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Last updated: September 16, 2025View editorial policy

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Differential Diagnosis for a 10-year-old Male with Positive Heterophile Antibodies, Enlarged Spleen, and Negative EBV Antibodies

  • Single Most Likely Diagnosis:
    • Infectious Mononucleosis (IMN) due to Epstein-Barr Virus (EBV) infection: Despite the negative EBV antibodies, the presence of heterophile antibodies (which are often used as a screening test for IMN) and clinical findings such as an enlarged spleen are highly suggestive of IMN. The negative EBV antibodies could be due to early infection or a false-negative result.
  • Other Likely Diagnoses:
    • Cytomegalovirus (CMV) infection: CMV can cause a mononucleosis-like syndrome with splenomegaly and can sometimes cause false-positive heterophile antibody tests.
    • Toxoplasmosis: This infection can cause lymphadenopathy, splenomegaly, and atypical lymphocytosis, which might be considered in the differential diagnosis, especially if the patient has been exposed to cats or undercooked meat.
  • Do Not Miss Diagnoses:
    • Lymphoma: Although less likely, lymphoma (such as Hodgkin lymphoma or non-Hodgkin lymphoma) can present with splenomegaly and abnormal lymphocyte counts. Missing this diagnosis could be catastrophic.
    • Leukemia: Acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) can present with splenomegaly, anemia, thrombocytopenia, and abnormal white blood cell counts. These conditions require prompt diagnosis and treatment.
  • Rare Diagnoses:
    • Brucellosis: A zoonotic infection that can cause splenomegaly, fever, and lymphadenopathy. It's rare but should be considered in patients with a history of exposure to animals or contaminated animal products.
    • HIV infection: Although rare in this age group without specific risk factors, HIV can cause a variety of hematologic abnormalities, including lymphopenia or lymphocytosis, and splenomegaly.

Each of these diagnoses should be considered in the context of the patient's full clinical presentation, including history, physical examination, and additional laboratory or imaging studies as necessary.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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