Anaplastic Large Cell Lymphoma

Overview

What is anaplastic large cell lymphoma (ALCL)?

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma. Like all non-Hodgkin lymphoma, ALCL is a type of cancer. With non-Hodgkin lymphoma, white blood cells called lymphocytes grow out of control. Lymphocytes are part of your immune system. They help protect your body from germs and diseases.

Lymphocytes include two main types of cells: B cells (B lymphocytes) and T cells (T lymphocytes). In ALCL, your T lymphocytes grow abnormally. The condition's name — anaplastic large cell lymphoma — describes how the abnormal T lymphocytes look when viewed under a microscope.

  • Anaplastic: “Anaplastic” is a word used to describe odd-looking cancer cells. The cancer cells in ALCL look abnormal when compared to healthy T lymphocytes.
  • Large cell: The abnormal T lymphocytes appear larger than normal T lymphocytes when viewed under a microscope.
  • Lymphoma: Lymphoma is cancer that involves the out-of-control growth of white blood cells called lymphocytes. ALCL forms from T lymphocytes.

What are the different types of anaplastic large cell lymphoma?

The various types of ALCL are classified based on the cancer’s location in your body and the cancer cells’ characteristics. “Systemic” ALCL may affect your lymph nodes and organs, including your skin. Other types of ALCL primarily affect only a particular body part, like your skin or breasts.

Systemic ALCL

Systemic forms of ALCL are classified based on whether there’s a mutation (change) in the anaplastic lymphoma kinase (ALK) gene. Genes are the instructions that tell a cell (like a T lymphocyte) how to perform essential functions. Systemic ALCL that has a mutation on the ALK gene is called "ALK-positive" ALCL. Systemic ALCL that doesn’t have the mutation is called “ALK-negative.”

  • Primary systemic ALCL, ALK-positive, is a fast-growing (aggressive) cancer, most common in children and young adults. This type of cancer usually responds well to chemotherapy treatments.
  • Primary systemic ALCL, ALK-negative, is an aggressive cancer that primarily affects older adults. The cancer usually goes away for a short period following chemotherapy and then returns. ALK-negative ALCL is harder to treat and has a worse prognosis than ALK-positive ALCL.
Other types of ALCL

Other types of ALCL grow more slowly than the systemic types.

  • Primary cutaneous ALCL causes skin changes, like bumps or a rash. In most cases (90% of the time), it doesn’t spread beyond your skin.
  • Breast implant-associated ALCL (BIA-ALCL) forms around breast implants. BIA-ALCL is usually diagnosed about 10 years following a breast augmentation or breast reconstruction procedure.

Who is affected by anaplastic large cell lymphoma?

ALCL can affect people of all ages, but certain groups are more likely to develop certain types.

  • ALK-positive ALCL mostly affects pre-teens, adolescents and adults in their 20s and 30s. It’s significantly more common in men and people assigned male at birth (AMAB).
  • ALK-negative ALCL mainly affects people over 60. It’s slightly more common in men and people AMAB.
  • Primary cutaneous ALCL primarily affects adults over 40. It’s slightly more common in men and people AMAB and people who are white.
  • BIA-ALCL is usually diagnosed among people in their 50s. It affects people with both silicone and saline implants. It’s associated with textured (as opposed to smooth) breast implants.

How common is anaplastic large cell lymphoma?

Anaplastic large cell lymphoma is rare. Approximately 2% of adult non-Hodgkin lymphoma diagnoses are ALCL.

Symptoms and Causes

What are the symptoms of anaplastic large cell lymphoma?

Symptoms vary depending on the type of ALCL.

Systemic ALCL

Both ALK-positive and ALK-negative ALCL often cause swollen lymph nodes at the site where the cancer’s growing. The most common areas are your neck, underarm and groin. Other symptoms include:

  • Fever.
  • Fatigue.
  • Night sweats.
  • Unexplained weight loss.

Most people are diagnosed when the cancer is more advanced. In advanced stages, the cancer may have spread to organs, like your lungs, liver and bone. You may experience symptoms based on which body parts are affected. For example, pressure in your chest and a frequent cough may signify the presence of the ALCL in your chest.

Primary cutaneous ALCL

Primary cutaneous ALCL often appears as a single abnormal growth or multiple growths on a single area of your skin. The most common sites are your face, abdomen, buttocks, arms and legs. Rarely (about 20% of the time), growths appear in multiple places. Symptoms include:

  • Abnormal reddish or reddish-brown growths that get bigger over time.
  • Large (often bigger than a quarter), raised bumps that may be itchy.
  • Growths that form ulcers and scab over.

