JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

I-N17

 

Signalment (JPC# 2075587):  Horse

 

HISTORY:  Dermal mass from the tibial region at the site of a previous wire cut injury

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin, tibial region (per contributor):  Infiltrating the superficial dermis and elevating the overlying ulcerated and moderately hyperplastic epidermis is a 15 x 7 mm, unencapsulated, moderately cellular, pedunculated neoplasm composed of spindle cells haphazardly arranged in short, interlacing bundles, whorls and occasional streams on a moderate collagenous matrix. Neoplastic cells have indistinct borders, a moderate amount of fibrillar, pale eosinophilic cytoplasm, and an oval to elongate vesiculate nucleus with finely stippled chromatin and one variably distinct nucleolus. There is moderate anisocytosis and anisokaryosis. The mitotic rate is regionally variable, averaging 1 per 2.37mm². Multifocally at the dermal-epidermal junction, neoplastic cells are arranged perpendicularly to the basement membrane (“picket fencing”). The overlying epidermis is extensively ulcerated and replaced by a serocellular crust composed of many degenerate neutrophils, fibrin, hemorrhage, necrotic debris, and numerous colonies of cocci. At the margin of the neoplasm where it is not ulcerated, the epidermis is hyperplastic characterized by acanthosis as well as long, thin, branching rete ridges that dive deep into the spindle cell component of the neoplasm. The epidermis is also characterized by spongiosis, intracellular edema, and mild parakeratotic hyperkeratosis.  

 

MORPHOLOGIC DIAGNOSIS:  Haired skin, tibial region (per contributor):  Sarcoid, breed not specified, equine.

 

CAUSE:  Association with Bovine papillomavirus (BPV) types 1 and 2

 

CONDITION:  Equine sarcoid

 

GENERAL DISCUSSION:  

• Most common skin neoplasm of equids (horses, donkeys, mules, and zebras), up to 90% of horse skin tumors
• Sarcoids are locally aggressive, nonmetastatic fibroblastic skin tumors 
• Associated with nonproductive infection with BPV types 1, 2, and 13
• Breed predilection: Appaloosas, Quarter Horses, Arabians and Thoroughbreds

• Increased risk associated with MHC-1-A3 and W13 alleles, decreased/absent W13 allele associated with decreased risk

• Frequently develops in areas of previous trauma (6-8 months after wound healing)
• Spontaneous regression is reported but is infrequent
• Young horses 1-7 years higher risk
• Sarcoids have overlapping morphology with other spindle cell/soft tissue sarcomas, including fibrosarcoma and peripheral nerve sheath tumors (eg, schwannoma, neurofibroma) and can be difficult to distinguish histologically; additionally, a recent study found that BPV is found in many skin-associated spindle cell soft tissue tumors in horses in addition to sarcoids (Epperson, Vet Pathol. 2017)

 

PATHOGENESIS:  

• Combination of factors influence development including exposure to viral agent, cutaneous trauma, and a genetic predilection
• Bovine papillomavirus:

• Mode of transmission of BPV has not been established, but may spread to other locations on same horse or other horses by biting, rubbing, fomites, and insects
• Most sarcoids express BPV types 1 and 2 and major transforming viral protein E5
• E5 also down-regulates MHC 1 expression > evades immune destruction by cytotoxic T cells
• BPV is found in many skin-associated spindle cell soft tissue tumors in horses in addition to sarcoids (Epperson Vet Pathol. 2017)

 

TYPICAL CLINICAL FINDINGS:  

• Can occur anywhere, but most frequently found on the head, legs and ventral trunk; multiple sites common
• Often recurs after surgical excision and becomes hyperproliferative; up to 50% recurrence following removal

 

TYPICAL GROSS FINDINGS:

Six different types are identifiable grossly; multiple different types can be present on the same horse:

• Occult (flat):  focal areas of alopecia, scaling, hyperkeratosis, and hyperpigmentation
  • Neck, face, sheath, medial thigh, and shoulder
• Verrucous (wart-like):  Usually <6cm diameter, dry, rough, cauliflower-like surface with variable alopecia
  • Head, neck, axilla, and groin
• Nodular: Spherical dermal to subcutaneous masses; overlying skin can be normal or ulcerated; can remain static if not traumatized
  • Eyelid, groin, prepuce
• Fibroblastic (proud flesh-like):  More variable in appearance; fleshy, fibrous, variably-sized nodules; often ulcerated and covered with necrotic debris, resembles exuberant granulation tissue
  • Axilla, groin, legs, and periocular
• Mixed type:  More than one clinical form, often long standing lesions or those subject to repeated trauma. Can become more clinically aggressive as more fibroblastic transformation occurs
• Malignant/malevolent: Aggressive and locally infiltrative; extend widely into the adjacent skin and infiltrate lymphatic vessels
  • Any type of sarcoid can develop into this type if traumatized

