Pathology of CNS(Tumor of CNS)

DR Naila AwalDepartment of pathology

Neuronal tumor

• Ganglioglioma-• Neoplastic ganglion cells and neoplastic glial component (ganglioglioma)• Grade-WHO I Anaplastic variant rare– WHO grade III (grade II eliminated in 2007)• Age -Children/young adults • Site- common in temporal, parietal, frontal lobes.• MRI-

Solid or cystic or both or cyst /mural nodule variable calcification

• Gross Solid or cystic

• No hemorrhage or necrosis

• Single rounded mass about 5.5 cm in diameter, withsmooth outer surface, slightly lobed with large vessels.

C/S-Homogeneous , yellowish with whitish spots 

• M/E-• Hallmark –neoplastic ganglion cells that are identified by:

– Loss of cyto-architectural organization– Abnormal (subcortical) localization– Clustering– Large neurons (cytomegaly)– Coarse peripherally aggregated Nissl substance– Bi- or multinucleated neurons with prominent nucleoli

Poorly differentiated tumor

• Medulloblastoma-• Most common childhood tumor• (#2 after pilocytic astrocytoma of cerebellum)• Grade- IV of IV• Arise from cerebellum & projects into 4th ventricle• May grow rapidly and cause hydrocephalus,• 5% metastasize , commonly to bone• 5 year survival is 75% with surgery/radiation• Highly malignant

• Classification (WHO)

• Gross• Well circumscribed, gray-pink, soft/friable. 

well-circumscribedsoft, fleshy tumor with areas of softening & necrosisin the center.

• M/E-• Highly cellular • sheets of anaplastic cells with scanty cytoplasm,• hyperchromatic nuclei, that are often elongated & cresent shaped• Mitoses- abundant• Occasional Homer-Wright rosettes

• Homer-Wright rosettes (groups of tumor cells arranged in a circle around a fibrillary center). Similar rosettes are seen in adrenal neuroblastoma.

• Positive stains• NSE, synaptophysin• Focal GFAP• Molecular / cytogenetics description• Isochromosome (17q) or 17p-• 5-30% overexpress c-myc or N-myc;• C-myc overexpression is associated with poor prognosis 

• Differential diagnosis• Lymphoma: diffusely infiltrates CNS until it mixes with normal and reactive

fibrillar cells

• PNET• Ependymoma

• Desmoplasmic/nodular medulloblastoma•  nodular b/c of its architecture • desmoplastic because it is permeated by (reticulin) fibers that give it a firm

consistency• M/E-

• round pale nodules of tumor separated by zones of darker tumor cells. The pale nodules are composed uniform round to spindle shaped neuronal-appearing cells which are not as active mitotically as the surrounding darker tumor

• Higher magnification of one the paler tumor nodules showing a population of uniform round to oval cells in apale pink fibrillary background. The cells have a more mature neuronal appearance and are less active mitotically. The surrounding darker tumor cells are more primitive appearing with brisk mitotic activity. Desmoplastic medulloblastoma has a better prognosis than the classic form

• Medulloblastoma with extensive nodularity • M/E-• Low power view numerous pale islands• The nodules are composed of a uniform population of tumor cells. The background

is reticulin-free & rich in neuropil-like tissue. Mitosis is not significantly increased. The cells often show streaming in parallel rows

• Special stain-• Reticulin-rich areas of high cellularity

• Anaplastic Medulloblastoma • M/E-• Highly anaplasticnuclei • with high rate of mitosis & apoptosis. • Primitive looking cellswith nuclear molding.• Some are composed of large cells with rounded vesicular nuclei (i.e. no nuclear molding). • Poor prognosis. 

