What is the likely diagnosis for a patient with a nonenhancing, T2-hyperintense lesion in the motor cortex, presenting with progressive fine-motor impairment, tremors, and weakness?

Diagnosis: Low-Grade Glioma (WHO Grade II)

The most likely diagnosis is a low-grade diffuse glioma (WHO Grade II), specifically an astrocytoma or oligodendroglioma, given the nonenhancing T2-hyperintense lesion in the motor cortex with progressive fine-motor impairment, tremors, and weakness. 1, 2

Key Diagnostic Features Supporting Low-Grade Glioma

The clinical and radiological presentation is characteristic of low-grade glioma:

• Nonenhancing T2-hyperintense lesion in motor cortex is the classic MRI appearance of WHO Grade II diffuse glioma, which typically presents as T1-hypointense, T2-hyperintense lesions without contrast enhancement 1, 2
• Progressive neurological symptoms (fine-motor impairment, tremors, weakness) correlating with motor cortex involvement indicate a slowly growing infiltrative process rather than acute pathology 1, 3
• Superficial cortical location is typical for low-grade gliomas, particularly angiocentric gliomas and diffuse astrocytomas 1

Critical Differential Diagnoses to Exclude

While low-grade glioma is most likely, several entities must be systematically excluded:

Multiple Sclerosis (Less Likely)

• MS lesions are typically periventricular, juxtacortical, or infratentorial, not isolated to motor cortex 4, 5
• MS requires dissemination in space: at least 3 of 4 criteria including ≥1 infratentorial lesion, ≥1 juxtacortical lesion, ≥3 periventricular lesions 4
• A single cortical lesion does not meet MS diagnostic criteria 4, 5
• Progressive motor symptoms without relapsing-remitting pattern argues against MS 4

NTRK-Fused Fibroblastic Tumor (Rare but Important)

• Can present as T2-hyperintense lesion in temporal/cortical regions mimicking low-grade glioma 6
• Requires molecular testing (NTRK fusion panel) for definitive diagnosis 6
• Critical to identify due to availability of selective kinase inhibitor therapies 6

Acute Stroke Mimics

• Distribution inconsistent with vascular territory and progressive (not acute) onset excludes stroke 7
• DWI restriction would be expected in acute infarction, not typical for low-grade glioma 7

Diagnostic Algorithm

Immediate Imaging Requirements

• Complete brain MRI with gadolinium contrast to assess enhancement patterns and exclude higher-grade features 4, 1
• T2-weighted and FLAIR sequences with 3mm slice thickness to characterize lesion extent 4, 1
• Diffusion-weighted imaging (DWI) to exclude acute ischemic process 7
• Gradient-echo sequences to exclude vascular malformations (look for flow voids or blooming artifact) 8

Tissue Diagnosis is Mandatory

• Histopathological analysis of surgical specimen is required for definitive diagnosis of low-grade diffuse glioma 2
• Resection specimen preferred over biopsy to minimize sampling error, as these tumors can have heterogeneous histology 2
• Frozen section and cytopathologic/smear evaluation should be used intraoperatively 2

Essential Molecular Testing

• IDH1 R132H immunohistochemistry and/or IDH1/2 mutation sequencing is highly specific for low-grade diffuse glioma and mandatory for classification and prognosis 2
• 1p/19q loss-of-heterozygosity testing (by FISH, array-CGH, or PCR) is required for oligodendroglial tumors for prognosis and treatment planning 2
• Ki-67/MIB1 immunohistochemistry is recommended for prognostic assessment 2
• NTRK fusion panel should be considered, especially in younger patients, given therapeutic implications 6

Critical Management Considerations

Avoid "Wait and See" Approach

• Acute malignant transformation to glioblastoma can occur even in asymptomatic patients with untreated low-grade glioma 3
• One case demonstrated sudden acceleration of growth rate with development of contrast enhancement and transformation to glioblastoma within 5 months, despite patient remaining asymptomatic 3
• Earlier surgical resection should be considered systematically rather than observation, as lack of symptoms does not protect from malignant transformation 3

Surgical Planning

• Awake craniotomy with intraoperative electrical mapping is recommended for motor cortex lesions to maximize resection while preserving function 3
• Goal is maximal safe resection (>90% of FLAIR abnormality) as extent of resection impacts prognosis 3

Common Pitfalls to Avoid

• Do not assume acute stroke based on sudden symptom onset—DLGGs can present with acute neurological deficits and may be misdiagnosed as stroke 7
• Do not delay tissue diagnosis—imaging alone cannot reliably distinguish low-grade glioma from other entities 2
• Do not overlook molecular testing—IDH mutation status and 1p/19q codeletion are essential for accurate classification, prognosis, and treatment decisions 2