What is Sézary Syndrome & How is it Treated?

Cutaneous T-Cell Lymphoma is a cancer of T-cells of the skin and belongs to the broad group of diseases of Non-Hodgkin’s Lymphoma. It has two subtypes, Mycoid Fungoides and Sézary Syndrome. In Mycoid fungoides, the cancerous T-cells affect the skin. It progresses slowly and takes years to advance. While in Sézary syndrome, cancerous T-cells affect both the skin and the peripheral blood. As compared to mycoid fungoides, sézary syndrome spreads more rapidly.

Sézary syndrome is a lymphoma of skin-homing T-cells. Sézary syndrome is a more aggressive form of cutaneous T-cell lymphoma. It can occur de-novo (on its own) or at times it is an evolved form of mycoid fungoides. Malignant T-cells are known as Sézary cells and are found in the blood, skin and lymph nodes. It is characterized by the presence of abnormally shaped nucleus called Cerebriform.

Sézary syndrome is named after its discoverer Dr. Albert Sézary. It is also called as Sézary Lymphoma and Sézary Erythroderma.

In patients affected with Sézary syndrome, the skin all over the body is covered with red rash, it is itchy, peeling and painful. It is due to the fact that the malignant T-cells (sézary cells) move from the blood to the skin and are found in these rash. In addition, there may be red patches, plaques and tumors on the skin. Patients with sézary syndrome often show enlarged lymph nodes.

The other common symptoms associated with this condition include:

• Hair loss
• Thickened skin on the palms of hands and soles of the feet
• Variable amount of scaling of skin
• Abnormalities of the fingernails and toenails
• Lower eyelids turned outward.

These malignant T-cells move to other parts or organs of the body such as lymph nodes, spleen, bone marrow and liver to form cancer.

The treatment decision is based on the stage of Sézary syndrome. There are four main stages each having its characteristic feature. Generally, initial stages show less symptoms and show good response to treatment. While advanced stages become aggressive and do not respond to treatment. The TNM classification for sézary syndrome is as follows:

• Sézary Syndrome Stage I: Stage I is divided into:
  • Stage IA of Sézary Syndrome: Patches and/or plaques cover less than 10% of the skin.
  • Stage IB of Sézary Syndrome: Approximately, 10% of the skin surface has patches and/or plaques.
• Sézary Syndrome Stage II : This stage is further divided as follows:
  • Stage IIA of Sézary Syndrome: Any amount of the skin is covered with papules, patches and/or plaques. Although, lymph nodes are enlarged, cancer has not yet spread to them.
  • Stage IIB of Sézary Syndrome: This stage includes one or more tumors of 1 centimetre or larger size are found on the skin. Lymph nodes may be enlarged but cancer has not yet spread.
• Sézary Syndrome Stage III: In this stage, almost the entire skin is reddened and might have plaques, papules, patches, or tumors. Lymph nodes might be enlarged but spreading of cancer is not yet noticed.
• Sézary Syndrome Stage IV: This Stage is divided into stage IVA and stage IVB as follows:
  • Stage IVA of Sézary Syndrome: Majority of the skin of the body is reddened and is covered with papules, patches, plaques, or tumors. Lymph nodes enlarge and cancer has spread to lymph nodes and also other organs.
  • Stage IVB of Sézary Syndrome: Most of the skin is reddened and the skin surface is covered with patches, plaques, or tumors. Cancer has spread to other organs in the body. Lymph nodes may be enlarged and cancer may have spread to them.

Stages of the Sézary syndrome may also have a B factor in classification. The B factor is based on how many abnormal lymphocytes are found in the blood.

Sézary syndrome is an uncommon type of cancer. It is the second most common cutaneous T-cell lymphoma and accounts for 3-5% of these cases. It occurs in adults from the age of 50-60 years and progresses rapidly. It is slightly more common in men than women. There is no report of family history and of inheritance pattern regarding this syndrome noticed as yet.

