In a patient with stage IV follicular lymphoma, prior diffuse large B‑cell lymphoma, receiving obinutuzumab (Gazyva) and regular intravenous immunoglobulin, who has had a persistent headache for 4–5 months, is a contrast‑enhanced brain CT (or MRI) indicated?

Brain Imaging is Strongly Indicated in This High-Risk Patient

Given the combination of persistent 4-5 month headache, stage IV follicular lymphoma, prior DLBCL, and immunosuppressive therapy (obinutuzumab and IVIG), contrast-enhanced brain MRI is the imaging modality of choice, with contrast-enhanced CT as an acceptable alternative if MRI is unavailable or contraindicated. This patient has multiple high-risk features that dramatically elevate the probability of serious intracranial pathology well above the general population threshold.

Critical Risk Factors Present

This patient has several red flags that mandate neuroimaging:

• Progressive/persistent headache over months is a primary indication for imaging, as headaches that worsen progressively over days to weeks warrant CT imaging according to the American Academy of Family Physicians 1
• Active hematologic malignancy (stage IV follicular lymphoma with prior DLBCL transformation) creates substantial risk for CNS involvement, either from lymphoma itself or opportunistic infections 2
• Immunosuppression from obinutuzumab increases risk of CNS infections including progressive multifocal leukoencephalopathy (PML), toxoplasmosis, and fungal infections 3, 4
• IVIG therapy suggests significant hypogammaglobulinemia, further elevating infection risk 3

The American College of Radiology explicitly states that risk factors associated with intracranial findings include history of malignancy, and that determination of imaging need falls on clinical judgment when these risk factors are present 2.

Recommended Imaging Approach

First-Line: MRI Brain With and Without Contrast

MRI with contrast is superior to CT for detecting:

• CNS lymphoma involvement, which can be subtle and isodense on CT but enhances prominently on MRI 2
• Opportunistic infections including PML, toxoplasmosis, and fungal abscesses, where MRI provides superior soft tissue characterization 2, 5
• Leptomeningeal disease, which requires contrast enhancement for detection 5
• Small parenchymal lesions that may be missed on CT 2, 6

The American College of Radiology recommends MRI brain without and with IV contrast as the preferred imaging when intracranial infection, tumor, or inflammatory pathologies are suspected 2.

Alternative: Contrast-Enhanced CT Brain

If MRI is contraindicated or unavailable, contrast-enhanced CT is acceptable:

• CT with IV contrast can detect suppurative fluid collections, abscesses, and enhancing masses 2
• The American College of Radiology states that contrast-enhanced CT examinations can be considered if intracranial infection, tumor, or inflammatory pathologies are suspected 2
• However, CT has lower sensitivity than MRI for detecting subtle parenchymal lesions, early ischemia, and certain infections 2, 6

Specific Pathologies to Exclude

CNS Lymphoma

• Follicular lymphoma can involve the CNS, though less commonly than DLBCL 7
• Prior DLBCL history increases concern for CNS relapse or secondary CNS involvement 7
• MRI with contrast is essential as lymphoma lesions may be nearly isointense on non-contrast imaging 6

Opportunistic Infections

• Obinutuzumab causes profound B-cell depletion and immunosuppression 3, 4
• IVIG requirement indicates significant hypogammaglobulinemia 3
• PML, toxoplasmosis, cryptococcal meningitis, and aspergillosis are all considerations 2
• MRI with contrast is superior for detecting these infections, with T2 FLAIR sensitive for vasogenic edema and post-contrast sequences sensitive for meningeal enhancement 2

Other Considerations

• Venous sinus thrombosis (can occur with malignancy and immunosuppression) 2
• Medication-related complications 2
• Progressive mass effect from any intracranial process 2

Common Pitfalls to Avoid

• Do not dismiss this as a primary headache simply because the patient may have had headaches previously—the 4-5 month duration and context of immunosuppression and malignancy change everything 1, 5
• Do not order non-contrast imaging only—contrast is essential for detecting enhancing lesions, infections, and lymphomatous involvement 2, 5
• Do not delay imaging based on the assumption that symptoms will resolve—persistent headaches in immunocompromised patients with malignancy require urgent evaluation 2, 1
• Do not assume normal neurologic exam excludes serious pathology—in immunocompromised patients with malignancy, the threshold for imaging should be much lower than in the general population 2

Urgency of Imaging

While not necessarily requiring emergent same-day imaging (unless acute neurologic changes develop), this evaluation should be expedited within days, not weeks, given the immunocompromised state and potential for rapidly progressive CNS infections or lymphomatous involvement 2.