from WHO of CNS

1. Meninges and related
tumors
Dr. Bahoran Singh

2. Meninges

3. Protection of the Brain: The Cranial Meninges
•Cranium is covered with protective membranes =
meninges
–Cranial meninges are continuous with spinal
meninges
–3 layers: 1. outer, fibrous dura mater – forms sheets
(falx) that separate the cerebrum and the
cerebellum into the hemispheres and the cerebellum
from the cerebrum
–comprised of an outer endosteal layer and and
inner meningeal layer
2. middle arachnoid mater – avascular layer
-named for the spider-like struts (trabeculae)
that connect the arachnoid to the underlying pia
mater
3. inner, thin pia mater – vascular connective tissue
-makes direct contact with brain tissue
-cells of the pia mater are impermeable to the
passage of many substances
-this membrane is pierced by tiny capillaries
that nourish the brain tissue – arise from the larger
capillaries that travel within the dura mater

4. Dural Extensions
 Dural Extensions
 Falx Cerebri
 The largest dural reflection
 Location:
 Extends longitudinally in the
interhemispheric fissure
 Between the two hemisphere
 Forms a vertical partition in the cranial
cavity between two cerebral
hemispheres
 Cavity Formations:
 Dorsal edge of the interhemispheric
fissure
 Forms the cavity for the Superior
Sagittal Sinus
 Inferiorly within this fissure above the
corpus callosum
 Inferior Sagittal Sinus is along the free
inferior margin of the falx cerebri

5. Meningeal tumors
 Primary Meningeal Neoplasms
 • Meningioma (arachnoid cap cell):
 Meningioma (typical and metaplastic)
 Atypical Meningioma
 Anaplastic (Malignant) Meningioma
 Papillary Meningioma
 • Mesenchymal (non-meningothelial)
 • Primary Melanocytic Lesions
 • Uncertain Origin
 Hemangiopericytoma (pericyte)
 Hemangioblastoma (mesenchyme)Meningioma-

6. Meningiomas
 Meningiomas are the most common extra-axial tumours in adults and most
common non-glial tumour of the central nervous system.
 Meningiomas are primary neoplasms of the central nervous system (CNS),
believed to arise from arachnoidal (meningothelial) cells concentrated at the
apex of arachnoid granulations and line the inner dura mater.
 Incidence
 20% of all intracranial neoplasms and 25% of all spinal neoplasm.
 More common in women and the peak age is 50 to 60 years.
 Spinal meningioma shows marked predominance in female.
 Most meningiomas have “typical imaging”
 Hemispheric, homogeneous, broad based on the dura, hyperostosis, hormonally
sensitive
 Normally solitary may be multiple in <10% of case.
 Multiple meningiomas are associated with hereditary conditions such as
neurofibromatosis type 2, but can also be sporadic.

7.  Common locations- 90% of meningiomas are supratentorial.
 parasagittal or convexity locations (50%)
 sphenoid wing(20%)
 olfactory groove/planum sphenoidale(10%)
 the parasellar regions (10%).
 Most spinal meningioma occur in thoracic region
 Clinical features:
 Depends on the site and subsequent pressure effects and focal deficit.
 Asymptomatic ( slow growing)
 Seizures and headache

8.  Meningioma - Etiologic Factors
 • Trauma
 • Radiation
 • Viruses
 • Familial (Non-NF2) Meningioma
 • Neurofibromatosis – Type – 2
 Meningioma - Radiation
 • Low Dose (<800 cGray)
 Tinea Capitis (ringworm)
 High Incidence of Meningioma
 • High Dose (>2000 cGray = 2000 RADS)
 Used for Skull Base Tumors
 Pituitary Adenoma

9. Genetic model of meningioma tumourigenesis
and malignant progression
 Benign meningioma-
 Chromosome 22 deletion(40-70%)
 NF2 mutation(30-60%)
 Loss of 4.1B expression (30-50%)
 PR expression (50-90%)
 EGFR, PDGFRB activation
 Atypical meningioma
 -1p (40-75%)
 -6p (30%)
 -10q (30-40%)
 -14q (40-60%)
 -18q (40%)
 Loss of TSLC1 expression (70%)
 Loss of PR expression (60-80%)
 Telomerase/ hTERT activation (60- 95%)

