It’s important to note, though, that these diseases are not skin cancer. The affected skin cells themselves are not cancerous. Instead, cancer develops in the white blood cells known as T lymphocytes, or T cells, which regulate the immune system and help the body stave off infections. These malignant T cells travel from the blood to the skin tissue, accumulating in the skin and forming patches, plaques, or tumor nodules. (1,2 PDF) With Sézary syndrome (also called Sézary’s lymphoma), however, the malignant T cells (called Sézary cells) are also found in the lymph nodes and blood, according to the National Institutes of Health. (3) Sézary syndrome is still not well understood, but it’s thought to be a more advanced or aggressive form of mycosis fungoides (thus categorized as stage 4 of mycosis fungoides). But it also may be a different illness altogether. (4,5) Either way, Sézary syndrome is the more fast-moving cancer of the two cutaneous T-cell lymphomas. (3) And mycosis fungoides (also called Alibert-Bazin syndrome or granuloma fungoides) is slow-moving and develops over several years, notes MedlinePlus. (6) Individuals with mycosis fungoides are likely to experience the following symptoms:
Extreme Itching This is a common symptom, according to the Cutaneous Lymphoma Foundation. (7)Red Patches These eczema- and psoriasis-like patches — the first visible sign of mycosis fungoides — appear over the torso or other areas of the body that are shielded from sun exposure, notes the National Organization for Rare Diseases. (8)White Spots Children, teens, and people of color can develop light spots on the skin instead of red, scaly patches, per the American Academy of Dermatology. (9)Raised Skin Changes Bluish-red circular or oval shaped plaques begin small and raised, usually on the buttocks. They may enlarge and start to slowly run together, covering about 10 percent of the body, and can mimic the look of the skin disorder exfoliative dermatitis. (8)Tumors Bluish or red-brown, these raised and thickened nodules (½ to 6 inches in diameter) are often located on the upper thighs and groin, breasts, armpits, and in the inside crook of the elbow. (The name mycosis fungoides comes from the fact that these tumors can resemble mushrooms, which are a type of fungus.) If the tumors ulcerate, infection can occur. (6,8)Insomnia Trouble sleeping may occur, likely due to the itch. (8)Malaise and WeaknessElevated TemperatureWeight LossAnemiaEnlarged Liver and Spleen (8)
Like mycosis fungoides, Sézary syndrome can take on the appearance of skin conditions, such as eczema, and generally appears on areas of the body that are not exposed to the sun. Sézary syndrome is more aggressive than mycosis fungoides and as such brings about additional symptoms, which can include:
Extensive Rash A thickened red rash covering at least 80 percent of the body, also called erythroderma, gives the appearance of a severe sunburn, according to the Cutaneous Lymphoma Foundation. (10)Widespread Itching (10)Skin Peeling (4)Swollen SkinSkin Thickening on the Palms or Soles of the Feet (9)Enlarged Lymph NodesHair Loss This is also known as alopecia.Fingernail and Toenail AbnormalitiesDry, Droopy Eyes This is called ectropion.Hepatosplenomegaly This indicates an enlarged liver and spleen. (3)
Sex Men are nearly twice as likely to be diagnosed as women. (6)Age Mycosis fungoides mostly impacts individuals older than 40, and Sézary syndrome most often develops in those older than 60. (8,11 PDF)Chromosomal Abnormality Most individuals with either disease have at least one chromosomal abnormality, which can lead to genetic hiccups that allow cells to grow and divide uncontrollably. For instance, oftentimes a person with mycosis fungoides has extra DNA in regions of chromosomes 7 and 17. Or individuals with mycosis fungoides experience a loss of DNA from regions of chromosomes 9 and 10. Meanwhile, those with Sézary syndrome often have gains or losses of DNA from regions of chromosomes 10 and 17 or chromosomes 8 and 17. (6,11)Genes While neither mycosis fungoides nor Sézary syndrome are considered inherited diseases, it is thought a variant of human leukocyte antigens (HLA) class 2 genes is associated with developing mycosis fungoides. (6) HLA genes work to help the immune system distinguish benign and natural proteins from those produced by viruses and bacteria. (6)
Other causation theories include retroviruses, such as human T-cell lymphotropic viruses, and exposure to carcinogenic (cancer-causing) substances. (8)
