Case Report Open Access
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World J Clin Cases. Nov 16, 2023; 11(32): 7876-7880
Published online Nov 16, 2023. doi: 10.12998/wjcc.v11.i32.7876
Primary pulmonary lymphoepithelioma-like carcinoma misdiagnosed as lung squamous cell carcinoma: A case report
Chang-Jie Yin, Guang-Jie Wang, Xiao-Mei Su, Dong Li, Department of Oncology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
ORCID number: Chang-Jie Yin (0009-0009-2284-8487); Dong Li (0000-0002-9669-4873).
Author contributions: Yin CJ collected all the data related to the case report and drafted the manuscript; Wang GJ and Su XM collected and produced the relevant pictures; Li D provided expert analysis and revised the manuscript; and all authors have read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Dong Li, MD, Associate Chief Physician, Department of Oncology, The General Hospital of Western Theater Command, No. 270 Rongdu Avenue, Jinniu District, Chengdu 610083, Sichuan Province, China.
Received: August 12, 2023
Peer-review started: August 12, 2023
First decision: October 10, 2023
Revised: October 22, 2023
Accepted: November 9, 2023
Article in press: November 9, 2023
Published online: November 16, 2023


Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an uncommon subtype of squamous cell carcinoma (SCC) of the lung, closely associated with Epstein-Barr virus (EBV) infection. The pathological features of PPLELC closely resemble those of SCC, which makes it prone to misdiagnosis. Surgical intervention constitutes the primary treatment approach for PPLELC.


This report describes a 44-year-old woman who was hospitalized for 1 mo due to left chest pain. Computed tomography revealed a mass shadow in the anterior basal segment of the left lower lobe, and a subsequent needle biopsy suggested SCC. The patient underwent radical tumor resection in the lower left lobe of the lung, and postoperative pathological examination indicated lymphoepithelial carcinoma, and the test for EBV encoded small RNA was positive. Following surgery, the patient was scheduled to receive four cycles of adjuvant chemotherapy, using the paclitaxel + carboplatin regimen, but the patient refused further treatment.


PPLELC is an exceptionally rare subtype of lung SCC and is prone to misdiagnosis.

Key Words: Primary pulmonary lymphoepithelioma-like carcinoma, Lung cancer, Squamous cell carcinoma, Misdiagnosis, Epstein-Barr virus, Case report

Core Tip: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of squamous cell carcinoma (SCC) of the lung, closely associated with Epstein-Barr virus infection. The pathological features of PPLELC bear similarities to those of SCC, which makes it prone to misdiagnosis. Surgery is the primary treatment for PPLELC. Here, we present a recent case of PPLELC at our hospital, initially misdiagnosed as SCC of the lung.


Lung cancer has the highest incidence rate among cancers worldwide. Non-small cell lung cancer is the most common type, accounting for about 85% of cases[1], including squamous cell carcinoma (SCC) and adenocarcinoma. Among subtypes of lung SCC, primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is rare and its specific pathogenesis remains unknown, but it may be associated with Epstein-Barr virus (EBV) infection[2,3]. PPLELC displays a higher incidence rate in Southeast Asia compared with Europe and the United States[4]. PPLELC lacks specific clinical manifestations, and its pathological changes are similar to those of lung SCC. Typical features include extensive lymphocyte infiltration and better prognosis in comparison with other types of non-small cell lung cancer[5]. Currently, surgery is the primary treatment method for PPLELC, and there is no universally accepted standard for postoperative adjuvant treatment. In this report, we present a case of PPLELC initially misdiagnosed as lung SCC, highlighting a rare subtype prone to misdiagnosis. This case report might serve as a valuable reference for improving diagnosis and treatment of PPLELC.

Chief complaints

Dull pain in the left chest for 1 mo.

History of present illness

The patient developed dull pain in the left chest in February 2023, with no other accompanying discomfort such as chest tightness or breathing difficulties. However, the patient did not seek further examination or treatment at that time.

History of past illness

The patient had rheumatoid arthritis for > 7 years that was effectively managed with stable control through oral medication.

Personal and family history

No history of smoking or drinking.

Physical examination

The performance status score was 1, and there was no peripheral lymphadenopathy. Additionally, no positive signs were found in the heart, lungs, or abdomen.

Laboratory examinations

Tumor markers: α-fetoprotein 3.86 ng/mL; carcinoembryonic antigen 0.68 ng/mL; carbohydrate antigen (CA)199 5.20 U/mL; CA125 79.70 U/mL; CA153 27.90 U/mL.

Imaging examinations

Computed tomography (CT) showed a lobulated mass shadow in the anterior basal segment of the left lower lobe, with a size of approximately 3.3 cm × 3.6 cm × 3.5 cm. There was adjacent pleural thickening and adhesion, indicating the possibility of a neoplasm. However, no tumors were detected during magnetic resonance imaging (Figure 1).

