Treatment Approaches for Rare Cutaneous Lymphomas

What Are Rare Cutaneous Lymphomas?

Rare cutaneous lymphomas include primary cutaneous lymphomas that represent a diverse collection of neoplastic conditions involving both T- and B-cells, affecting numerous individuals worldwide each year. In 2018, the World Health Organization introduced updated diagnostic criteria for the various subtypes within this category of tumors. There are two types of cutaneous lymphomas-

• Cutaneous T-cell Lymphomas (CTCL) - These are a relatively uncommon form of non-Hodgkin's lymphoma, distinguished by the presence of malignant T cells infiltrating the skin. The diversity in CTCL manifestations poses challenges in both diagnosing the disease and formulating effective treatment strategies.

• Cutaneous B-cell lymphomas (CBCLs) - These are frequently characterized by their relatively slow and non-aggressive clinical behavior. One distinctive feature often observed is the notable presence of B cells infiltrating the skin's dermal layers. This is noteworthy because B cell accumulations are not typically encountered in healthy skin and are rarely seen in reactive conditions or other forms of cutaneous lymphomas.

What Are the Treatment Approaches for Rare Cutaneous Lymphomas?

Treatment Approaches for Cutaneous T-cell Lymphomas (CTCL) - Cutaneous T-cell lymphomas exhibit a higher incidence among men and individuals designated male at birth, with a twofold increased risk compared to women and individuals designated female at birth. Typically, these lymphomas manifest in individuals aged 40 to 60. Notably, Black individuals have a greater propensity to develop these conditions in comparison to their white or Asian American counterparts. Presently, the treatment of CTCL encompasses various approaches, including skin-targeted therapies such as topical mechlorethamine, topical corticosteroids, topical Bexarotene, ultraviolet phototherapy, and localized radiotherapy. Additionally, more intensive therapies like total skin electron beam therapy and systemic treatments are employed. A deeper understanding of the molecular and signaling pathways responsible for the development of CTCL has paved the way for the exploration of innovative and personalized treatment regimens.

• Phototherapy: This approach is suitable for managing early-stage disease. Phototherapy employs either ultraviolet A (UV-A) or B (UV-B) light, sometimes in conjunction with Psoralen (referred to as PUVA treatment). Following Psoralen administration affected skin areas are exposed to UV light, activating the medication and effectively targeting cancer cells.

• Skin-Directed Treatments: Healthcare professionals employ topical ointments, creams, or light therapies as initial interventions for early-stage cutaneous T-cell lymphoma.

• Extracorporeal Photophoresis (ECP): ECP involves the use of ultraviolet light and Psoralen. Healthcare providers extract a sample of the blood to isolate white blood cells, which are then combined with Psoralen. This makes the cancerous cells susceptible to ultraviolet (UV) light. Subsequently, these treated white blood cells are exposed to UV light, leading to the eradication of cancer cells, after which they are reintroduced into the bloodstream.

• Immunotherapy: This treatment regimen fortifies the immune system through either laboratory-generated substances or the body's own components. Immunotherapy is instrumental in slowing the proliferation of cancer cells or facilitating their elimination.

• Radiation Therapy: Using X-rays or other radiation sources, medical professionals precisely target cancer cells, either impeding their growth or causing their demise.

• Chemotherapy: Chemotherapy can be administered in various forms, including pills, intravenous injection (IV), gels, creams, or lotions directly applied to the affected skin areas. This approach is employed to combat cutaneous T-cell lymphoma.

Treatment Approaches for Cutaneous B-cell Lymphomas (CTCL) - Primary cutaneous B-cell lymphomas make up less than a third of all cutaneous lymphomas. The three main subtypes of primary cutaneous lymphomas, each with its own significance in terms of treatment options and prognosis, include primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) are considered indolent diseases, characterized by a 95 to 99 percent five-year survival rate. In contrast, DLBCL, leg type, follows a more aggressive disease course with a five-year survival rate of less than 50 percent. To confirm the diagnosis of primary cutaneous B-cell lymphoma, a negative staging evaluation is required after the initial clinical and histopathological diagnosis. It is worth noting that in indolent cases like PCMZL, a bone marrow biopsy is typically not necessary for routine staging. However, clinically intermediate to aggressive forms of cutaneous B-cell lymphomas may necessitate a bone marrow biopsy as part of the staging process.

• Chemotherapy - The primary treatment for B-cell lymphoma typically involves chemotherapy. When the disease is localized to one specific area of the body, the treatment approach may incorporate surgical intervention along with a shorter and less intensive course of chemotherapy. However, in cases where the disease has advanced or spread, the standard treatment usually involves high-dose chemotherapy.

• Hematopoietic Stem Cell Transplantation (HSCT) - HSCT is a procedure where hematopoietic stem cells, which give rise to blood cells, are transplanted into a patient. It is used in the treatment of various hematologic malignancies, including some types of B-cell lymphomas. HSCT can help to replace damaged or cancerous cells with healthy ones and may be considered when other treatments have not been effective or in cases of aggressive lymphomas.

• Targeted B-cell Agents - These are medications designed to specifically target B cells or proteins involved in B-cell lymphomas. One example is the drug rituximab, which targets CD20 proteins in B cells and is commonly used in combination with chemotherapy to treat B-cell lymphomas.

• Immunotherapy, Including CAR-T Cell Therapy (Tisagenlecleucel and Axicabtagene Ciloleucel) - Immunotherapy is a rapidly advancing field in cancer treatment. CAR-T cell therapy, utilizing medications like Tisagenlecleucel and Axicabtagene ciloleucel, involves genetically modifying a patient's own T cells to target and attack cancer cells more effectively. This therapy has shown remarkable success in treating certain types of B-cell lymphomas, especially when other treatments have failed.

Conclusion

Primary cutaneous lymphomas (CLs) constitute a diverse group of lymphoproliferative neoplasms characterized by localized lymphatic proliferation solely within the skin, devoid of involvement in lymph nodes, bone marrow, or internal organs upon initial diagnosis. These cutaneous lymphomas develop from fully mature lymphocytes, encompassing mature T-lymphocytes (representing 65 percent of cases), mature B-lymphocytes (making up 25 percent), or natural killer (NK) cells. The cornerstone of diagnosis relies on histopathological assessment, accompanied by immunophenotyping of the skin biopsy specimen. However, it is imperative to complement this diagnosis with a meticulous staging of the disease and the identification of prognostic factors. Such comprehensive evaluation serves a dual purpose: facilitating the selection of the most suitable treatment approach and assessing the outcomes of the chosen treatment modality.