10.  Anaplastic meningioma
 -1p (70-100%)
 -6p ( 50%)
 -9p21 ( 60-80%)
 -10 ( 40-70%)
 -14q ( 60-100%)
 18q ( 60-70%)
 NDRG2 hypermethylation ( 70%)
 Loss of TSLC1 expression (70%)
 Loss of PR expression (80-90%)

11.  Macroscopy
 Most meningiomas are rubbery or firm, well-demarcated or lobulated,
rounded mass with broad dural attachment.
 Invasion of underlying dura or of dural sinuses is common.
 Meningiomas may attach to or encase cerebral arteries, but only rarely do
they infiltrate arterial walls.

12. Macroscopic features of meningioma. A Large parasaggital
meningioma compressing the adjacent parietal lobe. B Meningioma
of the medial sphenoid wing encasing the carotid artery. C Large
meningioma of the lateral ventricles and the third ventricle. D
Spinal meningioma compressing the spinal cord.

13. Subtypes of meningioma

14. Grade- I meningioma
 There are nine subtypes of meningioma classified as Grade I (benign).
 Account for over 90% of all meningiomas.
 <4 mitoses per 10 hpf
 No invasion to brain
 And will have no more than two (and usually none) of the following
 Increased cellularity
 Foci of small neoplastic cells with a high nuclear: cytoplasmic ratio
 Prominent nucleoli
 Sheet-like growth pattern
 Foci of 'geographic' necrosis

15. 1. Meningothelial Meningioma (
syncytial/endothelial)
 It is classic and common variant
 Tumour cells form lobules, some partly demarcated by thin collagenous
septae.
 Tumor cells are largely uniform, with oval nuclei with delicate chromatin that
on occasion show central clearing or the formulation of cytoplasmic-nuclear
inclusions.
 Whorls and psammoma bodies are not common.
 Within the lobules, tumour cells appear to form a syncytium as delicate cell
processes can not be discerned at light microscopy.
 Differential diagnosis
 It occasionally appears epithelioid and simulate ependymoma but it lack GFAP.
 Oligodendroglioma- EMA reactivity identifies meningioma.

16. A. Its indistinct cellular boundaries and syncytial appearance. nuclei are round to oval
with smooth membranes, finely stippled chromatin, and small nucleoli.
B. Nests of meningioma cells are highlighted by their brown nuclei stained for
progesterone receptors (PR). Vascular septae that segregate these nests are negative
for PR.

17. 2. Fibrous (fibroblastic) meningioma
 consists of spindle cells forming parallel, storiform and interlacing bundles in
a collagen-rich matrix.
 Whorl formation and psammoma bodies are infrequent.
 Tumour cells form wide fascicles, with varying amounts of intercellular
collagen.
 Focally show nuclear features characteristic of meningothelial meningioma.
 It often have thick bundles of collagen with in parenchyma
 It may be confused with Schwannoma, fibrillary astrocytoma , and pilocytic
astrocytoma.
 It express EMA that differentiate from Schwannoma and pilocytic
astrocytoma.

18. A. Fibroblastic meningioma- bosselated surface of
multiple tan nodules separated by fibrous tissue.
Fibroblastic meningioma (A) The tumor has elongated cells and nuclei
that resemble a schwannoma. (B) Epithelial membrane antigen
expression confirms meningioma

19. 3. Transitional (mixed) meningioma
 It composed of syncytial and fibroblastic components.
 Vaguely lobular and fascicular arrangements often appear side by side.
 Prominent whorls, psammoma bodies, and clusters of syncytial cells make
easily identify on H & E.
Transitional meningioma. S-100 protein is only focally present in this
cerebellopontine angle transitional meningioma with lipoid metaplasia and
whorls.

