Brain tumors

Brain tumors are masses of abnormal cells within the brain. They can be primary or metastatic, benign or malignant. Common tumors in children are pilocytic astrocytomas, medulloblastomas, ependymomas, and craniopharyngiomas. The most common brain tumors in adults are glioblastomas, meningiomas, hemangioblastomas, schwannomas, oligodendrogliomas, and pituitary adenomas. Clinical features and radiological findings vary according to the type, location, and onset of the tumor. Magnetic resonance imaging (MRI) is the primary diagnostic method. The histological grade of the tumor is an important factor in determining the prognosis. Removal of the entire tumor is a prerequisite for remission. Malignant tumors usually require additional treatment with radiotherapy and/or chemotherapy.

Meningiomas, pituitary adenomas, schwannomas, and neoplastic meningitis are discussed in separate articles.

• Approx. 30% of brain tumors are primary brain tumors, while approx. 70% are metastases.
• Approx. 40% of primary brain tumors are benign.
• Sex: ♂ > ♀ (except meningiomas, which occur more frequently in women) ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Initial evaluation ^[2]

Clinical assessment

• Obtain a thorough patient history and neurological examination.
• Suspect a brain tumor in patients with clinical features including:
  • Headaches (especially with headache red flags)
  • Other signs of elevated intracranial pressure (ICP), e.g., papilledema
  • New onset seizures ^[3]
  • Focal neurological deficits; depending on tumor location, e.g., sensory deficits
  • Nonfocal neurological deficits
  • Cognitive, behavioral, and personality changes

Symptom onset in patients with primary brain tumors is usually insidious, while symptom onset in patients with brain metastases is typically acute or subacute.

Diagnostic testing

• Obtain neuroimaging.
  • Gadolinium-enhanced MRI head: preferred
  • CT head and neck with IV contrast: if MRI is not possible
• Further testing depends on imaging findings.
  • Findings suggestive of primary brain tumor: Consult neurosurgery for diagnostic confirmation, e.g., via brain biopsy or resection
  • Findings suggestive of metastatic brain tumor
    • Initiate diagnostics of cancer of unknown primary.
    • Obtain biopsy of the brain metastasis if primary is not identified. ^[4]

Overview of MRI findings in brain tumors

• There is significant overlap between MRI findings in common primary brain tumors (e.g., gliomas) and brain metastases.
• Brain tumors typically appear hypointense to isointense on T1-weighted images and hyperintense to isointense on T2-weighted images.

Management

Principles of treatment

Management should be specialist guided; utilize a multidisciplinary approach and consult a tumor board if available.

• Management of metastatic brain tumor
  • Identify and treat primary malignancy.
  • See “Brain metastases” for details on treatment options.
• Management of primary brain tumor
  • Based on both tumor and patient characteristics
  • May include:
    • Maximal safe surgical resection
    • Radiation therapy: e.g., standard fractionated external beam radiation therapy
    • Systemic therapy: e.g., chemotherapy, cancer immunotherapy
  • Offer clinical trial enrollment and consider palliative care for patients with high-grade tumors (e.g., glioblastoma multiforme).

Management of complications of brain tumors ^[2]

See also ”Cancer-related complications” and “Cancer treatment-related complications.”

• Venous thromboembolism (VTE) ^[14][15]
  • Consider pharmacological VTE prophylaxis for select patients.
  • Offer therapeutic anticoagulation for patients with VTE (LMWH is the preferred agent).
  • Patients with brain tumors are at increased risk of intracerebral hemorrhage; use shared decision-making for anticoagulation treatment decisions.
• Seizures ^[16][17]
  • Primary prophylaxis is not recommended.
  • Secondary prophylaxis (i.e., history of seizures): Initiate treatment of epileptic seizures. ^[18]
• Vasogenic cerebral edema
  • Administer glucocorticoids (e.g., dexamethasone ) for patients with signs of elevated ICP. ^[19][20]
  • Follow local treatment protocols when available.

Certain types of metastatic brain tumor (e.g., melanoma, renal cell carcinoma) are more likely to hemorrhage, but are not an absolute contraindication to therapeutic anticoagulation. ^[16]

Taper and discontinue perioperative prophylactic medications within 7–10 days of surgery, unless otherwise indicated. ^[2]

Classification

Primary brain tumors arise within the CNS and are classified based on the growth characteristics and cell type from which the tumor arises.

