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

• Cutaneous Involvement in Hodgkin Lymphoma
• Hodgkin Disease with Skin Involvement
• Hodgkin Lymphoma Involving Skin

What is Skin Involvement in Hodgkin Lymphoma? (Definition/Background Information)

• Lymphocytes are a type of white blood cells that are responsible for providing immunity in the human body. B-cells, T-cells, and NK cells are the 3 different types of lymphocytes
• Hodgkin Lymphoma develops in the body's immune system, known as the lymphatic system. The function of the immune system is to protect the body from infections (bacterial, viral, or fungal), diseases, as well as from substances deemed foreign and harmful to the body
• Hodgkin’s lymphomas are broadly categorized into 2 main groups, depending on the types of cells affected and the extent of their malfunction. These include:
  • Classical type of Hodgkin lymphoma
  • Nodular lymphocyte predominant type of Hodgkin lymphoma
• Skin Involvement in Hodgkin Lymphoma is very rare and takes place secondary to systemic disease, meaning that the disease affects other body organs first, before affecting the skin. Very few cases of Primary cutaneous Hodgkin lymphoma is also reported (when the skin is involved first prior to systemic disease)
• Currently, skin involvement with the nodular lymphocyte predominant type has not been recorded. In a minority of cases, the classical type with skin involvement has been noted
• Both children and adults may be affected by Hodgkin lymphoma; the condition is more common in the age group 15-40 years. The risk factors for developing the condition include a family history of the condition and being immune-compromised. Infection with Epstein-Barr virus is believed to predispose an individual to Hodgkin lymphoma. The exact cause of this condition is unknown
• Individuals with Hodgkin lymphoma may experience non-specific symptoms such as fever, fatigue, swollen lymph nodes that are not painful (but may pain after intake of alcoholic beverages), itching all over the body, and unintended weight loss. The skin involvement may occur through direct tumor invasion from below the skin surface, or as part of primary disease, or when spread by blood to the skin
• The diagnosis of Hodgkin lymphoma may be established through a biopsy of the affected lymph node or the tumor. However, other tests and exams (such as blood tests and imaging studies) may be performed to examine the severity and extent of spread of the lymphoma
• The treatment of Hodgkin lymphoma depends on the type, the stage of the condition, the size of the tumor, and if there are any pre-existing conditions (such as pregnancy). An individual may be recommended chemotherapy, radiation therapy, stem cell transplantation from his/her own body (autologous stem cell transplantation), or other treatment modes, to successfully combat the condition
• The prognosis of Hodgkin lymphoma depends on the stage of the cancer when it is diagnosed, the extent of spread, and whether any internal organ is affected. If the cancer is diagnosed in its early stages, the prognosis is reported to be excellent. In many cases, the cancer is also considered curable when diagnosed during the later stages of the disease

General information on the lymphatic system: It is a component of the circulatory system and consists of the following components.

• Lymphocytes: These are the main white blood cells found in the lymph. They protect the body from infections, foreign entities, and tumors
  • Spleen: An organ located adjacent to the stomach that makes lymphocytes
  • Tonsils: Located at the back of the throat; this organ also makes lymphocytes
  • Thymus: An organ located in the chest, where lymphocytes grow and mature
  • Bone marrow: It is the soft center of the large bones that makes red blood cells, white blood cells, and platelets
• Lymph: Colorless liquid that carries lymphocytes through the lymphatic system
• Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream
• Lymph nodes: These structures, located along the lymph vessels in clusters and dispersed throughout the body (neck, underarms, and groin), store the lymphocytes

Additionally, there are lymph tissues, which are also located in the stomach, thyroid gland, brain, and skin.

Who gets Skin Involvement in Hodgkin Lymphoma? (Age and Sex Distribution)

In general, Skin Involvement in Hodgkin Lymphoma is an extremely rare occurrence. Less than 5% of the classical type of Hodgkin lymphoma shows skin involvement.

• Hodgkin lymphoma is observed in adults, as well as in children. This cancer is more prevalent in young individuals aged 15-40 years (predominantly in the 20s), and those over 55 years of age
• Children and teenagers are reported to account for 10-15% of Hodgkin Lymphoma cases
• Both male and female genders are affected; although, Hodgkin Lymphoma is more commonly observed in males
• The condition is found worldwide and no racial or ethnic predilection is observed in its occurrence

What are the Risk Factors for Skin Involvement in Hodgkin Lymphoma? (Predisposing Factors)

Studies have reported some risk factors for Hodgkin Lymphoma with Skin Involvement and these include:

• Immunocompromised individuals (particularly those with HIV infections) show a higher incidence of lymphoma cases involving the skin
• It is also more common in individuals with other forms of lymphoma, such as mycosis fungoides and certain lymphoproliferative diseases involving the T-cells
• Having been infected with Epstein-Barr virus (EBV)

The general risk factors for Hodgkin lymphoma development include:

• A family history of the condition
• Being a male and age in the 20s
• Obesity

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 Hodgkin Lymphoma? (Etiology)

The exact cause of Skin Involvement in Hodgkin Lymphoma is not known. However, the possible causes that are being actively researched upon include:

• Genetic mutation: The majority of these types of cancer ensue as a result of a genetic mutation in the B-lymphocyte.
  • This mutation is reported to facilitate uncontrolled proliferation of B cells, as well as their extended lifespan
  • These properties ensure that the abnormal cells outnumber and outlive normal healthy cells, leading to the cancer
• Epstein-Barr virus infection: Having been infected with EBV might lead to mutation(s) in the B-lymphocytes, causing the abnormal Reed-Sternberg cells to develop

What are the Signs and Symptoms of Skin Involvement in Hodgkin Lymphoma?

