, necrosis and invasiveness
Gross images: lateral ventricle tumor
Micro: sheets of anaplastic tumor cells with necrosis, frequent mitotic figures; focal papillary areas resemble papilloma but with more crowded and elongated cells
Micro images: markedly pleomorphic cells with loss of papillary pattern; various images #1; #2
Positive stains: EMA, keratin, S100, INI1; GFAP (20%)
DD: atypical rhabdoid tumor (INI1 negative, J Neuropathol Exp Neurol 2005;64:391),
Pineal tumors
Also called epiphysis, pineal body
Between superior colliculi at base of brain; 100-180 mg
Develops at month 2 of gestation as diverticulum in diencephalic roof of third ventricle
Replaced by connective tissue after puberty
Produces melatonin, which helps regulate circadian rhythms
Drawings: location in brain #1; #2 (at “p”)
Gross: shaped like a pine cone, midline, attached to posterior end of roof of third ventricle in front of cerebellum, 1 cm long, red-gray
Gross images: local anatomy (horse)
Micro: loose neuroglial stroma with nests of pineocytes containing well-defined neurosecretory (melatonin) granules; also astrocytes; has features of photoreceptors and concretions (“brain sand”)
Micro images: sagittal section #1; #2; #3; #4; concretions; pinealocytes
Positive stains: synaptophysin, retinal S-antigen
Up to 1% of adult tumors and 3-8% of childhood intracranial tumors
Most tumors are germinomas (resemble seminoma, radiation sensitive); also other germ cell tumors
Frozen sections are challenging
Tumors include those listed below; also astrocytoma, meningioma, metastases, cysts
Tumors often compress aqueduct of sylvius, causing hydrocephalus and requiring ventriculoperitoneal shunting
References: eMedicine
Papillary tumor of pineal region
First described in 2003 (AJSP 2003;27:505)
4 of 6 were women, ages 19-53 years
May derive from ependymal cells of subcommissural organ (also chordoid glioma)
Radiology: well circumscribed pineal mass
Micro: epithelial-like growth with vessels covered by a layer of tumor cells; cells are large, columnar/cuboidal with clear cytoplasm, round or infolded nuclei at basal pole of tumor cells; may have rosettes
Positive stains: cytokeratin, S100, NSE, vimentin
Negative stains: EMA, GFAP (may be weak)
EM: abundant rough endoplasmic reticulum with distended cisternae filled with secretory product; also microvilli and perinuclear intermediate filaments
DD: pineal parenchymal tumor (synaptophysin+, keratin-, vimentin-)
Grade IV of IV
Second most common pineal gland tumor after germ cell tumor
Usually age 20 years or less
Frequent CNS metastases or spinal seeding, which is the main cause of death
5 year survival is 58%
Poor prognostic factors: 7+ mitotic figures/10 HPF, presence of necrosis, no neurofilament staining
Case reports: 15 year old girl with midline intracranial mass (Archives 2004;128:707), cases with vertebral metastases (Archives 2001;125:939), osseous metastases (J Neurooncol 2005;74:53)
Treatment: surgery, variable radiation therapy; prognosis is usually poor
Gross: located in pineal gland, may appear well demarcated from surrounding brain tissue but usually infiltrates into surrounding structures
Micro: sheets of densely packed cells with high grade (anaplastic / undifferentiated) features including high N/C ratio with minimal cytoplasm and large hyperchromatic nuclei; also necrosis, frequent mitotic figures; focal nuclear molding; Homer-Wright or Flexner-Wintersteiner rosettes; may have lower grade features of pineocytoma and pineal parenchymal tumor of intermediate differentiation; often infiltrates into surrounding structures
Micro images: (1) highly cellular tumor composed of small, round and poorly differentiated cells #1; #2 with Homer-Wright rosettes; (3) various images #1; #2; #3; (6) figure 1: MRI shows tumor at midline of posterior brain; 2: touch imprint is highly cellular with primitive cells and a few Homer-Wright rosettes (arrow); 3: paraffin section shows highly cellular tumor with perivascular arrangements and Homer-Wright rosettes and frequent mitotic figures (arrows); 4: synaptophysin+
Positive stains: NSE, synaptophysin, retinal S-antigen
Negative stains: GFAP, myoglobin, HHF35
EM: occasional cytoplasmic dense core granules, short immature cell processes, occasional junctional complexes; no definite synapses
DD: medulloblastoma, pineocytoma (better differentiated cells with more cytoplasm, smaller cells, no/rare mitotic figures), glial neoplasms (GFAP+)
Grade I of IV
Mostly adults age 25-35 years, slow growing, average survival 7 years
Gross: well-circumscribed, gray, hemorrhagic
Micro: similar to normal pineal gland’s well differentiated cells but hypercellular; fibrovascular stroma highlights expansive lobules of tumor cells with uniform round nuclei; pinocytomatous rosettes (large, loose, Homer-Wright like rosettes with central fibrillar zones surrounded by neoplastic cells with round nuclei); may have features of neuronal differentiation (ganglion cells); non-infiltrative, no/rare mitotic figures, no necrosis, no/minimal atypia
Micro images: small cells and pineocytomatous rosettes; larger cells resembling pineocytes; various images #1; #2
DD: pineoblastoma (Cancer 1980;45:1408)
Pineal parenchymal tumor of intermediate differentiation
Features intermediate between pineocytoma and pineoblastoma
10% of pineal parenchymal tumors
Occasionally associated with CNS or extraneural metastasis, but otherwise difficult to predict prognosis
Better survival than pineoblastoma
Micro: marked hypercellularity, but relatively bland nuclear features, no/mild nuclear pleomorphism, no/rare pinocytomatous rosettes, minimal mitotic activity
Molecular: often +4q, +12q, -22 (Genes Chromosomes Cancer 2001;30:99)
References: Brain Pathol 2000;10:49
Meningeal tumors
Common (20% of brain tumors, 6 per 100K annually)
Derive from arachnoid cap cells (associated with dura mater, choroid plexus)
Grow along external surface of brain or within ventricular system
Difficult to diagnose correctly within choroid plexus, if intraparenchymal, at cerebropontine angle or along spinal cord, due to resemblance to more common tumors at these locations
Slow growing (may grow rapidly during pregnancy), symptoms vague or related to brain compression
Usually adults, 2/3 in brain occur in women, 90% in spinal cord occur in women
Usually solitary; multiple tumors (seen in 1-6%) are occasionally associated with neurofibromatosis 2
Usually benign; not considered malignant even if invades bone and skeletal muscle
May metastasize to lung or mediastinum
Metastases within a meningioma may be from breast cancer or CLL
Difficult to predict recurrence - incomplete resection and grade of tumor are most predictive
Treatment: can merely observe if asymptomatic; resection is usually curative; may recur if incompletely excised
Case reports: Case of the Week #104-meningioma, Case of the Week #259-microcystic meningioma, microcystic meningioma #2 (Arch Pathol Lab Med 2005;129:e173), intraosseous occipital meningioma (Arch Pathol Lab Med 2001;125:301, with leukemic infiltrate (AJSP 2001;25:127)
Gross: rounded, encapsulated and well circumscribed, firm with tiny nodules, well defined dural base, tumor separates readily from brain; may grow en plaque (along dural surface) and cause reactive (hyperostotic) bone changes
Gross images: tumor displaces brain without invading it #1; #2; compression of underlying cortex #1; #2; resected tumor; tumor being resected; adherent to falx cerebri
Micro: distinct margin with CNS parenchyma; whorled clusters of spindle cells, which may secrete collagen, die, calcify and form psammoma bodies (varies by tumor); intranuclear pseudoinclusions common; xanthomatous degeneration, moderate nuclear pleomorphism and metaplasia are common but have no prognostic significance; no necrosis or extensive hemorrhage
Grade I variants:
Angiomatous: grade I of IV; 2% of all meningiomas; vascular component should exceed 50% of total tumor area; may resemble hemangioblastoma or become sclerotic; meningothelial cells are wrapped around small blood vessels; also has large vessels; if entirely hemangioblastic, differentiate from hemangioblastoma by dural attachment and location; no atypia or anaplasia; mean Ki-67 index is 2%; do not recur if entirely resected
Fibroblastic: grade I of IV; firm tumors composed of spindle cells with indistinct cell boundaries; resemble schwannomas, fibrillary astrocytomas and pilocytic astrocytomas but are focally EMA+, often have thick bundles of collagen
Lipomatous: due to lipid accumulation, not lipomatous metaplasia (AJSP 2001;25:769)
Meningothelial: grade I of IV; most common variant; syncytial and epithelial cells, indistinct cell borders and classic whorls; may have sparse psammoma bodies; may appear epithelioid and resemble ependymoma, oligodendroglioma (EMA-, infiltrating margin); EM may be required for diagnosis
Microcystic: grade I of IV; rare to have extensive microcystic formation; cells have elongated processes and loose myxoid background; overall resembles microcysts; has focal “classic” features; variable pleomorphism; no cords or trabeculae; no inflammatory infiltrate; EM shows extracellular microcysts; resembles chordoid meningioma (grade II)
Psammomatous: grade I of IV; found in spinal region; numerous psammoma bodies; also syncytial cells
Transitional: grade I of IV; meningothelial and fibroblastic features; usually prominent whorls, psammoma bodies and clusters of syncytial cells
Other grade I variants: arachnoid trabecular, cartilaginous, lipomatous, lymphoplasmacytic-rich, microcystic, osteogenic, secretory (see below); still have meningothelial features, occasional whorls, finely granular chromatin; meningothelial cells flatten around or encircle vessels; no/rare mitotic figures; EM may be needed to diagnose
Cytology: small to medium sized cells with moderate well defined cytoplasm and short processes; some nuclei have grooves; cells form focal whorls; variable psammoma bodies
Micro images:
angiomatous (trichrome stains) - #1; #2 with microcystic features
fibroblastic variant - #1; #2; #3
lymphoplasmacytic rich variant - #1; #2; #3-CD45/LCA+
meningothelial variant - #1; #2; #3; #4 (A-C); occipital tumor; with focal hemosiderin deposition
microcystic variant - #1-lacelike pattern of fibrillary stellate cells with round/oval microcysts; #2 with pleomorphic cells; #3 with pseudo-astrocytic appearance; #4 with strong progresterone receptor+, EMA+
psammomatous - #1
xanthomatous - #1; #2; #3; #4 with cholesterol clefts; #5 with pleomorphic cells
Cytology images: meningothelial tumor #1; #2; whorl; whorl and psammoma body; scattered tumor cells with delicate and wispy cytoplasm
mass at base of skull with inclusions and grooves - image #1; #2; #3; #4
Virtual slides: meningothelial meningioma
Positive stains: vimentin (strong), EMA (70%); S100, ProgR (30%, usually women, tumor may grow during pregnancy), cytokeratin, CEA, PAS+/diastase resistant, IgA, IgM (secretory meningiomas), focal actin in 20% (Archives 1996;120:267)
Negative stains: GFAP, OCT4 (germ cell tumor marker)
Molecular: 22- may indicate aggressive behavior; seen in 50% of meningiomas that are not associated with neurofibromatosis type 2
Molecular images: 22q-; idiotype of deletion
EM: tightly interdigitating cellular processes held together by desmosomes
DD: fibrosis (collagen and reticulin positive), infectious granuloma (organisms and inflammation present)
References: eMedicine, AJSP 2004;28:390 (angiomatous), AJSP 1997;21:375 (oncocytic)
Grade I - syncytial (meningothelial), fibroblastic (with collagen), microcystic, transitional, psammomatous, angiomatous (includes hemangioblastic, angioblastic), secretory subtypes
Grade II - atypical, clear cell and chordoid subtypes
Grade III - rhabdoid and papillary subtypes, anaplastic/malignant
Grave IV - no meningiomas have this grade
Grade III; also called malignant meningioma
1% of meningiomas
Either denovo, associated with recurrent tumors or associated with prior radiation (J Neurooncol 2005;74:195, Med Pediatr Oncol 1995;24:265)
Associated with aberrant CpG island hypermethylation profile (Hum Path 2005;36:416)
Treatment: resection
Case reports: 61 year old woman with coexisting fibrous and anaplastic meningiomas (J Clin Neurosci 2003;10:622)