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Biphasic composed of pseudoepitheliomatous epidermal and fusiform dermal components in whorls, tangles, and/or herringbone patterns, but a neurofibroma-like proliferation exists
• The epidermal component may be minimal or absent (nodular or early occult forms), but if present will exhibit hyperkeratosis and irregular acanthosis with long, thin rete ridge formation that often extend deep into the dermal proliferation
• The dermal component consists of proliferation of fibroblasts and collagen in various proportions
• At the dermal-epidermal junction, fibroblasts are oriented perpendicularly to the basement membrane (“picket fence” pattern)
• Few mitotic figures, minimal atypia 
• Tumor margins often indistinct and it is difficult to determine complete excision

 

ADDITIONAL DIAGNOSTIC TESTS:  

• PCR to detect BPV DNA (although BPV DNA may be positive in many spindle cell tumors or in normal equine skin [Epperson, Vet Pathol. 2017])
• Strongly vimentin positive
• May be laminin, SMA, Type IV collagen positive
• GFAP negative, S100 historically thought to be negative but recent studies show that some sarcoids are positive

 

DIFFERENTIAL DIAGNOSIS: 

Grossly:

• Equine papilloma – common in young animals, spontaneously regress
• Squamous cell carcinoma
• Exuberant granulation tissue
• Infectious – dermatophytosis, dermatophilosis, demodicosis, cutaneous habronemiasis, staphylococcal folliculitis, onchocerciasis, infectious granulomas (Pythium insidiosum, Zygomycetes sp.)

 

Microscopically:

• Fibroma – well circumscribed, less cellular, no epidermal involvement
• Fibrosarcoma – more pleomorphic, no epidermal involvement
• Neurofibroma / neurofibrosarcoma:  well demarcated and cellular or diffusely collagenous and infiltrative
• PNST/Schwannoma – usually positive for S-100 (though sarcoids can be too); +/- GFAP; Verocay bodies, Antoni A and Antoni B; a recent study indicates in some cases the diagnosis “soft tissue sarcoma with nerve sheath tumor morphology” may be more appropriate than PNST or sarcoid (Epperson, Vet Pathol. 2017)
• Granulation tissue – fibrous tissue oriented at right angles to capillaries, often have inflammatory component

 

COMPARATIVE PATHOLOGY:  

Papilloma viruses associated with pre-neoplastic and neoplastic skin lesions in animals (adapted from Munday 2016, Mauldin 2016, and Vitiello 2017):

 

Animal species	Skin lesion	Papillomavirus
Cat	Feline viral plaque progressing to BISC	FcaPV-1, -2, -3
Cat	SCC	FcaPV-2
Dog	Canine pigmented viral plaque progressing to ISC and SCC	CfPV-3
Dog	Endophytic papilloma and SCC in immunosuppressed dogs	CfPV-2
Dog	In situ SCC	CfPV-7
Horse	Equine sarcoid	BPV-1, -2
Horse	Equine papillomas, ISC and SCC	EcPV2
Sheep	SCC	OaPV-3
Rabbit	Cutaneous SCC	CRPV

 

FcaPV, Felis catus papillomavirus; CfPV, Canis familiaris papillomavirus; COPV, canine oral papillomavirus; BPV, bovine papillomavirus; CRPV, cotton-tail rabbit papillomavirus; RaPV, rousettus aegyptiacus papillomavirus type I; MnPV, Mastomys natalensis papillomavirus; EcPV2, equine papillomavirus type 2; OaPV, Ovine aries papilloma virus

 

REFERENCES:  

2. Epperson ED, Castleman WL. Bovine Papillomavirus DNA and S100 Profiles in Sarcoids and Other Cutaneous Spindle Cell Tumors in Horses. Vet Pathol. 2017;54(1):44-52.
3. Gaynor AM, Zhu KW, Dela Cruz FN, Affolter VK, Pesavento PA. Localization of bovine papillomavirus nucleic acid in equine sarcoids. Vet Pathol. 2016; 53(3):567-573.
4. Mauldin E, 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; 2016:707-710.
5. Ogłuszka M, Starzyński RR, Pierzchała M, Otrocka-Domagała I, Raś A. Equine Sarcoids-Causes, Molecular Changes, and Clinicopathologic Features: A Review. Vet Pathol. 2021;58(3):472-482.
6. Tura G, Savini F, Gallina L, La Ragione RM, Durham AE, Mazzeschi M, Lauriola M, Avallone G, Sarli G, Brunetti B, Muscatello LV, Girone C, Bacci B. Fibroblast-associated protein-α expression and BPV nucleic acid distribution in equine sarcoids. Vet Pathol. 2021;58(6):1044-1050. 
7. Vitiello V, Burrai GP et al. Ovis aries papillomavirus 3 in ovine cutaneous squamous cell carcinoma. Vet Pathol. 2017;54(5):775-782.
8. Wobeser BK. Making the diagnosis: equine sarcoid. Vet Pathol. 2017;54(1):9-10.
9. Welle MM, Linder KE. The integument.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed., St. Louis, MO; Elsevier; 2022:1222.

 

Click the slide to view.

---