ONCOLOGY.
No. 13
Special Series on Peripheral T-cell Lymphomas
Current Management of Primary Cutaneous CD30+ T-cell Lymphoproliferative Disorders
By Marshall E. Kadin, MD
Professor
Department of Dermatology and Skin Surgery
Boston University School of Medicine and
Roger Williams Medical Center
Providence, Rhode Island |
November 30, 2009
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
Acknowledgement: Dr. Kadin is supported by NIH grant P20RR018757
• Primary Cutaneous Anaplastic Large-Cell Lymphoma—While spontaneous regression is characteristic of LyP, only 25% of primary cutaneous ALCL lesions will regress.[3] Nevertheless, this number is sufficiently high to warrant as initial management expectant follow-up for a period of 4 to 6 weeks. If spontaneous regression occurs, therapy is not indicated, and such patients should be observed for possible disease recurrence. A small number of patients whose disease spontaneously regresses will not have recurrence of their disease. Therefore, observation for spontaneous regression is an appropriate first step in managing this disease.[3,24,25]
Unfortunately, most patients with primary cutaneous ALCL have disease that does not regress spontaneously.[24-26] For these patients, choice of therapy depends on disease distribution and whether the lesions are singular or multiple. An exception to this approach may arise when other associated lymphoproliferative disorders such as mycosis fungoides or symptomatic LyP are simultaneously encountered, in which case the therapeutic approach should be directed against both diseases.[14]
Solitary lesions respond to local radiotherapy.[25,27] Although surgical excision represents an alternative approach, excision specimens may contain margins involved by disease.[23,25] For this reason, radiotherapy is the preferred treatment for solitary lesions. Radiotherapy consists of electron-beam irradiation (4–10 million eV) with a total radiation dose of 40 Gy. Because electron-beam therapy penetrates only to the dermis, there are no systemic effects, although side effects include alopecia, atrophy of sweat glands and skin, radio-dermatitis and edema.
In general, radiotherapy is impractical for patients with multiple non-regressing lesions, although total-skin electron-beam therapy may be a consideration if other diseases, like mycosis fungoides, are present. For this reason, systemic therapy is the treatment of choice for this group of patients.[28] Because long-term remissions are generally not achieved with multiagent chemotherapy, less toxic, single-agent therapies are preferred. As in LyP, methotrexate can be effective in inducing remissions, but higher weekly doses of methotrexate may be necessary.[17] In affected patients whose disease is refractory or progressive on methotrexate, oral etoposide has been shown to be safe and effective therapy for primary cutaneous ALCL.[29] Other potential therapies are purine nucleoside analogs (eg, pentostatin), retinoids, interferon-gamma, interleukin-12, imiquimod (Aldara), and monoclonal antibody against CD30.[24,30,31]
Finally, it is important to monitor patients for potential dissemination of primary cutaneous ALCL to lymph nodes and systemic organs, as well as development of associated malignancies, particularly mycosis fungoides, Hodgkin lymphoma, and B-cell non-Hodgkin lymphoma. Patients who develop systemic ALCL should be considered for multiagent systemic chemotherapies similar to those used in treatment of systemic ALCL, eg, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens.[25,27] High-dose chemotherapy followed by stem cell rescue may be indicated in affected patients who are at high risk.[25,27] Determination of high risk may be based on prognostic factors for survival in the International Prognostic Index.[32]
Personal Approach to Patients With CD30+ PCLPD
Patients are often frustrated because of the delay in establishing the correct diagnosis. They are also fearful of their prognosis because of the association of LyP with development of other lymphomas and the high-grade histology of their lesions. My priority is to reassure the patient about his or her favorable prognosis and to answer any questions about the disease. If the lesions scar or interfere with normal activity, I discuss alternatives to expectant treatment. I explain that low-dose methotrexate is the most effective treatment but is not indicated for women of childbearing age who expect to become pregnant, people with a history of liver disease, or those with blood dyscrasias. I discuss other options including PUVA/UVB and topical treatments.
I notify LyP patients of their increased risk for developing skin lesions of mycosis fungoides and ALCL, or enlarged lymph nodes of Hodgkin disease or non-Hodgkin lymphoma, and of the need to immediately bring these symptoms to the attention of their physician. For patients with suspected primary cutaneous ALCL, I confirm that appropriate clinical and pathologic studies have been done to exclude nodal/systemic ALCL. I recommend irradiation of localized skin tumors and methotrexate for multifocal cutaneous lesions. Follow-up of skin lesions should be carried out by a dermatologist and consultation by an oncologist when additional irradiation or multiagent chemotherapy is required.
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