Neoplasms

Primary CNS tumors are more common in children while metastases are more common causes of brain tumors in adults. Supratentorial or cerebral locations are more common in adults while infratentorial (cerebellum, brainstem) locations are more common in children.

(I) Meningiomas: They are benign, slow growing tumors arising from the arachnoid mater. They are most commonly seen in adult women and grow at a faster rate in pregnancy. Most common locations are lateral cerebral convexities, midline along the falx cerebri and olfactory groove. They may be located in the cerebral ventricles or spinal cord as well. There is an increased risk for multiple meningiomas in neurofibromatosis type 2. On histopathological examination, meningiomas are well circumscribed, solid, spherical masses, attached to the dura. On cut section, it is firm and fibrotic with foci of calcification. Characteristic Psammoma bodies are seen microscopically. Various patterns are seen on histology - syncytial with masses of polygonal cells and poorly defined cell membranes; fibrous with spindle shaped cells arranged in parallel or interlacing bundles; transitional or mixed which are a mix of the previous two patterns and have conspicuous Psammoma bodies; hemangioblastoma like pattern with high rate of recurrence; and anaplastic pattern which is a rare, malignant form of meningioma which invades surrounding structures and metastasizes to the lung. Most meningiomas show deletion of chromosome 22.

(II) Neurofibromas: They are benign tumors arising from Schwann cells in the PNS. They may be single or multiple. Multiple cutaneous neurofibromas are seen in neurofibromatosis type 1 or Von Recklinghausen disease.

Clinical features of neurofibromatosis types 1 and 2

NF type 1

• Multiple cutaneous neurofibromas
• Plexiform tumors (may become malignant)
• Optic gliomas
• Lisch nodules (hamartomas of the iris)
• Cafe au lait (coffee brown color) macules
• Axillary and inguinal freckling
• Sphenoid dysplasia and fibromuscular dysplasia of the arteries

NF type 2

• Bilateral vestibular Schwannomas
• III or V nerve Schwannomas
• Hearing loss, dizziness, headaches, diplopia, facial weakness
• Meningiomas, CNS gliomas
• Spinal ependymomas
• Cutaneous neurofibromas

Neurofibromatosis is inherited as an autosomal dominant syndrome. Type 1 shows mutations in the NF 1 gene on chromosome 17. NF 1 is a tumor suppressor gene that normally codes for the protein neurofibromin which is an inhibitor of the ras/MAPK pathway. Type 2 shows mutations in NF 2 gene on chromosome 22 which is a tumor suppressor gene that normally codes for merlin. Merlin regulates cell growth in the Schwann cells by inhibiting MAPK signalling. On histopathology, neurofibromas are un-encapsulated tumors that produce a fusiform enlargement of the nerve and show bundles of interlacing fascicles of spindle-shaped cells with wavy nuclei with a collagenous and mucoid matrix. It stains positive for S-100 and EMA (epithelial membrane antigen) by immunohistochemistry.

(III) Astrocytoma and glioblastoma multiforme: Astrocytoma is a type of glioma, other gliomas being ependymoma, glioblastoma and oligodendroglioma. Gliomas arise from neuroglial tissue. Astrocytoma and glioblastoma multiforme arise from astrocytes.

WHO grading system for astrocytomas

Grade I is the least malignant while Grade IV is the most malignant. Grade I is low grade and has a good prognosis. Pilocytic variant is more common in children and young adults and shows wavy, fibrillary processes or some cases have pleomorphic features; Grade II is also fibrillary, composed of well differentiated astrocytes, and is commonly seen in middle age; Grade III is anaplastic, hypercellular with nuclear atypia, hyperchromasia and characteristic vascular proliferation; Grade IV, also called glioblastoma multiforme is very aggressive, grossly appears as grey-white and yellow necrotic areas with interspersed areas of hemorrhages and palisaded layer of tumor cells, anaplasia, fusiform cells and small round poorly pleomorphic cells. Hypoxia driven vascular proliferation with formation of glomerulus-like structures are seen. Glioblastoma is most common in middle aged adults, in the frontal and temporal lobes.

All astrocytomas stain positive for GFAP or glial fibrillary acidic protein on immunohistochemistry. Imaging in glioblastoma shows a large irregular mass of variable density with cavitation, surrounded by a large area of edema. It may spread across the corpus callosum from one hemisphere to the other.

(IV) Medulloblastoma: It is a highly malignant tumor of embryonal origin, seen most commonly in small children and sometimes in young adults. It is located in the cerebellum or around the fourth ventricle. Patients with Turcot’s syndrome are at increased risk of developing medulloblastomas. It invades locally and shows distant metastases to the lungs, liver, vertebrae and pelvis. They can obstruct the fourth ventricle causing hydrocephalus. Microscopically it shows typical Homer-Wright rosettes which consist of small, poorly differentiated cells arranged around blood vessels. Cells may show glial, neuronal and other differentiation such as striated muscle and melanocytes. Some tumors may show extensive collagen production.

(V) Ependymoma: It is derived from the ependymal lining of the ventricles or the central canal. It is more common in children and young adults, most commonly in the fourth ventricle. Microscopically, ependymal cells can be seen forming canaliculi, rosettes and pseudorosettes. They may present with hydrocephalus.

(VI) Primary CNS Lymphoma: It is most commonly seen in immunocompromised adults above the age of 50 years such as organ transplant recipients or AIDS patients. They arise from microglia/histiocytes or lymphocytes. They are usually periventricular and frequently involve the corpus callosum and spread to both cerebral hemispheres. The tumor cells form dense perivascular sheaths or diffuse masses being histologically similar to diffuse large cell lymphomas.

(VII) Craniopharyngioma: It is a benign, suprasellar tumor derived from the epithelial remnants of the Rathke’s pouch. It is more common in children and adolescents. They are located in the region of the optic chiasma. It forms a reddish, cystic mass composed of sheets of squamous epithelial cells and keratin, set in a loose connective tissue stroma with areas of calcification. Cholesterol crystals are seen. Craniopharyngiomas clinically present with headaches, bitemporal hemianopsia, decreased visual acuity, papilledema and endocrine dysfunction due to compression of the hypothalamus and pituitary stalk. GH, GnRH, TSH, ACTH and ADH deficiencies may be seen.

(VIII) Metastatic tumors: They are more common than primary tumors. Most common tumors that metastasize to the brain include lung, breast, melanomas, colon and renal. ALL (acute lymphoblastic leukemia) frequently involves the brain. Breast cancer metastases can develop late, sometimes years after the diagnosis of primary cancer. Metastatic tumors to the brain are often multiple, supratentorial, spread by hematogenous route, well demarcated and located at the grey-white matter interface. Microscopically, they resemble the primary tumor. They typically present with symptoms of cerebral edema, increased intracranial pressure, seizures and focal deficits.

Meningeal carcinomatosis is a condition where secondary metastases diffusely involve the brain and spinal cord, presenting as multiple nodular growths. The syndrome results from tumor infiltration and inflammation of the leptomeninges. Access to the subarachnoid space is either by hematogenous dissemination or by direct extension from a tumor of the brain or spinal cord. It is seen in carcinoma of the lung, breast and ALL. It presents with headache, drowsiness, cranial nerve deficits, spinal root pain and paresthesias. The CSF in meningeal carcinomatosis shows high protein, low glucose, neoplastic cells and lymphocytes.