What is the appropriate lab workup for a patient presenting with persistent monocytosis and unintentional weight loss?

Laboratory Workup for Persistent Monocytosis and Unintentional Weight Loss

The appropriate laboratory workup for a patient presenting with persistent monocytosis and unintentional weight loss should include a complete blood count with differential, comprehensive metabolic panel, serum protein electrophoresis, bone marrow aspiration and biopsy, and appropriate imaging studies to rule out hematologic malignancies, particularly chronic myelomonocytic leukemia (CMML). 1

Initial Laboratory Evaluation

• Complete Blood Count (CBC) with differential and peripheral blood smear examination 2, 1

  • Look for other cytopenias, abnormal cell morphology, and Rouleaux formation
  • Quantify the degree of monocytosis (>1×10⁹/L is significant)
  • Assess monocyte morphology on peripheral smear

• Basic Chemistry Panel 2, 1

  • Blood urea nitrogen (BUN)
  • Serum creatinine and creatinine clearance
  • Serum electrolytes
  • Liver function tests
  • Serum calcium
  • Albumin
  • Lactate dehydrogenase (LDH)
  • Beta-2 microglobulin

• Inflammatory Markers 1

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)

Protein Studies

• Serum Protein Studies 2

  • Serum protein electrophoresis (SPEP)
  • Serum immunofixation electrophoresis (SIFE)
  • Quantitative immunoglobulins
  • Serum free light chain assay

• Urine Studies 2

  • 24-hour urine for total protein
  • Urine protein electrophoresis (UPEP)
  • Urine immunofixation electrophoresis (UIFE)

Advanced Testing

• Bone Marrow Evaluation 2, 1

  • Bone marrow aspiration and biopsy
  • Assessment of percentage of plasma cells and blast cells
  • Cytogenetic analysis
  • Flow cytometry for immunophenotyping
  • Molecular testing for genetic abnormalities

• Flow Cytometry 1

  • Assess for aberrancies in monocytic lineage
  • Look for abnormal CD11b/HLA-DR, CD36/CD14
  • Check for overexpression of CD56

• Cytogenetic and Molecular Testing 1

  • Conventional karyotyping
  • Testing for Philadelphia chromosome or BCR-ABL1 fusion gene
  • Next-generation sequencing for mutations in TET2, ASXL1, SRSF2, and other genes associated with myeloid neoplasms

Imaging Studies

• Skeletal Survey 2

  • X-rays to detect lytic bone lesions if multiple myeloma is suspected

• Advanced Imaging 2

  • Full-body FDG-PET-CT if lymphoma or multiple myeloma is suspected
  • MRI of specific areas if indicated by symptoms

Additional Testing Based on Clinical Suspicion

• Infectious Disease Workup 1

  • Blood cultures
  • Serologic testing for HIV, HCV, EBV, CMV
  • Testing for tuberculosis, brucellosis, or parasitic infections if clinically indicated

• Autoimmune Workup 1

  • Antinuclear antibodies (ANA)
  • Rheumatoid factor (RF)
  • Other autoimmune markers if inflammatory disease is suspected

Diagnostic Algorithm

1. Confirm persistent monocytosis (>1×10⁹/L for at least 3 months) 1

2. Rule out reactive causes:

   • Infections
   • Inflammatory conditions
   • Medications
   • Recovery from bone marrow suppression

3. If reactive causes are ruled out or monocytosis persists despite treatment:

   • Proceed with bone marrow evaluation
   • Perform cytogenetic and molecular testing

4. Evaluate for specific hematologic malignancies:

   • CMML (if ≥10% monocytes, <20% blasts, and dysplasia or genetic abnormalities) 1
   • Multiple myeloma (if M-protein present with end-organ damage) 2
   • Other myeloid neoplasms

Follow-up Recommendations

• For persistent unexplained monocytosis, repeat CBC every 2-4 weeks initially 1
• If monocytosis persists beyond 3 months without clear etiology, hematology referral is warranted 1
• For patients with weight loss, additional workup for malignancy should be considered, including gastrointestinal evaluation and imaging studies 3

Pitfalls to Avoid

• Don't attribute monocytosis solely to infection without appropriate workup, especially in the setting of weight loss
• Don't delay bone marrow evaluation in patients with persistent monocytosis and concerning features like weight loss
• Don't forget to assess for multiple myeloma in older patients with unexplained weight loss and cytopenias
• Don't miss the opportunity to diagnose CMML early by failing to perform appropriate genetic testing

The combination of persistent monocytosis and unintentional weight loss is concerning for a hematologic malignancy and warrants a thorough evaluation with the tests outlined above.