Faces of the Invisible Leukemia: A Three-Case Series of Chronic Eosinophilic Leukemia Unmasked Through Cutaneous, Molecular, and Geriatric Lenses
Chronic eosinophilic leukemia (CEL) is a rare clonal myeloproliferative neoplasm accounting for less than 1% of all MPNs. Its chameleon-like clinical presentations ranging from refractory dermatoses to incidental molecular findings frequently delay diagnosis and expose patients to inappropriate therapies. We present three cases that collectively illustrate the diagnostic, molecular, and therapeutic spectrum of CEL, each revealing a distinct and underrecognized face of this disease.
Materials and Methods/Case Presentation/Objective:
Case 1: A 73-year-old woman presented with refractory pruritus, blistering lesions, anasarca, and severe hip pain. Laboratory workup demonstrated leukocytosis (19.11 × 10⁹/L), normocytic anemia (Hb 8.7 g/dL), and marked eosinophilia (11.6 × 10⁹/L). Skin biopsy confirmed bullous pemphigoid (BP); however, refractoriness to standard immunosuppression prompted bone marrow evaluation, which revealed a clonal myeloid population (26%) with aberrant immunophenotype
(CD10-, CD15+, CD16+, CD33+, CD11b+, MPO+, HLA-DR-), establishing the diagnosis of CEL. BP was reinterpreted as a paraneoplastic manifestation. This case highlights how eosinophil-derived mediators can directly trigger subepidermal blister formation, mimicking primary autoimmune dermatosis and constituting a diagnostic trap that led to prolonged immunosuppression while an occult clonal neoplasm progressed.
Case 2: A 23-year-old phenotypic female with stage IIIC mucinous ovarian carcinoma was referred for investigation of hypereosinophilia (11-13.5 × 10⁹/L), fever of undetermined origin, and persistent leukocytosis. Extensive workup excluded infection, autoimmune, and allergic etiologies. Bone marrow aspiration demonstrated hypercellularity with myeloid predominance and pseudo-Pelger-Huët anomaly. BCR-ABL PCR was negative. Comprehensive genetic studies revealed an unprecedented dual anomaly: FIP1L1::PDGFRA fusion and a 48,XXYY karyotype a sex chromosome aneuploidy classically described in males with an estimated prevalence of 1:18,000-40,000 births. This case represents the first reported instance of a FIP1L1::PDGFRA-positive myeloproliferative neoplasm with a 48,XXYY karyotype in a phenotypic female with a concurrent solid malignancy, raising questions about shared oncogenic signaling particularly MAPK pathway dysregulation as a mechanistic link.
Case 3: A 97-year-old woman presented with erythematous, pruritic, and scaly skin lesions. Skin biopsy demonstrated eosinophilic dermatosis of hematologic malignancy. Bone marrow flow cytometry confirmed a clonal myeloid immunophenotype consistent with a myeloproliferative disorder with eosinophilia (CD45+, CD13+, CD15+, CD11b+, CD33+, and aberrant MPO+). Normal IgE effectively excluded reactive and lymphocyte-variant hypereosinophilic syndrome. Given her advanced age and frailty, a steroid-sparing approach combining low-dose prednisone with low-dose methotrexate leveraging its JAK/STAT inhibitory activity independent of DHFR was initiated. The patient achieved favorable clinical and hematologic response, demonstrating that effective and tolerable disease control is achievable even in the oldest-old.
Results/Description/Main Outcome Measure(s): These three cases expose the diagnostic and therapeutic pluralism of CEL. Case 1 illustrates the paraneoplastic masquerade as BP. Case 2 demonstrates previously undescribed oncogenomic complexity in an unexpected host. Case 3 challenges age-related therapeutic nihilism with a novel steroid-sparing framework.
Conclusion(s).:
Across all cases, CEL requires molecular profiling to identify imatinib-sensitive FIP1L1::PDGFRA fusions, demands a low threshold for bone marrow evaluation, and can be successfully managed across the full spectrum of patient complexity. Failure to recognize these faces of the invisible leukemia carries the risk of misclassification, inappropriate treatment, and disease progression. Comprehensive molecular and cytogenetic workup is not a luxury it is a clinical imperative.
Trademarked Items:
References:
