# Clinical Cases: White Blood Cell Disorders

## Case 1: Febrile Neutropenia

### Patient Presentation
**Demographics:** 54-year-old female

**Chief Complaint:** Fever and chills 10 days after chemotherapy

**History of Present Illness:**
The patient has Stage IIIA breast cancer and received her second cycle of dose-dense AC (doxorubicin and cyclophosphamide) chemotherapy 10 days ago. She developed fever to 38.8C this morning with chills and rigors. She reports mild fatigue but denies cough, dysuria, abdominal pain, or diarrhea. She has no obvious source of infection. She did not receive G-CSF prophylaxis after this cycle.

**Physical Examination:**
- Vital signs: BP 98/62, HR 112, RR 20, Temp 38.9C, SpO2 97% on room air
- General: Ill-appearing, rigoring
- HEENT: Oral mucosa with mild mucositis, no thrush
- Lungs: Clear to auscultation bilaterally
- Cardiac: Tachycardic, regular rhythm
- Abdomen: Soft, non-tender, no organomegaly
- Skin: Port-a-cath site without erythema or drainage
- Perirectal: No tenderness, fluctuance, or erythema

### Workup and Results

**Complete Blood Count:**
- WBC: 800/uL (severely low)
- Absolute Neutrophil Count (ANC): 120/uL (severe neutropenia)
- Hemoglobin: 9.8 g/dL
- Platelets: 95,000/uL

**Chemistry:**
- Creatinine: 1.1 mg/dL
- Lactate: 2.8 mmol/L (mildly elevated)

**Infectious Workup:**
- Blood cultures x 2 (peripheral and port): Pending
- Urinalysis: Normal
- Chest X-ray: No infiltrates

**MASCC Score:**
- Burden of illness (moderate symptoms): 3
- No hypotension: 5
- No COPD: 4
- Solid tumor: 4
- No dehydration: 3
- Outpatient at fever onset: 3
- Age <60: 2
- Total: 24 (high risk if <21)

### Clinical Image

![Chemotherapy-Induced Neutropenia](case_01_image.jpg)

*Peripheral blood smear demonstrating severe neutropenia following myelosuppressive chemotherapy, with markedly reduced white blood cells and absence of neutrophils.*

### Diagnosis
**Febrile Neutropenia - Medical Emergency**

Criteria met:
- ANC <500/uL (or <1,000/uL and expected to decline)
- Single temperature ≥38.3C or sustained ≥38.0C for 1 hour
- High-risk features: ANC <100/uL, anticipated prolonged neutropenia

### Treatment Plan
1. **Immediate antibiotic therapy (within 1 hour of presentation):**
   - Empiric anti-pseudomonal coverage: Cefepime 2g IV q8h
   - Alternatives: Piperacillin-tazobactam or meropenem

2. **Additional coverage considerations:**
   - Vancomycin if: hemodynamic instability, suspected catheter infection, skin/soft tissue infection, or known MRSA colonization
   - Antifungal (voriconazole or caspofungin) if: fever persists >4-7 days despite antibiotics

3. **Supportive care:**
   - IV fluid resuscitation
   - Monitor closely for sepsis and hemodynamic deterioration

4. **G-CSF:**
   - Consider filgrastim if high-risk features or expected prolonged neutropenia
   - Will use G-CSF prophylaxis with subsequent chemotherapy cycles

5. **Disposition:**
   - Inpatient admission given severe neutropenia and tachycardia
   - Daily monitoring until ANC recovery

### Teaching Points
1. Febrile neutropenia is a medical emergency requiring immediate empiric antibiotics
2. The nadir of neutropenia typically occurs 7-14 days after myelosuppressive chemotherapy
3. Patients may lack typical signs of infection (pus, infiltrates) due to absence of neutrophils
4. The MASCC score helps identify low-risk patients who may be candidates for outpatient management
5. Anti-pseudomonal coverage is essential given high mortality from gram-negative bacteremia
6. G-CSF prophylaxis should be considered for regimens with >20% febrile neutropenia risk

---

## 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

![Atypical Lymphocytes](case_01_image.jpg)

*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)

2. **Medications to avoid:**
   - Ampicillin/amoxicillin (causes rash in EBV infection)
   - Aspirin (Reye syndrome risk in viral illness)

3. **Monitoring:**
   - Activity restriction until splenomegaly resolves
   - Liver enzymes typically self-resolve

4. **Return precautions:**
   - Severe abdominal pain (possible splenic rupture)
   - Difficulty breathing or swallowing (tonsillar enlargement)
   - Severe headache or stiff neck

5. **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

---

## Case 3: Chronic Eosinophilia with Hypereosinophilic Syndrome

### Patient Presentation
**Demographics:** 48-year-old male

**Chief Complaint:** Progressive fatigue, shortness of breath, and skin rash for 3 months

**History of Present Illness:**
The patient reports gradually worsening fatigue and exertional dyspnea over 3 months. He has developed pruritic skin lesions on his trunk and extremities. He reports occasional palpitations. He has no history of asthma, allergies, or atopic conditions. He has not traveled internationally and has no pets. He takes no medications and has no occupational exposures.