By the spreading potential

By the cell type

• Gliomas (e.g., astrocytomas and oligodendrogliomas)
• Choroid plexus tumors (e.g., choroid plexus papilloma, choroid plexus carcinoma)
• Neuronal and mixed neuronal-glial tumors (e.g., paraganglioma, central neurocytoma)
• Meningiomas (see “Classification of meningiomas”)
• Embryonal neuroectodermal tumors (e.g., medulloblastoma: , CNS neuroblastoma)
• Pituitary tumors: a group of tumors that arise from the pituitary gland (e.g., pituitary adenoma, craniopharyngioma)
• Pineal tumors
• Tumors of the cranial and paraspinal nerves (e.g., schwannoma: , neuroma, neurofibroma)
• Mesenchymal nonmeningeothelial tumors (e.g., hemangiomas, hemangioblastoma, lipoma, hamartoma)
• Germ cell tumors (e.g., teratoma)
• Primary central nervous system lymphoma (PCNSL)

Metastasis

• Primary CNS tumors do not metastasize to organs outside the CNS.
• Drop metastases (intradural extramedullary spinal metastases ) and leptomeningeal metastases may occur. ^[21]
  • Typically manifest as nodules along the spine and cauda equina that can cause back pain with neurologic symptoms (e.g., limb weakness)
  • Can be detected by lumbar puncture

Overview

Astrocytomas are neuroepithelial tumors (gliomas) that arise from astrocytes, which are a specific type of glial cell.

Pilocytic astrocytoma ^{[27][28][29][30]}

• Description: slow-growing, circumscribed, non-invasive tumor
• Epidemiology
  • Most commonly affects children and young adults (< 20 years)
  • The most common primary brain tumor of childhood
• Associated conditions: neurofibromatosis type I
• Typical location
  • Cerebellum (most common)
  • Cerebral hemispheres (supratentorial)
• Clinical features
  • Insidious onset and slow progression of symptoms
  • Vomiting
  • Ataxia
  • Failure to thrive
• Diagnostics
  • MRI findings
    • Well-demarcated cystic lesion
    • Bright contrast-enhancing solid nodule in the wall of the cyst
  • Histopathology
    • Microcysts
    • Bipolar cells; hair-like projections
    • Eosinophilic fibers with corkscrew appearance (Rosenthal fibers)
• Treatment: Surgical resection
• Prognosis
  • Favorable prognosis: high rates of long-term survival
  • Curable with complete resection of the tumor
  • Median survival: > 10 years

Optic glioma ^[31]

• Description
  • Low-grade, slow-growing tumor that arises from the glial cells of the optic pathway
  • Typically a grade I pilocytic astrocytoma
• Epidemiology: most frequently in children (< 10 years)
• Associated conditions: neurofibromatosis type I
• Clinical features
  • Insidious onset and slow progression of symptoms
  • Proptosis
  • Strabismus
  • Asymmetric nystagmus
  • Impaired vision (in case of chiasmal involvement)
• Diagnostics
  • Fundoscopy findings: retinal pallor, papilledema
  • MRI findings: thickening of the optic nerve or optic chiasm; suprasellar mass
• Treatment
  • No treatment in asymptomatic patients with no signs of tumor growth
  • Surgical resection
  • Radiotherapy
    • Unresectable tumors, e.g., chiasmal or optic tract lesions in optic glioma
    • Adjuvant to surgery
• Prognosis
  • Favorable; high rates of long-term survival
  • Many patients have long-term visual impairment.

Diffuse astrocytoma

• Description: slow-growing, infiltrative tumor that arises from glial cells in the CNS and has the potential to progress to higher-grade tumors
• Epidemiology: peak age 20–40 years
• Location: cerebral hemispheres
• Clinical features
  • Insidious onset and slow progression of symptoms
  • Initially manifest with nonspecific features such as headaches, seizures
  • Focal symptoms may develop (e.g, progressive paralysis, aphasia)
• Diagnostics
  • CT: hypodense lesion with no contrast enhancement
  • MRI
    • T1 hypointense or isointense
    • T2 hyperintense
• Treatment
  • Complete surgical resection is often not possible. resection until definable margins can be attempted
  • Percutaneous radiotherapy for very diffuse, unresectable tumors
• Prognosis: incurable; median survival: 2–12 years