Physical Exam Any skin lesions, tumors, rashes, and anything else unusual will be examined and the skin will be photographed.Medical History Current and past health habits, routines, and treatments aimed at controlling skin issues will be discussed.Complete Blood Count With Differential This is a blood test to evaluate your overall health and detect an array of blood disorders.Skin Biopsy A small portion of the affected skin is removed and examined under a microscope by a pathologist. More than one skin biopsy is usually required.Immunophenotyping This laboratory test identifies antigens, or markers, on the surface of blood cells. It can also identify specific types of lymphoma.T-Cell Receptor (TCR) Gene Rearrangement Test A sample of cells is examined for a specific change in the genes that often leads to an excess of T cells.Flow Cytometry A sample of cells is stained with a special light-sensitive dye, placed in a fluid, and then passed through an instrument called a flow cytometer. Here, a laser measures certain characteristics, such as the size and shape of cells and the presence of biomarkers. (5)Imaging Tests Computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans may be used to determine whether lymph nodes or other organs are impacted. (2)Lymph Node Biopsy If lymph nodes feel swollen or if a PET scan identifies an enlarged lymph node, physicians may remove and examine tissue samples via a needle or surgery.Bone Marrow Aspiration and Biopsy Post-diagnosis, these tests determine if the disease has spread to the bone marrow. For the aspiration, a needle is used to extract a bone marrow sample from the back of the pelvis. For the biopsy, a piece of bone and solid marrow is removed from this same area. Both samples are evaluated under a microscope for signs of cancer. (4)
At the time of diagnosis, your healthcare team will also learn what stage your disease is in. Mycosis fungoides progresses slowly through several stages, but not all people impacted by mycosis fungoides progress through all of the stages. (6) Stage 1 The itchy, scaly, red rash (in patches or plaques) either appears on less than 10 percent of the body (stage 1A) or more than 10 percent (stage 1B), generally in areas not exposed to the sun, such as the lower abdomen, upper thighs, buttocks, and breasts. The rash can come and go for months or even years. It’s often difficult to diagnose at this stage, since the disease often resembles other skin disorders, like psoriasis. (5,6) Stage 2 At this point, any amount of the skin surface can be covered with patches or plaques, and the lymph nodes have become enlarged but are not cancerous (stage 2A). Also under the category of stage 2: The presence of any tumors (1 centimeter or larger) on the skin with noncancerous lymph node involvement (stage 2B). (5) Stage 3 Nearly the entire surface of the skin is reddened. Patches, plaques, or tumors are likely present. Lymph nodes may be enlarged, but still cancer-free. Abnormal lymphocytes may be detected in the blood, but they are not cancerous. During this stage, individuals may experience necrosis, when cells in the lower skin layers die. (5, 8) Stage 4 The progression to stage 4 means that the majority of the skin is red. Any amount of patches, plaques, or tumors are present, along with one of the following:
Cancer has spread to the lymph nodes and cancerous lymphocytes may be detectable in the blood; or lymph nodes are enlarged, but not cancerous, though cancerous lymphocytes are present in the blood. Both are considered stage 4A.Cancer has metastasized to other organs, possibly including the lymph nodes. Cancerous lymphocytes may be present in the blood (stage 4B). (5)
During stage 4, mycosis fungoides may spread throughout the body to other organs. The liver and spleen may become enlarged. At times, the heart muscle may be affected as well. Individuals often experience high temperatures, weight loss, anemia, and symptoms of malaise and weakness, too. Gastrointestinal symptoms (and possible ulcerations of the intestines), coughing, and difficulty swallowing may develop. If the brain is affected, eye pain and vision issues may occur. (8) Because Sézary syndrome is defined by the presence of malignant T cells in the lymph nodes and blood, this disease is also considered stage 4 mycosis fungoides. (5)
Prognosis of Mycosis Fungoides and Sézary Syndrome
