Tumours of the CNS PDF

TUMOURS OF THE CNS Classification of brain tumors: Primary intracranial tumors: Intra-axial (from the brain parenchyma'the neural axis'): Glial tumors (gliomas; most common primary brain tumors): Astrocytoma: either circumscribed or diffusely...

TUMOURS OF THE CNS Classification of brain tumors: Primary intracranial tumors: Intra-axial (from the brain parenchyma'the neural axis'): Glial tumors (gliomas; most common primary brain tumors): Astrocytoma: either circumscribed or diffusely infiltrative Ependymoma oligodendroglioma Choroid plexus tumors: Choroid plexus papilloma Choroid plexus carcinoma Neuronal and Glioneuronal tumors: Central neurocytoma Ganglioglioma Embryonal tumors (primitive tumors): Medulloblastoma (of the cerebellum) CNS neuroblastoma (& other embryonal tumors of the cerebellar hemispheres) Primary CNS lymphoma Germ cell tumors (of the midline structures of the brain): Germinoma of the pineal body Tumors of the pituitary gland and the sellar region: Pituitary adenoma (pituitary neuroendocrine tumor) Craniopharyngioma Meningeal tumors (Extra-axial tumors):Meningiomas 173 Secondary tumors [metastasis] Grading of brain tumors Histological grading is a means of predicting the biological behavior of a neoplasm, influencing the choice of therapy [chemo & radio]. The WHO grading of brain tumor is a ‘malignancy scale’ which is tailored for each tumor type. WHO Grade I: Biologically Benign, low proliferative potential circumscribed and the possibility of cure following surgical resectionalone. WHO Grade II: low grade malignancy or locally malignant, they are generally infiltrative in nature and, despite low-level proliferative activity, often recur. Tend to progressto higher grades. WHO Grade III: frank malignancy, histological evidence of malignancy, [nuclear atypia and brisk mitotic activity]. In most settings, patients with grade III tumors receive adjuvant radiation and/or chemotherapy. WHO Grade IV: highly malignant, cytologically malignant, mitotically active, necrosis-proneneoplasms typically associated with rapid evolution and fatal outcomes and widespread infiltration and craniospinal dissemination. Examples of grade IV: glioblastoma, most embryonal neoplasms (medulloblastomas) and many sarcomas as well. N.B. malignant brain tumors usually spread by CSF dissemination (cerebrospinal seedling) with rare extra-cranial spread. GLLAL TUMOURS (GLIOMAS) Types of gliomas: Astrocytomas Ependymomas Oligodendrogliomas 174  ASTROCYTOMAS Incidence:approximately 80% of primary brain tumors in adults. Site of origin: occurs primarily in the cerebral hemispheres. Astrocytomas are either: Well circumscribedAstrocytomas[gradeI] (prime example is pilocytic astrocytoma) shows good prognosis after surgical excision, with no recurrence and no increase of grade with time [stable tumors]. Diffusely infiltrating Astrocytomas [Grade II, III and IV] which infiltrate the surrounding brain tissue by scattered single cells [which may even reach the other hemisphere in the higher grade astrocytomas 'Glioblastoma Grade IV']. Diffusely infiltrating astrocytomas are capable also of progression i.e. increasing grade and aggressiveness with time, with transformation to higher grades. The adult diffuse infiltrating astocytomas are now furtherly divided into; those with mutation in IDH (Isocitrate Dehydrogenase Enzyme) [with favorable prognosis] and those without IDH mutation (i.e. IDH wild types) yet having mutation in many other signaling proteins; all of which lead to aggressive behaviors 'frequent recurrences, rapid progression of grade, CSF dissemination and death'. Grades of astrocytmas: 1) Grade I well circumscribed astrocytomas: the most common type is pilocytic astrocytoma. 2) Grade II diffuse fibrillary astrocytoma. 3) Grade III Anaplastic astrocytomas. 4) Grade IV Glioblastoma multiforme (recently termed Glioblastoma). The circumscribed astrocytomas Pilocytic astrocytomas(Grade I): 175 Extremely low grade tumors, which tend to occur in children, and generally are found in the cerebellumorregion of the 3rd ventricle. The tumor is cysticwith a mural nodulein the cyst wall. Microscopic picture: Fusiform "piloid" bipolar astrocytes, Arranged in Alternating dense and loose areas, Microcysts are found in the loose areas and may coalesce to form the macroscopic cysts. Eosinophilic "Rosenthal fibers" are characteristic. Progression: Usually stable, with rare cases of CSF dissemination and transformation reported Diffusely infiltrating astrocytoma Diffuse - Anaplastic - Glioblastoma fibrillary astrocytoma astrocytomas 1) Gross - They are -Gross: - Site: frequently grows slowly growing diffusely across the corpus callosum Site: usually the infiltrating into the contralateral white matter of glioma hemisphere (butterfly the cerebral -Site: glioma). hemispheres. preferentially - Gross picture: have a - Shape: ill- involves the variegated appearance defined mass cerebral (white/hemorrhagic/yellow (infiltrate the hemispheres, necrosis) hence the name tumor tissue). especially the multiforme. - Color: grayish white matter. white tumors. 