Anaplastic astrocytoma ^[22][23]

• Description: A high-grade infiltrative tumor with variable rates of growth that arises from glial cells in the CNS
• Epidemiology: peak age 30–50 years of age
• Clinical features
  • Headache
  • Seizures
  • Focal neurologic deficits
  • Altered mental status
• Diagnostics
  • MRI
    • Inhomogenous lesion with perifocal edema
    • No necrosis (in contrast to glioblastoma)
  • CT
    • Hypodense lesion with variable contrast enhancement
    • Positive mass effect
• Treatment
  • Tumor debulking through surgery. However, complete surgical resection is not possible.
  • Percutaneous radiotherapy/chemotherapy
• Prognosis: incurable; median survival between 18 months and 10 years

Glioblastoma multiforme

• Description: : a highly malignant tumor derived from glial cells (e.g., astrocytes)
• Epidemiology ^[32][33][34]
  • Most common malignant brain tumor
  • Accounts for approx. 16% of all CNS neoplasms
  • ♂ > ♀ (1.6:1)
  • Peak incidence: 64 years of age
    • Primary glioblastoma (∼ 90%): more frequent in elderly patients (6^th decade of life)
    • Secondary glioblastoma (∼ 10%): affects primarily younger patients (4^th decade of life)
• Etiology
  • Environmental factors: ionizing radiation
  • Genetic or chromosomal factors ^[33]
    • Primary glioblastoma: arises de novo
      • EGFR overexpression
      • PTEN gene mutations ^[35]
      • Loss of chromosome 10q
    • Secondary glioblastoma: arises from a preexisting low-grade tumor (e.g., diffuse astrocytoma, anaplastic astrocytoma)
      • Isocitrate dehydrogenase 1 (IDH1) mutations
      • p53 gene mutations
      • Loss of chromosome 19q
• Associated conditions: rare occurrence of glioblastoma in patients with certain genetic syndromes (e.g., type I and II neurofibromatosis, tuberous sclerosis, Li Fraumeni syndrome, Turcot syndrome)
• Classification: The 2016 WHO classification groups glioblastomas mainly on the basis of IDH mutation status. ^[36]
  • IDH-wildtype glioblastoma (∼ 90%): usually corresponds with the clinically defined primary glioblastoma
  • IDH-mutant glioblastoma (∼ 10%): usually corresponds with the clinically defined secondary glioblastoma
• Clinical features
  • General clinical features of brain tumors (e.g., signs of ↑ ICP, seizures, focal neurologic symptoms)
  • Short disease course with death within weeks (Rapid tumor growth)
  • Apoplectic glioma: mimics intracranial hemorrhage and manifests with signs of ↑ ICP
• Typical location
  • Primary glioblastoma
    • White matter of the cerebral hemispheres (supratentorial)
    • Possibly bilateral, crossing the corpus callosum: butterfly glioma
  • Secondary glioblastoma: frontal lobe
• Diagnostics
  • Characteristic features on MRI and CT
    • Irregularly shaped, inhomogeneous mass
    • Perifocal vasogenic edema
    • Mass effect: midline shift, ventricular distortion
    • Possibly hemorrhage
  • MRI (gadolinium-enhanced)
    • Garland-like, enhanced margins with a hypointense necrotic core
    • T1 hypointense
    • T2 hyperintense
    • May also have multifocal enhancements
  • Contrast-enhanced CT: irregular, heterogeneous enhancement of the margins and hypointense center
  • Evaluation of IDH mutation status (via immunohistochemistry or genome sequencing)
  • Biopsy
    • Dense, pleomorphic anaplastic cells that form pseudopalisades due to central necrosis or hemorrhage
      • A histopathologic finding characterized by elongated nuclei stacked in rows that often radiate away from a central area of necrosis
      • Classically associated with glioblastoma multiforme
    • Microvascular proliferation
    • GFAP positive
• Treatment
  • Surgical resection
  • Palliative radiochemotherapy with temozolomide
  • Adjuvant chemotherapy with temozolomide
  • Glucocorticoids
  • After recurrence
    • Reresection, temozolomide, and/or radiation (if tolerated)
    • The use of other chemotherapeutic agents (carboplatin, etoposide, irinotecan, nitrosoureas) can be tried as single agents or in regimens.
    • Bevacizumab
    • Tumor-treating fields (TTFields) ^[37]
      • Noninvasive treatment modality based on the transcutaneous delivery of alternating intermediate-frequency and low-intensity electric fields to disrupt tumor cell division and inhibit tumor growth
      • The electric field interferes with cancer cells in a number of ways, including the alteration of cell membrane polarization and inhibition of microtubule polymerization.
      • Can be given in combination with adjuvant chemotherapy (e.g., temozolomide)
• Prognosis ^[33]
  • Median survival: 15 months
  • Positive prognostic factors: IDH-mutant glioblastoma, lower patient age, higher Karnofsky performance score, accessible tumor location for surgery
  • Negative prognostic factors: large tumor size (> 5–6 cm), midline-crossing tumors

