Equine Squamous Cell Carcinoma Study Guide

Overview and Clinical Importance

Squamous cell carcinoma (SCC) is the second most common tumor in horses after equine sarcoid and the most common malignant skin tumor in the species. SCC arises from squamous epithelial cells that form the outermost layer of skin and line mucous membranes. This neoplasm predominantly affects non-pigmented skin areas exposed to ultraviolet radiation and is especially concerning because of its locally invasive nature and potential for metastasis if left untreated.

Understanding equine SCC is crucial for the NAVLE as questions frequently address risk factors, anatomic predilection sites, breed susceptibility, diagnostic approaches, and treatment options. Early recognition and intervention significantly improve prognosis.

Etiology and Pathogenesis

Risk Factors

Ultraviolet (UV) Radiation: Chronic UV exposure is the primary carcinogen for cutaneous and ocular SCC. UV light induces DNA damage in keratinocytes, particularly affecting the tumor suppressor gene p53. Non-pigmented skin lacks melanin protection, making these areas highly susceptible.

Genetic Factors - DDB2 Mutation: A missense mutation in the damage-specific DNA binding protein 2 (DDB2 c.1013C greater than T, p.Thr338Met) has been identified as a causal recessive risk factor for ocular SCC. The DDB2 protein normally repairs UV-damaged DNA. Horses homozygous for this mutation cannot effectively repair UV-induced damage, leading to significantly increased SCC risk. This mutation is found in Haflingers, Belgians, Rocky Mountain Horses, Connemara Ponies, Holsteiners, and Belgian Warmbloods.

Equine Papillomavirus Type 2 (EcPV2): EcPV2 has been strongly associated with genital SCC, particularly penile and preputial tumors. Approximately 43% of penile SCCs test positive for EcPV2 DNA. The virus is thought to initiate carcinogenesis through chronic inflammation and disruption of normal cellular regulation.

Chronic Irritation and Smegma: Smegma accumulation in the sheath of geldings acts as a carcinogen for penile SCC. Chronic skin irritation and non-healing wounds can also predispose to SCC development.

Breed Predispositions

Anatomic Locations and Clinical Presentations

Ocular Squamous Cell Carcinoma

Ocular SCC is the most common tumor affecting the equine eye and the most common form of equine SCC. It typically affects horses greater than 8-10 years of age.

Common Sites (in order of frequency)

• Third eyelid (nictitating membrane): Develops scalloped appearance or thickened mass, usually on leading edge
• Limbus: Raised, papillary, light pink mass at corneoscleral junction
• Eyelids: Smooth mass effect, often ulcerated, affects lower eyelid more commonly
• Conjunctiva: Bulbar or palpebral surfaces

Clinical Signs

• Excessive lacrimation (often first sign)
• Blood in tears (can be detected with urine dipstick)
• White, pink, or red friable growth
• Blepharospasm, photophobia
• Corneal ulceration or vascularization

Genital Squamous Cell Carcinoma

Genital SCC is the most common neoplasm of equine male external genitalia. It primarily affects older geldings (greater than 15-20 years), while stallions are rarely affected, suggesting smegma as a precipitating factor.

Penile/Preputial SCC

• Location: Glans penis most commonly affected, may involve shaft and prepuce
• Morphology: Proliferative (cauliflower-like), ulcerative, or combined
• Precursor lesions: Pink to yellow plaques, papillomas (EcPV2-associated)
• Signs: Preputial discharge (often blood-tinged), foul odor, difficulty urinating, swelling, inability to retract penis

Vulvar/Clitoral SCC (Mares)

• Occurs in older mares
• Can occur on pigmented skin
• Vulvar SCC: ulcerative when on vulvar lips; Clitoral SCC: proliferative

Cutaneous Squamous Cell Carcinoma

Cutaneous SCC develops on non-pigmented skin areas exposed to UV radiation.

Common Sites

• Facial region (unpigmented nose, muzzle, lips)
• Ears (particularly tips)
• Perineal region
• Perianal area

Appearance: Usually ulcerative/destructive rather than proliferative. May appear as poorly healing wounds, open scaly or crusted areas.