Prognosis of sézary syndrome depends on stage and type of lesions. It is an aggressive form of cutaneous T-cell lymphoma, difficult to cure and often has poor prognosis. The 5 year survival rate is approximately 20-27%. Once sézary syndrome is diagnosed, the survival rate is not more than 2-4 years. Although with advanced therapeutic strategies, there is a slight improvement in the overall survival rate of these patients. However, Sézary syndrome shows high rate of recurrence. Hence, the treatment is mostly palliative (pain relieving).

The exact cause of sézary syndrome is not known. The peripheral CD4+ T-lymphocyte is believed to be the cause. While in some case the involvement of CD8+/CD4- has also been seen. Loss or gains of genetic material from chromosomes 10 and 17 are also observed in the sézary cancerous cells.

There is no known risk factor for this type of cutaneous T-cell lymphoma.

The clinical diagnosis is performed as follows:

• Physical Examination and Evaluation of the History of Patient: To check for overall health, and examine the signs of the disease, such as red rash, lumps, the type and number of skin lesions, physical examination is done by the doctor. Questions are asked to ascertain the presence of family history of sézary syndrome and also to know, if there was a previous occurrence of any other cancer. A clinical diagnosis is necessary to determine the stage of sézary syndrome on which the effective treatment planning is dependent.
• Blood Tests to Diagnose Sézary Syndrome: These include:
  • RBC and WBC count
  • Determination of haemoglobin content
  • Peripheral blood smear
  • Immunophenotyping: To determine the type and amount of antigens present on the cells. It is used for differential diagnosis of leukemia and lymphomas.
  • Immunogenotyping: A tissue sample from skin biopsy is taken to determine the arrangement of genes of T-cell receptor proteins. Generally, sézary syndrome cell genes are arranged in a similar pattern.
  • Flow cytometry tests.
• Imaging Techniques to Evaluate Sézary Syndrome: Advanced imaging techniques such as MRI scan, CT scan and PET scan are used to determine the spread of sézary syndrome to lymph nodes or to other organs of the body.
• Lymph Node Biopsy for Diagnosing Sézary Syndrome: Biopsy of the lymph node tissue is also done check for the condition.
• Bone Marrow Aspiration to Diagnose Sézary Syndrome: Bone marrow aspiration is also done to check whether the cancer has spread to other areas of the body.

The treatment option depends on the stage of Sézary syndrome, the number of lesions and type of T-cell lymphocytes. The aim of the treatment is to kill the malignant lymphocytes. There are some standard treatments that are currently used; while some are being tested in various clinical trials.

• Immunotherapy to Treat Sézary Syndrome: It is a first line of treatment used for sézary syndrome. This form of therapy uses immune system based products to fight sézary syndrome. It is administered in the form of retinoids, monoclonal antibodies, Interferon alpha and Interleukin. These are given as combination therapy. Monoclonal based antibody therapy is a targeted therapy used specifically against sézary cells.
• Photodynamic Therapy for Treating Sézary Syndrome: Photodynamic therapy is a cancer treatment that uses a certain drug and then a particular type of laser light for killing cancer cells. For example: A photodynamic therapy, called Psoralen and Ultraviolet A (PUVA) therapy is given to patients, wherein, the patient is given a drug called psoralen and then ultraviolet ray is given to the skin to treat the condition.
• Treating Sézary Syndrome with Radiation Therapy: Sometimes, a radiation therapy called Total Skin Electron Beam (TSEB) is given where the entire skin of the body is exposed to rays of electrons.
• Chemotherapy for Treating Sézary Syndrome: Chemotherapy helps in treating cancer by using drugs by stopping the cancer cells from growing, either by stopping their cell division or by killing the cells. Vorinostat (Zolinza) is the most frequently used drug. Some drugs such as gemcitabine and doxorubicin are administered along with the monoclonal antibody.
• There are newer types of treatment being tested in clinical trials such as high-dose chemo- and radiation therapy along with stem cell transplant.

However, overall therapeutic management of sézary’s syndrome is challenging.

The cause and underlying pathogenesis cutaneous T-cell lymphomas and sézary syndrome is not yet clear. There is an urgent need to investigate its underlying molecular mechanisms. Unrevealing the process of carcinogenesis will enable better insight of sézary syndrome and will allow in development of specific therapeutics to improve the survival rate in these patients.