Leukemic Pleural Effusion as the Initial Presentation of TP53- Mutated Chronic Lymphocytic Leukemia: A Case Report.

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous mature B-cell neoplasm. While most patients present with peripheral blood lymphocytosis and/or lymphadenopathy, extranodal or serosal involvement is distinctly uncommon and is usually described in the setting of advanced disease or adverse biology. Disruption of TP53 (17p13), either by deletion or mutation, is detected in a minority of cases at diagnosis but carries major prognostic implications, including resistance to p53-dependent chemoimmunotherapy, rapid progression, and early relapse. Pleural effusion as the initial or predominant manifestation of CLL, particularly in the absence of mediastinal lymphadenopathy or organomegaly, represents a rare clinical scenario that may signal aggressive, tissue-infiltrative behavior. Case report: An 83-year-old woman with controlled hypertension and mild chronic kidney disease presented with several weeks of progressive dyspnea on minimal exertion and a nonproductive cough. She denied fever, chest pain, weight loss, or night sweats. Physical examination revealed decreased breath sounds and dullness to percussion over the lower two-thirds of the right hemithorax, without palpable lymphadenopathy, hepatosplenomegaly, or other signs of systemic disease. Chest radiography showed a massive right pleural effusion, and computed tomography confirmed a large effusion occupying nearly two-thirds of the hemithorax with passive compression and atelectasis, without mediastinal/axillary adenopathy, focal lesions, or organomegaly. Therapeutic thoracentesis drained 1.2 L of serous exudate with transient symptomatic relief. Peripheral blood showed marked leukocytosis (169.9×10^9/L) with absolute lymphocytosis; smear review demonstrated small mature lymphocytes and numerous smudge (Gumprecht) cells. Flow cytometry of peripheral blood identified 89% clonal B cells expressing CD45, bright CD19, dim CD20, CD5, CD23, CD200, and dim surface Igλ, consistent with CLL. Pleural fluid immunophenotyping revealed a concordant clonal B-cell population (13.9% of total cellularity), establishing leukemic pleural involvement. Targeted next-generation sequencing using an 87-gene somatic DNA panel (hybridization-capture; Twist Bioscience) on the PacBio Onso platform identified a pathogenic TP53 c.809T>G (p.Phe270Cys) variant within the DNA-binding domain with high variant allele frequency (VAF 82.4%), with no additional reportable variants. The patient was classified as Rai 0/Binet A; nevertheless, symptomatic leukemic pleural effusion met iwCLL treatment criteria. After one cycle of CVP, therapy was switched to oral ibrutinib due to TP53 disruption, achieving complete clinical and hematologic response after approximately three months. Conclusion: TP53-mutated CLL may debut with isolated serosal disease as the sole treatment-triggering feature. Comprehensive molecular profiling was pivotal to guide management, and BTK inhibition achieved an excellent response in a context traditionally resistant to chemoimmunotherapy.