SQUAMOUS CELL CARCINOMA

Biologic Behaviour

•nasal planum SCC is common in cats and rare in dogs

•tumors: LSA, FSA, hemangioma, melanoma, MCT, and fibroma

•non-neoplastic conditions of the nasal planum include eosinophilic granuloma and immune-mediated disease

•SCC associated with ultraviolet irradiation (UVA and UVB) from sunlight

•damaging photochemical effects of sunlight are related to hair density, wave length, and intensity of radiation

•genetic inheritance is related to distribution of keratin and melanin and quantity of Langerhans cells

•white-haired cats have 13.4-times greater risk of developing SCC than cats of other coat colours

•non-white-haired cats develop SCC in areas of poor pigmentation and poorly haired areas

•melanin protects skin against solar energy

•role of FeLV and FIV is unknown, but 24% (7/29) cats with FIV have concurrent SCC

•tumor-suppressor gene p53 mutations found in 82% (9/11) cats with pinna SCC and 50% (7/14) with other SCC

•histologic type depends on the timing of biopsy: carcinoma in situ, superficial SCC, and deeply infiltrative SCC

   •locally invasive tumor but rarely metastasize

Clinical Signs

•progression of clinical signs:

•crusty and erythematous lesion

•superficial erosion and ulceration (i.e., carcinoma in situ or early SCC)

   •deeply invasive and erosive lesion

•SCC originates from cornified external surface of nasal planum in cats and mucous membrane of nostril or nasal planum in dogs

•other sites in cats include head and neck (especially pinna and eyelids) (>80%) with multiple lesions in 30%

Diagnosis

•wedge or incisional biopsy of erosive or proliferative lesions to determine histology and depth of invasion

•general anesthetic usually required due to sensitivity of nasal planum

•impression smears or superficial biopsies are rarely useful due to superficial inflammation which frequently accompanies both SCC and non-neoplastic lesions

•regional and thoracic radiographs are rarely indicated

•CT or MRI of the nose is important to determine caudal extent of tumor and planned resection in dogs

Palliative Management

•progression of preneoplastic lesions may be minimized or prevented by limiting exposure to ultraviolet light

•tattoo and sunscreen are rarely helpful in preventing SCC

Surgery

•nasal planum resection is the most effective treatment for invasive SCC (i.e., T3 and T4) of the nasal planum

•closure: skin-to-mucosal apposition or purse-string suture

•inappetence for up to 3 days postoperatively but enteral feeding is rarely required

•scab forms over surgery site but healing usually complete by 4 weeks

•nasal planum resection is associated with acceptable cosmetic results and good functional results:

•median DFI 594 days for nasal planum lesions alone and 426 days when concurrent with pinna SCC

•local tumor recurrence 57% (4/7) cats with incomplete excision and 33% (1/3) cats with complete excision, with 12-month DFI > 80%

•MST 673 days for nasal planum lesions alone and 530 days when concurrent with pinna SCC

•complication: nasal stenosis (treatment options include wide skin excision and resection of rostral nasal septum, laser ablation, rubber stents, or permanent placement of stainless steel intraluminal expansile stents)

•combined resection of premaxilla-maxilla and nasal planum

Radiation Therapy

•radiation can be delivered either as local or external beam therapy

•local radiation therapy with strontium-90 is indicated for cats with superficial SCC as strontium does not penetrate > 2 mm, with 1-year DFI 89%, 3-year DFI 82%, and median DFI 34 months

•external beam radiation therapy can be used for superficial and deep lesions

•median DFI 361 days to 16.5 months

•1-year DFI 60%-64% and 5-year DFI 10%

•MST 383-946 days with proton beam irradiation

•T is and T 1 SCC have significantly better tumor control with 56% 5-year DFI

Cryosurgery

•cryosurgery is indicated for cats with superficial, small and non-invasive SCC

•disadvantage: margins are difficult to determine

•cryosurgery response is site dependent with 100% eyelid and pinna lesions resolving after 1 treatment, but 19% of nasal planum SCC failing to respond after 2-3 treatments

•median DFI 254 days

•local tumor recurrence rate 17%-73% (8/11) with 1-year DFI 84% and 3-year DFI 81%

•MST 682 days

Photodynamic Therapy

•photodynamic therapy is indicated for superficial tumors (< 3-4 mm deep) due to limited penetration of wavelength of light used to activate photosensitizer

•disadvantage: margins are difficult to determine

•photodynamic therapy involves administration of photosensitizer that is preferentially retained by tumor tissue and results in formation of oxygen free radicals when irradiated with light of wavelength absorbed by photosensitizer

•77%-85% response rate with DFI 3-18 months for responders

•response rate is better for:

•superficial lesions with 75%-100% CR for Tis and T1 lesions but < 30% for higher grade lesions

•small lesions (< 5.0 cm)

•topical 5-aminolevulinic acid cream and subsequent exposure to red light of wavelength 635 nm has been used in 13 cats with cutaneous SCC with an 85% CR after 1 treatment but 64% local tumor recurrence rate after a median 21 weeks

•complications include no exposure to sunlight for minimum 2 weeks and facial edema, erythema, and necrosis which can be slow to resolve over 3-6 weeks

Intralesional Chemotherapy

•cytotoxic agents have been combined with substances such as sesame oil, bovine collagen, and epinephrine to prevent or minimize systemic absorption and increase local concentration of chemotherapy

•cytotoxic agents that have been investigated include carboplatin, cisplatin, and fluorouracil

•73.3%-83.0% overall response rate with 64.0%-73.3% CR and 19.0% PR

•no evidence of systemic toxicity

Systemic Chemotherapy

•carboplatin: 210-240 mg/m 2 IV q 3-4 weeks

•doxorubicin (20-30 mg/m 2 IV q 3 weeks) and bleomycin (10 IU/m 2 IM or IV for 4 days then once weekly) has resulted in sustained remission in 25% (1/4) cats with metastatic SCC

Immunotherapy

•retinoids, or synthetic derivatives of vitamin A, increase epithelial differentiation

•retinoids may reverse or limit preneoplastic lesions but are rarely effective against advanced lesions

•carotenoid therapy (i.e., β-carotene and canthaxanthin) improves solar dermatitis in 75% (9/12) cats

•isotretinoin (13-cis-retinoic acid) or etretinate are not effective for cats with SCC with only 1 (6.7%) of 15 precancerous or SCC lesions responding to therapy

•recombinant feline IFN has marked antitumor affect against SCC in vitro