What neoplasms can cause fever?

Common Neoplasms That Can Cause Fever

Hematologic malignancies and certain solid tumors can cause fever through direct tumor effects or immune dysregulation, requiring differentiation from infectious causes for appropriate management.

Hematologic Malignancies

• Leukemias (acute and chronic) are commonly associated with fever due to bone marrow infiltration, immune dysfunction, and neutropenia 1
• Non-Hodgkin's lymphoma presents with fever as a paraneoplastic phenomenon, particularly in advanced disease 1
• Hodgkin's lymphoma is associated with neoplastic fever, though less commonly documented in clinical trials than NHL 2, 3
• Multiple myeloma can cause fever, especially in advanced disease stages 1

Solid Tumors

• Renal cell carcinoma is well-known to present with neoplastic fever as a paraneoplastic syndrome 2, 3
• Non-small cell lung cancer can present with fever at both initial diagnosis and relapse, even without metastatic disease 2
• Breast cancer may present with tumor-associated fever, particularly with liver, bone marrow, or lung metastases 4
• Tumors causing anatomic obstruction (endobronchial, genitourinary, or hepatobiliary) can lead to fever through postobstructive complications 1
• Abdominal tumors that obstruct the biliary tract may cause fever through cholangitis 1

Mechanisms of Neoplastic Fever

• Cytokine-mediated mechanisms are suspected to be the primary cause of neoplastic fever 3
• Tumor necrosis due to outgrowth of blood supply creates a nidus for inflammation 1
• Direct invasion through mucosal barriers (e.g., colonic) can cause local abscess formation and systemic inflammatory response 1
• Advanced malignancy often causes malnutrition, which further increases risk of fever 1

Diagnostic Considerations

• Neoplastic fever is a diagnosis of exclusion after ruling out infectious causes 3, 5
• Patients with hematologic malignancies who develop fever have infections in approximately 50-60% of cases 1
• Fever may be the first manifestation of cancer recurrence or progression 4
• Granulocytopenia significantly increases the risk of infectious fever versus neoplastic fever 5

Clinical Pearls

• The naproxen test (prompt response to NSAID therapy) can help differentiate neoplastic from infectious fever 6, 3
• Fever that responds to tumor-directed therapy suggests neoplastic origin 4
• Excessive sweating and symptomatic improvement often follow the resolution of neoplastic fever with NSAIDs 6
• Fever may recur when NSAID therapy is discontinued if the underlying malignancy persists 6

Management Approach

• Exclude infectious causes before attributing fever to malignancy, especially in neutropenic patients 1, 5
• Consider naproxen or other NSAIDs for symptomatic management of confirmed neoplastic fever 6, 3
• Disease-specific therapy (chemotherapy, immunotherapy, or hormonal therapy) is the definitive approach to treating neoplastic fever 4
• Steroids may be considered as an alternative antipyretic approach in cases where NSAIDs are contraindicated 2

High-Risk Scenarios

• Patients with neutropenia (<100/mcL) have >10-20% risk of bloodstream infection when febrile 1
• Advanced or refractory malignancies carry greater risk of both infectious and neoplastic fever 1
• Patients receiving multiple lines of chemotherapy have increased susceptibility to both neoplastic and infectious causes of fever 1
• Patients with hematologic malignancies and fever should be presumed to have infection until proven otherwise 5