Brain Tumors UMST

Introduction

• Brain tumors are a diverse group of neoplasms arising from various cell types within the brain, spinal cord, or meninges.
• Tumors can be primary (originating from the CNS) or secondary (metastasis from other parts of the body).
• The estimated incidence of brain tumors is 5-20 per 100,000 people.
• All ages are affected, with distinct peaks in childhood (3-12 years) and adulthood (55-65 years).
• CNS tumors account for about 20% of childhood cancers (second most common after leukemia).
• Childhood CNS tumors differ from adult tumors in histological subtype and location (usually subtentorial in children versus supratentorial in adults).
• Approximately 1¼-1½ of brain tumors are metastatic.
• Tumors vary in behavior, from benign to highly malignant cancers.
• They are a significant cause of morbidity and mortality due to their critical location, affecting vital neurological functions even if histologically benign.

Primary Brain Tumor

• Originate from cells intrinsic to the CNS or its coverings.
• Lack premalignant or in situ stages.
• Even low-grade lesions are infiltrative, sometimes affecting large parts of the brain.
• Patient course is influenced by growth patterns and location.
• Rarely spread outside the CNS, infiltrating locally or reaching the subarachnoid space, potentially causing multiple implants in the brain or spinal cord.

Etiology and Pathogenesis

• Genetic Factors:
  • Mutations in isocitrate dehydrogenase (IDH) genes are linked to grade II astrocytomas and oligodendrogliomas. This leads to increased 2-hydroxyglutarate production, affecting enzymes regulating gene expression.
  • Promoter mutations for telomerase contribute to tumor cell immortality.
  • P53 mutations are also implicated.
  • Chromosome 1p and 19q co-deletions are found in oligodendrogliomas.
  • Overexpression of platelet-derived growth factors is associated with astrocytomas.
  • Inherited genetic mutations are a major component of certain disorders, like neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau syndrome.

Risk Factors

• Radiation: Meningioma is an example.
• Immunosuppression: Primary CNS lymphoma in HIV patients.

Pathology

• Tumors produce neurological features by directly invading, infiltrating, and damaging brain tissue, disrupting function.
• Intracranial tumor growth often accompanied by edema leads to increased intracranial pressure which may hinder/interrupt blood supply or cause herniation.
• Tumors close to the ventricles can obstruct cerebrospinal fluid flow, resulting in hydrocephalus.

Diagnosis

• Clinical Features: Patient age, gender, and neurological symptoms are assessed.
• Radiological Diagnosis: Imaging Studies (X-rays, MRI, CT scans) are used to visualize the tumor.
• Laboratory Diagnosis: Biopsy and genetic studies aid further characterization.

Clinical Features of Brain Tumors

• Even small tumors can cause symptoms.
• Symptoms of increased intracranial pressure include headache, vomiting, blurred vision, etc.
• Convulsions, focal neurological deficits, mental changes, and hydrocephalus may occur.
• A head lump can also be a symptom.

Features of Increased Intracranial Pressure

• Headache (frontal, parietal, or occipital).
• Nausea and/or vomiting.
• Papilledema.

Focal Neurological Deficits

• Bitemporal hemianopsia
• Mental status changes
• Speech and personality changes.
• Motor weakness, seizures, or hypasthesias.
• Balance difficulties

Clinical Features Related to CNS

• Skull lump.

Classification of Brain Tumors

• Classified by WHO based on presence of four morphological parameters.
• Parameters impact how the tumor progresses.
• Histological Features:
  • Nuclear atypia.
  • Mitosis.
  • Vascular proliferation.
  • Necrosis.

Classification of Brain Tumors based on 4 Grades

• Classified from grade I (benign) to grade IV (malignant).

• Specific grade types carry distinct names.

  • Astrocytoma grade IV = Glioblastoma Multiform.
  • Astrocytoma grade III = Anaplastic astrocytoma.
  • Astrocytoma grade II = Diffuse astrocytoma
  • Additional classifications may exist based on cell or origin.

Gliomas

• Most frequent group (40-45%) of primary tumors.
• Classification is based on the glial cells they resemble.
  • Astrocytomas.
  • Oligodendrogliomas.
  • Ependymomas.

Astrocytoma

• Glioma that shows astrocytic differentiation.

• Subclassifications:

  • Diffuse astrocytoma: Diffuse infiltration of brain tissue.
  • Pilocytic astrocytomas.

Pilocytic Astrocytoma

• Benign, slow-growing tumor with good prognosis.
• Typically occurs in children and young adults.
• Commonly located in the cerebellum, floor, and walls of the third ventricle.

