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1. Pathology of CNS
(Tumor of CNS)
DR Naila Awal
Department of pathology

3. 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

4. • Gross
Solid or cystic
• No hemorrhage or necrosis
• Single rounded mass about 5.5 cm in diameter, with
smooth outer surface, slightly lobed with large vessels.
C/S-
Homogeneous , yellowish with whitish spots

5. • 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

6. 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

7. • Classification (WHO)

8. • Gross
• Well circumscribed, gray-pink, soft/friable.
well-circumscribed
soft, fleshy tumor with
areas of softening & necrosis
in the center.

9. • 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

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

11. • 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

12. • Differential diagnosis
• Lymphoma: diffusely infiltrates CNS until it mixes with normal and reactive
fibrillar cells
• PNET
• Ependymoma

13. • 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-

14. • 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

15. • 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

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

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

18. • 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

19. • 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

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

21. • Positive stains
Vimentin, EMA, smooth muscle actin & keratin.
• Negative stains
Desmin, Myoglobin
• D/D
PNET/medulloblastoma (no rhabdoid cells, no 22q11 deletions, IN1+,
• Chordoma
• Ependymoma
• Germ cell tumors

22. 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

23. Metastaic tumor

24. Peripheral nerve sheath tumor
• Arise form cells of peripheral nerve including schwann cells,
perineurial cells & fibroblast.
• Include-
• Schwannoma
• NEUROFIBROMA

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

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

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

28. • Positive stains
•
EMA (capsule), S100 (Schwann cells),
calcinurin, laminin, type 4 collagen, vimentin, CD68, GFAP
• Differential diagnosis
• Fibrous histiocytoma
• Leiomyoma
• Leiomyosarcoma

29. • 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

30. 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

31. • Positive stains
S100, CD34+ (focal), Factor 13a (focal)
• Differential diagnosis
Myxoid liposarcoma
Myxoma

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

33. • 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

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

35. Malignant peripheral nerve sheath tumor (MPNST)
• Highly malignant
• Locally aggressive,
• Involve medium to large size artery
• Recurrence
• Gross- poorly defined mass

36. • 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

37. • Positive stains
p53; variable S100
• Differential diagnosis
Metastatic MPNST