Figure 1
Figure 1 Computed tomography images of the chest. A and B: The tumor size was approximately 3.3 cm × 3.6 cm × 3.5 cm (orange arrow).
Pathological findings

On March 10, 2023, the patient underwent a needle biopsy, and the pathological diagnosis indicated SCC (Figure 2), with CD56(-), cytokeratin (CK)8/18(+), chromogranin A (CgA)(-), Ki-67 (+, 30%), P40(+), synaptophysin (Syn)(-), and thyroid transcription factor 1 (TTF-1)(-) on immunohistochemistry. According to the results, the patient underwent radical lung cancer surgery on March 18, 2023. Postoperative pathology suggested no lymph node metastasis. The findings showed positivity for EBV encoded small RNA (EBER), CK5/6, CK8/18, Ki-67 (60%), and P40, while TTF-1 was negative (Figure 2), leading to a diagnosis of PPLELC.

Figure 2
Figure 2 Immunohistochemistry staining of biopsy specimens and Epstein-Barr virus encoded small RNA testing indicate primary pulmonary lymphoepithelioma-like carcinoma (magnification 400 ×). A: Immunohistochemistry (IHC) staining of needle biopsy specimens (orange arrow); B: IHC staining of postoperative specimens (orange arrow); C: Presence of Epstein-Barr virus encoded small RNA in postoperative specimens (orange arrow).

Based on the pathological examination results, the patient was diagnosed with PPLELC (pT2aN0M0 IB).


The patient was scheduled to undergo four cycles of postoperative adjuvant chemotherapy. The chosen protocol for chemotherapy was paclitaxel + carboplatin.


The patient refused further treatment and examination, and no further follow-up was carried out.


PPLELC is a rare type of lung cancer, accounting for about 0.92% of all lung malignancies[6]. It was first reported in the 1980s[3], and was classified as other unclassified cancer by the World Health Organization (WHO) in 2015. However, in the current 2021 5th edition of WHO classification of thoracic tumors, lymphoepithelial carcinoma of the lung is defined as a subtype of SCC [International Classification of Diseases for Oncology code: 8082/3]. The incidence of PPLELC is low in Western countries, but it has a higher prevalence in Asia, particularly in Taiwan, Hong Kong, and Guangdong, China[6,7]. This disease primarily affects young nonsmoking patients, with a higher prevalence among women. Clinical manifestations of PPLELC are mostly nonspecific, and in the early stage, patients typically exhibit no obvious symptoms. As the tumor progresses, symptoms such as cough, phlegm, hemoptysis, and chest pain may manifest[8].

Most Asian patients with PPLELC are diagnosed with EBV infection, suggesting a strong correlation between EBV and PPLELC[6]. In this report, we performed in situ hybridization of EBER on patient specimens, and the results were positive, further indicating the association between EBV infection and PPLELC. However, the specific pathogenic mechanism of EBV has not been fully elucidated to date.

Typical PPLELC is a solitary nodule near the pleura, and the lesion is generally < 3.5 cm. The CT imaging features often include a burr sign and a lobed sign[9]. Although the imaging manifestations are not distinct from those of other types of lung malignancies, lymph node metastasis is uncommon[10]. In this case, PPLELC grew under the pleura, with a size of approximately 3.3 cm × 3.6 cm × 3.5 cm as measured by CT. No lymph node metastasis was observed, and the imaging findings were consistent with typical PPLCLE characteristics.

The histopathological manifestations of PPLELC closely resemble those of nasopharyngeal carcinoma. A distinctive feature of PPLELC is the presence of a large number of tumor-infiltrating lymphocytes in the tumor background[2], and positivity for EBER. However, in biopsy specimens, these characteristics may not be obvious due to the small sample size. Research has identified common immune markers for PPLELC, such as P40, P64, and CK5/6, which are similar to those seen in SCC, leading to a potential risk of misdiagnosis[11]. In this case, the patient underwent lung biopsy, which yielded a small gray-white tissue sample of about 1.5 cm. The immune markers observed were: CD56(-), CK8/18(+), CgA(-), Ki-67 (+, 30%), P40(+), Syn(-), and TTF-1(-). Due to the limited amount of biopsied tissue, the typical microscopic characteristics of PPLELC were not observed, and the immune markers appeared to align with SCC, resulting in a misdiagnosis. However, during surgical treatment, a larger specimen was obtained, and the postoperative pathological examination revealed a significant number of tumor-infiltrating lymphocytes. The immune markers observed were CK5/6(+), CK8/18(+), Ki-67(+,60%), P40(+), and TTF-1(-). Additionally, the in situ hybridization examination suggested EBER(+). These findings ultimately led to the correct diagnosis of lymphoepitheliomatous carcinoma. It is notable that EBER, a crucial diagnostic test that distinguishes SCC from PPLELC, is highly affordable, costing approximately 240 Chinese yuan, making it accessible to the majority of patients.