Glial fibrillary acidic protein (GFAP) is an important diagnostic marker for astrocytomas; it is almost always positive in glioblastoma multiforme!

Brainstem glioma ^[38]

• Description: a tumor arising from the glial cells in the brainstem that may be low-grade (I-II) or high-grade (III-IV)
• Epidemiology: peak age 3–10 years
• Clinical features
  • Vomiting
  • Cranial nerve deficits
  • Ataxia
  • Hydrocephalus
  • Upper motor neuron signs
• Diagnostics: MRI
  • No contrast enhancement
  • T2 hyperintense lesion
• Treatment
  • Radiation and/or chemotherapy
  • Surgical resection is often impossible
• Prognosis
  • Poor, especially in diffuse pontine gliomas
  • Median survival: ∼ 10 months

• Description: : a tumor that arises from oligodendrocytes
• Epidemiology
  • Median age: 40–50 years
  • Relatively rare: ∼ 10% of primary CNS tumors
• Clinical features: : the most common location is the cerebral hemisphere (typically the frontal lobe) → seizures, focal neurological deficits, personality changes
• Diagnostics
  • Imaging: intra-parenchymal tumor with calcifications ^[39]
    • CT: hypodense lesion
    • MRI
      • T1: hypointense or mixed lesions
      • T2: hyperintense lesions
  • Biopsy ^[40]
    • Cells with a clear cytoplasm and round nucleus (fried egg cells)
    • Chicken-wire pattern of capillary anastomoses
  • Molecular testing: assessment of 1p/19q codeletion ^[41]
• Treatment
  • Resection
  • Adjuvant radiotherapy and chemotherapy
  • Common chemotherapeutic regimens ^[42]
    • Procarbazine PLUS lomustine PLUS vincristine
    • Temozolomide monotherapy
• Prognosis
  • Recurrence rate ∼ 100%
  • 5-year survival rate 50–60%

• Description: a tumor that arises from ependymal cells of the ventricular system
• Epidemiology: peak incidence in children and young adults
• Associated conditions: neurofibromatosis type II
• Clinical features: the 4^th ventricle is the most common location in children → noncommunicating hydrocephalus → features of increased intracranial pressure (e.g., papilledema, headache)
• Diagnostics
  • Imaging: intra-parenchymal tumor with calcifications and cystic components due to necrosis and/or hemorrhage
  • Biopsy
    • Perivascular pseudorosettes
    • Rod-shaped bodies (blepharoplasts) near the nucleus
• Treatment
  • Resection
  • Adjuvant radiotherapy
• Prognosis
  • Depends on the WHO grade, but usually poor
  • Overall 5-year survival rate: 65–90% ^[43][44]

• Description: a highly malignant tumor derived from primitive, neuroectodermal tissue ^[45]
• Epidemiology
  • Peak incidence: 1^st decade
  • Most common malignant pediatric brain tumor (20–25% of all cases)
• Associated conditions: Turcot syndrome
• Clinical features ^[46]
  • The most common location is the cerebellum → cerebellar defects (e.g., broad-based gait)
  • Most tumors arise within the cerebellar vermis (midline) → truncal ataxia
  • Invasion or compression of the 4^th ventricle → noncommunicating hydrocephalus → features of raised intracranial pressure (e.g., papilledema, vomiting, headache)
  • Drop metastases to the spinal cord are common → paraplegia
• Diagnostics ^[47]
  • Imaging: intraparenchymal contrast-enhancing mass ^[48]
    • CT scan: isodense or hyperdense mass
    • MRI
      • T1: hypointense mass
      • T2: isointense mass
  • Biopsy: anaplastic small round blue cells; that surround a central neuropil (Homer-Wright rosettes) ^[49]
• Treatment ^[50]
  • Resection
  • Adjuvant therapy
    • Children ≥ 3 years: chemotherapy and craniospinal radiotherapy
    • Children < 3 years: chemotherapy
  • Common chemotherapeutic agents: vincristine, cisplatin, cyclophosphamide, lomustine ^[50]
• Prognosis
  • 5-year survival rate: 60–80% ^[51][52]
  • Poor prognostic factors ^[53]
    • Inadequate resection
    • Presence of drop metastases
    • HER2/neu mutation

