A 68-year-old woman presents with an itchy, scaly red rash on her back for 9 months. She denies history of eczema, psoriasis, or other skin diseases. She smokes a half-pack of cigarettes per day but is otherwise healthy. On examination, erythematous, scaly patches, plaques, and nodules of irregular size and shape are seen on the back. She has no lymphadenopathy and no other symptoms. Skin biopsy of one plaque demonstrates neoplastic T cells with a halo appearance and Pautrier microabscesses.
What is your diagnosis?
Submit your diagnosis to see full explanation.
Mycosis fungoides is the most prevalent form of cutaneous T-cell lymphoma. It is classified as an indolent lymphoma and has a classical form and other variants and subtypes. Mycosis fungoides generally occurs in older individuals and incidence increases throughout age; however, pediatric cases of mycosis fungoides have been reported.1 The condition is more prevalent in men and African Americans, with mycosis fungoides developing twice as often in men as in women.1
Currently, the exact etiology of mycosis fungoides is unknown. Researchers have extensively explored possible hypotheses regarding its etiology, including an underlying viral argent or persistent antigen activation (such as Staphylococcus aureus), epigenetic alteration, and immune dysregulation.1,2 Some possible risk factors that have been studied include higher body mass index, cigarette smoking, eczema, and various industrial/occupational exposures.3
Classic mycosis fungoides is a slowly progressive disease. Patients can initially present with erythematous pruritic patches or plaques with scaling and variability in size and/or shape. The lesions are usually present in areas of the body that are not exposed to sunlight, including the buttocks, upper thighs, and trunk.1 Staging of mycosis fungoides ranges from I-IV, with later stages of the disease being characterized by tumors, erythroderma, invasion into peripheral lymph nodes, and visceral organ involvement.1 Folliculotropic mycosis fungoides is the most common subtype; it carries a worse prognosis with lesions typically located in the head and neck regions.1 Less common subtypes include pagetoid reticulosis, which generally presents with a large, single, scaly and erythematous plaque; hypopigmented mycosis fungoides, which occurs most commonly in patients with dark skin; and granulomatous slack skin, which is characterized by granulomatous infiltrate and loss of elastic fibers.4
The patches and plaques of mycosis fungoides exhibit atypical band-like T-cell infiltrate in the upper dermis, along with neoplastic T cells with cerebriform nuclei in the epidermis. The neoplastic T cells are often described as having a halo appearance due to the surrounding clear cytoplasm. T cells can also build up in the epidermal basement membrane.1 A specific but insensitive marker in individuals with mycosis fungoides is the presence of Pautrier microabscesses, which contain Langerhans cells and malignant T cells.5
Further laboratory testing for diagnosis can include immunohistochemical staining and examining T-cell clonality. Most often, immunohistochemical staining is positive for CD4+ T cells; however there have been cases of CD8+ mycosis fungoides.6 Other findings supporting the diagnosis of mycosis fungoides can be the loss of T-cell antigens (CD2, CD3, CD7, etc).1 T-cell clonality can be used as a confirmatory diagnostic test for mycosis fungoides. Increasingly sensitive methods such as next-generation sequencing have been studied for testing T-cell clonality.7 Next-generation sequencing examines T-cell receptor gene arrangements and scans for an overrepresentation of a sequence.
It is worthwhile to note that mycosis fungoides is often difficult to diagnose, especially in earlier stages of the disease, as some histopathologic features may not be present in early patches. It resembles other common skin diseases, including eczema, psoriasis, and inflammatory dermatitis.1 Therefore, biopsy is important for diagnosis. To differentiate between the possible diagnoses, it is crucial to consider and integrate clinical, histopathologic, and laboratory findings. The International Society for Cutaneous Lymphoma has established a 4-point algorithm for helping diagnose early-stage mycosis fungoides.5 Studies have shown the algorithm to be a valid method for diagnosing the condition, but further modifications to the algorithm may be needed to improve its specificity.8
Medical treatments for mycosis fungoides focus on controlling the extent of the disease. Mycosis fungoides is characterized by a chronic relapsing course; as a result, patients frequently receive multiple rounds of therapy. Generally, treatment options for patients in earlier stages of the disease are categorized as topical treatments (ie, nitrogen mustard and topical corticosteroids or retinoids) and/or ultraviolet light-based phototherapies.9 Total body skin electron beam is effective phototherapy and is generally used for patients with increased patch/plaque coverage.9 Patients who have a later stage of mycosis fungoides or refractory, early-stage mycosis fungoides benefit from systemic therapy. For systemic therapy, interferons, retinoids, and histone deacetylase inhibitors are utilized.9 Immunosuppressive therapies are generally avoided unless the patient has aggressive, late stages of mycosis fungoides.9 Allogeneic hematopoietic stem cell transplantation for refractory or advanced mycosis fungoides has also been reported as a treatment option.9 Targeted immunotherapy is a relatively new area of therapy that has become integrated into mycosis fungoides treatment. Currently, alemtuzumab, a monoclonal antibody against CD52, has been found to be effective for mycosis fungoides but does increase the risk of opportunistic infections.9 A recently completed phase 3 clinical trial of mogamulizumab, a promising new monoclonal antibody against CCR4, reported prolonged progression-free survival in patients with cutaneous T-cell lymphoma.10
The patient in our case was diagnosed with stage I mycosis fungoides and prescribed a high-potency topical corticosteroid to be applied twice daily to her skin lesions. At 6-month follow-up, she was found to have had complete remission.
Annie Dai, BA, is a medical student; Talia Noorily, BA, is a medical student; and Christopher Rizk, MD, is a dermatology fellow at Baylor College of Medicine, in Houston, Texas.
1. Hwang ST, Janik JE, Jaffe ES, Wilson WH. Mycosis fungoides and Sézary syndrome. Lancet. 2008;371(9616):945-957.
2. McGirt LY. Latest insights into pathogenesis of mycosis fungoides and cutaneous T-cell lymphoma. G Ital Dermatol Venereol. 2017;152(2):158-168.
3. Aschebrook-Kilfot B, Cocco P, La Vecchia C, et al. Medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and Sézary syndrome: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014(48):98-105.
4. Nashan D, Faulhaber D, Stander S, Luger TA, Stadler R. Mycosis fungoides: a dermatological masquerader. Brit J Dermatol. 2007;156(1):1-10.
5. Pimpinelli N, Olsen EA, Santucci M, et al. Defining early mycosis fungoides. J Am Acad Dermatol. 2005;53(6):1053-1063.
6. Burg G, Kempf W, Cozzio A, et al. WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects. J Cutan Pathol. 2005;32(10):647-674.
7. Sufficool KE, Lockwood CM, Abel HJ, et al. T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides. J Am Acad Dermatol. 2015;73(2):228-236.
8. Vandergriff T, Nezafati KA, Susa J, et al. Defining early mycosis fungoides: validation of a diagnostic algorithm proposed by the International Society for Cutaneous Lymphomas. J Cutan Pathol. 2015;42(5):318-328.
9. Duvic M. Choosing a systemic treatment for advanced stage cutaneous T-cell lymphoma: mycosis fungoides and Sézary syndrome. Hematology Am Soc Hematol Educ Program. 2015;2015(1):529-44.
10. Kim YH, Bagot M, Rook AH, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9):1192-1204.