Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutanecus T-cell lymphoma (CTCL). Mycosis fungoides accounts for 60% of new cases of cutaneous T-cell lymphoma, while SS accounts for only 5%. Mycosis fungoides is a mature T-cell extranodal non-Hodgkin’s lymphoma (NHL) of cutaneous origin.Sezary syndrome is an erythrodermic leukemia variant of cutaneous T-cell lymphoma characterized by marked blood invasion and lymph node enlargement. In the updated EORTC and WHO classifications of cutaneous T-cell lymphoma, mycosis fungoides is a tumor characterized by inert presentation, whereas SS is characterized by aggressiveness. However, the literature suggests that conversion to large T-cell lymphoma can occur in some patients with mycosis fungoides, the diagnostic criterion for which is a large cell count of >25% in biopsies of MF lesions. Cutaneous mycosis fungoides, a malignant neoplasm originating in the lymphoreticular tissue of the skin, has been shown to be a cutaneous T-cell lymphoma of primary origin of T cells, particularly T helper cell subsets. The course of the disease is slow and chronic, but it may involve lymph nodes, bone marrow and viscera and develop into a systemic lymphoma. It is more common in middle-aged and elderly people, but can also be seen in adolescents, and is slightly more common in men than in women, with a male to female ratio of 1.6 to 2.3:1. Etiology of the disease: The cause of the disease is unknown. Genetic, infectious and environmental factors (chemical agents such as air pollutants, insecticides, solvents, inhalants, decontaminants, disinfectants; drugs such as supra-pain medications, tranquilizers, thiazides; certain occupations such as petrochemical industry, textile industry, metal manufacturing and machine manufacturing) may be related to the development of the disease. In recent years, an RNA retrovirus, human T-cell leukemia/lymphoma virus (HT-LY), was found and isolated from fresh and cultured lymphocytes of some cTcL patients, and natural antibodies were found in the patient’s serum, suggesting that the disease is related to The disease was associated with viral infection. Pathologic pattern: The disease is generally divided into 3 stages according to the histologic changes exhibited at different levels of disease progression: ① Non-specific stage. ②Infiltrative stage. ③Neoplastic stage. The early diagnosis of the erythema stage is difficult, and often only a non-specific inflammatory infiltration is seen in the upper dermis, but even in the early stage, the phenomenon of epidermotrophism is often seen, that is, the appearance of scattered single mononuclear cells in the epidermis, separated from the surrounding keratinocytes by a transparent interval or halo. Occasionally, several single nucleated cells may be seen together with a halo-like interval around them, suggesting a small pautrier microabscess. This pro-epidermal phenomenon is often suggestive of early mycosis fungoides, which differs from the usual exOcytosis common in prepared dermatitis in that mycosis fungoides usually has no or little spongiform edema. Second, the plaque stage in most cases, the tissue image has diagnostic value. A band of pleomorphic cellular infiltrate appears in the upper dermis, including normal lymphocytes, histiocytes, eosinophils, plasma cells and a significant proportion of mycosis fungoides (T cells with darkly stained nuclei and irregular shape). Patchy infiltrates were also seen in the lower dermis. The presence of pro-epidermal phenomena and pautrier microabscesses within the epidermis are diagnostic features of the disease. The difference from the erythematous stage is that the single nucleated cells within the epidermis in the plaque stage, some of which are myxoid granuloma cells, and the scattered single nucleated cells invading not only in the epidermis but also in the epithelium of the appendages, especially the hair follicles, are seen. Third, two histological manifestations can be seen in the tumor stage. In some patients, the infiltrate is a plaque-like pleomorphic infiltrate, but in most cases the infiltrate consists mainly of mycosis fungoides cells, which extend into the subcutaneous fat layer; the epidermis may be typically pro-epidermal or uninvolved, and there may even be a non-infiltrative zone in the upper dermis. In other patients, the infiltrate is monomorphic and consists almost exclusively of tumor cells pro-epidermis is no longer characteristic. Two histological manifestations of transition from pro-epidermal to non-epidermal can be seen in the same patient. Clinical manifestations: According to the changes in different 3 stages of disease development, certain signs and symptoms appear clinically: 1. Non-specific stage: The prodromal symptoms of this stage include fever, joint pain, skin pruritus, followed by rash. The rash can spread over the entire body, but is more common on the lower extremities, lower back, and neck. The lesions may be erythematous, papular, pemphigoid, purpuric or blistering, moss-like changes with scaly flaking on the surface. The skin color of the lesions rapidly darkens to purplish red or purplish brown, and this period can last for months to decades. 2. Infiltrative phase: The infiltrative phase develops from the non-specific phase, and can also be the beginning of this phase, which is characterized by the appearance of irregular infiltrative plaques on the original lesions or on the skin with normal appearance. The surface of the plaque is smooth, but it can be uneven and dark red. The plaque can fade by itself, or it can only have pigmentation after ulceration and healing, and it can last for more than ten years, but it usually turns into tumor stage after several months. 