Cutaneous Lymphoma - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Lymphoma is cancer that develops in lymphocyte cells that plays a vital role in the body's immune system. Rarely, lymphoma develops in the skin and is called cutaneous lymphomas.

Two types of skin lymphoma are:

• Cutaneous T-cell lymphoma (CTCL) is the most common kind of skin lymphoma.

• Cutaneous B-cell lymphoma (CBCL).

What Causes Cutaneous Lymphoma?

Specific DNA changes inside the normal lymphocytes (immune cells) might cause lymphoma.

Some genes control the cell's growth, cell division, and cell death at the appropriate time. They are:

• Genes that regulate cell growth, division, or lifespan are called oncogenes.

• Genes that control cell division or cell death are called tumor suppressor genes.

Cancers develop when changes in the DNA excite the oncogenes or suppress the tumor suppressor genes.

Cancer can also be inherited. However, it is usually acquired after birth.

Who Is at Risk for Cutaneous Lymphoma?

The exact cause of cutaneous lymphoma is not known. Yet, some factors that influence are:

Most skin lymphomas occur in people between 50 years and 60 years. However some forms of skin lymphoma can also appear in children and younger people. It is more common in males than in females; blacks than in whites. People withweak immune systems such as AIDS, organ transplants, or under immunosuppression therapy. Infection can cause skin lymphomas.

For example, HTLV-1 virus infection can cause adult T-cell leukemia or lymphoma; Epstein-Barr virus (EBV) infection is associated with extranodal nasal natural killer or T-cell lymphoma; Lyme's disease is linked to skin lymphomas.

What Are the Signs and Symptoms of Cutaneous Lymphoma?

Skin lymphomas appear red to purple, small, pimple-like, thick, flat, raised, or lowered lesions; larger lumps or bumps may be present under the skin. The lesion is often itchy and scaly. The lymphoma can occur in any part of the skin that is mostly not exposed to the sun. Some skin lymphomas look like a rash known as erythroderma. Sometimes larger lesions break open and cause ulcers.

Other general symptoms include:

• Fever.

• Unexplained weight loss.

• Profuse sweating, particularly at night time.

• Severe itch.

• Lymph node swelling in the underarm, neck, or groin area.

How Is Cutaneous Lymphoma Diagnosed?

Although skin lymphoma is often quickly noticed, the actual diagnosis might be delayed as it resembles other common skin problems. A skin biopsy is required to confirm the skin lymphoma.

1) Other tests that might be needed are as follows.

2) Complete personal and family medical history.

3) Complete physical exam.

4) Biopsy:

• Skin biopsies like punch biopsies, incisional, and excisional skin biopsies are done to confirm the clinical diagnosis.

• Lymph node biopsies like Excisional or incisional lymph node biopsies are done to determine the spread of cancer to the lymph nodes.

• Needle biopsies such as fine-needle aspiration (FNA) or a core needle biopsy are done.

• Bone marrow aspiration and biopsy are usually taken from hip bone to determine the extent of lymphoma that is already diagnosed.

• Lumbar puncture is done to investigate lymphoma cells in the cerebrospinal fluid (CSF).

5) Lab Investigations:

• Flow cytometry and immunohistochemistry, chromosome tests, cytogenetics, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR) are performed to investigate the changes in the DNA structure.

6) Blood Test:

• A blood test investigates the extent of specific cell types and chemicals present in the blood. During the treatment, they are also helpful to monitor bone marrow and other organ functioning.

• Complete and differential blood count, blood chemistry tests, and lactate dehydrogenase (LDH) tests may be done.

7) Imaging Test:

• Imaging tests use x-rays, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, ultrasound, and positron emission tomography (PET) scan to picture the inside of the body. It helps determine the suspicious areas, the spread of lymphoma, prognosis with treatment, and possible signs for recurrence of lymphoma.

How to Treat Cutaneous Lymphoma?

1) Skin-Directed Treatment:

For early-stage skin lymphomas, the first-line treatment is direct skin treatment while trying to avoid side effects on other body parts.

