Benign vs. Malignant Neoplasia and Nervous System Tumors

• Benign neoplasia exhibits slow growth, well-differentiated cells, and localized behavior without invading nearby tissues or metastasizing.
• Benign neoplasia is morphologically characterized by uniform cells, a low mitotic rate, and clear margins.
• Malignant neoplasia shows rapid, invasive growth with poorly differentiated cells and the capacity to metastasize.
• Malignant neoplasia is morphologically characterized by high cellular atypia, high mitotic activity, necrosis, and vascular proliferation.

Classification of Tumors of the Nervous System and Coverings

• Primary nervous system tumors include gliomas, glioneuronal and neuronal neoplasms, pineal neoplasms, cranial and paraspinal nerve neoplasms and meningeal neoplasms
• Further primary nervous system tumors include embryonal neoplasms, choroid plexus neoplasms, mesenchymal and non-meningothelial neoplasms, neoplasms of the sellar region, lymphoma and histiocytic neoplasms, and germ cell neoplasms.
• Metastatic tumors spread to the brain/spinal cord parenchyma or meninges.

General Grading Principles of Primary CNS Tumors

• Grade 1 tumors have low proliferative potential and slow growth.
• Grade 2 tumors show infiltrative growth, a low mitotic rate, and potential for recurrence after treatment.
• Grade 3 tumors exhibit malignant behavior, nuclear atypia, and moderate mitotic activity.
• Grade 4 tumors are highly malignant with a high mitotic rate, necrosis, and vascular proliferation.
• CNS tumors are considered to have a malignant course due to limited space within the skull, compression of vital brain structures, and local invasion/tissue destruction.
• Even slow-growing CNS tumors can lead to severe neurological deficits.
• CNS tumors rarely metastasize outside the CNS.

Primary CNS Tumor Examples

• Gliomas (astrocytoma, oligodendroglioma, glioblastoma)
• Meningiomas
• Ependymomas
• Medulloblastomas
• Choroid plexus tumors
• Schwannomas
• Craniopharyngiomas
• Lymphomas

Spread of Primary Nervous System Tumors

• Primary nervous system tumors spread locally within the CNS via cerebrospinal fluid (CSF) dissemination.
• Primary nervous system tumors rarely metastasize outside the CNS.
• Primary nervous system tumors can show invasive growth into brain parenchyma or adjacent structures.

Adult-Type Diffuse Gliomas

• Astrocytoma is IDH-mutant.
• Oligodendroglioma is IDH-mutant with 1p/19q codeletion
• Glioblastoma is IDH-wildtype

Astrocytoma Morphological Features

• Macroscopic features include poor definition, infiltrative nature, firm texture, and frontal lobe location.
• Grade 2 astrocytomas are well-differentiated with a low mitotic rate
• Grade 3 astrocytomas exhibit cellular atypia and increased mitotic activity
• Grade 4 astrocytomas show necrosis, microvascular proliferation, and a high mitotic rate.

Oligodendroglioma vs. Glioblastoma

• Oligodendroglioma has clear cytoplasm (fried-egg appearance), microcalcifications, and a low mitotic rate.
• Glioblastoma is characterized by high cellularity, pleomorphism, necrosis, and vascular proliferation.

Importance of Molecular Profiling

• Molecular profiling is crucial for diagnosis, prognosis, and therapeutic decisions.

Molecular Profiling Examples

• IDH mutation indicates a better prognosis in astrocytomas and oligodendrogliomas.
• 1p/19q codeletion is diagnostic of oligodendrogliomas.
• TERT mutation indicates a poor prognosis in glioblastomas

Methods for Molecular Profiling

• Immunohistochemistry (IHC)
• Fluorescence In Situ Hybridization (FISH)
• Polymerase Chain Reaction (PCR)
• Next-Generation Sequencing (NGS)

Molecular Profiles Comparison

• Astrocytoma has IDH-mutant, ATRX-mutant, and p53-mutant profiles.
• Oligodendroglioma has IDH-mutant, ATRX-wildtype, and 1p/19q codeletion profiles.
• Glioblastoma has IDH-wildtype, ATRX-mutant, and p53-mutant profiles.

Meningeal Tumors

• Meningioma encompasses 15 histological types, with common subtypes including meningothelial, fibrous, and transitional variants.

Grade 1 vs. Grade 2 Meningioma

• Grade 1 meningiomas have clear margins, slow growth, and no brain invasion.
• Grade 2 meningiomas show increased mitotic activity, brain invasion, and a risk of recurrence.

Complications and Causes of Death

• Complications and causes of death can include cerebral edema, herniation, neurological deficits, and stroke.
• Secondary complications include pneumonia and thromboembolism.

Damage by Metastatic Tumors

• Metastatic tumors cause damage through direct compression and destruction of brain tissue.
• Metastatic tumors can induce cerebral edema, hemorrhage, and increased intracranial pressure.

Common Primary Sources of CNS Metastases

• Common primary sources are lung carcinoma (especially small-cell), breast carcinoma, gastrointestinal cancers, and melanoma.

Morphologic Features of Cerebral Metastases

• Cerebral metastases are well-demarcated, located at the grey-white junction, and exhibit central necrosis and edema.

Peripheral Nervous System (PNS) Tumors

• Benign PNS tumors include schwannoma and neurofibroma.
• Malignant PNS tumors include malignant peripheral nerve sheath tumor (MPNST).

Morphologic Features of PNS Tumors

• Schwannoma exhibits mixed cellularity and a palisading pattern.
• Neurofibroma exhibits wavy spindle cells and encapsulation.

Genetic Syndromes Affecting CNS/PNS

• Neurofibromatosis (Type I and II)
• Tuberous Sclerosis
• Von Hippel-Lindau Disease

Affected Structures and Morphologic Features in Genetic Disorders

• Neurofibromatosis is associated with schwannomas, neurofibromas, and optic gliomas.
• Tuberous sclerosis is associated with cortical tubers and subependymal nodules.
• Von Hippel-Lindau disease is associated with hemangioblastomas and renal cell carcinoma.