Gross: firm, white
Micro: circumscribed and lobulated; exhibit frank histologic features of malignancy far in excess of the abnormalities present in atypical meningiomas; either 20 or more mitotic figures/10 HPF or anaplastic cytology (increased cellularity, hyperchromatic, high N/C ratio, necrosis); invasive front is discrete or proceeds along vessels trapping gliotic areas
Note: invasion alone is insufficient for diagnosis
Micro images: anaplastic foci; pseudopapillary tumor with necrosis and mitotic figures; H&E and cytokeratin
Positive stains: vimentin (100%), Ki-67/MIB1 (high), strong EMA (89%, although often decreases if a recurrence), cytokeratin (75%), strong claudin1 (54%), weak/focal CD99 (15%), weak/focal bcl2 (31%)
Negative stains: BerEP4, CEA, B72.3, CD15
Molecular: 1p- (94%), 14q- (67%), NF2- (100%)
EM: membrane basal-like substance, no desmosomes (Ann Pathol 2000;20:492)
DD: anaplastic glioma, glioblastoma (more invasive margin than meningioma, forms secondary structures of Scherer), hemangiopericytoma (EMA-, CD99+, bcl2+, usually none of above deletions, Hum Path 2004;35:1413), metastatic carcinoma (usually positive for BerEP4, CEA, B72.3, CD15, negative for vimentin, Mod Path 2004;17:1129)
References: Ann Diagn Pathol 2003;7:214 (immunophenotypic changes in recurrences)
Grade II
5-15% of meningiomas
Either: (a) 4-19 mitotic figures/10 HPF or (b) three of these histologic features: increased cellularity, small cells with high N/C ratio, large and prominent nucleoli, patternless or sheetlike growth, foci of “spontaneous” or geographic necrosis
Note: invasion of dura, bone or soft tissue is not a feature; neither is pleomorphic or atypical nuclei not associated with mitotic activity or necrosis
May be associated with prior irradiation (J Neurosurg 2004;100(5 Suppl Pediatrics):488)
29% recur (vs. 9% of classic meningiomas and 50% of anaplastic meningiomas)
10 year survival is 79%, but 26% will assume a malignant phenotype
In one study, cyclin A and topoisomerase II staining predicted recurrence (Archives 2002;126:1079)
Treatment: gross total resection
Case reports: with lung metastases (J Clin Neurosci 2000;7:69)
Micro images: A: whorls in classic meningioma; B: mitotic figures in atypical variant; various images
DD: meningioma with atypical features (atypical features insufficient for criteria above); necrosis due to preoperative embolization (which is not considered spontaneous)
References: Cancer 2002;94:1538
Grade II due to tendency to recur
<1% of all meningiomas
Usually adults (mean age 47 years) with no systemic symptoms, although initial reports were primarily children/young adults with microcytic anemia or dysgammaglobulinemia
Cases with Ki-67 index > 5-10% are more likely to recur
Treatment: complete excision; overall 40% may recur, often when incompletely excised
Case reports: 39 year old woman (Case of Week #242), 50 year old woman with progressive headaches (Arch Pathol Lab Med 2004;128:e115), with fever and IL6 production (J Neurosurg;103:555), with IL6 production and Castleman’s disease (J Neurosurg 2005;102:733), tumor at skull base (Australas Radiol 2004 Jun;48:233)
Gross: large, supratentorial
Micro: resembles chordoma with trabeculae / cords of epithelioid and spindle cells with cytoplasmic vacuoles between myxoid collagen, but has meningothelial features and whorls and is cytokeratin negative; often heavy lymphocytic infiltrate with germinal centers
Cytology: cords of polygonal tumor cells with bland nuclei and nuclear pseudoinclusions; occasional loose cells with abundant, metachromatic, pink-purple cells without cytoplasmic vacuoles; also lymphoplasmacytic infiltrate (Acta Cytol 2004;48:259, Acta Cytol 2004;48:397)
Micro images: cells with clear cytoplasm in myxoid stroma; various images #1; #2; EMA+; figure 1: abnormal trabeculae of vacuolated eosinophilic cells in myxoid matrix; 2: small areas of whorled epithelial cells; stroma is Alcian blue+
Cytology images: vacuolated cells
Positive stains: vimentin, EMA
Negative stains: GFAP, keratin, CEA, S100
EM: abundant rough endoplasmic reticulum, intercellular desmosomes, intermediate filaments, complex interdigitating cell processes
DD: chordoma, metastatic carcinoma, myxoid chondrosarcoma, metastatic myxoid meningioma, chordoid glioma
References: AJSP 2000;24:899, AJSP 2003;27:131
Grade II due to aggressiveness
More common in lumbar and cerebellopontine areas and in younger patients (mean age 29 years)
More aggressive in skull than spinal cord
Case reports: fourth ventricle tumors (AJSP 2003;27:131), 41 year old woman with L3-L4 intradural lesion (J Spinal Disord Tech 2005;18:539),
Treatment: resection, variable radiation therapy; often recurs
Micro: sheets of polygonal cells with clear cytoplasm; also cells with meningothelial features (vague whorls); often extensive stromal and perivascular hyalinization; no/rare mitotic figures
Cytology: whorled, syncytial architecture composed of spindle to polygonal cells with vacuolated cytoplasm and bland nuclei (Diagn Cytopathol 1998;18:131)
Micro images: extensive vacuoles and fibrous walled vessels; sheets of clear cells with bland nuclear features #1; #2; H&E and EMA+; H&E and stains; vimentin+ cells
Positive stains: PAS+ diastase sensitive (glycogen), vimentin, EMA, progesterone receptor (77%)
Negative stains: S100, CAM 5.2, estrogen receptor, chromogranin A, rare MIB/Ki-67
EM: abundant cytoplasmic glycogen, intermediate filaments, interdigitation of cell membranes, desmosomes, occasional cytoplasmic lumina (Ultrastruct Pathol 1999;23:51)
DD: metastatic renal cell carcinoma (J Clin Neurosci 2005;12:685), oligodendroglioma, hemangioblastoma, seminoma, lipid-rich glioblastoma, ependymoma
References: AJSP 1995;19:493
Invasion of adjacent cerebral parenchyma or vascular invasion (within tumor); surgical specimen must contain infiltrative interface with the brain to make the diagnosis
Associated with higher risk of recurrence, but does not change the tumor grade
Brain invasion is considered worse than dural invasion (common in low-grade and high-grade meningioma)
SPARC may be associated with invasiveness (Clin Cancer Res 1999;5:237)
Micro images: SPARC in invasive and noninvasive tumors #1; #2; #3
Grade III due to high rates of local recurrence, metastases and invasion
Rare; tends to occur in children
Difficult to recognize if not associated with dura
Case reports: recurrent cerebellar tumor (AJSP 1999;23:844), associated with prior chemotherapy for ALL (Childs Nerv Syst 2005 Jun 14; [Epub]), tumor of jugular foramen (Brain Tumor Pathol 2004;21:143), 15 year old girl with cystic tumor (Childs Nerv Syst 2005;21:322), rhabdoid and papillary tumor (AJSP 2001;25:964), pleural metastases (Acta Neurol Scand 2000;102:200), spinal tumor (Acta Neurochir (Wien). 2000;142:703)
Micro: papillae composed of syncytial cells making rosettes around vessels; may form by edematous or necrotic loosening of tumor cells surrounding vascular core; usually has areas of classic meningioma and mitotic figures; papillary areas may be focal
Micro images: papillary architecture #1 with fibrovascular core
Positive stains: vimentin, NSE
Negative stains: GFAP, CAM 5.2, EMA (often), S100, synaptophysin
EM: meningioma features; interdigitating cell processes, desmosomes and intermediate filaments (Histopathology 2001;38:318)
DD: papillary ependymoma, choroid plexus papilloma, carcinoma
Grade III due to marked aggressiveness
Rhabdoid component is often only apparent in recurrences
Case reports: recurrent tumor #1, #2 (Skull Base 2003;13:51, free full text) rhabdoid papillary tumor (AJSP 2001;25:964), without mitotic activity or atypia (Clin Neuropathol 2004;23:16)
Micro: barely cohesive cells with abundant eosinophilic cytoplasm, paranuclear inclusions, eccentric nuclei; also meningothelial features, high mitotic activity
Cytology: abundant large cells with dense eosinophilic cytoplasm, eccentric nuclei, single prominent nucleoli (resembles melanoma or metastatic carcinoma (Diagn Cytopathol 2003;29:297, Diagn Cytopathol 2003;29:292)
Micro images: tumor cells have eosinophilic glossy cytoplasm and eccentric, mildly atypical nuclei; various images
Positive stains: vimentin, EMA, INI1 (Mod Path 2005;18:951), increased Ki-67 index
EM: hyaline perinuclear inclusions contain whorls of intermediate filaments that push nucleus to side
DD: gemistocytic glioma, epithelioid glioma (different location and pattern of brain invasion, negative for vimentin and EMA, different ultrastructure)
References: AJSP 1998;22:1482, AJSP 1998;22:231
Grade I
May have increased serum CEA
1-9% of all meningiomas; 90% female
Case reports: 46 year old woman (Archives 2000;124:787), 54 year old woman with headache and vomiting, containing lung tumor metastasis (Br J Neurosurg 2002;16:66), with lipomatous component (Brain Tumor Pathol 1999;16:77, Neuroradiology 1998;40:656)
Micro: acini-like structures with PAS+ diastase resistant hyaline inclusions (also called pseudopsammoma bodies) within microvillus lined intracellular lumina; meningothelial cells without atypia; often associated with mast cells and peritumoral edema (Neurosurg Rev 2006;29:41)
Cytology: hypercellular cohesive clusters of uniformly dense cells with eosinophilic cytoplasm, smooth nuclear outlines and even chromatin; also cells with syncytial arrangements, whorls and nuclear pseudoinclusions (Acta Cytol 1999;43:121)
Micro images: cells with lumina containing PAS+ inclusions #1; #2; #3; trichrome; Alcian blue; cytokeratin; H&E and PAS; various images #1; #2
Cytology images: various images #1; #2; #3 (figures 2-4)
Positive stains: CAM 5.2, CEA, CK7, EMA, progesterone receptor, IgA, IgM, CA 19-9
Negative stains: CK20
EM: hyaline inclusions are intracellular and within intercellular lumina lined by microvilli; inclusions contain granular material forming a dense core; microvesicles, dense bodies and lamellar structures
DD: microcystic, clear cell or chordoid meningioma, metastatic carcinoma (usually CK7-, CK20+, Adv Clin Path 1999;3:47)
References: J Clin Neurosci 2001;8:335, Cancer 1997;79:2003, AJSP 1986;10:102
Rare, benign, hamartomatous lesion of children and young adults characterized by leptomeningeal and meningovascular proliferation
Presents with seizures and headaches
Mean age 21-28 years, range 1-70 years
25% associated with neurofibromatosis II
Case reports: 7 year old girl with seizures, 30 year old man with coexisting meningioma, 11 year old boy with seizures (Archives 2003;127:e349), with oligodendroglioma (Archives 1996;120:587), 16 year old boy without stigmata of neurofibromatosis (AJSP 2002;26:125), associated with meningioma (AJSP 1999;23:872), associated with sudden death in otherwise healthy 13 year old boy (Pediatr Dev Pathol 2005;8:240), 16 year old boy without neurofibromatosis but with microsatellite instability of 2 markers flanking the NF2 gene (AJSP 2002;26:125)
Treatment: surgical excision cures most seizures
Gross: thick and opaque leptomeninges with abnormal vessels, but no evidence of neoplasia
Micro: prominent perivascular meningothelial cell proliferation with collagen deposition involving the cortex and sometimes the underlying white matter; also increased cortical vascularity; often leptomeningeal calcification; variable psammoma bodies and osteoid; also variable neurofibrillary tangles; no/rare mitotic activity, no necrosis, no marked pleomorphism
Cytology: numerous thin walled capillaries, bland spindle cells, occasional large cells with prominent nucleoli, variable meningothelial whorls and neurons (Acta Cytol 2001;45:1069)
Micro images: (1) prominent psammoma bodies; (2) figure 2: perivascular meningothelial cells and proliferation of blood vessels; 3: psammoma bodies; (3) degenerative changes; (4) various images #1; #2; #3
Positive stains: vimentin, EMA, focal S100 in 20%, variable CD34
Negative stains: S100
DD: invasive meningioma (infiltrative growth into brain parenchyma with destruction, no prominent vascular component), atypical meningioma (increased mitotic activity and either increased cellularity, high N/C, prominent nucleoli, sheet-like growth or necrosis), desmoplastic infantile astrocytoma (prominent desmoplastic stroma with neuroepithelial cells), schwannoma (encapsulated, Schwann cells in palisading or myxoid patterns, strong S100+, EMA-), vascular malformation (Sturge-Weber syndrome or arteriovenous malformation)
