ALK-positive anaplastic large cell lymphoma

by Jason Wasserman MD PhD FRCPC and Aleksandra Paliga MD FRCPC
July 19, 2023

What is ALK-positive anaplastic large cell lymphoma?

ALK-positive anaplastic large cell lymphoma (ALCL) is a type of cancer that starts from specialized immune cells called T cells. It typically involves lymph nodes, but it can also be found in the skin and lungs among other sites.

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

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

What causes ALK-positive anaplastic large cell lymphoma?

ALK-positive anaplastic large cell lymphoma is caused by a genetic change called a rearrangement that combines the ALK gene with another gene, typically NPM1. As a result, the ALK gene is ‘switched on’ leading to increased and abnormal production of the Anaplastic Lymphoma Kinase (ALK) protein. Cells with increased production of ALK protein can grow and divide faster and avoid immune checkpoints designed to remove abnormal cells. At the present time, doctors do not know why some people develop this genetic change.

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

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

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

The diagnosis of ALK-positive 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-positive anaplastic large cell lymphoma look like under the microscope?

When examined under the microscope, ALK-positive 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 and ALK protein. Markers of normal T cells, such as CD3, CD5, and CD8 are frequently negative while other T cell markers such as CD2 and CD4 are often positive. Markers of other types of immune cells such as CD20, CD15, and PAX5 are negative.