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Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin lymphoma, representing a type of cancer affecting the immune system. Unlike the majority of non-Hodgkin lymphomas, which are typically associated with B cells, CTCL arises from a mutation in T cells. These malignant T cells primarily migrate to the skin, where they cause various types of lesions that evolve as the disease progresses. Initially, these lesions may resemble a rash that is often intensely itchy. Over time, they can develop into plaques and tumours, eventually spreading to other parts of the body.

Micrograph showing cutaneous T-cell lymphoma. H&E stain
Micrograph showing cutaneous T-cell lymphoma. H&E stain

Signs and Symptoms

CTCL can present in several forms, with mycosis fungoides and Sézary syndrome being the most common types. The symptoms associated with these conditions include:

  • Enlarged lymph nodes
  • Enlarged liver and spleen
  • Non-specific dermatitis

The skin manifestations start as itchy rashes and can progress to form more pronounced plaques and tumours.


The exact cause of CTCL remains largely unknown. However, several external risk factors have been proposed as potential triggers or promoters of the disease. These factors include:

  • Use of hydrochlorothiazide diuretics
  • Therapy-induced immunosuppression
  • Possible infections by various viral and bacterial pathogens such as HTLV-1, HTLV-2, HIV, Epstein-Barr virus, Cytomegalovirus, HHV-6, HHV-7, HHV-8 (KSHV), Merkel cell polyomavirus, Staphylococcus aureus, Mycobacterium leprae, Chlamydophila pneumoniae, and dermatophytes.

The strength of evidence linking these factors to CTCL varies.


The diagnosis of early forms of CTCL can be challenging and was addressed by the International Society for Cutaneous Lymphomas in 2005 with a point-based algorithm. CTCL is categorised into several subtypes, with mycosis fungoides being the most common. The WHO-EORTC classification includes:

  • Pagetoid reticulosis
  • Sézary syndrome
  • Granulomatous slack skin
  • Lymphomatoid papulosis
  • Pityriasis lichenoides chronica
  • Pityriasis lichenoides et varioliformis acuta
  • CD30+ cutaneous T-cell lymphoma
  • Secondary cutaneous CD30+ large cell lymphoma
  • Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
  • Pleomorphic T-cell lymphoma
  • Lennert lymphoma
  • Subcutaneous T-cell lymphoma
  • Angiocentric lymphoma
  • Blastic NK-cell lymphoma
  • Primary cutaneous anaplastic large-cell lymphoma



There is no cure for CTCL, but various treatment options are available that can help manage the condition. Some patients are able to live relatively normal lives, although symptoms can be debilitating and painful even in the earlier stages. FDA-approved treatments include:

  • Denileukin diftitox (Ontak) (1999)
  • Bexarotene (Targretin) a retinoid (2000)
  • Vorinostat (Zolinza) a hydroxymate histone deacetylase (HDAC) inhibitor (2006)
  • Romidepsin (Istodax) a cyclic peptide HDAC inhibitor (2009)
  • Poteligeo (mogamulizumab-kpkc) (2018)

Histone deacetylase (HDAC) inhibitors have shown antiproliferative and cytotoxic properties against CTCL. Other off-label treatments include:

  • Topical and oral corticosteroids
  • Bexarotene (Targretin) gel and capsules
  • Carmustine (BCNU, a nitrosourea)
  • Mechlorethamine (nitrogen mustard)
  • Phototherapy (broad and narrow band UVB or PUVA)
  • Electron therapy
  • Conventional radiation therapy
  • Photopheresis
  • Interferons
  • Alemtuzumab (Campath-1H)
  • Methotrexate
  • Pentostatin and other purine analogues (Fludarabine, 2-deoxychloroadenosine)
  • Liposomal doxorubicin (Doxil)
  • Gemcitabine (Gemzar)
  • Cyclophosphamide
  • Bone marrow/stem cell transplantation
  • Allogenic transplantation
  • Forodesine (inhibits purine nucleoside phosphorylase)

In 2010, the U.S. Food and Drug Administration granted orphan drug designation for naloxone lotion as a treatment for pruritus in CTCL.


CTCL accounts for approximately 2% of all lymphocyte-related cancers. It is more prevalent in men and African-American individuals, with an incidence rate in men 1.6 times higher than in women. There is some evidence suggesting a link between human T-lymphotropic virus (HTLV) and the adult T-cell leukaemia/lymphoma subtype, though no definitive association with other CTCL subtypes has been established.

Self-assessment MCQs (single best answer)

What type of cells are primarily involved in Cutaneous T-cell Lymphoma (CTCL)?

Which of the following is the most common form of CTCL?

Which of the following is NOT a proposed external risk factor for CTCL?

What is the primary symptom that skin manifestations of CTCL may initially resemble?

Which FDA-approved treatment for CTCL is a cyclic peptide HDAC inhibitor?

Which of the following types of lymphoma is NOT classified under the WHO-EORTC subtypes of CTCL?

What is the incidence rate of CTCL in men compared to women?

Which of the following viruses has evidence suggesting a link to the adult T-cell leukaemia/lymphoma subtype of CTCL?

What type of therapy involves the use of UV light in the treatment of CTCL?

Which of the following is an orphan drug designated by the FDA for the treatment of pruritus in CTCL?


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