JPC SYSTEMIC PATHOLOGY

INTEGUMENT SYSTEM

September 2016

I-M17 (NP)

 

Signalment:  A three-year-old spayed female mixed breed dog

HISTORY:  This dog had nodular eruptions over the muzzle and around the nares. 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin: Infiltrating and expanding the dermis, elevating the mildly hyperplastic epidermis, and surrounding, separating and replacing the adnexa are multifocal to coalescing, densely cellular inflammatory infiltrates that track linearly along hair follicles and form poorly defined, elongate (“cigar-shaped”) nodules up to 2 mm in length. The nodules are composed of abundant epithelioid macrophages, lymphocytes, plasma cells, fewer multi-nucleated giant cells (foreign body type) and neutrophils admixed with individual cell necrosis, few reactive fibroblasts, and small amounts of loose collagenous connective tissue (fibrosis). Multifocally, apocrine and sebaceous glands, and lymphatics are ectatic (edema) and blood vessels are lined by hypertrophied endothelium (reactive). Multifocally throughout the dermis are areas of hemorrhage and increased clear space that separates fibrous connective tissue (edema). The multifocally mildly hyperplastic epidermis is characterized by hyperplasia of the stratum spinosum (acanthosis) and multifocal epidermal hyperpigmentation, and mild orthokeratotic hyperkeratosis.

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Dermatitis, periadnexal and nodular, granulomatous, multifocal to coalescing, moderate, with mild edema, acanthosis, and orthokeratotic hyperkeratosis, mixed breed, canine.

ETIOLOGIC DIAGNOSIS:  Idiopathic granulomatous dermatitis

CONDITION:  Sterile granuloma/pyogranuloma syndrome (SPGS)

SYNONYM:  Periadnexal multinodular granulomatous dermatitis (PMNGD)/ Pyogranuloma syndrome; Idiopathic sterile granuloma/pyogranuloma

GENERAL DISCUSSION: 

• Common condition in dogs, rare in cats
• 5 types: Cutaneous SGPS; Juvenile sterile granulomatous dermatitis and lymphadenitis; Cutaneous xanthoma; Sterile nodular panniculitis; Canine sarcoidosis
• May spontaneously resolve after several months in cats and dogs

PATHOGENESIS:

• Response to steroids and histiocytic nature of inflammation suggests an immune dysfunction
• May be an infectious agent present in small numbers or have incomplete clearing of antigens associated with an infectious agent
• Sterile nodular panniculitis type: Considered to be idiopathic and primary in origin or associated with other diseases, including pancreatic nodular hyperplasia, pancreatic neoplasia, pancreatitis, or immune-mediated diseases such as systemic lupus erythematosus.

TYPICAL CLINICAL FINDINGS: 

• Dogs: Multiple, firm, non-pruritic, well demarcated, partially alopecic nodules or plaques that vary from 0.5-2 cm in diameter
• Cats: Pruritic, symmetric, bilateral, periauricular coalescent papules forming well circumscribed plaques; or multiple, pruritic, erythematous papules and nodules located on the head and pinnae

TYPICAL GROSS FINDINGS:

• Alopecic nodules are most commonly found on the muzzle, pinna and periorbital skin of dogs and cats

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Has a typical granuloma appearance (discrete dermal nodules of macrophages/multi-nucleated giant cells bound by fibrosis)
• Inflammatory infiltrate is devoid of foreign material or infectious agents detected by routine techniques (polarization, special stains)
• Pyogranulomatous type: Discrete pyogranulomas with central neutrophils and cuffs of macrophages and lesser numbers of lymphocytes and plasma cells
• Periadnexal type: Granulomatous inflammation around adnexa;  histiocytes, lymphocytes and neutrophils coalesce in later stages; sausage-shaped granulomas are vertically oriented and track hair follicles but do not invade them; there is no associated folliculitis
• Preauricular type (xanthogranulomas - cats): Diffuse infiltrates of pale, epithelioid-spindled, foamy histiocytes with giant cells; a grenz zone (a zone of relatively normal collagen demarcating the boundary between normal epidermis and a dermal lesion such as a granuloma or a neoplasm) of uninvolved superficial dermis may be present
• Nodular panniculitis type: Lobular to diffuse infiltrate in the subcutis and deep dermis composed predominantly of neutrophils and macrophages; the presence of fat and fat necrosis is associated with pancreatic disease and vitamin E deficiency in cats
• Sarcoid type: Granulomas of epithelioid macrophages forming “naked tubercles” with few to no lymphocytes and rare giant cells