3.Tumor stage: Subcutaneous nodules gradually or suddenly appear on the edge of infiltrative plaques or on the skin with normal appearance, hemispherical, lobulated or irregular in shape, ranging from 2 to 6 cm in diameter, grayish white or brownish red in color, rarely ulcerated. However, once ulcerated, there is often severe local pain, leaving atrophic scars with hyperpigmentation after healing. Systemic symptoms include emaciation, weakness, loss of appetite, generalized muscle and joint pain, fever, etc. Diagnosis: The erythematous lesions are non-specific in clinical and histopathological aspects, so it is often difficult to make a diagnosis; for those with special morphology and color, severe pruritus without obvious scratch marks and tinea, chronic progressive course, atypical lesions, difficult to be summarized by a skin disease, and difficult to be controlled by general treatment for a long time, the disease should be suspected, and biopsy should be made in time, and if necessary, serial sections or multiple times and various parts should be taken to look for If necessary, biopsies should be taken in successive sections or multiple times and from various sites to look for mononuclear cells infiltrating the epidermis (pro-epidermal phenomenon) without the characteristic histopathological manifestations of spongiform edema, and to make early diagnosis. In the plaque and tumor stages, the diagnosis can be made based on the lesions combined with histopathological manifestations. The recent advent of anti-T-cell antigen hybridoma antibodies has provided a reliable basis for the classification and differentiation of malignant lymphomas. It has been shown that the majority of T cells (80%-90%) in mycosis fungoides dermal infiltrates are T helper cells and only 20%-10% are T suppressor cells. Staging: The TNM staging system developed by the mycosis fungoides cooperative group (MFCG) has become the standard for staging and classification of patients with MF and SS. Recently, the ISCL and EORTC have recommended a revision of this staging system based on new data on immunohistochemistry, biology and prognosis of MF and SS following the publication of the MFCG staging system. In this revised staging system, patients should have a clear MF/SS diagnosis for all different stages, defined as less than 10% skin surface invasion with patchy or plaque-like lesions for T1 and at least 80% diffuse skin invasion for erythrodermic disease for T4. Only clinically abnormal lymph nodes (≥1.5 cm in diameter) are biopsied for staging. Invasion of internal organs other than skin, lymph nodes or blood should be confirmed by imaging. There are 3 types of blood invasion: B0 for no significant blood invasion (Sezary cells ≤ 5%); B1 defined as low tumor load (Sezary > 5% but not meeting the criteria of B2); and B2 for high tumor load with Sezary cells > 1,000/μl. According to the updated staging system, patients with stage III are further divided into two groups, IIIA and IIIB, to distinguish the degree of blood invasion (B0 and B1, respectively). Treatment : The early stage was based on enhancing the patient’s immunity. For example, intramuscular or intradermal injection of interferon and transfer factor injection. Topical treatment with nitrogen mustard, x-ray or electron beam irradiation and photochemotherapy are available; extracorporeal photochemotherapy (extracorporea1 photochemOtherapy) can be applied to patients with erythrodermic type if available. Advanced damage (lymph node involvement, extensive skin lesion involvement, and especially visceral involvement) can be treated with chemotherapy, such as cyclophosphamide, nitrogen mustard phenylbutyrate, and methotrexate as commonly used cytotoxic agents, which can be applied alone or in combination, or in combination with local nitrogen mustard therapy or electron beam irradiation or photochemotherapy for better efficacy. Aromatic retinoic acid can be applied simultaneously in the treatment. The main targeted therapeutic agents are retinoids, all-trans retinoic acid (ATRA), and bexarotene (Targretin). Other emerging targeted therapies include histone deacetylase (HDAC) inhibitors, alemtuzumab (anti-CD25 antibody, Campath), and denibulin. One of the more efficacious is the HDAC inhibitor, Vorinostat, which was the first HDAC inhibitor approved by the FDA for skin-invasive T-cell lymphoma. Retinoic acid [all-trans retinoic acid (ATRA) and isotretinoic acid (13-cis retinoic acid)] has been used for many years to treat cutaneous lymphomas. Bexarotene is a novel synthetic retinoic acid analogue that binds selectively to retinoid X receptor (RXR) subunits (RXRa, RXRb, RXRg), thus allowing for selective function and reduced clinical toxicity; it inhibits the growth of hematopoietic and squamous cell malignant cell lines; it induces programmed death in some malignant cell lines It can inhibit the transplantation growth of human squamous cell tumors. Bexarotene is a new anti-cancer drug developed by Ligand Pharmaceuticals, Inc. and was approved by the FDA in 2000 for the treatment of cutaneous T-cell lymphoma in the U.S. It was approved for marketing in Europe in 2001. However, the drug is not listed in the pharmacopoeia and has not been imported into China. According to the new drug approval method, it belongs to category 3.1 new drugs. Two multicenter clinical trials have evaluated oral bexarotene for the treatment of refractory or recalcitrant early-stage and progressive cutaneous T-cell lymphoma. For early-stage cutaneous T-cell lymphoma, bexarotene was well tolerated at 300 mg/m2/d and was effective in 54% of patients; a 45% clinical complete and partial remission rate was observed in patients with progressive