Feline Cutaneous Paraneoplastic Disease
Introduction
A cutaneous paraneoplastic disease is defined as a neoplastic process in one organ system resulting in disease in the skin. The dermatosis occurs after the development of the cancer and the cancer and skin lesions follow parallel courses. Removal of the tumour should result in resolution of skin lesions, and recurrence of the cancer causes a relapse of the dermatosis. In some cases, disease morbidity and effects on quality of life are more due to the paraneoplastic effects than the primary tumour. Several cutaneous paraneoplastic diseases have been recognised in the cat.
Feline Paraneoplastic Alopecia
Rare, paraneoplastic disease described exclusively in cats.1 Characterised by progressive symmetrical alopecia associated with underlying pancreatic neoplasia, either a biliary carcinoma or exocrine adenocarcinoma. Resolution of the dermatosis with excision of the tumour has been demonstrated.2
Clinical Signs
Seen in middle-aged to older cats. Main presenting sign is dramatic alopecia with easily epilated hair affecting the ventral surfaces and medial limbs with later involvement of the pinnae and periorbital areas. Lesions evolve over one to three months. Alopecic skin has a smooth shiny appearance and is inelastic but not fragile. Brown-coloured adherent crust and scale and secondary Malassezia dermatitis and bacterial overgrowth are common. Overgrooming may be a feature. Systemic signs include weight loss, vomiting, diarrhoea, inappetence and lethargy.
Diagnosis and Prognosis
Suggestive clinical signs are confirmed on histopathological examination. Biopsy punch samples are taken from areas of complete alopecia with a shiny appearance. There is an atrophic dermatosis with miniaturisation of hair follicles, acanthosis, parakeratosis and orthokeratosis. Haematology and serum biochemistry are frequently unrewarding. Ultrasound or CT scanning, and/or surgical abdominal exploration may be indicated along with chest radiographs to rule out thoracic metastasis.
The prognosis is guarded and most cats are euthanased within weeks to months due to progressive clinical signs as a result of tumour metastasis. One cat had a temporary resolution of clinical signs following excision of the pancreatic carcinoma but was later euthanased because of tumour metastasis.2
Superficial Necrolytic Dermatitis
Superficial necrolytic dermatitis (necrolytic migratory erythema, hepatocutaneous syndrome) is a condition mainly reported in the dog and is associated with a hepatopathy or glucagonoma. It is thought that hypoaminoacidaemia and deficiency of other essential nutrients leads to epidermal cellular necrosis. SND has only rarely been described in the cat in association with pancreatic carcinoma,3 thymic amyloidosis, hepatic necrosis with intestinal lymphosarcoma, and hepatopathy. Hypoaminoacidaemia was demonstrated in one cat.
Clinical Signs
Anorexia, depression and vomiting, gingivitis and stomatitis. Skin lesions are variable and consist of ventral, interdigital, and mucocutaneous alopecia, excoriations, crusting and scaling. Secondary Malassezia dermatitis may occur. Pruritus is variable.
Diagnosis
Systemic illness with skin lesions is suggestive. Definitive diagnosis is based on a combination of dermatohistopathology, blood work, abdominal imaging, aspiration of a possible hepatic or pancreatic lesion, and surgical exploration.
Histopathological changes are characteristic with parakeratotic hyperkeratosis; upper epidermal pallor (inter- and intracellular oedema) and hyperplasia of basal and suprabasal keratinocytes. These histopathological changes are pathognomonic in the cat.4
Prognosis
All reported cats were euthanased. To the author's knowledge, there are no reports of cases to date where a pancreatic tumour has been excised and clinical signs resolved.
Feline Exfoliative Disease (FED)
Feline exfoliative dermatitis is a syndrome of exfoliative erythroderma associated with a thymoma that is seen middle-aged to older cats. Resection of the thymoma can result in complete remission of the dermatosis. Thymomas are uncommon neoplasms of the cranial mediastinum derived from thymic epithelium and have variable lymphocytic infiltration. Most are benign. It is thought that the thymoma may be responsible for the production of autoreactive, cytotoxic T-cells that target keratinocytes.
Clinical Signs
Initial signs consist of nonpruritic scaling and mild erythema of the head and pinnae in middle-aged to older, otherwise healthy, cats. There is progressive generalization over weeks to months with increasing scaling, alopecia and exfoliative erythroderma. Sheets of exfoliating stratum corneum may be a feature and crusting and ulceration may also become evident.5 The cat may develop systemic signs including coughing, dyspnoea, lethargy and weight loss.
The differential diagnosis includes cheyletiellosis, Malassezia dermatitis, demodicosis, dermatophytosis, FeLV and FIV dermatitis, sebaceous adenitis, erythema multiforme, drug eruptions, systemic lupus erythematosus and epitheliotropic lymphoma.
Diagnosis
The diagnosis is based on history and clinical signs, dermatohistopathology and demonstration of a thymoma. Skin scrapes, cytology, fungal culture and histopathological examination are indicated.
