Clinical features and treatment outcome of lymphoepithelioma-like carcinoma from multiple primary sites: a population-based, multicentre, real-world study

Meiting Chen, Yungchang Chen, Xiaojie Fang, Zhao Wang, Xingxiang Pu, Chaoyong Liang, Hongqiang Guo, Qian Li, Fei Pan, Huangming Hong, He Huang, Jiman Li, Tongyu Lin, Meiting Chen, Yungchang Chen, Xiaojie Fang, Zhao Wang, Xingxiang Pu, Chaoyong Liang, Hongqiang Guo, Qian Li, Fei Pan, Huangming Hong, He Huang, Jiman Li, Tongyu Lin

Abstract

Background: Lymphoepithelioma-like carcinoma (LELC) is a rare and unique subtype of cancer that histologically resembles undifferentiated nasopharyngeal carcinoma (NPC). The population-based analysis of LELC and the optimal treatment remains unclear.

Materials and methods: This real-world, retrospective study investigated 770 patients with LELC for primary site, treatment, and survival outcomes from 2005 to 2019 from five cancer centres in China. The overall survival (OS) of different subgroups was appraised by log-rank tests and Kaplan-Meier analysis.

Results: Primary sites LELC included the lung (597 cases, 77.5%), salivary gland (115 cases, 14.9%), and others. The median progression-free survival (PFS) of LELC patients was 47.4 months. The median overall survival (OS) was not reached. The 5-year survival rate for LELC patients was 77.8%. Most patients in stages I and II received surgery. The majority of patients in stage III received surgery and radiotherapy. More than half of the patients in stage IV received chemotherapy. Among relapsed or metastatic cases receiving chemotherapy, patients who received immunotherapy at any time presented with a superior OS than those without immunotherapy (P < 0.0001, HR = 0.39, 95% CI 0.25-0.63). Compared with the SEER database, patients with LELC had a better prognosis than NPC, with a 5-year overall survival of 77.3% vs. 56.8% (P < 0.001).

Conclusion: Our data provide treatment patterns and outcomes for LELC from various primary sites. Randomized controlled studies are necessary to further define the standard of care for patients with LELC. Trial registration This clinical trial was registered at ClinicalTrials.gov (No. NCT04614818).

Keywords: Lymphoepithelioma-like carcinoma; Multicentre study; Rare cancer; Survival; Treatment pattern.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
The distribution of origin of LELC (A) and initial staging of LELC (B)
Fig. 2
Fig. 2
PFS (A) and OS (B) in total LELC patients. PFS (C) and OS (D) for LELC patients according to different stage. OS for LELC patients according to different primary site (E)
Fig. 3
Fig. 3
OS compared LELC with NPC in seer data base. Survival for total patients (A) and according to patients at stage I (B), II (C), III (D) and IV (E). OS compared PLELC with squamous carcinoma of lungs in seer data base (F)
Fig. 4
Fig. 4
DFS in patients receiving adjuvant chemotherapy at stage I (A) and II (B). DFS in patients receiving adjuvant radiotherapy at stage III (C). PFS (D) and OS (E) in patients receiving pemetrexed-based chemotherapy as first-line regimen at stage IV or after relapsed. OS in patients at stage IV or after relapsed receiving immunotherapy at any time (F)

