Rhinitis as a Clinical Symptom of Primary Pulmonary Lymphoepithelioma-Like Carcinoma

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Rhinitis as a Clinical Symptom of Primary Pulmonary Lymphoepithelioma-Like Carcinoma: An Incidental Discovery During COVID-19 Pandemic Surveillance

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) represents a rare subset of non-small cell lung cancer (NSCLC), accounting for only 0.25% to 0.9% of cases in China. This malignancy is closely associated with Epstein–Barr virus (EBV) infection and shares histopathological similarities with nasopharyngeal carcinoma. The clinical presentation of PPLELC often overlaps with common lung cancer symptoms, such as cough, hemoptysis, and chest pain. However, a unique case reported during the COVID-19 pandemic highlights rhinitis as an unexpected clinical manifestation of PPLELC, underscoring the importance of EBV monitoring and imaging in high-risk populations.

Clinical Presentation and Diagnostic Pathway

A 48-year-old non-smoking female from Hunan Province, China, presented to a local hospital during the COVID-19 pandemic with acute exacerbation of chronic rhinitis, including sneezing, nasal congestion, and rhinorrhea. Her rhinitis had persisted for over two years, characterized by mild nasal secretions interspersed with severe episodes that resolved spontaneously within 5–7 days. Adhering to pandemic protocols, she underwent routine COVID-19 screening, including a throat swab, chest computed tomography (CT), and additional viral testing of nasal secretions and serum due to flu-like symptoms.

Notably, EBV was detected in both nasal secretions and serum. Chest CT revealed a suspicious mass in the left upper lung’s lingula lobe, measuring 34 mm × 32 mm. Subsequent 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET/CT) confirmed hypermetabolic activity in the lung lesion, with a maximum standardized uptake value (SUVmax) of 23.9 kBq/mL. Intriguingly, abnormal FDG uptake was also observed in the nasal cavity (SUVmax 6.6 kBq/mL), suggesting chronic viral or bacterial infection. Preoperative staging classified the tumor as T2aN1M0 according to the 8th Union for International Cancer Control (UICC) guidelines.

Surgical Intervention and Pathological Findings

The patient underwent left video-assisted thoracoscopic surgery (VATS) pneumonectomy on May 15, 2020, after intraoperative evaluation revealed tumor extension across the upper and lower lung lobes. Histopathological analysis of the resected specimen confirmed PPLELC, characterized by undifferentiated epithelial cells surrounded by dense lymphocytic infiltration. Metastatic carcinoma was identified in group 11 lymph nodes, while nodes from groups 5, 7, 9, and 10 remained unaffected.

Immunohistochemical staining demonstrated positivity for panCK, CK5/6, P40, P63, Ki-67 (30%), EBER (Epstein–Barr virus-encoded small RNA), and PD-L1 (80%), with negative results for TTF-1, CK7, and CD56. These findings aligned with PPLELC’s diagnostic criteria: (1) histological features resembling nasopharyngeal carcinoma and (2) confirmed EBV presence in tumor tissue.

Genetic Profiling and Therapeutic Implications

Postoperative genetic testing of the tumor tissue screened 20 common oncogenic targets, including EGFR (exons 18/19/20/21/T790), FGFR2/3, ROS1, RET, PIK3CA (exons 10/12), ALK, KRAS (codons 12/13/61/146), NRAS (codons 12/13/61), KIT (exons 9/11), BRCA1/2, and ERBB2 (exon 20/copy number amplification). No mutations or amplifications were detected, reinforcing PPLELC’s distinct molecular profile compared to conventional NSCLC subtypes.

EBV’s Role in PPLELC and Nasopharyngeal Carcinoma

The case underscores EBV’s oncogenic potential in epithelial malignancies. Persistent EBV infection is a well-established risk factor for nasopharyngeal carcinoma, with viral proteins like LMP1 activating NF-κB pathways to drive carcinogenesis. Similarly, PPLELC exhibits EBV-driven pathogenesis, as evidenced by EBER positivity in tumor cells. The patient’s concurrent EBV-related rhinitis and PPLELC suggest a systemic EBV influence, potentially linking chronic nasal infection to pulmonary malignancy.

Pandemic-Driven Diagnostic Serendipity

The incidental discovery of PPLELC during COVID-19 screening highlights the unintended benefits of pandemic-era imaging mandates. Routine chest CT scans, initially intended to detect SARS-CoV-2 pneumonia, facilitated early tumor identification in an otherwise asymptomatic individual. The authors advocate for integrating EBV monitoring and periodic imaging in patients with chronic rhinitis, particularly those with confirmed EBV persistence, to enable early PPLELC detection.

Clinical Recommendations and Future Directions

  1. EBV Surveillance: Patients with EBV-associated rhinitis should undergo regular serum and nasal secretion testing to monitor viral load.
  2. Imaging Protocols: Annual chest CT scans are recommended for high-risk individuals, even in the absence of respiratory symptoms.
  3. Differential Diagnosis: PPLELC must be distinguished from nasopharyngeal carcinoma metastasis, as both share EBV etiology and histopathological overlap.
  4. Therapeutic Strategies: Given the lack of targetable mutations, surgical resection remains the cornerstone of PPLELC management, supplemented by PD-L1-directed immunotherapy in advanced cases.

Conclusion

This case illustrates rhinitis as a potential sentinel symptom of PPLELC in EBV-infected individuals. The COVID-19 pandemic’s imaging requirements inadvertently facilitated early cancer diagnosis, emphasizing the value of proactive surveillance in at-risk populations. Future research should explore EBV’s systemic effects across epithelial tissues and optimize protocols for viral load monitoring and imaging in chronic rhinitis patients.

DOI: https://doi.org/10.1097/CM9.0000000000001541

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