Grade II or III of IV
Formerly called angioblastic meningioma
<1% of all primary CNS tumors
60% men, mean age 43 years
Usually single mass attached to meninges of brain or spinal cord; more often in occipital region attached to venous sinuses
Similar to meningioma - origin from same cells, attaches to outer meninges, does not invade brain
Recent 5 year survival reported as 93% (J Neurosurg 2003;98:1182)
Resembles hemangiopericytomas elsewhere in body, although different molecular phenotype (Mod Path 2001;14:197)
May cause lytic destruction of adjacent bones
60-90% recur, 23-64% metastasize to bone, liver, lung, CNS; mean survival after metastasis is 2 years
Radiology: sharply demarcated tumors attached to dura, with smooth margins and intense contrast enhancement
Case reports: 52 year old woman with pleural metastasis (Archives 2004;128:1061)
Gross: solid, well-demarcated from adjacent brain; red-brown cut surface with vascular spaces; bleeds profusely during excision
Micro: sheets of cells with uniform hypercellularity, cells are homogeneous with abundant cytoplasm, oval nuclei, small nucleoli, moderate pleomorphism; mitotically active, staghorn vascular pattern lined by flat endothelial cells; cells tend to bulge into vascular lumina without bursting through endothelium; mild nuclear atypia, no “ropy” collagen of solitary fibrous tumor
Micro images: sheets of tumor cells; irregular blood vessels #1; #2 (may not be CNS); #3 (may not be CNS); CD34+ and CD31 negative; reticulin stain (may not be CNS); meningeal and soft tissue tumors
Positive stains: pericellular reticulin, type IV collagen or silver stains highlight pericellular basement membrane; strong bcl2 (86%) strong CD99 (85%) factor XIIIa (scattered, 78-100%), Leu7 (70%), CD34 (33%, weak), vimentin (85%), p53 (52%), EMA (33%), variable smooth muscle actin, cytokeratin (20%), desmin (20%), claudin1 (3%)
Negative stains: CD31
EM: extensive basement membrane around every cell; small bundles of intermediate filaments; no desmosomes; no gap junctions
DD: fibrous meningioma (80% EMA+, 80% S100+), glioma, metastatic carcinoma, solitary fibrous tumor (strong CD34 in 100%), anaplastic meningioma (chromosomal deletions, strong EMA+, weak/negative bcl2 and CD99, Hum Path 2004;35:1413)
References: AJSP 1997;21:1354
Primary intracranial melanocytic tumors are rare - most arise in leptomeninges
In children, associated with neurocutaneous melanosis, a rare congenital syndrome with giant congenital pigmented skin nevi and high rate of CNS melanoma (Semin Cutan Med Surg 2004;23:138)
Two types of primary leptomeningeal melanoma (diffuse or nodular); both are aggressive with metastases to liver and bones
Focal leptomeningeal melanosis is common; usually melanocytes are sparse in leptomeninges, but more numerous over anterior/lateral cord, brainstem and base of brain
Case reports: metastasizing melanocytoma-like leptomeningeal tumor, 11 year old girl with malignant blue nevus of ear associated with large multinodular blue nevus at same location and 2 intracranial melanocytic tumors with different grade of malignancy, probably representing metastases (Hum Path 2004;35:1292), intraventricular melanoma (AJNR Am J Neuroradiol 1999;20:691-free full text)
Gross: melanocytomas are unilocular and nodular attached to dura
Micro: melanocytomas are hypercellular with cells in nests or sheets; oval nuclei with fine chromatin and prominent nucleoli; no/rare mitotic figures, usually no hemorrhage, necrosis or CNS invasion
Micro images: metastasizing melanocytoma-like leptomeningeal tumor-various images; intermediate grade melanocytoma; intraventricular melanoma (figure H: H&E; I: HMB45)
Positive stains: vimentin, S100, HMB45
Negative stains: EMA
EM: basal lamina around cell groups, no desmosomes
DD: metastatic melanoma, melanotic meningioma (EMA+, desmosomes), melanotic schwannoma (basal lamina surrounds each cell)
References: AJSP 1999;23:745
Germ cell tumors
<2% of intracranial neoplasms in children or adults < 20 years old in US (50 new cases annually in US); higher frequency in Japan and Taiwan
95% are midline in pineal or suprasellar regions, 10% involve both regions
Sacrococcygeal teratoma occurs at base of spine
Specimens are usually biopsies, not surgical resections
Divided into germinomas and non-germinomas
Germinomas have better prognosis than non-germinomas (Pediatr Neurol 2002;26:369)
Radiation therapy rarely causes cortical laminar necrosis (Pediatr Blood Cancer 2005;44:412)
References: eMedicine, National Cancer Institute (USA), Childs Nerv Syst 1999;15:578, Oncologist 2000;5:312 (free full text)
Most common intracranial germ cell neoplasm
Often teenagers and young adults; 2/3 male
May be mixed with other germ cell tumors
May derive from ectopic rests, transformation of resident germ cells or migration of germ cells late in development
Most common site is pineal region; also anterior or posterior third ventricle, rarely fourth ventricle
Rarely associated with dysgenetic syndromes
Immunostains useful because biopsy is often small
Relatively good prognosis (5-10 year survival is 75-95%) vs. 25-40% for non-germinoma germ cell tumors (Pediatr Neurol 2002;26:369)
Very sensitive to radiotherapy and chemotherapy; nongerminomatous germ cell tumors are less radiosensitive
Metastases may be due to surgical displacement of tumor; spinal cord metastases occur in 10-15% of patients
Staging:
T1: Smaller than 5 cm in diameter and located in the suprasellar, intrasellar, or pineal region
T2: Larger than 5 cm in diameter and located in the perisellar region
T3: May be smaller than 5 cm in diameter but invades and encroaches on the third ventricle
T4: Extends into the anterior, middle, or posterior fossa
N: not indicated for CNS tumors
M0: No evidence of gross subarachnoid or hematogenous metastasis
M1: Microscopic tumor cells found in the CSF
M2: Gross nodular seeding in the ventricular system or cranial subarachnoid spaces
M3: Gross nodular seeding in the spinal subarachnoid spaces
M4: Metastasis outside the cerebrospinal axis
Case reports: intramedullary tumor (free full text), 23 year old man with headaches and visual difficulties (Archives 2003;127:497)
Treatment: resection difficult due to high collagen content; radiation therapy helpful
Gross: soft, gray-pink, homogenous; variable encapsulation; usually poorly circumscribed and infiltrative
Micro: resembles seminoma/dysgerminoma; large, epithelioid cells with abundant PAS+ cytoplasm, large, round nuclei and irregular and pleomorphic nuclei; may have prominent nests of lymphocytes with occasional granulomatous inflammation that may obscure tumor cells (Neurol Med Chir (Tokyo) 2005;45:415); lymphocytes may smear in small biopsies; frequent mitotic activity and necrosis; syncytiotrophoblasts in 14%; less anaplasia than embryonal carcinoma; no cells intermediate in size between lymphocytes and large germinoma cells
Cytology: loose fragments or single large pleomorphic and polygonal cells with vacuolated cytoplasm, enlarged oval nuclei and prominent nucleoli; frequent mitotic figures, naked nuclei, foamy background; also smashed lymphoid cells with streaking
Micro images: (1) large glycogen rich cells with clear cytoplasm, vesicular nuclei, large nucleoli; frequent mitotic figures; often extensive lymphoplasmacytic infiltrate #1; #2; #3; #4; #5; #6; (7) infiltration of optic nerve; (8) various images #1; #2; #3; #4; #5; (13) granulomas-PDF file; (14) PLAP+
Cytology images: large pleomorphic cells with vacuolated cytoplasm, large nuclei and streaking of lymphoid cells
Positive stains: PLAP, PAS+ cytoplasm, CD117/c-kit, OCT4 (strong, often diffuse)
Negative stains: keratin, EMA, hCG and AFP (except for syncytiotrophoblasts)
EM: glycogen in cytoplasm, sparse cytoskeletal elements, prominent nucleoli
EM images: cytoplasmic glycogen and prominent nucleoli
DD: embryonal carcinoma (25% are PLAP+), carcinoma (usually metastatic, keratin+, EMA+, 13% are PLAP+)
References: eMedicine #1, #2 (pineal germinoma), AJSP 2005;29:368 (OCT4 staining)
Prognosis poorer than germinoma
May be associated with precocious puberty
Characterized by rapid and bulky growth and spread to liver and lungs; 60% have metastases at presentation
Treatment: chemotherapy, radiation therapy, surgery
Positive stains: alpha-fetoprotein
Rare intracranial tumor, usually in pineal or suprasellar regions
Also called endodermal sinus tumor
Prognosis poorer than germinoma (median survival 2 years or less)
Case reports: 22 year old man with Down’s syndrome and pineal tumor with solid pattern, 15 year old girl with frontal lobe tumor (free full text)
Gross: usually large
Micro: tubulopapillary structures with vacuolated cuboidal cells, cystic spaces with eosinophilic hyaline bodies, and Schiller-Duval bodies
Micro images: various images-solid pattern in pineal gland
Positive stains: alpha-fetoprotein
References: J Neurosurg 1999;90:133
Prognosis poorer than germinoma - median survival 22 months in cases with high hCG levels (Neurooncol 2004;66:225)
Serum levels of hCG are helpful
Case reports: neonatal intracranial tumor in one month old infant who died from extensive intracerebral hemorrhage, presumed from a placental metastasis (Archives 1990;114:1079), 8 year old boy with precocious puberty (J Paediatr Child Health 1993;29:464)
Micro: syncytiotrophoblasts (large multinucleated cells) and cytotrophoblasts
Positive stains: hCG
DD: metastatic choriocarcinoma (from gonads or placenta)
Tissue derived from ectoderm, endoderm and mesoderm (at least 2 of 3 germinal layers)
Usually well differentiated / grade I of IV
Incidence varies with age: 30-50% of congenital brain tumors, 2% of brain tumors in infants and children, 0.5% at all ages
Congenital cases are usually fatal; may replace cerebral hemispheres (Pediatr Pathol 1987;7:333)
Mature teratomas: have well differentiated tissue from all three germinal layers, including neuroectoderm, including epithelium that is solid, cystic, glandular or tubular, cartilage or other mesenchymal elements, glial and neuronal tissue
Immature teratomas: have less differentiated tissue from any of the three germinal layers; 50% with intracranial tumors die within one year
Poor prognosis: tissue resembling medulloepithelioma, neuroblastoma, retinoblastoma or ependymoblastoma
Pineal teratomas are more common in males, but saccrococcygeal teratomas are more common in females
Must sample thoroughly for correct diagnosis
Growing teratoma syndrome: enlarging teratoma after tumor treatment (Neurosurgery 2005;56:188)
Treatment: newborns - complete surgical excision (difficult)
Case reports: 27 week fetus with immature intracranial teratoma causing skull rupture and death (Archives 2004;128:102), congenital tumor of lateral ventricle (Neurol India 2001;49:170-free full text; Neurol Res 2005;27:53-free full text)
Gross/micro images: immature intracranial tumor - figure 1: massive fetal head (arrows); 2: mass (thick arrows) and brain (thin arrows); 3: coronal section shows variegated appearance; 4: immature neuroepithelial tissue forming rosette-like structures and tubules; rapidly enlarging immature congenital intracranial tumor causing death
References: J Pediatr Hematol Oncol 2004;26:712 (associated with perioperative coagulopathy)
Tumors of the sellar region (see also Pituitary chapter)
Grade I of IV
Relatively rare; usually children (6-10% of intracranial malignancies), usually in sellar region near third ventricle
300 new cases per year in US, 1/3 are ages 0-14 years
Tumors may also have features of Rathke pouch cysts, and may arise from epithelial remnants of Rathke’s pouch that are trapped in pituitary stalk
Grows slowly and damages hypothalamus (causing endocrine abnormalities), compresses optic chiasm (causing bitemporal hemianopsia), blocks third ventricle (causing hydrocephalus)
Histologically benign but frequently recurs due to incomplete excision; rarely metastasizes or transforms to squamous cell carcinoma
Adamantinomatous subtype: usually children (ages 5-14 years); associated with beta-catenin mutations
Papillary subtype: usually older adults (ages 50+)
