What is Mycosis Fungoides?
Primary cutaneous lymphomas are a type of non-Hodgkin’s lymphoma, a cancer that starts in cells called lymphocytes, which are part of the body’s immune system. These lymphomas are the second most common form that develops outside of the lymph nodes. They can start in either T cells, B cells, or NK cells, all of which are types of immune cells.
The Cutaneous T-Cell Lymphomas (CTCL) are a varied group of these kinds of lymphomas which behave differently from similar types found elsewhere in the body, despite looking the same under a microscope.
Mycosis fungoides is the most common type of CTCL. It is a cancer that starts in T-cells that are in the outermost layer of the skin, particularly in a specific type of T-cell known as ‘memory T-cells’. These cells retain a record of past illnesses, helping the immune system respond faster and more effectively when the same threat is encountered again. These memory T cells are equipped with specific proteins, CD4+ and T-cell receptor (TCR), on their surfaces.
What Causes Mycosis Fungoides?
The cause of mycosis fungoides, a type of skin lymphoma, isn’t fully understood. However, several theories have been suggested:
* Changes in a person’s genes, like missing or moving parts of several different chromosomes or chromosome sections. This means that the body’s normal functions get disrupted, leading to diseases like mycosis fungoides.
* Contact with certain solvents and chemicals in the environment or at work is thought to play a part in causing the disease.
* Some experts believe that a type of virus known as human T-lymphotropic virus Type 1 might cause mycosis fungoides. However, there’s not enough evidence to confirm this yet.
Additionally, certain substances in the body, called cytokines (such as IL-2 and IL-4), might also play a role. These cytokines are found at high levels in patients with mycosis fungoides and a related condition called Sézary syndrome. Cytokines are proteins that can affect the immune system, leading to inflammation and potentially other problems.
Risk Factors and Frequency for Mycosis Fungoides
Mycosis fungoides, a type of non-Hodgkin lymphoma, affects around 6 people per million each year in Europe and the United States. This condition makes up 4% of all non-Hodgkin lymphoma cases. It is mainly observed in adults over 50 years old, and occurs more frequently in men than women, with a ratio between 1.6 and 2. Interestingly, it’s more common amongst individuals of Black ethnicity compared to Caucasians or Asians.
Signs and Symptoms of Mycosis Fungoides
Mycosis fungoides is a type of skin disease, and its symptoms can change based on how advanced the condition is. Its clinical signs tend to be different in every stage of the disease:
- Patch stage: The first visible signs of mycosis fungoides might be red or brown patches on the skin, which could be a bit thin. These patches can be in various sizes and locations, often in areas that are usually covered by clothing like the buttocks or upper thighs. These patches are sometimes wrongly referred to as “plaque parapsoriasis” as they’re not plaques but patches.
- Plaque stage: During this stage, bigger lesions appear on the skin, along with new ones. The outer edges of the lesions become raised and well-defined. They often have shapes like rings or horseshoes. Sometimes they show up on the face and scalp.
- Tumor stage: In this stage, people may see larger red-purple lumps or nodules. The likelihood of the disease spreading to lymph nodes or other organs becomes higher as it progresses from the patch stage to the plaque stage, and finally, the tumor stage.
There are also less common or unique forms of this skin disease, with atypical symptoms:
- Blisters or vesicles
- Purplish spots or patches
- Changes in the color and texture of the skin
- Localized skin changes caused by damage to sweat glands
- Lighter patches of skin (Primarily found in children)
There are clinical forms of mycosis fungoides according to the WHO-EORTC Classification for Cutaneous Lymphomas:
- Follicular or folliculotropic mycosis fungoides
- Pagetoid reticulosis or Woringer-Kolopp type
- Granulomatous slack skin
One of the forms of cutaneous lymphoma is the Sezary syndrome, which is characterized by severe skin redness and itching, swollen lymph nodes, and unusual lymphocytes in the blood (known as Sezary or Lutzner cells). Sezary syndrome is understood as a leukemic phase of T-cell cutaneous lymphomas. This syndrome can cause other issues including lagophthalmos (inability to close the eyes completely), hair loss, thickening of the skin on the palms and soles, and nail deformities. Sezary Syndrome needs to be differentiated from total body redness seen in mycosis fungoides progression. The WHO-EORTC classifies mycosis fungoides and the Sezary Syndrome as separate diseases.
Testing for Mycosis Fungoides
If your doctor suspects you have mycosis fungoides/Sezary syndrome, they will follow several steps to confirm this diagnosis.
Firstly, they will carry out a thorough physical examination, focusing on your skin. They will check the type, size, and extent of any skin lesions, as well as look for any signs of ulcers in these lesions. For more advanced lesions (ones that are categorized as ‘tumor stage’), they will check the number, size, and location of these. They will also check for swelling in your lymph nodes and organs.
Next, they might perform a skin biopsy. A biopsy involves taking a small sample of skin from the most hardened area of the skin lesion. The sample will be analyzed to see what kind of immune cells (like CD2, CD3, CD4, CD5, CD7, CD8, and CD20) are present and to check if the T-cells (a type of immune cell) show signs of abnormal changes.
