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

2. Classification of CNS tumor

3. • Primary tumor-
• Meninges- Meningioma
• Glial cell-
Glioma- Astrocytoma, Oligodendroglioma, Ependymoma
• Embryonal-
Medulloblastoma, Neuroblastoma, Teratoma
• Blood vessel- Angioma, Angiosarcoma
• Others- Epithelial, Pituitary, Pineal gland tumor.
• Secondary tumor-
Common- Breast, Lung, GIT, Melanoma

6. CNS-Tumours
• 70% of childhood CNS tumors arise in posterior fossa
• In adult tumors arise within the cerebral hemispheres above the tentorium.

8. Astrocytoma
• Most Frequent
• Types-Infiltrative & Non infiltrative
• WHO Grade (I – IV)
• Increased cellularity
• Nuclear Pleomorphism
• Mitotic activity
• Endothelial proliferation
• Necrosis - palisading

10. • Pilocytic astrocytoma
• WHO grade- I/IV
• Most common CNS neoplasm of childhood
• Relatively benign
• Sites
• Commonly cerebellum
• MRI-
• mural nodule (arrow),
cyst wall enhancement (arrowheads).

11. Gross-
Partially cystic pilocytic astrocytoma of the cerebellum.
The tumor forms a typical mural nodule.

12. • M/E-
• Elongated Bipolar cells
( elongated hair like
processes)
• Rosenthal fibers with
eosinophilic protein droplets
• mural nodule may be
highly vascular; often
calcifications
• Vascular changes are
common –
glomeruloid vascular
proliferation and vascular
hyalinization

14. • Rosenthal fibers-
tapered corkscrew-shaped,
brightly eosinophilic, hyaline
masses

15. • Positive stains
• GFAP (strong), PTAH, PAS (protein droplets), alpha-1-antichymotrypsin (protein
droplets)
• Neoplastic astrocytes have intermediate cytoplasmic filaments. These filaments, has protein-glial
fibrillary acidic protein (GFAP), can be detected by I/H/C
• GFAP- positive

16. • D/D-
• Diffuse astrocytoma-Age 30-40, site-cerebral hemisphere, Diffuse infiltration,
No vascular proliferation
• Gliosis-Hypertrophy & hyperplasia of astrocytes
• Pleomorphic xanthoastrocytoma cyst-mural nodule architecture
• Piloid gliosis: hypocellular, no spongy areas, numerous Rosenthal fibers

17. • Pleomorphic xanthoastrocytoma
• WHO grade II
• Occurs in temporal lobes of children and young adults
• Gross
• Usually cystic
• M/E-
• Pleomorphic cells (occasional xanthomatous change),
• Perivascular lymphocytic cuffing, scattered eosinophilic granular bodies,
reticulin rich network
• No necrosis and no mitosis.

18. Pleomorphic xanthoastrocytoma. Xanthic cells, expressed as
vacuolization of the neoplastic cells, are shown (arrow).

19. • Positive stains
• GFAP and S100
• Reticulin, class III beta tubulin (73%)
• Variable expression of neuronal markers including synaptophysin

20. • D/D-
• Glioblastoma and giant cell glioblastoma
• Malignant fibrous histiocytoma
• Other cystic lesions, especially those with a cyst-mural nodule
architecture (pilocytic astrocytoma and ganglioglioma

21. Infiltrative astrocytoma
• Site-
Infiltrative astrocytomas are usually found in the cerebral
hemispheres,
• Age-
most common in patients between 30 and 60.
• Presentation-
Patients most commonly present with seizures, headaches, and
focal neurologic deficits (depending on where the tumor is).

22. Infiltrating astrocytoma
Grade-II/IV
Diffuse
astrocytoma
Grade-III/IV
Anaplastic
astrocytoma
Grade-IV/IV
Glioblastoma

23. • Diffuse astrocytoma
• Most common adult tumor.
• 80% of adult primary brain tumors
• Location: Usually supratentorial
• Age-4th to 6th decades
• MRI-
• Ill defined, non enhancing lesion with mass effect and variable peritumoral
edema.

