Pathology of CNS tumors (II) Dr. Noha R. Noufal Assistant Professor of Pathology

Objectives of the lecture: Upon completion of this lecture, students should be able to: Appreciate how the anatomy of the skull and the spinal column influences the prognosis of both benign and malignant primary CNS tumors. List the principal clinicopathological features of some of the main types of tumors that can arise within the central and the peripheral nervous systems اسم ورقم المقرر – Course Name and No. 6/2/2019

Medulloblastomas (Embryonal/ Primitive neuroectoderm Neoplasm) Occurs predominantly in children Located in the midline of the children cerebellum, but lateral locations are more often found in adults Rapid growth may occlude the flow of CSF, leading to hydrocephalus The tumor disseminate through CSF fluid The tumor is highly malignant & associated with bad prognosis

Medulloblastomas (Embryonal/ Primitive neuroectoderm Neoplasm) Medulloblastoma cells have a tendency to: Infiltrate through cerebellar cortex Penetrate the pia seed into the subarachnoid space Medulloblastoma is radiosensitive اسم ورقم المقرر – Course Name and No. 6/2/2019

Medulloblastomas Gross: Microscopic: The tumor is often well circumscribed, gray, and friable Microscopic: Extremely cellular tumor, with sheets of anaplastic cells Individual tumor cells are small, with scant cytoplasm and hyperchromatic nuclei Mitoses are abundant The tumor may express neuronal (neurosecretory granules or Homer Wright rosettes)

GROSS The tumor is often well circumscribed, gray, and friable. Cerebellum and brainstem, medulloblastoma – Gross, sagittal section The tumor in this image replaces much of the cerebellum, compresses the fourth ventricle, and distorts the brainstem The tumor is often well circumscribed, gray, and friable.

Microscopic appearance of medulloblastoma Multiple nodules of small cells in medulloblastoma Homer Wright rosettes

Meningiomas Meningiomas are non glial tumors arising from meningothelial cells of the arachnoid It is a common benign neoplasm in adult usually attached to dura Meningiomas may be found along the external surfaces of the brain and within the ventricular system Slow growing ,common in females Previous radiation therapy is a risk factor for development of this tumors

Meningiomas Extension into the overlying bone may be present Most meningiomas have a relatively low risk of recurrence or aggressive growth (WHO grade I) اسم ورقم المقرر – Course Name and No. 6/2/2019

Meningiomas Gross: Meningiomas are usually rounded encapsulated masses with well-defined dural bases Tumor mass compress underlying brain but are easily separated from it Dural base Mass

Microscopically, Characterized by formation of whorls by spindle cells and by psammoma bodies Menengothelial whorls

Grading of Meningiomas: WHO Grade I / Meningiomas Commonest and shows varied histological patterns Grade II /Atypical meningioma Characterized by mitoses and necrosis Lesions with a higher rate of recurrence and more Aggressive local growth Grade III /Anaplastic meningioma Extensive mitoses and necrosis Aggressive tumoral behavior

Summary Bad prognosis Densely cellular,sheets of anaplastic blue clles Microscopic Macroscopic Location Incidence Types Bad prognosis Densely cellular,sheets of anaplastic blue clles Hommer Wright rosettes Well circumscribe, gray and friable cerebellum Children Medulloblastoma Increased grim prognosis with grade Whorls of meningothelial cells Psammoma bodies. Well defined mass attached to dura Arachnoid meningothelial cells Attached to dura Adults Meningiomas (WHO I) Increased cellularity Higher atypia Frequent mitosis Aggressive local growth and invasion Atypical Meningiomas (WHOII) Anaplastic cells Atypical mitosis necrosis Anaplastic Meningiomas (WHO III)

Metastatic Tumors The terms metastatic brain tumor or brain metastasis refer to cancer that begins elsewhere in the body and spreads to the brain Brain metastasis can present as a single tumor or multiple tumors Metastatic tumors account for approximately 25%-50%of intracranial tumors The most common primary sites are lung, breast, skin (melanoma), kidney, and gastrointestinal tract

Metastatic Tumors Dissemination occurs by the bloodstream, less often by direct invasion from neighboring malignancies Common sites of metastases are the brain parenchyma and the meninges, less often the spinal cord and peripheral nerves Metastases to the nervous system are serious, even fatal, complications of malignancies اسم ورقم المقرر – Course Name and No. 6/2/2019

