Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma (NHL). Non-Hodgkin lymphomas and Hodgkin lymphomas (or Hodgkin disease) are blood cancers that affect lymphocytes, a type of white blood cell. Lymphomas are related to other cancers: leukemia, myeloma, and myeloproliferative neoplasms (MPNs). Lymphomas originate in the lymphatic system — part of the immune system that is made up of multiple organs including the lymph nodes, bone marrow, spleen, thymus, and tonsils. The purpose of the lymphatic system is to remove waste and bacteria from the body and drain excess fluid from tissue.

What Is Anaplastic Large Cell Lymphoma?

ALCL is a rare subtype of T-cell NHL. It accounts for only 1 percent to 2 percent of all types of lymphoma. ALCL is also classified as a peripheral T-cell lymphoma and is related to null-cell ALCL (ALCL involving lymphocytes that are neither T cells nor B cells). ALCL usually affects children and young adults but can also occur in older adults. ALCL can be an aggressive form of cancer, but it is very treatable.

There are many types of non-Hodgkin lymphoma, but they can be categorized as B-cell, T-cell, or natural killer (NK)-cell lymphomas based on the type of lymphocytes that become cancer cells. ALCL is a type of T-cell lymphoma, meaning that it comes from T lymphocytes, a type of white blood cell that is an important part of the body’s immune system.

There are three types of ALCL with distinctive defining features: primary cutaneous anaplastic large cell lymphoma, systemic anaplastic large cell lymphoma, and breast implant-associated anaplastic large cell lymphoma. Other than in breast implant-associated ALCL (BIA-ALCL), there are no known risk factors for ALCL.

Types of Anaplastic Large Cell Lymphoma

The three types of ALCL have different defining features and respond to different treatments.

Primary Cutaneous ALCL

Primary cutaneous ALCL (PCALCL) is considered to be low-grade ALCL because it grows slowly. PCALCL primarily affects the skin but can sometimes spread to other parts of the body. Then it is treated the same way as systemic ALCL.

Systemic ALCL

Systemic ALCL is considered high grade, or aggressive. It typically affects lymph nodes and other organs in the body (including the skin). Systemic ALCL is further classified based on whether or not cancer cells have elevated levels of the anaplastic lymphoma kinase (ALK) protein: The condition can be either ALK-positive or ALK-negative

ALK-positive ALCL usually occurs in children and young people and responds well to standard chemotherapy. ALK-positive ALCL is associated with nucleophosmin ALK, a type of tyrosine kinase (an enzyme found in ALK-positive ALCL cells).

ALK-negative ALCL usually occurs in adults over 55. People with this disease are prone to relapse after successful treatment.

Breast Implant-Associated ALCL

BIA-ALCL is a very rare type of ALCL that occurs in women who have breast implants.

Signs and Symptoms of Anaplastic Large Cell Lymphoma

ALCL signs and symptoms vary based on the type of ALCL and the location of tumors, but ALCL shares many common signs and symptoms with other types of NHL.

Signs and Symptoms of Primary Cutaneous ALCL

The primary and usually the only sign of cutaneous ALCL is a skin lesion (tumor):

• Usually a single lesion, but sometimes multiple lesions
• Usually on the head, neck, arms, or legs
• Raised, discolored nodule or lump usually 1 inch wide (or larger)
• May be itchy but usually painless
• May ulcerate (the skin may break down on the surface of the lesion) and cause bleeding
• Usually does not go away without treatment

Signs and Symptoms of Systemic ALCL

Signs and symptoms of systemic ALCL include swollen lymph nodes and B symptoms (unexplained fever, unexplained weight loss, and drenching night sweats).

