What diagnostic tests should be run in this case?

Diagnostic Tests for Suspected Eosinophilia and Myeloid/Lymphoid Neoplasms

For patients with suspected eosinophilia, a comprehensive diagnostic workup should include complete blood count with differential, comprehensive metabolic panel, serum tryptase, vitamin B12 levels, and bone marrow evaluation with cytogenetic and molecular testing to identify potential tyrosine kinase fusion gene rearrangements. 1

Initial Laboratory Evaluation

• Complete blood count (CBC) with differential to document eosinophilia and assess for other blood count abnormalities (monocytosis, dysplasia, circulating blasts) 1
• Comprehensive metabolic panel including liver function tests, uric acid, and lactate dehydrogenase 1
• Serum tryptase levels (elevated in myeloproliferative variants of hypereosinophilia and systemic mastocytosis) 1
• Vitamin B12 levels (commonly elevated in myeloid neoplasms with PDGFRA fusion gene) 1
• Peripheral blood smear review to evaluate for dysplasia and other abnormalities 1

Additional Laboratory Testing Based on Clinical Presentation

• Serology testing for Strongyloides and other parasitic infections to rule out secondary causes 1
• Testing for antineutrophil cytoplasmic antibodies and antinuclear antibodies to evaluate for autoimmune causes 1
• Stool ova and parasites test and gastrointestinal polymerase chain reaction (PCR) to exclude parasitic causes 1
• Quantitative serum immunoglobulin levels, including IgE (elevated in allergic conditions and lymphocytic variants of hypereosinophilic syndrome) 1
• Erythrocyte sedimentation rate and/or C-reactive protein to assess inflammatory status 1
• Aspergillus-specific IgE to evaluate for allergic bronchopulmonary aspergillosis 1
• Ferritin and glycosylated ferritin (if Adult-Onset Still's Disease is suspected, as very high ferritin levels with low glycosylated fraction <20% are characteristic) 1

Bone Marrow Evaluation

• Bone marrow aspirate and biopsy with immunohistochemistry for CD117, CD25, tryptase, and reticulin/collagen stains for fibrosis 1
• Conventional cytogenetics to identify chromosomal abnormalities 1
• Fluorescence in situ hybridization (FISH) and/or nested reverse transcription PCR (RT-PCR) to detect tyrosine kinase fusion gene rearrangements 1
• Confirmatory FISH testing to identify breakpoints associated with tyrosine kinase fusion gene rearrangements 1
• Next-generation sequencing (NGS) via myeloid mutation panels to establish clonality when no tyrosine kinase fusion gene rearrangements are detected 1

Flow Cytometry and Immunophenotyping

• Flow cytometry (preferred) and/or immunohistochemistry to identify aberrant T-cell populations if lymphocytic variant of hypereosinophilic syndrome (L-HES) is suspected 1
• Molecular analysis to confirm T-cell clonality in suspected L-HES cases 1
• Typical immunophenotype of L-HES is CD3-, CD4+, CD7-, and CD5+ 1

Imaging Studies

• If organ involvement is suspected, appropriate imaging studies should be performed based on symptoms and clinical findings 1
• PET/CT scan may be considered if lymphoma is suspected in the differential diagnosis 1

Diagnostic Algorithm

1. First, rule out secondary causes of eosinophilia with appropriate testing
2. Perform bone marrow evaluation with cytogenetic and molecular testing to identify potential myeloid/lymphoid neoplasms with eosinophilia
3. If no clonal markers are identified, consider idiopathic hypereosinophilic syndrome (HES) as a diagnosis of exclusion

Important Considerations

• Hypereosinophilia of undetermined significance (HEUS) and idiopathic HES are diagnoses of exclusion after ruling out primary (clonal/neoplastic) and secondary (reactive) causes 1
• An elevated serum tryptase and/or vitamin B12 level is commonly observed in myeloproliferative variants of hypereosinophilia 1
• Mutations detected by NGS may provide prognostic information and guide treatment decisions 1
• Early identification of specific genetic abnormalities (particularly tyrosine kinase fusion genes) is crucial as they may respond to targeted therapies 1