The prognosis for those with mycosis fungoides varies depending on a number of factors, including how slowly or rapidly the disease is progressing. In any case, both mycosis fungoides and Sézary syndrome are difficult to cure. Because of this, the treatment goal is often to relieve symptoms (palliative care) and to improve quality of life, not to completely eradicate the disease. It’s not unusual for individuals to live normal lives for several years while in the midst of treatment. (2) It’s estimated that 65 to 85 percent of individuals with mycosis fungoides have early stage 1A or 1B disease. And the majority of those with early-stage mycosis fungoides never progress to a more advanced-stage of the disease, according to a report published in the International Journal of Health Sciences. (12) In addition, the same study noted that those with stage 1A disease have an almost unchanged life expectancy compared with those who never had cancer. But individuals who have an advanced-stage disease (stages 2B, 3, or 4A) that includes tumors, erythroderma (Sézary syndrome), or lymph node or blood involvement have a survival rate of about two to five years. (12) Those with advanced-stage mycosis fungoides or Sézary syndrome may want to consider stem cell therapy, such as allogeneic hematopoietic stem cell transplantation (SCT), which has yielded positive results, with some achieving long-term remissions, according to report published in October 2015 in the journal Dermatologic Clinics. (13)
Medications and Therapy Directed at the Skin
Treatment often begins here and it’s often effective for years. Options include:
Corticosteroids These steroids relieve red, swollen, and inflamed skin. They also can help to halt the growth of new cells, which means they work to eliminate cancerous T cells. (Long-term use can result in thinning and weakening of the skin.) (14 PDF)Retinoids These drugs, including bexarotene and tazarotene, are related to vitamin A and can boost immune reactions and kill cancer cells. (14)Imiquimod Cream Cream containing Aldara (imiquimod) is a type of immunotherapy used off-label in early-stage mycosis fungoides. (14)Topical chemotherapy Valchor gel (mechlorethamine) is FDA-approved for treating stage 1A and 1B mycosis fungoides who’ve received skin-directed therapy prior. There’s also the off-label topical CBiCNU (carmustine). Both petrolatum-based ointments are applied daily. (14)Phototherapy This is also called light therapy and there are two basic types: Narrow-band UVB therapies and PUVA (psoralen plus ultraviolet A) therapy. For Narrow-band UVB, a laser light is used to kill cancer cells. For PUVA, light-activated medication is paired with laser light to kill cancer cells. (Both of these phototherapies are used in combination with the biologic agents interferon or bexarotene.) (14)Electron Beam Radiation Therapy Here, radiation therapy can be applied to either the entire skin surface or to a specific area, without impacting internal organs. Total skin electron beam therapy is often used for those with thick, widespread plaques. (This therapy can be used as a stand-alone, as a combined treatment, or used sequentially with other therapies.) (14)
Systemic Therapies
These are often used alone or in combination with one another. They are also given along with skin-directed therapies.
Biologic or Immune Therapies These meds either help cancer cells die faster or bolster an individual’s own immune response to fight cancer. Medications can include oral retinoids, interferons, extracorporeal photopheresis, targeted antibody therapies, and imiquod cream. (14)Targeted Therapies Medications zero in on a specific molecule in cancer cells, allowing the therapy to kill the cells without damaging healthy cells. Alemtuzumab is an example of an FDA-approved targeted therapy for both mycosis fungoides and Sézary syndrome. (14)Chemotherapy Chemotherapy kills cancer cells that divide quickly. It also kills healthy cells. Some single-drug chemotherapies, like Folotyn (pralatrexate) and Gemzar (gemcitabine), have been shown to benefit those with very aggressive disease or those who have not responded to milder systemic therapies. Chemotherapy is generally only given if skin-directed therapy has failed or if the disease has spread beyond the skin. (14)Allogeneic Stem Cell Transplant Here, individuals are given high-dose chemotherapy or radiation to kill existing stem cells. Those killed-off stem cells are then replaced with stem cells from a matched donor that will form new, healthy white blood cells. This procedure is most used for those with advanced disease or failed standard therapies. (14)
Alternative and Complementary Therapies
Mycosis fungoides and Sézary Syndrome both require conventional medical treatments. That said, a variety of complementary and alternative therapies can be a successful part of an overall treatment plan, notably reducing stress. Any alternative or CAM approaches should be okayed by your healthcare team first. Some to consider, include: (11)
Guided imageryTai chiYogaMeditation
Take short showers. Max shower time should be 15 minutes and hot water should be avoided.Use a mild cleanser and laundry detergent. This means fragrance- and dye-free products.Avoid wash cloths or sponges. These can be too harsh on the skin.Apply thick ointments. Do this after gently patting skin dry post-shower and at least two other times daily.Wear breathable clothing. Loose-fitting clothes made of cotton help keep skin cool and sweat-free. (Sweating can worsen itch.)Use meds to help the itch. Antihistamines (like Benadryl or Claritin) may help ease itch. So may antidepressants like Zonalon or Remeron. (14)
