Hematology Oncology · Year 2 · from Hematology Oncology

Case 2: Infectious Mononucleosis with Atypical Lymphocytosis

Patient Presentation

Demographics: 19-year-old male college student

Chief Complaint: Fever, sore throat, and fatigue for 1 week

History of Present Illness: The patient developed fever, severe sore throat, and profound fatigue over the past week. He has noticed swollen glands in his neck. He reports difficulty swallowing due to throat pain. He denies cough, rash, or joint pain. His roommate had similar symptoms 3 weeks ago. He is sexually active with one partner and denies IV drug use.

Physical Examination:

  • Vital signs: BP 115/72, HR 88, RR 16, Temp 38.4C
  • General: Fatigued-appearing young man
  • HEENT: Tonsillar hypertrophy with exudates, palatal petechiae, bilateral tender cervical and posterior auricular lymphadenopathy
  • Cardiac: Regular rhythm, no murmurs
  • Abdomen: Mildly tender LUQ, splenomegaly (3 cm below costal margin)
  • Skin: Faint maculopapular rash on trunk (patient reports receiving amoxicillin from urgent care)

Workup and Results

Complete Blood Count:

  • WBC: 14,200/uL
  • Differential:
  • Lymphocytes: 68% (absolute 9,660/uL - marked lymphocytosis)
  • Atypical lymphocytes: 22% (reported by pathologist)
  • Neutrophils: 24%
  • Hemoglobin: 14.2 g/dL
  • Platelets: 145,000/uL (mildly low)

Peripheral Blood Smear:

  • Numerous large lymphocytes with abundant basophilic cytoplasm
  • Cytoplasm indented by adjacent red blood cells
  • Characteristic atypical lymphocyte morphology

Additional Labs:

  • AST: 125 U/L (elevated)
  • ALT: 98 U/L (elevated)
  • Heterophile antibody (Monospot): Positive
  • EBV VCA IgM: Positive
  • EBV VCA IgG: Positive
  • EBV EBNA IgG: Negative (confirms acute infection)

Clinical Image

Peripheral blood smear demonstrating atypical lymphocytes (reactive lymphocytes) with abundant basophilic cytoplasm, irregular nuclear contours, and cytoplasm that appears to "hug" adjacent red blood cells.

Diagnosis

Infectious Mononucleosis (Epstein-Barr Virus) with Reactive Lymphocytosis

Supporting evidence:

  • Classic triad: Pharyngitis, lymphadenopathy, fever
  • Splenomegaly (present in ~50%)
  • Positive heterophile antibody (Monospot)
  • EBV serology pattern consistent with acute infection
  • Atypical lymphocytes >10% on smear
  • Aminotransferase elevation
  • Rash after amoxicillin (classic association)

Treatment Plan

  1. Supportive care:
  • Rest and hydration
  • Acetaminophen or ibuprofen for fever and pain
  • Avoid contact sports for 4-6 weeks (splenic rupture risk)
  1. Medications to avoid:
  • Ampicillin/amoxicillin (causes rash in EBV infection)
  • Aspirin (Reye syndrome risk in viral illness)
  1. Monitoring:
  • Activity restriction until splenomegaly resolves
  • Liver enzymes typically self-resolve
  1. Return precautions:
  • Severe abdominal pain (possible splenic rupture)
  • Difficulty breathing or swallowing (tonsillar enlargement)
  • Severe headache or stiff neck
  1. Not indicated:
  • Antivirals (acyclovir not effective)
  • Steroids (reserved for airway compromise or severe complications)

Teaching Points

  1. Atypical lymphocytes are reactive CD8+ T cells responding to EBV-infected B cells
  2. The heterophile antibody test (Monospot) may be negative in first week; EBV serology is more sensitive
  3. EBV VCA IgM and IgG positive with negative EBNA IgG indicates acute infection
  4. The rash with amoxicillin occurs in 70-100% of EBV patients and is not a true drug allergy
  5. Splenic rupture is rare but potentially fatal; avoid contact sports for 4-6 weeks
  6. Atypical lymphocytes can also be seen with CMV, HIV, toxoplasmosis, and drug reactions

All cases for this lecture as Markdown