Unilateral Tongue Deviation in a Breast Cancer Survivor: Diagnostic Approach and Management
Most Likely Diagnosis
The most likely cause is leptomeningeal carcinomatosis or skull-base metastasis involving the hypoglossal nerve, and the negative brain MRI from [DATE] does not exclude these diagnoses—immediate contrast-enhanced MRI of the brain and skull base with dedicated hypoglossal nerve imaging is mandatory. 1
Critical Diagnostic Pitfall
A routine brain MRI—even if recently negative—is insufficient to evaluate hypoglossal nerve palsy because standard protocols often miss leptomeningeal disease, perineural tumor spread, and skull-base lesions along the hypoglossal canal. 1, 2 The hypoglossal nerve travels from the medulla through the skull base to the sublingual space, and pathology anywhere along this trajectory can cause isolated tongue deviation 3. Standard brain MRI protocols frequently fail to adequately image the skull base and hypoglossal canal, leading to missed diagnoses 2.
Immediate Diagnostic Work-Up
Required Imaging
Obtain gadolinium-enhanced brain and skull-base MRI immediately, specifically requesting imaging of the entire hypoglossal nerve pathway from the medulla through the hypoglossal canal to the sublingual space. 1, 3 This is distinct from standard brain MRI protocols.
Add post-contrast FLAIR sequences to the MRI protocol to evaluate for leptomeningeal disease, which is particularly common in HER2-positive and triple-negative breast cancer. 1 Leptomeningeal carcinomatosis is the primary concern when isolated cranial neuropathy occurs in metastatic breast cancer 1.
Do not rely on MR angiography (MRA) alone—MRA evaluates only vascular structures and will miss parenchymal, leptomeningeal, and bony lesions that commonly cause cranial neuropathies in cancer patients. 1
Cerebrospinal Fluid Analysis
If leptomeningeal disease is suspected on imaging—or if MRI is negative despite high clinical suspicion—perform lumbar puncture with CSF cytology. 1 MRI sensitivity for leptomeningeal carcinomatosis is imperfect, and CSF cytology may provide the definitive diagnosis 1.
Do not delay CSF analysis when leptomeningeal disease is suspected, as early confirmation impacts treatment planning. 1
Management Based on Findings
If Leptomeningeal Metastases Confirmed
Convene a multidisciplinary discussion immediately, as no universally accepted standard of care exists for leptomeningeal disease. 1 Treatment options include intrathecal chemotherapy, systemic therapy, and radiation therapy 4.
For focal symptomatic lesions causing the hypoglossal neuropathy, focal radiation therapy is recommended. 1
Do not combine intrathecal methotrexate with radiation therapy due to increased risk of neurotoxicity. 1
If Skull-Base Metastasis Identified
- When a skull-base metastasis involving the hypoglossal canal is identified, stereotactic radiosurgery or fractionated radiation to the lesion is the primary treatment. 1 Skull-base metastases are frequently missed on routine imaging but are a common cause of hypoglossal palsy in cancer patients 2.
Systemic Therapy Considerations
Continue systemic HER2-targeted therapy in HER2-positive patients if extracranial disease is otherwise controlled. 1 Up to 40-50% of patients with advanced HER2-positive breast cancer will experience brain or leptomeningeal relapse 5, 4.
For triple-negative breast cancer, recognize that brain metastases occur in up to 40-50% of advanced cases with shorter intervals from primary diagnosis to CNS involvement. 5
If All Imaging Is Negative
Institute serial MRI surveillance every 2-4 months to detect subsequently apparent disease. 1 Isolated hypoglossal nerve palsy in a breast cancer survivor warrants close monitoring even when initial imaging is negative 6, 3.
Consider idiopathic isolated hypoglossal nerve palsy as a diagnosis of exclusion only after thorough investigation. 6 This is extremely rare and requires stepwise exclusion of all other causes 6.
Key Clinical Pearls
Breast cancer is the second most common cause of brain metastases after lung cancer, but routine surveillance imaging is not recommended in asymptomatic patients. 4 However, clinicians should have a low threshold for performing diagnostic brain MRI in the setting of any neurologic symptoms suggestive of brain involvement. 4
The presence of neurologic symptoms fundamentally changes the diagnostic approach—symptomatic patients require immediate comprehensive imaging regardless of recent negative studies. 4
Tongue denervation on imaging can be misinterpreted as a primary tongue base mass, showing T2-weighted hyperintensity of the involved hemitongue, protrusion into the oropharynx, and variable fatty infiltration. 2 Recognition of these patterns prevents misdiagnosis.
Internal carotid artery dissection at the skull base is another potential cause of hypoglossal palsy that must be excluded. 2