JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
September 2022
I-M31

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). Hair follicles do not extend into the deeper dermis or panniculus, and there is attenuation of the external root sheath epithelium and a lack of internal root sheath epithelium (telogenization). There are occasional small basophilic clusters of secondary hair germ at the base of attenuated follicles. Multifocally there is rare atrophy of sebaceous glands; otherwise sebaceous glands appear prominent adjacent to attenuated follicles. The stratum corneum is thinned and parakeratotic, and there is mild epidermal hyperplasia with acanthosis, spongiosis, and intracellular edema (hydropic degeneration).

 

MORPHOLOGIC DIAGNOSIS:  Haired skin: Follicular atrophy, diffuse, severe, with stratum corneum thinning, parakeratosis, follicular telogenization, and mild epidermal hyperplasia, breed unspecified, feline

 

CONDITION: Paraneoplastic alopecia

 

SYNONYMS: Pancreatic paraneoplastic alopecia

 

GENERAL DISCUSSION:

• Paraneoplastic alopecia is a rare dermatosis associated with internal neoplasms (malignant or less often benign); the skin disease often serves as a harbinger for malignancy; the skin disease and the tumor follow a parallel course
• Has been reported in older cats with pancreatic carcinoma, biliary carcinoma, hepatocellular carcinoma, neuroendocrine pancreatic neoplasia, hepatosplenic plasma cell tumor, and metastatic intestinal 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

 

PATHOGENESIS:

• Unknown
• In humans, unproven relationship with overexpression of transforming growth factor alpha (TGF-α) and concurrent overexpression of epidermal growth factor receptor (EGFR)
• Some cats groom excessively; suggested that the smooth shiny appearance of the skin is because of the absence of the stratum corneum

 

TYPICAL CLINICAL FINDINGS:

• Non-pruritic, rapidly progressive, 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
• Pawpads are painful and appear either dry with circular rings and scales, or erythematous and moist

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Non-scarring alopecia with follicular telogenization, miniaturization, and atrophy; moderate to severe acanthosis
• Reduction or absence of the stratum corneum, though there may be areas of orthokeratotic or parakeratotic hyperkeratosis
• Superficial follicles are occasionally plugged with parakeratotic debris
• Petite basophilic clusters of secondary hair germ frequently are present at the base of attenuated follicles
• Secondary infection with Malassezia pachydermatis is sometimes identified
• Pawpads may have a fractured or flaky keratin layer with concentric circular scales or fissures
• Sebaceous glands are usually unaffected but atrophy is sometimes observed; may appear large compared to atrophic follicles
• Dermal inflammation is absent to moderate, and is more intense when occurring in conjunction with erosion and crusting, and is typically composed of lymphocytes, histiocytes, and fewer neutrophils; neutrophils are most prominent in areas of erosion and crusting that may be prominent; mast cells are often numerous

 

DIFFERENTIAL DIAGNOSIS:

• Highly clinically distinctive, so there are few differential diagnoses
• Pawpad lesions may resemble superficial necrolytic dermatitis (SND, I-M16), but SND is not alopecic
• Differentials for feline symmetrical alopecia:
• Feline acquired skin fragility syndrome secondary to endogenous or iatrogenic hyperadrenocorticism (I-M23): Markedly thin skin that tears easily, especially on the dorsum of the trunk; reduced dermal collagen, hair follicle lesions less prominent than in dogs, epidermal and follicular infundibular atrophy; calcinosis cutis is NOT reported in cats
• 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

 

COMPARATIVE PATHOLOGY:

Principle cutaneous paraneoplastic syndromes:

• Paraneoplastic alopecia and internal malignancies in the cat
• Exfoliative dermatitis and thymoma (H-N01) in the cat, dog, and rabbit – characterized by a cell-poor hydropic interface dermatitis; single case in Rock Alpine goat (Byas AD 2019)
• Superficial necrolytic dermatitis (necrolytic migratory erythema, hepatocutaneous syndrome) (I-M16) in the dog and the cat; secondary to hepatic dysfunction
• 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– German shepherd and other large breed dogs; multiple, firm, well-circumscribed collagenous nodules ranging from 2 to 5 mm, associated with renal cystadenocarcinoma or cystadenoma and 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

 

REFERENCES:

1. Byas AD, Applegate TJ, Stuart A, Byers S, Frank CB. Thymoma-associated exfoliative dermatitis in a goat: case report and brief literature review. J Vet Diagn Invest. 2019: 31(6);905-908.
2. 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.
3. 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.

Welle MM, Linder KE: The Integument. In: McGavin MG, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO; Elsevier: 1120, 1144-1145,1175,1209,1261-1262.

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