Internal Squamous Cell Carcinoma

Internal SCC carries a poor prognosis due to late diagnosis. Locations include: gastric (stomach), sinonasal (paranasal sinuses, nasal cavity), oropharyngeal, guttural pouch, and bladder. Gastric SCC often presents with weight loss, anorexia, and vague GI signs similar to ulcers.

Diagnosis and Staging

Diagnostic Approach

• Clinical Examination: Presumptive diagnosis based on signalment, lesion appearance, and location
• Histopathology (DEFINITIVE): Biopsy with microscopic evaluation is required for definitive diagnosis
• Regional Lymph Node Evaluation: Palpation and FNA if enlarged; mandibular and submandibular nodes for ocular SCC
• Advanced Imaging: CT recommended for large tumors to determine extent of invasion prior to surgery
• Genetic Testing: DDB2 mutation testing available for at-risk breeds (UC Davis VGL)

Histological Grading

SCC is graded 1-3 based on degree of differentiation. Grading has significant prognostic implications.

Exam Focus: Well-differentiated (G1) tumors produce abundant keratin and have low metastatic rate. Poorly-differentiated (G3) tumors produce virtually no keratin, are highly aggressive with rapid spread. Remember: MORE keratin = BETTER prognosis.

Treatment Options

Treatment selection depends on tumor location, size, invasiveness, and owner considerations. Multimodal therapy (surgery plus adjunctive treatment) generally provides better outcomes than single modality treatment.

Treatment Modalities by Location

Treatment Modality Details

Surgical Excision: Mainstay of treatment. Goal is complete removal with tumor-free margins (ideally 2cm for cutaneous, as wide as possible for ocular). Recurrence is common with inadequate margins.

Cryotherapy: Liquid nitrogen freezing using multiple freeze-thaw cycles. Effective for small lesions and as adjunct post-surgery. Tissue sloughs over several weeks.

Radiation Therapy: SCC is highly radiosensitive. Beta radiation (Strontium-90) penetrates 1-2mm; excellent for superficial lesions. Gamma radiation (Iridium-192 brachytherapy) for deeper tumors. Considered gold standard for difficult locations.

Chemotherapy: Usually local/intralesional rather than systemic. Cisplatin (injectable or implantable beads), 5-fluorouracil (topical cream or injection). Oral piroxicam may inhibit tumor cell growth.

Photodynamic Therapy (PDT): Photosensitizing agent injected then activated by specific wavelength laser. Emerging treatment option.

Enucleation: Removal of the entire eye. Reserved for advanced ocular SCC with orbital invasion or when other treatments fail. Often curative with no long-term complications.

Penile SCC Surgical Procedures

Prognosis

Prognosis depends on tumor location, size at diagnosis, histological grade, and presence of metastasis.

Metastasis

SCC is locally invasive but typically slow to metastasize. When metastasis occurs, it is usually lymphogenic (via lymphatics to regional lymph nodes first). Distant metastasis to lungs can occur. Overall metastatic rate is 10-15% for ocular SCC. Internal SCC (gastric, sinonasal) has higher metastatic potential.

Prevention Strategies

• UV Protection: UV-protective fly masks for horses with unpigmented periocular skin
• Sun Avoidance: Stable during peak sunlight hours (10am-4pm)
• Regular Sheath Cleaning: For geldings to prevent smegma accumulation
• Genetic Testing: DDB2 testing for at-risk breeds; routine eye exams for homozygous horses
• Breeding Considerations: Avoid mating two DDB2 carriers to prevent homozygous offspring
• Regular Monitoring: Early detection of any suspicious lesions or non-healing wounds

Memory Aids for NAVLE

SCC Location Mnemonic - "LEGS": L = Limbus (eye) E = Eyelids and third Eyelid G = Genitalia (penis, vulva) S = Skin (unpigmented areas)

Risk Factor Memory - "PUGS": P = Pink skin (unpigmented) U = UV radiation G = Genetic (DDB2 mutation) S = Smegma (penile)

DDB2 Breeds - "HBR + CP": Haflinger Belgian Rocky Mountain Horse + Connemara Pony