What is Anaplastic Large Cell Lymphoma?
Anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma (ALCL) is a specific type of lymphoma, which is a cancer of the lymph nodes. This type of lymphoma is characterized by unusually large lymphoid cells – these are a type of white blood cell that form part of our body’s immune system. These cells have a lot of cytoplasm (the jelly-like substance that fills cells), and their nuclei (the cell’s control center) are shaped like horseshoes. They also strongly react to a particular stain for CD30, a marker used in lab tests to help identify certain types of cancer cells.
ALK+ ALCL is known to have a recurrent rearrangement of two genes – the ALK gene and nucleophosmin (NPM1) gene. In the past, this type of lymphoma was often referred to as Ki-1 lymphoma due to its positive reaction to Ki-1 antigen, now known as CD30. This type of lymphoma also shares some features with the classic Hodgkin’s lymphoma, a different type of lymphoma.
According to the revised 2016 classification from the World Health Organization (WHO), there are four key subtypes under the umbrella of ALCL. These are: systemic ALK-positive ALCL (ALK+ ALCL, the one we’ve just discussed), systemic ALK-negative ALCL (ALK- ALCL, a form of the disease that lacks the ALK gene rearrangement), primary cutaneous ALCL (pC ALCL, which primarily affects the skin), and breast implant-associated ALCL (BI-ALCL, a rare type associated with breast implants).
What Causes Anaplastic Large Cell Lymphoma?
ALCL, in its ALK-positive form, typically originates from a type of white blood cell called a T cell. This disease can occur as a primary condition or as a secondary condition connected to another disease. It has also been linked with HIV, a skin condition called mycosis fungoides, lung conditions, and inflammatory pseudotumors, which are benign growths that resemble tumors. However, it’s important to note that ALK-positive ALCL has not been shown to be connected with the Epstein-Barr Virus, also known as EBV.
Risk Factors and Frequency for Anaplastic Large Cell Lymphoma
ALK+ ALCL, a type of cancer, is usually seen in children and teenagers more than adults. It’s mainly found in people under the age of 30 and is slightly more common in males. When diagnosed, it’s often in the advanced stages (stage III or IV) and symptoms include persistent fevers, weight loss, and heavy night sweats.
- ALK+ ALCL is more often diagnosed in children and teenagers than adults.
- It’s especially common in people in their first three decades of life.
- It’s slightly more common in males (with a male-to-female ratio of 1.5:1).
- Most people are at stage III or IV when diagnosed.
- Common symptoms include persistent fevers, weight loss, and heavy night sweats.
Signs and Symptoms of Anaplastic Large Cell Lymphoma
Patients with ALK-positive ALCL, a type of lymphoma, often come forward with a variety of symptoms. Most patients are in advanced stages (Stage III or IV) of this disease when they first report symptoms. These can include:
- Swelling in the lymph nodes in the arms, legs, or abdomen
- Abnormal cells infiltrating tissues outside of the lymph nodes
- The disease affecting the bone marrow
- ‘B symptoms’ including fever and weight loss
In instances where the disease has affected the bone marrow, patients may additionally present with:
- Anemia or a deficit of all types of blood cells (pancytopenia)
- Increased number of a type of white blood cell called eosinophils (eosinophilia)
- High levels of an enzyme found in many body tissues, LDH
Finally, a specific type of ALK-positive ALCL can have symptoms similar to leukemia, showing abnormal cells in the peripheral blood.
Testing for Anaplastic Large Cell Lymphoma
Immunohistochemistry (IHC) is a lab test that uses antibodies to check for certain antigens (proteins) in a sample of tissue. It is required to confirm a diagnosis of ALCL (ALK-positive), a type of lymphoma. There are some substances that, when detected in the sample, supports ALCL diagnosis, and some that, if they’re absent, also supports the diagnosis. Positive stains (proteins that should be found) include CD30, EMA, CD2, CD4, among others. Negative stains (proteins that should not be found) include CD15, CD20, CD79a, and others.
