This document discusses various tumors of the central nervous system (CNS). It provides details on: - The classification and incidence of different CNS tumors. Primary CNS tumors account for 20% of childhood cancers, with 70% occurring in the posterior fossa. - The molecular genetics and morphology of common tumor types, including gliomas, astrocytomas, oligodendrogliomas, ependymomas, and medulloblastomas. Factors like location, growth patterns, and genetic mutations influence tumor behavior. - The clinical features and prognosis of different tumor types. More malignant tumors are associated with worse outcomes, though treatments like surgery and radiation can improve survival for some tumors. Location within the

1. Tumors of CNS
Dr. Arpit Gohel
Assistant professor

2. • The annual incidence of intracranial CNS
tumors is 10 to 17 per 100,000 population;
• The intraspinal tumor incidence is 1 to 2 per
100,000.
• Primary CNS tumors account for 20% of all
childhood cancers; 70% of these arise in the
posterior fossa.
• In adults 70% of CNS tumors occur above the
tentorium.

3. Classification of intracranial tumours

4. Classification of intracranial tumours

5. Classification of intracranial tumours

6. Classification of CNS tumours
according to presumed cell of origin

7. Relative incidence of primary CNS
neoplasms

8. Outcomes of CNS tumors
• Consequences of location: Resectability of CNS
tumors is by functional anatomic considerations;
thus even benign lesions can have lethal
consequences due to the location.
• Patterns of growth: Most glial tumors, including
many with histologic features of a benign
neoplasm, infiltrate extensively leading to
clinically malignant behavior.
• Patterns of spread: Tumors can spread through
the CSF; however, even the most malignant
gliomas rarely metastasize outside the CNS.

9. The anatomic distribution of common intracranial tumours.

10. various non-specific clinicopathological
effects of a tumour within the skull

11. Gliomas
• Most common group of primary brain tumors;
• Include astrocytomas, oligodendrogliomas, and
ependymomas.
• All have characteristic histologic features but
derive from a progenitor cell that differentiates
along a particular cellular lineage rather than
their respective mature cell types.
• The tumors have typical anatomic localizations,
age distributions, and clinical courses.

12. Astrocytoma
• Infiltrating Astrocytomas
• account for 80% of adult primary brain
tumors; typically arising between ages 30 and
60, most occur in the cerebral hemispheres.
• Patients typically present with seizures,
headaches, and focal neurologic deficits
related to the anatomic site of involvement.

13. Astrocytoma
• Infiltrating Astrocytomas
• Tumors range from diffuse astrocytoma (grade II/IV) to
anaplastic astrocytoma (grade III/IV) to glioblastoma
(grade IV/IV);
• There are no World Health Organization (WHO) grade I
infiltrating astrocytomas.
• Glioblastoma tends to occur as either a new-onset
disease in older individuals (primary glioblastoma) or
progression in younger patients from a lower-grade
astrocytoma (secondary glioblastoma).

14. Molecular Genetics
• A common theme in these tumors is sustained
proliferative signaling and evasion of growth
suppressors.
• There are four molecular subtypes:
– Classic subtype
– Proneural type
– Neural type
– Mesenchymal type

15. • Classic subtype (majority of primary
glioblastomas) has mutations of the PTEN
tumor suppressor gene, deletions of
chromosome 10, and amplification of the
EGFR oncogene; hemizygous deletions of the
CDKN2A tumor suppressor gene are also
common, affecting the activity of RB and p53.

16. • Proneural type, the most common type
associated with secondary glioblastoma, is
characterized by mutations of TP53, and point
mutations in the isocitrate dehydrogenase genes,
IDH1 and IDH2, often with an overexpression of
the receptor for platelet-derived growth factor
receptor α (PDGFRA).
• IDH1 mutations create a new enzyme activity that
generates 2-hydroxyglutarate, which drives
oncogenesis by inhibiting enzymes that regulate
DNA methylation.

17. • Neural type is characterized by higher levels
of expression of neuronal markers, including
NEFL, GABRA1, SYT1, and SLC12A5.

18. • Mesenchymal type is characterized by
deletions of the NF1 gene on chromosome 17
and lower expression of the NF1 protein;
genes involved in the TNF and NF-κB pathways
are also highly expressed.

19. • Among the WHO grades III and IV
astrocytomas, mutant IDH1 has a significantly
better outcome than wild type.

20. Morphology of Infiltrating
Astrocytomas
• Histologic differentiation (WHO grades II to IV)
correlates well with the clinical course:
– Diffuse astrocytomas (grade II)
– Anaplastic astrocytomas (grade III)
– Glioblastomas (grade IV; previously called
glioblastoma multiforme [GBM])

21. Diffuse astrocytomas (grade II)
• Poorly defined, gray-white, infiltrative tumors
that expand and distort a region of the brain;
• They show hypercellularity and some nuclear
pleomorphism, and the transition from
normal to neoplastic is indistinct.

22. Diffuse astrocytoma
On coronal section at autopsy, the left frontal white matter is expanded, and there is
blurring of the corticomedullary junction due to infiltrative tumor (circled region).

23. Diffuse astrocytoma
This histologic section from the white matter shows enlarged, irregular,
hyperchromatic nuclei that appear embedded within the native fibrillary matrix of
the brain; the smaller round and oval nuclei are native oligodendrocytes and reactive
astrocytes, respectively. Inset, An immunostain for IDH1 R132H is positive for mutant
protein in tumor cells, some of which surround the larger immunonegative cortical
neurons (“perineuronal satellitosis”).

24. Anaplastic astrocytomas (grade III)
• Exhibit increased nuclear anaplasia with
numerous mitoses.

25. Glioblastomas (grade IV; previously called
glioblastoma multiforme [GBM])
• Composed of a mixture of firm white areas,
softer yellow foci of necrosis, cystic change,
and hemorrhage;
• There is also increased vascularity.
• Increased tumor cell density along the
necrotic edges is termed pseudopalisading.

26. Glioblastoma
Contrast T1-weighted coronal magnetic resonance image shows a large mass in the
right temporal lobe with “ring” enhancement.

27. Glioblastoma
Glioblastoma appearing as a necrotic, hemorrhagic, infiltrating mass

28. Glioblastoma
Glioblastoma. Serpiginous foci of palisading necrosis (tumor nuclei lined up around
the red anucleate zones of necrosis). Inset, Microvascular proliferation.

29. Clinical Features of infiltrating
astrocytoma
• Patients typically present with focal neurologic
deficits, headaches, or seizures, attributable
to mass effects and/or cerebral edema;
• high-grade lesions have leaky vessels that
exhibit contrast enhancement on imaging.
• The prognosis for glioblastoma is poor;
despite resection and chemotherapy, mean
survival is only 15 months and only 25% are
alive at 2 years.

30. Pilocytic Astrocytoma
• Occurs in children and young adults,
• Usually in the cerebellum but also in the floor
and walls of the third ventricle, the optic nerves,
and occasionally the cerebral hemispheres;
• They are WHO grade I/IV.
• These tumors have a relatively benign behavior;
they grow slowly and are rarely infiltrative.
• They rarely exhibit p53 mutations or other
genetic changes associated with more aggressive
astrocytomas but do often show alterations in
the BRAF signaling pathway.

31. Morphology of Pilocytic astrocytoma
• Gross:
• Lesions are often cystic with a mural nodule in
the wall of the cyst.

32. Pilocytic astrocytoma
Grossly, this cerebellar tumor forms a mural nodule within a cyst.

33. Morphology of Pilocytic astrocytoma
• Microscopic:
• Tumors are composed of bipolar cells with
long, thin hairlike processes; Rosenthal fibers
and microcysts are often present.
• There is a narrow infiltrative border with the
surrounding brain.

34. Pilocytic astrocytoma
(B) At low magnification, one can appreciate atrophic cerebellar cortex (top), sharp
circumscription, and a biphasic pattern with alternating loose (middle) and compact
(bottom) regions of tumor growth.
(C) Higher magnification reveals oval to irregular tumor nuclei resembling those of
diffuse astrocytoma, but with numerous Rosenthal fibers (brightly eosinophilic
corkscrew-shaped inclusions) in the background.

35. Pleomorphic Xanthoastrocytomas
• Typically occur in the temporal lobes of young
patients, often with a history of seizures.
• The tumor (usually WHO grade II/IV) exhibits
neoplastic, occasionally bizarre astrocytes,
abundant reticulin and lipid deposits, and
chronic inflammatory cell infiltrates;
• 5-year survival nears 80%.

