Your pathology report for ALK-negative anaplastic large cell lymphoma

Jason Wasserman MD PhD FRCPC and Aleksandra Paliga MD FRCPC
September 9, 2025

ALK-negative anaplastic large cell lymphoma (ALCL) is a type of cancer that starts in T cells, which are specialized white blood cells that help the body fight infections. Because it begins in immune system cells, it is classified as a non-Hodgkin lymphoma (NHL). This disease can start in many different parts of the body. Common locations include lymph nodes, bone, liver, digestive tract, and breast.

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

This cancer is called ALK-negative because the tumour cells do not contain a genetic change involving the ALK gene.

There is a closely related condition called ALK-positive anaplastic large cell lymphoma, which appears similar under the microscope but contains a mutation in the ALK gene. Pathologists distinguish between these two diseases because the presence or absence of ALK has significant implications for how the cancer behaves and how it is treated.

What causes ALK-negative anaplastic large cell lymphoma?

Doctors do not yet know why some people develop this type of lymphoma. Most tumours show genetic changes that affect genes normally involved in T-cell growth and function, such as JAK1 and STAT3. About 30% of cases also show changes involving a gene called DUSP22. These changes happen inside the cancer cells and are not inherited from parents or passed down to children.

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

The symptoms depend on where the tumour is located in the body.

General symptoms include:

  • Unexplained fever.

  • Night sweats.

  • Unintentional weight loss.

  • Enlarged lymph nodes.

Other symptoms may develop if the tumour grows in a particular organ, such as abdominal pain in the digestive tract or a mass in the breast.

How is the diagnosis made?

The diagnosis can only be made after a biopsy, a procedure in which a small sample of tissue is removed and examined under a microscope by a pathologist.

In addition to looking at the tissue with routine stains, pathologists often order special tests, including:

  • Immunohistochemistry, which looks for specific proteins in the tumour cells.

  • Flow cytometry, which analyses the types of cells present and their features.

  • Molecular tests, which look for changes in genes that are commonly altered in this disease.

These tests are necessary because several different types of lymphomas can appear similar under the microscope, and they help confirm the diagnosis.

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

When examined under a microscope, this lymphoma is composed of large, abnormal T cells. The tumour cells can be scattered as single cells, grouped in clusters, or arranged in large sheets. Sometimes the cancer cells are seen growing inside blood vessels.

A distinctive type of tumour cell called a hallmark cell is often present. Hallmark cells have an unusual horseshoe-shaped nucleus that is pushed off to the side of the cell. Pathologists also frequently see mitotic figures, which are tumour cells dividing, and areas of necrosis, which are dead cells.

What special tests are performed?

Pathologists use immunohistochemistry to help confirm the diagnosis.

In ALK-negative anaplastic large cell lymphoma:

  • The tumour cells are positive for CD30, a marker often used to identify this lymphoma.

  • Markers usually seen in normal T cells, such as CD2, CD3, CD5, and CD8, are often negative.

  • Other T-cell markers, such as CD4, are often positive.

  • Markers of other immune cells, such as CD20, CD15, and PAX5, are negative.

  • Unlike ALK-positive ALCL, the tumour cells are negative for ALK protein.

These results, together with the microscopic features, confirm the diagnosis.

What is the prognosis for ALK-negative anaplastic large cell lymphoma?

Prognosis refers to the expected outcome or outlook for someone with this disease. For ALK-negative anaplastic large cell lymphoma, the prognosis is generally less favorable compared to ALK-positive anaplastic large cell lymphoma.

Several factors influence prognosis:

  • ALK status: Being ALK-negative is associated with a higher risk of aggressive disease and relapse compared to ALK-positive cases.

  • Stage at diagnosis: Patients with disease limited to lymph nodes or a single region tend to do better than those with widespread involvement of organs such as the liver, bone, or digestive tract.

  • Genetic changes: Some patients have tumours with changes in the DUSP22 gene. These cases appear to have a better outcome compared to other ALK-negative cases. In contrast, tumours with changes in TP63 have a poorer prognosis.

  • Age and overall health: Younger, healthier patients often tolerate treatment better and may have better outcomes.

With current treatments, many patients achieve remission, but relapse is common, and long-term survival rates are lower than for ALK-positive disease. Because of this, doctors often consider aggressive treatment strategies and may discuss participation in clinical trials.

Questions to ask your doctor

  • What tests were done to confirm the diagnosis of ALK-negative anaplastic large cell lymphoma?

  • Has the lymphoma spread to other parts of my body?

  • What treatment options are recommended for me?

  • Are there clinical trials available for this type of lymphoma?

  • What symptoms should I look out for that might indicate progression or recurrence?

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