Squamous Cell Carcinoma
Squamous Cell Carcinoma -Skin
Squamous cell carcinoma (SCC) is a common tumor involving
the skin and accounts for approximately 15% of cutaneous
tumors in the cat and 5% of those in the dog. SCCs are usually found in unpigmented or lightly pigmented skin. In many instances there is a recognized solar exposure relationship and these tumors are often referred to as "actinic" SCC. The most common cutaneous locations for SCC in the cat are the sparsely haired areas of the nasal planum, eyelids, and pinnae Multiple facial lesions are present in nearly 30% of affected cats. Squamous cell carcinoma usually afflicts older animals (mean age of 12 years in the cat, 8 years in the dog). Siamese cats are under-represented, as would be expected because of pigmented skin color.
SCC may present as either a proliferative or erosive lesion. Proliferative lesions may vary from a red firm plaque to a
cauliflowerlike lesion that often ulcerates. The erosive lesion, which is most common in the cat, initially starts as a shallow crustinglesion that may develop into a deep ulcer. Histologically, the initial crusting lesions often represent carcinoma in situ or preinvasive carcinoma..
Generally, SCCs involving the facial skin of cats are locally invasive but late to metastasize. The degree of local invasion can be
quite severe and response to therapy is much more successful for Tis to T1 lesions than for those with significant invasion. The
behavior of subungual (nail bed)
Many therapeutic modalities have been applied to SCC involving the facial skin in cats. Surgery or Cryosurgery are most
commonly used and remain the mainstay for treating these lesions, although numerous reports now exist detailing the use of
radiotherapy and photodynamic therapy. Outcomes are generally good for most modalities if the tumors are treated early (i.e., Tis to T1) in their course. In general, lesions of the pinna are more manageable than those of the nasal planum because the location allows a more aggressive surgical or cryosurgical dose. Surgical excision of lesions of the pinnae result in long-term control (> 1.5 years) in the majority of cases. In a report of 102 cats with 163 lesions, aggressive cryotherapy was nearly 100% effective for managing pinnae and eyelid tumors; however, only 70% of nasal planum, tumors responded. 0rthovoltage radiotheropy using 40 Gray total dosage in 10 fractions was applied in 90 cats with nasal planurn SCC. Turnor stage was found to be highly prognostic, as Tis and Ti lesions enjoyed 5-year progression-free survivals of 56%, while tumors of higher stages responded poorly. Survival in this report could also be predicted by determining the proliferation fraction of the tumor using an immunohistochernical stain for PCNA (proliferating cell nuclear antigen). Similarly, the use of strontium plesiotherapy, a form of superficial radiotherapy, has provided long-term control (1 and 3-year control rates of 89 and 82%, respectively) in 25 cats with early superficial lesions. Plesiotherapy is limited to very early, shallow lesions because the radiation dose drops off significantly below depths of 2 mm. Photodynamic therapy has also been studied extensively for the treatment of superficial SCC in both the dog and cat. Once again, if applied to early lesions, results are generally positive. Complete response rates of approximately 75% are reported for Tis to T2 staged tumors and drop off quickly to 30% for tumors of higher stages. The bottom line with respect to treating local SCC lesions is to treat small lesions aggressively. Presently, combinations of surgery and radiation therapy for infiltrative nasal planum SCC are being evaluated and show early promise.
Chemotherapy for cutaneous SCC has shown little consistent efficacy in the veterinary literature. Agents that have been
investigated on a limited basis for SCC in the dog and cat include mitoxantrone, actinomycin D, doxorubicin/ cyclophosphamide combinations, bleomycin, and cisplatin (not used in cats). Response rates are generally low and short-lived in duration. Chemotherapy in an adjuvant setting for microscopic disease following surgery or in conjunction with radiotherapy should be investigated for high-grade lesions. Intralesional sustained release cisplatin and 5-FU have also been investigated in dogs, along with local hyperthermia and alone in cats with superficial SCC. Long-term results are lacking; however, nearly half of the cats and dogs with actinic-related SCC have achieved a complete response.