cutaneous T-cell lymphoma receiving bexarotene at 300 mg/m2/d; and a 55% remission rate at doses above 300 mg/m2/d, including a 13% clinical complete remission rate. Side effects were reversible and manageable. Combinations of several therapies may provide better therapeutic efficacy. The most frequently used forms of combination therapy are phototherapy combined with interferon/systemically applied retinoic acid, extracorporeal photodisplacement therapy combined with interferon or/and systemically applied retinoic acid. Psoralen combined with A-wave UV irradiation in combination with interferon alfa resulted in an overall remission rate of 93% with a median remission duration of more than 25 months in patients with stage IB to IVB. In another prospective phase III trial, low-dose interferon alfa and osteopontin combined with A-wave UV irradiation for early mycosis fungoides resulted in an 84% complete remission rate. Adding psoralen to the combination regimen of extracorporeal photodisplacement therapy, interferon, and bexarotene for mycosis fungoides with A-wave UV irradiation resulted in rapid and durable remission of the lesions. In a long-term follow-up study of patients with advanced and poorly prognosed cutaneous lymphoma, the combined treatment modality (extracorporeal photodissociation replacement therapy combined with interferon and/or systemically applied vincristine) resulted in a higher remission rate compared with ECP therapy alone (84% versus 75%). The median survival was longer in patients receiving combination therapy (74 months vs. 66 months). Combination therapy was well tolerated. Bexarotene combined with psoralen in combination with A-wave UV irradiation, extracorporeal photo-displacement therapy and/or interferon also achieved higher remission rates in patients with advanced disease. The combination of systemic retinoic acid therapy with biological response modifiers has also been studied in patients with advanced disease. The treatment of each stage is discussed below: Stage IA Treatment Stage IA is a localized lesion and the treatment strategy is topical. The long-term prognosis is similar, with an overall remission rate of 70% to 80% and a median time to normalization of the skin of 6 to 8 months. After discontinuation of treatment, more than 50% of patients relapse locally, but retreatment remains effective. Topical dermal nitrogen mustard treatment is a dilution of nitrogen mustard in an ointment base or saline and applied topically once daily until the lesions disappear, with 20% achieving more than 10 years of remission. Other treatments include medium-wave ultraviolet light therapy (UVB), psoralen with ultraviolet A radiation (PUVA), etc. PUVA is more penetrating than UVB and is suitable for treating lesions that invade deeper into the dermis. Stage IB-IIA treatment The treatment strategy is still localized. Local electron beam radiotherapy is suitable for deeper lesions in the skin, and is preferable to complementary A-wave UVB irradiation. The recommended total dose of local electron beam radiotherapy is 36 Gy, with a break of 1 week at doses of 18-20 Gy, and a total course of >10 weeks. Usually, the skin on the top of the head, perineum, foot plantar (sole), inframammary folds or abdominal skin folds do not receive enough dose and require an additional 20 Gy of localized 6 MeV E-ray, with a complete remission rate of 80%-90% after treatment. If local single drug administration is ineffective, combination therapy can be used. Common combinations are nitrogen mustard + local electron beam radiotherapy, nitrogen mustard + psoralen with A-wave UV irradiation, interferon (IFN) or retinoid. Stage IIB treatment is based on combination therapy. If only a few solid tumors are present, local EBRT + HN2 or EBRT + PUVA is preferred; if extensive solid tumors are present, systemic cutaneous EBRT + HN2, PUVA + IFN or PUVA + retinoid is preferred. The complete remission rate for stage IIB mycosis fungoides with systemic EBRT is 45% to 75%. PUVA + interferon improved the long-term survival rate of stage IIB MF compared to PUVA alone and increased the complete remission rate by 33%. Stage III treatment Treatment is low-dose psoralen + low-dose long-wave UV irradiation. Photodissociation and replacement or photochemotherapy can be the first treatment of choice for individual erythrocytic MF and Sezary syndrome, which has an efficiency of 60% for all patients without invasion of internal organs or limited lymphadenopathy, and can be used as appropriate. Stage IV treatment is mainly palliative treatment with radiation therapy or INF-alfa combined with conventional dose chemotherapy. Although palliative, the treatment is still effective up to 80%, and the duration of effectiveness is often shorter than 1 year. Single agent chemotherapy is methotrexate, etoposide, bleomycin, vincristine, fludarabine, etc. Combination chemotherapy regimens are available as CHOP or CVP regimens. Prognosis: The most important survival prognostic factors include the patient’s age, the extent and type of skin invasion, overall staging (T-classification), the presence of extracutaneous lesions and peripheral blood invasion. Patients with a limited patch/plaque stage have a better prognosis, while those with a tumor stage or erythrodermic infiltration have a worse prognosis, and those with extracutaneous lesions have an even worse prognosis. In a retrospective study including 525 patients with mycosis fungoides and SS, 5-year OS was significantly higher in patients <57 years of age than in those ≥57 years of age (80% vs. 56%). The risk of disease progression, development of extracutaneous lesions, or death from mycosis fungoides was associated with initial staging.