Lymphoepithelial carcinoma

by Jason Wasserman MD PhD FRCPC
March 11, 2023

What is lymphoepithelial carcinoma?

Lymphoepithelial carcinoma is a type of cancer made up of large tumour cells surrounded by non-cancerous immune cells. This type of cancer is more common in young adults of Asian descent.

Where does lymphoepithelial carcinoma get its name?

This type of cancer is called lymphoepithelial carcinoma because when examined under the microscope, the ‘epithelial’ tumour cells are typically surrounded by ‘lymphoid’ (immune) cells.

What type of cancer is lymphoepithelial carcinoma?

Lymphoepithelial carcinoma is a type of cancer called non-keratinizing squamous cell carcinoma because the tumour cells express markers normally found in squamous cells. It is described as non-keratinizing because the squamous cells in the tumour do not produce a protein called keratin which is found in most squamous cells.

Where is lymphoepithelial carcinoma normally found in the body?

Lymphoepithelial carcinoma can start anywhere in the body but the most common locations for this tumour are the head and neck and lungs.

What causes lymphoepithelial carcinoma?

The most common cause of lymphoepithelial carcinoma is infection with Epstein-Barr virus (EBV). This virus is responsible for lymphoepithelial carcinoma in approximately 90% of patients, in particular those of Asian descent.

What are the symptoms of lymphoepithelial carcinoma?

The symptoms of lymphoepithelial carcinoma depend on the size of the tumour and its location in the body. For example, small tumours in the lungs may not cause any symptoms while larger tumours can lead to coughing and difficulty breathing, especially if the tumour is located near one of the large airways. Tumours in the head and neck (with the exception of the nasopharynx) may not cause any symptoms until the tumour is large enough to be seen on felt as a lump on the face or neck.

What is the difference between lymphoepithelial carcinoma and nasopharyngeal carcinoma?

Lymphoepithelial carcinoma and nasopharyngeal carcinoma are both types of non-keratinizing squamous cell carcinoma associated with EBV. Both of these tumours also look almost identical when examined under the microscope. By convention, the tumour is called nasopharyngeal carcinoma when it starts in a part of the upper respiratory tract called the nasopharynx. In other areas of the body, it is called lymphoepithelial carcinoma.

How is lymphoepithelial carcinoma diagnosed?

The diagnosis is made after part or all of the tumour is removed and examined under the microscope by a pathologist.

What does lymphoepithelial carcinoma look like under the microscope?

When examined under the microscope, lymphoepithelial carcinoma is made up of large pink tumour cells. The tumour cells have large round nuclei (the part of the cell that holds the genetic material) and the nuclei contain prominent clumps of genetic material called nucleoli. The tumour cells may be arranged as single cells or in groups. The tumour cells are typically surrounded by large numbers of immune cells, specifically B cells and T cells. These immune cells are not part of the tumour but rather a response by the immune system to the tumour. Mitotic figures (tumour cells dividing to create new tumour cells) are usually seen but the number varies greatly between tumours.

Lymphoepithelial carcinoma
Lymphoepithelial carcinoma. Large tumour cells are surrounded by non-cancerous immune cells.

What other tests may be ordered to confirm the diagnosis?

Other tests including immunohistochemistry may be performed to confirm the diagnosis and to rule out other conditions that can look very similar to lymphoepithelial carcinoma under the microscope. When immunohistochemistry is performed the tumour cells commonly express markers normally found in squamous cells including cytokeratin 5 (CK5), p40, and p63. These markers may be described as positive or reactive. Markers of other cell types are usually not expressed and may be described as negative or non-reactive. The surrounding non-cancerous immune cells typically express various markers normally found in immune cells including CD45, CD3, and CD20.

What is EBER and why is it important?

EBER (Epstein-Barr virus-encoded small mRNAs) is a small piece of genetic material called messenger RNA produced by cells infected with EBV. Pathologists perform a test called in situ hybridization to look for EBER inside the tumour cells. This test is important both for confirming the diagnosis and for showing that the tumour is associated with EBV.

Other helpful resources

Atlas of Pathology

A+ A A-