Cutaneous T-cell lymphomas (CTCLs) is the second most common type of extranodal lymphomas (after primary GI lymphomas).1,2 The incidence of CTCLs increases with age, with a median age of diagnosis in the mid 50s.1 This type of lymphoma affects more men than women and is more common among black individuals than white individuals.3 Mycosis fungoides (MF) is the most common subtype of primary CTCL.1 Also known as Alibert-Bazin syndrome, MF was first described in 1806 by Jean-Louis-Marc Alibert.4
As a T-cell lymphoma, MF is caused by an expansion of malignant skin-homing T cells.1,2 These cancer T cells can extend from the lesions to nearby skin regions, leading to patches, plaques, and tumors. In later stages, T cells can spread to the blood, lymph nodes, and viscera.2
Several risk factors are associated with a predisposition to T-cell lymphoma. In addition to older age and male sex, genetic factors have been associated with MF, such as the presence of HLA-DRB1*11 or HLA-DQB1*03 alleles.4-6 Environmental factors also have been associated with MF. Workers with the highest risks include glass formers, potters, ceramic workers, and factory workers in the paper and wood industries.7 However, specific carcinogens, if any, have yet to be determined. Infectious agents such as human T-cell lymphoma virus-1 (HTLV-1) and Epstein-Barr virus have been identified as risk factors for other cutaneous lymphomas, but current data do not suggest they play a role in the development of MF.8,9
Patients present with multiple patches, plaques, and/or skin tumors in sun-protected areas of the body.1 They often describe a long history (10-15 years) of chronic dermatitis consisting off itchy patches that appear and spontaneously resolve.1 In the early patch stage, patients will have numerous erythematous, scaly patches, as well as macules that vary in size and have well-defined borders.1,2 The lesions, which range in color from orange to purplish red, often erupt and disappear spontaneously without scarring.1,4 In the early stages, diagnosis can be difficult and often requires numerous biopsies.2 Itching is a common complaint during these stages.
Differential diagnosis of MF includes tinea corporis, vitiligo, eczema, contact dermatitis, and psoriasis in the early patch or plaque stages and B-cell lymphoma, sarcoidosis, deep fungal infection, carcinoma cutis, and atypical mycobacterial infection in the tumor stage.1,2 Patients with dark skin can develop hypopigmented MF, which needs to be differentiated from other hypopigmenting diseases, such as vitiligo.1,2
Histologically, MF samples contain an infiltration of reactive T cells and neoplastic T lymphocytes in the upper dermis.1 These cells are characterized by hyperconvoluted cerebriform nuclei. Neoplastic T cells also display an epidermotropism and form intraepidermal Pautrier microabscesses. During the tumor stage of the disease, there can be nodular infiltrates in the dermis. Immunohistologic staining shows CD4+ mature T cells within lesions.1,2
Patients with MF can experience symptoms such as fever, chills, weight loss, and malaise.1,3 Other findings include scaling and cracking of the palms and soles, hair loss, nail dystrophy, and ankle edema.1
Once patients are diagnosed, workup includes evaluation of the extent of skin lesions, localization and measurement of lymph nodes involved, identification of visceral symptoms, as well as blood work and imaging to assess tumor burden and identify systemic spread.1,2
Treatment for MF depends on the stage of the disease and whether the condition is limited to the skin or has spread to lymph nodes. First-line treatment of topical disease includes topical corticosteroids, ultraviolet B phototherapy, psoralen and ultraviolet A (PUVA), and localized radiotherapy.1,2,10 Systemic treatment includes interferon alpha or gamma, oral retinoids (vitamin A), low-dose methotrexate, total skin electron beam therapy, and/or chemotherapy.1,2,10 Targeted therapies also can be used as alternatives to chemotherapy to debulk large tumors. Alemtuzumab, a monoclonal antibody that binds to CD52 on mature lymphocytes, is an example of targeted therapy.11 In August 2018, the FDA approved mogamulizumab, a monoclonal antibody targeting the CC chemokine receptor 4 on T cells, for patients with relapsed or refractory MF.12
With early detection, the overall prognosis for patients with MF is good. Patients with disease limited to the skin have a 5-year survival rate close to 100%, whereas patients with lymph node or visceral involvement have 5-year survival rates of 68% (low-risk), 44% (intermediate-risk), or 28% (high-risk).3,13
The patient in the above case was treated with topical corticosteroids and ultraviolet B phototherapy for the rash. His lesions resolved, and he has not had a relapse.
Click to the next page for Case 2.