• Investigating the Epidemiology and Prognosis of Primary Lung Lymphoepithelioma-Like Carcinoma (PPLELC) and the Impact of Immunotherapy on its Clinical-Pathological Characteristics
  • Maryam Sanaye,1 Ali Ahmadi,2,*
    1. M.Sc. Student of Genetics, Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
    2. M.Sc. Student of Genetics, Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.


  • Introduction: Primary Pulmonary Lymphoid Epithelial-Like Carcinoma (PPLELC) is a rare histological subtype of non-small cell lung cancer (NSCLC). Comprising less than 1% of NSCLC cases, it is a rare lung tumor with distinct clinicopathological features. It predominantly affects middle-aged (51-55 years), primarily non-smoking, and predominantly Asian and South Chinese female individuals. This tumor can occur in the submandibular gland, parotid gland, thymus, lung, stomach, uterus, bladder, and skin. It is associated with Epstein-Barr virus (EBV) infection. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are rarely found in this disease, while high expression levels of programmed death-ligand 1 (PD-L1) are observed. Due to its rarity, there is currently no established treatment protocol. Although subtype-specific mortality has been widely reported, some rare pathological types of lung cancer, such as PPLELC, remain poorly characterized in terms of incidence and prognosis. Moreover, this disease requires further research to understand its clinical features. It was first reported by Begin and colleagues in 1987 in a 40-year-old Southeast Asian woman in Canada. This epithelial tumor, associated with EBV infection, is histologically similar to nasopharyngeal carcinoma (NPC). Studies have shown that PPLELC is usually diagnosed at early stages and has a better prognosis compared to other NSCLC subtypes. However, the majority of reported PPLELC cases have been from Asia, and limited studies have focused on its incidence and prognosis in Western countries. This study aims to determine the epidemiology and prognosis of primary pulmonary lymphoid epithelial-like carcinoma (PPLELC) and the impact of immunotherapy on its clinicopathological features.
  • Methods: This review study was conducted in 2024 by searching keywords such as: Epidemiology, PPLELC, Immunotherapy and Clinical-Pathological Characteristics in reliable databases such as: PubMed, Scopus and Web of Science.
  • Results: PPLELC is a rare malignant lung tumor classified as a subtype of non-small cell lung cancer (NSCLC). Most patients with PPLELC do not present with obvious clinical symptoms at diagnosis. Treatment approaches for PPLELC often follow NSCLC regimens. Additionally, due to low mutation rates of EGFR, ALK, Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), ROS1 proto-oncogene receptor tyrosine kinase (ROS1), and tumor protein p53 (TP53), advanced PPLELC patients are less likely to benefit from targeted therapy. However, the high expression of programmed death-ligand 1 (PD-L1) in PPLELC suggests that PD-L1 inhibitors such as Nivolumab and Pembrolizumab may be suitable treatment options. The efficacy of Nivolumab in treating advanced NSCLC is significantly correlated with tumor mutational burden (TMB), and it is more effective in patients with high TMB compared to chemotherapy. Although PPLELC has a low TMB, a large volume of copy number variations (CNVs), especially amplification of 11q13.3 and deletion of 9p21.3, has been observed. According to studies, a number of patients underwent chemotherapy or immunotherapy. Immunotherapy drugs included Pembrolizumab, Nivolumab, or Atezolizumab. Chemotherapy regimens included platinum-based doublet chemotherapy, paclitaxel albumin-bound, or Pemetrexed monotherapy. In total, 2106 patients with LELC were identified, with the most common primary tumor site being nasopharyngeal LELC (56.22%), followed by head and neck non-nasopharyngeal LELC (21.32%) and respiratory system (7.83%). Additionally, the overall age-adjusted incidence of LELC was 0.091 per 100,000. The cancer-specific survival (CSS) rates of LELC patients at 5, 10, 15, and 20 years were 76%, 69%, 65%, and 61%, respectively. Over the past decade, a decreasing trend in the incidence of LELC has been observed.
  • Conclusion: The prognosis of PPLELC is better than other NSCLC subtypes, and immunotherapy may be a promising treatment to improve survival in advanced PPLELC patients. Whether the efficacy of immunotherapy in PPLELC can be predicted by PD-L1 and TMB requires further clinical investigation. Genetic alterations in CYLD may contribute to EBV-driven tumorigenesis in PPLELC and provide a novel therapeutic target. Current treatment options for PPLELC include surgical resection, chemotherapy, radiotherapy, and immunotherapy. Consequently, extensive research and clinical trials are necessary to develop effective treatment guidelines for PPLELC.
  • Keywords: Epidemiology, PPLELC, Immunotherapy and Clinical-Pathological Characteristics