Case reports: metastatic tumor (Archives 2000;124:1356; AJNR Am J Neuroradiol 1999;20:1059-free full text), 47 year old woman with headaches and visual blurring, 12 year old girl with sphenoid sinus tumor (Archives 2005;129:e73)
Gross: solid and cystic; contents of adamantinomatous tumors resemble motor oil (color due to blood proteins, protein and cholesterol crystals secondary to hemorrhage)
Gross images: autopsy image; video of suprasellar tumor removal
Micro: either adamantinomatous (pediatric type), papillary (adult type) or mixed Adamantinomatous: relatively poorly circumscribed, nests and trabeculae of epithelium in fibrocollagenous stroma; peripheral cells show nuclear palisading; central cells are loose and termed “stellate reticulum”, often shows abundant keratin with “wet” appearance, may undergo cystic degeneration, calcification, xanthogranulomatous reaction; cyst fluid contains cholesterol crystals, cholesterol clefts, reactive giant cells; variable necrosis, inflammation and Rosenthal fibers; no keratohyaline granules
Papillary: well-circumscribed, composed of cores of fibrovascular stroma lined by well differentiated squamous epithelium that may separate to form pseudopapillae; resembles squamous papilloma; no stellate reticulum, no “wet” keratin, no calcification, no xanthogranulomatous inflammation; cystic fluid does not resemble motor oil
Micro images: epithelial island with keratin and cystin change #2; #3; #4; #5; #6; #7; benign squamous pearl; adamantinomatous epithelium; metastatic tumor; various images; stains-figure 1; figure 1: MRI; 2: nests of epithelial cells; 3: squamous areas with “wet” keratin and calcification; 4: cholesterol clefts; adamantinomatous tumor with transformation to squamous cell carcinoma
Negative stains: CK8, CK20 (Archives 2002;126:1174)
DD: metastatic carcinoma (usually no calcifications, no squamous epithelium), pilocystic astrocytoma (if only gliosis is sampled, more cellular, has microcysts), Rathke cleft cysts (CK8+, CK20+; both negative in craniopharyngioma)
References: eMedicine #1 (pediatric); #2, AJSP 1984;8:57
Ganglion cell tumor of pituitary
Rare; hamartomatous or neoplastic ganglion cells in sella turcica
May be associated with pituitary adenoma or hyperplasia
May be associated with acromegaly or Cushing’s syndrome or be apparently nonfunctioning
May represent neuronal differentiation of pituitary adenoma
Micro: adenoma with ganglion cell areas
References: AJSP 2000;24:607
Also called infundibuloma
Rare low grade glioma of sella and suprasellar region
May be derived from neurohypophyseal pituicytes (a specialized glial cell of the stalk and posterior lobe of the pituitary gland with supportive role for vasopressin and oxytocin-producing neurons)
Mean age 48 years, range 30-83 years; 6 of 9 were men
Visual symptoms, headaches or hypopituitarism
Radiology: solid, discrete, contrast enhancing masses within sella or suprasellar space
Treatment: total resection; may recur if incompletely excised
Case reports: 66 year old man with other endocrine neoplasms also (Archives 2001;125:527)
Micro: sheet, fascicles or storiform arrangement of plump bipolar spindle cells with abundant, slightly fibrillar eosinophilic cytoplasm without vacuoles and without granulation, mildly pleomorphic and oval nuclei with pinpoint nucleoli; rich capillary network with vessels often surrounded by radiating spindle cells; no infiltration of adjacent tissue, no Rosenthal fibers, no granular bodies, no granular axonal dilations (Herring bodies, normally present in neurohypophysis), no/rare mitotic figures
Micro images: storiform-like pattern
Positive stains: vimentin, S100, variable GFAP; low Ki-67 labeling index
Negative stains: synaptophysin, neurofilament, collagen type IV (not present between tumor cells), usually EMA
EM: bipolar spindle cells with abundant intermediate filaments; no meningothelial or ependymal features
DD: normal neurohypophysis (has axons, Herring bodies, perivascular anucleate zones with axonal terminations), pituitary adenomas (synaptophysin+, often chromogranin+, S100-, GFAP-), meningioma (whorls, psammoma bodies, nuclear inclusions, collagen deposition; EMA+, S100+ in fibrous variant, GFAP-; well defined desmosomes and interdigitating cell membranes), schwannoma (biphasic, hyalinized vessels, pericellular reticulin), benign fibrous histiocytoma (S100-), granular cell tumor, pilocytic astrocytoma
References: AJSP 2000;24:362
May grow into base of brain and resemble oligodendroglioma, ependymoma or meningioma
May be nonfunctional, particularly if gonadotropin-producing (no increase in plasma hormones)
Invasion of sella is associated with prolactin production (Arch Neurol 1977;34:742)
Most grow slowly and are considered benign, but others with benign histologic features invade the cavernous sinus, sphenoid sinus and base of brain
Often classified by hormone production (growth hormone, prolactin, TSH, ACTH, FSH or alpha-glycoprotein subunit)
Adenoma with uncertain malignant potential: high Ki-67, p53+ or invasive but not metastatic
Case reports: large tumor invading into cavernous sinuses (Neurol India 2005;53:105-free full text), ectopic pituitary adenoma with malignant transformation after multiple relapses (AJSP 2002;26:1078)
Micro images: relatively bland cells with mild nuclear pleomorphism; sheets of round cells invading bony trabeculae
Positive stains: chromogranin, pituitary peptide hormones
EM: neurosecretory granules
0.2 to 0.5% of adenohypophyseal tumors
Considered to derive from pituitary adenomas
Defined as tumors that have metastasized, since cannot differentiate based on histology (like other endocrine tumors)
Usually secrete ACTH or prolactin; “silent” pituitary tumors rarely metastasize
Highly aggressive, eventually causing death
Case reports: ectopic pituitary adenoma with malignant transformation after multiple relapses (AJSP 2002;26:1078)
Micro: may have nuclear pleomorphism with prominent nucleoli, mitotic activity
Positive stains: may have high Ki-67 labeling index, p53
DD: pituitary adenoma
References: AJSP 2003;27:477
Spindle cell oncocytoma of adenohypophysis
Described in 2002 (AJSP 2002;26:1048)
Mean 62 years, range 53-71 years
Associated with panhypopituitarism and variable visual field defect
Benign; no recurrence if totally excised
May derive from adenohypophyseal folliculostellate cells
Radiology: suprasellar extension; resembles pituitary adenoma; no dural involvement
Micro: fascicles of spindle cells with granular and eosinophilic cytoplasm; no/rare mitotic figures; no necrosis
Positive stains: vimentin, EMA, S100, galectin3
Negative stains: pituitary hormones, synaptophysin, chromogranin, GFAP, CAM 5.2, smooth muscle actin, CD34, CD68
EM: mitochodria rich in lamellar cristae; intermediate junctions and desmosomes, rough endoplasmic reticulum; no secretory granules
DD: metastatic extracranial oncocytic tumor, pituitary adenoma with oncocytic change (keratin+, synpatophysin+, neurosecretory granules+; chromogranin+, S100-, vimentin-, EMA-), meningioma with oncocytic change (EMA+ but intrasellar extension is rare; also whorls, interdigitation of cell membrane, S100- [except in fibrous meningioma]), ectopic salivary gland rests undergoing oncocytic transformation
Lymphoma and other hematopoietic lesions
Formerly called reticulum cell sarcoma or diffuse histiocytic lymphoma
By definition, occurs first in CNS without evidence of systemic lymphoma
<2% of brain tumors
Usually in cerebrum, but also elsewhere
May develop subsequent systemic lymphoma
Increased incidence (1000x) with AIDS and immunosuppression; also older immunocompetent patients
Most are high grade, diffuse large B cell lymphoma; other subtypes are rare (plasmacytoma, angiotropic lymphoma, Hodgkin’s lymphoma, MALT); but high incidence of T cell subtypes in Korea (17%, similar in Japan, vs. <5% elsewhere, AJSP 2003;27:919)
Steroid pre-treatment causes necrosis and makes diagnosis difficult
Pathogenesis uncertain since CNS lacks a regular lymphatic system
In previously healthy individuals, arise at age 50+ years, 60% male vs. mean age 10 years with inherited immunodeficiency, 37 years for transplant recipients, 39 years for AIDS patients
Often present with focal neurologic deficits (50-80%), neuropsychiatric symptoms (20-30%), increased intracranial pressure (10-30%), seizures (5-20%), eye symptoms (5-20%)
Usually discrete masses; rarely presents as diffuse, infiltrating condition without a cohesive mass, called lymphomatosis cerebri, associated with rapidly progressive dementia (Hum Path 2005;36:282)
CSF cytology helpful in diagnosing lymphoma of dura, leptomeningeal space or nerve roots
Radiology: bilateral, symmetric, subependymal, high signal foci on CT/MRI are suggestive; AIDS cases have multifocal, ring-enhancing lesions with central necrosis, resembling toxoplasmosis
Poor prognostic factors: multiple lesions, periventricular or meningeal involvement, associated immunodeficiency, age 60+ years, preoperative Karnofsky score 70 or less (J Clin Oncol 2003;21:266), expression of p53, c-myc or bcl6 in immunocompetent patients in one study (Archives 2003;127:208)
Survival: in immunocompetent patients treated with radiotherapy and chemotherapy, 2 year overall survival in 40-75% and 5 year overall survival in 25-45%; AIDS patients have median survival of 2-6 months, increasing to 13 months with multimodal therapy
Treatment: radiotherapy and chemotherapy
Case reports: Waldenstrom macroglobulinemia with CNS involvement (Archives 2002;126:1243), AIDS+ man with EBV+, KSHV+ primary effusion lymphoma in subarachnoid space (Hum Path 1999;30:981), 89 year old woman with peripheral T-cell lymphoma of cytotoxic/suppressor phenotype (AJSP 2003;27:682, 21 year old woman with B cell lymphoblastic lymphoma in middle cranial fossa (Surg Neurol 2004;62:80),)
Gross: single or multiple, discrete or infiltrative, often deep-seated and periventricular; tissue may be variegated, friable, granular, necrotic, hemorrhagic, gray-tan and resemble infarct or glioblastoma; tumors of dura mimic meningioma
Micro images: (1) figures A/B: MRI shows white matter lesions; C: perivascular large cell lymphoplasmacytoid infiltrate; D: IgM+; (2) CD20+, c-myc+, p53+, bcl6+
DD: toxoplasmosis, glioblastoma (more nuclear and cellular pleomorphism, vascular proliferation, necrosis with pseudopalisading of tumor cells, GFAP+, CD45-, CD20-), metastatic lymphoma (tumor outside CNS), inflammatory lesions, metastatic carcinoma (more cohesive, no perivascular deposition, keratin+, CD45-, CD20-), demyelinating disorder (macrophage rich with preservation of axons), infarct (macrophage rich, axonal destruction)
References: eMedicine, National Cancer Institute (USA), RadioGraphics 1997:17
Defined as peripheral lymphoma with secondary involvement of CNS
9% of lymphoma patients in one study (Eur J Cancer Clin Oncol 1989;25:703); CSF involvement in 9% of mantle cell lymphomas (Mod Path 2002;15:1073)
May involve dura, leptomeninges, cranial or peripheral nerves, vessels or CNS parenchyma
Short median survival of 5 months (Ann Hematol 2006;85:45)
Micro images: mantle cell lymphoma in CSF #1; #2; #3
Post-transplantation lymphoproliferative disease (PTLD)
Associated with organ transplantation or immunosuppression
CNS involvement in 19% of cases of PTLD, associated with high mortality (88% at 6 months in one study)
Almost all are high grade lymphomas (AJCP 2004;121:246)
Lymphoma cases are usually EBV+
Case reports: EBV+ low-grade lymphoproliferative disorder in 7 year old, HIV+ girl (not post-transplant, Archives 1999;123:83), clonally distinct EBV+ abdominal and CNS lesions (Hum Path 1999;30:1262)
Anaplastic large cell lymphoma
Rare in CNS (either primary or secondary)
Aggressive (rapidly fatal)
Favorable prognostic factors: ALK1+, young age (AJSP 2003;27:487)
Case reports: 46 year old AIDS patient with ALK negative tumor (Archives 2004;128:324), CD30+, ALK+ tumor (An Oncol 2002;13:1827-free full text), CNS relapse in patient without initial CNS disease (J Pediatr Hematol Oncol 2003;25:975), 2 year old boy (Med Pediatr Oncol 1997;28:132), leptomeningeal seeding with hydrocephalus after chemotherapy (Acta Haematol 1996;95:135), early detection of relapse with low CSF involvement (Pediatr Blood Cancer 2005;44:400)
