Cutaneous lymphoma

What is cutaneous lymphoma?

Cutaneous lymphoma (or skin lymphoma) is a very rare form of cancer in the skin. Altered lymph cells – the lymphocytes – settle in the skin. This special type of white blood cell is normally an important part of the immune defense. They combat invading pathogens such as bacteria, viruses, fungi and parasites.

As with all types of cancer, the genetic material of a cell changes first. It mutates and becomes a cancer cell. In contrast to healthy cells, cancer cells can divide and multiply unchecked. They can grow into surrounding tissue and spread to other, more distant organs.

Cutaneous lymphoma – wide variety of forms

Experts classify cutaneous lymphoma in the group of “extranodal non-Hodgkin’s lymphomas”. The word “extranodal” means that the cancer develops outside the lymph nodes. Most other lymphomas, however, develop within the lymph nodes (nodal lymphomas).

A distinction must also be made between the following:

• Primary cutaneous lymphomas that develop in the skin.
• Secondary cutaneous lymphomas that develop elsewhere and form “offshoots” in the skin. These are usually primary nodal lymphomas or leukemias (blood cancers).

There are many different forms of skin lymphomas with a wide variety of appearances. They can be divided into two groups.

• T-cell lymphomas: The majority of cutaneous lymphomas (around 65 percent) are T-cell lymphomas, i.e. they develop from T-lymphocytes. In turn, there are many different subgroups of T-cell lymphomas.
• B-cell lymphomas: Approximately 25 percent of cutaneous lymphomas fall into the group of B-cell lymphomas, i.e. they originate from altered B lymphocytes. Here, too, there are various subgroups.

The other skin lymphomas are very rare and arise from other cells of the immune system.

Cutaneous lymphoma is difficult to recognize

Cutaneous lymphoma is often not easy for patients and healthcare professionals to recognize because it develops slowly and initially causes no or hardly any symptoms. In contrast to other types of skin cancer, it does not cause any typical skin changes. Some patients have dry, itchy skin or red patches. However, this occurs in the context of many skin diseases and is not a clear symptom of cutaneous lymphoma.

Treatment always depends on the type, aggressiveness and spread of the cutaneous lymphoma. For example, surgery, light therapy, radiation or medication can be used.

Cutaneous lymphoma – frequency and age

Cutaneous lymphoma is a rare type of skin cancer. We estimate that only around 100 people in Switzerland are diagnosed with skin lymphoma each year. This means that only 1 in 100,000 of the population suffers from the disease. Other forms of skin cancer are much more common.

The typical age of onset depends on the type of skin lymphoma. In principle, skin lymphoma can occur at almost any age – from young to old. Cutaneous T-cell lymphoma is significantly more common in men than in women (around 75 percent).

Cutaneous lymphoma: causes and risk factors

Like any cancer, cutaneous lymphoma begins when the genetic material (DNA) of a cell changes – it mutates and becomes a cancer cell. The malignant lymphocytes then divide and multiply uncontrollably. They can invade neighboring tissue and form cancer metastases in other organs. However, it often remains unclear why a healthy cell becomes a malignant cancer cell. The causes of cutaneous lymphoma are therefore still largely unknown.

An intact immune system is normally able to recognize and eliminate such pathological cells. If it is weakened, control sometimes no longer works. In addition, cancer cells can change in such a way that they can evade immune control.

One risk factor for cutaneous lymphomas is exposure to high doses of radioactive radiation, which alters the genetic material of the lymphocytes. In contrast to other types of skin cancer, neither excessive sun exposure, frequent sunburns in childhood and adolescence, nor diet or genes play a role in skin lymphoma.

Symptoms: Cutaneous lymphoma is often inconspicuous

Cutaneous lymphoma usually develops slowly and causes no or hardly any symptoms for a long time. Typical skin changes as in light or black skin cancer often do not occur. There are also many different forms and subgroups of cutaneous lymphomas – with many facets and a wide variety of manifestations. The symptoms sometimes resemble eczema and other harmless skin conditions.