Other symptoms of systemic ALCL are caused by spread to different parts of the body:

• Chest and neck — Chest pain, chest pressure, chronic cough, difficulty breathing
• Abdomen — Swollen or painful belly, bloating, loss of appetite, nausea, vomiting, diarrhea
• Bone marrow — Fatigue (persistent tiredness) due to anemia (low red blood cells or hemoglobin), increased bleeding or slow clotting due to thrombocytopenia (low platelets in the blood)
• Skin lesions (like primary cutaneous ALCL)

Signs and Symptoms of Breast Implant-Associated ALCL

Signs and symptoms of BIA-ALCL include one or more lumps or fluid around the breast implant and pain around the breast implant.

This type of ALCL rarely spreads to other parts of the body.

Diagnosis of Anaplastic Large Cell Lymphoma

Diagnosis of ALCL involves a thorough medical history and physical exam, followed by a biopsy, imaging, blood tests, and specialized tests on cancer cells.

Biopsy

A surgical or incisional biopsy to remove all or part of a tumor is the best way to identify what kind of cancer cells are present. However, biopsies using a needle (core needle biopsy and fine-needle aspiration) are used if tumors are in difficult-to-reach places, such as the back of the abdominal wall. Bone marrow biopsy and bone marrow aspiration are used to identify cancer cells when the doctor suspects bone marrow involvement.

Imaging

Imaging tests for ALCL and other types of lymphoma are important to identify the location of tumors and see how far the disease has spread in the body. Common imaging tests used for ALCL and other lymphomas include:

• Computed tomography (CT), in which X-rays are used to build 3D images and cross-sections of the body
• Positron emission tomography (PET) or PET-CT, in which radioactive tracers are injected and imaged to find cancer cells based on their higher-than-normal metabolism
• Magnetic resonance imaging (MRI), which uses a strong magnetic field to image the soft tissues of the body (unlike X-rays, which can identify bone)

Blood Tests

A complete blood count is one of the most important tests for lymphoma and other blood cancers because it can identify abnormal blood cells and reveal what effect the cancer is having on normal blood cell production. Other diagnostic blood tests include standard tests for kidney and liver function as well as tests for HIV and viral hepatitis.

Immunohistochemistry

Immunohistochemistry is a type of laboratory test performed on tumor tissue and bone marrow biopsies. It is used to identify specific proteins inside and on the surface of cancer cells. This procedure is called immunophenotyping. In ALCL, proper diagnosis and treatment involves identifying cells that have the ALK protein. Cell surface antigens (proteins that can bind to antibodies) — including CD20, CD30, CD45, and others — can also help identify exactly what kind of cancer cells are present and what treatments will be most effective. ALCL cells are CD30 positive, meaning they express the CD30 cell surface protein.

Surface antigens on cancer cells are important for targeted immunotherapy. This treatment uses drugs that are antibodies to those specific antigens. They can provoke a healthy immune response or deliver chemotherapy drugs directly to the cancer cells.

Treatment of Anaplastic Large Cell Lymphoma

The different types of ALCL respond best to different treatments depending on their location, spread, and the types of cancer cells in the tumors.

Primary Cutaneous ALCL Treatment

Surgery to remove tumors in the skin or radiation therapy are often used to treat single skin lesions that have not spread. If the cancer cells have spread throughout the body, then treatments for systemic ALCL are used, including chemotherapy and targeted therapy with Adcetris (brentuximab vedotin).

Systemic ALCL Treatment

Systemic ALCL is usually treated with chemotherapy, sometimes combined with targeted immunotherapy. Radiation may be used after chemotherapy for limited early-stage systemic ALCL. Frontline chemotherapy regimens have success treating both types of systemic ALCL, but ALK-positive ALCL seems to respond better than ALK-negative ALCL.

Initial chemotherapy regimens for ALCL include:

• B-CHP — Brentuximab vedotin plus cyclophosphamide (sold as Cytoxan), doxorubicin (also known as hydroxydaunorubicin and sold as Adriamycin, and prednisone (a corticosteroid)
• CHOEP — Cyclophosphamide, doxorubicin, vincristine sulfate (formally sold as Oncovin), etoposide (also known as VP-16), and prednisone
• CHOP — Cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone

Targeted immunotherapy for ALCL may include Adcetris, which uses a monoclonal antibody to the CD30 cell surface protein conjugated (joined) to vedotin, a very strong chemotherapy drug. The drug combination makes it possible to target ALCL cancer cells and deliver the chemotherapy drug directly to those cells, minimizing the effect of the chemotherapy on healthy tissue.

