What is the likelihood of pulmonary embolism (PE) versus pneumonia in a patient with a history of stage 4 melanoma, brain metastases, and recent intracranial hemorrhage, presenting with asymmetric leg swelling?

Likelihood of Pulmonary Embolism vs Pneumonia

In this patient with stage 4 melanoma, brain metastases, recent intracranial hemorrhage, and asymmetric leg swelling, pulmonary embolism is substantially more likely than pneumonia and must be actively excluded before attributing symptoms to any alternative diagnosis. 1, 2

Critical Risk Factors Favoring PE

This patient has multiple high-risk features that dramatically elevate PE probability:

• Metastatic melanoma carries a 25% prevalence of venous thromboembolism in stage IV disease, comparable to lung and gastrointestinal cancers 3
• Brain metastases are present in 11% of melanoma patients on immunotherapy who develop thromboembolism, and this population has a 20.6% overall TE incidence 4
• Asymmetric leg swelling is a clinical sign of deep vein thrombosis, which is found in 70% of patients with proven PE and adds 3 points to the Wells score 5, 1
• Advanced malignancy is recognized as a major independent risk factor for venous thromboembolism, particularly with metastatic disease 5

Why PE Takes Diagnostic Priority

The combination of malignancy, brain metastases, and unilateral leg swelling creates a high pretest probability that mandates direct imaging with CT pulmonary angiography without D-dimer testing. 5, 1

Key considerations:

• In melanoma patients, 50% of deep venous thromboses are associated with concurrent pulmonary embolism 3
• 25% of pulmonary emboli in cancer patients are asymptomatic and discovered incidentally on staging scans 3, 6
• The absence of dyspnea, tachypnea, or pleuritic pain does NOT exclude PE—only 3% of PE patients lack all three symptoms 5
• Up to 40% of PE patients have normal oxygen saturation, making hypoxia unreliable for exclusion 2

Pneumonia as Alternative Diagnosis

While pneumonia remains in the differential diagnosis, several factors make it less likely:

• Pneumonia can often be detected or excluded by routine chest radiography and clinical features 5
• The presence of asymmetric leg swelling is not explained by pneumonia and points specifically toward thromboembolic disease 5
• In the PIOPED study, conditions like pneumonia were among alternative diagnoses in patients investigated for PE, but clinical features usually distinguish them 5

Recommended Diagnostic Algorithm

Proceed directly to CT pulmonary angiography without D-dimer testing because:

1. High clinical probability based on Wells score (malignancy + clinical DVT signs = minimum 4.5 points) places this patient in the "PE likely" category 5, 1
2. D-dimer has extremely limited utility in cancer patients due to frequent elevation from malignancy, metastases, and inflammation 1
3. A negative D-dimer cannot safely exclude PE in high-probability patients 5
4. CTPA has >95% sensitivity for segmental or larger emboli and will simultaneously evaluate for pneumonia or other alternative diagnoses 1, 2

If CTPA cannot be performed immediately, obtain lower extremity venous ultrasound to document DVT, which has 96% specificity and would be sufficient to warrant anticoagulation 5

Critical Management Considerations

The recent intracranial hemorrhage does NOT contraindicate anticoagulation if PE is confirmed. Studies in melanoma patients with brain metastases show:

• Only 4% of anticoagulated patients developed intracranial hemorrhage, not significantly different from non-anticoagulated patients 7
• Therapeutic enoxaparin does not increase intracranial hemorrhage risk in brain metastases patients (cumulative incidence 19% vs 21% in controls) 8
• Melanoma patients have fourfold higher baseline ICH risk regardless of anticoagulation, but anticoagulation itself does not increase this risk 8
• Survival trends favor anticoagulation (4.2 vs 1.2 months median OS) 7

Important Pitfalls to Avoid

• Do not rely on clinical gestalt alone in cancer patients—the threshold for PE investigation should be low given the 25% prevalence in stage IV melanoma 3
• Do not delay imaging while pursuing alternative diagnoses, as PE and pneumonia can coexist 1
• Do not withhold anticoagulation due to brain metastases if PE is confirmed, as the thromboembolism mortality risk exceeds the hemorrhage risk 7, 8
• Do not use PERC criteria in this patient—age >50, malignancy, and leg swelling all violate PERC prerequisites 1