Pathology of brain tumors (part 1)       

Significance of brain tumors Annual incidence: 10-17/100,000 persons Half to three quarters are primary tumors , rest are metastatic. Histologic distinction: between benign and malignant subtle Grading : I- IV according to WHO grading system. Consequences of location: surgical resection may not be possible. Benign lesions may be lethal Patterns of growth: most glial tumors infiltrate brain Patterns of spread: CSF(some tumors), v. rarely outside CNS (GBM) Normal brain cells

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Figure labelling As amazingly complex as the CNS is, even more amazing is the fact that its components are so remarkably simple----Neuron body, dendrites, axon. NB: Nissl goes into the dendrites but not the axons. Section from spinal cord. Is this grey matter or white matter? Neurons with nucleus, nissl (Franz Nissl) granules, nerve fibers, glia. Glia are many times more common than neurons Blood vessel with endothelium and/or smooth muscle. Various glia This particular stain shows why the most common glial cell is called an “astro”cyte. What are the “haloed” cells? Oligodendrocytes, the CNS myelinators. Note the clear space around their nuclei, much in the same way myelin washed out from schwann glial calls as well.

10. Ependymal cells look exactly like ciliated columnar cells and like the ventricular spaced and choroid. 11. Choroid plexus is “papillary” in configuration

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CNS TUMORS Benign? Malignant?, Primary vs. met? Location?

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Age? X-ray Density? MRI signals? Calcifications? Vascularity? Necrosis? Liquefaction? Edema? Compression of neighbors? Classification of brain tumors 1. Glial neoplasms (GLIOMAS): - Astrocytomas - oligodendrogliomas - ependymomas 2. Neuronal tumors; - ganglion cell tumors - tumors with glial & neuronal components - tumors with neuronal components only 3. Poorly differentiated neoplasms; - Medulloblastomas -Primary CNS lymphomas -Germ cell tumors 4. Meningiomas 5. Metastatic tumors Glial neoplasm(Gliomas) ASTROCYTOMAS FIBRILLARY ASTROCYTOMAS  Represent 80% of adult primary brain tumors  Location: cerebral hemispheres(commonest), cerebellum, brain stem, spinal cord.  Morphology: neoplastic astrocytic nuclei distributed amid astrocytic processes of varying density, grade is determined histologically. ASTROCYTOMAS  Well differientiated astrocytomas, WHO grade II : Poorly defined , gray white , infiltrative, expand and distort surrounding brain. Show increased cellularity (compared to normal brain parenchyma) and mild nuclear pleomorphism. Most fibrillary astrocytomas are WHO grade II.

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ASTROCYTOMAS Anaplastic Astrocytomas, WHO Grade III; More aggressive tumors. Increased cellularity, moderate nuclear pleomorphism, mitotic activity and vascular proliferation.

ASTROCYTOMAS GLIOBLASTOMA MULTIFORME (GBM), WHO Grade IV; Gross: solid with cystic degenerative changes, foci of necrosis, gray white, large, infiltative, Butterfly gliomas: cross midline of brain. Morphology: marked nuclear pleomorphism, mitosis, tumor necrosis with palisading of tumor cells, vascular endothelial proliferation. Clinical course: Signs & Symptoms: Head ache, seizures, focal neurological deficits related to site involved. Treatment: Curative/ Palliative. Surgical resection, radiotherapy, chemotherapy. Prognosis: low grade astrocytomas may remain static or progress slowly over years patients usually enter a period of rapid growth, corresponding to appearance of anaplastic features.

1. Glioma, high grade, Note NECROSIS. NECROSIS is needed for the diagnosis of a HIGH grade glioma. 2. The higher grade gliomas merit the term GBM (GlioBlastome Multiforme), which need the presence of NECROSIS for a correct diagnosis, but pleormorphism and palisading usually can be easily demonstrated as well. 3. Glioblastoma (multiforme). Why is it called “multiforme”? Note the 1) palisading and 2) necrosis which are hallmarks of GBM. 4. Central necrosis is a sign of rapid growth. It outgrows its blood supply, and therefore liquefies centrally, like an abscess.