24. • Gross-
Poorly defined infiltrative
tumor that distorts
the brain.
C/S-
Firm / soft & gelatinous, Cystic degeneration

25. • M/E-
• Mild to moderate glial
cellularity
• Variable nuclear
pleomorphism
• Fibrillary background
due to astrocytic process

26. Diffuse astrocytoma characterized by modest hypercellularity,
nuclear pleomorphism, and numerous small microcysts

27. • Special stain-
• GFAP-positive astrocytic cell processes

28. • Anaplastic astrocytoma
• Grading: WHO grade III/IV
● Age and sex: mean age 45 years; male predominance
● Site: usually supratentorial, but can be anywhere in CNS;
● MRI:
• Usually heterogeneous or
patchy enhancement

29. Gross-
Anaplastic astrocytoma
predominantly
occupying the right temporal lobe.
The tumour is ill-defined and
appears as a homogeneous mass.
Note the large cyst in the periphery
of the neoplasm and shift of
midline structures
towards the left hemisphere.

30. This astrocytoma
had densely cellular
areas with back-to-
back nuclei,
moderate nuclear
pleomorphism, and
increased mitotic
activity. However,
necrosis or
endothelial
proliferation - the
two hallmarks of
Glioblastoma - were
absent.

31. • M/E-
• Increase in cellularity
• Nuclear pleomorphism
• Hyperchromasia
• May have mitosis
• No necrosis

32. • D/D-
● Anaplastic oligodendroglioma:
• hypercellular with loosely cohesive and single cells, moderate
pleomorphism, vacuolated background, mitotic activity
● Anaplastic oligoastrocytoma:
• conspicuous oligodendroglioma and astrocytoma components
• Glioblastoma

33. • Anaplastic astrocytoma Glioblastoma
• Increase in cellularity Dense cellularity
• Nuclear pleomorphism
• Hyperchromasia
• May have mitosis Mitosis
• No necrosis Necrosis & vascular proliferation

34. Gemistocytic astrocytoma
Dense eosinophilic cytoplasm & eccentrically
displaced nucleus.
Gemistocytes are frequently
found in other fibrillary
astrocytomas &
oligodendrogliomas. Some
authors require at 20% of
tumor cells to be gemistocytic
before using the designation of
gemistocytic astrocytoma.
This tumor appears to be
composed of an almost
pure population of gemistocytic cells.

35. • Positive stains
• GFAP,
• Vimentin

36. • D/D-
• Gliosis:
• Hypertrophy of cells rather than hyperplasia, even distribution
• Subependymal giant cell tumor: intraventricular, larger nuclei,
non-infiltrative
• Ganglioglioma: neoplastic neurons

37. • Glioblastoma
• WHO grade IV
• "Multiforme" due to variegated gross appearance (firm white areas, yellow necrotic
areas, hemorrhagic areas and cystic areas) as well as diverse histological features
• Sites
• Usually supratentorial;
• Either primary (de novo, with with p53 mutation) or secondary (transformed from
grade II/III astrocytoma)
• MRI
• Contrast enhancing (ring pattern),
• large surrounded by peritumoral edema.
• (parietal lobe)

38. • Gross-
glioblastoma is a poorly defined
intra-axial mass with variegated
(multiform) appearance due to
necrosis and hemorrhage.
• A 9.0 cm tumor with foci of
hemorrhage and necrosis
involving the left temporal lobe.

39. • M/E-

40. • M/E-
• Densely cellular with nuclear
pleomorphism
• Necrosis in a serpentine pattern
• Tumour cells crowded along the
edges of necrosis - pseudopalisading
• When vascular cell proliferation
is extreme, the tuft forms a ball-like
structure, the glomeruloid body

41. • Besides necrosis with nuclear pseudopalisading, the presence of endothelial
proliferation is another histologic hallmark of glioblastomas.

