What is the most likely diagnosis for a 47-year-old male presenting with progressive morning headaches, nausea, personality changes, ataxic gait, bilateral temporal visual field loss, weight loss, lymphadenopathy, a skin lesion, and respiratory findings, considering the top differential diagnoses of brain metastasis from melanoma, glioblastoma, and chronic subdural hematoma?

Brain Metastasis from Melanoma, Glioblastoma, and Chronic Subdural Hematoma: Illness Scripts

---

1. Brain Metastasis from Melanoma

Mechanism(s) of Disease

Melanoma cells disseminate hematogenously to the brain, preferentially seeding at the grey-white matter junction and vascular border zones where blood flow slows. 1 The tumor cells establish metastatic foci that can hemorrhage spontaneously due to melanoma's inherent vascular fragility and neoangiogenesis. 2, 3 Approximately 75% of brain metastases localize to cerebral hemispheres, 21% to cerebellum, and 3% to brainstem. 1 Melanoma has particular propensity for hemorrhagic transformation compared to other solid tumors. 1

Key History Features + Risk Factors

• Progressive morning headaches worsening with Valsalva maneuvers or bending (indicating raised intracranial pressure) 1
• Personality and mood changes reflecting frontal lobe or diffuse cerebral involvement 1
• Nausea and vomiting from increased intracranial pressure 1
• History of cutaneous melanoma (the small lesion behind the right ear is highly suspicious for primary melanoma) 4
• Stage IV melanoma carries highest risk for brain metastasis development 1
• Rapid symptom progression over weeks rather than months 1
• Weight loss suggesting systemic metastatic disease 4

Physical Exam Findings That Increase Likelihood

• Posterior auricular lymphadenopathy strongly suggests melanoma with regional lymphatic spread 4
• Small pigmented lesion behind the right ear (potential primary melanoma site) 4
• Ataxic gait with left-sided cerebellar signs indicating cerebellar metastasis 1
• Bilateral temporal visual field loss suggesting chiasmal/suprasellar involvement or bilateral occipital lobe metastases 1
• Decreased breath sounds RML with diffuse crackles suggesting pulmonary metastases (melanoma commonly metastasizes to lungs) 1
• Focal neurological deficits depending on metastasis location 1

Helpful Diagnostic Studies

First-line imaging:

• Cranial MRI with gadolinium contrast at ≥1.5-T field strength is the gold standard 1, 4
• Required sequences: pre- and post-contrast T1-weighted, T2-weighted and/or T2-FLAIR, diffusion-weighted imaging (DWI) 1
• 3D post-gadolinium T1-weighted sequences for optimal sensitivity 4
• Characteristic findings: solid or ring enhancement, perifocal edema, grey-white matter junction predilection 1

Confirmatory studies:

• Biopsy of the skin lesion behind the ear to confirm melanoma histology 4
• Excisional biopsy of posterior auricular lymph node if skin lesion non-diagnostic 4
• Chest CT to evaluate pulmonary findings (decreased RML breath sounds) 1
• Brain biopsy only if imaging cannot distinguish from other pathologies (abscess, primary tumor) with certainty 1
• PET-CT for systemic staging once melanoma confirmed 1

Pre-test Probability for This Case: HIGH

Points FOR brain metastasis from melanoma:

• Small lesion behind right ear (potential primary melanoma) with posterior auricular lymphadenopathy creates classic pattern of melanoma with regional spread 4
• Progressive morning headaches, personality changes, and ataxia are characteristic of brain metastases 1, 4
• Bilateral temporal visual field loss suggests multiple lesions or midline involvement 1
• Weight loss indicates systemic metastatic disease 4
• Respiratory findings (decreased RML breath sounds, crackles) suggest pulmonary metastases, common in melanoma 1
• Age 47 fits typical melanoma demographic 2
• Rapid progression over weeks typical for metastatic disease 1

Points AGAINST:

• No documented history of melanoma (though undiagnosed primary is possible) 2
• Chronic subdural hematoma can mimic metastatic melanoma radiologically 5

Sources

1. Soffietti R, et al. (2021). EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours. Annals of Oncology, 32(11):1332-1347. https://doi.org/10.1016/j.annonc.2021.07.016

2. Agarwal S, et al. (2008). Melanoma-induced brain metastases. Expert Review of Anticancer Therapy, 8(5):743-755. PMID: 18471047

3. American Academy of Neurology/American College of Radiology/National Comprehensive Cancer Network guidelines (as cited in Praxis Medical Insights summary, 2026)

---

2. Glioblastoma (Primary High-Grade Glioma)

Mechanism(s) of Disease

Malignant transformation of glial cells leads to rapidly proliferating, infiltrative tumor characterized by necrosis, vascular proliferation, and significant mass effect. 4 Glioblastomas arise from astrocytes and demonstrate uncontrolled cellular proliferation with invasion along white matter tracts. 4 The tumor causes vasogenic edema, disrupts normal brain architecture, and increases intracranial pressure through mass effect and potential obstructive hydrocephalus. 1 Unlike metastases, glioblastomas typically originate as single lesions at subcortical grey-white junction with irregular margins. 6

Key History Features + Risk Factors

• Progressive neurological symptoms over weeks to months (slower than metastases but faster than low-grade gliomas) 4
• Morning headaches worse with Valsalva from increased intracranial pressure 1
• Personality and mood changes reflecting frontal lobe or diffuse cerebral involvement 4
• Middle-aged adult presentation (peak incidence 45-70 years; patient is 47) 4
• No prior cancer history distinguishes from metastatic disease 4
• Progressive cognitive decline occurs in 30-40% of primary malignant brain tumors 6

