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Epstein-Barr Virus–Associated Pulmonary Carcinoma

Proposing an Alternative Term and Expanding the Histologic Spectrum of Lymphoepithelioma-like Carcinoma of the Lung

Yeh, Yi-Chen, MD*,†; Kao, Hua-Lin, MD‡,§; Lee, Kang-Lung, MD†,∥; Wu, Mei-Han, MD†,∥; Ho, Hsiang-Ling, PhD*,¶; Chou, Teh-Ying, MD, PhD*,§

The American Journal of Surgical Pathology: February 2019 - Volume 43 - Issue 2 - p 211–219
doi: 10.1097/PAS.0000000000001173
Original Articles

Lymphoepithelioma-like carcinoma (LELC) of the lung is a rare Epstein-Barr virus (EBV)-associated carcinoma. It is histologically characterized by a syncytial growth pattern with marked lymphocytic infiltration that is indistinguishable from the histology observed in undifferentiated nasopharyngeal carcinomas. However, it has been noted that LELC can display nonclassic morphology and lack significant lymphocytic infiltration. In this study, we conducted a comprehensive clinicopathologic analysis of 61 patients with pulmonary LELC and performed automatic quantification of the lymphocytic infiltrate using the IHC Profiler software. We demonstrated that pulmonary LELCs have a morphologically continuous spectrum, ranging from classic poorly differentiated tumors with intense lymphocytic infiltration to nonclassic morphology with little lymphocytic infiltration. These EBV-associated tumors represent a distinct entity and usually occur in female and nonsmoking patients. Tumors with low lymphocytic infiltration can closely resemble nonkeratinizing squamous cell carcinoma and tend to be larger in size, have higher maximum standardized uptake values on radiography, and exhibit shorter times to recurrence than those with high lymphocytic infiltration. Through detailed pathologic examination, we observed several distinct morphologic features in pulmonary LELCs, including granulomatous inflammation, focal keratinization, spread through alveolar spaces, and lepidic spreading pattern. We also found that patients with tumors exhibiting granulomatous inflammation have favorable outcomes; however, spread through alveolar spaces did not significantly correlate with prognosis. As many of these “LELCs” do not resemble undifferentiated nasopharyngeal carcinoma or lymphoepithelioma, we propose using an alternative term, EBV-associated pulmonary carcinoma, to encompass the entire morphologic spectrum of this distinct disease entity.

Departments of *Pathology and Laboratory Medicine

Radiology, Taipei Veterans General Hospital

School of Medicine

§Institute of Clinical Medicine

Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University

Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan

Conflicts of Interest and Source of Funding: Supported by Ministry of Science and Technology, Taiwan (MOST 106-2320-B-075-001, MOST 107-2320-B-075-004). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Teh-Ying Chou, MD, PhD, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City 11217, Taiwan (e-mail:

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