References

    1. Sathirareuangchai S, Hirata K. Pulmonary lymphoepithelioma-like carcinoma. Arch Pathol Lab Med. 2019;143(8):1027–1030. doi: 10.5858/arpa.2018-0149-RS.
    1. Qin Y, Gao G, Xie X, Zhu Z, Guan W, Lin X, Xie Z, Ming O, Chen R, Zhong N, et al. Clinical features and prognosis of pulmonary lymphoepithelioma-like carcinoma: summary of eighty-five cases. Clin Lung Cancer. 2019;20(3):e329–e337. doi: 10.1016/j.cllc.2018.12.014.
    1. Ding Y, Sun Z, You W, Zhang S, Chang C, Yan S, Wang W. Lymphoepithelioma-like intrahepatic cholangiocarcinoma with Epstein-Barr virus infection: report of a rare case. Ann Transl Med. 2019;7(18):497. doi: 10.21037/atm.2019.08.105.
    1. Kawagishi S, Ose N, Minami M, Funaki S, Kanou T, Kimura K, Taniguchi S, Morii E, Shintani Y. Total thymectomy for thymic lymphoepithelioma-like carcinoma-report of two cases. Surg Case Rep. 2019;5(1):158. doi: 10.1186/s40792-019-0706-6.
    1. Labgaa I, Stueck A, Ward S. Lymphoepithelioma-like carcinoma in liver. Am J Pathol. 2017;187(7):1438–1444. doi: 10.1016/j.ajpath.2017.02.022.
    1. Suster D, Pihan G, Mackinnon A, Suster SJ, Mpaojot US. Canadian Academy of Pathology I: Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus. Modern Pathol. 2018;31(12):1801–1806. doi: 10.1038/s41379-018-0097-4.
    1. Hsiung C, Huang C, Wang C, Huang E, Huang H. Lymphoepithelioma-like carcinoma of salivary glands: treatment results and failure patterns. Br J Radiol. 2006;79(937):52–55. doi: 10.1259/bjr/17905092.
    1. Lin Z, Fu S, Zhou Y, Zhang X, Chen C, He L, Li H, Wang Y, Chen T, Zhang L, et al. First-line platinum-based chemotherapy and survival outcomes in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma. Lung Cancer. 2019;137:100–107. doi: 10.1016/j.lungcan.2019.09.007.
    1. Hong S, Liu D, Luo S, Fang W, Zhan J, Fu S, Zhang Y, Wu X, Zhou H, Chen X, et al. The genomic landscape of Epstein-Barr virus-associated pulmonary lymphoepithelioma-like carcinoma. Nat Commun. 2019;10(1):3108. doi: 10.1038/s41467-019-10902-w.
    1. Fang W, Hong S, Chen N, He X, Zhan J, Qin T, Zhou T, Hu Z, Ma Y, Zhao Y, et al. PD-L1 is remarkably over-expressed in EBV-associated pulmonary lymphoepithelioma-like carcinoma and related to poor disease-free survival. Oncotarget. 2015;6(32):33019–33032. doi: 10.18632/oncotarget.5028.
    1. Chen J, Zhou L, Qiu X, Yang R, Liang J, Pan Y, Li H, Peng G, Shao C. Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in EBV-associated gastric carcinoma from Guangdong, an endemic area of nasopharyngeal carcinoma. J Med Microbiol. 2018;67(11):1614–1627. doi: 10.1099/jmm.0.000839.
    1. Chan A, Zhang Z, Chong C, Tin E, Chow C, Wong N. Genomic landscape of lymphoepithelioma-like hepatocellular carcinoma. J Pathol. 2019;249(2):166–172. doi: 10.1002/path.5313.
    1. Kumar V, Dave V, Harris J, Huang Y. Response of advanced stage recurrent lymphoepithelioma-like carcinoma to nivolumab. Immunotherapy. 2017;9(12):955–961. doi: 10.2217/imt-2017-0067.
    1. Chen M, Wang Z, Yuan M, Fang X, Lin T. Treatment of pembrolizumab and chemotherapy results in pulmonary lymphoepithelioma-like carcinoma progression through harboring secondary amplification of PI3KCA and IL-7R. Lung Cancer. 2020;144:87–89. doi: 10.1016/j.lungcan.2020.03.018.
    1. Chen B, Zhang Y, Dai S, Zhou P, Luo W, Wang Z, Chen X, Cheng P, Zheng G, Ren J, et al. Molecular characteristics of primary pulmonary lymphoepithelioma-like carcinoma based on integrated genomic analyses. Signal Transduction Targeted Ther. 2021;6(1):6. doi: 10.1038/s41392-020-00382-6.
    1. Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45(2):228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Kim Y, Hong H, Jeong S, Lee E, Jung MJM. Lymphoepithelial carcinoma of the salivary glands. Medicine. 2017;96(7):e6115. doi: 10.1097/MD.0000000000006115.
    1. Welch P, Williams S, Foss R, Tomaszewski M, Gupta A. Ojha JJOs, oral medicine, oral pathology, oral radiology, endodontics: Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2011;111(1):78–86. doi: 10.1016/j.tripleo.2010.05.075.