20. 4. Psammomatous meningioma
 It contains predominance of psammoma bodies over that of the tumour cells.
 The neoplastic cells usually have a transitional appearance with whorl
formation.
 characteristically occur in the thoracic spinal region and usually in middle-
aged women.

21. 5. Angiomatous meningioma
 Predominance of blood vessels over that of the tumour cells.
 The vascular channels may be small- or medium-sized, thin walled or thick
 Most are small with markedly hyalinized walls.
 Moderate to marked degenerative nuclear atypia is common majority are
benign.
 Differential diagnosis
 Vascular malformation and hemangioblastoma, depending on the prominence
of vessels and occasionally.
 Unlike hemangioblastoma, most of these meningiomas contain meningothelial
cells concentrically wrapped around small blood vessels and capillaries.
 Confirmation on positive staining for EMA/ PR
 Hemangioblastoma is positive for NSE/ or EGFR.

22. In the angiomatous meningioma, hyalinized blood vessels are
admixed with small nests of meningothelial cells in syncytial
arrangements

23. 6. Microcystic meningioma
 This is characterized by cells with thin, elongate processes encompassing
microcysts containing pale, eosinophilic mucinous fluid.
 Pleomorphic cells may be numerous but it is benign.
 Accompanying cerebral edema may be seen.
Microcystic meningioma is composed of an admixture of syncytial
and meningothelial patterns with microcystic zones.

24. 7. Secretory meningioma
 It is characterizes by presence of focal epithelial differentiation in the form
of intracellular lumina containing PAS-positive, eosinophilic secretion.
 These structure known as pseudopsammoma bodies.
 This show immunoreactivity to CEA and other epithelial and secretory marker
while the surrounding tumour cells are both CEA and cytokeratinpositive.
 It is associated with blood CEA level, on resection CEA level decreased.
 Mast cells may be numerous.
 Peritumoural edema may be significant

25. Secretory meningioma. Although most meningioma cells are negative, these strikingly
CAM5.2 cytokeratin-positive (A) structures resemble acini. Unlike carcinoma, its
cytologic features are benign and meningothelial. Typically, focal clusters of
immunoreactive cells surround ‘‘secretory’’ globules that are periodic acid-Schiff–
positive (B).

26. 8. Lymphoplasmacyte-rich meningioma
 It is characterised by extensive chronic inflammatory infiltrates often over-
shadowing the inconspicuous meningothelial component.
 Raraest.
 Systemic hematological abnormalities are seen like hyperglobulinemia and
iron refractory anemia.

27. 9. Metaplastic meningioma
 Meningioma with focal or widespread mesenchymal components including
osseous, cartilaginous, lipomatous, myxoid or xanthomatous tissue, singly or
in combinations.
 Intraoperative correlation is needed to distinguish ossified meningioma from
one exhibiting bone invasion.
C. Metaplastic/lipomatous meningioma.
D Metaplastic/xanthomatous meningioma.

28. GRADE II (Atypical) Meningioma
 WHO Grade II includes
 1. Chordoid meningioma, 2. Clear cell meningioma & 3. Atypical meningioma.
 5-15% of meningiomas
 Diagnostic criteria either:
 4-19 mitotic figures/10 HPF OR
 Brain invasion OR
 Three of these histologic features:
 Increased cellularity
 Small cells with high N/C ratio
 Large and prominent nucleoli
 Patternless or sheetlike growth (loss of lobular architecture)
 Foci of "spontaneous" or geographic necrosis

29. 1. Chordoid meningioma
 It is found in childhood.
 large, supratentorial tumours that exhibit a very high rate of recurrence
following subtotal resection .
 Consists of tissue histologically similar to chordoma.
 Tumor arranged in cords and trabeculae of eosinophilic often vacuolated cells
in abundant mucoid matrix background.
 These are interspersed with more typical meningioma tissue and lack
cytokeratin.
 Chronic inflammatory infiltrate is prominent.

30. Chordoid meningioma. Cords of cells between myxoid
collagen resemble chordoma except for their meningothelial nuclei
and whorl formation.

