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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