Diffuse Astrocytoma

• Common site is cerebral hemispheres.
• May also occur in cerebellum, brainstem, and spinal cord.
• Typically occurs in fourth to sixth decades.

Well-differentiated Astrocytoma

• Macroscopically: Poorly demarcated, infiltrative tumor.
• Microscopically: Increased cellularity due to astroglial tumor cells, mild nuclear pleomorphism.
• Immunohistochemistry: Positive for GFAP (glial fibrillary acidic protein).

Radiological Findings

• Diffuse ill-defined tumor.

Anaplastic Astrocytomas

• Poorly demarcated infiltrative tumor.
• Increased cell numbers.
• Increase cellular and nuclear pleomorphism.
• Increased presence of mitotic figures (mitosis).

Glioblastoma

• Gross: Variable consistency and color. May show firm white, soft yellow, and/or red areas, often caused by necrosis or hemorrhage.
• Can show cystic degeneration.

High-Grade Brain Tumors

• Morphology features: Necrosis, hemorrhage, infiltration.

Microscopy

• Similar to anaplastic astrocytoma with necrosis or vascular-endothelial cell proliferation.
• Marked increased cellularity.
• Marked cellular and nuclear pleomorphism.
• Anaplasia.
• Frequent mitoses.
• Necrosis.
• Vascular or endothelial cell proliferation & glomeruloid body formation.

Primary Glioblastoma

• Develops de novo without a previous low-grade astrocytoma.
• Usually occurs in older adults.

Secondary Glioblastoma

• Develops from a pre-existing lower-grade astrocytoma
• Often occurs in younger patients

Treatment and Prognosis

• Treatment strategies include surgical removal, chemotherapy, and radiation therapy.
• Well-differentiated diffuse astrocytomas can remain stable or progress slowly over years.
• Glioblastoma carries a poor prognosis, where death generally occurs within 1.5 years of diagnosis.

Embryonal Tumors

• Originate from neuroectodermal cells, lacking differentiation (small blue round cells).
• Medulloblastoma is a common example.

Medulloblastoma

• Highly malignant embryonal/undifferentiated tumor.
• Neuronal and glial markers may or may not be present.
• Predominantly affects children (mostly at the end of the first decade of life).
• Accounts for approximately 20% of childhood brain tumors.

Morphology (Medulloblastoma)

• Exclusively in the cerebellum in children

• Midline of cerebellum.

• Lateral locations in adults

• Microscopically: Highly cellular with sheets of anaplastic small blue cells, numerous mitotic figures.

Medulloblastoma Microscopy

• Homer-Wright rosettes (central neutrophils surrounded by primitive tumor cells) are characteristic.
• Immunohistochemistry: Positive for GFAP (glial fibrillary acidic protein).

Spread

• CSF dissemination, may present as nodular masses throughout CNS.
• Drop metastases to the cauda equina.

Clinical Features (Medulloblastoma)

• Cerebellar dysfunction or issues.
• Hydrocephalus due to CSF flow occlusion caused by rapid tumor growth.

Treatment and Prognosis (Medulloblastoma)

• Treatment includes surgery, chemotherapy, and irradiation.
• Poor outcome for untreated patients.
• Good outcome with extensive excision, chemotherapy, and radiation therapy.
• MYC amplification is associated with poor prognosis.

Meningioma

• Occur in adults (females more than males).
• Arises from meningeal arachnoid cells.
• Associated with an NF2 gene defect.
• Classifications:
  • Typical meningioma (WHO grade I) - benign
  • Atypical meningioma (WHO grade II)
  • Anaplastic meningioma (WHO grade III)

Morphology (Meningioma)

• Highly variable, with large polygonal cells, psamomma bodies, and potential bone invasion.

Lymphoma

• May occur as primary CNS lymphomas or from extra-CNS spread.
• Primarily high-grade diffuse B-cell lymphomas.
• Several systemic lymphomas can potentially spread to the CNS, but Hodgkin lymphoma exceptionally rarely does.

Primary CNS Lymphomas

• Some associated with Epstein-Barr virus reactivation, especially in immunocompromised individuals.
• Often exhibit a periventricular distribution.

Metastatic Brain Tumors

• Constitute about 25% of all brain tumors.
• Often originate from lung, kidney, breast, or malignant melanoma, most commonly
• Varying metastatic patterns linked to specific tumor types.
• Diffuse metastases can manifest as carcinomatous encephalitis.

Test your knowledge on the various genetic mutations associated with brain tumors and their implications in tumor cell immortalization. This quiz covers factors contributing to tumor types, risks associated with radiation, and related neurological features. Perfect for those studying oncology or neurobiology!