Cutaneous T-cell lymphoma (CTCL) has two major subgroups in its clinical spectrum: mycosis fungoides (MF) and Sézary syndrome.
They usually display CD4 positivity and show a propensity to infiltrate the epidermis (epidermotropism).
The etiology of CTCL is unknown, but an association with industrial exposures and genetic factors has been implicated.
The incidence of MF in the United States has hit a plateau at an annual incidence of 5 new cases per 1,000,000 population.
It occurs more frequently in men than in women, by a ratio of approximately 2:1, and blacks are twice as likely to be afflicted as whites.
As with other lymphomas, the incidence of CTCL increases sharply with age, with peak incidence being between the ages of 70 and 80.
NATURAL HISTORY
Lesions of MF can be found anywhere in the body; however, they are most often seen in “sun-shaded” areas.
Most cases of MF evolve slowly and progressively through three clinical phases: patch/premycotic phase, infiltrated plaque/mycotic phase, and tumor/fungoid phase.
The patch phase of classic MF is the most variable in clinical appearance and duration. These early lesions are frequently mistaken for other dermatoses. After many years, they ultimately develop superimposed infiltrative plaques or tumors more typical of MF.
The plaque and the tumor phases of MF are characterized by clinically palpable lesions, as a result of the accumulation of atypical lymphoid cells within the skin. Individual lesions tend to regress spontaneously or merge with adjacent lesions to form larger lesions of irregular shape. Cutaneous ulcerations and secondary infections frequently are encountered in the tumor stage.
Most investigators consider Sézary syndrome to be an erythrodermic and leukemic expression of CTCL. Sézary syndrome is differentiated from MF with erythroderma by the presence of malignant T cells in the peripheral blood possessing an atypical cerebriform microscopic appearance (Sézary cells).
Seventeen percent of patients with CTCL present with generalized erythroderma; about 50% of these have clear-cut Sézary syndrome (16).
The median duration from onset of skin lesions to histologic diagnosis of CTCL is 8 to 10 years, with considerable variation from patient to patient.
The median survival for all patients has historically been less than 5 years (6, 12). However, earlier diagnosis and improvement in treatment approaches have increased the median survival to approximately 10 years (18, 36).
Extracutaneous infiltration is present in greater than 80% of cases at autopsy. It is associated with a significantly worse prognosis than disease confined to the skin (10).
TABLE 10-1 Diagnostic Workup for Cutaneous T-Cell Lymphoma
General
History with attention to pace of disease evolution
Dermatologic examination to assess degree of lesion infiltration and surface involvement
Routine physical examination, including palpation for lymphadenopathy, hepatosplenomegaly, and other visceral abnormalities
Radiographic Studies
Chest x-ray
Computed tomography of abdomen and pelvis
Isotope scans of liver and spleen or bone (when clinically indicated)
Laboratory Studies
Complete blood cell count, blood chemistry
Blood smear for presence and quantification of atypical mononuclear (Sézary) cells
Biopsy Studies
Punch biopsy samples from most infiltrated lesions
Biopsy of palpable lymph nodes
Bone marrow biopsy
Any organ may be infiltrated by malignant lymphocytes; however, the most common sites are lymph nodes (68%), spleen (56%), lungs (50%), liver (49%), and bone marrow (42%) (34).
The median survival of patients with confirmed lymph node or visceral disease is 2 years and 1 year, respectively (3).
DIAGNOSTIC WORKUP
Procedures used in staging and evaluation are outlined in Table 10-1.
Several punch biopsy specimens should be taken from the most infiltrated lesions to establish the diagnosis and define the character of the malignant infiltrate.
The status of the lymph nodes in the cervical, axillary, and inguinal regions should be evaluated. If there are any palpable lymph nodes, a biopsy should be obtained. An effort should be made to confirm the presence of extracutaneous involvement, if suspected.
STAGING SYSTEMS
A unifying staging system based on the tumor-node-metastasis (TNM) system was originally proposed at a Mycosis Fungoides Cooperative Group Workshop on CTCL at the National Cancer Institute. This system was revised in 2007 (30) as suggested by the International Society for Cutaneous Lymphoma (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) and emphasizes the prognostic importance of cutaneous tumors, lymphadenopathy, and extracutaneous involvement. The AJCC’s 7th edition (1) TNM definitions and anatomical staging groups are in Tables 10-2 and 10-3.
TABLE 10-2 AJCC Staging for Primary Cutaneous Lymphoma
Primary Tumor (T) skin
TX
Primary tumor cannot be assessed
T1
Limited patches,a papules, and/or plaquesb covering <10% of the skin surface.
May further stratify into T1a (patch only) vs. T1b (plaque ± patch).
T2
Patches, papules, or plaques covering >10% of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque ± patch).
High blood tumor burden: >1,000/µL Sézary cellsg with positive clone
a For skin, patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted.
b For skin, plaque indicates any size skin lesion that is elevated or indurated. Presence or absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as folliculotropism or large-cell transformation (>25% large cells), CD30+ or CD30-, and clinical features such as ulceration are important to document.
c For skin, tumor indicates at least one 1-cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note total number of lesions, total volume of lesions, largest size lesion, and region of body involved. Also note if histologic evidence of large-cell transformation has occurred. Phenotyping for CD30 is encouraged.
d For node, abnormal peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed or 1.5 cm or larger in diameter. Node groups examined on physical examination include cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which are not generally amenable to pathologic assessment, are not currently considered in the nodal classification unless used to establish N3 histopathologically.
e A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene.
f For viscera, spleen and liver may be diagnosed by imaging criteria.
