Internal medicine resident Centre Hospitalier de L'Université de Montréal (CHUM) Montréal, Quebec, Canada
Case background: A 61-year-old white Caucasian woman with a history of hypertension, dyslipidemia, and gastroesophageal reflux disease presented on March 3, 2025, with neurological symptoms progressing over several weeks. She had a 40 pack-year smoking history and radiological evidence of emphysema, despite no clinical symptoms or prior evaluation for chronic obstructive pulmonary disease. She complained of generalized limb weakness, ataxia, and visual floaters. The patient also reported fatigue and an unintentional weight loss of 5 pounds over the past few months. She had no significant travel history and no other specific cardiac, respiratory, gastrointestinal, dermatologic, or systemic symptoms. Physical examination revealed normal vital signs, a normal cardiac exam with no jugular venous distension, no S3 or S4 gallops, and no murmurs. On neurological examination, motor strength was graded 4/5 in both upper and lower limbs bilaterally. Patellar reflexes were brisk at 3/4 bilaterally. Heel-to-shin testing revealed possible dysmetria on the right, without other focal deficits. Splinter hemorrhages were observed in the fingernails of both hands. Lung auscultation was clear bilaterally, and there were no signs of peripheral edema.
Brain Magnetic Resonance Imaging (MRI) revealed multiple acute-appearing subcortical punctate ischemic lesions maximal at the level of the frontoparietal coronas radiata bilaterally. Initial investigations also notably revealed a significant hypereosinophilia (absolute eosinophil count of 20 × 10⁹/L). Transthoracic echocardiography (TTE) identified an apical and mid-ventricular wall thickening and obliteration which limited the precise assessment of regional contractility and left ventricular (LV) ejection fraction (EF). Diastolic function and right ventricular (RV) size and function were normal on TTE, with no significant valvular abnormalities. Cardiac MRI showed myocardial edema in the LV apex and an endoluminal defect corresponding to apical obliteration, likely related to thrombus. Cardiac MRI estimated LVEF at 50% and RVEF at 59%, and showed normal LV and RV dimensions. No late gadolinium enhancement was observed. Cardiac biomarkers showed elevated high-sensitivity Troponin I level up to 243 ng/L and N-terminal pro Brain Natriuretic Peptide (NT-proBNP) of 12015 ng/L. Electrocardiograms (ECG) demonstrated normal sinus rhythm with widespread T-wave inversions and occasional ventricular ectopic beats displaying a right bundle branch block pattern with superior axis. No episodes of atrial fibrillation were recorded during ECG or in-hospital cardiac monitoring. Liver and renal panels were unremarkable, as were pulmonary function tests.
Management Challenges: An extensive etiological workup for hypereosinophilia was conducted. Hematologic investigations did not reveal any clonal markers. Next-generation sequencing (NGS) using a Qiagen (Hilden, Germany) myeloid neoplasm panel on an Illumina platform (San Diego, California, USA) showed no pathogenic mutations. BCL-ABL1 rearrangement and FIP1L1-PDGFRA fusion were both absent. Tryptase and vitamin B12 levels were not elevated. Total immunoglobulin E (IgE) was mildly elevated at 175 kU/L without atopic symptoms, and Aspergillus-specific IgE was negative. Autoimmune workup including antineutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA) and antiphospholipid antibodies were negative. A marked neutrophilia (>20 × 10⁹/L) raised concerns for infection, but multiple cultures (blood, bronchoalveolar lavage, urine) were negative. Strongyloides stercoralis serology, was also negative. A positron emission tomography imaging with 2-[(18)F]fluoro-2-deoxy-D-glucose (PET-FDG) scan revealed a large hypermetabolic lesion in the right lower pulmonary lobe. Chest computed tomography (CT) showed a 9.5 cm mass with pleural invasion and suspicious lymphadenopathies at the hilar and tracheal levels. An initial CT-guided transthoracic biopsy was non diagnostic. Subsequently, transbronchial biopsy and endobronchial ultrasound (EBUS)-guided sampling were performed. Pathological examination of the lung mass showed a poorly differentiated non-small cell carcinoma with immunohistochemistry tests favouring pulmonary adenocarcinoma, high PD-L1 expression, and KRAS p.Q61H mutation on NGS studies. Staging investigations, including PET-FDG and EBUS revealed no evidence of distant metastases or nodal involvement. Following the extensive investigations, the most likely diagnosis was an embolic ischemic stroke secondary to a left ventricular thrombus caused by an eosinophilic endomyocardial disease (Löffler endocarditis) in the context of a hypereosinophelic syndrome, which is likely paraneoplastic in the setting of an underlying lung adenocarcinoma. An endomyocardial biopsy was not performed, given the clinical, laboratory, and imaging findings were sufficient to support the diagnosis and guide initial management.
Management of the hypereosinophilia was initiated with oral prednisone 1 mg/kg daily starting March 7. However, the eosinophilia worsened, peaking at 32 × 10⁹/L on March 25. Given this progression, hydroxyurea was subsequently added to the treatment regimen and gradually titrated. The presence of an intracardiac thrombus and multiple embolic ischemic strokes warranted systemic anticoagulation with low molecular weight heparin, which was subsequently transitioned to apixaban. The patient remained euvolemic and there was no indication for heart failure therapy. The patient was discharged home on April 2, 2025. At discharge, the patient was hemodynamically stable, and her cardiac biomarkers showed an NT-proBNP of 2722 ng/L and a high-sensitivity Troponin I of 46 ng/L. The patient’s stroke-related symptoms had also significantly improved; residual deficits were limited to mild ataxia without functional impairment and the presence of a single visual floater. As of April 10, the eosinophil count had decreased to 15 × 10⁹/L. Chemotherapy with carboplatin and pemetrexed was initiated on May 5, 2025 for her lung adenocarcinoma as part of a treatment plan that will include subsequent radiation therapy. In addition to her oncology follow-up, the patient will also be monitored by cardiology and internal medicine.