36. Brainstem Glioma
• occurs mostly in the first two decades of life.
• Their course depends on location, with pontine
gliomas (most common) having an aggressive
course, tectal gliomas with a relatively benign
course, and corticomedullary junction tumors
somewhere intermediate.
• These tumors often have a specific histone
mutation affecting acetylation and methylation
events that influence chromatin structure and
gene expression.

37. Oligodendrogliomas
• Constitute 5% to 15% of gliomas and are most
common in middle life.
• The most common genetic alterations involve
mutations of IDH1 and IDH2; loss of
heterozygosity (LOH) in chromosomes 1p and
19q occurs in 80% of cases, and additional
mutations (e.g., CDKN2A) accrue in more
anaplastic lesions.

38. Morphology of Oligodendroglioma
• Gross:
• Tumors have a white matter predilection; they
are wellcircumscribed, gelatinous, gray
masses, often with cysts, focal hemorrhage,
and calcification.

39. Morphology of Oligodendroglioma
• Microscopic:
• Tumors consist of sheets of regular cells with
round nuclei containing finely granular
chromatin, often surrounded by a clear halo of
cytoplasm and sitting in a delicate capillary
network.
• Calcification is present in 90% and ranges from
microscopic to massive.

40. Oligodendroglioma
Tumor nuclei are round, with cleared cytoplasm forming “halos” and vasculature
composed of thin-walled capillaries. Similar to diffuse astrocytoma (see Fig. 28.46B),
tumor cells are usually positive for IDH1 R132H–mutant protein (inset).

41. Clinical Features of
Oligodendroglioma
• Prognosis is typically better than for
astrocytomas, and current therapies yield an
average 5- to 10-year survival.
• Progression from low- to high-grade lesions
can occur, typically over approximately 6
years.

42. Ependymomas and Related
Paraventricular Mass Lesions
• Arising from the ependymal lining.
• In the first two decades of life, the fourth
ventricle is the most common site;
• the spinal cord central canal is a common
location in middle age and in NF2, where the
NF2 gene is mutated.

43. Morphology of Ependymoma
• Gross:
• Tumors are moderately well-demarcated solid
or papillary lesions.

44. Ependymoma
Tumor of the fourth ventricle, distorting, compressing, and infiltrating
surrounding structures

45. Morphology of Ependymoma
• Microscopic:
• Lesions have regular, round-oval nuclei with
abundant granular chromatin; they can form
elongated ependymal canals or perivascular
pseudorosettes.
• Most are WHO grade II/IV; anaplastic lesions
(grade III/IV) exhibit greater cell density,
mitoses, and necrosis with less evident
ependymal differentiation.

46. Ependymoma
The microscopic appearance includes both true rosettes (with a glandlike central
lumen) and perivascular pseudorosettes (nuclear-free zone composed of fibrillary
processes radiating toward a central blood vessel).

47. Myxopapillary ependymomas
• Distinct but related lesions arising in the filum
terminale of the spinal cord.
• Cuboidal cells, sometimes with clear
cytoplasm, are arranged around papillary
cores; myxoid areas contain neutral and acidic
mucopolysaccharides.

48. Clinical Features of Ependymoma
• Posterior fossa ependymomas often present
with hydrocephalus;
• CSF dissemination is common, and 5-year
survival is only 50%.
• Spinal cord lesions usually do better.

49. Related Paraventricular Mass Lesions
• Subependymomas
• Choroid plexus papillomas
• Colloid cysts of the third ventricle

50. Poorly Differentiated Neoplasms
• Some neuroectodermal tumors express few
mature phenotypic markers and are described
as poorly differentiated or embryonal.
• Medulloblastomas
• Atypical Teratoid-Rhabdoid Tumor

51. Medulloblastomas
• Account for 20% of childhood brain tumors;
• They occur exclusively in the cerebellum.
• Medulloblastoma can be divided into four genetic
groups:
– WNT type (WNT signaling pathway mutations)
– SHH type (sonic hedgehog signaling pathway
mutations)
– Group 3 (MYC amplification and isochromosome 17)
– Group 4 (isochromosome 17 without MYC
amplification, but sometimes with MYCN
amplification)

52. Morphology of Medulloblastoma
• Gross:
• Tumors are well circumscribed, gray, and
friable.

53. Medulloblastoma
Sagittal section of brain showing medulloblastoma replacing part of the superior
cerebellar vermis.

54. Morphology of Medulloblastoma
• Microscopic:
• Lesions are usually extremely cellular, with sheets
of anaplastic cells exhibiting hyperchromatic
nuclei and abundant mitoses;
• cells have little cytoplasm and are often devoid of
specific markers of differentiation,
• although glial and neuronal features (e.g.,
Homer-Wright rosettes) can occur.
• Extension into the subarachnoid space can elicit
prominent desmoplasia.