Micro: large lymphoid cells with abundant cytoplasm and pleomorphic nuclei, often horseshoe or kidney-shaped; usually necrosis and mitotic activity; variants include small cell and lymphohistiocytic
Micro images: H&E, stains and molecular studies; medium to large cells; CD30+ (inset ALK1+)
Positive stains: CD30, ALK1 (often)
Molecular: T cell receptor gene rearrangements; t(2;5) involving ALK1 and NPM
DD: Hodgkin’s lymphoma, CD30+ T cell lymphomas, metastatic tumors, mycobacterial infection (Hum Path 1999;30:978)
Also called malignant angioendotheliomatosis, intravascular lymphoma
Uncommon cause of primary CNS lymphoma
Presents as rapidly progressive dementia with multifocal neurologic deficits, usually ages 60+ years
Mean survival 9-13 months
May present with CNS mass lesion (Pathol Int 2004;54:231)
Treatment: chemotherapy; may be curative
Case reports: 47 year old man with presumed CNS vasculitis (AJNR Am J Neuroradiol 2002;23:239-free full text); causing spinal cord stroke with paraplegia (AJNR Am J Neuroradiol 2004;25:1831), causing cauda equina syndrome (Clin Neurol Neurosurg 1992;94:311)
Micro: large, noncohesive, pleomorphic lymphoid cells (diffuse large B cell lymphoma type) within small and intermediate blood vessels
Micro images: intravascular tumor cells are CD20+
Positive stains: CD45, usually B cell markers; also bcl2
DD: intravascular dissemination of angiosarcoma (AJSP 1997;21:1138)
References: Hum Path 2000;31:220
By definition, primary CNS disease arises exclusively in central nervous system with no obvious lymphoma outside CNS at diagnosis; excludes lymphomas of the dura, intravascular lymphomas and immunodeficiency-associated lymphomas (note: the WHO 2008 classification excludes immunodeficiency associated lymphomas)
5-10% of CNS neoplasms in patients ages 75+ (Hum Path 2003;34:1137)
2-12% of AIDS patients at autopsy
Usually EBV- in immunocompetent patients vs. EBV+ in AIDS patients
Mean age: 10 years old if inherited immunodeficiency, 37 years for post-transplant, 39 years for AIDS patients
Favorable prognostic factors: single lesion, no periventricular or meningeal involvement, no immunodeficiency, age < 60 years, Karnofsky score > 70; also negative for p53, c-myc and bcl6 in one study (Archives 2003;127:208)
Median survival: 17-45 months if immunocompetent and chemoradiation therapy; 13.5 months with AIDS and multimodal therapy
Post-transplant: present nonspecifically, progress rapidly, stereotactic brain biopsy has significant mortality, survival is poor (Neuro-oncol 2000;2:229)
Xray images: CT of dural mass
Case reports: dural tumor presenting as intracranial mass (Archives 2000;124:1700), 49 year old man with progressive dementia, cryoglobulin deposition within tumor bed in immunocompetent patient (Hum Path 2003;34:720)
Treatment: steroids cause tumor cell necrosis with foamy histiocytes, so-called “vanishing tumors”
Micro: dense cellular aggregates of atypical lymphoid cells with dense perivascular aggregates; may infiltrate parenchyma diffusely, mix with gliosis and resemble glioma; often smearing of lymphoma cells with needle biopsy
Micro images: (1) dural mass; (2) diffuse infiltrates of large malignant cells #1; #2; perivascular infiltrate; figure 1: MRI shows brain stem and basal ganglia lesion; 2: large atypical cells with perivascular cell aggregation and necrosis; CD20-#1; #2
Positive stains: CD20, CD79a, monoclonal immunoglobulin; trichrome, type IV collagen and GFAP are helpful in identifying lymphoma invasion of vessels and parenchyma and differentiating from desmoplasia; may have reactive CD3+ T cells
Also CD10, bcl6, intense IRF4/MUM1 in 90% (Clin Cancer Res 2006:12:1152)
Molecular: immunoglobulin gene rearrangement
References: Archives 2004;128:595
DD: PNET (synaptophysin+), undifferentiated small cell carcinoma (keratin+), Langerhans cell histiocytosis (abundant cytoplasm, reniform nuclei, S100+, CD1+), tuberculoma (J Neurol Neurosurg Psychiatry 2004;75:1636-free full text), progressive multifocal leukoencephalopathy (Rinsho Ketsueki 2000;41:507)
Erdheim-Chester disease of CNS
Very rare (<100 cases reported), nonfamilial, neoplastic, xanthogranulomatous, non-Langerhans cell systemic histiocytosis first identified by William Chester in 1930
Usually associated with disease of long bones
Etiology not well understood
Mean age 57 years, range 25-76 years, no gender preference
Three year survival is 50-65%; prognosis usually depends on extent of extraosseous disease
Rarely involves CNS; usually hypothalamus and posterior pituitary (causing diabetes insipidus), retroorbital space; may affect dura
Case reports: 55 year old woman with tumors attached to pituitary, tentorium and brainstem (Clin Neuropathol 2003;22:246), brain stem infiltration by both Langerhans cell histiocytosis and Erdheim- Chester disease (Clin Exp Pathol 1999;47:71)
Micro: diffuse infiltration with large, foamy histiocytes, lymphoid aggregates, fibrosis, rare Touton-like giant cells
Cytology: lymphohistiocytic elements and large multinucleated cells with abundant cytoplasm, vesicular nuclei and prominent nucleoli (Diagn Cytopathol 2004;31:420)
Micro images: histiocytes are CD68+, rare S100+
Positive stains: CD68 and factor XIIIa (strong), S100 (weak or negative)
Negative stains: CD1a
EM: lipid droplets in cytoplasm but no Birbeck granules
DD: meningiomas (AJNR Am J Neuroradiol 2004;25:134-free full text, J Neurol Neurosurg Psychiatry 1999;66:72-free full text)
References: J Neurosurg 1997;86:888 (2 CNS cases); not CNS - AJSP 1999;23:17, Hum Path 2000;31:734, Hum Path 1999;30:1093
Very rare
Often fever, weight loss, hepatosplenomegaly and intestinal obstruction
Case reports: occipital lobe mass also involving meninges as a thick exudate (AJSP 2003;27:258)
Micro: large groups or sheets of large cells with abundant eosinophilic cytoplasm, pleomorphic vesicular nuclei, distinct nucleoli; also necrosis, neutrophils (variable abscesses) and chronic inflammatory cells, hemophagocytosis; no infiltration of vascular walls
Positive stains: CD68, lysozyme, HAM56; Ki-67 index > 20%; variable S100
Negative stains: myeloperoxidase, dendritic markers, CD30, ALK1, CD3, CD20, CD21/CD35, CD1a, ALK1, GFAP, cytokeratin
Molecular: no t(2;5); polyclonal
EM: abundant cytoplasm with irregularly folded or multisegmented nuclei, lysosomes; no Birbeck granules, no interdigitating cell processes, no cell junctions
DD: other lymphomas and histiocytic neoplasms (use immunohistochemistry), inflammatory processes
References: AJSP 2001;25:1372
Case reports: 54 year old with intracerebral disease without dural attachment (AJSP 1999;23:477)
Also called spindle cell pseudotumor, plasma cell granuloma, inflammatory myofibroblastic tumor
Rare, nonneoplastic lesion
May be intracranial extension of extracranial tumor
Usually in lung and airways; rarely intracranial or within spinal cord affecting young men
Treatment: complete resection, variable radiation therapy or steroids; may recur
Case reports: 70 year old man with intracranial tumor (Archives 2003;127:e220), 38 year year old man receiving steroids for sarcoidosis with Mycobacterium avium intracellulare (AJSP 1999;23:1294)
Micro: inflammatory proliferation of polyclonal plasma cells with variable lymphocytes, neutrophils, eosinophils and histiocytes; fibrovascular background; variable giant cells, calcifications, circular fibrosis of small veins
Micro images: mature plasma cells with Russell bodies (intracytoplasmic hyaline bodies)
Stains: plasma cells are polyclonal; acid fast bacilli if due to Mycobacteria
DD: plasmacytoma, lymphoplasmacyte-rich meningioma (has areas of classic meningioma, EMA+), lymphoma (monoclonal)
References: Hum Path 2003;34:253
Rare lytic skull lesion or parasellar mass
Children and young adults
May arise from primary histiocytic proliferation with secondary atrophy or from demyelination and gliosis of unknown origin (J Child Neurol 2000;15:150)
Case reports: 29 year old woman with post-traumatic frontal bone mass, 13 year old girl with temporal bone mass, brain stem infiltration by both Langerhans cell histiocytosis and Erdheim- Chester disease (Clin Exp Pathol 1999;47:71), necrotic, hemorrhagic, focally infiltrative (but benign) tumor (Clin Neuropathol 1993;12:179),
Micro: cells with abundant eosinophilic cytoplasm and reniform (kidney / coffee bean shaped) nuclei with grooves; variable collagen, gliosis and infiltrating T cells; may be partially infiltrative of surrounding CNS parenchyma or circumscribed granulomas
Micro images: various images #1; #2
Positive stains: S100, CD1a; also CD68 (macrophages and giant cells)
Negative stains: GFAP
EM: Birbeck granules
References: Brain 2005;128(Pt 4):829, Neurosurg Rev 1996;19:247
See also Leukemia chapter
Usually diagnosed by CSF cytology
Blast crises of >300K may be associated with parenchymal or meningeal mass lesions and intravascular leukostasis, particularly in AML
Case reports: acute monocytic leukemia presenting as temporal lobe mass (Archives 1999;123:327), AML relapse presenting as cerebellar granulocytic sarcoma / myeloblastoma (Mod Path 1999;12:1186)
Lymphoproliferative disorder with features of inflammation, vasculitis and neoplasm; usually B cell disorder with reactive T cells
Has high rate of CNS involvement (20-50%), often associated with pulmonary disease
Rarely is isolated to CNS
May progress to lymphoma, particularly in AIDS patients
Micro: angiocentric inflammation due to atypical lymphocytes with vessel wall destruction; usually no well formed granulomas
Micro images: perivascular lymphocytes, microglia and macrophages; perivascular small lymphocytes with atypia #1; #2
Positive stains: EBV (Mod Path 1990;3:435)
References: AJNR Am J Neuroradiol 2001;22:1283 (free full text)
Also called sinus histiocytosis with massive lymphadenopathy
Often (25-43%) has extranodal involvement
Rare (100 cases/year in US), and isolated CNS findings are extremely rare
Benign, but may be associated with systemic disease
Children and young adults (mean age 41 years, range 22-63 years)
CNS tumors usually associated with dura
Treatment: surgical biopsy or excision
Case reports: 50 year old woman with leptomeningeal disease, dural based masses, 48 year old woman with dural based intracranial tumor (Archives 2001;125:1115), relapsing intracranial disease treated with radiation (J Neurol Neurosurg Psychiatry 2001;71:538-free full text), 68 year old woman with isolated dural disease (AJNR Am J Neuroradiol 2003;24:515-free full text)
Micro: proliferation of variably sized, pale staining histiocytes, the larger ones may exhibit emperipolesis (engulf intact lymphocytes); often extensive lymphoplasmacytic infiltrate and collagen
Cytology: Rosai-Dorfman histiocytes (voluminous pale pink cytoplasm, single or multiple nuclei, large and hyperchromatic, with lymphagocytosis); also scattered lymphoid aggregates with loose mixture of lymphocytes, plasma cells and classic histiocytes (Acta Cytol 2003;47:1111)
Micro images: (1) emperipolesis #1; #2, S100+; (3) various images #1; #2; (5) figure 1: MRI shows extra-axial mass with adjacent edema; 2: inflammatory infiltrate with histiocytes, lymphocytes and plasma cells; 3: histiocytic emperipolesis ; 4: S100+ histiocytes; (6) pale staining histiocytes and inflammatory cells #1 in fibrotic background; #2; (8) emperipolesis of small lymphocytes; (9) S100+ histiocytes
Positive stains: CD68, S100
Negative stains: CD1a
DD: Langerhans cell histiocytosis, inflammatory pseudotumor, meningioma-lymphocytoplasmic rich subtype, nodular sclerosing Hodgkin’s lymphoma
References: Mod Path 2001;14:172, Clin Neuropathol 2005;24:112 (isolated CNS disease)
Mesenchymal and other tumors
Arises from bones of skull
Rarely in meninges or CNS parenchyma
Angiography: vascular mass displacing adjacent cortical vessels (GE medcyclopaedia)
Case reports: intracranial chondroma (AJNR Am J Neuroradiol 1997;18:889-free full text), arising from falx (AJNR Am J Neuroradiol 1997;18:573-free full text), associated with previous depressed skull fracture (Acta Neurochir (Wien) 2005;147:343), intradural convexity chondroma (W V Med J 2000;96:612), cystic falcine chondroma (Br J Neurosurg 1999;13:426)
Micro: mature hyaline cartilage
Micro images: mature hyaline cartilage with surrounding small vessels (page 891-PDF file)
