Paraneoplastic Hypereosinophilia Associated with Lung Squamous-Cell Carcinoma

Introduction Eosinophilia poses a unique diagnostic challenge due to association with a wide range of clinical presentations and underlying pathophysiology. Paraneoplastic syndromes represent an exceptionally rare cause for hypereosinophilia, though should be considered in association with solid tumors where infectious, inflammatory, and neoplastic evaluations are otherwise unrevealing. Case Description A 69-year-old man with a history of cardiovascular disease, type 2 diabetes, tobacco use, and recently diagnosed lung squamous cell carcinoma with extensive liver metastases was admitted to the hospital for altered mental status. The exam was unremarkable, and MRI brain noted interval small area of restricted diffusion in bilateral cerebral hemispheres which was ultimately felt to be artifactual; however, during admission, he developed intermittent fever and rigors with leukocytosis (WBC 44.8 K/μL) and progressive eosinophilia (peak 5.9 K/μL from ∼2 K/μL) as well as elevated absolute neutrophil, monocyte, and granulocyte counts without blasts. Quantitative lymphocyte subsets reflected normal absolute counts with elevated CD4:CD8 ratio (3.08). Additional infectious evaluation included negative blood cultures, respiratory viral panel, HSV qPCR, Cryptococcal/Histoplasma/Blastomyces antigen, and Coxiella/Echinococcus/Strongyloides/Toxicara antibodies with no culture growth from IR-guided aspiration of liver lesions. Further targeted evaluation of eosinophilia reflected negative ANCA and MPO/PR3, stable troponin, normal tryptase level, negative KIT D816V mutational and clonal TRG rearrangement analyses, and eosinophilia FISH panel without evidence of FIP1LI::PDGFRA gene fusion or PDGFRA/PDGFRB/FGFR1/JAK2 rearrangements. Discussion Given the negative laboratory evaluation, lack of rash or defining features of EGPA, and inconsistent temporal association with any specific medications, the persistently rising eosinophil count was felt most likely secondary to underlying squamous cell carcinoma. Multidisciplinary discussion surrounding corticosteroid treatment was initiated in light of concurrent malignancy and septic presentation, though while infectious evaluation remained pending, the focus of care was ultimately transitioned to comfort, so this has thus far been deferred. This case represents a rare but recognized phenomenon in the literature, particularly with carcinomas arising from mucin-secreting epithelium such as that found in the bronchus and gastrointestinal tract, which should be considered among the differential for eosinophilia and may portend more aggressive disease with poor prognosis.