Skin Infections It’s not unusual for those with mycosis fungoides or Sézary syndrome to have cracked skin, which can lead to bacterial skin infections and viral herpes skin infections. Signs of infection may include redness, swelling, increased pain, or weeping fluid. (14) Second Primary Cancer Those with mycosis fungoides (especially women) are at increased risk for a second primary malignancy, including non-Hodgkin lymphoma; Hodgkin lymphoma; melanoma; and lung, female breast, prostate, colon, and renal cancers, according to research published in August 2020 in the Journal of the American Academy of Dermatology. (15) Secondary cancers usually occur during the first year of diagnosis, noted an article published in 2017 in the Turkish Journal of Hematology. (16) Nervous System Involvement Central nervous system (CNS) involvement is very rare, but can include confusion, slowed thinking, lethargy, blurred vision, blindness, eye pain, and swelling of the optic nerve. These complications typically occur three to five years after the initial diagnosis, per research published in 2017 in Leukemia Research Reports. (17) There are about 3,000 new cases of mycosis fungoides confirmed in the United States each year. (11) While Sézary syndrome is the second most common form of cutaneous T-cell lymphoma after mycosis fungoides, its exact prevalence is unknown, says MedlinePlus. (19) There are likely a diverse set of reasons for this disparity, including access to information, insurance coverage, occupational exposures, and also a lack of education among dermatologists regarding mycosis fungoides presentations on skin of color. (20) While white patients with mycosis fungoides tend to experience red, eczema-like patches, Black patients and dark-skinned Latinos often have scaly, ring-shaped white spots that are thin and depressed in the center, notes Maritza Perez, MD, professor of dermatology at the University of Connecticut School of Medicine in Farmington. Because of this presentation, mycosis fungoides is frequently misdiagnosed in darker skinned individuals as atopic dermatitis, tinea versicolor, and vitiligo, according to the same report in Cogent Medicine. (20) Beyond differing presentation, age likely factors into many misdiagnoses, as well. “Mycosis fungoides in Black people tends to occur in one’s forties, as opposed to their fifties like Caucasians. Because of this, dermatologists are likely less inclined to suspect it’s cutaneous T-cell lymphomas in Black patients,” says Dr. Perez. “To diagnose this condition in Black patients at an earlier stage, there needs to be a high level of suspicion and you’ll likely need to see a dermatologist with experience in immunology.”
Diffuse large B-cell lymphomaFollicular lymphomaChronic lymphocytic leukemiaSmall lymphocytic lymphomaMantle cell lymphoma
Some rarer types of NHL include:
Cutaneous B-cell lymphomas, like mycosis fungoides and Sézary syndrome, that also attack the skinPrimary central nervous system lymphomaWaldenstrom macroglobulinemiaBurkitt lymphoma
NORD advocates for individuals with rare diseases and for the organizations that aim to improve the lives of these patients. On their site, you’ll find up-to-date info on mycosis fungoides, including diagnosis, treatment, the latest investigational therapies, and clinical trials. Cutaneous Lymphoma Foundation (CLF) This foundation is devoted to helping people with CTCL and their loved ones and caregivers. Their comprehensive coverage ranges from the basics — symptoms, diagnosis, and treatment — of this disease, to the most recent research developments. If you’re looking to engage with others who may be going through a similar experience, consider joining CLF’s Connections, an online community with private discussion boards. CancerCare CancerCare aims to help people cope with the emotional, physical, and financial difficulties of cancer. If you’re struggling with practical challenges, you can connect with a professional oncology social worker for free case management (over the phone). And online support groups, also led by oncology social workers, can provide guidance, as well. When it comes to CTCL, specifically, CancerCare has a wealth of info, from tips on dealing with symptoms to advice for working with your treatment team. Genetic and Rare Disease Information Center GARD, funded by the National Institutes of Health, provides up-to-date and accessible information on rare or genetic diseases, including CTCL. Beyond the basics, their website includes tips on finding a specialist as well as details on the latest CTCL research.