176 2) -They are -They are: - composed of different Microscopic composed of: - Higher types of cells: - Astrocytes cellularity. - Small round cells. show: - More nuclear - Bizarre giant cells. 1- Minimal pleomorphism. - Anaplastic astrocytes. hypercellularity. - Frequent - Most important features 2- No very rare mitoses. are: Foci of necrosis mitoses. - Overtime, it surrounded by palisaded - Fibrillary may progress to tumor cells background (in glioblastoma (pseudopalisading which the multiforme. necrosis) and astrocytes are microvascular found). proliferation. - Overtime, low- grade astrocytomas may progress to the anaplastic Fig. (95)Palisading variant. necrosis 3)Grade Grade II Grade III Grade IV 4) Prognosis Best prognosis. Poorer Worst prognosis. prognosis. 177 EPENDYMOMA Tissueof origin: from ependymal cells (line all ventricles). Sites: 1) In the 1st two decades: a. They are found in the 4th ventricle where they often cause obstruction and hydrocephalus. b. The prognosis: poor (because their location prevents complete removal). 2) In adults: a. They usually occur in the spinal cord (the most common glioma of the spinal cord of adults, with a special variant of the filum terminale called myxopapillary ependymoma). b. They are in the form of fusiform swelling of the cord. Microscopic picture. 1) Tumor cells have oval nuclei and located within fibrillary stroma 2) The tumor cells show attempts of differentiation toward ependymal structures in the form of Ependymal canals and true ependymal rosettes. 3) Formation of perivascular pseudo-rosettes by the tumor cells is very important for diagnosis. Grading: Ependymoma is WHO grade II, but may undergo malignant transformation into anaplastic ependymoma(WHO grade III) OLIGODENDROGLLOMA Fig. 96: Ependymal rosettes Site of origin: the cerebral hemispheres mainly frontal and temporal. Age: adults. Gross picture: 1) Shape:well-circumscribed mass. 178  2) Consistency:gelatinous. 3) Color: gray. Microscopic picture. 1) There are sheets of monotonous cells with: a. Uniform central nuclei. b. Clear halo of cytoplasm (surrounding the central nucleus), producing fried egg appearance. 2) There is a delicate network of capillaries. 3) Many contain foci of calcification. Molecularly characterized by simultaneous deletions (co-deletion) of the short arm of chromosome 1 and the long arm of chromosome 19 [del 1p19q]. Fig. (97): Clear halo cytoplasmwith central nuclei in oligodendrogliomas Grading: Oligodendroglloma is WHO grade II but may rarely undergo malignant transformation into anaplasticoligodendroglloma(WHO grade III). It is the least of gliomas to recur or to progressto malignancy EMBRYOMAL (PRIMITIVE) TUMOR OF THE CNS [WHO GradeIV by definition] Types: 1) Medulloblastoma (of the cerebellum; the most common site of primitive tumors of the CNS). 179  2) CNS Neuroblastoma (primitive tumors of the cerebral hemispheres; synomyn: central neuroblastoma, which is a different tumor than the sympathetic chain neuroblastoma, the so called peripheral neuroblastoma). 3) Retinoblastoma (primitive tumor of the retina). MEDULLOBLASTOMA: Undifferentiated highly malignant embryonal tumor [WHO grade IV]. Tissueof origin: neuroepithelial stem cells, strictly cerebellar in location [does not occur outside the cerebellum]. Age: infants and young children (but recently reported in young adults also). Microscopicpicture:They are composed of sheets of small round cells which: a) May have a diffuse pattern (classic) or nodular pattern (nodular/desmoplastic medulloblastoma) b) Composed of small primitive cells with hyperchromatic nuclei and scanty cytoplasm. c) Occasionally form pseudo-rosettes around fibrillary cores [Homer Wright pseudo-rosettes]. Prognosis. 1) Without therapy: they are rapidly fatal. 2) Surgical excision, chemotherapy and radiotherapy produced 70% 5-year survivals. TUMORS OF MENINGES MENINGIOMA It is a very common intracranial extra-axial (i.e. outside the brain substance) tumor Tissue of origin: meningothelial cells (especially those within the arachnoid villi). 180  Sites:most common sites are: 1) Parasagittal area. 2) Falx cerebri. 3) Sphenoidal ridge. 4) Olfactory groove. Age: 45-60 years. Sex:female: male ratio is (1.5: 1). Gross picture: well-circumscribed tumors attached to the dura matter [extra-axial dura-based tumors]. The overlying skull bone may be invaded and/or thickened (hyperostosis) Fig.