Brain Neoplasm, Benign and Low Grade

• Emma H. Weiss B.B.A.
• Nicole J. Ullrich, M.D., PH.D.
• Joseph S. Kass, M.D., J.D.

 Basic Information

Definition

Brain neoplasms are a diverse group of primary (nonmetastatic) tumors arising from one of many different cell types within the central nervous system (CNS). Specific tumor subtypes and prognosis depend on the tumor cell of origin and pattern of growth. The diffuse low-grade gliomas (LGGs) include World Health Organization Grade II astrocytomas, oligodendrogliomas, and oligoastrocytomas.

Synonyms

1. Low-grade glioma (LGG)

2. Glioneuronal tumor

3. Meningioma

4. Primary brain tumor

ICD-10CM CODES
D33.2	Benign neoplasm of brain, unspecified

Epidemiology & Demographics

Incidence

U.S. incidence rate of a new brain tumor is approximately 6.4/100,000 persons per yr for all primary brain tumors (Table 1). One third of these are considered malignant and the remainder benign or borderline malignant. The incidence rate in children aged 0 to 19 years is lower (5.6 per 100,000 children). Primary brain neoplasms account for ∼2% of all cancers, with a disproportionate share of cancer morbidity and mortality. It is the most common cause of cancer death in children up to 15 yr.

Peak Incidence

Depends on histology, though highest peak at ∼age 50 yr.

Predominant Sex and Age

Slight male predominance of malignant brain tumors (8.0 vs. 5.5/100,000 person/yr). Men account for slightly less than half of cases of both benign and malignant brain tumors, as meningiomas have a higher incidence in women.

Genetics

Most primary CNS neoplasms are sporadic; 5% is associated with hereditary syndromes that predispose to neoplasia. The most common of these include:

1. •

   Li-Fraumeni syndrome: p53 mutation on chromosome 17q13, gliomas

2. •

   Von Hippel-Lindau: VHL, chromosome 3p25, hemangioblastoma

3. •

   Tuberous sclerosis: TSC1/TSC2 (chromosome 9q34/16p13), subependymal giant cell astrocytoma

4. •

   Neurofibromatosis type 1: NF1, chromosome 17q11, neurofibroma, optic nerve glioma, low-grade glioma

5. •

   Neurofibromatosis type 2: NF2, chromosome 22q12, schwannoma, meningioma, ependymoma

6. •

   Retinoblastoma: pRB, chromosome 13q, retinoblastoma

7. •

   Gorlin’s syndrome: PTCH, chromosome 9q31, desmoplastic medulloblastoma

8. •

   Hereditary nonpolyposis colorectal cancer (HNPCC): mismatch repair deficiency, high-grade gliomas

Risk Factors

Exposure to ionizing radiation has been implicated in meningiomas, gliomas, and nerve sheath tumors. No convincing evidence has shown a link with trauma, occupation, cellular phone use, diet, or electromagnetic fields.

Physical Findings & Clinical Presentation

1. •

   In general, the location, size, and rate of growth will determine the symptoms and signs of a brain tumor.

2. •

   Headache is common and is the worst symptom in nearly half of all patients. The headaches are usually dull, constant pain that is often worse at night. Symptoms of increased intracranial pressure may also be present, including nausea and vomiting, and may worsen with changes in body position that increase thoracic pressure (coughing, sneezing, Valsalva maneuver). Papilledema is suggestive of obstructive hydrocephalus.

3. •

   Seizures occur in 33% of patients and are among the most common symptoms, particularly with brain metastases and low-grade gliomas. The type of seizure and clinical presentation depend on the location of the brain tumor. Tumor-related seizures are typically repetitive and have similar presentation patterns. It is thought that patients with seizures typically have smaller tumors at the time of diagnosis compared with those with other symptoms, because the onset of seizures prompts an imaging study, leading to an earlier diagnosis.

4. •

   Focal neurologic signs and symptoms, including muscle weakness, sensory changes, or visual disturbances are also quite frequent. In addition, cognitive dysfunction, accompanied by changes in memory or personality change, may be recounted, often in retrospect.

Etiology

Most cases are idiopathic, though specific chromosomal abnormalities have been implicated in some tumor types.

Diagnosis

1. •

   Diagnosis is typically based on clinical presentation and imaging characteristics. Specifically, neuroimaging is critical for preoperative planning and tumor etiology.

2. •

   Tumors are best seen on brain MRI with and without contrast; calcifications are sometimes present.

3. •

   Benign and low-grade tumors, typically in the glioma family, are heterogeneous and are generally seen as an infiltrating hemispheric lesion.

Laboratory Tests

1. •

   Ultimately, only histologic examination can provide the exact diagnosis. Additional features such as proliferative index, immunohistochemical stains, and electron microscopy can also be used to aid in diagnosis.

2. •

   The current classification schema for gliomas is based on pathologic and microscopic criteria. Tumor histology/histologic diagnosis (World Health Organization [WHO] grading system), includes number of mitoses, capillary endothelial proliferation, and necrosis. However, even tumors with benign histology can cause significant morbidity due to their location and effect on surrounding structures.

3. •

   Genetic analysis of tumors is rapidly becoming important for genetic classification, stratification of treatments, and predicting outcome. Different subtypes of gliomas have distinct gene-expression profiles, which can be distinguished from one another and from normal tissue; these differences typically involve pathways of cell proliferation, energy metabolism, and signal transduction. In adults, global expression profiling identified differences in 360 genes between low-grade and high-grade tumors.

