Cutaneous T-Cell Lymphoma
About cutaneous T-cell lymphoma
Cutaneous T-cell lymphomas are a heterogeneous group of non-Hodgkin’s lymphomas characterized by the malignant proliferation of CD4+ T-lymphocytes that infiltrate the skin.
Cutaneous T-cell lymphoma (CTCL) typically has a slow growing course, but in some patients it may progress to involve lymph nodes, blood, and visceral organs.
Types of cutaneous T-cell lymphoma
Cutaneous T-cell lymphoma is an umbrella term used to describe several related lymphomas. The most common forms — and the first to be identified — are mycosis fungoides (MF) and Sézary syndrome (SS). The term, however, now includes a number of additional diseases characterized by malignant T-cell expansions.
Mycosis fungoides is the most common form of CTCL, accounting for 50% to 60% of all cases.17,18
Mycosis fungoides has an indolent course, with slow progression over many years or decades. It typically progresses from patches to plaques, and eventually to tumour development.17
While MF is generally limited to epidermal involvement, in some patients the disease slowly spreads to the lymph nodes and internal organs.17
Sézary syndrome is an aggressive form of disease that affects approximately 5% of patients with CTCL.18
Additional cutaneous T-cell lymphoma classifications17
Other, less common forms of CTCL may be categorized according to their clinical form — indolent and aggressive. THERAKOS™ Photopheresis has not been evaluated in these less common forms.
- Mycosis fungoides variants and subtypes
- Folliculotropic MF
- Pagetoid reticulosis
- Granulomatous slack skin
- Primary cutaneous CD30+ lymphoproliferative disorders
- Primary cutaneous anaplastic large cell lymphoma
- Lymphomatoid papulosis
- Subcutaneous panniculitis-like T-cell lymphoma
- Primary cutaneous CD4+ small/medium pleomorphic T-cell lymphomas
Aggressive clinical form
- Primary cutaneous NK/T-cell lymphoma, nasal type
- Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional)
- Primary cutaneous γ/δ T-cell lymphoma (provisional)
- Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (provisional)
Symptoms of cutaneous T-cell lymphoma
Mycosis fungoides is characterized by patches that develop over time into infiltrated plaques, and eventually into tumours.17 In some patients with advanced disease, lymphadenopathy and involvement of internal organs develops.17 Initial MF lesions have a propensity to affect sun-protected areas such as the buttocks.17
Sézary syndrome is characterized by erythroderma, and can include edema, marked exfoliation, and lichenification. Lesions may be intensely pruritic. Lymphadenopathy, onychodystrophy, alopecia, and palmoplantar hyperkeratosis are also common features.17
Tumour phase of CTCL
Diagnosis of cutaneous T-cell lymphoma
Diagnosis of CTCL is based on the combination of clinical, histopathological, immunopathologic, and molecular biological findings.18
As CTCL can mimic other disease states, delays in diagnosis are not uncommon. One long-term study found that the median time to diagnosis is 4.2 years.11
Complete skin examination and biopsy with immunohistochemical studies of suspicious sites are necessary to confirm a diagnosis. In the absence of a definitive skin diagnosis, suspicious lymph node biopsy and peripheral blood assessment for Sézary cells are recommended.18
Patients with early stage disease and without evidence of lymphadenopathy, peripheral blood involvement, or unfavorable features need only a chest X-ray. Other patients should undergo either a computerised tomography (CT) or a positron emission tomography (PET)/CT scan of the neck/chest/abdomen/pelvis.18
Bone marrow biopsy may be helpful in patients with an unexplained hematological abnormality or suspected bone marrow involvement.18
If SS is suspected, T-cell receptor gene rearrangement analysis of peripheral blood lymphocytes is recommended.18
Stages of cutaneous T-cell lymphoma
A revised CTCL staging system has been developed by the International Society of Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC).
In this system, all staged patients should have a definitive diagnosis of MF or SS.14
ISCL/EORTC revision to the classification of mycosis fungoides and Sézary syndrome. This research was originally published in Blood. Olsen E, et al. Blood. 2007;110:1713-1722. © the American Society of Hematology14
N1a Clone negative#
N1b Clone positive#
N2a Clone negative#
N2b Clone positive#
B0a Clone negative#
B0b Clone positive#
B1a Clone negative#
B1b Clone positive#
*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.
†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.
‡For skin, tumour 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.
§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.
¶For viscera, spleen and liver may be diagnosed by imaging criteria.
║For blood, Sézary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sézary cells are not able to be used to determine tumour burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of 10 or more, (2) expanded CD4+ cells with abnormal immunophenotype including loss of CD7 or CD26.
#A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene.
ISCL/EORTC revision to the staging of MF and SS. This research was originally published in Blood. Olsen E, et al. Blood. 2007;110:1713-1722. © the American Society of Hematology14
Epidemiology and prognosis
Approximately 1500 people in the United States and 1200 people in Europe are diagnosed with CTCL each year.3,24
The average age at diagnosis is 55 years.2
Men are twice as likely as women to get the disease.2
Important prognostic factors include the patient’s age at initial presentation, type and extent of skin involvement, overall stage, peripheral blood involvement, and presence of extracutaneous disease.18
People who have early stage (Stage IA) CTCL have excellent prognoses, with life expectancies similar to gender- and age-matched controls.17 However, people with more advanced CTCL have been shown to have a poorer prognosis.11
In a long-term study of 525 patients by Kim and colleagues, the median survival by stage was:11
- 12.9 years for Stage IB/IIA
- 4.0 years for Stage IIB/III
- 1.5 years for Stage IV
Treatment of cutaneous T-cell lymphoma
Treatment of CTCL is determined by disease stage. Early stage CTCL frequently responds to skin-directed therapy, while advanced stage CTCL generally requires systemic therapies. Combination therapy may be required in many patients.
Due to the chronic nature of this disease, patients will usually require repeat treatment and chronic maintenance regimens.7 This list is not comprehensive; some therapies may not be listed below.
- Phototherapy (ultraviolet-B or psoralen plus ultraviolet-A light [PUVA])
- Topical retinoids (bexarotene gel*)
- Denileukin diftitox*
- Extracorporeal photopheresis (ECP) with methoxsalen sterile solution
*Product labelling based on local regulatory approval
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