Cutaneous paraneoplastic disease: Sometimes prognosis remains poor

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May 01, 2006

Q. Please review inappropriate urination/cystitis in cats.

A. Dr. Stephen D. White at the 2005 American College of Veterinary Internal Medicine Forum in Baltimore gave a lecture on cutaneous paraneoplastic syndromes. Some relevant points in this lecture are provided below.

Cat diseases

Feline paraneoplastic alopecia presents as a ventral alopecia in which the abdominal skin appears to glisten but is not fragile. This syndrome can have a secondary Malassezia infection and also can be associated with dry, fissured foot pads. Necropsy usually reveals an exocrine pancreatic adenocarcinoma and can metastasize to the liver and elsewhere. Histopathologic examination of the skin shows severe atrophy and miniaturization of the hair follicles. Temporary resolution of the skin disease can occur when the primary tumor is removed. Prognosis is poor.

Feline skin fragility syndrome is seen in older cats in association with hepatic neoplasia, hyperadrenocorticism or hepatic lipidosis. Serum concentrations of progesterone and testosterone are increased when compared with a group of normal cats, and the clinical signs of skin fragility are attributed to hyperprogesteronemia. Diagnosis of hyperadrenocorticism can be made either by ultrasonography of the adrenal glands or an ACTH stimulation test protocol of synthetic solution of 125 micrograms intravenously with collected post samples at one and two hours. Therapy has not been standardized — bilateral adrenalectomy, ketoconazole (10 to 15 mg/kg SID) and metyrapone (65 mg/kg BID) are all recommended.

Thymomas are associated with an exfoliative dermatitis in older, and often orange, cats. The causative mechanism is unknown, but an erythema multiforme-type reaction has been proposed. If detected, the tumor's removal usually will lead to resolution of signs. Recently, radiotherapy has been reported as a therapeutic option.

Paraneoplastic pemphigus appears to be a combination of pemphigus foliaceus (exfoliative dermatitis) and pemphigus vulgaris (ulcers, especially in the oral cavity). Thymic lymphoma and cutaneous lymphoma are among the neoplasms implicated. The auto-antibodies in paraneoplastic pemphigus target different proteins than those of pemphigus foliaceus or pemphigus vulgaris.

Metastatic pulmonary adenocarcinomas have been reported in cats. The lesions occur on the distal extremities, especially the front feet, and look more like inflammatory pododermatitis than a neoplastic process. Their presence can be observed before pulmonary signs are noted. The neoplasm may be either a bronchogenic or squamous cell carcinoma. Palliative treatment to reduce the discomfort may be attempted (topical or systemic corticosteroids to reduce edema or piroxicam). Finally, clinicians should remember that malignancies of all kinds may metastasize to the skin and even mimic inflammatory dermatoses.

Dog diseases

Nodular dermatofibrosis syndrome in German Shepherds and occasionally other breeds is associated with renal cystadenocarcinomas or cystadenomas. Intact females may have multiple uterine leiomyomas. Histopathologic study of the nodules reveals dense collagen fibrosis. These nodules are most often found on the distal extremities. Diagnosis of renal lesions is best done by ultrasound study. This should be repeated at six-month intervals if the disease is suspected but original ultrasound study is normal. While the prognosis is serious, some dogs with benign renal cysts have survived for five years or more after diagnosis. In German Shepherds, this syndrome might be caused by a mutation in a previously unidentified tumor suppressor gene.

Glucagonoma syndrome is a less common cause of superficial necrolytic dermatitis; the more common cause is the hepatocutaneous syndrome. This disease has been reported in a small number of dogs. The cutaneous lesions include crusting, erythema, exudation and alopecia periorally and periocularly, around the genitals, and the distal extremities, as well as hyperkeratosis and ulceration of the footpads. The skin disease may precede the onset of the signs of the internal disease. Histopathologic findings include superficial perivascular-to-lichenoid dermatitis, with marked diffuse parakeratotic hyperkeratosis and striking intercellular and intracellular edema limited to the upper half of the epidermis (red, white and blue sign). Diagnosis may be problematic; typical physical and histopathologic findings in the absence of a hepatic ultrasound findings of both hyperechoic and hypoechoic areas in the liver (Swiss-cheese or honey-comb pattern) should prompt suspicion. Ultrasonography may show a tumor in the pancreas region. Dogs are often hyperglycemic or diabetic and have hypoaminoacidemia. Serum glucagon may be measured but is not always elevated; there are concerns that there might be different forms of glucagon, not all of which are detectable with current tests. Special immunohistopathologic stains for glucagons secreting cells may be done on tumors found in the pancreas. These tumors often, but not always, metastasize. These dogs also commonly have secondary skin infections (bacterial and/or yeast); appropriate treatment can make the dog more comfortable.