Meninges and related tumors

Dr. Bahoran Singh

Meninges

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 layer2. middle arachnoid mater – avascular layer

-named for the spider-like struts (trabeculae) that connect the arachnoid to the underlying pia mater3. 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

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

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-

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.

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

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

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%)

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%)

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.

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.

Subtypes of meningioma

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

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.

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.

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.

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

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.

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.

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.

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

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.

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

Secretory meningioma. Although most meningioma cells are negative, these strikinglyCAM5.2 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).

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.

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.

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

1. Chordoid meningioma It is found in childhood. large, supratentorial tumours that exhibit a very high rate of

recurrencefollowing 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.

Chordoid meningioma. Cords of cells between myxoidcollagen resemble chordoma except for their meningothelial nucleiand whorl formation.

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.

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).

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%

Atypical meningioma with increased mitotic activity

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

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.

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

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

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.

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

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.

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

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.)

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%.

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

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.

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

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.

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.

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).

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

Hemangiopericytoma: Reticulin surrounds each individual cell

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

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

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.

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.

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

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.

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.

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.

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.

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;

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.

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

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

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

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

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.

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)

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

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

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.

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

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.

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,

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.

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.

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

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