What is the management approach for a patient with eosinophilia, breast cancer, and an ovarian mass?

Management of Eosinophilia with Breast Cancer and Ovarian Mass

The management requires immediate exclusion of clonal/neoplastic eosinophilia through cytogenetic and molecular testing for tyrosine kinase fusion genes, followed by parallel evaluation of the ovarian mass with imaging and tumor markers, while recognizing that eosinophilia may represent either a paraneoplastic phenomenon or an independent hematologic disorder requiring distinct therapeutic approaches. 1, 2

Initial Diagnostic Workup for Eosinophilia

Exclude Clonal Eosinophilia First

• Obtain cytogenetic and molecular testing immediately to identify tyrosine kinase fusion genes (PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, ABL1) as these define myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and dramatically alter treatment 1
• Perform bone marrow biopsy with morphologic review, standard cytogenetics, fluorescence in situ hybridization, flow immunophenotyping, and T-cell clonality assessment 2, 3
• Note that eosinophilia is frequently observed but not a prerequisite for diagnosis of MLN-Eo—patients may present with other blood count abnormalities and organ damage irrespective of eosinophil count 1

Assess for Organ Damage

• Conduct thorough evaluation for eosinophilic organ involvement including cardiac (endomyocardial fibrosis), pulmonary, dermatologic, gastrointestinal, and neurologic manifestations 4, 2
• Obtain baseline cardiac evaluation as eosinophil-mediated cardiac damage significantly impacts prognosis 2

Ovarian Mass Evaluation

Imaging and Biomarkers

• Perform transvaginal ultrasound as the primary imaging modality for characterizing the adnexal mass 1
• Measure CA-125 levels, recognizing this is the most important biomarker for ovarian cancer detection, though not all ovarian tumors elevate CA-125 1
• Obtain CT scan of abdomen and pelvis if malignancy is suspected based on ultrasound findings or elevated CA-125 1
• MRI may be useful when surgical management would be altered by involvement of rectosigmoid, bladder, or pelvic wall 1

Surgical Planning

• Refer to gynecologic oncologist if imaging suggests malignancy, as initial management by a gynecologic oncologist is the second most important prognostic factor after stage 1
• Avoid fine-needle aspiration for cytology of ovarian masses—this is contraindicated for solid or mixed masses 1
• Surgical exploration with histopathological examination is necessary for definitive staging except in stage IV disease 1

Relationship Between Eosinophilia and Malignancies

Evidence on Breast Cancer

• Interestingly, mild eosinophilia (≥0.5-1.0 × 10⁹/L) is associated with decreased risk of breast cancer [OR 0.51, p=0.0005] compared to normal eosinophil counts 5
• This suggests eosinophilia in the context of breast cancer may represent a host anti-tumor immune response rather than tumor-driven eosinophilia 5

Paraneoplastic vs. Primary Eosinophilia

• Solid tumors can cause secondary (reactive) eosinophilia as a paraneoplastic phenomenon 2, 6
• However, primary clonal eosinophilia must be excluded first as it requires fundamentally different treatment (tyrosine kinase inhibitors vs. corticosteroids) 1, 2

Treatment Algorithm

If Tyrosine Kinase Fusion Gene Identified

• Imatinib is first-line therapy for PDGFRA or PDGFRB rearrangements due to exquisite responsiveness 1, 2, 3
• Management requires multidisciplinary team approach, preferably in specialized medical centers 1

If No Clonal Eosinophilia (Reactive or Idiopathic HES)

• Corticosteroids are first-line therapy for lymphocyte-variant hypereosinophilia and idiopathic hypereosinophilic syndrome 2, 3
• Hydroxyurea and interferon-alpha have demonstrated efficacy in steroid-refractory cases 2, 3
• For mild eosinophilia (<1.5 × 10⁹/L) without organ involvement, watch-and-wait with close follow-up is appropriate 2, 3

Concurrent Cancer Management

• Proceed with standard breast cancer treatment according to hormone receptor status and stage 1
• For the ovarian mass, surgical staging and cytoreduction remain standard if malignancy is confirmed 1
• Monitor eosinophil counts during cancer treatment as chemotherapy may affect eosinophilia 6

Critical Pitfalls to Avoid

• Do not assume eosinophilia is simply reactive without molecular testing—missing FIP1L1-PDGFRA fusion means missing a highly treatable condition with imatinib 1, 2
• Do not perform fine-needle aspiration of the ovarian mass as this is contraindicated and risks tumor spillage 1
• Do not delay referral to gynecologic oncologist if ovarian malignancy is suspected—only 33% of women with ovarian cancer receive appropriate initial subspecialty care 1
• Recognize that eosinophilia may resolve with treatment of underlying malignancy if truly paraneoplastic 6

Follow-up Strategy

For Eosinophilia

• Regular monitoring of eosinophil counts and assessment for organ damage 2, 6
• Repeat bone marrow evaluation if clonal evolution is suspected 1

For Ovarian Cancer (if confirmed)

• Clinical examination and CA-125 monitoring every 3-4 months for first 2 years, then every 6 months for years 3-5 1
• Imaging only if clinically indicated by symptoms, examination, or rising CA-125 1