Anaplastic Large Cell Lymphoma T- and Null-Cell Types
ALCL, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Anaplastic large cell lymphoma T-/null-cell type, Large cell (Ki1+) lymphoma
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Anaplastic large cell lymphoma T- and null-cell types is a rare form of cancer affecting white blood cells that help protect the body from disease. While this cancer can be aggressive and spread quickly, especially in its systemic forms, modern treatments offer hope for many patients, particularly those with certain genetic features.
Table of contents
- What is anaplastic large cell lymphoma?
- Different types of ALCL
- Who is affected by this disease
- How the cancer cells look
- Causes and risk factors
- Signs and symptoms
- How the disease is diagnosed
- Treatment options
What is anaplastic large cell lymphoma?
Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma, which means it is a cancer that affects the lymphatic system[1]. Non-Hodgkin lymphoma occurs when white blood cells called lymphocytes grow out of control. Lymphocytes are part of your immune system and help protect your body from germs and diseases[2].
There are two main types of lymphocytes: B cells and T cells. In ALCL, the cancer develops from T lymphocytes (T cells), or in some cases from cells that are neither T cells nor B cells, called null cells[3]. This is why the disease is specifically called “anaplastic large cell lymphoma, T- and null-cell types.”
The name of this disease describes what the cancer cells look like under a microscope. “Anaplastic” means the cancer cells look very abnormal compared to healthy cells. “Large cell” means these abnormal cells appear larger than normal lymphocytes[2].
ALCL is a rare disease. It accounts for only about 1% to 2% of all types of lymphoma[3]. Despite being uncommon, the biology of ALCL is better understood than many other more common types of lymphoma[3].
Different types of ALCL
ALCL can be divided into different types based on where the cancer appears in the body and whether the cancer cells have certain genetic changes. The main types include systemic ALCL, primary cutaneous ALCL, and breast implant-associated ALCL[1].
Systemic ALCL
Systemic ALCL may affect lymph nodes and organs throughout the body, including the skin. This type is further classified based on the presence of a specific protein called anaplastic lymphoma kinase (ALK)[1].
ALK-positive ALCL means the cancer cells produce the ALK protein. This form is associated with a genetic change called a translocation, specifically t(2;5), which involves the ALK gene and a gene called nucleophosmin (NPM1)[1]. ALK-positive ALCL is more common in children and young adults. It is considered an aggressive cancer that grows quickly, but it usually responds well to chemotherapy treatments[2].
ALK-negative ALCL means the cancer cells do not produce the ALK protein. This form mainly affects people over 60 years old. While it is also aggressive, the cancer often comes back after treatment, making it harder to treat than ALK-positive ALCL[2].
Primary cutaneous ALCL
Primary cutaneous ALCL affects only the skin at first. It causes skin changes like bumps or a rash. In most cases (about 90% of the time), it does not spread beyond the skin[2]. This type grows more slowly than systemic ALCL[4].
Breast implant-associated ALCL
Breast implant-associated ALCL (BIA-ALCL) is a very rare type that forms around breast implants. It can occur with both silicone and saline implants but is more commonly associated with textured (rather than smooth) implants. This type is usually diagnosed about 10 years after breast augmentation or reconstruction surgery[2].
Who is affected by this disease
ALCL can affect people of all ages, but different types of ALCL are more common in certain age groups. ALK-positive ALCL is more common in children and adolescents compared to adults. It occurs most often in the first three decades of life and affects more males than females, with a ratio of about 1.5 to 1[1].
ALK-positive ALCL mostly affects pre-teens, adolescents, and adults in their 20s and 30s. It is significantly more common in men[2].
ALK-negative ALCL mainly affects people over 60. It is slightly more common in men[2].
Primary cutaneous ALCL primarily affects adults over 40. It is slightly more common in men and people who are white[2].
How the cancer cells look
ALCL shows diverse appearances under the microscope. Most cases show large abnormal cells that have invaded areas of lymph nodes called interfollicular T zones and nodal sinuses. These cells are called “hallmark cells” because they are present in all forms of ALCL[1].