References: eMedicine
Classic subtype
Case reports: parafalcine tumor (AJNR Am J Neuroradiol 2003;24:245-free full text)
Micro images: tumor is mild-moderately cellular with mildly pleomorphic tumor cells and mitotic figures; S100+
Mesenchymal chondrosarcoma
Rare
Intracranial or spinal meninges or cauda equina
Children or young adults
Treatment: surgery; radiation may be more helpful than chemotherapy (J Exp Clin Cancer Res 2005;24:317)
Case reports: craniocervical junction (Clin Neurol Neurosurg 1990;92:343), 13 year old girl with huge intracranial tumor (Kaohsiung J Med Sci 2004;20:240), with rhabdomyosarcomatous differentiation (Br J Neurosurg 2001;15:419)
Micro: dimorphic pattern of well differentiated cartilage with abrupt boundary from undifferentiated stroma composed of small round/oval cells resembling lymphoma, hemangiopericytoma or Ewing’s sarcoma/PNET; occasional spindle cells; minimal pleomorphism, no/rare mitotic figures
Micro images: not necessarily CNS - cellular with round tumor cells and adjacent hyaline cartilage
Positive stains: vimentin (100%), S100 (100% in cartilaginous component), cytokeratin (25%), GFAP (25%)
Molecular: usually diploid
DD: small blue cell tumors (Ewing’s/PNET, lymphoma, small cell osteosarcoma; all usually lack chondroid lobules)
References: Cancer 1996;77:1884
Myxoid chondrosarcoma
Case reports: intracranial tumor (Acta Neurochir (Wien) 2002;144:735), tumor of jugular foramen (Clin Neuropathol 2004;23:232)
Micro: rows of cuboidal cells in myxoid background, resembling chordoma
Positive stains: S100, vimentin
Negative stains: keratin
Molecular: t(9;22)(q22-31;q11-12): TEC/CHN and EWS genes
Poorly differentiated chondrosarcomas
Rare
Usually involve meninges
Micro: cartilage production may be sparse
Positive stains: S100, but many other CNS tumors are S100+
DD: other sarcomas, meningeal gliomatosis, carcinomatosis (lack cartilage production)
Rare malignant midline bone tumor arising from fetal notocord, usually within vertebral bodies, but possibly also in intervertebral discs or presacral soft tissue
May arise from intraosseous benign notochordal cell tumors (AJSP 2007;31:1573, Mod Path 2005;18:1005)
Usually males, age 40-60 years
Slow growing with repeated recurrences; late distant metastases to skin, bone, ovary (Archives 1990;114:208)
Invasiveness may be due to expression of cathepsin K (Hum Path 2000;31:834)
Sites: 50% sacrococcygeal (ages 40-59 years), 35% spheno-occipital / clivus (particularly children, image of clivus), 15% thoraco-lumbar spine
Sacrococcygeal: sacrum destroyed by osteolytic tumor; tumor may extend into retroperitoneum, presents as palpable extrarectal mass
Spheno-occipital: presents as nasal, paranasal or nasopharyngeal mass involving cranial nerves
Posterior mediastinum: Xray presentation is well-circumscribed, encapsulated soft tissue mass separate from spine (Hum Path 1995;26:1354)
Xray images: sagittal MRI of sacral tumor
Poor prognostic factors: large tumor size, positive surgical margins, tumor necrosis, high proliferative activity, areas of dedifferentiation; also up regulation of N cadherin and down regulation of E cadherin (AJSP 2005;29:1422)
Treatment: aggressive surgery, often leading to long survival (Oncologist 2007;12:1344); in children, external radiation is often successful for base of skull tumors (AJSP 2006;30:811); some tumors may dedifferentiate to high grade spindle cell sarcomas
Case reports: Case of the Week #110, chordoma of distal ulna (chordoma periphericum, AJSP 2001;25:263), lumbo-sacral tumor with high grade malignant cartilaginous and spindle cell components (AJSP 1990;14:384), spheno-occipital tumor evolving to an acute pontocerebellar hemorrhage (Archives 1989;113:1075)
Gross: soft, gelatinous, hemorrhagic, gray tumor
Gross images: chordoma at base of skull; drawing of clival chordoma
Micro: cords and lobules of physaliferous (having bubbles or vacuoles) cells separated by fibrous septa with extensive myxoid stroma; cells may be very large, with vacuolated cytoplasm, prominent vesicular nucleus (Archives 2004;128:1457); also small tumor cells with small nucleus; rare mitotic figures
Micro images: physaliferous cells #1; #2; #3; #4; sacral tumor #1; #2; #3; quiz case; incipient chordoma #1; #2; benign notocordal cell tumor #1; #2
stains: pan-keratin; synaptophysin; Alcian blue; neural type cadherin (figure 2D)
Cytology images: Diff Quik
Positive stains: S100, keratin (CK 8/18, CK19, AE1-AE3), EMA, 5' nucleotidase, glycogen, neural-type cadherin (Archives 2002;126:425), variable CK903, vimentin, CEA and lysozyme
Negative stains: CK7, CK20, chromogranin (Hum Path 1998;29:119)
Molecular: aneuploid
EM: mitochondria-endoplasmic reticulum complexes, parallel bundles of crisscrossing tubules, desmosomes (Archives 1993;117:1055)
DD: metastatic renal cell carcinoma (prominent vascularity, not lobulated, S100 negative) or other carcinoma, chondrosarcoma (not midline, no fibrous septa, EMA and keratin negative), signet cell adenocarcinoma of rectum, myxopapillary ependymoma (negative for epithelial markers), parachordoma (soft tissue tumor composed of epithelioid cells, smaller “glomoid” cells and spindle cells, negative for CK7, CK19, CK20, CEA)
References: Archives 1988;112:553 (stains), Mod Path 1997;10:545 (keratin stains), more information
Chondroid chordoma
Chordoma with prominent cartilaginous component - a controversial entity
Usually spheno-occipital region
Better prognosis than classic chordoma
Some consider them to be chondrosarcomas
Micro: matrix of amorphous blue ground substance with lacunae containing enlarged and slightly atypical cells; admixed areas of conventional chordoma
Cytology: low cellularity with loose round or stellate cells in myxoid background; cells have variably vacuolated cytoplasm, round/oval nuclei, mild cellular pleomorphism (Diagn Cytopathol 1999;21:335; Acta Cytol 1997;41:913)
Positive stains: both components - keratin, EMA, vimentin; often S100, occasionally CEA
EM: well formed tonofilament desmosome complexes, crystalline tubular structures within prominent and dilated rough endoplasmic reticulum, intracytoplasmic glycogen aggregates, abundant fibrillogranular matrix (AJSP 1983;7:625)
References: AJSP 1992;16:1144
Epithelioid hemangioendothelioma
Rare; usually cerebral hemispheres
Intermediate grade between hemangioma (benign) and angiosarcoma (high grade)
All ages, but 2/3 male
Usually unifocal
Favorable prognosis with complete resection; may recur or seed neuraxis; deaths are rare
Radiologic: associated with peritumoral vasogenic edema and homogenous contrast enhancement
Treatment: surgical excision, possibly radiation therapy (if incomplete excision) or alpha-interferon
Case reports: 49 year old woman with suprasellar tumor (Archives 2004;128:1289)
Micro: histiocytoid, epithelioid and spindled areas with intracytoplasmic lumina; vascular lumina are not apparent or focal; often chronic inflammatory cells, eosinophils and mast cells; variable mitotic figures; no dilated vascular spaces of cavernous hemangioma; no significant hemorrhage; no marked atypia
Micro images: H&E, CD34+ and CD31+; lower extremity tumor; pleura: factor VIII+
Positive stains: CD31, CD34, factor VIII related antigen
EM: endothelium with Weibel-Palade bodies, abundant intermediate filaments, surrounded by basal lamina
EM images: pleural tumor shows Weibel-Palade bodies
Molecular: t(1;3)(p36.3;q25) in some cases (involves PAX7)
DD: metastatic tumor from known primary (Eur Respir J 2004;23:483) or undisclosed primary (J Neurooncol 2004;67:337)
References: AJSP 1996;20:707
Also called calcifying pseudoneoplasms of neural axis
Uncommon
May be associated with dura along vertebral column
Probably reactive
Treatment: wide excision
Micro: various combinations of palisading spindle cells, epithelioid cells and multinucleated cells in fibrous stroma and bone; nodular chondromyxoid-like matrix
References: AJSP 1999;23:1270
WHO Grade I of IV (benign); slow growing and indolent, but symptoms due to mass effect and peritumoral edema
1-2% of intracranial tumors
Often in cerebellum; also spinal cord, meninges
Either part of von Hippel-Lindau disease (25-30%, inherited mutation of VHL gene on 3p25-26; autosomal dominant, hemangioblastomas of cerebellum and retina, cysts of liver and pancreas, pheochromocytoma, kidney tumors) or sporadic (often with somatic mutation of VHL gene)
Loss of VHL promotes increased production of vascular endothelial growth factor and erythropoietin
May be associated with loss of unknown tumor suppressor gene at 22q13 (Hum Path 2004;35:1105)
VHL patients often have new multiple, small, remote tumors (Brain Tumor Pathol 2004;21:75)
Radiologic images: CT, MRI and angiography
Case reports: cerebral tumor (Archives 2003;127:e382), intradural extramedullary spinal mass, 27 year old woman with cerebellar mass
Gross: well circumscribed mural nodule (containing tumor) associated with large fluid filled cyst
Gross images: cerebellar tumor
Note: obtain frozen section from mural nodule, NOT cyst wall
Micro: proliferation of capillaries with variable sized, closely packed, thin walled vessels and large neoplastic stromal cells with pink to clear foamy cytoplasm with fine vacuoles containing PAS+ lipid; nuclei are hyperchromatic; cyst wall has gliosis and Rosenthal fibers (resembling pilocytic astrocytoma); numerous mast cells in tumor mass (Folia Neuropathol 1999;37:138), usually no atypia; no fibrillar cells, no necrosis, no/rare mitotic figures
Micro images: abundant thin walled vessels and lipidized stroma; vascular tumor with adjacent gliosis; various images #1; #2; #3 with more clear cells; H&E, NSE, S100 and CD34; A: hemangioblastoma vs. B: metastatic renal cell carcinoma; CD10- and inhibin alpha+
Cytology: nonfibrillar stromal cells with large nuclei and vacuoles
Cytology images: nonfibrillar stromal cells and central mast cell with metachromatic staining
Positive stains: stroma is positive for NSE, lipid (at frozen section), reticulin, CD34; also VEGF, inhibin alpha (AJSP 2003;27:1152); occasionally erythropoietin, GFAP, S100
Negative stains: EMA, keratin, CD10 (Mod Path 2005;18:788)
EM: variable secretory granules
Molecular images: idiogram of VHL mutation
DD: endocrine neoplasm (no endocrine gland of origin nearby), fibrillary astrocytoma (at frozen section due to bursting from lipid), renal cell carcinoma (nuclear atypia, large nucleoli, mitotic figures, cytokeratin+, EMA+, NSE-, inhibin-)
References: eMedicine (VHL); molecular-VHL
Rare; either congenital malformation or no other pathologic findings (Clin Neurol Neurosurg 2005 May 11; [Epub ahead of print])
Often midline near corpus callosum, quadrigeminal plate, hypothalamus, spinal canal, cauda equina, tuber cinereum
Causes headache, seizures or no symptoms
Associated with epidermal nevus syndrome (Neuropediatrics 2000;31:175), encephalocraniocutaneous lipomatosis (Am J Med Genet 2000;91:261), Goldenhar-Gorlin syndrome (Childs Brain 1984;11:285), agenesis of corpus callosum (Pediatr Neurol 2005;32:94)
May be due to focal disturbances in cerebral cortical development (AJNR Am J Neuroradiol 2000;21:1718-free full text, Acta Neuropathol (Berl) 2005;109:339)
Case reports: parietal lipomeningocele (Neurol Med Chir (Tokyo) 2005;45:112-free full text), 10 year old with lipoma of tuber cinereum (Archives 2005;129:708)
Micro: mature adipose tissue; also Schwann cells, bone, cartilage, hamartomatous blood vessels
Micro images: tuber cinereum; mature adipose tissue-PDF file page 113; lipochoristoma-various images
References: Archives 2003;127:1475 (lipomatous choristomas of cranial nerve VIII)
Malignant peripheral nerve sheath tumor (MPNST)
Grade III or IV
Locally aggressive, metastasizes late
Usually arises in peripheral nerves, usually is a transformed plexiform neurofibroma (associated with neurofibromatosis 1), but may also be associated with radiation therapy or arise denovo; only rarely arises from malignant degeneration of schwannomas
Very rare in cranial cavity; rarely involves cranial nerves V and VIII
Case reports: trigeminal nerve tumor with loss of S100+ at recurrence (Acta Neurochir (Wien) 2000;142:591), collision tumor of MPNST with rhabdomyoblastic differentiation (triton tumor) and ependymoma at cerebellopontine angle (Archives 2001;125:1113)
