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

• Acral CD8+ T-Cell Lymphoma of Skin
• Primary Cutaneous Acral CD8 Positive T-Cell Lymphoma

What is Primary Cutaneous Acral CD8+ T-Cell Lymphoma? (Definition/Background Information)

• Primary Cutaneous Acral CD8+ T-Cell Lymphoma is a primary cutaneous T-cell non-Hodgkin’s lymphoma. It is a rare and less aggressive form of T-cell lymphoma
• This is a type of primary cutaneous non-Hodgkin lymphoma, which means that it is a lymphoma that originates first in the skin. In vast majority of cases, this type of lymphoma is confined to the skin and does not spread to the lymph nodes or bone marrow
• The skin signs and symptoms include the presence of a mostly solitary nodule in the head and neck region, or in the hands or feet. Generally, no significant complications are observed, although it can recur following surgery, in some cases
• A combination of treatment measures may be used to treat Primary Cutaneous Acral CD8+ T-Cell Lymphoma including surgery, radiation therapy, and chemotherapy. In some cases, the healthcare provider may undertake a ‘wait and watch’ approach to evaluate the growth of the tumor
• The prognosis depends on many factors including the symptoms noted, response to treatment, and overall health of the individual. In general, the prognosis of Primary Cutaneous Acral CD8+ T-Cell Lymphoma is good with appropriate treatment

General information on lymphoma and lymphocytes:

• Lymphoma is a type of cancer stemming from uncontrollably dividing lymphocytes (type of white blood cells). There are two types of lymphomas:
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
• Lymphocytes are the main white blood cells found in the lymph, which is the fluid of the lymphatic system; just as blood is the fluid of the circulatory system
• Lymphocytes are made in bone marrow, and can develop into either B-cells or T-cells. T-cells mature in the thymus; Primary Cutaneous Acral CD8+ T-Cell Lymphoma arises from cancerous T-cells
• Lymph, also called lymphatic fluid, results from filtration of blood as it travels to and from tissues. Lymph is colorless because it lacks red blood cells; instead, it contains lymphocytes. It is central to the immune system
• There are 3 different kinds of lymphocytes:
  • T-lymphocytes or T cells: They help combat infections and abnormalities within the cells (cell-mediated immunity). They fight viruses and cancerous cells
  • B-lymphocytes or B cells: They produce antibodies that are bodily defense proteins, which target foreign invaders outside the cells (humoral immunity). They fight bacterial cells, cell fragments, and other immunogenic elements
  • Natural killer cells or NK cells: They perform diverse functions related to both cell-mediated and humoral immunity. They also scout for cancer cells, a process called immune surveillance

Who gets Primary Cutaneous Acral CD8+ T-Cell Lymphoma? (Age and Sex Distribution)

• Primary Cutaneous Acral CD8+ T-Cell Lymphoma is a rare condition that generally affects middle-aged adults around 50 years old (median age of 54 years)
• Both males and females are affected, although a male predominance is noted
• All races and ethnic groups can be affected

What are the Risk Factors for Primary Cutaneous Acral CD8+ T-Cell Lymphoma? (Predisposing Factors)

No specific risk factors have been identified for Primary Cutaneous Acral CD8+ T-Cell Lymphoma. However, the following factors may contribute towards lymphoma formation and development:

• Family history of immune disease
• Age 60 years and older
• Decreased immunity, especially due to HIV/AIDS
• The presence of any systemic disease
• Smoking
• Exposure to radiation and industrial chemicals
• Chemotherapy
• Viruses (in some rare cases); Epstein-Barr virus infection
• X-ray and CT scan exposure
• Profession involving radiation exposure, which may include nuclear plant workers, pilots, astronauts, etc.
• Certain medications and drugs

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Primary Cutaneous Acral CD8+ T-Cell Lymphoma? (Etiology)