The treatment approach for PPLELC currently lacks unified guidelines, and there are no specific National Comprehensive Cancer Network guidelines for its management. However, radical surgery is usually considered the primary treatment method. According to a study involving 52 PPLELC patients who underwent radical surgery alone, only six experienced relapse, with recurrence developing between 10.6 and 41.1 mo[8]. Overall, the prognosis was favorable. Currently, it is believed that early-stage patients usually do not require postoperative adjuvant therapy, while chemotherapy can extend the overall survival of advanced-stage patients. In clinical practice, platinum-based dual-drug combination chemotherapy is commonly used as the first-line treatment for advanced PPLELC[7]. Therefore, in this case, we suggested the patient to undergo four cycles of postoperative adjuvant chemotherapy with the paclitaxel + carboplatin regimen, but the patient refused further treatment and examination, and no further follow-up was carried out.


PPLELC is a rare subtype of lung cancer that is frequently misdiagnosed due to its microscopic appearance and immune markers closely resembling those of SCC. Currently, there are no standardized treatment guidelines for PPLELC. Surgical intervention is a common treatment approach, and patients may benefit from postoperative adjuvant chemotherapy.


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1.  Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83:584-594.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 386]  [Cited by in F6Publishing: 1292]  [Article Influence: 86.1]  [Reference Citation Analysis (0)]
2.  He J, Shen J, Pan H, Huang J, Liang W, He J. Pulmonary lymphoepithelioma-like carcinoma: a Surveillance, Epidemiology, and End Results database analysis. J Thorac Dis. 2015;7:2330-2338.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 24]  [Reference Citation Analysis (0)]
3.  Bégin LR, Eskandari J, Joncas J, Panasci L. Epstein-Barr virus related lymphoepithelioma-like carcinoma of lung. J Surg Oncol. 1987;36:280-283.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 153]  [Cited by in F6Publishing: 162]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
4.  Chan JK, Hui PK, Tsang WY, Law CK, Ma CC, Yip TT, Poon YF. Primary lymphoepithelioma-like carcinoma of the lung. A clinicopathologic study of 11 cases. Cancer. 1995;76:413-422.  [PubMed]  [DOI]  [Cited in This Article: ]
5.  Jiang RR, Feng XL, Zhu WT, Guo MX, Tan XL, Jiang XJ, Dou XM, Liu L. A Rare Subtype of Non-small Cell Lung Cancer: Report of 159 Resected Pathological Stage I-IIIA Pulmonary Lymphoepithelioma-Like Carcinoma Cases. Front Surg. 2021;8:757085.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
6.  Chang YL, Wu CT, Shih JY, Lee YC. New aspects in clinicopathologic and oncogene studies of 23 pulmonary lymphoepithelioma-like carcinomas. Am J Surg Pathol. 2002;26:715-723.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 86]  [Cited by in F6Publishing: 92]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
7.  Huang CJ, Feng AC, Fang YF, Ku WH, Chu NM, Yu CT, Liu CC, Lee MY, Hsu LH, Tsai SY, Shih CS, Wang CL. Multimodality treatment and long-term follow-up of the primary pulmonary lymphoepithelioma-like carcinoma. Clin Lung Cancer. 2012;13:359-362.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 38]  [Article Influence: 3.5]  [Reference Citation Analysis (0)]
8.  Liang Y, Wang L, Zhu Y, Lin Y, Liu H, Rao H, Xu G, Rong T. Primary pulmonary lymphoepithelioma-like carcinoma: fifty-two patients with long-term follow-up. Cancer. 2012;118:4748-4758.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 81]  [Cited by in F6Publishing: 96]  [Article Influence: 8.7]  [Reference Citation Analysis (0)]
9.  Mo Y, Shen J, Zhang Y, Zheng L, Gao F, Liu L, Xie C. Primary lymphoepithelioma-like carcinoma of the lung: distinct computed tomography features and associated clinical outcomes. J Thorac Imaging. 2014;29:246-251.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 21]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
10.  Hoxworth JM, Hanks DK, Araoz PA, Elicker BM, Reddy GP, Webb WR, Leung JW, Gotway MB. Lymphoepithelioma-like carcinoma of the lung: radiologic features of an uncommon primary pulmonary neoplasm. AJR Am J Roentgenol. 2006;186:1294-1299.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 29]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
11.  Lin L, Lin T, Zeng B. Primary lymphoepithelioma-like carcinoma of the lung: An unusual cancer and clinical outcomes of 14 patients. Oncol Lett. 2017;14:3110-3116.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 17]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]