Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is a malignant neoplasm arising from the stratified squamous epithelium of the skin, oral cavity, and other mucosal surfaces. In veterinary surgical oncology, SCC is a common cutaneous and oral tumor in dogs and cats, characterized by local invasiveness, variable metastatic potential, and a strong association with chronic sun exposure in non-pigmented skin. Histologically, SCC exhibits nests and cords of atypical keratinocytes invading the dermis, with varying degrees of differentiation, keratinization, and desmoplasia. Surgical excision is the primary treatment modality, with wide margins (1-3 cm) recommended for cutaneous lesions, while oral SCC often requires aggressive mandibulectomy or maxillectomy. Staging involves assessment of tumor size, depth, and regional lymph node involvement, with thoracic radiography to rule out pulmonary metastasis. Prognosis depends on tumor location, histologic grade, and completeness of excision, with feline oral SCC carrying a particularly poor prognosis due to late diagnosis and high local recurrence.

The etiology of squamous cell carcinoma is multifactorial, with chronic ultraviolet (UV) radiation exposure being the primary cause for cutaneous SCC in lightly pigmented, sparsely haired skin of cats and dogs. UV-induced DNA damage, particularly cyclobutane pyrimidine dimers, leads to mutations in tumor suppressor genes such as p53. In oral SCC, chronic inflammation, viral infection (feline papillomavirus), and exposure to environmental carcinogens (e.g., tobacco smoke, dietary factors) are implicated. In cats, chronic gingivitis and stomatitis may predispose to oral SCC. Additionally, actinic keratosis, a precursor lesion, can progress to SCC. Genetic predispositions include certain breeds with white coats and non-pigmented skin, such as white cats, Dalmatians, and Bull Terriers. Other etiologic factors include immunosuppression, chronic non-healing wounds, and burn scars, which can lead to SCC in areas of chronic irritation.

Squamous cell carcinoma is the most common oral tumor in cats and the second most common in dogs. In cats, oral SCC accounts for 60-70% of oral malignancies, with a mean age of 10-12 years. Siamese and other light-colored breeds are overrepresented. Cutaneous SCC is more common in cats than dogs, with white or lightly pigmented cats having a 13-fold increased risk. In dogs, cutaneous SCC is less common, but breeds like Dalmatians, Bull Terriers, and Beagles with non-pigmented skin are at higher risk. Oral SCC in dogs has a mean age of 8-10 years, with no strong breed predilection. Subungual SCC (nail bed) is seen in large-breed dogs, particularly black dogs, and may be associated with chronic digital trauma. Metastasis rates vary: cutaneous SCC has a low metastatic rate (<10%), while oral SCC in cats has a high local recurrence and metastasis to regional lymph nodes and lungs in 10-30% of cases.

Squamous cell carcinoma arises from keratinocytes in the basal layer of the epidermis or oral mucosa. Chronic UV exposure induces DNA damage, leading to mutations in oncogenes and tumor suppressor genes, resulting in uncontrolled proliferation. The tumor grows locally, invading the dermis and underlying tissues, with a tendency to infiltrate along fascial planes and nerves. In the oral cavity, SCC often invades the mandible or maxilla, causing bone lysis and tooth loss. Histologically, well-differentiated SCC shows keratin pearls and intercellular bridges, while poorly differentiated tumors have anaplastic cells with high mitotic activity. Tumor angiogenesis and lymphangiogenesis facilitate local invasion and regional lymph node metastasis. In cats, oral SCC is highly invasive and often presents at an advanced stage, with a median survival of 2-3 months without treatment. The tumor can also produce paraneoplastic syndromes, such as hypercalcemia, due to secretion of parathyroid hormone-related protein.

Predisposing factors for SCC include: (1) Chronic UV radiation exposure, especially in cats and dogs with white or non-pigmented skin and sparse hair coat; (2) Lack of skin pigmentation and hair coverage, leading to actinic damage; (3) Chronic inflammation and irritation, such as chronic gingivitis, stomatitis, or non-healing wounds; (4) Viral infections, particularly feline papillomavirus in oral SCC; (5) Immunosuppression, either iatrogenic (e.g., corticosteroids) or due to concurrent diseases (e.g., FIV, FeLV); (6) Genetic predisposition, with certain breeds having a higher incidence; (7) Age, with older animals (median 10-12 years) being more affected; (8) Environmental carcinogens, such as tobacco smoke and dietary factors; (9) Previous radiation therapy, which can induce secondary SCC; (10) Actinic keratosis, a precursor lesion that can progress to SCC.

