Small lymphocytic lymphoma (SLL)

What is small lymphocytic lymphoma?

Small lymphocytic lymphoma (SLL) is a type of cancer that starts from specialized immune cells called B-lymphocytes. The tumour cells in SLL are identical to the tumour cells found in another type of cancer called chronic lymphocytic leukemia (CLL). The only real difference between CLL and SLL is where the tumour cells are found. When the tumour cells are found in lymph nodes and other solid organs but not in the blood the disease is called SLL. When the tumour cells are found in the blood the disease is called CLL. Because of these differences, SLL is classified as a type of lymphoma while CLL is classified as a type of leukemia.

Patients that present with SLL can eventually develop CLL, or vice-versa, and patients can present with both at the same time. For that reason, the disease is often described under the name CLL/SLL.

The immune system

Your immune system is made up of many different kinds of cells including lymphocytes, plasma cells, neutrophils, eosinophils, and macrophages. Each type of cell plays a special and important role in protecting your body from infections and helping it heal after an injury.

Unlike other types of organs, your immune system is spread throughout your body. Most immune cells are found in small bean-shaped structures called lymph nodes, although many are also found in the blood, skin, gastrointestinal tract, and bones.

Symptoms of small lymphocytic lymphoma

The symptoms of small lymphocytic lymphoma (SLL) may be mild, and many patients do not experience any symptoms until later in the disease. For many people, the disease will be discovered during a routine blood test.

Common signs and symptoms of SLL include:

  • Swollen lymph nodes that can be felt in the neck, groin, or under the arm.
  • Enlarged spleen.
  • Fatigue, weight loss, fever, or night sweats.
  • Frequent and prolonged infections.
  • Increased bruising or bleeding.

How do pathologists make this diagnosis?

The diagnosis of SLL can be made after a small sample of tissue is removed in a procedure called a biopsy. The tissue sample will often be from the bone marrow or an enlarged lymph node.

When examined under the microscope, the tumour is usually made up of small cells. When the tumour is found in a lymph node, the tumour cells usually replace the normal lymph node tissue. Some larger tumour cells may be seen in round groups called proliferation centers. A test called immunohistochemistry is often performed on the tissue sample to confirm the diagnosis. See the Immunohistochemistry section below for more information.

Transformation

Over time, SLL can change into a more aggressive type of lymphoma. Pathologists call this a transformation. Your pathologist will carefully examine the sample to look for any evidence of transformation.

SLL can transform in one of three ways:

  1. Prolymphocytoid transformation.
  2. Diffuse large B-cell lymphoma.
  3. Classic Hodgkin lymphoma.

Because these conditions are more aggressive, they require different treatment than CLL/SLL without transformation.

Immunohistochemistry

Your pathologist will perform a test called immunohistochemistry to learn more about the tumour and to exclude other diseases that can look similar to SLL under the microscope. Immunohistochemistry is a test that allows pathologists to see the different types of proteins produced by cells in a tissue sample. When the cells produce a protein, pathologists describe the result as positive or reactive. When the cells do not produce the protein, the result is described as negative or non-reactive.

Because the cancer cells in SLL come from specialized immune cells called B-lymphocytes, they produce proteins normally made by this type of cell. These proteins include CD20, CD19, PAX5, and CD79a. The expression of CD20 is usually weaker than normal, healthy B-lymphocytes. The cancer cells also usually produce CD5, CD23, CD43, and LEF1. CD10 and CyclinD1 are found in other types of B-cell lymphomas and are not produced by the cancer cells in CLL/SLL.

Flow cytometry

Flow cytometry is a special test that is used to examine the immune cells in a blood, bone marrow, or tissue sample. Another name for this test is flow immunophenotyping. Unlike other types of laboratory tests, flow cytometry can examine millions of individual cells very quickly and collect information about each cell. The information collected includes the cell size and shape and the types of proteins being made by each cell.

When examined by flow cytometry, the tumour cells in SLL will show strong expression of the protein CD200. Expression of the protein CD38 in more than 30% of the tumour cells can be associated with more aggressive disease.

Molecular tests

Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce a piece of the machine called a protein.

Pathologists test for changes involving chromosomes by performing fluorescence in situ hybridization (FISH). When FISH is performed on SLL an abnormal number of chromosomes may be found. The test may also show that a piece of a chromosome has been lost.

The most common changes seen in SLL are:

  • Trisomy 12 – The cancer cells have an extra copy of chromosome 12.
  • 13q deletion – Part of chromosome 13 is lost.
  • 11q23 or ATM – Part of chromosome 11 is lost.
  • 17p deletion – Part of chromosome 17 is lost The lost genetic material includes a gene called TP53.

Tumours that have lost part of chromosome 11 or chromosome 17, and those that show complex changes (multiple gains or losses), can behave more aggressively than tumours without these changes.

Some tumours will show a change (a mutation) in a gene called immunoglobulin heavy chain. This gene produces a protein that helps B-cells recognize foreign proteins in the body (such as those on viruses). Tumours with this mutation are less aggressive and may have a more favorable prognosis compared to tumours without the mutation.

By Rosemarie Tremblay-LeMay MD FRCPC (updated August 4, 2021)
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