31. 2. Clear cell meningioma
 Common sites crebellopontine angle and cauda eqiuna region.
 Occur in younger patients both children and young adults.
 Patternless meningioma composed of polygonal cells with clear, glycogen-rich
cytoplasm and prominent blocky perivascular and interstitial collagen.
 Shows prominent PAS-positive, diastase sensitive cytoplasmic clearing.
 Whorl formation is vague and no psammoma bodies.
 Associated with more aggressive behavior including frequent recurrence and
CSF seeding.

32. Clear-cell meningioma. This tumor has recurred several times in the lumbar
spinal dura . Its cells contain glycogen seen with the periodic acid-Schiff stain
(A) and confirmed by digestion with diastase (B).

33. 3. ATYPICAL MENINGIOMA—GRADE II
 It is meningioma with increased mitotic activity (>4/10hpf)
 three or more of the following histologic features-
 increased cellularity (defined as 53 nuclei/ hpf diameter )
 small cells with a high nuclear:cytoplasmic ratio,
 prominent nucleoli,
 uninterrupted patternless or sheet-like growth, and
 foci of ‘spontaneous’ or ‘geographic’ necrosis.
 Ki-67 is not a true diagnostic criteria, however it is usually greater than 4% and up to
20%

34. Atypical meningioma with increased mitotic activity

35. MENINGIOMAS OF GRADE III
 Only 2% of meningiomas are classified as Grade III (anaplastic/malignant).
 The features required for the diagnosis of a Grade III meningioma are:
 20 or more mitoses per 10 high power fields
 Or anaplastic cytology
 Or the histological appearances of a papillary or rhabdoid meningioma
 Malignant meningiomas may also resemble haemangiopericytomas
 Histological Subtypes of Grade III (Anaplastic/Malignant) Meningiomas
 Anaplastic (malignant)
 Papillary
 Rhabdoid

36. 1. Papillary meningioma
 Occur in young patients including children.
 Presence of a perivascular pseudopapillary pattern.
 Composed of epithelial-like cells with cuboidal or columnar shape and well-
defined cytoplasmic borders.
 Papillary configuration is rare but are prognostically associated with high rate
of local recurrence and metastasis.
 Papillae have vascular core and may form by edematous or necrotic loosing of
the surrounding tumor cells.
 Local invasion and invasion of the brain have been noted in 75% of cases,
recurrence in 55%, & metastasis in 20% and death in half patients.

37. Papillary meningioma. Papillary meningiomas exhibit cuboidal to columnar cells
arranged in pseudopapillae

38. Papillary meningioma with papillary pattern on a collageneous stroma. B Papillary
meningioma characterized by discohesive growth with pseudopapillae and
perivascular pseudorosettes.

39. 2. Rhabdoid meningioma
 Highly aggressive tumor.
 It contains sheets of rhabdoid cells, i.e.
 plump cells with eccentric nuclei, often open chromatin, a prominent nucleolus,
and prominent inclusion-like eosinophilic cytoplasm.
 It has high proliferative index.
 Differential diagnosis
 Epithelioid and gemistocytic gliomas
 Identified by location, pattern of brain invasion, vimentin predominance and
EMA reactivity.

40. A Rhabdoid meningioma with eccentrically placed vesicular nuclei, prominent
nucleoli, and eosinophilic globular/fibrillar paranuclear inclusions (A) and
cytoplasmic immunoreactivity for vimentin (B).

41. 3. Anaplastic (malignant) meningioma
 It is lobulated and circumscribed neoplasms.
 Histological criteria to confer malignant meningioma is
 (a) 20 or more mitotic figures per 10 hpfs, or
 (b) regions with malignant, anaplastic cytology, resembling a sarcoma,
carcinoma, or melanoma
 MIB-1 labeling indices is high
 Median survival is 2 years.