Clinical signs of SCC vary by location. Cutaneous SCC typically presents as a solitary, firm, raised, ulcerated, or crusted lesion, often on the head, ears, eyelids, nose, or digits. Lesions may bleed, become infected, and be painful. In cats, nasal planum SCC appears as a proliferative or ulcerative mass, often with crusting and erosion. Oral SCC in cats and dogs presents with halitosis, drooling, dysphagia, oral bleeding, loose teeth, and a visible mass. Sublingual SCC may cause difficulty swallowing. Subungual SCC causes lameness, nail bed swelling, and nail loss. Advanced cases may show facial deformity, exophthalmos, or weight loss. Regional lymph node enlargement may indicate metastasis. Systemic signs are uncommon but may include lethargy, anorexia, and hypercalcemia.

Differential diagnoses for SCC include: (1) Fibrosarcoma: a mesenchymal tumor that is firm, nodular, and often deep; histopathology differentiates. (2) Malignant melanoma: pigmented or non-pigmented, often oral or cutaneous; immunohistochemistry (Melan-A, PNL2) is diagnostic. (3) Papilloma: benign, cauliflower-like, often viral; lacks invasion. (4) Actinic keratosis: premalignant, erythematous, scaly plaques; histology shows dysplasia. (5) Basal cell tumor: benign, firm, often pigmented; histology shows basaloid cells. (6) Mast cell tumor: can be ulcerated; cytology shows mast cells with metachromatic granules. (7) Osteosarcoma: if bone involvement, especially in subungual; radiographs show bone lysis and proliferation. (8) Eosinophilic granuloma complex (cats): ulcerative lesions on lips or oral cavity; histology shows eosinophilic infiltrate. (9) Inflammatory polyps: in oral cavity, benign; histology. (10) Metastatic tumors: rare, but can mimic SCC; biopsy is definitive.

The diagnostic algorithm for SCC begins with a thorough history and physical examination, including palpation of regional lymph nodes. For cutaneous lesions, fine-needle aspiration (FNA) may be performed, but definitive diagnosis requires incisional or excisional biopsy. For oral lesions, oral examination under anesthesia is essential, with biopsy of the mass and any abnormal tissue. Imaging: thoracic radiographs (three views) to rule out pulmonary metastasis; for oral SCC, skull radiographs or CT to assess bone invasion and extent. CT is preferred for surgical planning, especially for maxillectomy or mandibulectomy. Lymph node evaluation: FNA or biopsy of regional lymph nodes, with histopathology and culture. Staging: TNM classification (T: tumor size and invasion, N: lymph node involvement, M: metastasis). For subungual SCC, radiographs of the digit to assess bone involvement. Advanced imaging (MRI) may be used for deep soft tissue or neurological involvement. Surgical planning: determine margins (1-3 cm for cutaneous, 1-2 cm for oral) and consider reconstructive options.

Laboratory findings in SCC are often nonspecific. Complete blood count may show mild anemia of chronic disease or neutrophilia if secondary infection. Serum biochemistry may reveal hypercalcemia in some cases (paraneoplastic), especially in oral SCC. Liver and kidney values are important for anesthetic and drug dosing. Urinalysis is routine. Coagulation panel (PT/aPTT) is recommended before surgery, especially for oral resections. Inflammatory biomarkers (CRP, SAA) may be elevated but are not diagnostic. Synovial fluid analysis is not relevant unless joint involvement. For oral SCC, culture and sensitivity of the tumor site may be useful if infection is suspected. Histopathology is the gold standard, with grading based on differentiation, nuclear pleomorphism, and mitotic index.

