Long-term remission of tumor-stage mycosis fungoides following total-skin electron-beam radiotherapy

ARTICLE

Mycosis fungoides usually follows an orderly progression from limited eczematoid lesions and patches to more generalized plaques and tumors and eventually lymph node and/or visceral involvement. Depending on the stage of the disease several therapeutic modalities are available and include topical chemotherapy with nitrogen mustard [1, 2] and carmustine [2, 3], UVB phototherapy or psoralen photochemotherapy (PUVA) [4-6] as well as total electron beam radiation (TSEB) and interferons alone or in combination with retinoids [7-10]. All of these treatments are effective for early stage disease and have been reported to provide long-term remissions, some of them with limitations of effectiveness, side effects, or compliance.

Here we report on the successful treatment with TSEB of a patient with extensive stage II B mycosis fungoides who presented a therapeutical challenge because of logistic problems and poor compliance.

Case report

A 50-year-old, mentally retarded woman presented with a 10 year history of eczematous patches and plaques and more recently tumors which were disseminated over the entire body. The patient had refused to see a physician. Upon admission to the hospital the undernourished and severely anemic patient presented with generalized eczematous lesions, sharply defined and confluent, flat and scaly plaques of a reddish color, poikilodermatous atrophic lesions and ulcerated, tomato-type tumors, up to several centimeters in diameter, which were distributed over the face, and upper and lower limbs (Figs. 1A and 2A). Eczematous and ulcerated lesions were secondarily infected and heavily crusted. There was diffuse, palmoplantar hyperkeratosis with fissures and confluent polycyclic ulcerations on the soles and prominent axillary and inguinal lymphadenopathy. Except for a few remaining tufts of hair on the occipital region there was universal alopecia. Skin biopsies from a tumor of the right upper arm and a plaque on the lateral trunk were read as cutaneous T cell lymphoma, tumor stage, and immunophenotyping revealed a dense pleomorphic lymphocytic infiltrate extending into the deep dermis and consisting of mainly small, mature lymphocytes which were positive for CD3, CD4, CD5, CD45, CD45Ro, with a smaller number of larger CD30 positive cells and some CD2 positive cells interspersed between them. No anaplastic or immunoblastic transformation or follicular mucinosis could be seen. The patient was anemic (red blood, count 1.96 x 10⁶/l; hemoglobin, 43 g/l; hemotacrit, 13.2%) and the CD4/CD8 ratio in the peripheral blood was 6.5. Anemia was interpreted as secondary due to the chronic inflammatory, ulcerative skin process with secondary infection which resolved after antibiotic and radiation therapy. Bone marrow aspirates revealed prominent myelopoiesis with a predominance of CD4-positive cells but no morphological evidence of bone marrow involvement. T cell receptor (TCR) rearrangement studies performed on skin biopsy specimens revealed TCRß rearrangement (Southern blot) and TCR-gamma rearrangement by PCR. T cell receptor rearrangement studies of peripheral blood and bone marrow did not show clonal growth. X-ray studies and abdominal ultrasound showed no signs of systemic, organ or lymph node involvement and ultrasound examinations of peripheral lymph nodes showed large, echo-rich lymph nodes which returned to normal size after treatment. Lymph node biopsy was refused and since the axillary and inguinal lymph nodes were considered as reactive the patient was staged as stage IIB (T3, NX, M0, B0) cutaneous T cell lymphoma (mycosis fungoides).

In this patient, topical chemotherapy or PUVA for the eczematoid and plaque lesions appeared impractical or difficult to perform owing to the patient's poor compliance and tumors would have required additional ionizing radiation. The decision was therefore made to submit her to TSEB. Supportive measures included topical antiseptic bandages and systemic antibiotics. The patient's anemia was corrected by several red blood cell transfusions.

Tumors were first boosted with single-dose of 2 Gy in an 80% isodose with 6 MeV up to a total dose of 14.4 Gy. Subsequently, the entire skin including palms and soles was irradiated with single doses of 0.5 Gy, up to a total dose of 5 Gy. The total tumor dose applied over a period of six weeks was 19.4 Gy.

After six weeks, the eczematous lesions and plaques had completely disappeared leaving residual pigmentation. The tumors had regressed completely leaving only some residual erythema and minimal infiltration (Figs. 1B and 2B). Plamoplantar hyperkeratosis had disappeared and the plantar ulcers had epithelialized. During therapy there was transient generalized erythema followed by extremely dry skin which persisted after cessation of therapy. At the end of the treatment period there were no residual lesions but hyper- and hypopigmented macules and atrophy were present at the sites of previous tumors and there was prominent ectropion and total alopecia. Blood counts returned to normal and lymph nodes were of normal size. The patient gained 8 kg of bodyweight. After more than three years the patient was admitted with relapsing disease with generalized erythematous plaques and a few slightly elevated tumors without ulceration.

Discussion

In cutaneous T cell lymphoma, the choice of treatment modality depends on the extent and stage of the disease, concurrent diseases, the general condition and compliance of the patient as well as the availability of treatment techniques. For stage II B mycosis fungoides, TSEB therapy with boost irradiation of tumors is considered a first-line therapy and was initiated in this case as the most appropriate approach especially in view of her poor compliance excluding other treatment modalities. Results were dramatic with the complete resolution of tumors and plaque-like infiltrates and the disappearance of the poikilodermatous and eczematoid lesions. Radiation-induced side effects, such as generalized but transient erythema during the first weeks of treatment, severe dryness of skin and ectropion were counteracted by appropriate topical measures.

Response rates of tumor stage CTCL to TSEB are reported to be 36% with relapse within five years [9, 11]. Consequently, and in order to maintain longer periods of remission, follow-up PUVA radiation or topical chemotherapy were considered in this patient, but at the same time it was understood that these types of therapy would probably be impossible to perform considering her mental retardation, her lack of understanding of the severeness of the disease and the fact that she lives in a remote rural area with only her 80-year-old father to look after her. The patient regarded herself healed at the time of discharge from hospital and maintenance therapy and follow-up were refused. After more than three years without any treatment the patient returned to us with relapsing disease.

Long-term freedom from relapse in CTCL is dependent upon the initial extent of skin involvement and type of therapy employed. Despite the high likelihood of relapse after successful TSEB therapy, a significant palliative benefit is achieved with this treatment and relapses are often limited in extent and may be managed by small field orthovoltage or electron beam irradiation. In this particular case, the patient benefited from TSEB therapy with a good quality of life for more than three years. Even now she is in good general condition. After restaging, TSEB therapy of the tumors was initiated and maintainence therapy with retinoids/PUVA is being considered.

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