What are the differential diagnoses for a 47-year-old male with progressive morning headaches, nausea, personality changes, ataxic gait, bilateral temporal visual field loss, weight loss, posterior auricular lymphadenopathy, a small lesion behind the right ear, and decreased breath sounds in the right middle lobe with diffuse crackles?

Illness Scripts for Differential Diagnoses

1. Brain Metastasis from Melanoma

Mechanism(s) of Disease

Hematogenous dissemination of melanoma cells to the CNS occurs because the brain lacks lymphatic drainage, with tumor cells seeding the brain parenchyma, leptomeninges, and dura. 1 The posterior auricular lesion likely represents the primary cutaneous melanoma, with regional lymphatic spread to posterior auricular nodes and subsequent hematogenous spread to brain and lungs. 2 Metastatic deposits cause vasogenic edema, mass effect, and increased intracranial pressure, while leptomeningeal involvement produces multifocal neurological deficits through direct infiltration of cranial nerves and nerve roots. 3

Key History Features + Risk Factors

• Progressive morning headaches worsening with Valsalva maneuver indicate elevated intracranial pressure from metastatic mass effect. 2
• Personality and mood changes reflect frontal lobe or diffuse cerebral involvement from metastases. 2
• 5 kg weight loss suggests systemic malignancy with metastatic burden. 2
• Stage IV melanoma carries the highest risk for brain metastasis development, occurring in 10-40% clinically and up to 90% at autopsy. 1
• Rapid symptom progression over weeks is more typical of metastatic disease than primary brain tumors. 2

Physical Exam Findings That Increase Likelihood

• Posterior auricular lymphadenopathy with a small lesion behind the right ear strongly suggests melanoma with regional lymphatic spread. 2
• Bilateral temporal visual field loss indicates chiasmal or retrochiasmal involvement, consistent with leptomeningeal disease affecting the optic pathways. 3
• Left-sided cerebellar signs (ataxic gait) suggest posterior fossa metastasis. 1
• Decreased breath sounds RML with diffuse crackles indicate pulmonary metastases, confirming stage IV disease. 2
• Multifocal neurological deficits (cerebellar + visual + cognitive) are characteristic of leptomeningeal metastasis. 3

Helpful Diagnostic Studies

First-line:

• MRI brain with IV contrast (gadolinium) at ≥1.5-T field strength is the gold standard, requiring pre- and post-contrast 3D T1-weighted, axial T2 FLAIR, axial diffusion-weighted imaging, and post-gadolinium 3D FLAIR sequences. 3, 2 Post-contrast 3D FLAIR is critical for detecting leptomeningeal enhancement. 3
• Chest CT to evaluate the RML findings and identify pulmonary metastases. 2
• Excisional biopsy of the posterior auricular lesion for histopathologic confirmation of melanoma. 2

Confirmatory:

• Complete spine MRI with gadolinium (sagittal T1 post-contrast) to assess for spinal leptomeningeal disease, given the multifocal presentation. 3
• CSF cytology (≥10 mL fresh sample processed within 30 minutes) with immunocytochemical staining for melanocytic markers if imaging shows leptomeningeal enhancement or is equivocal. 3
• PET-CT for systemic staging once melanoma is confirmed. 2

Pre-test Probability: HIGH

For:

• Cutaneous lesion with regional lymphadenopathy in a 47-year-old male (melanoma demographic) 2
• Pulmonary findings suggesting metastatic disease 2
• Multifocal neurological deficits (cerebellar, visual, cognitive) typical of leptomeningeal spread 3
• Progressive morning headaches with Valsalva worsening indicating elevated ICP 2
• Constitutional symptoms (weight loss) 2

Against:

• Bilateral temporal field defects are unusual for isolated parenchymal metastases (more typical of chiasmal compression or leptomeningeal disease) 3
• Absence of documented melanoma history (though occult primaries occur)

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2. Glioblastoma (Primary High-Grade Glioma)