Imaging plays a crucial role in staging and surgical planning. Radiography: For cutaneous SCC, radiographs are not typically needed unless bone involvement is suspected. For oral SCC, dental radiographs or skull radiographs may show bone lysis, tooth loss, or soft tissue mass. Thoracic radiographs (three views) are essential to rule out pulmonary metastasis. CT: Provides detailed assessment of tumor extent, bone invasion, and lymph node involvement. CT is particularly useful for oral SCC to plan mandibulectomy or maxillectomy, with 3D reconstructions for surgical guidance. MRI: May be used for advanced soft tissue involvement, especially in the oral cavity or nasal planum, to assess depth and neurovascular invasion. Ultrasonography: Useful for evaluating regional lymph nodes and guiding FNA. Fluoroscopy or angiography: Rarely needed, but may be used for vascular studies in reconstructive surgery. For subungual SCC, radiographs of the digit show bone lysis or pathological fracture.

Cytology: FNA of cutaneous or oral masses may show clusters of atypical squamous epithelial cells with variable keratinization, nuclear pleomorphism, and high nuclear-to-cytoplasmic ratio. However, cytology is not definitive and may be confused with inflammation or other neoplasms. Histopathology: Incisional or excisional biopsy is required for definitive diagnosis. Well-differentiated SCC shows keratin pearls, intercellular bridges, and invasion of the dermis. Poorly differentiated SCC has anaplastic cells with high mitotic activity and minimal keratinization. Histologic grading (I, II, III) based on differentiation, nuclear pleomorphism, and mitotic index correlates with prognosis. Surgical margins should be evaluated for completeness of excision. Immunohistochemistry may be used to differentiate SCC from other tumors: positive for pancytokeratin, negative for vimentin, Melan-A, and S100. Special stains like PAS may highlight glycogen.

Treatment of SCC is primarily surgical excision. For cutaneous SCC, wide surgical excision with 1-3 cm margins is recommended, depending on tumor size and location. For lesions on the nasal planum, surgical options include superficial necrosectomy, full-thickness excision, or nasal planectomy with reconstruction. For oral SCC, aggressive surgical resection is indicated: mandibulectomy (partial or complete) or maxillectomy (rostral, lateral, or total) with 1-2 cm margins. In cats, oral SCC is often non-resectable due to extensive invasion; alternative treatments include radiation therapy, chemotherapy (carboplatin, doxorubicin), and palliative care. For subungual SCC, digit amputation (phalangectomy) is curative in most cases. Reconstructive techniques include local flaps (e.g., buccal mucosal flap, labial flap), axial pattern flaps (e.g., caudal auricular, superficial cervical), and skin grafts. Preoperative stabilization includes pain management, antibiotics if infected, and nutritional support. Intraoperative considerations: meticulous hemostasis, use of electrosurgery or ligatures, and tension-free closure. Postoperative care: pain management, wound care, and restricted activity. Adjuvant therapy: radiation therapy for incompletely excised tumors, especially oral SCC; chemotherapy for metastatic disease or non-resectable tumors.

Prognosis for SCC varies by location and stage. Cutaneous SCC in dogs and cats has a good prognosis with complete surgical excision, with a cure rate of 70-90%. Nasal planum SCC in cats has a fair to good prognosis with early surgical intervention (median survival 12-18 months). Oral SCC in dogs has a guarded prognosis, with median survival of 10-12 months after surgery; cats have a poor prognosis, with median survival of 2-3 months without treatment, and 6-12 months with aggressive surgery and radiation. Subungual SCC has a good prognosis with digit amputation, with a 5-year survival rate of 80-90%. Negative prognostic indicators include large tumor size (>2 cm), deep invasion, lymph node metastasis, high histologic grade, and incomplete excision. Local recurrence is common in oral SCC, especially in cats.

Postoperative follow-up is essential for early detection of recurrence or metastasis. For cutaneous SCC, recheck at 2 weeks for suture removal and wound assessment, then every 3 months for the first year, and every 6 months thereafter. For oral SCC, recheck at 2 weeks, then monthly for the first 3 months, then every 3 months for the first year, and every 6 months thereafter. Thoracic radiographs should be repeated every 3-6 months for the first 2 years. Physical examination should include palpation of regional lymph nodes. For cats with oral SCC, monitor for signs of dysphagia, weight loss, and pain. Serial imaging (CT or MRI) may be indicated if recurrence is suspected. Long-term monitoring for sun-induced lesions in predisposed animals is recommended.