Skin Involvement in Hodgkin Lymphoma may manifest in the following manner:

• Primary involvement of the skin, before other parts of the body are affected
• Spread of the systemic disease through blood to the skin
• The skin and tissues underlying the skin are affected by direct invasion (from below the skin); this is frequently seen in individuals with massive involvement of the mediastinum by the lymphoma (where the chest wall is affected)
• Regional lymph nodes are affected, which then spreads to the skin through the lymphatic system

When the skin is affected, red and inflamed skin lesions that are nodular or papular in appearance may be seen. The skin over the surface can be ulcerated and bleeding may be noticed. In some cases, extensive involvement of the skin may be seen.

The following signs and symptoms may be reported in individuals with Hodgkin lymphoma:

• Swollen lymph nodes that occur in the underarm, neck, groin, and other regions of the body; these are often painless
• Pain in the lymph nodes after alcohol ingestion; increased sensitivity to alcoholic drinks
• Fever
• Excessive night-time sweating
• Appetite loss
• Unexplained weight loss
• Fatigue
• Itching of skin

How is Skin Involvement in Hodgkin Lymphoma Diagnosed?

In order to diagnose Skin Involvement in Hodgkin’s Lymphoma accurately, a healthcare provider might perform or request many of the following tests and exams:

• A thorough physical examination
• An evaluation of the individual’s personal and family history (of lymphoma)
• An assessment of the signs and symptoms
• Blood tests that may include the following:
  • Complete blood count (CBC) to ascertain hemoglobin, red blood cells, white blood cells, and other components of blood
  • Blood chemistry to check for any abnormality in the amounts of certain chemicals in blood (released by organs and tissues)
  •  Estimation of sedimentation rate to check for abnormality, which might denote an inflammation
• Tissue biopsy: Biopsies of the affected region including swollen lymph nodes (partial or whole), bone marrow, or tumors to check for any malignancy through various tests performed by a pathologist. Many different types of biopsies could be performed depending on the type and extent of the cancer
• Imaging studies of the affected region that may include x-rays, computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI), and whole body bone scan
• Differential diagnoses, to eliminate other tumor types (including lymphoproliferative disorders) 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 Skin Involvement in Hodgkin Lymphoma?

The potential complications arising from Hodgkin Lymphoma with Skin Involvement could include those from the growth and spread of the lymphoma, as well as from the side effects of treatment measures (such as radiation or chemotherapy) employed.

• Complications as a result of the malignancy:
  • Headaches
  • Changes in vision
  • Numbness of face
  • Meningitis
  • Anemia
  • Intestinal blockage
  • Kidney disease
• Complications due to treatment of the cancer:
  • An allergic reaction to therapy
  • Fatigue, dizziness
  • Nausea, vomiting, and diarrhea
  • Heart, lung, and thyroid abnormalities
  • Infertility
  • Leukemia and other bone marrow diseases; development of other types of cancers
  • Vulnerability to infections owing to a weakened immune system
  • Birth defects in children, if the mother was pregnant and was treated with chemotherapy

Apart from the above complications, the condition can return after being in remission, also known as recurrent Hodgkin’s lymphoma.

How is Skin Involvement in Hodgkin Lymphoma Treated?

Once a definitive diagnosis has been made, staging is used to describe how far the cancer has spread. The staging helps describe:

• The number of lymph nodes affected and their location(s)
• If the condition has spread to the internal organs

The following stages are used for adult Hodgkin lymphoma:

Stage I: It is subdivided into stage I and stage IE.

• Stage I: The cancer is detected in a component of the lymphatic system, such as in the
  • Lymph node(s) at a particular site
  • Lymphatic tissue known as Waldeyer's tonsillar ring
  • Thymus
  • Spleen
• Stage IE: Cancer is detected in an organ or tissue that is not a component of the lymphatic system

Stage II: It is subdivided into stage II and stage IIE.

• Stage II: The cancer is detected in more than one lymph node groups, which could be located above or below the diaphragm
• Stage IIE: Apart from the cancer being detected in two or more lymph node groups, it has also spread to the organ or tissue adjacent to the lymph nodes 

Stage III: It is subdivided into stage III, stage IIIE, stage IIIS, and stage IIIES.

• Stage III: The cancer is detected in lymph node groups, which could be located above or below the diaphragm
• Stage IIIE: Apart from the cancer being detected in two or more lymph node groups, it has also spread to the organ or tissue adjacent to the lymph nodes
• Stage IIIS: The cancer is detected in lymph node groups, as well as in the spleen
• Stage IIIES: The cancer is detected in lymph node groups, organ or tissue adjacent to the lymph nodes, as well as in the spleen

Stage IV: This is considered as an advanced stage of cancer, wherein the lymphoma is detected in several lymph nodes, organs, tissues, and at other locations, near and distant from the affected lymph nodes. The organs that have been found to contain metastasized cancer during this stage are the liver, lungs, bone marrow, and many others.