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Multiple biopsies using sterile technique for aerobic, anaerobic, fungal and mycobacterial culture and/or special stains (B&B, B&H, GMS, PAS) or PCR to rule out infectious etiologies, especially of Leishmania in southern Europe and Mycobacterium

DIFFERENTIAL DIAGNOSIS:

Gross:

• Cutaneous neoplasms
• Bacterial, fungal, algal, protozoal, parasitic or foreign body granulomatous dermatitis
• Reactive histiocytosis: Similar to PMNGD but usually more diffuse sheets of large histiocytes without formation of distinct granulomas/pyogranulomas; separation of these two entities may be artificial; histiocytes infiltrate vessel walls (vasoinvasion), causing vascular degeneration, obstruction and thrombosis
• Canine juvenile cellulitis: Pyogranulomatous to granulomatous perifollicular, dermatitis with furunculosis
• Canine cutaneous histiocytoma: Solitary benign dome-shaped neoplasm; tracks follicles, with epithelial hyperplasia and ulceration and deep lymphoid aggregates
• Sterile nodular panniculitis: Pyogranulomatous inflammation originates in the subcutis rather than dermis, often with necrosis and fistulous tracts, accompanied by fever, lethargy and anorexia
• Juvenile sterile granulomatous dermatitis and lymphadenitis – pustular to suppurative

Microscopic:

• Nodular granulomatous form of sebaceous adenitis: Occurs in cats and dogs with Vizslas, Akitas, Samoyeds, and Standard Poodles predisposed; similar histologically, with discrete perifollicular granulomas that replace sebaceous glands and spare other adnexa
• Bacterial, fungal, algal, protozoal, parasitic or foreign body granulomatous dermatitis

COMPARATIVE PATHOLOGY: 

• Cats: Sterile dermal granuloma and pyogranuloma are rare; the gross lesions of preauricular xanthogranuloma of cats consist of orange plaques that bruise easily
• Horses: Equine idiopathic generalized or systemic granulomatous disease (sarcoidosis) is a chronic wasting disease with granulomatous infiltrates around follicles in the dermis, and in multiple organ systems; cause is unknown

REFERENCES: 

1. Carpenter JL, Thornton GW, Moore FM, King NW Jr. Idiopathic periadnexal multinodular granulomatous dermatitis in twenty-two dogs.  Vet Pathol.  1987 Jan;24(1):5-10.
2. Cornegliani L, Fondevila D, Vercelli A, Mantero G, Fondati A. PCR technique detection of Leishmania but not Mycobacterium spp. in canine cutaneous ‘sterile’ pyogranuloma/granuloma syndrome. Vet Dermatol. 2005;16(4):233-238.
3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. 2nd ed. Oxford, UK: Blackwell Publishing Co.; 2005: 410-415.
4. Mauldin EA, Peters-Kennedy J. Integumentary system.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2015:699-702.   
5. Santoro D, Prisco M, Ciaramella P. Cutaneous sterile granulomas/pyogranulomas, leishmaniasis and mycobacterial infections.  J Small Anim Pract.  2008;49(11):552-61.
6. Scott DW, Miller WH, Griffin CE. In: Muller & Kirk’s Small Animal Dermatology. 6th ed. Philadelphia, PA: WB Saunders Company; 2013:1136-1140.

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