ALK-positive anaplastic large cell lymphoma (ALCL) is a type of cancer that starts in T cells, which are specialized white blood cells that normally help the body fight infections. Because it develops from immune cells, it is classified as a non-Hodgkin lymphoma (NHL).
This disease most often involves lymph nodes, but it can also appear in other parts of the body, including the skin and lungs.
ALK-positive ALCL is caused by a genetic change inside the lymphoma cells. The most common change involves the ALK gene, which becomes rearranged and fused with another gene, usually NPM1.
This rearrangement causes the ALK gene to be “switched on” all the time. The abnormal ALK protein that is produced allows the lymphoma cells to grow quickly, divide uncontrollably, and avoid being removed by the immune system.
Doctors do not know why this change happens in some people, but it is not something that is inherited or passed down to children.
The symptoms depend on where the tumour is located in the body.
Common symptoms include:
Unexplained fever.
Night sweats.
Unintentional weight loss.
Enlarged lymph nodes.
Other symptoms may develop if the lymphoma grows in a particular organ. For example, skin involvement may cause visible nodules or plaques, while lung involvement may cause cough or shortness of breath.
The diagnosis can only be made after a biopsy, which is a procedure where a sample of the tumour is removed and examined under the microscope by a pathologist.
In addition to examining the tissue, pathologists often order additional tests such as:
Immunohistochemistry, which looks for specific proteins including ALK.
Flow cytometry, which analyzes the types of lymphocytes present.
Molecular tests, which confirm the ALK rearrangement.
These tests are essential to distinguish ALK-positive ALCL from ALK-negative ALCL and from other types of lymphoma that may look similar under the microscope.
When examined under the microscope, this lymphoma is made up of large, abnormal T cells. The tumour cells may be scattered as single cells, collected in small groups, or arranged in sheets.
A distinctive feature is the presence of hallmark cells. These are large tumour cells with a horseshoe-shaped nucleus that is pushed to the side of the cell. Pathologists often also see mitotic figures, which are tumour cells dividing, and areas of necrosis, which are dead cells.
Sometimes the tumour cells can also be seen growing inside blood vessels.
Pathologists use immunohistochemistry to confirm the diagnosis.
In ALK-positive ALCL:
The tumour cells are positive for CD30 and positive for ALK protein.
Markers that are normally found on healthy T cells, such as CD3, CD5, and CD8, are often negative.
Other T-cell markers such as CD2 and CD4 are often positive.
Markers of other immune cell types, such as CD20, CD15, and PAX5, are negative.
These results, combined with the microscope appearance, confirm the diagnosis of ALK-positive ALCL and distinguish it from ALK-negative ALCL and other lymphomas.
Prognosis refers to the expected outlook for someone with this disease. Compared to ALK-negative ALCL, ALK-positive ALCL generally has a much better prognosis.
Several factors influence prognosis:
ALK status: Being ALK-positive is associated with higher remission rates and longer survival.
Age: Younger patients often respond better to treatment.
Stage at diagnosis: Patients with lymphoma limited to lymph nodes or a single region have a better outlook than those with widespread disease.
With current therapies, many patients achieve long-term remission, and overall survival rates are significantly higher than in ALK-negative ALCL.
What tests confirmed my lymphoma is ALK-positive?
What stage is my lymphoma, and how far has it spread?
How does being ALK-positive affect my prognosis compared to ALK-negative ALCL?
What treatment options are recommended for me?
Are there clinical trials available for this type of lymphoma?
How will my response to treatment be monitored?
What symptoms should I watch for that might suggest recurrence?