Gross: fusiform or plexiform enlargement of nerve with thin capsule; homogeneous gray cut surface
Micro: infiltrates nerve (important criteria since histologic features vary) and soft tissue with necrosis; also marked hypercellularity (varies within tumor) with cells having spindle-shaped nuclei with tapered ends, nuclear pleomorphism, brisk mitotic activity with abnormal forms
Patterns: fibrosarcoma, MFH, Schwann cells, triton tumor (rhabdomyosarcoma regions), chondrosarcoma
Micro images: metastatic tumor-PDF file page 117; not necessarily brain - spindle tumor #1; #2 with adipocyte-like areas; extracranial trigeminal nerve tumor with hyperchromatic nuclei and mitotic figures; various images
Positive stains: p53; variable S100
DD: metastatic MPNST (Neurol Med Chir (Tokyo) 2000;40:116-free full text, Folia Neuropathol 2004;42:43, Clin Neuropathol 1990;9:290-pigmented spinal tumor)
Epithelioid MPNST
Very rare; aggressive
Case reports: tumor of mandible and skull base (J Craniofac Surg 1997;8:417), cerebral metastasis from forearm tumor (Neurosurgery 1991;29:906)
Micro: tumor cells have distinct cell borders and epithelial cell nests
Cytology: discohesive cells with plasmacytoid or epithelioid appearance (Diagn Cytopathol 1997;17:200)
Micro images: trigeminofacial tumor
Positive stains: S100
Negative stains: cytokeratin
Benign (grade I)
Arises within nerves and infiltrates them
Having multiple tumors or plexiform subtype is associated with neurofibromatosis 1
Case reports: plexiform tumor of cauda equina (Surg Neurol 2005;63:182), lateral wall of cavernous sinus (Aust N Z J Surg 1988;58:594), combined neurofibroma-granular cell tumor of middle cranial fossa (Pathol Res Pract 1978;163:378)
Gross: fusiform enlargement of nerve from which it arises
Micro: spindled Schwann cells with wire like collagen fibrils mixing with axons, stromal mucosubstances, mast cells, Wagner-Meissner corpuscles, fibroblasts; no Antoni A or B areas; vessels are thin walled without perivascular hemosiderin
Micro images: collagen rich bundles in a loose matrix; reticulin stain; not necessarily CNS - various images
Positive stains: S100, Leu7, variable GFAP
Negative stains: EMA, cytokeratin
Sarcoma (other than chondrosarcoma)
Very rare (<1% of CNS tumors); more likely to be another tumor that is misdiagnosed
Usually cerebral, but may be cerebellar or spinal cord
Median age 28 years, range 3-63 years
Often associated with prior radiation therapy (such as for craniopharyngioma or pituitary adenoma); these sarcomas cause rapid death from local invasion
Better prognosis if low grade, but even high grade sarcomas have better survival than glioblastoma multiforme (AJSP 2002;26:1056)
Case reports: meningeal sarcomas with meningothelial and leiomyoblastic differentiation (AJSP 2000;24:1273), 15 month old boy with hypomelanosis of Ito and primary meningeal rhabdomyosarcoma (Archives 2000;124:762), follicular dendritic cell sarcoma (J Neurosurg 2003;99:1089), 9 year old boy with fibrosarcoma (J Neurooncol 2004;68:161)
Gross: median size 4 cm (1-8 cm)
Micro: fibrosarcoma, MFH or undifferentiated subtypes are most common; often high grade; no glial or meningothelial features
Micro images: meningeal rhabdomyosarcoma #1; #2 with cross striations
Negative stains: EMA, GFAP
DD: lymphoma, PNET, giant cell glioblastoma
References: fibrosarcoma (Neurol India 2000;48:396-free full text), Ewing’s sarcoma in CNS (Clin Neuropathol 2005;24:184; Acta Neurochir (Wien) 1991;113:48)
Also called neurilemoma; improperly designated as acoustic “neuroma”
Benign (grade I)
7% of intracranial neoplasms
More common in older adults, women
Derived from Schwann cells (neural crest derivation)
Tend to arise on and compress peripheral aspects of nerves, 90% on CN VIII (“acoustic schwannoma”); rare on CN V or VII or other cranial nerves
In spinal cord, usually attached to dorsal spinal nerve root, and may extend into cord
Bilateral CN VIII tumors: associated with neurofibromatosis type 2 (NF2); NF2 patients also have tumors at unusual locations, meningeal proliferations and gliomas; poorer prognosis is associated with tumors 2 cm or larger and earlier age at onset (J Neurosurg 2003;99:480)
Symptoms associated with compressed nerve (tinnitus or hearing loss with CN VIII)
Treatment: radiation therapy may cause malignant transformation, particularly in children or NF patients (J Med Genet 2005 Sep 9; [Epub ahead of print])
Case reports: intracranial subfrontal tumor (Neurol India 2004;52:248-free full text), patient with spinal and intracranial melanotic schwannomas (J Neurooncol 2004;68:249), intracerebral tumor (Pathol Int 2005;55:514)
Gross: firm gray masses; may have cystic and xanthomatous change and hemorrhage; attached to nerve, but can be separated from it; does not invade but can displace brainstem and spinal cord
Drawings: anatomy of acoustic tumor
Gross images: acoustic neuroma #1; #2; fish-flesh tan cut surface
Micro: circumscribed and often encapsulated; biphasic (less common at cerebellopontine angle); composed of uniformly spindled Schwann cells with Antoni A (cellular fascicular) and Antoni B (myxoid; vacuolated) regions; vessel walls with perivascular hemosiderin; variable Verocay bodies (eosinophilic cores and nuclear palisading); cells are spindled with ill defined cytoplasm, dense chromatin; no axons, no mitotic figures
Degenerative changes (ancient change) - nuclear pleomorphism, xanthomatous change, vascular hyalinization; common but no significance
May have Rosenthal fibers or eosinophilic granular bodies (Archives 1997;121:1207)
Micro images: Antoni A areas and Verocay bodies #2 (Antoni B on right); #3 (black arrow-Antoni A, blue arrow-Antoni B); high power; various images
Cytology images: schwannoma
Positive stains: S100, Leu7; type 4 collagen (stains abundant parenchymal reticulin), CD34 (Antoni B areas), calretinin (Antoni A areas); silver stain shows minimal axons; variable GFAP
Negative stains: EMA, cytokeratin, CD31, ER, PR, BCL2
Molecular: 22q- due to mutations of neurofibromatosis 2 gene in these patients
EM: continuous basement membranes along exterior surface of cells
DD: fibroblastic meningioma (whorls, psammoma bodies, EMA+), solitary fibrous tumor, tanycytic ependymoma (no abundant parenchymal reticulin), subependymoma, astrocytoma (no abundant parenchymal reticulin), hemangiopericytoma
References: eMedicine (Schwannoma, cranial nerve)
Rare; often not recognized when found in dura
Usually dural based lesion of cranium or spinal canal; occasionally lateral ventricle or spinal cord
May recur (if inadequately resected); rarely metastasizes but still has indolent course
Treatment: gross total resection; may recur if incomplete resection (Clin Neuropathol 2005;24:252)
Case reports: 67 year old man with tumor at spinal nerve root (Archives 2004;128:335), quadriplegic patient with recurrent paraspinal tumor (Archives 2002;126:987), 61 year old woman with malignant tumor, meningeal tumor, 53 year old woman with solitary fibrous tumor and salivary gland heterotopia at cerebellopontine angle (AJSP 2004;28:139), infiltrative tumor involving cavernous sinus, sphenoid sinus and pituitary fossa (Ann Diagn Pathol 2003;7:169), brain invasive tumor (Int J Surg Pathol 2002;10:217), with CSF dissemination (J Neurosurg 2004;101:1045), tumor of hypoglossal nerve (AJNR Am J Neuroradiol 2003;24:343-free full text)
Gross: smooth surface, no capsule; white-tan, firm, slightly rubbery, compresses adjacent parenchyma
Gross images: tumor attached to dura
Micro: haphazard (patternless) arrangement of monomorphic spindle cells with abundant ropy collagen mixed with tumor cells; may have alternating hypo- and hypercellular areas with perivascular hyalinization or myxoid degeneration; usually has hemangiopericytoma-like vascular pattern; no mitotic figures or necrosis
May have more aggressive behavior if hypercellular, pleomorphism, mitotic activity, necrosis (Brain Pathol 2001;11:485)
Micro images: (1) H&E, CD34, BCL2; (2) other stains; (3) various images from meningeal tumor #1; #2; (4) various images from malignant tumor; (5) tumor of hypoglossal nerve #1; #2 (CD34+); (6) paraspinal tumor with frequent mitotic figures
Positive stains: CD34, CD99, BCL2, vimentin; variable ER, PR
Negative stains: EMA, S100, smooth muscle actin, desmin, keratin, CD31
EM: resemble fibroblasts
DD: hemangiopericytoma (80% recurrence rate, often causing death, has delicate prominent pericellular reticulin fibers, usually no dense collagen bands, focal CD34+), fibrous meningioma (cellular whorls and psammoma bodies, more common, no dense collagenous bands, usually EMA+, S100+, weak/negative CD34 staining), schwannoma (alternating Antoni A and B areas, strongly S100+)
References: Archives 2003;127:432, Am J Clin Pathol 1996;106:217 (meningeal tumors)
Also called gossypiboma, gauzoma, muslinoma
Foreign body tumor composed of nonresorbable or resorbable substances used for hemostasis in neurosurgical procedures
Micro: core of degenerating hemostatic agent with surrounding inflammation
Micro images: recurrent hemostatic agents used in neurosurgery; textiloma and residual gliosarcoma; gelfoam textiloma; mixed avitene-cotton textiloma; avitene textiloma
DD: recurrent tumor (by MRI), radiation necrosis
References: Archives 2004;128:749
Metastatic tumors to CNS
Most common brain tumor seen in community hospitals are metastases (50% of intracranial tumors in hospitalized patients)
Primary is usually known - melanoma or carcinoma, occasionally germ cell tumor
80% from lung, breast, skin (melanoma), kidney, GI
Common with choriocarcinoma
Common presentation is adult with seizures or ataxia
Dural metastases are often from breast and prostate, but also unusual primaries; may have survival of 2+ years (Archives 2001;125:880)
Case reports: metastatic salivary gland pleomorphic adenoma to spinal cord (Archives 2003;127:887)
Gross: sharply demarcated lesion at gray-white matter junction, surrounded by edema
Micro images: metastatic pleomorphic adenoma - figure 1: epidural tumor; 2: epithelial cells in fibromyxoid stroma; 3: focal areas of increased cellularity and nuclear pleomorphism; 4: tumor involves cortical bone and marrow space
Metastases to brain: lung, breast, kidney, GU
Metastases to vertebral column: often prostate, breast or hematopoietic neoplasm
Metastases with unknown primary: lung, colon, kidney
Rarely produces carcinomatous meningitis, with poor prognosis
Multiple lesions are suggestive of metastasis vs. primary CNS tumor
Usually to cerebrum, but no distinct patterns
Favorable prognostic factors: single metastasis, younger age, surgical resection of metastasis, primary in lung (non-small cell), breast, melanoma, renal cell or ovary
Meningeal carcinomatosis: represents 4-8% of metastatic brain tumors; diffuse spread of tumor in subarachnoid space; associated with carcinoma of lung and breast and ALL; poor prognosis; repeat lumbar punctures and immunocytochemistry may be helpful in differentiating from aseptic meningitis (Archives 2000;124:759)
Case reports: meningeal carcinomatosis - from gallbladder carcinoma (Archives 2001;125:1120), from renal collecting duct carcinoma (Archives 1999;123:638); from melanoma (Hum Path 2003;34:625), from contralateral adenoid cystic carcinoma of external ear canal (Archives 2002;126:87)
Gross images: lung metastasis
Micro: epithelial cells with discrete cell boundaries, pushing margin except for small cell carcinoma (infiltrative)
Micro images: meningeal carcinomatosis - (1) from gallbladder adenocarcinoma (figure 2: gallbladder, 3: leptomeninges); (2) adenoid cystic carcinoma from external ear canal
Cytology images: primary not indicated - papillary fronds of pleomorphic tumor cells; metastatic GI carcinoma (signet ring cells)
Recommended stain panels: TTF1 (lung and thyroid), cytokeratin and CAM 5.2, CK7, CK20, PSA
Breast carcinoma: CK7+, CK20-, CAM5.2+ but TTF1 negative
Lung adenocarcinoma: CK7+, CK20-, CAM5.2+ but TTF1+
Colon carcinoma: CK7-, CK20+, TTF1 negative
Renal cell carcinoma: RCC+, CAM5.2+, vimentin+ DD: glioblastoma, anaplastic glioma (no distinct
borders, have fibrillary cytoplasmic processes), meningioma (syncytial
borders), hemangioblastoma vs. renal cell carcinoma, PNET vs. metastatic small