Furthermore, the doctor may order blood tests, including a complete blood cell count, a test to check your liver’s health, and lactate dehydrogenase (LDH) which is an enzyme found in your blood that can increase when tissues are damaged or a disease is present. In addition, a test to check the arrangement of TCR genes (which form part of your immune response) and count of Sezary cells (a type of white blood cell) may be performed, often using a method called flow cytometry, a technology that can count and sort cells quickly.
Radiologic tests such as chest X-rays, ultrasound scans of peripheral lymph nodes (nodes that are not in your chest or abdomen), CT (computed tomography) scans of the chest, PET (positron emission tomography) scans using a type of sugar called fluorodeoxyglucose (FDG), and MRI (magnetic resonance imaging) may also be used. These tests can help the doctor see if your lymph nodes or organs are affected, depending on the stage of your disease.
Lastly, if there are concerns about certain lymph nodes (for example, they are unusually firm, irregular, large (over 1.5 cm in diameter), or fixed in place), the doctor may order a lymph node biopsy. This procedure involves removing a piece of a lymph node to analyze it for any signs of disease. The lymph node is typically chosen based on its size or the results of an FDG-PET scan, and the removed tissue is analyzed further with microscopy, flow cytometry, and checking the arrangement of T-cell receptor genes.
Treatment Options for Mycosis Fungoides
Mycosis fungoides is a type of skin cancer that progresses slowly. The treatment strategies for early-stage and advanced-stage mycosis fungoides differ.
Early Stage (IIA or below):
In the early stages, the disease might be treated with several different methods, like applying certain creams or ointments to the skin (topical treatments), such as corticosteroids, nitrogen mustards, bexarotene, or imiquimod. Other options might involve special light therapy treatments such as psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB). When the disease is confined to specific areas, radiation can be used to treat these localized skin changes. If a patient has extensive large patches on the skin that are causing significant discomfort and treatment response is urgently needed, doctors may suggest total skin electron beam therapy (TSEBT) or a combination of topical treatment and medication.
If the disease does not respond to skin-directed therapies or if the skin symptoms are severe or extensive, alternative systemic therapies (medication that works throughout your entire body) might be suggested. This includes drugs like retinoids or interferons, histone deacetylase (HDAC) inhibitors, or low-dose methotrexate. This approach might also be chosen for patients with a worse prognosis, which means their disease may cause more serious problems down the line.
Advanced Stage (IIB to IV):
When the disease progresses to advanced stages, it becomes more diverse in how it affects people, particularly because it starts to involve areas outside of the skin or creates advanced skin lesions, like tumors. This stage is often chronic, or long-term, and persistent, with relapses occurring over time. The main goals of treatment during this stage are controlling the disease long-term, relieving symptoms quickly, and managing potentially life-threatening aspects of the disease.
If a patient’s tumors affect a limited part of their body (typically less than 10% of the body’s surface area), localized radiation might be recommended in addition to skin-directed therapy for additional skin patches or plaques. For more widespread tumors, total skin electron beam therapy (TSEBT) or systemic therapies might be used. After TSEBT, other skin-directed or systemic therapies can help prolong the beneficial effects of the treatment. For more extensive disease, a combination of skin-directed therapies and systemic therapies might be required. These might include medications like methotrexate, bexarotene, targeted immunotherapy. In some cases where the disease is difficult to control, a patient might be considered for a transplant procedure where they receive healthy cells from a donor to replace their own cells.
What else can Mycosis Fungoides be?
Mycosis fungoides, a type of skin condition, can often be confused with more common skin disorders such as eczema, psoriasis, parapsoriasis, photodermatitis, or drug reactions. When diagnosing this condition, it’s important to also consider other possibilities that might show similar symptoms.
- Atopic dermatitis, contact dermatitis, drug eruptions, or erythrodermic psoriasis: These conditions can all cause itchy, red, and inflamed skin that looks similar to mycosis fungoides.
- Psoriasis: Another skin disorder that can be mistaken for mycosis fungoides.
- Sezary syndrome: This condition may resemble the more extreme, erythrodermic (red and inflamed) form of mycosis fungoides.
- Other types of lymphomas: Certain lymphomas, including subcutaneous panniculitis-like T cell lymphoma, primary cutaneous anaplastic large cell lymphoma, cutaneous gamma/delta T cell lymphoma, or cutaneous B cell lymphoma, can also present skin symptoms that are similar to mycosis fungoides.
What to expect with Mycosis Fungoides
The outcomes for mycosis fungoides and Sezary syndrome, two types of skin cancer, can greatly vary. How these conditions progress and the chances of recovery depend heavily on their stage at the time of diagnosis. This staging is referred to as “TNMB staging”.
In some cases, several factors can imply a less favourable outcome:
1. If the disease has spread beyond the skin (known as stage IV),
2. If the patient is older than 60,
3. If there is a presence of large cell transformation (LCT), which means that the cancer cells have changed and grown,
4. If the LDH (lactate dehydrogenase, a chemical often found in higher amounts in the body when tissue damage occurs) levels are increased,
5. If the type of mycosis fungoides is folliculotropic, which means it primarily affects hair follicles,
6. If the cancer is distributed across several regions of the body at the point of diagnosis.
Possible Complications When Diagnosed with Mycosis Fungoides
Marked itching
- Swelling of the lymph nodes
- Nail disorders
- Inflammation of the fatty layer under your skin
- Skin ulcers
- Scarring hair loss