An Unexpected Culprit: Leukemic Pulmonary Infiltration in Early-Stage Chronic Lymphocytic Leukemia
Introduction/Background/Significance Chronic lymphocytic leukemia (CLL) typically follows an indolent course and is often managed expectantly in early stages such as Rai stage 0. Pulmonary complications are most commonly infectious, whereas direct leukemic infiltration of the lungs is rare, particularly in the absence of progressive systemic disease. Prompt recognition is crucial, given its therapeutic and prognostic implications and its ability to mimic other pulmonary conditions Materials and Methods/Case Presentation/Objective An 81-year-old female with Rai stage 0 CLL with 13q deletion, diagnosed 13 years prior and managed by expectant observation, presented with cough, chest discomfort, and progressive dyspnea on exertion. She also reported fatigue, intermittent night sweats, anorexia and 15-lb weight loss over four months. Prior outpatient evaluation, including high-resolution computed tomography (HRCT), echocardiogram, and pulmonary function testing (PFT), was unrevealing except for reduced lung volumes and diffusion capacity. In the emergency department, she was tachycardic, tachypneic and hypoxic to 86% on room air. Breath sounds were diminished bilaterally without wheezes or crackles; no lymphadenopathy or hepatosplenomegaly was noted on physical examination. CT angiography was negative for pulmonary embolism but demonstrated diffuse ground-glass and nodular opacities, concerning for multifocal pneumonia or pulmonary metastases, minimally enlarged supraclavicular and axillary lymph nodes and moderate splenomegaly. Review of labs revealed an increase in absolute lymphocyte count from 52.1 to 86.8 x 103 cells/μL and a hemoglobin drop from 12.9 to 10.9 g/dl over five months. The leukocytosis was attributed to a recent upper respiratory infection. The patient was admitted for acute hypoxemic respiratory failure, presumed secondary to atypical pneumonia, and started on empiric antibiotics. Her cough and oxygen dependence persisted, prompting bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Histopathology revealed infiltration of the lung parenchyma by small mature lymphocytes, with flow cytometry demonstrating a 5.3% monotypic B-cell population with an immunophenotype consistent with her known CLL. No evidence of Richter transformation or secondary malignancy was identified. Given symptomatic pulmonary involvement, she was initiated on acalabrutinib and six cycles of Obinutuzumab. Subsequent imaging showed resolution of pulmonary infiltrates, reduction in spleen size, and no lymphadenopathy. Repeat PFT demonstrated improvement in total lung capacity, although diffusion capacity remained mildly reduced. She remains on acalabrutinib monotherapy with clinical and radiographic response.
Results/Description/Main Outcome Measures This case highlights the diagnostic challenge of pulmonary leukemic infiltration in early-stage CLL, where imaging findings are nonspecific and often mimic infection or other pulmonary processes. In our patient, persistent symptoms despite appropriate antimicrobial therapy and lack of alternative explanations prompted tissue biopsy, which remains essential for definitive diagnosis. Symptomatic pulmonary involvement represents an indication for CLL-directed therapy regardless of Rai stage. Our patient was treated with acalabrutinib and obinutuzumab, resulting in resolution of pulmonary infiltrates, improvement in pulmonary function, and clinical stabilization. This case underscores the need for a high index of suspicion and histopathologic confirmation in unexplained respiratory failure in CLL patients.
Conclusions Pulmonary leukemic infiltration, though rare, should be considered in CLL patients with unexplained respiratory symptoms, regardless of disease stage. Early tissue diagnosis guides appropriate therapy, and targeted treatments can achieve favorable outcomes, even in older adults with comorbidities.
