Cutaneous Paraneoplastic Syndromes in Small Animals

Nodular dermatofibrosis (ND) is a rare but highly specific paraneoplastic syndrome associated with multiple slowly growing cutaneous collagenous nodules, predominantly on the limbs, in association with bilateral renal cystadenocarcinomas or cystadenomas.

ND occurs almost exclusively in German Shepherd dogs and likely has autosomal dominant inheritance. It is associated with genetic mutation in the BHD gene (also known as the FLCN gene) on chromosome 5, which encodes the protein folliculin (1).

Patients with ND have multifocal to diffuse, small, nonpruritic cutaneous nodules that, on biopsy, are consistent with well-differentiated dense collagen bundles in the dermis and subcutis (see ND image). 

Nodular dermatofibrosis, dog

Image

Courtesy of Dr. Brooke Britton.

There is a predominant limb distribution in ND; involvement of the head, neck, and trunk develops in more advanced stages of the condition. ND typically precedes systemic signs of illness from tumor-induced renal failure or metastasis by months to years. Females with ND typically have concurrent uterine leiomyomas.

There is no known effective treatment for ND, and the mean time from development to death is approximately 2.5 years (1).

Paraneoplastic superficial necrolytic dermatitis (SND) occurs most commonly in dogs with glucagon-secreting tumors of the liver and pancreas (2). 

Dermatological findings can include erosions and ulcerations with alopecia; exudation from pressure points, feet, the flank, perineal area, ventrum, and oral cavity/muzzle; crusting; and hyperkeratosis of footpads. These findings are associated with "hepatocutaneous syndrome," in which hepatopathy is also present.

Footpad hyperkeratosis is the hallmark of paraneoplastic SND and occurs in all patients. Lesions can be very painful and pruritic.

Sustained gluconeogenesis and amino acid catabolism in SND patients with these tumors is thought to lead to hypoaminoacidemia, which in turn leads to epidermal protein depletion and keratinocyte necrolysis (2). 

Most dogs affected by paraneoplastic SND have metastatic disease at the time of diagnosis; however, resolution can occur with resection of solitary tumors. Amino acid infusions and somatostatin analogues have been reported for palliative treatment, to limited effect.

In cats, paraneoplastic alopecia is a nonpruritic, symmetrical, progressive alopecia reported with pancreatic carcinoma and biliary carcinoma.

Hair is epilated easily, and skin appears shiny and thin (see alopecia image). The footpads (softening and hyperkeratosis of the pads) can also be involved. Other clinical signs can include anorexia and weight loss, lethargy, and difficulty standing or ambulating (because of pathological footpad changes) (3).

Paraneoplastic alopecia, cat

Image

Courtesy of Dr. Brooke Britton.

Histopathological changes in the affected skin include marked follicular and adnexal atrophy with an absence of stratum corneum (4).

Resolution of paraneoplastic alopecia is rare, given the aggressive and often metastatic nature of the underlying cancer.

Exfoliative dermatitis has been rarely reported in cats as a paraneoplastic syndrome associated with thymoma. The underlying mechanism might be immune mediated.

Exfoliative dermatitis is characterized by nonpruritic scaling, crusting, and alopecia, eventually progressing to the neck, trunk, and limbs, with accumulation of keratosebaceous debris between the digits, within the nail beds, and in the ear canals.

Differential diagnoses include systemic lupus erythematosus, drug-induced skin reactions, epitheliotropic T-cell lymphoma, erythema multiforme, cheyletiellosis, demodicosis, Malassezia dermatitis, dermatophytosis, retroviral dermatosis, parapsoriasis, and sebaceous adenitis.

Histopathological changes include abundant exfoliation of keratin squames and layers, and interface dermatitis with predominantly CD3+ lymphocytes, as well as fewer mast cells and plasma cells (5).

Paraneoplastic exfoliative dermatitis might resolve with thymoma resection.

• Bailey DB. Paraneoplastic syndromes. In: Vail DM, Thamm DH, Lipták JM, eds. Withrow & MacEwen's Small Animal Clinical Oncology. 6th ed. Elsevier; 2020:98-100.

• Turek MM. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. Vet Dermatol. 2003;14(6):279-296. doi:10.1111/j.1365-3164.2003.00346.x

• Also see pet owner content regarding peripheral nerve disorders in dogs and cats.

1. Lingaas F, Comstock KE, Kirkness EF, et al. A mutation in the canine BHD gene is associated with hereditary multifocal renal cystoadenocarcinoma and nodular dermatofibrosis in the German shepherd dog. Hum Mol Genet 2003;12(23):3043-3053. doi:10.1093/hmg/ddg336

2. Turek MM. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. Vet Dermatol. 2003;14(6):279-296. doi:10.1111/j.1365-3164.2003.00346.x

3. Grandt L-M, Roethig A, Schroeder S, et al. Feline paraneoplastic alopecia associated with metastasising intestinal carcinoma. JFMS Open Rep. 2015;1(2):2055116915621582. doi:10.1177/2055116915621582

4. Pascal-Tenorio A, Olivry T, Gross TL, Atlee BA, Ihrke PJ. Paraneoplastic alopecia associated with internal malignancies in the cat. Vet Dermatol. 1997;8(1):47-52. doi:10.1111/j.1365-3164.1997.tb00263.x

5. Rottenberg S, von Tscharner C, Roosje PJ. Thymoma-associated exfoliative dermatitis in cats. Vet Pathol. 2004;41(4):429-433. doi:10.1354/vp.41-4-429