What is the diagnostic workup for a middle-aged man with persistent monocytosis, weight loss, and intolerance to solid food?

Diagnostic Workup for Persistent Monocytosis with Weight Loss and Intolerance to Solid Food

The diagnostic workup for a middle-aged man with persistent monocytosis, weight loss, and intolerance to solid food should prioritize evaluation for chronic myelomonocytic leukemia (CMML) and gastrointestinal disorders, with bone marrow examination and endoscopic evaluation as essential components of the initial assessment.

Initial Laboratory Evaluation

• Complete blood count with differential to confirm monocytosis (>1×10⁹/L)
• Peripheral blood smear examination to assess monocyte morphology
• Comprehensive metabolic panel including liver and renal function tests
• Inflammatory markers (ESR, CRP)
• Serum protein electrophoresis with immunofixation to rule out monoclonal gammopathy
• Serum free light chain assay
• HIV, hepatitis panel, and other infectious disease testing based on risk factors

Hematologic Workup for Persistent Monocytosis

1. Bone marrow aspiration and biopsy - Essential for patients with persistent monocytosis (>3 months) to evaluate for CMML 1, 2

   • Morphologic assessment for dysplasia
   • Flow cytometry to detect aberrant monocytic populations
   • Cytogenetic analysis to exclude Philadelphia chromosome and other rearrangements
   • Molecular testing for mutations in TET2, SRSF2, and ASXL1 genes (absence has ≥90% negative predictive value for CMML) 3

2. CMML diagnostic criteria (WHO) 1:

   • Persistent peripheral blood monocytosis >1×10⁹/L
   • No Philadelphia chromosome or BCR-ABL1 fusion gene
   • No rearrangement of PDGFRA or PDGFRB
   • <20% blasts in peripheral blood and bone marrow
   • At least one of: dysplasia in one or more cell lines, acquired clonal cytogenetic/molecular genetic abnormality, or persistence of monocytosis for ≥3 months with no other cause

Gastrointestinal Evaluation

Given the patient's intolerance to solid food and weight loss, a thorough gastrointestinal evaluation is crucial:

1. Upper endoscopy with biopsies to evaluate for:

   • Celiac disease (with serologic testing for tissue transglutaminase antibodies)
   • Inflammatory conditions
   • Malignancy
   • Infection (e.g., giardiasis)

2. Colonoscopy with biopsies to evaluate for:

   • Inflammatory bowel disease (IBD) - notably, monocytosis is a biomarker of IBD severity 4
   • Malignancy
   • Microscopic colitis

3. Small bowel evaluation:

   • CT enterography or MR enterography
   • Video capsule endoscopy if small bowel pathology is suspected

Additional Considerations

• Seronegative enteropathies: For patients with negative celiac serology but persistent symptoms, evaluation for other causes of villous atrophy is warranted 1

  • Medication review (particularly for angiotensin II receptor antagonists)
  • Testing for tropical sprue, small intestinal bacterial overgrowth, autoimmune enteropathy

• Monoclonal gammopathy workup if protein electrophoresis is abnormal 1:

  • Bone marrow examination for plasma cell assessment
  • Skeletal survey or low-dose whole-body CT if IgG M-protein >15 g/L or IgA M-protein >10 g/L

• Imaging studies:

  • Chest X-ray
  • Abdominal and pelvic CT scan to evaluate for organomegaly, lymphadenopathy, or masses

Diagnostic Algorithm

1. Confirm persistent monocytosis (>1×10⁹/L for ≥3 months)
2. Rule out reactive causes (infections, inflammation, medications)
3. Perform bone marrow examination if monocytosis persists without clear cause
4. Conduct gastrointestinal evaluation with endoscopy and imaging
5. Consider specialized testing based on initial findings:
   • Flow cytometry for monocyte subsets
   • Molecular testing for myeloid mutations
   • Advanced GI testing (breath tests, specialized biopsies)

Pitfalls to Avoid

• Premature diagnosis of CMML: Ensure persistent monocytosis for at least 3 months and exclude reactive causes
• Missing gastrointestinal causes: Weight loss and intolerance to solid food strongly suggest GI pathology that requires thorough evaluation
• Inadequate bone marrow assessment: Both aspiration and biopsy are needed for complete evaluation
• Overlooking medication effects: Certain medications can cause both monocytosis and enteropathy
• Reducing gluten before testing: This can limit the accuracy of both serologic and histologic results for celiac disease 1

By systematically addressing both the hematologic and gastrointestinal aspects of this presentation, clinicians can efficiently identify the underlying cause of the patient's symptoms and develop an appropriate treatment plan focused on improving mortality, morbidity, and quality of life outcomes.