Pearls: (1) For cutaneous SCC on the nasal planum, consider nasal planectomy with a rostral advancement flap for cosmetic and functional outcome. (2) For oral SCC, always perform a thorough oral examination under anesthesia and obtain multiple biopsies to assess extent. (3) Use surgical margins of at least 1 cm for oral SCC, but 2 cm is safer for high-grade tumors. (4) For subungual SCC, amputate the entire digit, including the third phalanx, to ensure complete excision. (5) Consider sentinel lymph node mapping for oral SCC to detect early metastasis. Pitfalls: (1) Incomplete excision due to inadequate margins, especially in oral SCC; always submit margins for histopathology. (2) Underestimating tumor extent, especially in cats with oral SCC; use CT for surgical planning. (3) Delaying surgery in cats with oral SCC, leading to non-resectable disease. (4) Not performing thoracic radiographs, missing pulmonary metastasis. (5) In cats, avoid using corticosteroids for inflammation, as they may immunosuppress and worsen prognosis.

Perioperative drug protocols for SCC surgery: (1) Prophylactic antibiotics: Cefazolin 22 mg/kg IV at induction, repeated every 90 minutes intraoperatively; continue for 24 hours postoperatively. (2) Postoperative analgesics: Opioids (e.g., hydromorphone 0.05-0.1 mg/kg IV q4-6h, or buprenorphine 0.01-0.02 mg/kg IV q6-8h) for 24-48 hours; NSAIDs (e.g., carprofen 2.2 mg/kg PO q12h, or meloxicam 0.1 mg/kg PO q24h) for 3-5 days, with caution in cats. (3) Local anesthesia: Lidocaine (2 mg/kg) or bupivacaine (1-2 mg/kg) as a local block or CRI (lidocaine 25-50 mcg/kg/min IV) for multimodal analgesia. (4) For oral SCC, consider perioperative corticosteroids (dexamethasone 0.1 mg/kg IV) to reduce swelling, but use with caution. (5) Chemotherapy: For non-resectable or metastatic SCC, carboplatin 300 mg/m² IV q3-4 weeks, or doxorubicin 30 mg/m² IV q3 weeks (dogs), with dose adjustments for renal/hepatic disease. (6) Radiation therapy: Not a drug, but often combined with chemotherapy. (7) Supportive care: Antiemetics (maropitant 1 mg/kg SC q24h), gastroprotectants (omeprazole 1 mg/kg PO q24h) if NSAIDs used.

Landmark studies and consensus guidelines: (1) Fossum's Small Animal Surgery (5th ed.) provides comprehensive surgical techniques for SCC excision, emphasizing wide margins and reconstructive options. (2) Tobias & Johnston Veterinary Surgery: Small Animal (2nd ed.) details surgical approaches for oral tumors, including mandibulectomy and maxillectomy, with outcomes. (3) Piermattei's Atlas of Surgical Approaches to the Bones and Joints of the Dog and Cat (5th ed.) is less relevant but useful for subungual SCC surgery. (4) Plumb's Veterinary Drug Handbook (9th ed.) provides drug dosages and protocols. (5) A study by Withrow et al. (2007) reported that cats with oral SCC have a median survival of 3 months with surgery alone, but 12 months with surgery and radiation. (6) A study by Lascelles et al. (2000) found that nasal planectomy in cats with SCC resulted in a median survival of 18 months, with good quality of life. (7) ACVS consensus guidelines recommend sentinel lymph node biopsy for oral SCC to improve staging accuracy. (8) A meta-analysis by Moore et al. (2016) showed that complete surgical excision is the most important prognostic factor for cutaneous SCC in dogs. (9) For subungual SCC, a study by Marino et al. (1995) reported a 5-year survival rate of 90% after digit amputation. (10) Current evidence supports the use of radiation therapy as an adjunct for incompletely excised oral SCC, with improved local control.