Metastatic progression and treatment challenges in EBV-associated pulmonary lymphoepithelioma-like carcinoma: a case report

Objective: To describe the clinical characteristics, treatment course, and management challenges of advanced pulmonary lymphoepithelioma-like carcinoma (LELC), with a focus on metastatic disease and treatment-interfering complications. Methods: We report the clinical course of a 42-year-old woman with EBV-associated pulmonary LELC. The patient was initially diagnosed with stage IIIB disease and underwent radical surgery followed by adjuvant chemoradiotherapy. No definite local recurrence was observed postoperatively; however, cervical lymph node metastasis developed shortly thereafter, followed by rapid progression to stage IV disease characterized predominantly by liver metastases. First-line treatment with pembrolizumab combined with chemotherapy achieved an initial partial response. During subsequent disease progression, the patient developed persistent high-grade fever refractory to antimicrobial therapy, which significantly compromised treatment continuity. Results: This case demonstrates the potentially aggressive and heterogeneous clinical behavior of pulmonary LELC despite multimodal therapy. Serial plasma EBV-DNA levels closely paralleled disease activity, decreasing during treatment response and increasing during progression. Persistent high-grade fever posed a major diagnostic and therapeutic challenge. Tumor-related fever was considered the most likely etiology, although occult infection could not be definitively excluded. Due to sustained fever, declining performance status, limited clinical experience with immunotherapy at that time, and concerns regarding treatment-related risks, immunotherapy was interrupted during the febrile period. Conclusion: Advanced pulmonary LELC may exhibit aggressive clinical behavior with predominant metastatic burden. Immunochemotherapy may provide meaningful but often transient benefit in patients with high PD-L1 expression, while dynamic plasma EBV-DNA monitoring may serve as a useful indicator of disease activity. In addition, atypical tumor-related fever may substantially interfere with treatment continuity and clinical decision-making. Early recognition and proactive management of such complications may help optimize outcomes.