What are the other Names for this Condition? (Also known as/Synonyms)

• Angioimmunoblastic T-Cell Lymphoma with Skin Involvement
• Cutaneous Involvement in Angioimmunoblastic T-Cell Lymphoma
• Skin Involvement in AITL

What is Skin Involvement in Angioimmunoblastic T-Cell Lymphoma? (Definition/Background Information)

• Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive type of nodal or soft tissue non-Hodgkin lymphoma. Nodal lymphomas are restricted to lymph nodes, and generally do not enter the bloodstream, until later stages of the disease
• Skin Involvement in Angioimmunoblastic T-Cell Lymphoma is common and takes place secondary to systemic disease, meaning that the disease affects other body organs first, before affecting the skin. Primary cutaneous AITL, where the skin is involved first before other body regions are affected, is generally uncommon
• Common signs and symptoms of AITL are non-painful enlarged lymph nodes, fluid accumulation, joint inflammation, weight loss, excessive night sweats, and low red blood cell counts
• When the skin is involved, a widespread erosion of the skin may be observed.  The manifestation may be in the form of multiple macules or nodules. In many cases, the skin signs are often mistaken for other benign conditions such as skin rashes due to side effects of medication or viral infections
• The specific cause of angioimmunoblastic T-cell lymphoma is currently unknown; however, a poorly functioning immune system is known to play a role towards its formation
• Angioimmunoblastic T-cell lymphoma is most commonly treated with a combination of chemotherapy, radiation, and supportive care. However, the prognosis of AITL is very poor, with a high chance of relapse

Who gets Skin Involvement in Angioimmunoblastic T-Cell Lymphoma? (Age and Sex Distribution)

Skin Involvement in Angioimmunoblastic T-Cell Lymphoma is observed in nearly 50% of all AITLs.

• Middle-aged and older adults have the highest risk for AITL. It is very rare in young adults and children
• Both males and females are affected, though some studies inform that males are more likely to develop this lymphoma type than females
• There is no specific ethnic or racial predisposition observed

What are the Risk Factors for Skin Involvement in Angioimmunoblastic T-Cell Lymphoma? (Predisposing Factors)

The risk factors associated with Angioimmunoblastic T-Cell Lymphoma Involving Skin include:

• A diagnosis of Epstein-Barr virus (a virus causing mononucleosis) has been made in 90% of AITL cases; although, the connection between the two, is unknown
• Other viruses and infections that have been linked to AITL are human immunodeficiency virus, herpes virus, hepatitis C, cytomegalovirus, cryptococcus, and tuberculosis. It is unknown what is the potential risk for developing AITL from these factors
• Dysfunctional vascular endothelial growth factor A (VEGF-A) may be linked to AITL, because it normally helps create new blood vessels and if mutated, may help tumors form blood vessel networks
• Exposure to chemicals, such as pesticides and fertilizers, as well as smoking and diet, has been suggested as links to other forms of non-Hodgkin lymphoma.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Skin Involvement in Angioimmunoblastic T-Cell Lymphoma? (Etiology)

• Currently, the exact cause of Angioimmunoblastic T-Cell Lymphoma with Skin Involvement is not completely understood
• AITL may arise from a dysfunctional immune system reacting to one’s own body (an autoimmune reaction), or due to an unknown foreign invader (antigen)

What are the Signs and Symptoms of Skin Involvement in Angioimmunoblastic T-Cell Lymphoma?

The general signs and symptoms of angioimmunoblastic T-cell lymphoma may include:

• ‘Non-painful’ swelling of lymph nodes in the neck, armpits, or groin
• Autoimmune disorders, which can cause joint and muscle pain, heat intolerance, recurrent rashes, abdominal pain, and a general feeling of illness
• Loss of appetite and weight loss
• Fatigue
• High temperatures and excessive night sweats
• Anemia (low red blood cell count)

The involvement of skin by AITL is often mild and subtle leading to frequent misdiagnosis initially. The signs and symptoms of Skin Involvement in Angioimmunoblastic T-Cell Lymphoma may include:

• Lesions that occur as skin eruptions; these are often misdiagnosed as drug allergies, or skin rashes due to viral infections, or as toxic erythema
• The lesions may be present as a nodule, urticarial plaque, or erythroderma
• The chest, back, arms and legs may be involved
• In some cases, bleeding and skin ulceration may be noted

Other signs and symptoms of AITL may include:

• Neurological symptoms, such as:
  • Confusion
  • Tinnitus
  • Hearing and visual impairment
• Gastrointestinal symptoms, such as:
  • Ulcers
  • Diarrhea
  • Inflammation
  • GI bleeding
  • Liver and spleen enlargement, joint inflammation, and fluid accumulation (edema)

How is Skin Involvement in Angioimmunoblastic T-Cell Lymphoma Diagnosed?

It often takes multiple tests to diagnose lymphoma. It is critical that the specific sub-type of lymphoma be diagnosed correctly, in order to create a proper treatment plan. Angioimmunoblastic T-Cell Lymphoma with Skin Involvement diagnosis may involve the following:

• A physical examination and a complete medical history by a doctor can help determine, if symptoms like lymph node swelling, are likely caused by an infection, or if there is a risk of lymphoma
• Biopsies of enlarged lymph nodes are taken and examined in a lab, to determine if the cells are malignant or benign. The biopsies may be performed under general or local anesthesia. Normally, the entire lymph node is removed to help determine the sub-type of lymphoma
• Bone marrow biopsies may be performed, to determine if the bone marrow is involved
• Blood tests to evaluate red and white blood cells, as well as platelet counts
• Lumbar puncture to determine, if AITL involves the brain
• X-rays of chest and abdomen, to look for enlarged lymph nodes, liver, or spleen.
• Whole body CT-PET scan - to determine the spread of lymphoma, by determining the size and metabolic rate (a reflection of uncontrolled growth) of lymph nodes, throughout the body. This can also determine if the cancer has spread to other organ systems.
• Brain MRIs are used if neurologic symptoms are present, to determine if cancer has spread to the brain, or to the tissue that covers the brain (meninges)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Skin Involvement in Angioimmunoblastic T-Cell Lymphoma?