• Description: a benign dysontogenetic tumor arising from a remnant of the Rathke pouch (ectodermal derivative)
• Epidemiology
  • Bimodal distribution: 5–14 years; second peak at 50–75 years
  • Most common childhood supratentorial tumor
• Clinical features: The tumor arises in the suprasellar region and can extend into the intrasellar region. ^[54]
  • Compression of the pituitary gland due to intrasellar extension → hypopituitarism
    • Hypogonadotropic hypogonadism
    • Failure to thrive
    • Central diabetes insipidus
  • Compression of the ventromedial hypothalamic nucleus → hyperphagia and obesity
  • Compression of the infundibular stalk → disconnection hyperprolactinemia
  • Compression of the optic chiasm → bitemporal hemianopsia
  • Compression of interventricular foramina and/or aqueduct → obstructive hydrocephalus
• Diagnostics ^[55]
  • Imaging: suprasellar calcified cyst with a lobulated contour
  • Biopsy: cholesterol crystals found in a motor oil-like fluid on gross examination
  • Consider obtaining diagnostics for hypopituitarism.
• Histological variants
  • Adamantinomatous (common)
    • Reticular epithelial cells
    • Frequently associated with calcifications
    • Cysts and keratin nodules
  • Papillary
    • Metaplastic squamous cells
    • Calcifications and cysts are rare.
    • No keratin nodules
• Differential diagnoses
  • Pituitary adenoma
  • Rathke cleft cyst
• Treatment
  • Resection
  • Adjuvant radiotherapy
  • Treatment of hypopituitarism
• Prognosis: generally good, with a 10-year survival rate of ∼ 90%; however, the recurrence rate is high ^[56][57][58]

• Description: a tumor that forms in or near the pineal gland and includes pineocytomas, pineoblastomas, and pineal germinomas
• Epidemiology
  • ♂ > ♀
  • < 1% of all CNS tumors in adults
• Clinical features
  • Compression of dorsal midbrain leads to:
    • Compression of tectum → vertical gaze palsy (Parinaud syndrome)
    • Compression of cerebral aqueduct → noncommunicating hydrocephalus
    • Compression of hypothalamic inhibiting pathways → increased hCG secretion → precocious puberty
• Diagnostics: MRI of the brain and biopsy
• Histology
  • Approx. 70% are germinomas (similar appearance to testicular seminoma)
  • Large vacuolated cells with round nuclei (fried egg cells)
  • Lymphoid stroma
• Treatment
  • Resection
  • Adjuvant radiochemotherapy

• Description: : a benign, highly vascularized neoplasm
• Epidemiology
  • Rare
  • Peak incidence: 20–50 years
• Associated conditions: von Hippel-Lindau disease
• Clinical features
  • The cerebellum is the most common location → cerebellar defects
  • Compression of the 4^th ventricle → non-communicating hydrocephalus → features of raised ICP (e.g., papilledema, headache)
  • Erythropoietin production by tumor cells → secondary polycythemia
• Diagnostics
  • MRI; : sharply demarcated intra-parenchymal cystic mass with a non-enhancing wall and an enhancing mural nodule in ∼ 60% of cases ^[59][60]
    • T2: hyperintense mass
    • T1: hypointense or isointense mass
  • Biopsy: thin-walled capillary vessels, densely packed together with scarce parenchyma
• Treatment
  • Resection
  • Antiangiogenic therapy (e.g., bevacizumab)
• Prognosis: Recurrence risk is < 20% in sporadic cases. ^[61]

Definition ^[9][62]

PCNSL is a rare form of extranodal non-Hodgkin lymphoma that affects the CNS (e.g., brain, eyes, spinal cord, CSF).

