Differential Diagnosis for a 12-year-old Male with Positive Monospot Test

Given the clinical presentation and laboratory results of a 12-year-old male with a positive Monospot test, negative CMV and EBV antibodies, normal CBC, CMP, and ESR, and a spleen size greater than the 90th percentile, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis
  • Infectious Mononucleosis (IM) due to EBV infection with a false-negative serology: Despite the negative EBV antibodies, the positive Monospot test (which detects heterophile antibodies) and the clinical presentation are highly suggestive of infectious mononucleosis. The negative serology could be due to a window period where the antibodies have not yet developed or a false-negative result. The fact that he had a positive Monospot test 2 years prior could indicate a previous infection, but it's also possible that the first test was a false positive or that this is a new infection.
• Other Likely Diagnoses
  • Cytomegalovirus (CMV) Infection: Although CMV antibodies were negative, CMV can cause a mononucleosis-like syndrome. However, the positive Monospot test makes this less likely.
  • Toxoplasmosis: This infection can cause a mononucleosis-like syndrome, but it is less common in this age group and the clinical presentation would typically include other symptoms such as lymphadenopathy.
• Do Not Miss Diagnoses
  • Hodgkin Lymphoma: Although rare, it's crucial to consider lymphoma in the differential diagnosis of a patient with a significantly enlarged spleen and a history of positive Monospot tests. Lymphoma can cause false-positive Monospot tests due to the production of heterophile antibodies.
  • Leukemia: Similar to lymphoma, leukemia can cause splenomegaly and alterations in blood cell counts, although the CBC was reported as normal in this case.
• Rare Diagnoses
  • Other Viral Infections (e.g., HIV, Hepatitis): These infections can cause a mononucleosis-like syndrome but are less likely given the clinical context and the specific test results provided.
  • Autoimmune Hemolytic Anemia (AIHA): This condition can cause a positive Coombs test and sometimes a positive Monospot test due to the production of heterophile antibodies, but it would typically present with anemia and other hematologic abnormalities.

Recommended Next Steps

Given that the patient is now recovered and back to normal activity, the focus should be on confirming the diagnosis and ruling out other potential causes of his symptoms. Recommended steps include:

• Repeat EBV serology: To confirm whether the patient has developed antibodies against EBV, which would support the diagnosis of infectious mononucleosis.
• Clinical follow-up: Monitor for any signs of complications or recurrence of symptoms.
• Consider further testing if symptoms recur or if there's a significant change in clinical status: This could include imaging studies (e.g., ultrasound) to assess spleen size more accurately, or additional blood tests to rule out other conditions if clinically indicated.