INTRODUCTION	Section 2 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Background: In 1979, the term cutaneous T-cell lymphoma (CTCL) was coined at an international workshop sponsored by the National Cancer Institute. CTCL was used to describe a heterogenous group of malignant T-cell lymphomas with primary manifestations in the skin. In 1806, the term mycosis fungoides (MF) was first used by Alibert, a French dermatologist, when he described a severe disorder in which large necrotic tumors resembling mushrooms presented on a patient's skin. MF is the most common type of CTCL.

Sézary syndrome (SS) is a variant of MF, occurring in about 5% of all cases of MF. The patient with SS has generalized exfoliative erythroderma, lymphadenopathy, and more than 1000 per mm³ atypical T lymphocytes with cerebriform nuclei circulating in the peripheral blood or other evidence of a significant malignant T-cell clone in the blood such as clonal T-cell gene rearrangement (identical to that found in the skin). The T-cell gene rearrangement is demonstrated by molecular or cytogenetic techniques and/or an expansion of cells with a malignant T-cell immunophenotype (an increase of CD4⁺ cells such that the CD4/CD8 ratio is >10, and/or an expansion of T cells with a loss of 1 or more of the normal T-cell antigens, eg, CD2, CD3, CD5). The circulating malignant cells tend to be CD7 and CD26^-.

Pathophysiology: MF is a malignant lymphoma characterized by the expansion of a clone of CD4⁺ (or helper) memory T cells (CD45RO⁺) that normally patrol and home to the skin. The malignant clone frequently lacks normal T-cell antigens such as CD2, CD5, or CD7. The normal and malignant cutaneous T cell homes to skin by virtue of interactions with dermal capillary endothelial cells. Cutaneous T cells express cutaneous lymphocyte antigen (CLA), an adhesion molecule that mediates tethering of the T lymphocyte to endothelial cells in cutaneous postcapillary venules via its interaction with E selectin.

Further promoting the proclivity of the cutaneous T cell to home to the skin is the release by keratinocytes of cytokines, which infuse the dermis, coat the luminal surface of the dermal endothelial cells, and upregulate the adhesion molecules in the dermal capillary endothelial lumen, which react to CCR4 found on cutaneous T cells.

Extravasating into the dermis, the cells show an affinity for the epidermis, clustering around Langerhans cells as seen microscopically as Pautrier microabscesses. However, the malignant cells that adhere to the skin retain the ability to exit the skin via afferent lymphatics. They travel to lymph nodes and then through efferent lymphatics back to the blood to join the circulating population of CLA-positive T cells. Then, the disease fundamentally is a systemic disease, even when the disease appears to be in an early stage and clinically limited to the skin.

Frequency:

• In the US: Approximately 1000 new cases of MF occur per year (ie, 0.36 cases per 100,000 population).

Mortality/Morbidity:

• A recent analysis of 20-year trends reporting on incidence and associated mortality shows a decline in the mortality rate in the United States, perhaps related to an increased recognition and earlier diagnosis of the disease. The overall mortality rate is 0.064 per 100,000 persons; however, the mortality rate widely varies depending on the stage of disease at diagnosis.

• Late-stage MF or SS is associated with declining immunocompetence. Death most often results from systemic infection, especially with Staphylococcus aureus, Pseudomonas aeruginosa, and other organisms. Secondary malignancies, such as higher-grade non-Hodgkin lymphoma, Hodgkin disease, colon cancer, and cardiopulmonary complications (eg, high output failure, comorbid cardiopulmonary disease) also contribute to mortality.

Race: MF is more common in black than in white patients (incidence ratio 1.6).

Sex: MF occurs more frequently in men than in women (male-to-female ratio of 2:1).

Age: The most common age at presentation is 50 years; however, MF also can be diagnosed in children and adolescents with apparently similar outcomes.

	CLINICAL	Section 3 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

History:

• Skin rash

• This may consist of flat patches, plaques, or tumors, which may have a long natural history.

• The median duration from the onset of skin symptoms to diagnosis is 6 years. Early in the course of mycosis fungoids (MF) as well as in erythrodermic cases, skin lesions may be nonspecific, with a nondiagnostic biopsy result, so confusion with benign conditions is common.

• Obtain repeated biopsies in those patients who have progressive chronic dermatosis or whose condition is refractory to topical treatments.

• Pruritus, erythroderma: Often, diagnosis is made possible through the examination of a noncutaneous site (eg, blood, lymph nodes).

Physical:

• Flat skin patch, plaque, and tumors

• Patch phase MF is characterized by flat, usually erythematous, macules that may have a fine scale, may be single or multiple, and may be pruritic. In dark-skinned individuals, the patches may appear as hypopigmented or hyperpigmented areas. As patches become more infiltrative, they evolve into palpable plaques.

• Plaques tend to be raised, demonstrating fine-scale, well-demarcated, erythematous shapes with irregular borders. Annular or serpiginous patterns with central clearing and pruritus are common.

• Patches and plaques may affect any area of the skin, but they often are distributed asymmetrically in the areas that a bathing suit would cover (ie, hips, buttocks, groin, lower trunk, axillae, breasts). When the disease affects the scalp, it often is accompanied by alopecia.

• Stage IA disease (as defined by the tumor, node, metastases, blood [TNMB] system) is defined as patchy or plaquelike skin disease involving less than 10% of the skin surface area (T1 skin disease).

• Stage IB disease is defined as patchy or plaquelike skin disease involving greater than or equal to 10% of the skin surface area (T2 skin disease).

• Skin tumors

• Patients with evidence or a history of patchy or plaquelike skin lesions also can have tumors.

• Tumors are red-violet nodules that may be dome-shaped, exophytic, or ulcerated.

• Stage IIB disease is defined by the presence of tumors (T3 skin lesions).

• Skin erythroderma

• Generalized erythroderma often is intensely symptomatic, with pruritus and scaling that can be profound. The patients experience thickening of the skin folds in the face (leonine facies), hyperkeratosis and fissuring of the palms and soles, onychodystrophy, ectropion of the eyelids, alopecia, and edema. Sun exposure may be painful as well as pruritic.

• Stage III disease is defined by the presence of generalized erythroderma.

• Lymph nodes

• Extracutaneous involvement is more clinically evident as the stage and extent of MF increases.

• Peripheral lymphadenopathy is the most frequent site of extracutaneous involvement in MF.

• Evaluate palpable lymphadenopathy by obtaining a biopsy because the result influences the patient's stage, prognosis, and treatment.

• Stage IVA disease is defined by a lymph node biopsy result demonstrating large clusters of atypical cells (ie, >6 cells [LN3 node]) or showing total effacement by atypical cells (LN4 node).

• Liver, lung: Stage IVB disease is defined by the presence of visceral involvement (eg, liver, lung, bone marrow).