Brain, metastatic carcinoma – Gross, coronal section This section contains at least three metastatic deposits. Carcinomas that metastasize to the brain parenchyma reach the brain via arterial channels. Similar to other embolic processes, parenchymal metastases are most commonly encountered in the territory of the middle cerebral artery, often implant at gray-white junctions, and are often multiple. They are typically well circumscribed. This patient's primary tumor was in the lung.  اسم ورقم المقرر – Course Name and No. 6/2/2019

Peripheral Nerve Sheath Tumors These tumors arise from cells of the peripheral nerve, including Schwann cells, perineural cells, and fibroblasts In most peripheral nerve sheath tumors, the neoplastic cells show evidence of Schwann cell differentiation Peripheral nerve sheath tumors are important features of the familial tumor syndromes NF1 and NF2 Such tumors may manifest as Soft tissue masses With pain or loss of function related to Compression of nerves or other surrounding structures

Peripheral Nerve Sheath Tumors These tumors usually occur in adults These tumors include: Schwanoma Neurofibroma Malignant peripheral nerve sheath tumors Schwannomas and neurofibromas are benign nerve sheath tumors اسم ورقم المقرر – Course Name and No. 6/2/2019

Schwannoma Benign tumor composed of Schwann cells Found in all ages, most commonly in the fourth through sixth decades Most commonly involves peripheral nerves in skin and subcutaneous tissues of the head and neck region and flexor surfaces of extremities Accounts for about 10% of intracranial tumors (usually arises from sensory cranial nerves, most often eighth cranial nerve) and about 30% of spinal tumors

Schwannoma Associated with neurofibromatosis type 2 (NF2) (bilateral vestibular schwannomas) Peripheral tumors typically present as asymptomatic masses Spinal tumors often present with radicular pain or signs of spinal cord compression tumors of cranial nerve VIII cause hearing difficulties or tinnitus. اسم ورقم المقرر – Course Name and No. 6/2/2019

Schwannoma Gross: Encapsulated, tumors that abut the nerve of origin Microscopic: Mixture of Hypercellular (Antoni A) and hypocellular areas (Antoni B) in schwannoma Antoni (A): spindle cells with nuclear palisading Antoni (B): the spindled cells spared by mucoid extracellular matrix اسم ورقم المقرر – Course Name and No. 6/2/2019

Antoni A area with the nuclei of tumor cells aligned in palisading rows اسم ورقم المقرر – Course Name and No. 6/2/2019

Neurofibroma Common benign tumor composed of Schwann cells, fibroblasts, and perineural cells Occur sporadically most frequently but also associated with NF1 Neurofibromas may manifest as a sporadic subcutaneous nodule as a large, poorly defined soft tissue lesion a growth within a nerve

Neurofibroma Neurofibromas are not encapsulated The cells have wavy and pointed ends nuclei The background stroma often contains loose wavy collagen bundles but also can be myxoid or contain dense collagen Residual axons are found embedded within the diffuse neoplastic Schwann cell proliferation اسم ورقم المقرر – Course Name and No. 6/2/2019

No capsule Wavy nuclei with fibrous tissue No pleomorphism اسم ورقم المقرر – Course Name and No. 6/2/2019

Neurofibromatosis Type 1 (NF1) This is an autosomal-dominant disorder caused by mutations in the tumor suppressor neurofibromin The tumors arising in the setting of NF1 include: Neurofibromas Malignant peripheral nerve sheath tumors Optic gliomas, and other glial tumors Patients with NF1 exhibit: learning disabilities seizures skeletal abnormalities vascular abnormalities pigmented nodules of the iris & pigmented skin lesions

Neurofibromatosis Type 2 (NF2) This is an autosomal-dominant disorder caused by loss of function mutation of the merlin gene NF2 patients are at risk of developing: multiple schwannomas meningiomas ependymomas Neurofibromas are NOT a feature of NF2

Summary of peripheral Nerve Sheath Tumors Prognosis Microscopic Macroscopic origin Incidence Types Benign Good prognosis Mixture of Antoni (A) and Antoni (B) Encapsulated, circumscribed mass Schwann cells of peripheral nerves May be sporadic in adult & NF2 in young Shwannoma May develop MPNST wavy nerve fibers Non capsulated mass peripheral nerve fiber elements Occurs with NF1 Neurofibroma

Take Home Message Histological distinction between benign and malignant lesions may be more subtle in comparison to other body system. Even low grade tumors or benign tumors can have a poor clinical outcome depending on their location. Glioblastoma is the most aggressive and poorly differentiated glial tumor. Metastatic spread of brain tumors to other regions is rare, but brain is not comparable protected against spread of tumors elsewhere.