Tumours of Neuroepithelial Tissue

Tumours of Neuroepithelial Tissue These include those that arise from cell lineages inherent to the brain and spinal cord parenchyma. Astrocytic Tumours  Pilocytic (hairlike appearance) astrocytoma (grade I) - Relatively circumscribed, slow-growing and often cystic - Occurs in children and young adults - 2/3 arise in the cerebellum  therefore less likely to have seizures - Histologically, often has a biphasic appearance – cell rich areas (long bipolar tumour cells) and cell poor cystic areas (multipolar, round, nucleated cells, Rosenfal fibers = eosinophilic granular bodies/hyaline droplets)  Diffuse astrocytoma (grade II) - Diffusely infiltrating ill-defined lesion blurring anatomical boundaries - Typically affects young adults - Slow growing, but tends to progress to grade 3 and 4 tumours - Cerebral hemispheres are most often involved, resulting in seizures, subtle changes in senses or, with frontal lobe involvement, behaviour and personality changes - Involves a proliferation of fibrillary or gemistocytic (rounded with eccentric nucleus and eosinophilic cytoplasm) astrocytes on a background of loosely-textured and often microcystic tumour matrix - Difficult to distinguish histologically from reactive gliosis (diffuse astrocytoma would be more dysformic)  Anaplastic astrocytoma (grade III) - Can arise de novo or from a grade II tumour - The main distinctions from grade II tumours are that these tend to occur in a slightly older age range (45-51 years) and nuclear atypia with increased cellularity and mitoses  Glioblastoma (grade IV) - This is the most frequent primary brain tumour, occurring in even older ages (mean ~60 years) and with a dismal prognosis - Preferentially in cerebral hemispheres - Most occur de novo with progression - Grossly necrotic and haemorrhagic, often surprisingly large at first presentation Oligodendroglial • These tumours typically involve the cerebral hemispheres in adults, including the grade II oligodendroglioma and the grade III anaplastic oligodendroglioma. • No grade IV • Chromosomal loss of 1p/19q • Longer patient survival and tumour sensitivity to chemotherapy • Possible calcification which shows on the CAT scan • Cells with round nuclei, fine branching vasculature Ependymal These include the grade II ependymoma and grade III anaplastic ependymoma, found on the walls of the ventricles and spinal canal. Rosettes: cells line up around thin vessels There is also the grade I myxopapillary ependymoma, which occurs almost exclusively at the distal end of the spinal cord. Molecular markers – IDH1/IDH2  Often IDH1 and IDH2 mutations followed by TP53 and 1p/19q loss  IDH1 and IDH2 mutations are mutations in isocitrate dehydrogenase type 1 and 2 in gliomas  It is present in 80% of grade II and III astrocytomas and oligodendrogliomas  It is present in 15% of glioblastomas     IDH1/IDH2 mutations are nearly always heterozygous and are tightly associated with TP53 mutations in astrocytomas and 1p/19q codeletions in oligoastrocytomas These mutations occur early in tumour development Mutant IDH1 acquires the ability to convert alpha ketoglutarate to 2 hydroxyglutarate 2 hydroxyglutarate accumulates in gliomas with mutant IDH1 Embryonal Tumours These occur as childhood tumours:  Medulloblastoma (grade IV) – occurs in the cerebellum, predominantly showing neuronal differentiation and tends to metastasise through the CSF pathway.  Atypical teratoid/rhabdoid tumour (gradeIV) – shows divergent differentiation along the epithelial, mesenchymal or neuroglial lines. Other CNS Tumours These include those that occur primarily within the CNS parenchyma, but are not of the CNS cell lineage:  Lymphomas – these need to be distinguished from secondary brain involvement by systemic lymphoma.  Germ cell tumours – the whole range that occur in the gonads can occur in the brain, preferentially in the midline at the region of the pineal gland. There are also tumours of the meninges (meningiomas, ranging from grade I to III):  Derived from meningiothelial cells  Usually well-demarcated masses on the inner surface of the dura mater  The underlying brain and spinal cord is often compressed but rarely become compressed which, together with more superficial location, makes surgical resection more achievable There are also tumours of the cranial and paraspinal nerves:  Tumours of nerve sheath; differentiation to Schwann and perineural cell types  Identical lesions in peripheral nerves  Schwannoma, neurofibroma and malignant peripheral nerve sheath tumour (MPSNT) Metastatic Tumours This is the most common type of tumour occurring in the CNS. In adults, the most frequent examples are:  For brain – lung, breast, skin/melanoma  For spinal (epidural) – breast, lung, prostate and lymphoma Familial Tumour Syndromes Neurofibromatosis Both types 1 and 2 are autosomal dominant disorders. NF1 Also called von Recklinghausen disease, with a prevalence of 1 in 3000. Common signs and symptoms include:  Cafe au lait spots on skin  Freckling of armpit or groin  Pilocytic astrocytoma involving the optic nerve  Two or more Lisch nodules (pigmented hamartomas on the surface of the iris)  Bony abnormalities  First degree relative with NF1 These patients are also at a significantly increased risk of developed MPNST, that significantly reduces life expectancy. NF2 Has a prevalence of 1 in 40 000 – 50 000. The diagnostic criteria includes:  Bilateral schwannomas of CN VIII (vestibulocochlear nerve; acoustic neruoma), or  1st degree relative with NF2 and either: - Unilateral acoustic neuroma <30 years old or - Any 2 or meningioma, schwannoma, glioma or posterior lens opacity