cell carcinoma (nonfibrillar cells), melanoma References: Hum
Path 2002;33:642 (TTF1), eMedicine Metastatic choriocarcinoma to CNS Primaries
frequently metastasize to CNS Often
is hemorrhagic Rarely
occurs during pregnancy (Obstet
Gynecol 2003;102:1380, J
Neurosurg 2002;97:477) Positive
stains: beta hCG References:
Cancer
1983;52:1728. Neurol
India 2001;49:231-free full text Melanoma
has high rate of CNS metastases (10-40% in clinical studies, higher in autopsy
studies) Melanoma
is third most common cause of cerebral metastases in most series (after lung
and breast primaries) Metastases
may be multiple To
make the diagnosis, must consider melanoma in advance Poor
survival (mean 3 months) after metastases detected Case
reports: initial presentation as
extensive metastatic leptomeningeal melanomatosis (Hum
Path 2003;34:625) Gross: well circumscribed nodules, solid or partially
cystic; marked peritumoral edema; variable hemorrhage or necrosis Micro: variable pigment, epithelial or spindle cells Micro
images: tumor
cells in Virchow-Robin space Cytology
images: pleomorphic
tumor cells with brown pigment Positive
stains: S100 (not specific), HMB45,
MelanA/MART1 DD: melanocytoma (benign cells normally in arachnoid),
primary melanoma References: eMedicine Other metastatic tumors to CNS top Nervous
system dysfunction associated with cancer but without direct tumor invasion,
infection or vascular complications of neural tissue May
precede clinical recognition of tumors Occurs
in <1% of cancer patients; usually small cell carcinoma of lung, breast
cancer, ovarian cancer Often
due to autoantibodies May
respond to treatment of the underlying tumors Cerebellar
degeneration: destruction of
Purkinje cells (antibody mediated) with perivascular lymphocytes; causes
progressive bilateral leg and arm ataxia, dysarthria, variable vertigo and
diplopia; associated with breast, gynecologic, Hodgkin’s lymphoma, small cell
carcinoma of lung; often associated with anti-Yo antibody in serum or CSF References:
Brain
2003;126(Pt 6):1409-free full text Lambert-Eaton
myasthenic syndrome: destruction
of neuromuscular junction (presynaptic terminals) by small cell lung cancer;
due to IgG antibody Limbic
encephalitis: associated with subacute
dementia - perivascular inflammatory cuffs, microglial nodules, neuronal loss,
gliosis of temporal lobe, resembles infectious process; also in brainstem; most
common with small cell lung cancer Myelopathies: necrotizing myelopathy due to leukemia, lymphoma,
lung carcinoma; myelitis due to Anti-Hu antibody associated with small cell
lung carcinoma Opsoclonus/myoclonus
(spontaneous chaotic eye movements): affects brain stem, but site unknown; due to breast and small cell lung
cancer; also neuroblastoma; may be associated with anti-Ri autoantibody Peripheral
neuropathy: most common
paraneoplastic syndrome; may be associated with anti-Hu antibody in lung cancer
patients Primary
lateral sclerosis: rarely caused
by breast cancer; 50% develop lower motor neuron signs eventually Retinal
degeneration: destruction of
photoreceptors; due to small cell carcinoma and gynecologic tumors Stiff-man
syndrome: destruction of spinal
interneurons by amphiphysin antibody; usually breast cancer, also lung cancer
and thymoma Subacute
sensory neuropathy: may occur
with limbic encephalitis; loss of sensory neurons from dorsal root ganglia,
associated with inflammation; due to small cell lung cancer Micro
images: dorsal
root ganglionitis References: Neurol
Neurosurg Psychiatry 1997;63:133-free full text (paraneoplastic encephalomyelitis) Subacute
motor neuronopathy: degeneration
of anterior horn cells; rare, painless lower motor neuron weakness of
extremities; associated with lymphoma Case
reports: neuropathy associated with
lymphoma and IgM antibodies against disialosyl residues (Muscle
Nerve 2005;32:216) DD: metabolic brain disease, meningeal carcinomatosis,
progressive multifocal leukoencephalopathy References: eMedicine, J
Neurol Neurosurg Psychiatry 2004;75 Suppl 2:ii43-free full text Miscellaneous Intraoperative consultation / frozen
sections Indications:
(a) determine if lesional tissue is present, (b) determine if adequate
sampling, (c) provide preliminary information to assist neurosurgeon (see
below), (d) perform special techniques (culture, B5 for lymphoma, touch
preparations) Need
not give definitive diagnosis Should
not grade astrocytic glial neoplasm unless is clearly a glioblastoma (since
tumors often have variable grades) For
some tumors, attempts at total resection are made (meningioma, schwannoma,
solitary metastases, cysts, ependymoma, hemangioblastoma, cerebellar pilocytic
astrocytoma, craniopharyngioma), so intraoperative consultation may be helpful Recommended
to assess undefined lesions by both frozen section and cytologic preparation Cytologic
preparation: adds fine nuclear detail, reveals glial-type processes or
epithelioid features of carcinomas; shows discohesiveness associated with
pituitary adenoma, oligodendroglioma, medulloblastoma or lymphoma; may be more
accurate than frozen section (Stereotact
Funct Neurosurg 1995;65:187) Recommended
to obtain touch preparations (touch glass slide to wet tissue, fix before it
dries, then stain) Artifacts: long empty cavities in parenchyma (due to cryostat)
vs. microcysts which contain cells and eosinophilic proteinaceous material) References:
Archives
2005;129:1635, Archives
1997;121:481, Mod
Path 1988;1:378, J
Neurol Neurosurg Psychiatry 1988;51:332, Archives
2005;129:1653 (assessment of pediatric tumors) Either
primary biopsy to determine diagnosis; secondary biopsy to determine diagnosis
or monitor therapy effect; or therapeutic resection Primary
biopsy: may be able to totally
resect meningiomas, carcinomas, adenomas, schwannomas, pilocytic astrocytomas,
ependymomas Stereotactic
needle biopsy: through small hole in
skull; tissue may be nondiagnostic (necrotic, may have missed lesion);
important for pathologist to indicate if lesional tissue is obtained; perform
cytology by touching slide to gauze; report presence of large vessel to
neurosurgeon Secondary
biopsy: repeat biopsies of lesion or
its immediate vicinity; avoid by monitoring primary biopsy with intraoperative
consultation Post-therapy
biopsy: must know nature of prior
therapy Therapeutic
resection: if tumor was not
previously completely excised; may be gross total resection (100% removal of
known mass), radical subtotal (95-99% removal), subtotal (75-95% removal),
partial (10-75% removal); compare to prior slides to determine treatment
response (fibrosis, necrosis) Evaluate
the arachnoid, gray and white matter Section,
if possible, from the arachnoid through the gray to the white matter Sample
interface between the lesion and normal appearing brain EM
helpful for poorly differentiated or unusual tumors (clear cell ependymoma),
toxic-metabolic disease, infection; recommended to save tissue for EM in
challenging cases Infarcts: section perpendicular to surface of brain, submit
sections of arachnoid, gray and white matter; save gray matter for EM if
considering CADASIL or mitochondrial disease Hematopoietic
lesions: also B5, cell culture media
(for flow cytometry), touch preparations, flash frozen tissue for molecular
analysis Infectious
disorders: recommended that surgeon
obtain cultures from sterile operating field Toxic-metabolic
disorders: recommend fixation of
gray and white matter in formalin, glutaraldehyde, frozen tissue bank Gross features of various disease entities Abnormal
mass: solid tissue not identifiable
as gray or white matter Cyst
wall: flat tissue from 0 to 3 mm
thick - compare to surgeon’s impression or radiographs Gliosis: often yellow or gray and firm Necrosis: soft, friable, often cavitates Semiliquid
or gelatinous masses: usually
tumors, including oligodendroglioma, lymphoma, pituitary adenoma Vascular
malformation: vessels larger than
usual aggregate of arachnoid vessels, often associated with hemorrhage, may
involve meninges or parenchyma Margins: usually impossible to assess due to piecemeal nature
of resection or infiltrative growth pattern; may be able to determine for
childhood pilocytic astrocytoma of cerebellum, cerebral dysembryoplastic
neuroepithelial tumor, meningioma Safety: recommended that surgeon contact lab if patient is
HIV+ (use cytology, not frozen section) or may have Creutzfeldt-Jakob disease
(decline frozen sections since cannot decontaminate cryostat); decontaminate
cryostat used for HIV+ tissue by replacing blade, removing frozen debris and wiping
surfaces with 10% bleach in water; for CJD specimens that are sectioned,
recommended to place cassettes in formalin for 24 hours, then transfer to 100%
formic acid for one hour, then return to fresh formalin for 48 hours, then
process; label cassettes with pencil (formic acid dissolves ink), wrap needle
biopsies in lens paper, handled embedded tissue as if infectious, dispose of
blade, section waste, wipe microtome and cutting station with bleach,
incinerate all towels, gloves and waste References:
Univ
of Pittsburgh grossing manual Features to report-excludes
pituitary neoplasms Specimen
type Specimen
size (greatest dimension, additional dimensions are optional) Tumor
site Tumor
size (greatest dimension, additional dimensions are optional) Histologic
type Histologic
grade (WHO I-IV, other, cannot be determined, not applicable) Margins
(involved, uninvolved, cannot be assessed, not applicable) Results
of additional studies performed (electron microscopy, cytogenetics, molecular
testing, immunohistochemistry) References:
Archives
2001;125:1162 No TNM
classification exists for CNS tumors (AJCC
Cancer Staging Manual (7th ed)) for these reasons: For T
component, histology and location are more important than tumor size For N
component, brain and spinal cord have no lymphatics, so lymph nodes cannot be
staged For M
component, most patients die before metastatic disease is identified (except
for CSF seeding in some pediatric tumors Generally
favorable prognostic factors: younger age, total resection vs. subtotal
resection; higher Karnofsky performance scale Standard
CNS sections: spinal cord (2-3
levels), medulla, pons, midbrain, cerebellum, hypothalamus, basal ganglia,
hippocampus, thalamus, parietal cortex, occipital cortex, cingulate gyrus,
superior temporal gyrus, paracentral cortex, pituitary Sample
gross description: The
scalp and skull are entered in a standard biparietal, post-auricular
manner. Then dura is intact and the sagittal sinus is patent. The
pre-fixation brain weight is __ grams. The formalin fixed brain weights
__grams. The cerebral and cerebellar hemispheres are symmetrical with no
masses, areas of discoloration or gross lesions identified. There is no
evidence of midline shift. There is no uncal, subfalcine or tonsillar
softening or grooving. The sulci/gyri are unremarkable, with no atrophy
identified. The leptomeninges are thin, translucent and without
hemorrhage. The circle of Willis is intact, with no atherosclerotic
plaque. Coronal sections of the cerebral hemispheres show well delineated
gray and white matter structures. The ventricles are symmetric and not
dilated. Distal blood vessels are unremarkable. Axial
sections of the midbrain, pons and medulla are symmetrical with well delineated
gray and white matter structures. The substantia nigra and locus ceruleus
are well pigmented. The aqueduct and fourth ventricle are
unremarkable. Parasagittal sections of the cerebellum show well
delineated white and gray matter structures with prominent folia. The
pituitary is removed from the sella and is grossly unremarkable. The
spinal cord is removed by an anterior approach. Axial sections of the
spinal cord are symmetric with well delineated gray and white
matter. Sample
microscopic description: The
spinal cord shows ... The midbrain, pons and medulla show mild neuronal
loss and gliosis consistent with the patient’s age. The cerebellum, basal
ganglia and thalamus are unremarkable. The hippocampus shows no senile
plaques or neurofibrillary tangles. The cerebral neocortex is
unremarkable. End of CNS tumor chapter
Case reports: 18 year old woman with primary alveolar soft part sarcoma in tongue when 8 years old and multiple pulmonary metastases (Case of Week #222)