42.  Differential diagnosis-
 Anaplastic gliomas and glioblastomas, ( when Glioma stain equivocally for
GFAP and invades the meninges; or, alternatively, when an anaplastic
meningioma stains poorly for EMA.)
 Meningioma invasion of brain has more discrete margins than glioma.
 Meningioma does not form secondary structures of Scherer.
 Invasion of meningioma proceeds along vessels, trapping island of gliotic CNS
parenchyma along the way.
 While in glioma, individual neoplastic glial cells, which wander many
centimeters throughout the CNS parenchyma

43. Anaplastic meningioma. Focal papillary patterns in densely cellular fields may be present in
anaplastic meningiomas (A). Moderate to high Ki67 proliferative index can be seen in anaplastic
meningiomas (B). (MIB-1–ABC immunoperoxidase with hematoxylin counterstain.)

44. Prognostic and predictive factors
 Clinical factors
 Extent of resection – influenced by site.
 Extent of invasion
 Attachment to vital intracranial structures, and the skill and experience
of the surgeon.
 young age and male gender, are less predictors of recurrence.
 Histopathology and grading-
 Benign have recurrence of about 7–25%, atypical meningiomas recur in 29–52%
of cases and anaplastic meningiomas at rates of 50–94%.

45.  Progesterone receptor status-
 The following three factors progesterone receptor score of 0, a mitotic index
greater than 6, and malignant (WHO III) tumour grade, was a highly significant
predictor of poor outcome.
 progesteronereceptor- negative meningiomas tend to be larger than receptor-
positive tumours

46. Hemangiopericytoma Grade II or III
 A highly cellular and vascularized mesenchymal tumour exhibiting a
characteristic monotonous low-power appearance and a well-developed,
variably thick-walled, branching “staghorn” vasculature; almost always
attached to the dura and having a high tendency to recur and to metastasize
outside the CNS.
 It correspond to WHO grade II or III.
 Incidence-
 Approximately .4% of all primary CNS tumor.
 Younger age group than meningioma (mean age- 43).
 More common in men.
 It is solitary and attached to dura, more common in occipital region.

47.  Clinical features:
 Based on the site and indistinguishable from meningioma.
 Neuroimaging:
 a well-demarcated, lytic lesion of adjacent bone.
 The hypervascularity seen on angiography explains the tendency to bleed.
 CT and MRI show a sharply demarcated tumour with dural attachment.
 smooth or nodular margin and intense contrast enhancement.
 Significant edema in underlying brain parenchyma.
 Lack calcification

48.  Macroscopy:
 solid, well-demarcated tumour.
 has a tendency to bleed during removal.
 globoid, slightly lobulated and rather firm.
 Cut surfaces are fleshy, greyish to red-brown or frankly hemorrhagic with a
number of visible vascular spaces.
 Histopathology:
 This highly cellular and mitotically active neoplasm.
 Has uniform cellularity distinguishes from meningioma.
 It is monomorphous tumor composed of packed, randomly oriented tumour
cells with little intervening fibrosis.
 Cytoplasm is scant and cell borders are indistinct.
 Nuclei are round to oval, occasionally elongated, with moderately dense
chromatin and inconspicuous nucleoli, lacking the pseudo-inclusions
characteristic of meningiomas.

49.  Nuclear atypia and mitotic activity is variable.
 Anaplastic (grade III) tumours show a
 high degree of mitotic activity (at least 5 mitoses per 10 HPF) and/or
 necrosis,
 plus at least two of the following: haemorrhage, moderate to high nuclear
atypia and cellularity.
 A rich network of reticulin fibers, typically investing individual cells, is most
characteristic.
 Numerous slit-like vascular channels lined by flattened endothelial cells and
frequent gaping, thin-walled and branching vascular spaces, so-called
“staghorn sinusoids”.
 Necrosis is uncommon and calcification and psammoma bodies not seen.
 May invade and destroy adjacent bone, without the hyperostotic reaction.

50. Hemangiopericytoma show hypercellularity with a rich network of delicate vascular clefts
(A). In other areas of the same tumor, dense collagen stroma is seen intermixed with the
more cellular areas (B).