42. • Positive stains
• GFAP, vimentin, S100, AE1-AE3 (>95%)
• Differential diagnosis
• Lymphoma: angiocentric and angioinvasive patterns, no fibrillary
background, CD45+
• Meningioma, malignant: EMA+, may contain entrapped GFAP+
glia
• Metastatic carcinoma: discrete, no fibrillary background, GFAP-,
CAM5.2+

43. • Giant cell glioblastoma (IV/IV)
• M/E-
• Abundant bizzare appearing
tumor giant cell, many MNG cell
• Extensive necrosis, mitosis

44. • Gliomatosis Cerebri-
• WHO Grade- III/IV
• Neoplastic astrocyte infiltrates
• the multiple region of brain or
• in some cases the entire brain .
• H/P-
• Largely composed of elongated,
hyperchromatic glial cells
Mitosis.
No necrosis or
microvascular proliferation

45. Prognosis
Diffuse
Astrocytoma
(G-II/IV)
Anaplastic
Astrocytoma
(G-III/IV)
Glioblastoma
(G-IV/IV)

46. Oligodendroglioma
• WHO grade- II/IV
• Gross
• well-circumscribed, gelatinous,
gray masses, often with cysts,
focal hemorrhage,
& calcification

47. • M/E-
• Sheets of regular cells with
spherical nuclei & perinuclear halo
(fried egg)
(perinuclear halo artifact due to fixation,
and is not present in frozen sections)
• Calcifications-90% cases,
• Arborizing thin capillaries
• (chicken
wire pattern)

49. • Positive stains
OLIG2, Leu7, S100, MAP2 (strong)
• D/D-
• Clear cell ependymoma: enhancing, well-circumscribed, perivascualr
pseudorosettes, dot- or ring-like EMA+
• Clear cell meningioma: extra-axial, enhancing, PAS+, EMA+
• Metastatic clear cell carcinoma: enhancing, well-circumscribed,
EMA+, CK+; molecular testing for 1p/19q deletion may be helpful, but some
oligodendrogliomas are negative for the deletion
• Pituitary adenomas: chromogranin+, pituitary hormone+

50. • Anaplastic oligodendroglioma
• WHO grade -III/IV
• M/E-
• Increased cellular density
• Nuclear atypia
• Mitosis
• Necrosis

51. • D/D-
Metastatic carcinoma:
• Renal cell carcinoma is EMA+,
• usually no calcifications

52. Ependymoma
• Slowly growing tumor of ependymal cells arising from walls of
ventricles or spinal canal
• Grade II/!V
• MRI-
• Well circumscribed lesions
with variable enhancement

53. • Gross-
• Typically solid or papillary
masses extending from
4th ventricle

54. • M/E-
• Tumor cells resemble normal ependymal cells with round to oval nuclei &
abundant granular chromatin.
• Rosette &
Perivascular pseudorosette
• Fig- Ependtmoma with true rosette

55. • True rosette
• Pseudorosette--------------

56. • D/D-
Glioma:
• no true rosettes,
• no cell-cell junctions,
• no intracytoplasmic microvilli-lined lumina

57. Anaplastic Ependymoma
• Grade- III /IV
• Rare; usually infants and children
• Cerebrum/ cerebellum of children / young adults, but all ages and locations
• M/E-
Marked hypercellularity,
nuclear atypia
high mitosis &
necrosis

58. Myxopapillary ependymoma
• Grade - I / IV
• M/E-
• Well differentiated Cuboidal to elongated tumor cells arranged around the
papillary cores with a myxopapillary appearance.
• Usually no atypia,
• no/low mitotic activity

59. MOLECULAR CHANGES IN ASTROCYTOMA-GLIOBLASTOMA
• Isocitrate dehydrogenase (IDH)
• IDH is a citric acid cycle enzyme that catalyzes that convert isocitrate to a-
ketoglutarate.
• IDH1 and IDH2 are frequently mutated in gliomas.
• IDH1 mutated in 70-80% of grade II and III astrocytomas,
oligodendrogliomas, oligoastrocytomas, & in secondary but not primary
glioblastomas.
• IDH2 mutations are more common in oligodendrogliomas
• Detection of IDH1 mutations by I/H/C is an important tool in the diagnosis of
gliomas.

60. • Tumor Protein 53 (TP53)
• It repairs DNA damage and induces apoptosis when damage
cannot be repaired. Its mutation promotes tumor formation
• TP53mutations  common in diffuse astrocytoma, anaplastic
astrocytoma, and secondary glioblastoma, and help distinguish
glioma from gliosis.
• Mutations can be detected by I/H/C  shows strong nuclear
staining for p53.

61. • Epidermal Growth Factor Receptor (EGFR)
Overexpression of EGFR, on 7p, occurs in 40 % of glioblastomas
(more commonly primary ones) and less frequently in lower
grade astrocytomas .