JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2780588): Cat, breed and age unspecified
HISTORY: This cat had weight loss and areas of alopecia around all mucocutaneous junctions, the legs, and axillary regions for 4 weeks. The cat also had multiple masses in the liver.
HISTOPATHOLOGIC DESCRIPTION: Haired skin: There is a diffuse paucity of hair follicles and hair shafts. Remaining hair follicles are small (atrophy), located primarily in the superficial dermis and surrounded by fibroblasts and smudgy collagen (fibrosis). There is attenuation of the external root sheath epithelium and a lack of internal root sheath epithelium (telogenization) and there are occasional small basophilic clusters of secondary hair germ at the base of attenuated follicles. Multifocally there is rare atrophy of sebaceous glands. The stratum corneum is thinned and parakeratotic, and there is mild epidermal hyperplasia with acanthosis, rete ridge formation, spongiosis and intracellular edema (hydropic degeneration).
MORPHOLOGIC DIAGNOSIS: Haired skin: Follicular atrophy, diffuse, severe, with stratum corneum thinning, parakeratosis, and mild epidermal hyperplasia, breed unspecified, feline
CONDITION: Paraneoplastic alopecia
SYNONYMS: Pancreatic paraneoplastic alopecia
- Rare dermatoses associated with internal malignancies; the skin disease often serves as a harbinger for malignancy
- The dermatosis occurs after the development of a malignant tumor, and the skin disease and the tumor follow a parallel course
- Has been reported in older cats with pancreatic carcinoma, biliary carcinoma, and hepatocellular carcinoma
- Skin lesions are potentially reversible if malignancy is excised prior to metastasis
- Metastasis of the primary tumor to the liver or lungs has usually occurred by the time of diagnosis of the skin disease
- Ultimately poor prognosis due to malignant neoplasia
- Exploratory laparotomy and biopsy is often needed to confirm the neoplasia
- In humans, unproven relationship with overexpression of transforming growth factor alpha (TGF-α) and concurrent overexpression of epidermal growth factor receptor (EGFR)
TYPICAL CLINICAL FINDINGS:
- Non-pruritic, rapidly progressive, largely ventrally distributed, symmetric alopecia with characteristic shiny/glistening appearance
- Alopecia commences on the ventral abdomen, thorax, and legs, and then generalizes; the ears and periocular skin are less frequently involved
- Remaining hair epilates easily
- Systemic signs of anorexia, vomiting, diarrhea, weight loss, and lethargy
TYPICAL GROSS FINDINGS:
- Alopecic skin is inelastic (but not fragile), smooth, soft, and often has a distinctive shiny or glistening appearance even in areas that have not been groomed
- The pawpads are painful and appear either dry with circular rings and scales, or erythematous and moist
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Nonscarring alopecia with follicular telogenization, miniaturization, and atrophy with a reduction or absence of the stratum corneum
- Some cats groom excessively and it has been suggested that the smooth shiny appearance of the skin is because of the absence of the stratum corneum
- Variable orthokeratotic and parakeratotic hyperkeratosis
- Secondary infection with Malassezia pachydermatis is sometimes identified
- Moderate to severe acanthosis
- Pawpads may have a fractured or flaky keratin layer
- In some cases, neutrophilic scale/crusting are prominent
- Superficial follicles are occasionally plugged with parakeratotic debris; petite basophilic clusters of secondary hair germ frequently are present at the base of attenuated follicles
- Sebaceous glands are usually unaffected and may appear large in relation to severe follicular attenuation; sebaceous atrophy is sometimes observed
- Dermal inflammation is absent to moderate, and is more intense when occurring in conjunction with erosion and crusting
