Extranodal NK/T cell lymphoma

by Jason Wasserman MD PhD FRCPC
November 26, 2024

Extranodal NK/T cell lymphoma is a rare type of cancer that starts in natural killer (NK) cells or T cells, which are parts of the immune system. The term “extranodal” means that it typically begins outside the lymph nodes, often in areas like the nasal passages, skin, digestive system, or other organs. This type of lymphoma is strongly associated with the Epstein-Barr virus (EBV), a common virus that can sometimes contribute to cancer development.

What are the symptoms of extranodal NK/T cell lymphoma?

The symptoms of extranodal NK/T cell lymphoma vary depending on where the cancer is located. Common symptoms include:

  • Nasal congestion or nosebleeds if the nasal passages are involved.
  • Swelling or ulcers in the affected area.
  • Skin lumps or rashes if the skin is involved.
  • Unexplained fever, night sweats, and weight loss.
  • Fatigue and general weakness.
  • Abdominal pain, nausea, or diarrhea if the digestive system is affected.

What causes extranodal NK/T cell lymphoma?

The exact cause of extranodal NK/T cell lymphoma is not fully understood. However, most cases are associated with the Epstein-Barr virus, which is present in cancer cells. Genetic changes in NK or T cells may also play a role in their uncontrolled growth and spread. Risk factors include a weakened immune system and certain genetic predispositions.

How is this diagnosis made?

The diagnosis of extranodal NK/T cell lymphoma is made by examining tissue taken from the affected area, such as a biopsy of a mass or lesion. Pathologists study the cells under a microscope to look for features of lymphoma. Additional tests, including immunohistochemistry and in situ hybridization, help confirm the diagnosis and determine the type of lymphoma.

Microscopic features

When pathologists examine extranodal NK/T cell lymphoma under the microscope, they see specific patterns:

  • The cancer cells grow densely and spread through tissues. These areas often have necrosis (dead cells) and scattered apoptotic bodies (dying cells).
  • Cancer cells can cause ulceration (open sores) and inflammation in areas like the skin or mucosal linings. The surface tissue may grow abnormally, resembling squamous cell carcinoma (a type of cancer).
  • Cancer cells frequently surround and damage blood vessels, which can lead to changes in the vessel walls (fibrinoid changes).
  • Many inflammatory cells, including small lymphocytes, plasma cells, histiocytes, and eosinophils, are often present in the tumour, making it look like an infection or inflammation.
  • The cancer cells vary in size, ranging from small to large. Most have irregularly shaped nuclei and pale or clear cytoplasm. Larger cells may have a granular appearance in the nucleus. These cells divide frequently, and larger, more abnormal cells may dominate as the disease progresses.

Extranodal NK/T cell lymphoma viewed under the microscope.

Immunohistochemistry and in situ hybridization

These are special tests used to study lymphoma cells in detail.

  • Immunohistochemistry: This technique uses dyes that attach to specific proteins on the cancer cells. These proteins help determine whether the lymphoma comprises NK or T cells. Common markers in extranodal NK/T cell lymphoma include CD2, CD56, and cytotoxic molecules like TIA1 and granzyme B. Some cases may show markers typically associated with T cells, such as CD5 or CD8, while others may lack specific NK or T cell markers.
  • In situ hybridization: This test detects a molecule called EBER, produced by cells infected with Epstein-Barr virus (EBV). Since EBV infection is found in most extranodal NK/T cell lymphoma cases, the presence of EBER in the cancer cells confirms the association with this virus.

These tests help pathologists confirm the diagnosis and provide information that can guide treatment.

Expression of EBER in extranodal NK/T cell lymphoma
Extranodal NK/T cell lymphoma. The brown tumour cells are positive for EBER by in situ hybridization.

Prognosis

The outlook for extranodal NK/T cell lymphoma depends on the stage of the disease, the patient’s overall health, and the treatments available.

  • For early-stage disease, combining chemotherapy and radiation therapy can result in a five-year survival rate of over 70%.
  • For advanced-stage disease, treatments that include L-asparaginase have been effective, with about 80% of patients responding to therapy.
  • Newer treatments, such as immune checkpoint inhibitors, show promise for patients whose disease has come back or does not respond to initial treatment. These drugs target specific proteins, like PD-L1, found on cancer cells.

Certain factors, such as being older than 60, having advanced disease, or having detectable levels of EBV in the blood, may indicate a less favorable outcome. Regular monitoring with imaging tests like PET-CT and EBV blood tests helps assess how well the treatment is working. Early detection and tailored therapy improve the chances of successful treatment.

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