الفهرس 
EPIDEMIOLOGY OF CUTANEOUS T CELL LYMPHOMAOnly 14 pages are availabe for public view
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Abstract
Primary cutaneous lymphomas (PCLs) are defined as non-Hodgkin lymphomas that present in the skin with no evidence of extracutaneous disease at the time of diagnosis.
After the gastrointestinal lymphomas, PCL are the second most common group of extranodal non-Hodgkin lymphomas with an estimated annual incidence of 1/100 000. These PCLs must be distinguished from nodal or systemic malignant lymphomas involving the skin secondarily, which often have another clinical behavior, have a different prognosis and require a different therapeutic approach.
Cutaneous T cell lymphoma constitutes 75%–80% of all PCLs and Cutaneous B cell lymphoma 20%–25%. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common CTCL subtypes worldwide, comprising 54% of the CTCLs. Clinical presentation and disease stage are strongly correlated with overall prognosis for patients with CTCL.
Mycosis fungoides is the prototype of CTCL, characterized by a proliferation of epidermotropic small-to medium-sized T lymphocytes with cerebriform nuclei. Sézary syndrome has traditionally been considered a leukemic variant of CTCL, characterized by generalized lymphadenopathy, erythroderma, and the presence of neoplastic T cells in the skin, lymph nodes, and peripheral blood.
The neoplastic cells in MF/SS corresponds to an effector memory/central memory type of T-helper cell and is typically characterized by a CD4+CD26− CD7− phenotype, with the expression of CLA and CCR4 cutaneous homing molecules.
MF classically presents with an indolent clinical course, with slow progression over years or sometimes decades. The disease can evolve from patches to more infiltrated plaques and eventually to tumors. Sézary syndrome, on the other hand, is much more aggressive, with an estimated 5 year survival of 24%.
The overall diagnosis and management of cutaneous T-cell lymphoma (CTCL), including MF and SS, has evolved over the past two decades. Historically patients were diagnosed and managed almost exclusively by dermatologists. Many patients are managed by multidisciplinary teams or clinics that include dermatologists, hematologic pathologists, medical oncologists, and radiation oncologists. Even staging has evolved to routinely include an analysis of the presence of Sézary cells and the addition of diagnostic imaging including PET/CT (positron emission tomography/computed tomography) for patients with more advanced presentations.
Prognosis correlates with the extent of skin disease & status of the lymph nodes, blood & visceral involvement. MF behaves in a manner similar to other low grade or indolent NHL with prolonged survival despite recurrent relapses. Patients with SS have relatively poor prognosis with a median survival of 3 to 4 years.
Patients with early-stage mycosis fungoides often present with disease limited to the skin without systemic involvement; in these patients, a durable response can be achieved in approximately 60%–80% of cases with skin-directed therapies.
Patients with early-stage disease may be effectively treated with topical agents, because previous data have demonstrated that there is no benefit to aggressive use of systemic chemotherapy. Existing therapeutic approaches include phototherapy with psoralen plus ultraviolet A (PUVA), narrowband ultraviolet B (NB-UVB), total electron beam irradiation (TSEBT), and topical formulations of corticosteroids, nitrogen mustard, and retinoids/rexinoids.
Patients with advanced disease (stage IIB–IVB) may have disseminated disease into lymph nodes and other organs, and may exhibit multiple immune derangements necessitating systemic therapy. While no regimen has been proven to prolong survival in the advanced stages, immunomodulatory regimens should be used initially to reduce the need for cytotoxic therapies. Decreased cell-mediated immunity with a dominant Th2 cytokine profile is observed in advanced stages of mycosis fungoides and Sézary syndrome. Bexarotene, immunomodulatory cytokines such as IFN-α, IFN-γ, and IL-12, and extracorporeal photopheresis enhance the host antitumor response.
Denileukin diftitox is an IL-2 diphtheria toxin fusion protein targeted against malignant T cells expressing CD25, the high-affinity IL-2 receptor. Denileukin diftitox was approved for the treatment of patients with CTCL refractory to standard treatment options.
HDAC inhibitors were initially developed to modulate chromatin condensation by acetylation of histones affecting gene expression. More recently, their effects on post-translational modification of many intracellular proteins have been recognized. Vorinostat, an orally administered HADC inhibitor, was approved for the treatment of relapsed/refractory CTCL.
Monoclonal antibodies target tumor cells via cell surface markers up-regulated on malignant T cells. Many types of monoclonal antibodies have been used in advanced CTCL such as Zanolimumab is a humanized anti-CD4 monoclonal antibody and Alemtuzumab, a humanized monoclonal antibody against CD52 surface antigen expressed on most malignant T cells.
Conventional systemic treatments include chemo-therapeutic agents and biologic immunomodulatory therapies. Gemcitabine and pegylated doxorubicin are being used as newer initial single-agent chemotherapeutic choices.
Research related to the use of stem cell transplantation in CTCL patients has indicated that autologous hematopoietic stem cell transplants (HCT) achieve a transient, short response, whereas allogeneic HCT has the potential for cure due to graft versus lymphoma effect. Therefore, HSCT should be considered in young healthy patients with advanced disease (i.e. stage IIB – IV) that is refractory to all primary and salvage therapy options, and who have matched donors.