Physical Exam Findings That Increase Likelihood

• Ataxic gait with cerebellar signs if tumor involves posterior fossa or cerebellar connections 1
• Bilateral temporal visual field loss if tumor involves optic pathways or causes hydrocephalus 1
• Focal neurological deficits corresponding to tumor location 1
• Cognitive impairment and personality changes from frontal involvement 4, 6

Helpful Diagnostic Studies

First-line imaging:

• MRI brain with and without IV gadolinium contrast at ≥1.5-T field strength 4
• Required sequences: axial T1-weighted, axial T2-FLAIR, post-gadolinium 3D T1-weighted, DWI 4
• Characteristic findings: irregular ring enhancement, central necrosis, surrounding vasogenic edema, subcortical grey-white junction location 6
• Magnetic resonance spectroscopy (MRS) shows tumor-specific metabolites (elevated choline, decreased N-acetylaspartate) 1
• Perfusion imaging demonstrates increased cerebral blood volume in tumor 1

Confirmatory studies:

• Stereotactic or open surgical biopsy for definitive histopathological diagnosis (WHO grading, molecular markers) 4
• Molecular testing: IDH mutation status, MGMT promoter methylation, 1p/19q codeletion status 4
• Systemic imaging (chest/abdomen/pelvis CT) to exclude metastatic disease if diagnosis uncertain 1

Pre-test Probability for This Case: MEDIUM

Points FOR glioblastoma:

• Age 47 fits typical demographic for glioblastoma 4
• Progressive morning headaches, personality changes, and ataxia consistent with primary brain tumor 4
• Single dominant lesion pattern more typical of glioblastoma than multiple metastases 1
• Bilateral temporal visual field loss could result from single midline/suprasellar glioblastoma 1

Points AGAINST:

• Posterior auricular lymphadenopathy and skin lesion behind ear strongly suggest melanoma rather than primary brain tumor 4
• Weight loss and systemic symptoms (respiratory findings) more typical of metastatic disease 4
• Rapid progression over weeks more consistent with metastases than glioblastoma 1, 4
• Glioblastomas rarely cause lymphadenopathy or extracranial manifestations 4
• Respiratory findings (decreased RML breath sounds, crackles) unexplained by isolated brain tumor 1

Sources

1. Soffietti R, et al. (2021). EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours. Annals of Oncology, 32(11):1332-1347. https://doi.org/10.1016/j.annonc.2021.07.016

2. Weller M, et al. (2014). EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncology, 15(9):e395-403. PMID: 25079102

3. American Academy of Neurology/National Comprehensive Cancer Network/European Association of Neuro-Oncology guidelines (as cited in Praxis Medical Insights summary, 2026)

---

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. 4 After initial trauma, bridging veins tear and bleed slowly into the subdural space. 4 Over weeks to months, the hematoma organizes with formation of a vascularized membrane that can re-bleed, causing hematoma expansion. 4 The gradual mass effect compresses brain parenchyma and increases intracranial pressure, producing progressive neurological symptoms. 4

Key History Features + Risk Factors

• History of minor head trauma (often weeks to months prior, may be forgotten) 4
• Progressive headaches developing gradually 4
• Fluctuating level of consciousness characteristic of chronic subdural hematoma 4
• Gait ataxia and imbalance common presentations 4
• Risk factors: anticoagulation, elderly age, alcohol use, falls 4

Physical Exam Findings That Increase Likelihood

• Gait ataxia and imbalance from mass effect 4
• Fluctuating mental status or confusion 4
• Focal neurological deficits depending on hematoma location and size 4
• Papilledema if significant intracranial pressure elevation 1

Helpful Diagnostic Studies

First-line imaging:

• Non-contrast CT head is initial imaging modality of choice 4
• Characteristic findings: crescent-shaped hypodense (chronic) or mixed-density (subacute) collection along cerebral convexity 4
• MRI brain provides superior characterization of hematoma age and membranes 4
• MRI sequences: axial T1-weighted, axial T2-FLAIR, post-gadolinium T1-weighted (shows enhancing membranes) 4

Confirmatory studies:

• Surgical drainage provides both diagnostic confirmation and therapeutic benefit 4
• Histopathology of hematoma membrane if surgical evacuation performed 4

Pre-test Probability for This Case: LOW

Points FOR chronic subdural hematoma:

• Progressive morning headaches could result from mass effect 4
• Ataxic gait consistent with subdural hematoma 4
• Age 47 within possible range (though more common in elderly) 4

Points AGAINST:

• No history of head trauma (essential feature of subdural hematoma) 4
• Posterior auricular lymphadenopathy and skin lesion unexplained by subdural hematoma 4
• Weight loss and systemic symptoms not explained by isolated intracranial process 4
• Respiratory findings (decreased RML breath sounds, crackles) incompatible with isolated subdural hematoma 1
• Bilateral temporal visual field loss extremely unusual for subdural hematoma (would require bilateral large hematomas or chiasmal compression) 1
• Personality changes and mood alterations less typical of subdural hematoma than tumor 4
• Metastatic melanoma can radiologically mimic subdural hematoma due to hemorrhagic nature 5
• Dural metastases can mimic chronic subdural hematoma on imaging 7

Sources

1. American Academy of Neurology/National Comprehensive Cancer Network/European Association of Neuro-Oncology guidelines (as cited in Praxis Medical Insights summary, 2026)

2. Rauhala M, et al. (2019). Chronic subdural hematoma—incidence, complications, and financial impact. Acta Neurochirurgica, 161(11):2253-2262. PMID: 31485795

3. Kolias AG, et al. (2014). Chronic subdural haematoma: modern management and emerging therapies. Nature Reviews Neurology, 10(10):570-578. PMID: 25224156

4. Santarius T, et al. (2009). Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet, 374(9695):1067-1073. PMID: 19782872