Epidemiology ^[9]

• ∼ 4% of CNS neoplasms ^[9]
• Highest incidence: adults aged 70–79 years ^[9]
• Commonly associated with immunosuppression (e.g., poorly controlled HIV/AIDS) and/or EBV infection

Clinical features ^[9]

• Focal neurological deficits
• Nonspecific cognitive or behavioral changes
• Signs of increased ICP, e.g., headache
• Seizures (less common)

Diagnostics ^[9][63]

Initial evaluation

• Neuroimaging
  • Gadolinium-enhanced MRI brain
    • Obtain for all patients.
    • Supportive findings include periventricular lesions with homogeneous enhancement.
  • Gadolinium-enhanced MRI spine: Obtain if there are symptoms of spinal cord lesions.
• Histopathology or cytopathology: necessary for diagnostic confirmation
  • Preferred: stereotactic brain biopsy
  • Alternatives
    • Lumbar puncture: CSF cytology or flow cytometry
    • Vitrectomy: vitreous fluid cytology or flow cytometry

When present, lymphoma cells in CSF or vitreous fluid may be sufficient to establish a diagnosis of PCNSL. ^[9]

Additional evaluation ^[63]

• Pretreatment evaluation
  • Clinical evaluation
    • Thorough physical examination including lymph nodes and testicles
    • Cognitive assessment to establish baseline cognitive function
  • Laboratory studies
    • CMP: Ensure hepatic and renal function are adequate for undergoing treatment.
    • LDH: Elevated LDH is a poor prognostic factor.
    • HIV testing
• Staging
  • Obtain NHL staging, including:
    • Lumbar puncture with CSF assessment
    • Whole-body imaging
    • Bone marrow biopsy
  • Refer for ophthalmology evaluation (including a slit-lamp examination).
  • Assess for secondary malignancies.

Treatment ^[9][62]

• Optimal treatment regimens are an area of ongoing investigation.
• Most regimens include rituximab, high-dose methotrexate, and an alkylating agent.
• Surgical resection is usually not indicated.
• Low-dose whole brain radiotherapy can be used as part of consolidation therapy or palliative therapy.
• Monitor for complications of brain tumors.

Glucocorticoids can decrease diagnostic yield in lymphoma. Except in situations of life-threatening increased ICP, avoid glucocorticoid use until diagnostic tissue and fluid samples have been obtained. ^[9]

Prognosis ^[9]

• Variable
• Typically better than other primary CNS tumors but less favorable than non-CNS lymphomas

Pediatric primary brain tumors ^[64][65][66]

• Most pediatric brain tumors are primary.
  • Most common type of benign pediatric primary brain tumor: pilocytic astrocytoma
  • Most common malignant pediatric primary brain tumor: medulloblastoma
• Brain tumors are the second most common cause of pediatric cancer; after leukemia, accounting for approx. 20% of all cases of pediatric cancer and the primary cause of pediatric cancer deaths in the US.

In children, most primary brain tumors arise infratentorial, craniopharyngiomas being an important exception.

Adult primary brain tumors ^[2]

• Primary brain tumors are less common than brain metastases in adults.
  • Most common benign primary brain tumor in adults: meningioma
  • Most common malignant primary brain tumor in adults: glioblastoma multiforme
• Primary brain tumors account for 1–2% of cancer cases in adults.

In adults, most primary brain tumors arise supratentorially, hemangioblastomas and schwannomas being important exceptions.

Definition

Brain metastases are secondary brain tumors due to metastasis of primary malignancies of other organs.

Epidemiology

• Most common cause of brain tumors in adults ^[11]
• Rare in children < 14 years of age ^[75]

Etiology ^[76]

• Lung cancer (most common) ^[76]
• Breast cancer
• Pancreatic cancer
• Malignant melanoma
• Renal cell carcinoma
• Colorectal carcinoma
• Testicular cancer ^[77]

Clinical features

• Onset: acute or subacute due to rapid tumor growth
• Seizures
• Focal neurological deficits
• Cognitive deficits
• Headaches

Diagnostics ^[2]

• Gadolinium-enhanced MRI
  • Well-circumscribed tumors at the junction of gray and white matter and/or watershed areas of the arterial system ^[78]
  • Small metastases: homogeneous enhancement
  • Large metastases: ring enhancement due to central necrosis
• Further evaluation
  • If the primary tumor is unknown: Obtain “Diagnostics of cancer of unknown primary.”
  • If no primary tumor is identified: Obtain