• Atypical teratoid/ Rhabdoid tumor• Highly malignant• Age- very young age (before 5 yrs of age)• Site-Usually posterior fossa or supratentorial• Very aggressive with poor prognosis ( survival <1 yr after

diagnosis)• Metastasizes throughout CSF• MRI-• Large heterogenous mass

• Gross-• Normal cerebellum is visible on right. The unnecessarily large green arrow on

left points sthows Atypical Teratoid/Rhabdoid Tumor (ATRT). • Large, soft in consistency

• M/E-• Large and pleomorphic rhabdoid cells withabundant eosinophilic cytoplasm • Eccentric round nuclei and prominent nucleolus+mesenchymal cell+Epithelial cell+Small cell• Mitosis, necrosis & dystrophic calcification are common 

• Positive stainsVimentin, EMA, smooth muscle actin & keratin.

• Negative stainsDesmin, Myoglobin

• D/DPNET/medulloblastoma (no rhabdoid cells, no 22q11 deletions, IN1+,

• Chordoma• Ependymoma•  Germ cell tumors

Other parenchymal tumor

• Primary CNS lymphoma• Arise from brain, spinal cord, or leptomeninges without prior or concurrent tumor outside the

CNS• Occurs-•  Immunocompromised patients-include HIV/AIDS (most common),after transplantation• Site- usually supratentorial.• Gross-•  Solitary or multiple and poorly circumscribed with hemorrhage and ncrosis.• M/E-• Perivascular growth of large atypical lymphoid cells. • With continued proliferation, the distribution becomes more diffuse and sheet-like. • Special stain-• Reticulin stain -Hooping

Metastaic tumor

Peripheral nerve sheath tumor

• Arise form cells of peripheral nerve including schwann cells, perineurial cells & fibroblast.

• Include-• Schwannoma• NEUROFIBROMA

• Schwannoma

• Gross• well, circumscribed , encapsulated mass attatched to nerve• C/s-• G/w cystic &xanthomatous changes. 

• M/E-• Biphasic: compact hypercellular Antoni A areas and myxoid hypocellular Antoni B

areas

• Cells , elongate, wavy with tapered ends arranged in fascicle• Nuclear palisading around fibrillary process (Verocay bodies) are often seen in

cellular areas.

• Positive stains•

EMA (capsule), S100 (Schwann cells), calcinurin, laminin, type 4 collagen, vimentin, CD68, GFAP

• Differential diagnosis

• Fibrous histiocytoma• Leiomyoma• Leiomyosarcoma

• NEUROFIBROMA• are peripheral nerve tumors composed of a mixture of Schwann

cells and fibroblasts.• Subtypes

Cutaneous NF: Discrete localized mass Plexiform NF: Growing within & expanding peripheral nerves .

associated with NF1

Cutaneous NF• M/E-• Dermis & s/c fat• Unencapsulated• Interlacing bundles of cells with ovoid-to-spindle, often curved, nuclei• myxoid matrix

non encapsulated proliferation of spindle cells with wavy nuclei, arranged haphazardly in a loose myxoid stroma

• Positive stainsS100, CD34+ (focal), Factor 13a (focal)

• Differential diagnosisMyxoid liposarcoma

Myxoma

• Plexiform NF-• Gross-• Affected nerve is irregularly expanded• Often resembles "bag of worms“

• M/E-• Individual fascicles in a nerve are enlarged due to proliferation of Schwann

cellls and fibroblasts.

showing bundles of nerve fibres arranged in concentric manner with Schwann cells and fibroblasts

• Positive stains• S100 in scattered cells (unlike strong staining in schwannoma)• Perineurial cells are EMA+ in plexiform but not in ordinary neurofibromas

• Differential diagnosisPlexiform schwannoma 

Malignant peripheral nerve sheath tumor (MPNST)

• Highly malignant• Locally aggressive, • Involve medium to large size artery• Recurrence• Gross- poorly defined mass

• M/E-• infiltrates nerve and soft tissue with necrosis• marked hypercellularity with spindle-shaped nuclei with tapered ends, nuclear

pleomorphism and brisk mitotic activity with abnormal forms• Patterns: fibrosarcoma, pleomorphic sarcoma,MFH, Schwann cells, triton

tumor (rhabdomyosarcoma regions) and chondrosarcoma

• Positive stainsp53; variable S100

• Differential diagnosisMetastatic MPNST