The possible complications from Angioimmunoblastic T-Cell Lymphoma with Skin Involvement may include:

• AITL is very aggressive, and can spread from the lymph nodes to all organ systems
• Many adverse symptoms are caused by an abnormal immune system, in addition to the tumor. This cancer can cause autoimmune disorders by causing cells to produce abnormal proteins that are recognized as foreign
• Treatments can cause secondary health problems, such as secondary forms of cancer and heart disease
• There is a high risk of relapse and a low percent of long-term survival

How is Skin Involvement in Angioimmunoblastic T-Cell Lymphoma Treated?

Once a definitive diagnosis of angioimmunoblastic T-cell lymphoma has been made, staging is performed to determine how far the cancer has spread. The stage can describe:

• How many lymph nodes are affected
• Their locations in the body
• And, if other organs are being affected

Staging is important because different treatment regimens are necessary, depending on the progression of the lymphoma.

• Stage 1: Only one group of lymph nodes in one location is affected
• Stage 2: Lymph nodes in multiple locations that are all above or below the diaphragm are affected
• Stage 3: Lymph nodes in multiple locations, both above and below the diaphragm are affected
• Stage 4:  Lymph nodes located throughout the body, the bone marrow, and other organs are affected
• Category A: No symptoms are present at the time of diagnosis
• Category B: Presence of one or more symptoms at the time of diagnosis

A combination of treatments is used to most effectively treat this cancer. The aggressiveness of the treatment is determined by the disease stage.

Skin-directed therapies are used (and often in combination) when Skin Involvement in Angioimmunoblastic T-Cell Lymphoma is mostly confined to the skin presenting associated signs and symptoms. This may include the following treatment measures:

• Sunlight therapy (or exposure to ultraviolet light)
• Use of topical steroids and chemotherapy
• Systemic chemotherapy
• Radiation therapy to affected (local) skin area
• Other systemic treatment measures, such as the use of interferons, retinoids, etc.
• Biological therapy

Surgery: After initial biopsies to diagnose AITL, surgery is generally a very uncommon treatment option, because lymphomas are systemic and may have already spread to more than one lymph node in most patients. Removing all affected lymph nodes would be extremely difficult.

Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used for patients, at all stages of angioimmunoblastic T-cell lymphoma.

• Commonly, the drug combination CHOP is used first, which includes doxorubicin, vincristine, cyclophosphamide, and prednisolone
• There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
• Many T-cell lymphomas can be resistant to chemotherapy. It can also damage healthy cells
• Chemotherapy can be administered as a pill, liquid, shot, or intravenously

Radiation: Radiation therapy is the use of high-energy radiation waves, to kill cancer cells by destroying their DNA.

• This treatment modality is generally used for early stage lymphomas. It is most commonly used in combination with chemotherapy
• The radiation may be administered by a machine placed outside the body, or by putting a radioactive material inside the body
• The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and a risk of heart disease
• Radiation can damage healthy cells in addition to cancer cells, causing further complications

Stem cell support: In combination with chemotherapy, blood stem cells can be taken from a patient before treatment and administered to them, later during the treatment, in order to help restore blood cells killed by chemotherapy. This treatment can have severe side effects; hence, it is not administered to all patients.

Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics, may also be used. In combination with other treatment measures, these can help combat the symptoms of immune deficiency.

Clinical trials: There are some new treatment options, currently on clinical trials that can be considered for some patients, depending on their risk factors.

Current drugs under investigation are:

• Bevacizumab: This helps prevent the formation of new blood vessels
• Cyclosporine: This helps treat immune deficiency, and has been shown to lead to remission
• Interferon alpha: This drug can be used for patients, who do not respond to other therapies. Some studies have shown that individuals may go into remission on this treatment
• Other drugs include: Lenalidomide, Alemtuzumab, Romidepsin, Pralatrexate, Thalidomide, and Rituximab

How can Skin Involvement in Angioimmunoblastic T-Cell Lymphoma be Prevented?

Currently, there are no definitive ways to prevent Angioimmunoblastic T-Cell Lymphoma with Skin Involvement.

• However, healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help decrease its risk
• Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory for those who have already endured the tumor, due to its metastasizing potential and possibility of recurrence. Often several years of active vigilance is necessary

What is the Prognosis of Skin Involvement in Angioimmunoblastic T-Cell Lymphoma? (Outcomes/Resolutions)

• Angioimmunoblastic T-Cell Lymphoma with Skin Involvement is an aggressive form of T-cell lymphoma, with a high risk of relapse. The prognosis is generally poor
• The overall survival rate for patients with AITL is between 30-50%. The median survival period is reported to be between 1 to 2.5 years
• The prognosis depends upon a set of several factors, which include:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely) - it is a rare option
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment

Additional and Relevant Useful Information for Skin Involvement in Angioimmunoblastic T-Cell Lymphoma:

• The term ‘angioimmunoblastic T-cell lymphoma’ comes from the words “angio-“, for blood vessels, and “immunoblast” for lymph cells. This form of T-cell lymphoma can increase the number of blood vessels in the affected regions of the body
• T-cell lymphomas are less common than B-cell Lymphomas