Differential Diagnosis

1. •

   Stroke/cerebral hemorrhage

2. •

   Abscess/parasitic cyst

3. •

   Demyelinating disease: multiple sclerosis, postinfectious encephalomyelitis

4. •

   Metastatic tumors

5. •

   Primary CNS lymphoma

Workup

1. •

   Neuroimaging studies and pathologic sampling are the most important diagnostic modalities in evaluation of brain tumors and may be critical for preoperative planning.

Imaging Studies

1. •

   MRI with gadolinium enhancement is highly sensitive and permits visualization of the tumor with relation to the surrounding tissue. Specifically, enhancing tumor can be distinguished from surrounding edema. Low-grade tumors often present as an infiltrating lesion without mass effect. MRI is superior to CT scanning for evaluating the meninges, subarachnoid space, and posterior fossa, and for defining relation to major intracranial vessels, although CT scanning is useful if calcification or hemorrhage is suspected (Fig. E1). Fig. E2 shows the appearance of astrocytoma in imaging studies.

   

   

2. •

   Magnetic resonance spectroscopy is increasingly being used as a diagnostic tool to help differentiate intracranial tumors from other intracranial processes using different chemical markers. For example, N-acetylaspartate is often decreased in brain tumors, whereas choline, a component of cell membranes, is often increased in brain tumors because of high cellular turnover.

3. •

   PET scan is helpful to distinguish neoplastic lesions (with high rate of metabolism) from other lesions such as demyelination or radiation necrosis (with a much lower metabolic rate). Such lesions take up greater amounts of glucose than surrounding tissues or tumors with slower metabolic rates. May be useful to help map functional areas of the brain before surgery or radiation.

4. •

   Functional MRI is now used as an adjunct in perioperative planning for patients whose lesion is in vital regions, such as those responsible for speech, language, and motor control.

Treatment

Nonpharmacologic Therapy

1. •

   Maximal surgical removal or debulking is the initial treatment of choice and provides tissue for diagnosis and molecular characterization. Maximal safe resection is often favored with a trend toward improved survival with this approach.

2. •

   Biopsy alone is performed if the tumor is located in eloquent regions of brain or is inaccessible; this is essential for histopathologic diagnosis. Biopsy can be performed under CT or MRI guidance using stereotactic localization.

3. •

   If the tumor is benign (e.g., meningioma, acoustic neuroma), often no further therapy is required.

Acute General Rx

Antiseizure medications have been used perioperatively and to control seizures resulting from focal lesions. Prophylactic use of anticonvulsants is not typically recommended without clear history of seizures.

Chronic Rx

1. •

   Chemotherapy (combination or single agent) may be used before, during, or after surgery and radiation therapy. In children, chemotherapy is often used to delay radiation therapy. A recent trial in patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone.¹

2. •

   Radiation is useful for certain types of tumors and is often used if there is residual tumor after surgery; conventional radiation uses external beams over a period of weeks, whereas stereotactic radiosurgery delivers a single, high dose of radiation to a well-defined area (usually <1 cm). Long-term effects of radiation therapy include radiation necrosis (particularly of white matter), blood vessel hyalinization, and secondary tumors (usually meningiomas, sarcomas, and malignant astrocytomas). Radiosensitizers may help increase the therapeutic effect of radiation therapy.

3. •

   Experimental therapies are continually in development and target molecular characterization of tumors and small molecule blockers of signal transduction cascades involved in tumor growth. Some of these therapies involve antisense molecules, biologic agents, immunotherapies, or angiogenesis inhibitors. Intratumoral drug infusions and convection-enhanced delivery of novel agents are currently under study.

Disposition

In general, younger age, high performance status, and lower pathologic grade have more favorable prognosis. For all histologic subtypes of brain tumors, pediatric and young adult patients have a better survival rate.

Referral

1. •

   All cases warrant evaluation by an oncologist and neurosurgeon.

2. •

   Patients should be evaluated for physical and occupational therapy.

3. •

   Children should undergo neuropsychologic evaluations and screening for learning disabilities.

Pearls & Considerations

Comments

In general, younger age, high performance status, and lower pathologic grade have more favorable prognosis. For all histologic subtypes of brain tumors, pediatric and young adult patients have a better survival.

Patient/Family Education

1. American Brain Tumor Association (http://www.abta.org)

2. National Brain Tumor Society (http://www.braintumor.org)

3. Pediatric Low Grade Astrocytoma (PLGA) (http://fightplga.org)

Suggested Readings

• J.C. Buckner, et al.: Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 374:1344–1355 2016 27050206

• A.S. Jakola, et al.: Comparison of a strategy favoring early surgical resection vs a strategy favoring watchful waiting in low-grade gliomas. JAMA. 308 (18):1881–1888 2012 23099483

• Q.T. Ostrom, et al.: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol. 17 (Suppl 4):iv1–iv62 2015 26511214

• A. Perkins, G. Liu: Primary Brain Tumors in Adults: Diagnosis and Treatment. Am  Fam Physician. 93 (3):211–217 2016 26926614

Related Content

1. Brain Cancer (Patient Information)

2. Astrocytoma (Related Key Topic)

3. Meningioma (Related Key Topic)