Lung
Squamous cell carcinoma
Lymphoepithelial carcinoma
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Last author update: 27 March 2023
Last staff update: 27 March 2023
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PubMed Search: Lymphoepithelial carcinoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Chen-Yost HI, Huang T. Lymphoepithelial carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lunglymphoepithelialcarcinoma.html. Accessed December 15th, 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
Terminology
- Formerly known as lymphoepithelioma-like carcinoma
ICD coding
Epidemiology
- Rare; 0.9% of all primary lung cancers (Oncol Lett 2017;14:3110)
- Predominately in Asian populations (Am J Surg Pathol 2002;26:715)
- M = F
- Median age: 51 - 57 years (Cancer Sci 2011;102:282)
Sites
- Lung parenchyma has an even distribution between central and peripheral (Clin Lung Cancer 2019;20:e329)
- Not typically associated with bronchi
Pathophysiology
- EBV induced carcinogenesis (Nat Commun 2019;10:3108)
- Driven by dysregulated NFkB pathway, loss of type I IFN genes, APOBEC family gene signature
Etiology
- Strongly associated with EBV infection (J Thorac Disc 2021;13:5683)
- Not associated with smoking history (Oncol Lett 2017;14:3110)
Clinical features
- No specific clinical manifestations
- Most common respiratory symptoms (Comput Math Methods Med 2022;2022:1086697)
- Cough
- Expectoration
- Chest pain
- ~33% of patients have no symptoms (J Thorac Imaging 2014;29:246)
Diagnosis
- 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
- Has better outcomes than conventional squamous cell carcinoma (Respir Res 2019;20:262)
- Favorable prognostic factors (Cancer 2012;118:4748)
- Early tumor stage
- Absence of lymph node metastasis
- Complete resection
- High PDL1 or wild type p53 expression (Signal Transduct Target Ther 2021;6:6)
- Unfavorable prognostic factors
- Tumor recurrence and necrosis (Am J Clin Pathol 2001;155:841)
- High serum EBV viral capsid antigen
Case reports
- 30 and 64 year old women with pulmonary masses (Medicine (Baltimore) 2018;97:e9976)
- 52 year old Asian woman with a mass (J Thorac Oncol 2018;13:e75)
- 59 year old woman with fever and cough (Clin Respir J 2017;11:1052)
- 60 year old Japanese woman with nodule on CT (Int J Surg Case Rep 2021;79:431)
Treatment
- 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
- Infiltrate can be scant and morphologically resemble nonkeratinizing squamous cell carcinoma (Am J Surg Pathol 2019;43:211)
- 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
- Squamous markers: CK5/6, p40, p63 (Front Surg 2021;8:757085)
- EBER ISH: desirable diagnostic criteria (Respir Res 2019;20:262)
Negative 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
- Poorly differentiated adenocarcinoma (Am J Clin Pathol 1995;103:35):
- NUT carcinoma:
- Both lymphoepithelial carcinoma and NUT carcinoma have areas of round blue cells with focal areas of abrupt squamous differentiation and extensive p63 / p40 expression
- NUT carcinoma is negative for EBER ISH
- NUT carcinoma is positive for NUT1 by IHC or has translocations involving the NUT gene; most common fusion is BRD4::NUT from a t(15;19) translocation (J Thorac Oncol 2015;10:951)
- Malignant melanoma:
- Lymphomas:
- Scant cytoplasm, stippled, fine chromatin
- Do not form sheets, clusters, nests
- Positive for lymphoid markers and negative for epithelial / squamous markers
- Metastatic undifferentiated carcinoma of nasopharynx (AJR Am J Roentgenol 2006;186:1294):
- Histologically similar, can also be EBV positive
- Requires clinical and imaging correlation
- Metastatic medullary carcinoma of breast or colon (Virchows Arch 2000;437:198, Int J Clin Exp Pathol 2012;5:105):
- Will also have strong lymphocytic infiltration
- No syncytial growth pattern, nuclear pleomorphism, high mitotic rate
- EBV negative
Additional references
Board review style question #1
Which of the following is most commonly associated with the lung lesion pictured above?
- EBV infection
- History of autoimmune disease
- Radiation exposure
- Smoking history
- 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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Reference: Lymphoepithelial carcinoma