51. Hemangiopericytoma Immunohistochemistry for vimentin for vascular network in
hemangiopericytomas (A). Marked immunoreactivity for CD34 accentuates both
vascular and cellular elements

52. Hemangiopericytoma: Reticulin surrounds each individual
cell

53.  Immunohistochemistry:
 Diffusely immunoreactive for vimentin (85%),
 factor XIIIa (80–100 %) in individual scattered cells, Leu-7 (70%), and, in
 33–100% of cases, for CD34.
 Focal immunoreactivity for EMA.
 Histogenesis:
 no evidence of pericytic differentiation and, instead, are fibroblastic in
nature.
 Prognostic and predictive factors:
 local recurrences are almost inevitable.
 Metastasize to the bones, lungs and liver.
 Differential diagnosis
 Meningioma and solitary fibrous tumor by IHC

54. Mesenchymal, non-meningothelial tumours
 Benign and malignant mesenchymal tumours originating in the CNS and histologically
corresponding to tumours of soft tissue or bone.
 It include:
 Lipoma ,
 Liposarcoma Angiolipoma
 Hibernoma ,
 Solitary fibrous tumour
 Fibrosarcoma ,
 Malignant fibrous histiocytoma (MFH)
 Leiomyoma Leiomyosarcoma
 Rhabdomyoma, Rhabdomyosarcoma
 Chondroma, Osteoma
 Osteochondroma Chondrosarcoma , Osteosarcoma,
 Haemangioma ,Epithelioid haemangioendothelioma
 Angiosarcoma , Kaposi sarcoma Ewing sarcoma-peripheral primitive
 neuroectodermal tumour

55. Solitary Fibrous Tumor
 An Uncommon mesenchymal neoplasm.
 Mostly adults with a mean age at fifth decade with male predominance.
 Present as dural based lesion in the cranium and spinal canal with occasional
intra-axial (lateral ventricle, spinal cord)
 posterior fossa and spinal cord (thoracic and lumbar regions.)
 Neuroimaging demonstrates a welldelineated, usually inhomogeneous mass
with diffuse, relatively prominent vascular enhancement.

56.  Histopathology and Immunohistochemistry:
 Non encapsulated with a well-defined “expansile” interface with adjacent
brain or spinal cord.
 Moderately cellular, monomorphous groups of undulating spindle-shaped cells
 arranged in a patternless fashion or poorly formed fascicles with abundant
band-like deposition of hyaline collagen fibers and prominent vascularity.
 Vessels are commonly branching.
 Nuclei are oval to elongate with delicate chromatin, with inconspicuous
nucleoli, and lack pseudoinclusions.

57. Solitary fibrous tumor. A, Spindle cells arranged in poorly formed fascicles are intermixed with dense
collagenous bands. B, The tumor cells are strongly immunoreactive for CD34

58.  Differential diagnoses
 fibroblastic meningioma
 and hemangiopericytoma.
 SFT lack features of typical cellular pattern of meningothelial or syncytial
whirling, nor psamoma bodies present.
 It contain abundant ropey collagen intimately admixed with thhe neoplastic
cells.
 neoplastic cells are
 diffusely and strongly immunoreactive for CD34.
 negative for EMA.

59. Chordoma
 Low- to intermediate-grade malignant tumors.
 More common in men.
 Occur at any age but not common below fourth decade.
 Located centrally.
 Developed from embryonal notochord.
 Most chordomas occur at either end of the primitive notochord 40% in the
clivus and 45% in the sacrum.
 Propensity to slowly invade surrounding tissues, including bone, the precise
anatomic origin of individual chordomas is often difficult.

60.  Clinical feature:
 Vary according to site- diplopia,
 visual field defects, headaches, pain, nasal obstruction,
 epistaxis, nasal discharge, soft tissue mass
 Radiographic appearance - expansile and destructive osteolytic lesion.
 Chordomas are well-demarcated or encapsulated, soft, mucoid, or gelatinous
tumors with a variegated appearance, including solid and cystic areas.

