Primary cutaneous lymphomas are the second most common extranodal non-Hodgkin Lymphomas. They may be of either T cell, B cell, or NK cell origin. Cutaneous T Cell lymphomas (CTCL) comprise a group of heterogeneous lymphomas which clinically differ from systemic lymphomas, even though they might show similar histology. 
Mycosis fungoides is the most common type of CTCL. It is a cutaneous lymphoma that originates in the peripheral epidermotropic T-cells, specifically the memory T-cells (CD45RO+), which express the T-cell receptor (TCR) and CD4+ immunophenotype.
The cause of mycosis fungoides is unclear. The following are various hypotheses proposed:
Mycosis fungoides has an incidence of around 6 cases per million per year in Europe and the United States. This accounts for 4% of all non-Hodgkin lymphoma cases. It is more common in adults over 50 years of age, with a male:female ratio between 1.6 and 2. The disease is more common amongst Blacks than Caucasians or Asians.
Among the cutaneous lymphomas, nearly two-thirds are of the T cell type. The most common immunophenotype is CD4 positive. In mycosis fungoides, there is a clonal expansion of CD4 cells that often lack the normal T cell antigens like CD7, CD5 or CD 2. These cells are attracted towards the skin by keratinocytes. As the cells accumulate in the dermis, they cluster around the langerhan cells- which is known as Pautrier microabscesses. Some of the malignant cells travel to the local lymph nodes and then pass into the bloodstream where they circulate with other CLA-positive T cells.
Histopathology of mycosis fungoides varies within stages of the disease. Superficial lymphoid infiltrate, epidermotropism with absent or rare spongiosis spongiosis, and lymphoid atypia are the predominant features.
Mycosis fungoides tumor cells are characterized by epidermotropic peripheral T lymphocytes whose phenotype is CD2+, CD3+, CD4+, and CD5+. In a minority of patients with mycosis fungoides, T lymphocytes may be CD4- and CD8+, CD4- and CD8-, or CD4+ and CD8+.The loss of CD7 expression can be observed even in the early phases of the disease. However, isolated negativity for CD7 is not a sufficient criterion for diagnosis as it can be shown in inflammatory dermatoses. The loss of CD26 expression seems to be specific to mycosis fungoides neoplastic cells.
The immunohistochemical pattern of Sezary syndrome is CD3+, CD4+, CD7-, and CD8- cells, which is identical to mycosis fungoides. Immunostaining for MUM-1 (multiple myeloma oncogene) might be used to differentiate these as it is positive in Sezary syndrome and negative in mycosis fungoides.
The clinical presentation of mycosis fungoides varies with the stage of the disease.
The frequency of lymph nodal or visceral dissemination increases as the lesions progress from the patch stage to the plaque stage and finally the tumor stage.
Less Common or Rare Clinical Variants
Clinical Variants (as described in the WHO-EORTC Classification for Cutaneous Lymphomas)
Sezary syndrome constitutes 3% of all cutaneous lymphomas and is characterized by a triad of manifestations: erythroderma with pruritus, lymphadenopathy, and atypical circulating lymphocytes (referred to as Sezary or Lutzner cells). The syndrome is understood as a leukemic phase of T-cell cutaneous lymphomas and bone marrow compromise is rarely found in advanced forms of the disease only. Associated clinical manifestations include lagophthalmos, alopecia, palmoplantar hyperkeratosis and onycodystrophy. Sezary Syndrome must be differentiated from erythroderma in mycosis fungoides progression. In the WHO-EORTC classification, MF and SS are listed as seperate diseases.
Complete Physical Examination
Lymph Node Biopsy
It is easy to confuse mycosis fungoides for common skin disorders such as eczema, psoriasis, parapsoriasis, photodermatitis, or drug reactions. The important differentials to keep in mind include:
The standard staging system for mycosis fungoides was the TNMB system, which was the strongest prognostic indicator for mycosis fungoides. Olsen et al. (2007) published the staging norms of mycosis fungoides and SS as a result of the ISCL-EORTC discussions, and modified the existing TNMB staging system in view of advances in cellular and molecular biology in diagnostic methods, as given below.
N0: No clinically abnormal peripheral lymph nodes; biopsy not required
N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2
N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3
N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3 to 4 or NCI LN4; clone positive or negative
Nx: Clinically abnormal peripheral lymph nodes; no histologic confirmation
M0: No visceral organ involvement
M1: Visceral involvement (must have pathology confirmation and organ involved should be specified)
B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary) cells
B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary) cells but does not meet the criteria of B2
B2: High blood tumor burden: 1000/microL or more Sezary cells with positive clone
The prognosis of mycosis fungoides and Sezary syndrome is variable. The TNMB staging is the strongest prognostic factor. The following factors may be associated with a poor prognosis:
The management of mycosis fungoides is best done with an interprofessional team of healthcare workers that includes an oncologist, internist, dermatologist, nurses, pharmacists, and social workers. The disorder has no cure, and the aim is to improve the quality of life. The patient should be encouraged to use ample moisturizer to prevent skin dryness and pruritus. The patient should be told to avoid the sun and wear long-sleeved garments when going out. A cool humidified environment is highly recommended. The patient should also be educated about the other treatment options like irradiation, Photodynamic therapy and UV light treatment enhanced with psoralen. Finally, the patient should be seen by a dietitian as many people develop moderate nausea from the treatment and lose significant weight. A high-calorie diet with regular exercise is recommended. (Level V)
Mycosis fungoides is an incurable disorder unless the patient has very early stage disease. The mortality and morbidity increase as the tumor advances. While early-stage patients have a 95% survival over ten years, those who advanced cancer only have a 3-4 year survival. Those with the advanced extra-cutaneous disease only have a survival of fewer than 18 months. Poor prognostic factors include male gender, advanced age, and elevated LDH. (Level V)
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