Sometimes, ALCL (ALK-positive) may show a loss of several proteins usually identified with T-cells, this is referred to as a null-cell phenotype. However, despite this absence, genetic testing can still detect evidence that these cells are derived from T-cells. Whether a patient presents T-cell or a null-cell phenotype does not affect their prognosis or treatment course.
ALK IHC along with other tests such as Fluorescence in situ hybridization (FISH), and Reverse-Transcription Polymerase Chain Reaction (RT-PCR) have been shown to have comparable use to confirm ALCL (ALK-positive) diagnosis. FISH and karyotype testing (examining the number, size, and shape of chromosomes in a sample of cells) are not necessarily needed if ALK staining is positive. RT-PCR is commonly used to search for evidence of minimal leftover disease in a person’s blood or bone marrow after treatment.
Additionally, genetic testing is important in supporting ALCL (ALK-positive) diagnosis. Assessment of the T cell receptor (TCR) gene rearrangement (a specific type of genetic change) that is present in most cases can be done with the help of testing methods like PCR or flow cytometry (a technology that is used to analyse the physical and chemical characteristics of particles in a fluid).
It should be noted that there are different types of genetic changes, all which result in increased activity of the ALK protein. The most common of these genetic changes is designated as t(2;5)(p23;q35), and there are also several others.
Further genetic research has uncovered differences between ALCL with positive and negative ALK, with the former showing unique higher count of BCL6, PTPN12, SERPINA1, and CEBPB proteins.
What else can Anaplastic Large Cell Lymphoma be?
Here are some conditions that can be linked with the presence of atypical CD30+ cells. These could be:
- ALK-negative ALCL
- ALK-positive diffuse large B cell lymphoma with immunoblastic/plasmablastic features
- Pleomorphic carcinoma
- Hodgkin lymphoma
- Lymphomatoid granulomatosis
- Histiocytic sarcoma
- Nonneoplastic disorders with atypical CD30+ cells
- Rhabdomyosarcoma
- Inflammatory myofibroblastic tumor
What to expect with Anaplastic Large Cell Lymphoma
ALCL, short for ALK-positive Anaplastic Large Cell Lymphoma, is a type of lymphoma, which is a cancer that starts in cells that are part of the body’s immune system. This specific type is somewhat aggressive, but not as much when compared to some other types of lymphoma. The good news is that the overall outlook for individuals with this form of lymphoma is better than many other types.
To put it into numbers, the chances of someone being alive 5 years after their diagnosis of ALK-positive ALCL is about 80%. This is considerably better than the outlook for those with ALK-negative ALCL, where the 5-year survival rate is closer to 48%.
There is a tool used by medical professionals called the International Prognostic Index (IPI) which can help predict how an individual’s disease might progress. Each patient is given a score, based on their age, how high levels of a certain enzyme, Asian dehydrogenase, are in their blood, their general health, the stage of their disease, and how much it has spread to areas outside of the lymph nodes.
Some factors may impact this prognosis negatively. For instance, if there’s a rearrangement of the MYC gene, or if particular forms of the disease are present (like the small-cell or lymphohistiocytic variant) the outlook may be worse than expected.
Relapses of this type of lymphoma are usually still responsive to chemotherapy treatments. In some cases where the disease is resistant to other treatments, a bone marrow transplant may be considered.
Possible Complications When Diagnosed with Anaplastic Large Cell Lymphoma
Complications of ALK-positive ALCL (Anaplastic Large Cell Lymphoma) often involve the suppression of bone marrow, organ dysfunction or adverse reactions linked to high dose chemotherapy.
Here are some key complications:
- Suppression of bone marrow
- Organ dysfunction
- Adverse reactions to high dose chemotherapy
Preventing Anaplastic Large Cell Lymphoma
Patients who have been recently diagnosed with ALCL (Anaplastic Large Cell Lymphoma) that is ALK-positive, meaning a specific genetic change is present, are treated with a type of chemotherapy that includes a drug group called anthracyclines. The aim of this treatment is to achieve a complete remission, which means having no signs of the disease present.