Following a definitive diagnosis of Hodgkin’s Lymphoma with Skin Involvement, and determination of the extent and spread of the condition, some standard and some newer therapy regimens may be adopted such as:

• Chemotherapy: It is the treatment with drugs to either kill the cancer cells or stop their proliferation. The type of cancer, the size of tumor, and the extent of spread dictates the kind of chemotherapy recommended. Sometimes, a mixture of chemotherapeutic drugs may be necessary
• Radiation therapy: It is the use of high-energy radiation to kill cancer cells or stop the proliferation of malignant cells. This type of treatment is mainly of 2 types:
  • External, or the radiation emitting device is placed outside the body, and
  • Internal, when a radioactive source sealed in a container is placed directly near the cancer, inside the body
• Surgery: This modality may be used for diagnostic as well as for treatment purposes.
  • Laparotomy: An incision is made in the affected area to check for cancer in the internal organs. If a tumor is detected, then the same is removed during the procedure
  • Rarely, when feasible, a surgical excision of the tumor may be performed

Skin-directed therapies are used (and often in combination) when Skin Involvement in Hodgkin 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

Other therapy modes to treat the condition may involve:

• Transplantation of stem cells or bone marrow:
  • Stem cells are undifferentiated cells that are capable of differentiating into many different types of cells. While embryos are rich in these types of cells, adult humans also possess such cells. They have been used in medicine to heal and replenish damaged tissue. In cancer therapy, stem cells are being used for the generation of healthy blood-forming cells. High-dose chemotherapy and high-energy radiation therapy are known to harm the blood forming cells. In order to help patient make healthy blood cells following such therapies, stem cells could be harvested from the patient himself/herself (autologous), or from a close relative such as a sibling (allogeneic).  Stem cells are generally derived from circulating blood, umbilical cord blood, or bone marrow
  • Bone marrows (of large bones) are seats of generation for different types of blood cells. In order for the patient to have healthy circulating blood cells, the marrow could be harvested before therapy and re-injected into the patient. This procedure is known as bone marrow transplantation. It is reported that within a few weeks of transplantation, the healthy bone marrow cells start generating new white blood cells and red blood cells
• Monoclonal antibody therapy: This is a kind of immune therapy, where cells from the immune system of a single type are propagated in the laboratory and introduced into the patient. The cells recognize the cancer cells by their unique chemical signature. It then attaches to the cancer cells and destroys them. The antibodies can be also be used to deliver drugs or radiation in a targeted manner, to the cancer cells

How can Skin Involvement in Hodgkin Lymphoma be Prevented?

The exact cause of Hodgkin Lymphoma with Skin Involvement is unknown, and hence, no guidelines exist for the prevention of this type of cancer. However, by addressing some risk factors that are common to many illnesses as well as to cancer, the condition may be avoided. It includes the following factors:

• Adhering to a healthy diet, including eating fresh vegetables and fruits
• Regular physical activity
• Smoking cessation
• Regular visits to a healthcare professional, especially with advancing age
• If an individual is diagnosed with this lymphoma type, keeping accurate documentation filed, can help start follow-up care without any delay; especially in case of cancer recurrence
• Follow-up visits with a healthcare professional as recommended, for monitoring health after cancer treatment

What is the Prognosis of Skin Involvement in Hodgkin Lymphoma? (Outcomes/Resolutions)

• The prognosis of Hodgkin Lymphoma with Skin Involvement is considered to be good with early diagnosis and prompt treatment. The 5-year survival rates reported for individuals diagnosed with stage I and stage II cancers are 90-95%
• This type of lymphoma is reported to be one of the most curable types of cancer, since it is also curable when diagnosed during the later stages of lymphoma development. In most cases, the prognostic values are not generally known to be adversely affected
• However, when skin involvement occurs through hematogenous dissemination (spreading through blood), the prognosis is known to be typically worse
• Several factors may contribute to the final outcome of the condition and these include:
  • Stage of tumor: Early stages with localized cancer are reported to have better outcomes than later stages
  • Age: Younger patients are known to have a better outcomes than older patients
  • Health: Overall good health of an individual portrays a better outcome than poor health
  • Tumor size: Individuals with smaller-sized tumors generally have better outcomes than those with larger tumors
  • Metastasis: If the cancer has spread to other parts of the body, particularly to the vital internal organs, the recovery may be hampered
  • Response: When an individual’s body tolerates harsh cancer therapies and responds favorably to the treatments undertaken, then the outcome is generally improved
  • Removability of tumor: When the tumor can be surgically removed (and completely), it can have an impact on the outcome
  • Recurrence: If the tumor is recurrent, then the outcome may not be favorable

Additional and Relevant Useful Information for Skin Involvement in Hodgkin Lymphoma:

For more information on clinical trials, please visit the following website - www.clinicaltrials.gov.