    1. Sekihara K, Okuma Y, Kawamoto H, Hosomi Y. Clinical outcome of thymic lymphoepithelioma-like carcinoma: Case report of a 14-year-old male. Oncol Lett. 2014;8(5):2183–2186. doi: 10.3892/ol.2014.2475.
    1. Attaran Y, Moghdam S, Monabati A, Sarkeshikian R. Lymphoepithelial-like carcinoma with papillary transitional cell carcinoma of the urinary bladder associated with carcinoma in situ changes of the urothelium; A case report and review of literature. Iran J Pathol. 2019;14(2):156–164. doi: 10.30699/ijp.14.2.156.
    1. Fadila K, Faycal A, Lamiaa J, Mohammed B, Nabil I. Lymphoepithelioma-like carcinoma of the breast: a case report and review of the literature. Pan Afr Med J. 2019;32:18. doi: 10.11604/pamj.2019.32.18.15978.
    1. Sairin M, Yahya N, Kuan C, Yunus M, Abdullah M. Management of a rare lymphoepithelial carcinoma of the submandibular gland in elderly. Indian J Otolaryngol Head Neck Surg. 2019;71:18–20. doi: 10.1007/s12070-015-0940-6.
    1. Almeida L, Silveira H, Silva E, Barbeiro C, de Paula J, Bufalino A, Ribeiro-Silva A, León JE. EBV-negative lymphoepithelial-like carcinoma of the lower lip. Autopsy Case Rep. 2020;10(1):e2020138. doi: 10.4322/acr.2020.138.
    1. Faisal M, Hartenbach S, Schratter A, Köstler W, Kaufmann H, Seemann R, Lill C, Hamzavi S, Wutzl A, Erovic BM. Lymphoepithelial carcinoma of larynx and hypopharynx: a rare clinicopathological entity. Cancers. 2020;12(9):2431. doi: 10.3390/cancers12092431.
    1. Whelan A, Al-Sayed A, Bullock M, Taylor SM. Primary parotid lymphoepithelial carcinoma: a case report and literature review of a rare pathological entity. Int J Surg Case Rep. 2020;72:610–614. doi: 10.1016/j.ijscr.2020.06.035.
    1. Fong P, Tan T, Kiong KL. Concurrent chemoradiation in locally advanced primary middle ear lymphoepithelial carcinoma: an effective treatment modality case report. J Otolaryngol Head Neck Surg. 2021;50(1):1. doi: 10.1186/s40463-020-00489-4.
    1. Monteiro F, Baldaia H, Ribeiro L, Sousa M, Oliveira P, Ferreira E, de Almeida M, Condé A. Epstein-Barr virus-associated with lymphoepithelial carcinoma: a rare tumor of the larynx. Clin Med Insights Ear Nose Throat. 2019;12:1179550619865551. doi: 10.1177/1179550619865551.
    1. Liu C, Huang SH. EBV-associated lymphoepithelioma-like thyroid carcinoma with favorable outcome: case report with cytopathologic and histopathologic study. Diagn Pathol. 2018;13(1):39. doi: 10.1186/s13000-018-0713-0.
    1. Chen B, Chen X, Zhou P, Yang L, Ren J, Yang X, Li W. Primary pulmonary lymphoepithelioma-like carcinoma: a rare type of lung cancer with a favorable outcome in comparison to squamous carcinoma. Respir Res. 2019;20(1):262. doi: 10.1186/s12931-019-1236-2.
    1. Wang J, Deng R, Liu H, Luo Y, Yang ZC. Clinicopathological characteristics and prognostic analysis of lymphoepithelial carcinoma of salivary gland: a population-based study. Gland Surg. 2020;9(6):1989–1997. doi: 10.21037/gs-20-464.
    1. Takakura H, Tachino H, Fujisaka M, Nakajima T, Yamagishi K, Ishida M, Shojaku HJM. Lymphoepithelial carcinoma of the maxillary sinus: a case report and review of the literature. Medicine. 2018;97(28):e11371. doi: 10.1097/MD.0000000000011371.
    1. Wu Q, Wang W, Zhou P, Fu Y, Zhang Y, Shao Y, Jiang L. Primary pulmonary lymphoepithelioma-like carcinoma is characterized by high PD-L1 expression, but low tumor mutation burden. Pathol Res Pract. 2020;216(8):153043. doi: 10.1016/j.prp.2020.153043.
    1. Wang L, Dong H, Ni S, Huang D, Tan C, Chang B, Sheng W. Programmed death-ligand 1 is upregulated in intrahepatic lymphoepithelioma-like cholangiocarcinoma. Oncotarget. 2016;7(43):69749–69759. doi: 10.18632/oncotarget.11949.
    1. Narayanan A, Knollmann F, Walby J, Lim S, Gandara D, Riess JW. EBV-positive primary pulmonary lymphoepithelioma-like carcinoma response to PD-L1 blockade. Clin Lung Cancer. 2019;20(3):e238–e241. doi: 10.1016/j.cllc.2018.12.015.
    1. Chau S, Tong J, Chow C, Kwan J, Lung R, Chung L, Tin E, Wong S, Cheung A, Lau R, et al. Distinct molecular landscape of Epstein-Barr virus associated pulmonary lymphoepithelioma-like carcinoma revealed by genomic sequencing. Cancers. 2020;12(8):2065. doi: 10.3390/cancers12082065.

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