JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
September 2022
I-M15 (NP)

Signalment (JPC #2237039):  2-year-old shar-pei

 

HISTORY:  None

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin: Diffusely, dermal collagen bundles are fragmented, distorted, and widely separated by abundant, wispy, amphophilic material (mucin) and increased clear space (edema) admixed with few mast cells, neutrophils, macrophages, lymphocytes, and plasma cells. Multifocally within the superficial dermis, low numbers of macrophages contain melanin granules (pigmentary incontinence). There is minimal hyperplasia and hyperkeratosis of the follicular epithelium. Multifocally, the epidermis is mildly hyperplastic with short rete ridges.

 

MORPHOLOGIC DIAGNOSIS:  Haired skin, dermis:  Mucinosis, diffuse, moderate, with minimal chronic-active dermatitis, Chinese Shar Pei, canine.

 

CONDITION:  Cutaneous mucinosis

 

SYNONYMS:  Idiopathic mucinosis, congenital myxedema

 

GENERAL DISCUSSION: 

• Cutaneous mucinosis is a dermal connective tissue disorder in which excessive mucin accumulates due to excessive production by dermal fibroblasts
• Clinical presentation of cutaneous mucinosis in dogs is highly variable and in the Chinese Shar Pei some degree is considered normal, rarely mucinosis is seen also in Chow Chows
• Mucin is a jelly-like, clear, viscous glycosaminoglycan
  • Hyaluronic acid (HA), a nonsulfated carboxylated glycosaminoglycan (GAG), is normally found in superficial and follicular epidermis and is the most common GAG in canine mucinosis
  • Sulfated carboxylated GAGs, such as chrondroitin 4-sulfate, chrondroitin 6-sulfate, and dermatan sulfate, may also be found in mucinosis
  • Production of GAGs decreases with age
• Cutaneous mucinosis is divided into two categories:
  • Primary mucinosis can be divided into hereditary mucinosis (can be generalized or multifocal, including tumor-like), myxedema, popular mucinosis, or nodular mucinosis
    • Generalized primary hereditary mucinosis involves no compromise of normal skin integrity
    • Multifocal hereditary mucinosis is often accompanied by some generalized mucinosis, but may result in multifocal compromise of skin integrity
    • Myxedema is a rare manifestation of canine hypothyroidism and presents as a symmetrical thickening of the facial skin, resulting in folds, the so-called “tragic face”
  • Secondary mucinosis: Usually clinically silent and is only detected histologically
    • Associated with inflammatory skin conditions (e.g. pyoderma, allergic skin disease, eosinophilic skin disease, and lupus erythematosus) as well as neoplastic diseases (e.g. mast cell tumors)

 

PATHOGENESIS: 

• Hyaluronan retains large amounts of water, which leads to dermal thickening
• Cutaneous mucinosis in the Chinese Shar Pei:
  • Genetic variation in hyaluronic acid synthase 2 (HAS2): Higher HAS2 mRNA expression results in higher HAS2 protein within dermal fibroblasts
  • Although histologically prominent mucin contributes to the unusual ‘normal’ folding seen in the Chinese Shar Pei, this breed may also demonstrate clinical mucinosis, presumed to be hereditary in origin
  • Certain mast cell subtypes are believed to have a role in the pathogenesis for clinically relevant disease in the Chinese Shar Pei

 

TYPICAL GROSS FINDINGS: 

• Exaggerated thickening and folding of spongy skin most pronounced on the head, ventrum, and the distal extremities
• Multifocal disease is characterized by variably sized mucinous vesicles in normal or edematous skin that discharge a thick, clear and sticky fluid when expressed
• If severe, skin integrity may be compromised and abraded areas may exude mucin

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• The primary lesion is dermal thickening due to increased accumulation of pale-staining, blue-purple, fibrillar to granular mucin strands arranged in a lacy network that separate dermal collagen bundles in the superficial and deep dermis
  • Can also see reduction in dermal collagen fibers and dilation of lymphatic channels
  • Clear spaces represent fluid removed during processing because of the hygroscopic nature of the glycosaminoglycan
• Focal mucinosis is characterized by lakes of mucin in the superficial and middle dermis that displace normal dermal collagen
• The epidermis is usually normal in uncomplicated cases; however, most Shar Peis have concurrent inflammatory skin disease (pyoderma or demodicosis)

 

ULTRASTRUCTURAL FINDINGS: 

• Amorphous granular material (mucin) within dilated cisternae of dermal fibroblasts and aggregated in the dermal interstitium

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Alcian blue stains mucin blue or blue-green (alcianophilic)
• Mucin stains metachromatically with toluidine blue and methylene blue.
• Mucicarmine stains mucin red (carminophilic)
• Periodic-acid Schiff reaction is negative because of the acid mucopolysaccharide nature of the increased dermal mucin
  • NOTE: PAS stains neutral mucopolysaccharides

 

DIFFERENTIAL DIAGNOSIS: 

• Skin thickening due to cutaneous mucinosis and myxedema can be a feature of hypothyroidism
• Papular mucinosis: Solitary or occasionally multiple, white or yellow papules or clear “blisters” most frequently localized to the head and neck, noted as incidental findings
• Urticaria: May be a primary differential histologically if there is high water content in the mucin; mucin stains can be used to differentiate
• Vesicular and bullous skin diseases

 

COMPARATIVE PATHOLOGY: 

• Dog: Relatively common in the Chinese Shar Pei but rare in other breeds
• Cat: Very rare
• Chicken: A similar condition is reported in a strain of Brown-egg laying chickens (Palmieri, Vet Pathol 2015), although combs and wattles (which generally have a large amount of dermal mucin) were not affected

 

REFERENCES: 

1. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat, Clinical and Histopathologic Diagnosis. 2nd ed. Ames Iowa: Blackwell Publishing; 2005:380-383.
2. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Edinburgh, England: Elsevier; 2016:522-523, 546.
3. Müntener T, Rüfenacht S, Di Palma S, et al. Scleromyxedema-like Syndrome With Systemic Involvement in a Cat. Vet Pathol. 2010 Mar;47(2):346-50.
4. Palmieri C, Anthenill L, Sjivaprasad HL. Cutaneous mucinosis in a strain of brown-egg laying chickens. Vet Pathol.2015;52(2):351-355.
5. Miller WH, Griffin CE, Campbell KL. Muller and Kirk’s Small Animal Dermatology. 7th ed. Louis, MO: Elsevier Mosby; 2013:611, 832-3.
6. Welle MM, Linder KE. The Integument. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:1233.

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