Mycosis Fungoides (Epitheliotrophic Lymphoma)
Mycosis Fungoides (MF) is a form of T-cell like lymphoma that attacks
the skin as its primary target organ. Because this malignancy mimics allergic,
pustular, parasitic and fungal disease in humans, dogs and cats, it earned
its “mycotic” or “fungal” like name early on and
is one of medicine’s famous misnomers. MF occurs seldom in older
dogs and is rarely seen in cats.
The Three Stages of MF
The clinical course of MF can be quite variable. It has several stages
of clinical appearance. Initially, MF may appear like an allergic skin
rash or fleabite dermatitis or pimphigus with or without itching and pruritis.
This has been called the “Premycotic Stage.” Some animals
will present scaling or abnormal redness of the skin (erythroderma). Others
develop pigmentation changes in the skin along their mucocutaneous junctions.
Some develop lesions of patchy alopecia, crusts and dandruff that resemble
cigarette ashes in the coat. Later, in the “Mycotic Stage,”
MF appears as a fungal infection with raised, round erythematous firm
plaques. This resemble ringworm lesions, which may form over the pre-existing
lesions or in de novo areas. Some of the plaques will ulcerate, peel,
form exudates and crust over.
The final nodular stage manifests ulcerated protruding lesions that may
appear in the mouth, nose, lips, eyelids, anus, prepuce, foot pads and
anywhere in the dermis. This tumor stage eventually spreads systemically
and involves lymph nodes and internal organs. The coetaneous lesions described
in the three stages above are generally resistant to most treatments administered.
Steroids and antibiotics may provide only minor and temporary palliation
of signs.
Occasionally a solitary lesion in the lips or in the buccal mucosa of
dogs may respond to radiation and or chemotherapy and will remain indolent
for several years.
Sezary Syndrome
In certain rare cases, MF may take on a leukemic form with helper T-cells
circulating in the peripheral blood stream (Sezary Syndrome). Despite
the dismal appearance of Sezary cells in the blood and its associated
splenomegaly, lymphadenopathy and erythroderma, the patient’s survival
is not adversely affected. Until recently, the skin lesions of MF have
been very difficult to control even with combination chemotherapy. Many
pets never got to the final nodular tumor stages of MF.
Cutaneous Lymphoma
Older dogs with multicentric B-cell lymphoma may develop dermal masses
as their disease progresses. Most dogs present multiple, ulcerated, plaque
type, dermal skin tumors, which developed following a chronic unresponsive
pruritic skin disease. There is not much difference in the appearance
of dogs with cutaneous lymphoma and MF.Early Diagnosis is the Key
We need to improve our recognition of the warning signs of MF for earlier
detection.
It is best to recommend repeatedly to the pet owner that a simple punch
biopsy of any stubborn skin lesions will establish the actual diagnosis.
Most skin lesions (blemishes, brusies, ulcers or raised sores) should
fall into the simple two to three week healing period. If the lesions
are not healed by that deadline, we tell the pet owner that a biopsy is
clearly indicated. Multiple samples should be taken from the edges and
the center of several lesions for histopathology.
The more samples take, the greater chance you will have for definitive
results especially if samples are taken in the early stages of disease
or in newly noticed lesions. Once the diagnosis is made, a full work up
is indicated to rule out systemic involvement and to differentiate between
primary cutaneous or metastatic lymphoma or MF and Sezary syndrome.
Nutritional Treatment for MF
Our profession has shown a wide acceptance of the use of supplements and
dietary changes as another effective tool in disease management. In 1992,
Iwamoto, Bennett and colleagues from UCLA published an article in Cancer
Letters that followed a clinical study we ran on 8 dogs with MF.
Overall, some dogs benefited from receiving 87% safflower oil at 3ml/kg
on 3 consecutive days weekly in their diet. At the Veterinary Cancer Society
Meeting in 1992, Dr. Christina Hutson, reported a case of MF that had
a dramatic and complete remission of a huge 6cm by 8 cm resistant mass
involving the gingival and buccal mucosa. The dog was a Golden Retriever
that received oral safflower oil under the same regimen. Simultaneously,
Dr. Elizabeth Hodgkins eloquently reported that fatty acids played a role
in cancer management. The early reports generated from clinical studies
conducted at our facility, were the first to demonstrate that fatty acids
exerted some benefit specifically in MF and may potentially act against
other cancers.
Dr. Craig Oglivie and co-workers at CSU developed a high fat and high
protein diet that is Hill’s n/d, the first commercial diet that
may assist patients in combating cancer. The diet contains high doses
of omega-3 fatty acids from Manhaden oil and argenine and contains 9.5%+
protein.
Dr. Oglivie reported that dogs with lymphoma that were fed this diet had
enhanced their survival rate and dogs undergoing radiation therapy benefited
as well. We can presume that n/d is potentially beneficial for pets with
MF and other tumors including diseases of dendritic (branched) cell abnormalities
such as cutaneous histiocytosis. We know that fatty acids exert anti-inflammatory
effects in skin disease. Dr. Villalobos and her UCLA colleagues, had two
dogs with mast cell cancer wind up in the emergency room for degranulation
of their mast cells while on linoleic acid in the form of safflower oil.
However, the mechanism by which fatty acids act to inhibit cancer cells
is multifaceted and warrants further discussion elsewhere. In addition
to diet changes, beta glucan and IP-6 for pets with MF can also be used
to improve conditions.
Chemotherapy for MF
The chemotherapy protocol that is suggested for MF combines: Lomustine
at 50-60 mg/M2 every 21 days if the platelets are holding above 100,000.
After 3-4 cycles of Lomustine, generally an increase of the interval between
doses should be lowered to every 4-5 weeks or the dosage should be lowered
to maintain the platelet count.
Prednisone at 1-2mg/kg orally is given on three consecutive days in a
row the morning of the same day the pet receives safflower oil. Safflower
oil at 3ml/kg is mixed in the food on 3 consecutive days per week. Our
UCLA colleagues selected a commercially available oil that was 87% safflower
(Hollywood Safflower Oil).
Radiation Therapy for MF
Over the years, radiation therapy has been used to manage solitary and
some specific lesions of MF; however, long-term survival for severely
affected cases has been dismal until recently. With the combination of
dietary management and chemotherapy, radiation therapy may be more instrumental
in controlling the tempest of resistant lesions. Whole body radiation
has been tried, but was found to be too toxic. Half body radiation therapy
may hold more promise in the successful management of MF, cutaneous lymphoma
and multicentric lymphoma. Dr. Villalobos found radiation of solitary
lesions that occur in the oral cavity is most rewarding for the dogs.
With the specific diet changes, the medications mentioned above and the
judicious use of radiation therapy, pets can be seen entering into a more
prolonged remission. With better survival through treatment, an even more
protracted clinical course in our patients may be created. Some day most
of the MF patients may live for an equivalent of 20+ pet years, similar
to the way MF smolders along in humans undergoing treatment.
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