We classify T- and B-cell lymphomas according to the so-called WHO-EORTC classification.

T-cell lymphomas: symptoms

T-cell lymphomas include various forms and subgroups, each of which is associated with different symptoms. An overview of the most important types and their symptoms:

1. mycosis fungoides: symptoms

Mycosis fungoides (MF) is the most common T-cell lymphoma, accounting for around 50 percent of cases. It usually progresses in three stages:

• Eczema stage: At the beginning, flat, slightly scaly and reddened “patches” develop, especially on the sides of the upper body and the inner thighs and arms. Visually, the skin change resembles eczema (hence the eczema stage). This can persist for years or even decades without changing. It often improves after sunbathing.
• Plaque stage: The skin lesions thicken and now protrude above the normal skin level – they are “raised”. The so-called plaques can occur anywhere on the body. Most people remain at this stage for the rest of their lives, but in 20 percent of cases the skin disease develops further.
• Tumor stage: The cancer cells multiply and form nodules. The cells die in the middle and open ulcers develop.

Rarely, mycosis fungoides manifests itself as a reddening of the entire skin (erythroderma) in combination with the three stages.

2 Sézary syndrome: symptoms

Sézary syndrome is a very aggressive variant of T-cell lymphoma of the skin. At around two percent, it is very rare. Characteristics of Sézary syndrome are

• Erythroderma: The entire skin is reddened and scaly.
• Swollen lymph nodes in the armpits and groin.
• The tumor cells leave the skin and enter the bloodstream, where they can be detected in large quantities.

3 CD30-positive lymphoproliferative diseases of the skin: symptoms

Two diseases belong to this group: Lymphomatoid papulosis and anaplastic large cell lymphoma. What both have in common is that the protein CD30 can be detected on the surface of the cancer cells.

Lymphomatoid papulosis is comparable to a chronic skin disease. It remains limited to the skin and does not spread to the lymph nodes or other organs.

The following symptoms are possible:

• Nodules on the skin: They usually measure only a few millimeters, but can also be two to three centimeters in size. They heal within a few weeks without treatment – the cancer cells also die in the process. Sometimes the skin turns black. Small ulcers can also develop.
• At the same time, new nodules form and the process starts all over again.

Some patients suffer from other lymphomas, such as mycosis fungoides or a lymphoma that affects the entire body. Further symptoms then develop.

Anaplastic large cell lymphoma can be recognized by the following symptoms:

• Lumps form on the skin, usually individually or in small groups.
• These lumps often develop into open ulcers.
• Only sometimes do the lumps heal on their own, as in lymphomatoid papulosis.

B-cell lymphomas: symptoms

B-cell lymphomas include the following forms – with the respective symptoms:

• Primary cutaneous marginal zone lymphoma (PCMZL): Individual or groups of papules and nodules develop on the skin, usually on the trunk of the body and the upper extremities. They are reddish to purple in color.
• Primary cutaneous germinal center lymphoma (PCFCL): Skin-colored to reddish, firm nodules and plaques form on the skin, usually on the head, neck, nape of the neck or upper trunk of the body.
• Primary cutaneous diffuse large B-cell lymphoma (leg type) (PCBLT): Typical are red-bluish nodules, usually on the skin of the lower legs – hence the name. They grow rapidly and can form ulcers.

Diagnosis of cutaneous lymphoma

The diagnosis of cutaneous lymphoma is not easy. On the one hand, skin lymphoma is a rare form of skin cancer that we do not often see in everyday life. And on the other hand, it produces many different forms and appearances.

Diagnostics always begins with a discussion of the patient’s medical history (anamnesis). Among other things, we ask questions about the type, intensity, duration and location of the symptoms. However, existing illnesses, risk factors such as X-ray exposure in everyday life and at work or the intake of medication can also provide initial indications of cutaneous lymphoma.