Lymphocytes are a type of white blood cells that are responsible for providing immunity in the human body. B-cells and T-cells are the two different types of lymphocytes. When under certain circumstances, the lymphocytes grow and multiply abnormally, it leads to a condition called as lymphoma, which is a most common type of cancer. There are 2 types of lymphoma:

• Hodgkin lymphoma
• Non-Hodgkin lymphoma

The cause of Primary Cutaneous Acral CD8+ T-Cell Lymphoma is unknown. It is believed that there may be the involvement of genetic mutations. Also, there may be certain genetic defects, such as translocation, which is a juxtaposition of regions of chromosomes resulting in:

• Change of regulatory elements of certain cancer-causing genes called as oncogenes, which can lead to increased production of their mRNA (overexpression), thus increasing their protein levels
• Exchange of protein coding regions of gene, giving rise to new proteins that can stimulate the inappropriate growth of cells

It is believed that the abnormal development of lymphocytes gives rise to cancerous cells leading to the formation of this condition. Nevertheless, how this occurs and the factors that cause it remain under investigation.

Note: Acral CD8+ T-Cell Lymphoma of Skin is non-contagious and is not transmitted from one individual to another. One cannot contract the condition through close physical interaction with the affected individuals.

What are the Signs and Symptoms of Primary Cutaneous Acral CD8+ T-Cell Lymphoma?

The signs and symptoms of Primary Cutaneous Acral CD8+ T-Cell Lymphoma include:

• Presence of an usually slowly-growing, single skin nodule
• The nodule may show a reddish discoloration (erythematous) and is usually confined to the skin. The involvement of lymph nodes is not observed
• It is generally present in the head and neck region and the upper and lower extremities
• The most common location is the ear; followed by the nose, hands, and feet
• Occasionally, the nodules may be multiple (more than one) and appear bilaterally
• The condition is not known to be associated with skin patches and plaques

How is Primary Cutaneous Acral CD8+ T-Cell Lymphoma Diagnosed?

Primary Cutaneous Acral CD8+ T-Cell Lymphoma diagnosis is performed by obtaining biopsy samples from the affected region and examining them under a microscope to detect the cancerous cells. The following diagnostic procedures and tests may help in the study:

• A thorough physical examination and a complete medical history, which is very important
• Blood tests that may include:
  • Absolute lymphocyte count on peripheral blood. The absolute lymphocyte count in this condition is usually normal
  • Complete blood cell count (CBC) blood test: This is usually within normal limits
  • Liver function blood test (LFT): The test is usually within normal limits
  • Lactate dehydrogenase (LDH) blood test - LDH blood levels are typically not elevated
• Skin biopsy from the affected area:
  • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
• Radiological imaging may be performed to determine the extent of lymphoma in the body. Usually, the lymphoma is confined to the skin and does not involve other parts of the body. The healthcare provider may perform the following radiological diagnostic tests to exclude involvement of other parts of the body that may be seen in other cutaneous T-cell lymphomas:
  • X-ray of the affected region
  • Ultrasound scan of the affected region
  • Computerized tomography (CT) scan of the affected region
  • Vascular radiological studies
  • Whole body bone scan
  • Whole body CT-PET scans to determine how far the lymphoma has spread, by checking the size and metabolic rate (a reflection of uncontrolled growth) of lymph nodes, throughout the body. This can also help determine if the cancer has spread to other organ systems
  • Brain MRIs are used if neurological symptoms are present, which can help determine if the cancer has spread to the brain, or to tissues that cover the brain
• Flow cytometry to identify cells as they flow through an instrument, called a flow cytometer. Flow cytometry measures the number and percentage of cells in a blood sample, and cell characteristics such as size, shape, and the presence of biomarkers on the cell surface. This method helps to sub-classify the condition and also to detect residual levels of disease after treatment. This tool can help in diagnosing relapse and restart treatment as needed. Since Cutaneous Acral CD8+ T-Cell Lymphoma is usually confined to the skin, flow cytometric analysis is normal. It is not helpful in detecting relapse or residual disease after treatment
• Fluorescence in situ hybridization (FISH): It is a test performed on the blood or bone marrow cells to detect chromosome changes (cytogenetic analysis) in blood cancer cells. The test helps in identifying genetic abnormalities that may not be evident with an examination of cells under a microscope
• Immunophenotyping to identify a specific type of cell in a sample, which can help determine the best treatment course to be followed
• Polymerase chain reaction (PCR): It is used to measure the presence of certain biomarkers in blood or bone marrow cells. The test is ultrasensitive and detects extremely low amounts of biomarkers remaining in blood, which can be missed by cytogenetic methods, such as FISH, karyotype, or flow cytometry. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is necessary
• Lumbar puncture to determine if the brain is involved. In addition, the cerebrospinal spinal fluid (CSF) may be collected by inserting a needle in the spine and subjected to microscopic, flow cytometric, PCR, and biochemical analysis, to diagnose central nervous system (CNS) involvement, if any. However, in this malignancy, brain involvement has not been reported so far

