CNS manifestations of Systemic Cancer

Dr Anil Khosla

Metastasis to the brain is the most feared complication of systemic cancer and the most common intracranial tumor in adults. Incidence is rising with improved survival of cancer patients. Currently, cancer patients live longer as a result of important advances in cancer diagnosis and management, and in particular, the widespread use of MRI to detect small metastases. Approximately, 40 per cent of intracranial neoplasms are metastatic. Multiple, large autopsy series suggest that, in order of decreasing frequency, lung, breast, melanoma, renal, and colon cancers are the most common primary tumors to metastasise to the brain.

Most metastases are round well-demarcated lesions located at the junction of gray and white matter. Leaky tumor vessels result in an extensive zone of edema surrounding the tumor. Lesions are located in the cerebrum (80-85 per cent), in the cerebellum (10-15 percent), and in the brain stem (3-5 per cent). Slightly more than 50 per cent of the time, multiple as opposed to solitary metastases occur, but this varies with the type of primary tumor. Melanoma, lung, and breast primaries are more likely to produce multiple metastases.

Intracranial metastases can be categorised by location as skull, dura, leptomeninges, and parenchymal brain metastases. Lesions of the brain and leptomeninges comprise 80 per cent of intracranial metastases. Meningeal carcinomatosis most commonly occurs in patients with breast carcinoma, malignant melanoma, and less commonly, with lymphoma, leukemia, and other tumors.

Brain metastases from unknown primary neoplasms are most likely to be from a primary lung cancer (72 per cent), followed in frequency by breast cancer, colon carcinoma, and melanoma.

Prognosis typically is poor. Therapeutic considerations must be individualised and depend on many factors, which include the patient's neurologic status, extent of systemic tumor, number and location of brain metastases, and sensitivity of the tumor to radiation and chemotherapy.

Approximately two thirds of brain metastases are symptomatic at some point. Symptoms are caused primarily by (1) increased intracranial pressure resulting in headache, nausea, vomiting, confusion, and lethargy and (2) focal irritation or destruction of neurons resulting in hemiparesis, visual field defects, aphasia, focal seizures, ataxia and other focal neurologic signs or deficits.

In 5-10 per cent of cancer patients, brain metastasis is the first clinical manifestation of systemic cancer. The primary site can be located in 45 per cent of patients, and in those in whom the primary site is discovered, lung carcinoma is the primary tumor in 45 per cent. Surgical resection is the preferred treatment in patients with one apparent metastasis detected on enhanced CT or MRI. Radiosurgery provides a simple, effective, noninvasive, cost-effective method to treat surgically inaccessible lesions and is a therapeutic option for 2-6 metastases.

When screening for intracranial metastases, no consensus has been reached concerning when to use CT or MRI for initial staging evaluation of a patient with cancer. However, brain MRI in patients with primary cancers that frequently metastasize to the brain (e.g., bronchogenic carcinoma) is probably cost effective. Numerous studies have shown that contrast-enhanced MRI detects two to three times as many lesions as contrast-enhanced CT, especially lesions less than 5mm diameter. In addition, approximately 20 per cent of patients with solitary metastatic lesions on CT show multiple lesions on MRI. Perform imaging on patients with other cancers based on their clinical evaluation.

In the presence of multiple cerebral metastases from an unknown primary source, a limited search for the primary tumor is of value and includes a chest X-ray, breast examination and mammography, and abdominal ultrasound (US). An extensive search for an occult malignancy is unrewarding. Surgery may be required in patients presenting with a solitary intracranial tumor or to search for a possible primary tumor.

Most patients with a known primary tumor receive imaging studies when neurologic signs and symptoms develop. MRI with contrast enhancement currently is the procedure of choice, since MRI is more sensitive and specific than other imaging techniques in determining the presence, location, and number of metastases. Contrast-enhanced CT is used widely because of its easy accessibility and low cost.

Medical care is influenced significantly by the additional information gained from gadolinium-enhanced MR studies. If a solitary metastasis is found, definitively ruling out the presence or absence of additional lesions is important for diagnosis and possible surgical management. Standard-dose or high-dose gadolinium-enhanced MRI can demonstrate the additional lesions that support suggested metastatic disease. Use of magnetisation transfer with single-dose gadolinium administration is roughly equivalent to triple-dose, postcontrast, spin-echo imaging in detecting lesions and lesion conspicuity.

Metastases frequently are multiple and seen at the junction of gray and white matter, usually with significant surrounding edema. CT findings are as follows: On non-contrast CT, metastatic lesions may be of a density less than, equal to, or greater than adjacent brain parenchyma. Most of the patterns are variable and nonspecific. Noncontrast CT is performed to detect hemorrhage into metastases. Most metastases enhance after a standard dose of IV contrast.

Detecting additional metastases has important diagnostic implications, since (1) if a solitary lesion is found on routine enhanced CT, an additional lesion may suggest a metastatic process in a patient with no known primary cancer (if the solitary lesion was believed to be a primary lesion); and (2) in a solitary metastatic lesion of the brain, detection of an additional lesion may modify or change treatment from surgical removal of the solitary lesion to chemotherapy, radiation, or both for multiple lesions. Contrast-enhanced CT is effective in detecting major leptomeningeal spread. Contrast-enhancing subdural or epidural metastases may be seen, usually secondary to calvarial lesions. Of breast, lung, prostrate, and renal-cell neoplasms, five per cent metastasize to the calvarium, and 15 per cent of these extend into the subdural space.

Routine cranial CT is useful in staging cancer in the patient with non-small-cell lung cancer and has 92 per cent sensitivity, 99 per cent specificity, and 98 per cent accuracy in detecting brain metastases. Contrast-enhanced CT is useful and perhaps the best method to identify calvarial metastases. Studies comparing contrast-enhanced CT with contrast-enhanced MRI indicate that approximately 20 per cent of patients who demonstrate a single lesion on CT may demonstrate multiple lesions on MRI. Mostly, the lesions missed on contrast-enhanced CT were smaller (<2 cm in diameter), located next to the bone, and in a frontotemporal location. Dural-based metastases may mimic meningioma.

(Dr Anil Khosla spoke during IRIA)
The writer is a Neuroradiologist, Mallinckrodt Institute of Radiology, Washington Univ School of Medicine and VA Medical