A Primer on Cutaneous T Cell Lymphoma for the Hair Doctor

October 09, 2022

A SHORT OVERVIEW OF CTCL FOR THE HAIR DOCTOR

Primary cutaneous lymphomas are a group of lymphomas that arise in the skin. They are considered a type of non-Hodgkin’s lymphomas (NHL) characterized by monoclonal proliferation of malignant lymphocytes in the skin. They can follow an indolent course or aggressive course depending on the type. Cutaneous lymphomas are a relatively rare compared to other cancers. About 3000 patients in Canada and 30,000 in USA are believed to be living with cutaneous lymphomas. There are roughly 10 new cases of CTCL each year for every 100,000 people in a given population. Patients usually present in 50s and 60s and males are more commonly affected than women (1.7 to 1 ratio).

Classification of Cutaneous T cell lymphomas

The main types of Cutaneous T cell lymphomas are: 1) mycosis fungoides (39% of all CTCL), MF variants (including follicullotopic MF, pagetoid reticulosis, and granulomatous slack skin (6 % of all CTCL), Sezary syndrome (2 %), Adult T cell leukemia/lymphoma (<1 %), primary cutaneous CD30+ lymphoproliferative disorders (20%), subcutaneous panniculitis-like T cell lymphoma (1%), extranodal T cell lymphoma, nasal type, chronic EBV infections and primary peripheral cutaneous T cell lymphomas (6-8%).

Different types of CTCL can coexist in the same patient.

Patients with CTCL are at risk for second malignancies, usually in the form of a different type of lymphomas.

MF is the most common form of CTCL

Mycosis Fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Mycosis Fungoides is characterized by the presence of small-medium atypical T lymphocytes infiltrating the epidermis. It is said to be an indolent (slow) type of CTCL, and generally follows a chronic course. This is very different than other types like Sezary syndrome which follows a more aggressive coarse.

Folliculotropic MF

Folliculotropic mycosis fungoides (FMF) is a subtype of MF that is characterized by invasion of hair follicles by atypical T-cells. FMF occurs particularly in men. It causes grouped perifollicular papules, plaques and discrete plaques. As mentioned, follicular lesions, including comedones, are a very typical presentation of FMF. These are often on the head and neck area. Eyebrow involvement is common. Up to 65 % have hair loss. It may cause a scarring alopecia. These three key areas of involvement in FMF- scalp, face, and neck are often spared in conventional MF.

In addition to head and neck area, there may be widespread follicular papules, comedones, and cysts on the abdomen and both lower legs. Itching (pruritus) is a typical features of FMF.

Follicular MF is a great mimicker

As mentioned, 65% of those with FMF can have hair loss. It’s a great mimicker! The clinical presentations of alopecia in FMF patients include scarring and non-scarring alopecia, diffuse hair loss or alopecia areata-like patterns.

Two Patterns of FMF

Two distinct histopathologic patterns have recently been proposed. These include early FMF (patch/thin plaque type) and advanced FMF (thick plaque/tumor type). The early FMF is characterized by follicle-based patch/flat plaques, keratosis pilaris-like lesions, acneiform lesions and has good prognosis, like early-stage classic MF. Advanced FMF is distinguished by follicle-based infiltrated/thick plaques and/or tumors with worse prognosis. Just like with classic MF, most patients remain in the early patch and plaque stage for life. It still remains unclear when and which patients will enter into the aggressive tumor stage.

On biopsy, FMF shows an infiltration of neoplastic CD4+ T cells in the epidermis and its adnexa. FMF variant is characterized by folliculotropic infiltration of atypical T lymphocytes, with or without follicular mucinosis or infiltration of epidermis.

Prognosis of Follicular MF

Recent studies reported 10-year survival rates of 72% in skin-limited early stages, 28% in skin-limited advanced stages, and 2% in FMF with extracutaneous localizations at first presentation.

It is generally said that prognosis for FMF is poorer than for classic MF. This is because of infiltration of deeper structures, a poor response to topical therapy and a delayed diagnosis. Although overall survival varies according to the stage of the disease, the prognosis is generally poor.

How is cutaneous T cell lymphoma diagnosed?

The exact clinical features depend on the type of lymphoma one is talking about. Patients with MF may have patches and plaques and these can progress to tumors over time. Patients with Sezary syndrome have a very different presentation altogether. Affected patients present with red skin (erythroderma) and enlarged lymph nodes. Other types like the CD30+ proliferative disorders may have papules.

The typical work up includes skin examination, skin biopsy +/- lymph node biopsy, blood tests including peripheral flow cytometry and radiologic imaging tests. Rarely, a bone marrow biopsy is done.

Skin examination can help determine the extent of the disease and give clues to the specific type. Mycosis fungoides lesions include flat, red, scaly patches, thicker raised lesions (plaques), and sometimes larger nodules or tumors. Patients with FMF might also notice areas of hair loss, especially around the face or scalp, pimples or blackheads, or increased infections within their plaques because of involvement of the hair follicles.bThe finding of lymph node enlargement on examination gives further clues about the extent of involvement.

Skin biopsies not only help confirm the diagnosis but special immunostains are used to further characterize the type of lymphoma. Most biopsies are stained for CD4, CD8, CD7, CD30. The biopsy is used to assess T cell receptor clonality by PCR. Biopsies are often taken from many area and involvement of hair bearing areas of the body is useful to assess for folliculotropic involvement.

Blood tests include CBC, complete metabolic profile, LDH, AST, ALT, HTLV-1, HIV, creatinine, CD4/CD8 ratio, blood smear for Sezary cells, ESR, CRP, TSH.

Imaging tests might include chest x ray, CT scans or PET-CT and abdominal ultrasound.

Staging

The stage of the CTCL influences the prognosis and 5 and 10 year survival. Staging ranges from Stage 1a where less than 10 % of the skin is involved with patches or plaque to stage IV where lymph nodes are involved.

Treatment

Treatment of CTCL depends on the type of CTLC and includes both skin directed therapies and systemic therapies. Skin directed therapies include topical steroids, phototherapy, local radiotherapy and local chemotherapy like agents. Systemic agents include systemic chemotherapy, stem cell transplants and systemic immunomodulatory agents. Treatments of MF may include topical steroids and phototherapy as first line agents. Treatment of Sezary syndrome may include extracorporeal photopheresis.

Treatment of FMF

In early stages of FMF (i.e., IA, IB, and IIA), first line options include skin-directed therapies (SDTs), such as topical corticosteroids, UVB, PUVA, localized radiation therapy and mechlorethamine.

Those refractory to the first line may be considered for systemic therapies, such as retinoids, interferon alpha, total skin electron beam therapy (TSEB) or low-dose methotrexate. These latter treatments are first-line treatments for stage IIB. Stage III patients may benefit from extracorporeal phototherapy (ECP), alone or in combination with skin-directed and other systemic therapies. Refractory and stage IV patients with FMF have tended to be treated with chemotherapy regimens (pegylated liposomal doxorubicin, gemcitabine, CHOP and CHOP-like polychemotherapy).

New treatments in development include monoclonal antibodies, such as anti-CD52 agents, anti-CD30 agents vedotin, anti-CCR4 agents, and histone deacetylase inhibitors. Many of these are not yet approved.

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