61.  Microscopy:
 The cells are arranged in cord, cells are characteristically ‘physaliferous’
 The cells contain large intracytoplasmic vacuoles.
 The vacuoles of physaliphorous cells contain mucin and glycogen.
 Due to arrangement in cord these vacuoles occasionally line up like beads on
a string.
 It may contain condroid elements- this has longer patients survival
 IHC :
 chordomas express S-100, cytokeratin, EMA, and 5′- nucleotidase.
 ‘‘chordoid meningioma’’ lacks cytokeratin expression.

62.  Differential diagnosis:
 chondrosarcoma and other chondroid neoplasms
 They have individual or paired cells embedded in myxoid matrix.
 On IHC Chondrosarcoma express S- 100 but lack cytokeratin, EMA, and 5′-
nucleotidase;

63. Chordoma forming lobules separated by bands, b. composed of tumor
cells arranged In cords surrounded by myxoid matrix.
The cells are positive for CAM5.2 cytokeratin and mucin.

64. Melanocytic lesions
 Arise from leptomeningeal melanocytes
 It includes
 (1) diffuse melanocytosis and melanomatosis,
 (2) melanocytoma
 and (3) malignant melanoma.
 Incidence
 0.06-0.1% with annual incidence 1/10 million
 Diffuse melanocytosis Present in stillbirth to 2nd decade
 Melanocytomas occur in all age (range 9–73 years), but are most frequent in
the fifth decade (45–50 years), female predominance
 Primary nodular melanomas arise in patients ranging from 15–71 years

65.  Localization:
 Diffuse melanocytosis and melanomatosis involve the supra- and infratentorial
leptomeninges and the superficial brain parenchyma.
 highest frequency include the cerebellum, pons, medulla and temporal lobes.
 Melanocytomas arise in the extramedullary, intradural compartment at the
cervical and thoracic spinal levels.
 Meckel’s cave is a site with a peculiar predilection for primary melanocytic
neoplasms.
 Clinical features:
 Melanocytosis and melanomatosis are associated with neurocutaneous
melanosis- large or numerous congenital cutaneous nevi together with benign
or malignant diffuse leptomeningeal melanosis.
 Neuropsychiatric symptoms, bowel and bladder dysfunction, and sensory and
motor disturbances.
 Increasing intracranial pressure

66.  Neuroimaging:
 CT and MRI of melanocytosis and melanomatosis shows diffuse thickening and
enhancement of the leptomeninges, often with focal nodularity.
 Melanocytomas: isodense or hyperintense on T1-weighted images and
hypointense on T2-weighted images.
 Macroscopy:
 Diffuse melanocytic lesion: dense black replacement of the subarachnoid
space or as dusky clouding of the meninges.
 Melanocytoma and malignant melanoma are solitary mass lesions, appear
black, red-brown, blue or macroscopically non-pigmented

67. Diffuse melanocytosis
involving the subarachnoid
space of the cerebral
hemisphere and invading
the cerebral cortex
Primary spinal melanoma
originating from the spinal
cord and invading the
subarachnoid space

68.  Histopathology:
 Most benign and malignant melanocytic lesions display melanin pigment finely
distributed within tumour cells and coarsely distributed within the tumour
stroma and the cytoplasm of tumoural macrophages (melanophages).
 Diffuse melanocytosis:
 it is proliferation of leptomeningeal melanocytes.
 Tumor cells are spindled, round, oval or cuboidal.
 Individual cells are cytologically bland.
 CNS parenchymal invasion should not be seen in melanocytosis.