2) Surgery:

• Surgery is done when only a few skin lesions can be removed entirely. Surgery can be used to take a biopsy of a skin lesion or other tissue to identify and classify a lymphoma.

3) Radiation Therapy:

• Radiation therapy uses high-energy rays to destroy cancer cells. It is painless and may require one or several days, depending on the extent of skin being treated.

• The radiation most often used for skin lymphomas is electron beam radiation. The major side effect of this therapy is a skin reaction like sunburn. Localized thicker lymphomas are treated using high-energy radiation like x-rays or gamma rays.

4) Phototherapy (UV Light Therapy):

• Phototherapy uses UV light to destroy skin cancer cells. Treatments may require several times a week.

5) Topical Medications:

• Topical corticosteroids, chemotherapy drugs (Mechlorethamine, Carmustine), retinoids (Bexarotene), and immunotherapy (Imiquimod) are applied to the skin.

6) Systemic Treatment:

Systemic treatments are helpful for advanced or fast-growing skin lymphomas and affect the whole body. Sometimes, systemic and skin-directed therapy is given for better results. Extracorporeal photopheresis (ECP) or photoimmunotherapy is occasionally used for T-cell skin lymphomas. It is believed to kill the lymphoma cells and boost the body's immune reaction. Treatment is given for two days continuously and repeated every few weeks.

7) Systemic Chemotherapy:

Systemic chemotherapy can be given intravenously, intramuscularly, or orally. It is preferred when the disease is in the more advanced stage, and no improvement is seen with other treatments. Chemo drugs used to treat skin lymphoma patients are Gemcitabine, Liposomal doxorubicin, Methotrexate, Chlorambucil, Cyclophosphamide, Fludarabine, Cladribine, Pentostatin, Etoposide, Temozolomide, Pralatrexate. Single or combination drugs are used. The combination chemo regimen is CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) and a monoclonal antibody (Rituximab). Likely side effects of chemotherapy are hair loss, mouth sores, increased infection, loss of appetite, nausea, vomiting, diarrhea, fatigue, bleeding or bruising, and shortness of breath.

8) Targeted and Biologic Therapy:

These drugs specifically target the lymphoma cells, affecting all the fast-growing cells. These drugs include histone deacetylase (HDAC) inhibitors (Vorinostat, Romidepsin), monoclonal antibodies (Rituximab, Mogamulizumab, Alemtuzumab), anti-CD30 antibody (Brentuximab vedotin), Interferons, systemic retinoids (All-trans retinoic acid (ATRA), Acitretin, Isotretinoin, and Bexarotene).

9) High-Dose Chemotherapy With Stem Cell Transplant (SCT):

Sometimes, stem cell transplants treat lymphoma when traditional treatments do not show any improvement.

Two main types of stem cell transplants are:

1) Allogeneic Stem Cell Transplant: The blood-forming stem cells are transplanted from another person, such as relatives whose tissue type matches the patient.

2) Autologous Stem Cell Transplant: The patient's stem cells are taken from the bone marrow or blood. Stem cells are collected over several days before treatment, frozen and stored, and then reinfused into the patient's blood during treatment. Autologous transplants are rarely used for skin lymphomas.

How to Prevent Cutaneous Lymphoma?

As the cause of skin lymphoma is unknown, there is no sure way to prevent it.

• As a weakened immune system increases the risk of skin lymphoma, maintaining a healthy immune system can limit the risk.

• Avoid smoking.

• Regular physical activity.

What Is the Prognosis of Cutaneous Lymphoma?

Some skin lymphomas have a good prognosis. However when the lymphoma recurs, other treatments can be tried. But the recurrence of lymphoma has a poor prognosis, as more treatments may have little effect on the body or cause side effects. Advanced skin lymphomas have a poor prognosis and are very hard to cure.

Conclusion:

Cutaneous lymphoma is a skin cancer that develops due to abnormality in white blood cells called lymphocytes. Early diagnosis can help treat lymphomas with no so little recurrence rate. But as the skin lymphoma progresses, the treatment may be a failure.