JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2237039): 2-year-old shar-pei
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 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. Diffusely, 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
· Chinese shar-peis have greater amounts of dermal mucin than other dog breeds; some degree of diffuse mucinosis in this breed is considered normal, but clinically relevant generalized mucinosis can occur and is most common in this breed
· An association between the shar-pei breed and genetic variation in hyaluronic acid synthase 2 (HAS2) has been demonstrated
· Higher HAS2 mRNA expression results in higher HAS2 protein within dermal fibroblasts
· Mucin is a jelly-like, clear, viscous glycosaminoglycan composed of hyaluronic acid bound to heparin and chondroitin sulfate B; it is produced in the skin by dermal fibroblasts and is a component of the normal dermal ground substance; it is also found in superficial and follicular epidermis
· Glycosaminoglycans (GAGs) in cutaneous mucinosis:
· Hyaluronic acid (HA), a nonsulfated carboxylated glycosaminoglycan, is the most common glycosaminoglycan in canine mucinosis
· Sulfated carboxylated glycosaminoglycan such as chrondroitin 4-sulfate, chrondroitin 6-sulfate, and dermatan sulfate may also be found in mucinosis
· Production of GAGs decreases with age
· Mucinosis may be divided into two categories:
· Primary mucinosis: can be further subdivided into hereditary (generalized or multifocal), papular, nodular, and myxedema forms
· 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; it results in symmetrical thickening of skin in the face to give the classic ‘tragic faces’ appearance
· Secondary mucinosis: usually clinically silent, only detected histologically; is 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)
· Mechanism of mucin deposition in cutaneous mucinosis is unknown
· Certain mast cell subtypes are believed to have a role in the pathogenesis for clinically relevant disease in Chinese shar-peis
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
· Snoring and snorting because of involvement of swollen oropharyngeal mucosa
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
· 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)
· 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)
· Mucicarmine stains mucin red (carminophilic)
· Periodic-acid Schiff reaction is negative because of the acid mucopolysaccharide nature of the increased dermal mucin
· Elevated serum HA concentration
· Hypothyroidism: Myxedema is used specifically to indicate the mucinosis seen with canine hypothyroidism; symmetrical thickening of facial skin that imparts the classic ‘tragic faces’ appearance
· Serum HA concentration is normal
· 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
· Dog: Relatively common in Chinese shar-peis 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
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.
3. Momoto Y, Yamamoto M, Yoshimastu H, Satoshi N, Shigihara K, Yasuda A, Hayakawa N, Ikezawa M, Tani, K, Mori A, Sako T. Nodular cutaneous mucinosis in a hypothyroid dog- a severe form of myxedema. Vet Derm. 2016; 27:61-63.
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. Scott DW, Miller WH, Griffin CE. Muller and Kirk’s Small Animal Dermatology. 6th ed., Philadelphia, PA: W.B Saunders; 2001:996-997.