What is the differential diagnosis of ring-enhancing lesions in the brain on computed tomography (CT)?

Differential Diagnosis of Ring-Enhancing Brain Lesions on CT

The differential diagnosis of ring-enhancing brain lesions includes neoplastic (metastases, glioblastoma, primary CNS lymphoma), infectious (abscess, tuberculosis, neurocysticercosis), demyelinating (multiple sclerosis, progressive multifocal leukoencephalopathy), and vascular (subacute infarction) etiologies, with clinical context and advanced imaging features being critical to distinguish between them. 1

Neoplastic Causes

Brain Metastases

• Most common cause of multiple ring-enhancing lesions in patients with known cancer history 1
• Typically appear as well-demarcated lesions at the subcortical gray-white junction with surrounding vasogenic edema 1
• Cystic metastases show thin, smooth ring enhancement with uniformly spherical or elliptical centers 1
• Necrotic metastases display irregular enhancing walls with non-uniform central regions 1
• Hemorrhagic metastases (melanoma, renal, ovarian, thyroid primaries) show T1 hyperintensity 1
• Enhancement typically increases over time without treatment, unlike infarction 1

Primary Brain Tumors

• Glioblastoma multiforme presents as multifocal/multicentric ring-enhancing lesions with irregular, thick walls 2
• High-grade gliomas (WHO grade 3-4) commonly show ring enhancement with central necrosis 2
• Primary CNS lymphoma can present as ring-enhancing lesions, particularly in immunocompromised patients 1, 2

Infectious Causes

Pyogenic Abscess

• Central cavity shows restricted diffusion (low ADC values) on diffusion-weighted imaging, unlike most metastases 1, 3
• However, restricted diffusion is not pathognomonic—one study found restricted diffusion in metastases and unrestricted diffusion in some abscesses 3
• Rim-enhancing with smooth walls, but central necrotic portion restricts diffusion unlike cystic metastases 1
• Common in immunocompromised patients but also occurs in immunocompetent hosts 4, 2

Tuberculosis and Atypical Infections

• Tuberculomas present as ring-enhancing lesions, often multiple 1, 2
• Fungal infections and septic emboli can mimic metastases 1
• Punctate or miliary enhancement suggests atypical infections, vasculitis, or CLIPPERS 1, 5

Neurocysticercosis

• Common parasitic cause of ring-enhancing lesions in endemic regions 2
• Multiple lesions at different stages of evolution (vesicular, colloidal, granular-nodular, calcified) 2

Demyelinating Diseases

Multiple Sclerosis

• Open-ring enhancement (open toward ventricles or gray matter) is characteristic and helps differentiate from neoplasm/abscess 1, 6
• Larger MS lesions can show closed-ring enhancement, making differentiation challenging 1
• Nodular enhancement is more common than ring enhancement in typical MS lesions 1, 6
• Leptomeningeal enhancement is extremely rare in MS; extensive leptomeningeal enhancement suggests alternative diagnosis like neurosarcoidosis 1, 5

Atypical Demyelinating Disorders

• Baló's concentric sclerosis shows band-like enhancement, a red flag for atypical demyelination 1, 7, 5
• Progressive multifocal leukoencephalopathy (PML) can present as ring-enhancing lesions mimicking glioma, even in presumed immunocompetent patients 8
• Tumefactive demyelinating lesions (>2 cm) show inhomogeneous enhancement and can mimic glioblastoma 1

Neuromyelitis Optica Spectrum Disorders (NMOSD)

• Cloud-like enhancement pattern helps differentiate from MS 1, 7, 5
• Patchy/punctate or large ring enhancement in brain and longitudinally extensive spinal cord lesions 1

Vascular Causes

Subacute Ischemic Infarction

• Infarcted tissue begins to enhance following the acute phase 1
• Wedge-like (non-nodular) shape involving white matter and overlying cortex distinguishes from tumor 1
• Lacks surrounding vasogenic edema in acute phase, unlike metastases 1
• Enhancement regresses over time on surveillance imaging, unlike tumor 1

Inflammatory/Granulomatous Diseases

Neurosarcoidosis

• Extensive leptomeningeal enhancement, especially at skull base, is characteristic 1, 5
• Trident sign (subpial enhancement combined with central spinal canal enhancement) on axial spinal images 1, 5
• Can present with ring-enhancing parenchymal lesions 1

Other Inflammatory Conditions

• Acute disseminated encephalomyelitis (ADEM) can show ring-enhancing lesions 1
• CNS vasculitis shows irregular leptomeningeal, cortical, and subcortical enhancement 1

Critical Distinguishing Features

Imaging Characteristics That Guide Diagnosis

• Diffusion restriction centrally: Suggests abscess (though not pathognomonic) 1, 3
• Open-ring enhancement: Suggests MS over neoplasm/abscess 1, 6
• Wedge-like shape: Suggests subacute infarction over tumor 1
• Thin, smooth ring with spherical center: Suggests cystic metastasis 1
• Irregular thick walls: Suggests necrotic metastasis or high-grade glioma 1, 2
• Subcortical gray-white junction location: Favors metastases 1

Clinical Context Priorities

• Known cancer history: Metastases are most likely, though mimickers exist 1
• Immunocompromised state: Consider abscess, CNS lymphoma, PML, atypical infections 1, 4, 2, 8
• Endemic region: Consider neurocysticercosis, tuberculosis 2
• Demyelinating disease history: Consider MS, PML (especially if on/previously on disease-modifying therapy) 1, 6, 8

Red Flags for Alternative Diagnoses

• Band-like enhancement: Baló's concentric sclerosis 1, 7, 5
• Cloud-like enhancement: NMOSD 1, 7, 5
• Extensive leptomeningeal enhancement: Neurosarcoidosis, leptomeningeal carcinomatosis (not MS) 1, 5
• Punctate/miliary enhancement: CLIPPERS, vasculitis, PML, Susac syndrome 1, 5
• Trident sign on spinal imaging: Neurosarcoidosis 1, 5

Diagnostic Algorithm

1. Assess number of lesions: Multiple lesions favor metastases (if cancer history), MS, or infection; single lesion broadens differential to include primary brain tumor 1, 2

2. Evaluate enhancement pattern: Open-ring favors MS; smooth thin ring favors cystic metastasis; irregular thick ring favors necrotic metastasis/glioblastoma 1, 2

3. Check diffusion-weighted imaging: Central restriction suggests (but doesn't confirm) abscess 1, 3

4. Assess lesion location and shape: Subcortical gray-white junction favors metastases; wedge-like shape favors infarction 1

5. Review clinical context: Cancer history, immunosuppression, geographic location, prior demyelinating disease 1, 4, 2, 8

6. Consider biopsy for definitive diagnosis when imaging and clinical context are inconclusive, particularly for single lesions or atypical presentations 2