What is the initial workup and laboratory evaluation for a patient suspected of having brain metastasis, including imaging studies, cerebrospinal fluid (CSF) analysis, and laboratory tests, such as complete blood counts (CBC), blood chemistry, and tumor markers, as well as the role of sarcoidosis labs, including serum Angiotensin-Converting Enzyme (ACE) levels and calcium levels?

Workup for Brain Metastasis

MRI with IV gadolinium contrast is the gold standard imaging modality for suspected brain metastasis and should be obtained immediately in any cancer patient with new neurological symptoms. 1, 2

Initial Imaging Evaluation

• Contrast-enhanced MRI of the brain (1.5-T field strength minimum) is mandatory and includes pre- and post-contrast T1-weighted, T2-weighted/FLAIR, diffusion-weighted imaging (DWI), and T2* or susceptibility-weighted sequences 1, 3
• CT with contrast may be used emergently only to exclude acute hemorrhage, herniation, or mass effect, but must be followed immediately by MRI with gadolinium for definitive evaluation 2
• Non-contrast CT is inadequate as metastases appear iso- or hypointense and cannot be distinguished from normal brain parenchyma 2
• Brain metastases characteristically appear as contrast-enhancing lesions at the gray-white matter junction with perifocal edema 1, 2

Laboratory Workup

Standard Laboratory Tests

• Complete blood count (CBC), serum electrolytes, renal and liver function tests, and serum lactate dehydrogenase (LDH) should be obtained at diagnosis 1
• Serum LDH has prognostic value in stage IV disease and should be measured, though it is not sensitive for detecting metastatic disease 1
• Routine blood chemistry helps assess organ function and guides treatment decisions 1

Tumor-Specific Markers

• Tumor markers are not routinely recommended for brain metastasis workup but may be obtained based on the suspected primary malignancy 1
• The focus should be on identifying the primary cancer source through systemic staging (chest/abdomen CT or FDG-PET) 1

Cerebrospinal Fluid (CSF) Studies

CSF analysis is NOT routinely indicated for parenchymal brain metastases but has specific indications:

When CSF Analysis is Indicated

• Suspected leptomeningeal metastasis (LM) based on clinical presentation (headache, cranial nerve palsies, cauda equina syndrome, radicular pain) or MRI findings of sulcal/ependymal enhancement 1
• CSF volume should ideally be >10 mL but at least 5 mL for adequate cytological analysis 1
• Fresh CSF samples must be processed within 30 minutes when feasible; alternatively, fix with ethanol/Carbowax (1:1 ratio) 1

CSF Analysis Components

• Cytology with Papanicolaou and Giemsa staining is the primary diagnostic test 1
• Immunocytochemical staining for epithelial and melanocytic markers should be performed when material is available 1
• A second CSF sample should be analyzed if the initial sample is negative for suspected leptomeningeal disease 1
• CSF ACE measurement is NOT useful for brain metastasis workup 4

Sarcoidosis Laboratory Evaluation

Sarcoidosis labs should be obtained when brain lesions are atypical for metastasis or when the differential diagnosis includes neurosarcoidosis:

Serum Tests for Sarcoidosis

• Serum angiotensin-converting enzyme (ACE) level correlates with disease activity and clinical status in sarcoidosis 5
• Serum calcium levels should be measured as hypercalcemia occurs in sarcoidosis 5
• Serial ACE measurements are more useful than single values for following disease course 5

CSF Tests for Neurosarcoidosis

• CSF ACE is elevated in 11 of 20 patients (55%) with neurosarcoidosis but in only 1 of 12 patients with systemic sarcoidosis without neurologic involvement 4
• CSF ACE fluctuations correlate with clinical course and can guide treatment decisions 4
• Important caveat: Elevated CSF ACE is not specific—high values also occur in bacterial meningitis and CNS malignancies 4

Systemic Staging

• CT chest and abdomen or FDG-PET scan should be performed to identify the primary tumor and assess systemic disease burden 1
• Determining whether disease progression is isolated to CNS versus systemic is valuable for treatment planning 1
• Bone scan should be obtained as part of comprehensive staging 1
• Brain MRI detects metastases in 10-15% of asymptomatic patients with small cell lung cancer at initial diagnosis, including 12% with otherwise limited-stage disease 1

Key Clinical Pitfalls

• Do not rely on CT alone—MRI detects 24% of brain metastases versus only 10% with CT 2
• Do not perform routine bone marrow biopsy—it should be reserved only for patients with peripheral cytopenia and no other evidence of metastatic disease 1
• Do not obtain prophylactic CSF studies for parenchymal brain metastases without clinical or radiographic suspicion of leptomeningeal involvement 1
• Biopsy should be considered if imaging findings are atypical or if the patient has no known primary malignancy 1