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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.
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.
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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