(98):Psammoma bodies Fig. (99):Meningioma attached to dura Microscopic picture: a) There are meningothelial whorls. b) The whorls may show central laminated calcifications called psammoma bodies. c) Histological typesof meningioma: 1. Meningothelial type: syncytial whorls of oval or rounded cells without evident cellular boundaries. 2. Fibrous type: cells are slender like fibroblasts 3. Transitional type: containing areas of meningothelial type and fibrous type 4. Psammomatous type: containing large number of psammoma bodies predominating the picture. Most common in the spinal cord. 181  5. Other types: angiomatous, chordoid, papillary, rhabdoid, Secretory, microcystic, clear cell..etc. Grading: Ordinary meningioma is Grade I, atypical meningioma is Grade II, and is characterized by highher incidense of recurrence 8 times than grade I, with brian invasion and local destructution and malignant meningioma is WHO Grade III. Clinical features:cause symptoms by: a) Compression of the adjacent brain tissue. b) Invasion of the brain if atypical (GII) or malignant (GIII). Behavior: a) Meningiomas are mostly benign, but one problem is local recurrences. b) Malignant meningioma is rare. Some meningiomas are found to be estrogen receptor ER and/or progesterone receptor PR positive [treated with anti-estrogen]. PRIMARY CEREBRALLYMPHOMA Incidence and predisposing factors: 1) Patients with late stages of AIDS frequently develop primary CNS lymphomas. 2) Sporadic cerebral lymphoma (unassociated with HIV) affects old age. Gross picture: 1) The tumor is usually periventricular. 2) It may be nodular or diffuse, and multiple masses are common. Microscopicpicture: these are always large cell B-cell non-Hodgkin’s lymphomas Prognosis:These have a poor prognosis with a mean survival of 18 months. 182 METASTATIC TUMOURS Metastasis is usually via the blood stream to: 1) Leptomeninges(CarcinomatousMeningitis): the following tumors are particularly prone to this type of spread: 1- Leukemia in relapse. 2) Lymphomas. 3) Oat cell carcinoma. 2) Brain: a) Usually from the lung, breast, melanoma, kidney and gastrointestinal tract. b) Metastases can involve the cerebrum, cerebellum or uncommonly, the brain stem. PERIPHERAL NERVE SHEATH TUMORS Benign: Schwannoma Neurofibroma Malignant: Malignant peripheral nerve sheath tumor MPNST [neurofibrosarcoma or malignant schwannoma] SCHWANNOMA Benign tumor arises from Schwann cell. Grossly: well-circumscribed, encapsulated, firm, grayish white or yellowish mass, attached to the nerve but can be separated from it. Microscopically:tumors show a mixture of two growth patterns. 1-Antoni A 'compact' tissue:elongated cells with cytoplasmic processes are arranged in fascicles in areas of moderate to high cellularity with little stromal matrix; the "nuclear-free zones" of cytoplasmic processes that lie between the regions of nuclear palisading are termed Verocaybodies. 2- Antoni B 'loose'tissue:inwhich the tumor is less densely cellular with a loose meshwork of cells along with microcysts and myxoid changes. 183 Symptoms are due to local compression of the involved nerve or to compression of adjacent structures (such as brain stem or spinal cord in case of acoustic nerve schwannoma, which is one of the common sites). Bilateral schwannomas of the acoustic [] vestibulocochlear (eighth cranial)] nerve occurs in Neurofibromatosis type II syndrome [bilateral acoustic schwannomas]. Malignant change is extremely rare in schwannomas. NEUROFIBROMA Benign nerve sheath tumor composed of multiple types of cells (Schwann cells, fibroblast and perineurial cells); that produces fusiform expansion of the nerve (the nerve melts into the tumor and the tumor cannot be removed surgically without cutting he nerve) Grossly: Well-delineated but unencapsulated tumors with the nerve irregularly expanded, as each of its fascicles is infiltrated by the neoplasm. The tumor causes fusiform expansion of the separate fascicles of the affected nerve. Unlike the case with schwannomas, it is not possible to separate the lesion from the nerve. Microscopically:it is composed of proliferation of delicate spindle cells of many types; Schwann cells, fibroblast and perineurial cells. They consist of a (of the above mentioned types), often within a myxomatous stroma. Axons are often present within these tumors. Some neurofibromas cause disfigurement, especially with the plexiform type (where all the nerve fascicles are affected). Neurofibroma may undergo malignant change, especially in neurofibromatosis syndrome NF1. Neurofibrosarcoma [Malignant Peripheral Nerve Sheath tumor MPNST] is the malignant counterpart of both neurofibroma and schwannoma. 184