Squamous cell carcinoma

Lymphoepithelial carcinoma

Last author update: 27 March 2023
Last staff update: 27 March 2023

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PubMed Search: Lymphoepithelial carcinoma

Heather I-Hsuan Chen-Yost, M.D.
Tao Huang, Ph.D.
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Page views in 2024 to date: 1,575
Cite this page: Chen-Yost HI, Huang T. Lymphoepithelial carcinoma. website. Accessed May 19th, 2024.
Definition / general
  • According to the 2021 WHO classification update, lymphoepithelial carcinoma is the currently designated name and is defined as a type of poorly differentiated squamous cell carcinoma associated with variable amount of lymphoplasmacytic infiltrate and frequent association with Epstein-Barr virus (EBV)
    • In the 2015 WHO classification, the preferred name was lymphoepithelioma-like carcinoma and it was in the category of other and unclassified carcinomas
Essential features
  • Characterized by distinct syncytial growth pattern, vesicular nuclei, prominent eosinophilic nucleoli and variable lymphoplasmacytic infiltrate
  • Immunohistochemical (IHC) staining is the same as that for conventional squamous cell carcinoma (diffusely positive for CK5/6, p40 and p63)
  • With complete surgical resection it has a favorable prognosis when compared with conventional squamous cell carcinoma
  • Formerly known as lymphoepithelioma-like carcinoma
ICD coding
  • Use the ICD code specific for location of tumor
  • ICD-9: 162 - malignant neoplasm of trachea bronchus and lung
  • ICD-10: C34.90 - malignant neoplasm of unspecified part of unspecified bronchus or lung
  • ICD-11: 2C25 - malignant neoplasms of bronchus or lung
  • EBV induced carcinogenesis (Nat Commun 2019;10:3108)
    • Driven by dysregulated NFkB pathway, loss of type I IFN genes, APOBEC family gene signature
Clinical features
  • CT images of the thorax and fiberoptic bronchoscopy with tissue biopsy
  • FNA cytology with IHC studies may assist
    • Can be limited by sampling errors
  • Endoscopic examination with or without radiographic imaging of nasopharynx performed to rule out metastatic lymphoepithelial carcinoma
  • Reference: Respirology 2006;11:539
Radiology description
  • Well defined, solitary, lobulated mass > 1 cm (Clin Radiol 2022;77:e201)
  • Homogeneous density
  • Vascular enhancement
  • High 18F-FDG uptake
Radiology images

Images hosted on other servers:

Xray and CT scans

Unenhanced thoracic CT

Prognostic factors
Case reports
  • Stage I: surgery is the primary form of treatment (Med Oncol 2020;37:20)
    • Complete resection is curative at stage I or II
  • Stage II or higher: surgery + postoperative radiology or chemotherapy
  • Potential options: PDL1 inhibitors
Gross description
  • Tends to be peripherally located versus central (Front Surg 2021;8:757085)
  • Well circumscribed with irregular borders
  • Not associated with bronchi
Frozen section description
  • Similar pitfalls to those found with lymphoepithelioma-like carcinomas in other sites (Int J Surg Pathol 2020;28:872)
    • Can resemble lymphoid tissue on low power
    • Epithelial component can look histiocytic
Microscopic (histologic) description
  • Syncytial growth pattern
  • Large polygonal cells with vesicular nuclei, prominent eosinophilic nucleoli and variably abundant eosinophilic cytoplasm
  • Variable mitosis
  • Variable lymphoplasmacytic infiltrate
  • Reported to also have granulomatous inflammation, focal keratinization and lepidic spreading pattern (Am J Surg Pathol 2019;43:211)
Microscopic (histologic) images

Contributed by Heather I-Hsuan Chen-Yost, M.D.

Lymphoid-like lesion

Lymphoid infiltrate and syncytial cells

EBER ISH stain

p63 immunostain

CK5/6 immunostain

Virtual slides

Images hosted on other servers:

Wedge excision of 74 year old woman

Left upper lobe lung resection

Cytology description
  • Spindle cells are arranged in large cohesive clusters with admixed small lymphocytes (Cytopathology 2019;30:653)
  • Nuclei: pleomorphic, oval, prominent nucleoli
  • Can mimic melanoma, synovial sarcoma
Positive stains
Molecular / cytogenetics description
  • TRAF3 makes up ~80% of deletion mutations in lymphoepithelial carcinoma and 5% of simple somatic mutations (Nat Commun 2019;10:3108)
  • Does not show C:G to A:T transversions from tobacco smoking
  • High PDL1 expression (Oncotarget 2015;6:33019)
  • Rarely shows the typical driver mutation for conventional non-small cell lung cancer, such as TP53, KRAS, EGFR mutations or ALK and ROS1 translocations
Sample pathology report
  • Lung, right lower lobe, lobectomy:
    • Lymphoepithelial carcinoma, 2.3 cm (see synoptic report)
Differential diagnosis
Additional references
Board review style question #1

Which of the following is most commonly associated with the lung lesion pictured above?

  1. EBV infection
  2. History of autoimmune disease
  3. Radiation exposure
  4. Smoking history
  5. Young age
Board review style answer #1
A. EBV infection. Lymphoepithelial carcinoma is a rare subtype of squamous cell carcinoma of the lung that is strongly associated with EBV infection. It tends to be associated with Asian patients in their 50s. Unlike other lung primary carcinomas, it is not known to be associated with a smoking history. It has also not been shown to be associated with radiation exposure or history of autoimmune disease. Radiation exposure can be associated with a differential diagnosis for Hodgkin lymphoma; however, the epithelial cells do not resemble Reed-Sternberg cells and are cohesive. History of autoimmune disease can be associated with lymphoid interstitial pneumonia, which also presents with lymphoid follicles but there will be a background of alveolar disruption and loose epithelioid granulomas. Furthermore, other inflammatory cells such as giant cells and macrophages will also be seen.

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Reference: Lymphoepithelial carcinoma
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