The hallmark cells have a distinctive horseshoe shape, wreath-like appearance, or multiple nuclei (the control centers of cells). They also have multiple nucleoli (small structures inside the nucleus), a perinuclear eosinophilic region (a pink-staining area around the nucleus), and occasional nuclear pseudoinclusions (structures that look like doughnut cells). These cells show rare mitotic activity, which means they are not dividing very frequently[1].
The anaplastic large cells can sometimes look similar to Reed-Sternberg cells (found in Hodgkin lymphoma), metastatic carcinoma cells (cancer cells from other organs that have spread), or megakaryocytes (large bone marrow cells)[1].
A key feature of ALCL cells is that they strongly express a marker called CD30 on their surface. CD30 is an activation marker for B or T cells. The cancer cells also typically do not express CD15, PAX-5, but do express CD45. About 60% of cases express one or more T-cell antigens such as CD3+, CD43, or CD45RO[4].
Causes and risk factors
ALCL usually originates from T cells. The disease can be primary (occurring on its own) or secondary (developing from another condition)[1].
The disease is associated with certain conditions including HIV infection, mycosis fungoides (a type of skin lymphoma), and pulmonary and inflammatory pseudotumors. However, ALCL has not been shown to be related to Epstein-Barr virus (EBV) infection[1].
Other than in breast implant-associated ALCL, there are no known specific risk factors for developing this disease[4].
Signs and symptoms
The symptoms of ALCL vary depending on the type and location of the cancer. Most patients with systemic ALCL present with advanced-stage III or IV disease. They often have B symptoms, which include persistent fevers, unintended weight loss, and profuse night sweats[1].
ALCL frequently involves lymph nodes and areas outside the lymph nodes (extranodal sites). The most commonly involved extranodal sites include skin, bone, soft tissue, lung, and liver. Involvement of the gastrointestinal system and central nervous system is rare[5].
Patients often have high fever as a symptom. Bone marrow involvement occurs in approximately 10% to 30% of cases, depending on the tests performed[5].
Primary cutaneous ALCL causes skin changes such as bumps, nodules, or a rash[2].
How the disease is diagnosed
A diagnosis of ALCL requires taking a biopsy (a sample of the tumor tissue) and examining the cells under a microscope[7]. The initial evaluation of patients should include a careful medical history and physical examination, with close attention to the presence of systemic B symptoms, lymph node involvement, organ enlargement, and evidence of skin involvement[4].
Immunophenotypic and immunohistochemical studies are critical for definitive diagnosis. These tests examine what markers the cancer cells express on their surface. Major features of ALCL include cells that are CD30+, CD15-, PAX-5-, and CD45+. About 60% of cases express one or more T-cell antigens[4].
ALK protein can be detected in most cases (60% to 70%) of systemic ALCL by immunohistochemistry[4]. Genetic testing may show a translocation t(2;5)(p23;q35), and T-cell receptor genes are clonally rearranged[5].
Additional tests may be conducted to determine how far the disease has spread in the body. These can include blood tests, computed tomography (CT) scans, positron emission tomography (PET) scans, magnetic resonance imaging (MRI) scans, and bone marrow biopsy[7].
Treatment options
Treatment for ALCL depends on the type of disease and how far it has spread.
Treatment for primary cutaneous ALCL
Treatment options for primary cutaneous ALCL depend on the extent of the skin lesions. If the disease is confined to a single lesion or area, radiation therapy or surgical removal will result in complete remission in approximately 95% of patients[10].
If there are multiple lesions or the disease has returned in the skin, radiation can eliminate the skin lesions but will not reduce the likelihood of new lesions developing. Patients with primary cutaneous ALCL in multiple sites on the body usually need systemic treatment (treatment that travels through the blood and affects many parts of the body)[10].
Several treatments are approved for cutaneous T-cell lymphoma, including bexarotene (Targretin), brentuximab vedotin (Adcetris), romidepsin (Istodax), and vorinostat (Zolinza)[10].
Treatment for systemic ALCL
Many patients with newly diagnosed systemic ALCL respond well to common first-line chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). However, long-term outcome depends on the subtype and other factors[10].
ALK-positive disease usually responds very well to CHOP or CHOEP (CHOP plus etoposide). In contrast, ALK-negative patients may be more likely to have the disease return after similar treatments[10].
In some circumstances, higher doses of chemotherapy followed by stem cell transplantation may be prescribed[10].
