Post on 15-Jan-2017
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Pathology of CNS(Tumor of CNS)
DR Naila Awal
Classification of CNS tumor
• 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
CNS-Tumours
• 70% of childhood CNS tumors arise in posterior fossa• In adult tumors arise within the cerebral hemispheres above the tentorium.
Astrocytoma
• Most Frequent
• Types-Infiltrative & Non infiltrative• WHO Grade (I – IV)
• Increased cellularity• Nuclear Pleomorphism• Mitotic activity• Endothelial proliferation • Necrosis - palisading
• 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).
Gross-
Partially cystic pilocytic astrocytoma of the cerebellum. The tumor forms a typical mural nodule.
• 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
• Rosenthal fibers-
tapered corkscrew-shaped,brightly eosinophilic, hyaline masses
• 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
• 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
• 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.
Pleomorphic xanthoastrocytoma. Xanthic cells, expressed as vacuolization of the neoplastic cells, are shown (arrow).
• Positive stains• GFAP and S100 • Reticulin, class III beta tubulin (73%)• Variable expression of neuronal markers including synaptophysin
• 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
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).
Infiltrating astrocytoma
Grade-II/IV
Diffuse astrocyto
ma
Grade-IV/IV
Glioblastoma
• 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.
• Gross-Poorly defined infiltrative tumor that distorts the brain.
C/S-Firm / soft & gelatinous, Cystic degeneration
• M/E-• Mild to moderate glial cellularity• Variable nuclear pleomorphism• Fibrillary background due to astrocytic process
Diffuse astrocytoma characterized by modest hypercellularity, nuclear pleomorphism, and numerous small microcysts
• Special stain-• GFAP-positive astrocytic cell processes
• 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
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.
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.
• M/E-• Increase in cellularity • Nuclear pleomorphism • Hyperchromasia • May have mitosis • No necrosis
• 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
• Anaplastic astrocytoma Glioblastoma• Increase in cellularity Dense cellularity
• Nuclear pleomorphism • Hyperchromasia • May have mitosis Mitosis • No necrosis Necrosis & vascular proliferation
Gemistocytic astrocytomaDense 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.
• Positive stains• GFAP, • Vimentin
• D/D-• Gliosis:• Hypertrophy of cells rather than hyperplasia, even distribution• Subependymal giant cell tumor: intraventricular, larger nuclei,
non-infiltrative• Ganglioglioma: neoplastic neurons
• 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)
• 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.
• M/E-
• 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
• Besides necrosis with nuclear pseudopalisading, the presence of endothelial proliferation is another histologic hallmark of glioblastomas.
• 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+
• Giant cell glioblastoma (IV/IV)• M/E-• Abundant bizzare appearing tumor giant cell, many MNG cell• Extensive necrosis, mitosis
• 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
Prognosis
Diffuse Astrocytoma
(G-II/IV)
Anaplastic Astrocytoma
(G-III/IV)
Glioblastoma(G-IV/IV)
Oligodendroglioma
• WHO grade- II/IV
• Gross• well-circumscribed, gelatinous,gray masses, often with cysts, focal hemorrhage,& calcification
• 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)
• Positive stainsOLIG2, 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+
• Anaplastic oligodendroglioma• WHO grade -III/IV• M/E-• Increased cellular density• Nuclear atypia• Mitosis• Necrosis
• D/D-Metastatic carcinoma:
• Renal cell carcinoma is EMA+,• usually no calcifications
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
• Gross-• Typically solid or papillary masses extending from4th ventricle
• M/E-• Tumor cells resemble normal ependymal cells with round to oval nuclei &
abundant granular chromatin.• Rosette & Perivascular pseudorosette
• Fig- Ependtmoma with true rosette
• True rosette
• Pseudorosette--------------
• D/D-
Glioma:• no true rosettes, • no cell-cell junctions, • no intracytoplasmic microvilli-lined lumina
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
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
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.
• 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.
• 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 .