Note: Differential diagnoses, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis.

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 Primary Cutaneous Acral CD8+ T-Cell Lymphoma?

With adequate and early treatment, no significant complications due to Primary Cutaneous Acral CD8+ T-Cell Lymphoma are observed. However, the tumor is known to recur after treatment (following its surgical removal), in some cases.

There may be complications related to chemotherapy used in treating the condition, which may include:

• Side effects such as dizziness, vomiting, appetite loss, mouth ulcers, and hair loss
• By damaging healthy cells, the individual is more open or vulnerable to secondary infections
• The treatment can also cause infertility in men and women. Hence, measures to protect the individual’s fertility must be considered, before starting chemotherapy

The treatment measures can also give rise to secondary cancers, such as other forms of skin cancer.

How is Primary Cutaneous Acral CD8+ T-Cell Lymphoma Treated?

Once a definitive diagnosis of Primary Cutaneous Acral CD8+ T-Cell Lymphoma has been made, a combination of treatment measures may be used to treat the condition. The treatment may involve the following procedures:

• Surgical excision and removal of the tumor
• Use of topical steroids
• Radiation therapy: The use of high-energy radiation waves to kill cancer cells, by destroying their DNA
• In some cases, the healthcare provider may undertake ‘watchful waiting’ of the condition

Other treatment modalities that have been used, especially for multi-focal disease include:

• Interferon therapy
• Psoralen and ultraviolet A (PUVA) phototherapy
• Chemotherapy medications such as methotrexate

The healthcare provider will determine the best course of treatment depending on one’s individual circumstances. Also, follow-up care with regular screening and check-ups are important post-treatment.

How can Primary Cutaneous Acral CD8+ T-Cell Lymphoma be Prevented?

The cause of Primary Cutaneous Acral CD8+ T-Cell Lymphoma is presently unknown. Hence, there are no known methods to prevent the tumor from occurring. Eliminating certain risk factors may help in avoiding the condition.

• Healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help decrease its risk
• Avoiding smoking
• Genetic testing in individuals with a family history
• Undertaking effective treatment of viral infections and other underlying disorders
• In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Primary Cutaneous Acral CD8+ T-Cell Lymphoma? (Outcomes/Resolutions)

• Primary Cutaneous Acral CD8+ T-Cell Lymphoma is comparatively less-aggressive skin tumor that responds well to treatment. The prognosis is typically good with adequate early treatment
• In general, the prognosis of the condition depends upon a set of several factors, which include: 
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Younger individuals generally have poorer prognosis than older individuals. However, it is important to note that the overall prognosis is good, since this is a less aggressive form of lymphoma
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • The surgical resectability of the tumor
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurrent tumors have a 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
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). These chiefly impact the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Primary Cutaneous Acral CD8+ T-Cell Lymphoma:

• T-cell lymphomas are less common than B-cell lymphomas

The following article link will help you understand leukemia and lymphoma (blood cancer):

https://www.dovemed.com/diseases-conditions/leukemia-and-lymphoma/