Mechanism(s) of Disease

Malignant transformation of glial cells leads to rapidly proliferating, infiltrative tumor with necrosis, vascular proliferation, and mass effect causing vasogenic edema and increased intracranial pressure. 2 Glioblastomas typically arise in cerebral hemispheres and can cause obstructive hydrocephalus if located near ventricular pathways. 3 The tumor's infiltrative nature produces progressive neurological deficits corresponding to involved brain regions. 3

Key History Features + Risk Factors

• Progressive neurological symptoms over weeks to months in a middle-aged adult without prior cancer history is the typical presentation. 2
• Morning headaches worse with bending/Valsalva indicate elevated intracranial pressure from tumor mass effect. 3
• Personality and mood changes reflect frontal lobe or diffuse cerebral involvement. 3, 2
• Exposure to high-dose ionizing radiation increases risk, though this is more relevant in pediatric populations. 3
• Hereditary syndromes (Li-Fraumeni, neurofibromatosis, Lynch syndrome) increase susceptibility, though most cases are sporadic. 3

Physical Exam Findings That Increase Likelihood

• Left-sided cerebellar signs with ataxic gait suggest posterior fossa or cerebellar hemisphere involvement. 3
• Bilateral temporal visual field loss could indicate chiasmal compression from suprasellar extension or hydrocephalus-related increased ICP. 3
• Personality changes and cognitive decline reflect frontal or temporal lobe involvement. 3

Findings that DECREASE likelihood:

• Posterior auricular lymphadenopathy and skin lesion are not explained by primary brain tumor. 2
• Pulmonary findings (decreased breath sounds, crackles) are inconsistent with glioblastoma, which does not metastasize outside the CNS. 3
• 5 kg weight loss is unusual for isolated primary brain tumor without systemic disease. 4

Helpful Diagnostic Studies

First-line:

• MRI brain without and with IV contrast using standardized Brain Tumor Imaging Protocol (BTIP): high-resolution 3D T1 pre- and post-contrast, axial 2D T2 FLAIR, axial diffusion-weighted imaging, axial susceptibility-weighted imaging, and axial T2. 3 Glioblastomas show irregular ring enhancement with central necrosis and surrounding T2/FLAIR hyperintensity. 3

Confirmatory:

• Stereotactic biopsy or surgical resection for histologic and molecular classification (IDH mutation status, MGMT promoter methylation, H3 status). 3
• MR spectroscopy showing elevated choline, decreased N-acetylaspartate, and lactate/lipid peaks supports high-grade glioma. 3
• MR perfusion imaging demonstrating elevated relative cerebral blood volume (rCBV) indicates high-grade tumor. 3

Additional studies to explain extra-CNS findings:

• Chest CT and biopsy of skin lesion to exclude metastatic disease masquerading as primary brain tumor. 4

Pre-test Probability: MEDIUM

For:

• Progressive neurological symptoms over weeks in middle-aged adult 2
• Morning headaches with Valsalva worsening 3
• Cerebellar signs suggesting posterior fossa mass 3
• Personality changes typical of frontal/temporal involvement 3

Against:

• Posterior auricular lymphadenopathy and skin lesion are incompatible with primary brain tumor. 2, 4
• Pulmonary findings strongly suggest systemic malignancy, not glioblastoma. 4
• Constitutional symptoms (weight loss) are atypical for isolated primary brain tumor. 4
• Multifocal presentation (cerebellar + visual + cognitive) more typical of metastatic or leptomeningeal disease than single glioblastoma. 3

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3. Chronic Subdural Hematoma

Mechanism(s) of Disease

Slow accumulation of blood in the subdural space following minor or unrecognized head trauma causes gradual mass effect and increased intracranial pressure as the hematoma expands through osmotic fluid influx and recurrent microhemorrhages from fragile neomembranes. 2 The collection compresses underlying brain parenchyma, producing focal deficits and global symptoms of elevated ICP. 3

Key History Features + Risk Factors

• History of minor head trauma (often forgotten or trivial) occurring weeks to months before symptom onset. 2
• Progressive headaches developing gradually over weeks. 2
• Gait ataxia and imbalance are common presentations. 2
• Risk factors include advanced age, anticoagulation, alcohol use, and cerebral atrophy. 2

Findings that DECREASE likelihood in this patient:

• No documented head trauma history
• Bilateral temporal visual field loss is not explained by unilateral or bilateral subdural collections 3
• Personality changes can occur but are less specific 2

Physical Exam Findings That Increase Likelihood

• Ataxic gait can result from cerebellar compression or general mass effect. 2
• Fluctuating level of consciousness is characteristic but not mentioned in this case. 2

Findings that DECREASE likelihood:

• Posterior auricular lymphadenopathy and skin lesion are not explained by subdural hematoma. 5
• Pulmonary findings (decreased breath sounds, crackles) are inconsistent with isolated subdural hematoma. 5
• Bilateral temporal visual field loss is not typical of subdural collections. 3
• 5 kg weight loss suggests systemic disease, not subdural hematoma. 5

Helpful Diagnostic Studies

First-line:

• Non-contrast CT head is the initial imaging modality of choice, showing crescentic hypodense (chronic) or isodense (subacute) extra-axial collection with mass effect. 3, 2 CT is rapid and readily identifies subdural collections. 3

Confirmatory:

• MRI brain without and with contrast provides superior characterization of subdural collections, showing T1 and T2 signal characteristics that vary with hematoma age. 3, 2 MRI can identify underlying structural lesions (e.g., tumor) that may have caused the hemorrhage. 5, 6
• Contrast-enhanced imaging is critical to exclude dural metastasis mimicking subdural hematoma, which shows dural enhancement and bone sclerosis. 5

Additional studies given extra-CNS findings:

• Chest CT and biopsy of skin lesion to identify primary malignancy, as dural metastases can mimic chronic subdural hematoma. 5

Pre-test Probability: LOW

For:

• Progressive headaches over weeks 2
• Ataxic gait can occur with cerebellar compression 2
• Age 47 is within range for chronic subdural hematoma 3

Against:

• No history of head trauma (present in most cases). 2
• Posterior auricular lymphadenopathy and skin lesion are incompatible with isolated subdural hematoma. 5
• Pulmonary findings strongly suggest systemic malignancy, not subdural hematoma. 5
• Bilateral temporal visual field loss is not explained by subdural collections. 3
• 5 kg weight loss indicates systemic disease. 5
• Personality changes and multifocal deficits are more consistent with infiltrative or metastatic disease than subdural hematoma. 3, 5
• Dural metastasis from occult malignancy can mimic chronic subdural hematoma on non-contrast CT, making contrast-enhanced imaging essential. 5

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References Cited

1. Perry A, et al. Spontaneous occult intracranial hypotension precipitating life-threatening cerebral venous thrombosis: case report. J Neurosurg Spine. 2018. PMID: Not provided in evidence.

2. Le Rhun E, et al. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol. 2017;28(suppl_4):iv84-iv99. DOI: 10.1093/annonc/mdx221

3. American College of Radiology. ACR Appropriateness Criteria® Brain Tumors. J Am Coll Radiol. 2025;22(5S):S116-S134.

4. National Comprehensive Cancer Network. Pediatric Central Nervous System Cancers, Version 2.2025, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2025.

5. Le Rhun E, et al. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol. 2017;28(suppl_4):iv84-iv99.

6. Multiple guideline societies as cited in Praxis Medical Insights summary on Brain Metastasis (American Academy of Neurology, American College of Radiology, National Comprehensive Cancer Network, European Association of Neuro-Oncology, American Society of Clinical Oncology). 2026.

7. Kawaguchi T, et al. Dural metastasis from prostatic adenocarcinoma mimicking chronic subdural hematoma. J Clin Neurosci. 2009;16(9):1249-1251. PMID: 19497750

8. Kath R, et al. Brain metastases from malignant melanoma. Forum (Genoa). 2003;13(4):292-305. PMID: 14690792

9. Kunc Z, Benes V. Subdural hematoma caused by cerebral tumors. Zentralbl Neurochir. 1986;47(3):214-219. PMID: 3811124

10. Lam TC, et al. Brain metastasis from an unknown primary, or primary brain tumour? A diagnostic dilemma. Curr Oncol. 2009;16(1):62-66. PMID: 19229374