- When inflammation occurs, inflammatory cells include lymphocytes, histiocytes, and fewer neutrophils; the latter are most prominent in areas of erosion and crusting; mast cells are often numerous
- Clinically, differential diagnoses are few, because the syndrome is highly visually distinctive
- Pawpad lesions may resemble superficial necrolytic dermatitis (SND), but SND is not alopecic
- Differentials for feline symmetrical alopecia:
- Feline endogenous or iatrogenic hyperadrenocorticism: Fragile skin, epidermal and follicular infundibular atrophy with sebaceous gland atrophy, increased tricholemmal keratin, and calcinosis cutis
- Feline telogen effluvium: Hair follicles in telogen with no atrophy or pathology in dermis or epidermis (acute synchronization in telogen following stress)
- Hyperthyroidism: Seborrhea, thin skin resembling hyperadrenocorticism
- Feline psychogenic alopecia: Notable histopathologic findings usually are not present; if present, there are broken hairs, undamaged underlying skin and normal hair follicles with occasionally trichomalacia
- Feline acquired skin fragility syndrome: Markedly thin skin that tears easily; especially on the dorsum of the trunk
Principle cutaneous paraneoplastic syndromes
- Paraneoplastic alopecia and internal malignancies in the cat
- Exfoliative dermatitis and thymoma in the cat, dog, and rabbit – characterized by a cell-poor hydropic interface dermatitis
- Superficial necrolytic dermatitis in the dog and the cat (due to hepatic dysfunction)– also known as hepatocutaneous syndrome in dogs
- Major findings include erosions and ulcerations, with alopecia, exudation and adherent crusts on the feet, pressure points such as the elbows and hocks, flank, perineal area, muzzle, facial mucocutaneous junctions and/or oral cavity; characteristic "red, white, and blue" epidermis: parakeratotic hyperkeratosis and crusting (red), edema and necrosis of keratinocytes in the stratum spinosum (white), and hyperplastic basal cells (blue)
- Pancreatic panniculitis (necrotizing panniculitis) in the dog (due to lipase presence within the panniculus)
- Nodular dermatofibrosis and renal or uterine tumors in dogs – skin lesions consist of multiple, firm, well-circumscribed collagenous nodules ranging from 2 to 5 mm, associated with renal cystadenocarcinoma or cystadenoma and concurrent uterine leiomyomas
- Paraneoplastic pemphigus – one case reported in a Bouvier dog with mediastinal lymphoma; skin lesions were epidermal acantholysis, keratinocyte necrosis, and vacuolar interface dermatitis
- One case of diffuse lymphoma with generalized pruritis and alopecia in a horse
- Caporali, C., Albanese, F., Binanti, D., and Abramo, F. Two cases of feline paraneoplastic alopecia associated with a neuroendocrine pancreatic neoplasia and a hepatosplenic plasma cell tumor. Vet Derm. 2016; doi:10.1111/vde.12375 [Epub ahead of print].
- Finley MR, Rebhun WC, Dee A, Langsetmo I. Paraneoplastic pruritus and alopecia in a horse with diffuse lymphoma. J Am Vet Med Assoc. 1998; 213:102-104.
- Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. Ames, IA: Blackwell Science; 2006:487-490, 498-501, 513-515.
- Hargis AM, Ginn PE: The integument. In: McGavin MG, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO; Elsevier: 1077.
- Marconato L, Albanese F, Viacava P, Marchetti V, Abramo F. Paraneoplastic alopecia associated with hepatocellular carcinoma in a cat. Vet Dermatol. 2007; 18:267-271.
- Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG Jubb, Kennedy,and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd. 2016:691-692.
- Roccabianca P, Rondena M, Paltrinieri S, Pocacqua V, Scarpa P, Faverzani S, et al. Multiple endocrine neoplasia type-I-like syndrome in two cats. Vet Pathol. 2006; 43:345-352.
- Sharpe, SJ, Meadows, RL, Senter, DA, and Kuroki, K. Pathology in Practice. J Am Vet Med Assoc. 2014; 244:1265-7.
- Turek MM: Cutaneous paraneoplastic syndromes in dogs and cats: A review of the literature. Vet Dermatol. 2003; 14:279-96.