BIA-associated ALCL

BIA-associated ALCL often causes noticeable breast changes. Symptoms include:

  • Breast pain.
  • Breast swelling.
  • Skin rash.
  • Swelling or a collection of fluid near your implant.
  • Solid mass (lump) near your implant.

Usually, just one breast changes, but you may notice changes in both breasts.

What causes anaplastic large cell lymphoma (ALCL)?

Anaplastic large cell lymphoma forms when lymphocytes multiply out of control and begin to overtake surrounding healthy tissue. Researchers haven’t yet found what causes lymphocytes to become malignant (cancerous). Still, they’ve identified several genetic mutations that frequently occur with ALCL. These mutations may cause healthy cells to transform into cancer cells.

For example, mutations in the ALK gene are the defining feature of ALK-positive ALCL. Other types of gene mutations are common with other forms of ALCL.

Diagnosis and Tests

How is anaplastic large cell lymphoma diagnosed?

Your healthcare provider will perform a physical exam to check for signs of ALCL, such as swelling in your lymph nodes. If they suspect ALCL, they’ll perform various tests and procedures.

  • Imaging: Imaging procedures allow your provider to identify the cancer’s location. The type of imaging you’ll need depends on the type of ALCL. A healthcare provider may perform a chest X-ray, CT scan or MRI to identify tumors. A PET/CT or PET scan can show if the cancer has spread throughout your body. A provider may perform a breast ultrasound if they suspect BIA-ALCL.
  • Bloodwork: A healthcare provider may perform various blood tests, like a complete blood count (CBC), to check for signs of ALCL. An abnormal amount of blood cells (red blood cells, white blood cells or platelets) may indicate ALCL. They may also check your blood for enzymes and other markers that may be signs of ALCL.
  • Biopsy: A biopsy is the only way to confirm an ALCL diagnosis. During a biopsy, your healthcare provider removes a tissue sample and examines the cells under a microscope. Studying the cells allows your provider to determine the type of ALCL and helps them plan the most effective treatments.

Management and Treatment

How is anaplastic large cell lymphoma treated?

Chemotherapy is the standard treatment for systemic ALCL. Surgery is the preferred treatment for primary cutaneous ALCL and BIA-ALCL.

Systemic ALCL

ALK-positive and ALK-negative anaplastic large cell lymphoma usually respond well to systemic chemotherapy. With systemic chemotherapy, drugs that destroy cancer cells are given in a vein and are distributed through your bloodstream to your body, killing cancer cells.

Chemotherapy treatments for systemic ALCL often include a combination of drugs that work together to destroy cancer cells. Drug combinations include:

  • BV-CHP: Drugs include brentuximab vedotin, cyclophosphamide, doxorubicin (hydroxydaunorubicin) and prednisone.
  • CHOP: Drugs include cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin®) and prednisone.
  • CHEOP: Drugs include cyclophosphamide, doxorubicin (hydroxydaunorubicin), etoposide, vincristine (Oncovin®) and prednisone.

These treatments usually eliminate all signs of cancer (remission) in the short term. Still, the cancer may return. If your physician believes it’s likely that your cancer will return, they may recommend a stem cell transplant while you’re in remission. During a stem cell transplant, your healthcare provider replaces the cells destroyed during chemotherapy with healthy cells. These cells develop into healthy (noncancerous) blood cells.

If the cancer returns, your provider may recommend various additional chemotherapy treatments designed to treat lymphoma.

Primary cutaneous ALCL

Surgery is the most common treatment for primary cutaneous ALCL. You may need radiation therapy if the cancer has spread to your lymph nodes. Radiation directs energy toward the cancer cells, destroying them.

Primary cutaneous ALCL often returns within five years of treatment. You may need additional surgery and radiation therapy if it comes back.

You may need other forms of treatment if the localized tumors can’t be removed with surgery or if your cancer keeps returning. Treatments may include:

  • Oral methotrexate: A drug designed to treat non-Hodgkin lymphoma.
  • Bexarotene: A drug designed to treat T-cell lymphomas affecting your skin.
  • Brentuximab vedotin: A drug designed to treat systemic ALCL and other forms of ALCL that return.
  • Interferon: A drug that helps your immune system recognize and fight cancer cells, including lymphoma.