People with ALCL that is refractory (does not respond well to chemotherapy) or has relapsed (come back after treatment) may be treated with targeted therapy using:

• Adcetris
• Istodax (romidepsin)
• Beleodaq (belinostat)
• Folotyn (pralatrexate)

Treatments under investigation for ALCL include a wide variety of targeted immunotherapy, small-molecule drugs, and chimeric antigen receptor T-cell therapy.

ALK-Negative Systemic ALCL Treatment

People with ALK-negative ALCL are usually treated with the same chemotherapy regimens as those with ALK-positive ALCL. Sometimes, more rigorous treatment with high-dose chemotherapy is used to minimize the risk of relapse. People treated with chemotherapy for ALK-negative ALCL, especially those treated with high-dose chemotherapy (which kills bone marrow cells), may benefit from a stem cell transplant. Unless ALCL has spread to the bone marrow before treatment, an autologous stem cell transplant may be recommended. An autologous transplant uses your stem cells taken from your bone marrow before chemotherapy. Otherwise, a donor stem cell transplant can be performed, called an allogeneic stem cell transplant.

Breast Implant-Associated ALCL Treatment

Surgery is the primary treatment for BIA-ALCL. Breast implants are removed along with the surrounding scar tissue “capsule” that forms around implants and the lymphoma itself. If the cancer is limited to the scar tissue capsule, then surgery and close follow-up are sufficient. If the cancer has spread beyond the scar tissue capsule, however, then further treatment may include radiation, chemotherapy, or targeted therapy.

Clinical Trials and Experimental Therapies

New treatments for ALCL are under investigation. Enrolling in clinical trials can be the best option for treating cancers that are very rare or do not respond well to standard treatment. Therapies being tested for ALCL include new and existing targeted therapy drugs (including monoclonal antibody drugs and small-molecule drugs) as well as new combinations of chemotherapy and targeted therapy.

How Does Anaplastic Large Cell Lymphoma Differ From Other Lymphomas?

ALCL lymphomas have a few distinguishing characteristics. ALCL is a T-cell lymphoma, which is much less common than B-cell lymphomas. ALCL cells also have the CD30 cell surface antigen (a protein on the surface of the cancer cells), which can be used to identify and treat ALCL. ALCL is rare, usually aggressive, and very treatable.

Breast implant-associated ALCL is a very rare lymphoma, more so than cutaneous and systemic ALCL. The cause of BIA-ALCL is not understood, but it may occur due in part to the body’s immune response to foreign material in the body (breast implants), an immune response to a bacterial infection, or chronic inflammation. Implants with a textured surface seem to be more likely to cause BIA-ALCL, but no other factors seem to be involved. Both saline-filled and older silicone-filled implants seem to cause BIA-ALCL at the same rate.

Prognosis for ALCL

The outcome of ALCL, like other lymphomas, depends on the stage of the disease at diagnosis. The larger the size and further the spread of tumors, the worse the prognosis is. Cutaneous ALCL occurring only in the skin has a very good outlook. It usually responds well to treatment and has a low risk of relapse. Five-year survival rates (the number of people who live past five years after diagnosis) for limited cutaneous ALCL are 90 percent. This number decreases to as low as 50 percent when the disease is more widespread throughout the skin. People with breast implant-associated ALCL also have a very good outlook with treatment, with five-year survival rates over 90 percent.

The most important prognostic factor for systemic ALCL is whether it is ALK-positive or ALK-negative ALCL. ALK-positive ALCL has a better prognosis and high survival rate, whereas ALK-negative ALCL has a much lower survival rate and increased risk of recurrence after treatment.

Talk With Others Who Understand

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