55. Medulloblastoma
The microscopic appearance of classic medulloblastoma includes primitive
appearing “small blue cells” that form sheets and Homer Wright (neuroblastic)
rosettes with central neuropil.

56. Medulloblastoma
The desmoplastic/nodular variant includes reticulin-rich internodular zones with
more primitive appearing cells and “pale nodules” representing centers of partial
neuronal differentiation; this variant is nearly always the SHH-activated molecular
subtype.

57. Medulloblastoma
The large cell/anaplastic variant features increased cell size, large cherry red
nucleoli, and cell wrapping (wherein tumor cells wrap around one another or
surround pyknotic nuclei of dying tumor cells).

58. Clinical Features of medulloblastoma
• Tumors tend to be midline in children and in
lateral locations in adults.
• Rapid growth can occlude CSF flow, leading to
hydrocephalus; CSF dissemination is common.
• The tumor is highly malignant, and if
untreated, the prognosis is dismal.
• However, it is exquisitely radiosensitive, and
with excision and radiation, the 5- year
survival rate is 75%.

59. Atypical Teratoid-Rhabdoid Tumor
• highly malignant tumor of the posterior fossa and
supratentorium of young children;
• Survival is usually <1 year.
• Chromosome 22 deletions occur in >90%; the
relevant gene is hSNF5/INI1, encoding a protein
involved in chromatin remodeling.
• These are large, soft tumors that spread over the
brain surface; they are highly mitotic lesions
histologically characterized by rhabdoid cells,
resembling those seen in rhabdomyosarcoma.

60. Other Parenchymal Tumors
• Primary Central Nervous System Lymphoma
• Germ Cell Tumors
• Pineal Parenchymal Tumors

61. Meningiomas
• predominantly benign tumors of adults that arise from
arachnoid meningothelial cells and are attached to the
dura;
• Prior radiation to the head and neck can be a risk factor.
• Often associated with loss of chromosome 22 (especially
the long arm, 22q), leading to deletions of the NF2 gene
encoding the protein merlin, and associated with greater
chromosomal instability.
• In meningiomas with wild-type NF2, TNF-receptor
associated factor 7 (TRAF7) mutations occur with a
tendency toward lower histologic grade and greater
chromosomal stability.

62. Morphology of Meningioma
• Gross:
• Tumors are usually rounded masses with well-
defined dural bases that compress underlying
brain but easily separate from it;
• lesions are usually firm, lack necrosis or
extensive hemorrhage and may be gritty due
to calcified psamomma bodies.

63. Meningioma
Resected meningioma specimen showing rounded contour and dural attachment.

64. Morphology of Meningioma
• Microscopic:
• Several histologic patterns exist (e.g.,
synctytial, fibroblastic, transitional,
psammomatous, secretory, and microcystic)
all with approximately comparable favorable
prognoses (WHO grade I/IV);
• Among these, proliferation index is the best
predictor of biologic behavior.

65. Meningioma
Meningioma with a whorled pattern of cell growth and numerous
psammoma bodies (calcifications with concentric rings).

66. Anaplastic (malignant) meningiomas
(WHO grade III/IV)
• Aggressive tumors that resemble sarcomas;
mitotic rates are high (>20 per 10 high-
powered fields).
• Papillary meningiomas (pleomorphic cells
arranged around fibrovascular cores) and
rhabdoid meningiomas (sheets of cells with
hyaline eosinophilic cytoplasm composed of
intermediate filaments) also have a high
recurrence rate (WHO grade III/IV tumors).

67. Clinical Features of Meningioma
• Typically solitary, slow-growing lesions that
manifest due to CNS compression or with
vague nonlocalizing symptoms; multiple
lesions suggest NF2 mutations.
• They are uncommon in children and have a
slight (3:2) female predominance; they often
express progesterone receptors and can grow
more rapidly during pregnancy.