ASTROCYTOMAS PILOCYTIC ASTROCYTOMAS, WHO Grade I: Children & young adults Location: cerebellum, floor of 4th. Ventricle, optic nerve, rarely cerebral hemispheres. Gross: cystic with a mural nodule. Morphology: bipolar cells with long, thin hair like processes, Rosenthal fibers, eosinophilic granular bodies and micro cysts. Necrosis and mitosis are absent. Prognosis: slow growing, recurrence from incomplete surgical excision.     

ASTROCYTOMAS PLEOMORPHIC XANTHOASTROCYTOMA(PXA), WHO Grade I,

In children & young adults with a Hx. Of seizures. Location: temporal lobe Morphology: Neoplastic astrocytes with bizarre nuclei, abundant reticulin & lipid deposits and chronic inflammatory cells.

ASTROCYTOMAS  BRAIN STEM GLIOMAS, WHO Grade II- IV:  Most in first 2 decades of life  5 year survival 20- 40% with radiotherapy. Glial neoplasm(Gliomas) Oligodendrogliomas, WHO grade II  5-15% of gliomas  Middle adult life  Location: cerebral white matter  Prognosis: better than astrocytomas, average survival of 5-10 years with treatment.  Gross; well circumscribed gray white with foci of hemorrhage, calcification & occ. Cysts.  Morphology: Sheets of regular cells, round nuclei, finely granular chromatin, surrounded by clear peri-nuclear halo. Delicate network of anastomosing capillaries and calcifications. Oligodendrogliomas  Anaplastic Oligodendrogliomas, WHO Grade III:  Morphology: Increased cellularity, moderate pleomorphism, increased mitosis, vascular proliferation and necrosis.  Genetics: Most consistent finding in Oligodendrogliomas is loss of hetozygosity for chromosomes 1p & 19q associated with a better prognosis and better response to chemo and radiotherapy.

1. What kinds of glial cells are these? 2. What is this? Could it be a TUMOR of glial cells that look like oligodendrocytes? 3. What is this? Could it be a TUMOR of glial cells that look like oligodendrocytes?

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Glial neoplasm(Gliomas) Ependymomas, WHO grade II Arise from the ependymal lining of ventricular system, including central canal of spinal cord. Children: 4 th. Ventricle Adults: spinal cord CSF dissemination is common Morphology: tumor cells have round-oval, regular nuclei with abundant granular chromatin. They may form ependymal rosettes (canals) & peri-vascular rosettes.

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What kinds of glial cells are these? Could this be a tumor of glial cells that look like ependymal cells? Might this “glioma” look like an adenocarcinoma, or even a papillary adenocarcinoma? Normal ependyma on the left. Where would most ependymomas have to me located? Would a choroid plexus tumor be a type of ependymoma? Ans: Sure Ependymomas MYXOPAPILLARY EPENDYMOMAS, WHO grade I Location: Filum-terminale Morphology: Cuboidal cells with clear cytoplasm, arranged around papillary cores containing connective tissue and blood vessels. Myxoid areas containing mucin.

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Ependymomas SUB EPENDYMOMAS, WHO grade I Solid nodules attached to ventricular lining and protruding into ventricle. Clump of ependymal appearing cells in dense fibrillar background. ANAPLASTIC EPENDYMOMAS, WHO grade III Increased cellularity, , increased mitotic activity, necrosis and loss of ependymal differentiation.

CHOROID PLEXUS PAPILLOMAS Children : lateral ventricles Adults: 4 th. Ventricle Hydrocephalus due to obstruction or CSF over-production. Morphology: papillae of connective tissue covered with cuboidal/ columnar ciliated cells like those of normal choroid plexus. COLLOID CYSTS OF THIRD VENTRICLE Benign cysts in foramina of Monro resulting in non-communicating hydrocephalus and may be rapidly fatal. Morphology: cyst with thin fibrous capsule, and lining of low cuboidal epithelium , cyst contents are proteinaceous, gelatinous material. Thankyou