This is followed by a physical examination, during which we take a closer look at the skin. We check what type of skin changes (e.g. papules, nodules, ulcers) are present, what they look like, where they are located, whether and how they are colored and how far they have spread. We also palpate the lymph nodes and check whether they are swollen.

It is important for the diagnosis to take a tissue sample (biopsy) from the suspected skin area. Dermato-pathology specialists then analyze the cells histologically under a microscope. They can recognize what the cells look like, whether they are benign or malignant and how far the disease has spread. There are many different appearances of the cells and categorizing them into a group or subgroup of cutaneous lymphomas is a challenge. The diagnosis of “cutaneous lymphoma” can be made with a high degree of certainty on the basis of the biopsy.

This is followed by further examination methods and imaging procedures to determine the stage, spread and aggressiveness of the skin cancer.

Further examination methods

• Blood test
• Molecular biological tests
• sometimes bone marrow examination
• X-ray examination
• Ultrasound examination (sonography)
• Computed tomography (CT)
• Magnetic resonance imaging (MRI = magnetic resonance imaging)
• PET/CT: Positron emission tomography in combination with CT
• PET/MR: Positron emission tomography in combination with MR

Based on the examination results, we classify cutaneous lymphoma according to the WHO-EORTC classification. Depending on the spread of the skin lymphoma, there are also different stages. The decisive factor is whether the skin cancer is still limited to the skin or has already spread to the neighboring lymph nodes or other organs such as the liver or lungs.

Cutaneous lymphoma: prevention, early detection, prognosis

The causes of skin lymphoma are still largely unclear. Therefore, you cannot prevent cutaneous lymphoma.

Researchers have so far identified radioactive radiation as the only risk factor. If you have to deal with this professionally, make sure you take adequate protective measures. Otherwise, consult a dermatologist if you notice any unusual changes to your skin.

There are no special measures for the early detection of cutaneous lymphoma. However, you can have a general skin cancer screening in Switzerland. Swiss health insurance companies pay for this skin examination every two years for people over the age of 35.

Course and prognosis of cutaneous lymphoma

The course and prognosis depend on the type of skin lymphoma and its aggressiveness and spread. In many cases, cutaneous lymphomas remain confined to the skin for many years or even for life. They do not spread to other tissues and organs. The prognosis in these cases is very good. However, there are also more aggressive variants that grow quickly and affect other organs. Then the prognosis is less favorable. In Sézary syndrome, the tumor cells spread via the bloodstream. The course and prognosis are less favorable.

Some figures on how many of those affected are still alive five years after diagnosis:

• Mycosis fungoides: about 80 percent
• Primary cutaneous anaplastic large B-cell lymphoma: approximately 90 percent
• Lymphomatoid papulosis: 100 percent
• Primary cutaneous germinal center lymphoma: approximately 98 percent
• Primary cutaneous marginal zone lymphoma: 100 percent
• Large B-cell lymphoma (leg type): approximately 63 percent

Cutaneous lymphoma: treatment depends on the type and spread

The treatment of cutaneous lymphoma depends on the type, aggressiveness and extent of the cancer. But your age and general state of health also play a role. Sometimes it is sufficient to treat the skin lymphoma locally. If the cancer has already affected other organs, we choose therapies that are effective throughout the entire body (systemic). We usually combine several treatments in order to increase the effectiveness of the treatment.

Sometimes the cutaneous lymphoma regresses on its own, for example in the case of lymphomatoid papulosis. In other cases, we opt for a wait-and-see strategy – we initially only observe and monitor the skin lymphoma.

Self-help groups

The exchange with people who are affected by the same disease can be a great support in coping with the disease. Advice on finding a suitable self-help group is available from Selbsthilfe Zürich. Self-Help Zurich and the University Hospital Zurich are cooperation partners in the national project “Health literacy thanks to self-help-friendly hospitals”.