69. Melanocytoma
 Melanocytomas are solitary, low-grade tumours that do not invade
surrounding structures.
 Tumor cells are spindled or oval containing variable melanin often form tight
nests.
 Heavily pigmented tumour cells and tumoural macrophages are seen at the
periphery of nests.
 Other variant demonstrate storiform, vasocentric and sheetlike
arrangements.
 Nuclei are oval or bean-shaped with small esosinophilic nucleoli.
 Cytologic atypia and mitoses are generally absent (on average, less 1/10 HPF)

70. Histological features of melanocytoma. A Loose or tight nests of low-grade, pigmented
spindle cells with intervening stroma containing higher levels of melanin pigment.
B Melanin containing macrophages (melanophages). C Melanocytoma cells showing
clear to eosinophilic cytoplasm with variable fine pigment. Nuclei are bean-shaped and
hav micronucleoli. Melanin within the cytoplasm of melanophages is typically in larger
aggregates

71. Malignant melanoma
 It is similar to melanoma of other site.
 Anaplastic spindled or epithelioid cells, arranged in loose nests, fascicles or
sheets, display variable cytoplasmic melanin.
 It may contain large cells with bizarre nuclei, numerous typical and atypical
mitotic figures, significant pleomorphism, and large, often red nucleoli.
 It is pleomorphic and have more anaplastic nuclei than melanocytoma.
 Immunohistochemistry:
 Most tumours react with the antimelanosomal antibodies HMB-45 or MART-1
(Melan-A),
 Also express S-100.
 Vimentin and neuron-specific enolase are variable

72. Malignant melanoma infiltrating the meninges around brain
stem and cerebellum
B Primary malignant CNS melanoma showing extensive invasion of the
cerebral cortex and subarachnoid space. C Highly polymorphic melanin-laden
cells of a malignant melanoma invading the cerebral cortex.

73.  Differential diagnosis:
 Metastatic malignant melanoma
 histogenetically different nervous system tumours undergoing melanization,
such as schwannoma, medulloblastoma paraganglioma and various gliomas.
 Prognostic and predictive factor:
 Diffuse melanosis carries a poo prognosis even in the absence of histologic
malignancy.
 Malignant melanoma is a highly aggressive and radioresistant tumour with
poor prognosis

74. Haemangioblastoma
 Definition
 A slowly growing, highly vascular tumour of adults, occurring in the
cerebellum, brain stem or spinal cord; histologically comprised of stromal
cells and small blood vessels; occurring in sporadic forms and in association
with von Hippel-Lindau (VHL) syndrome.
 WHO grade- I
 Incidence:
 Uncommon occur as sporadic as well as familial forms.
 Occur in any part of the nervous system
 Sporadic tumours occur predominantly in the cerebellum.
 VHL-associated haemangioblastomas may be multiple and affect the
 brain stem, spinal cord and nerve roots
 in addition to the cerebellum.

75.  Clinical features:
 Symptoms occurs due to impaired CSF flow- resulting hydrocephalus and
increase intracranial pressure.
 It produce erythropoietin, and this may cause secondary polycythaemia.
 Imaging :
 gadolinium-enhancing mass with associated cyst in approximately 75% of
cases.
 Angiography is useful to identify small lesions, showing a mass with a dense
tangle of vessels,

76.  Macroscopy:
 well-circumscribed, highly vascularized red nodules, often in the wall of large
cysts.
 At places, the tumour may appear yellow owing to its rich lipid content
Intraoperative view of a cystic
haemangioblastoma in the region of the
fourth ventricle and dorsal medulla
oblongata.

77.  Histopathology:
 It has two main components: stromal cells and abundant vascular cells.
 Stromal cells: large and vacuolated, can be cytoligically variable
 On the basis of stromal cells two variant : cellular and reticular.
 Numerous thin walled vessels and readily outlined on reticulin stain.
 Intratumoral hemorrhage may be seen.
 In adjacent reactive tissues, particularly in cyst and syrinx walls, astrocytic
gliosis and Rosenthal fibers are frequently observed.
 Tumor edge- well demarcated, infiltration rarely occur.
 The stromal cells represent the neoplastic component, with variable size
nuclei,
 Most characteristic is numerous lipid-containing vacuoles, resulting in the
typical ‘clear cell’ morphology.

78. Section of a cerebellar haemangioblastoma extending into the
fourth ventricle (A). Higher magnification shows the typical
distribution of tumour cells within a network of small
capillaries (B). hyalinised vascular stroma (left).
Haemanglioblastoma with accumulation of
lipid droplets within stromal cells

79. Thank you