Jason Wasserman MD PhD FRCPC and Aleksandra Paliga MD FRCPC
July 24, 2023

What is ALK-negative anaplastic large cell lymphoma?

ALK-negative anaplastic large cell lymphoma (ALCL) is a type of cancer that starts from specialized immune cells called T cells. Common locations for ALK-negative anaplastic large cell lymphoma include lymph nodes, bone, liver, digestive tract, and breast.

What type of cancer is ALK-negative anaplastic large cell lymphoma?

ALK-negative anaplastic large cell lymphoma is an immune system cancer and a type of non-Hodgkin’s lymphoma (NHL).

Why is this type of cancer called “ALK-negative”?

This type of cancer is called ALK-negative because the tumour cells do not contain a genetic change involving the ALK gene. This is important because it separates this cancer from the similarly named ALK-positive anaplastic large cell lymphoma which does contain a genetic change involving the ALK gene.

What causes ALK-negative anaplastic large cell lymphoma?

Currently, the cause of ALK-negative anaplastic large cell lymphoma is unknown. Most tumours contain genetic changes involving genes associated with normal T cell function including JAK1 and STAT3. Approximately 30% of cases contain a genetic change involving the DUSP22 gene. At the present time, doctors do not know why some people develop these genetic changes.

What are the symptoms of ALK-negative anaplastic large cell lymphoma?

Symptoms of ALK-negative anaplastic large cell lymphoma include unexplained fever, night sweats, weight loss, and enlarged lymph nodes.

How is the diagnosis of ALK-negative anaplastic large cell lymphoma made?

The diagnosis of ALK-negative anaplastic large cell lymphoma can only be made after a tissue sample from the tumour is examined under the microscope by a pathologist. The tissue is typically removed in a procedure called a biopsy. Additional tests such as immunohistochemistry and flow cytometry may be performed to confirm the diagnosis and to rule out other diseases that can look similar under the microscope.

What does ALK-negative anaplastic large cell lymphoma look like under the microscope?

When examined under the microscope, ALK-negative anaplastic large cell lymphoma is made up of large, abnormal-looking T cells. The tumour cells may be arranged as single cells, small groups, or large sheets. Tumour cells may also be seen inside blood vessels. Unique tumour cells called ‘hallmark cells’ may also be seen. Hallmark cells are characterized by an abnormal ‘horseshoe’ shaped nucleus that is pushed to the side of the cell. Mitotic figures (tumour cells dividing to create new tumour cells) and necrosis (dead cells) are also common.

When immunohistochemistry is performed, the tumour cells are positive for CD30. Markers of normal T cells, such as CD2, CD3, CD5, and CD8 are frequently negative while other T cell markers such as CD4 are often positive. Markers of other types of immune cells such as CD20, CD15, and PAX5 are negative. In contrast to ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma is negative for ALK protein by immunohistochemistry.