BIA-ALCL

Surgery to remove your implant and the surrounding cancer cells usually cures BIA-ALCL. If surgery isn’t an option, you may receive radiation therapy to destroy the cancer cells.

If the cancer returns or spreads beyond your breast, your healthcare provider may recommend chemotherapy treatments used to treat ALK-negative ALCL. Treatments may include CHOP chemotherapy and brentuximab vedotin.

Outlook / Prognosis

How serious is anaplastic large cell lymphoma?

Anaplastic large cell lymphoma is a serious cancer that requires careful monitoring and appropriate treatment, no matter the type. Still, your prognosis and care plan depend on what form of ALCL you have and other factors. These factors include your response to treatment and your score on the international prognostic index (IPI).

Cancer specialists (oncologists) created the IPI to help predict likely outcomes associated with aggressive forms of non-Hodgkin lymphoma, including systemic ALCL. The index assigns a score based on factors like:

  • Your age.
  • Your ability to perform everyday activities.
  • How widespread your cancer is (also called the “cancer stage”).
  • The number of affected lymph node sites.

Ask your healthcare provider how your IPI score will affect your prognosis if you have systemic ALCL.

What is the survival rate of anaplastic large cell lymphoma?

The survival rates associated with systemic forms of ALCL vary greatly. ALK-positive ALCL is associated with a longer survival timeline than ALK-negative ALCL. Depending on factors like your cancer type and your IPI score, the five-year survival rate of ALK-positive ALCL ranges from 33% to 90%. Similarly, the five-year survival rate of ALK-negative ALCL ranges from 13% to 74%.

The survival rates for primary cutaneous ALCL and BIA-ALCL are excellent. Although primary cutaneous ALCL usually returns within five years of remission, follow-up treatments can extend your life. The survival rate five years following diagnosis is 80%. With BIA-ALCL, completely removing the cancer surgically often eliminates the cancer for good.

Living With

What questions should I ask my doctor?

Questions to ask your healthcare provider include:

  • What type of ALCL do I have?
  • Is my cancer only in one site, or has it spread?
  • Which specialists will be on my care team?
  • What treatments would you recommend?
  • How can I manage treatment side effects?
  • What is my IPI score?
  • What are the odds that my cancer will go into remission?
  • How likely is it that my cancer will return?
  • How often will I need follow-up visits to monitor my condition?

A note from Cleveland Clinic

Learning of a cancer diagnosis may feel scary. Still, it’s important to remember that ALCL isn’t just one type of cancer with a single prognosis. The kind of ALCL you have will determine whether it spreads quickly or slowly. It will shape your treatment options and your outlook. In some people, ALCL spreads fast. In others, it develops more slowly, allowing plenty of time for you to receive treatments that can send your cancer into remission. Talk to your healthcare provider about likely outcomes based on your unique diagnosis.

Last reviewed by a Cleveland Clinic medical professional on 08/10/2022.

References

  • Geller S, Canavan TN, Pulitzer M, Moskowitz AJ, Myskowski PL. ALK-positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature. (https://pubmed.ncbi.nlm.nih.gov/29057463/) Int J Dermatol. 2018;57(5):515-520. Accessed 8/10/2022.
  • Ishizawa K, Yanai T. Hematopoietic stem cell transplantation and brentuximab vedotin for patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma. (https://pubmed.ncbi.nlm.nih.gov/31392578/) Adv Ther. 2019;36(10):2679-2696. Accessed 8/10/2022.
  • Marra A, Viale G, Pileri SA, et al. Breast implant-associated anaplastic large cell lymphoma: A comprehensive review. (https://pubmed.ncbi.nlm.nih.gov/31958739/) Cancer Treat Rev. 2020;84:101963. Accessed 8/10/2022.
  • Sarfraz H, Gentille C, Ensor J, et al. Primary cutaneous anaplastic large-cell lymphoma: a review of the SEER database from 2005 to 2016. (https://pubmed.ncbi.nlm.nih.gov/34081802/) Clin Exp Dermatol. 2021;46(8):1420-1426. Accessed 8/10/2022.
  • Shustov A, Soma L. Anaplastic large cell lymphoma: contemporary concepts and optimal management. (https://pubmed.ncbi.nlm.nih.gov/30596216/) Cancer Treat Res. 2019;176:127-144. Accessed 8/10/2022.

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