Histopathology shows a mainly cell poor interface dermatitis with a lymphohistiocytic infundibular and isthmic interface mural folliculitis along with variable involvement of sebaceous glands.6
Chest radiography is indicated in a cat with these histopathological findings to identify possible thymoma. Radiography demonstrates a soft tissue opacity causing caudal displacement of the cardiac shadow and dorsal displacement of the cardiac shadow in the ventral aspect of the mediastinum. It is important to differentiate between lymphoma and thymoma, as medical therapy is the recommended treatment for lymphoma whereas thymoma requires surgery.7
Prognosis and Treatment
In one study, four out of five cats were euthanased because of refractory skin disease but surgical removal can result in complete resolution of clinical signs.6 With thymoma, it is the degree of tumour invasiveness rather than the histology that is considered the main prognostical determinant.7 The prognosis for noninvasive tumours following surgery is good.
Feline Exfoliative Disease Without Thymoma (FEDw)
An exfoliative dermatosis that is indistinguishable from FEDt is recognized in cats that do not have thymoma.8 The histopathology is similar to that seen with FEDt. Most cases benefit from immunosuppressive therapy.
Feline Hyperadrenocorticism9
Naturally occurring feline hyperadrenocorticism (hypercortisolism) is a rare disease. Eighty percent of cases are due to a corticotropin secreting pituitary tumour, and 20% of cases result from an adrenal tumour (50% benign, 50% malignant).
Clinical Signs
Typically middle-aged to older cats with no breed or sex predisposition. Clinical signs include polyuria, polydipsia, weight loss, skeletal muscle atrophy, lethargy, recurrent infections, abscesses, a potbellied appearance, obesity, hepatomegaly, diabetes mellitus (50% of cases), GI symptoms, congestive cardiac failure and UTIs. Cutaneous signs include a poor hair coat, alopecia, seborrhea, pyoderma and thin, easily bruised skin. Cutaneous hyperfragility syndrome occurs in 15–30% of cases.
Note that HAC is not the only cause of cutaneous hyperfragility syndrome.
Diagnosis
History and clinical signs should lead the clinician to be suspicious of HAC. Laboratory findings include hyperglycaemia and glycosuria; elevated liver enzymes, hypokalaemia, hyperglobulinaemia, azotaemia. A stress leucogram may be evident. Radiographic changes include hepatomegaly, osteopenia and dystrophic mineralization.
Endocrine tests can give inconsistent results and a combination of tests may be necessary.9 Good screening tests to rule out HAC include urinary cortisol to creatinine ratio (UCCR) and the low-dose dexamethasone suppression test.
Eighty-five to 90% of cats with hyperadrenocorticism fail to suppress with the low-dose dexamethasone suppression test at 8 hours. False negative results occur in 30–40% of cases with the ACTH stimulation test.
Ultrasound, CT and MRI can be used to determine the shape and size of the adrenal glands and 50% of pituitary tumours may be identified on CT or MRI.
Prognosis and Therapy
The prognosis is poor without effective treatment. Therapeutic options include mitotane, metyrapone and trilostane, but there are few large-scale studies.
The current treatment of choice is trilostane with benefit reported in small numbers of cats.10
References
1. Bordeau W, Guaguere E, Bensignor E, Alhaidari Z. Feline paraneoplastic alopecia: a retrospective study of seven cases. Vet Dermatol. 2000;11(S1):30.
2. Tasker S, Griffon DJ, Nuttall TJ, Hill PB. Resolution of paraneoplastic alopecia following surgical removal of a pancreatic carcinoma in a cat. J Small Anim Pract. 1999;40(1):16–19.
3. Patel A, Whitbread TJ, McNeill PE. A case of metabolic epidermal necrosis in a cat. Vet Dermatol. 1996;7:221–226.
4. Gross TI, Ihrke PJ, Walker EI, Affolter VK. Superficial necrolytic dermatitis - necrotizing diseases of the epidermis. Skin Diseases of the Dog and Cat. Oxford: Blackwell Science; 2005:86–91.
5. Turek MM. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. Vet Dermatol. 2003;14(6)279–296.
6. Rottenberg S, von Tscharner C, Roosje PJ. Thymoma-associated exfoliative dermatitis in cats. Vet Pathol. 2004;41(4):429–433.
7. Zitz JC, Birchard SJ, Couto GC, Samii VF, Weisbrode SE, Young GS. Results of excision of thymoma in cats and dogs: 20 cases (1984–2005). J Am Vet Med Assoc. 2008;232(8):1186–1192.
8. Linek M, Rufenacht S, Brachelente C, et al. Nonthymoma-associated exfoliative dermatitis in 18 cats. Vet Dermatol. 2015;26(1):40–e13.
9. Gunn-Moore D. Feline endocrineopathies. Vet Clin North Am Small Anim Pract. 2005;35(1):171–210, vii. Epub 2015 Jan 4.