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

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

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.

Indolent form

• 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

Patch CTCL

Plaque CTCL

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

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.

Skin-directed therapies⁷

• Phototherapy (ultraviolet-B or psoralen plus ultraviolet-A light [PUVA])
• Topical retinoids (bexarotene gel*)

Systemic therapies

• Bexarotene*
• Denileukin diftitox*
• Extracorporeal photopheresis (ECP) with methoxsalen sterile solution
• Vorinostat*

*Product labelling based on local regulatory approval