**Physical Examination:**
- Vital signs: BP 128/78, HR 96 (irregular), RR 18, Temp 37.0C, SpO2 95% on room air
- General: Fatigued-appearing male
- Cardiac: Irregularly irregular rhythm, III/VI systolic murmur at apex
- Lungs: Bibasilar crackles
- Abdomen: Hepatomegaly, splenomegaly (4 cm below costal margin)
- Skin: Scattered erythematous papules and nodules
- Neuro: Mild peripheral sensory loss in stocking distribution

### Workup and Results

**Complete Blood Count:**
- WBC: 28,400/uL
- Differential:
  - Eosinophils: 58% (absolute 16,470/uL - marked eosinophilia)
  - Neutrophils: 32%
  - Lymphocytes: 8%
- Hemoglobin: 11.2 g/dL
- Platelets: 185,000/uL

**Additional Labs:**
- Troponin I: 0.45 ng/mL (elevated)
- BNP: 890 pg/mL (elevated)
- IgE: 350 IU/mL (mildly elevated)
- B12: Normal
- Tryptase: Normal

**Cardiac Workup:**
- ECG: Atrial fibrillation with RVR
- Echocardiogram: Restrictive pattern, apical thrombus, EF 40%
- Cardiac MRI: Endomyocardial fibrosis pattern

**Bone Marrow Biopsy:**
- Hypercellular with 45% eosinophils
- No blasts or dysplasia
- FISH: FIP1L1-PDGFRA fusion POSITIVE

**Other Studies:**
- Stool O&P: Negative x 3
- Strongyloides serology: Negative
- Chest CT: Patchy ground-glass opacities

### Clinical Image

![Eosinophilia Blood Smear](case_01_image.jpg)

*Peripheral blood smear demonstrating marked eosinophilia with numerous eosinophils characterized by bilobed nuclei and prominent orange-red cytoplasmic granules.*

### Diagnosis
**Hypereosinophilic Syndrome - FIP1L1-PDGFRA-Positive (Myeloproliferative Variant)**

Diagnostic criteria met:
- Absolute eosinophil count >1,500/uL for >6 months
- Eosinophil-mediated organ damage (cardiac, pulmonary, skin, neurologic)
- FIP1L1-PDGFRA fusion gene positive
- Secondary causes excluded (parasites, allergies, drugs)

### Treatment Plan
1. **First-line therapy:**
   - Imatinib 100 mg daily (dramatic response expected in FIP1L1-PDGFRA+ cases)
   - Check cardiac troponin before starting (risk of myocardial necrosis with rapid eosinophil death)
   - Consider concurrent prednisone 1 mg/kg for first 1-2 weeks

2. **Cardiac management:**
   - Anticoagulation for atrial fibrillation and LV thrombus
   - Heart failure management (diuretics, ACE inhibitor)
   - Rate control for atrial fibrillation

3. **Monitoring:**
   - CBC weekly initially, then monthly
   - Target AEC <500/uL
   - Repeat echocardiogram at 3 months

4. **Prognosis:**
   - FIP1L1-PDGFRA+ HES has excellent response to imatinib
   - Near-complete hematologic remission expected
   - Cardiac damage may be partially reversible if treated early

### Teaching Points
1. Eosinophilia causes: NAACP - Neoplasm, Allergic/Atopic, Adrenal insufficiency, Connective tissue disease, Parasites
2. Hypereosinophilic syndrome requires persistent eosinophilia with organ damage
3. The FIP1L1-PDGFRA fusion creates a constitutively active tyrosine kinase responsive to imatinib
4. Eosinophilic heart disease (Loeffler endocarditis) causes restrictive cardiomyopathy and mural thrombi
5. Major basic protein and other eosinophil granule contents cause direct tissue damage
6. Always exclude parasitic infection before immunosuppressive therapy for eosinophilia
7. FIP1L1-PDGFRA+ cases are male-predominant and exquisitely sensitive to low-dose imatinib