The vitamin A-related synthetic retinoids have also been evaluated in dogs and cats with solar-induced cutaneous SCC. Only
preneoplastic lesions were responsive to etretinate and early superficial lesions to a combination of isotretinoin and local
hyperthermia in the dog. No significant response was noted in 10 cats treated with isotretinoin.
The nonsteroidal anti -inflammatory drug piroxicam, also known for its immunomodulating effects, has also been evaluated for
efficacy in dogs with nonresectable SCC. Partial responses were noted in half of the 10 patients treated, with a resulting median survival of 150 days.
A relatively new variation of SCC reported in cats is best referred to as Multicentric SCC in situ (MSCCIS, also called Bowen's disease, or Bowenoid carcinoma in situ). Unlike actinic or solar-induced SCC in situ, MSCCIS is found in haired, pigmented areas of the skin and is unrelated to sunlight exposure. It has not been associated with either, FeLV or FIV viral infections. Multiple lesions are usually present in older cats, and lesions are confined to the epithelium, with no breachment of the basement membrane. The lesions are generally crusty, easily epilated, painful, and hemorrhagic when manipulated. They are felt to be preneoplastic, because three cats had true SCC adjacent to sites of MSCCIS. When excision is possible, recurrence has not been reported; however, similar lesions often develop at other sites. They are unresponsive to antibiotics and corticosteroids, and variably responsive to strontium plesiotherapy.
Tonsillar squamous cell carcinoma is 10 times more common in animals living in urban areas than in rural ones, implying an etiologic association with environmental pollutants. Most primary tonsillar cancer is squamous cell carcinoma. Lymphoma can affect the tonsils but is usually accompanied by generalized lymphadenopathy. Other cancer, especially malignant melanoma, may metastasize to the tonsil as well. Cervical lymphadenopathy, ipsi- or contralateral, is a common presenting sign, even with very small primary cancers. Fine-needle aspirates of these lymph nodes or excisional biopsy of the tonsil will confirm the diagnosis. Thoracic radiographs will be positive for metastasis in 10 to 20% of cases at presentation. In spite of disease apparently confined to the tonsil, this disease is considered systemic at diagnosis in more than 90% of patients. Simple tonsillectomy is almost never curative but probably should be done bilaterally because of the high percentage of bilateral disease. Cervical lymphadenectomy, especially for large and fixed nodes, is rarely curative and should be considered diagnostic only. Regional radiation (pharynx and cervical lymph nodes) is capable of controlling local disease in more than 75% of the cases; however, survival still remains poor, with only 10% of affected animals alive after 1 year. The cause of death is local disease early and systemic disease (usually lung metastasis) later. To date, no known effective chemotherapeutic agents exist for canine or feline squamous cell carcinoma, although cisplatin and bleomycin have been utilized with very limited success. Cisplatin should not be used in cats.
Rapid and progressive local invasion
of cords of neoplastic squamous epithelium arising from the tonsillar fossa into tonsillar
Local extension common
Quick to metastasize to lymph nodes (> 98%) and lung (> 63%)
Composes nearly 20-25% of all oral tumors and 50% of all intraoral tumors of dogs and cats
Commonly unilateral, affecting the right more than the left tonsil
Squamous Cell Carcinoma-Tongue
Cancer confined to the tongue is rare. Feline tongue tumors are usually squamous cell carcinoma and most are located on the ventral surface near the frenulum. The presentfng signs are similar to other oral cancers and mass lesions.
Under general anesthesia, the tongue may be biopsied with a wedge incision and closed with horizontal mattress sutures. The regional lymph nodes should be aspirated for staging purposes, if palpable. The treatment is generally with surgery, and irradiation is reserved for inoperable cancer or cancer metastatic to the lymph nodes. Partial glossectomy can be performed for more than half of the mobile tongue. Eating and drinking may be slightly impaired, but good hydration and nutrition can be maintained postoperatively. Grooming in cats will be compromised, with up to 50% removal and may result in poor hair-coat hygiene. Long-term control of feline tongue tumors is rarely reported.
The prognosis for tongue tumors will vary with the site, type, and grade of cancer. Cancer in the rostral (mobile) tongue has a better pattern of behavior for any of the following reasons:
1. Earlier detection, since the owner can see the lesion.2. The rostral tongue may have less abundant lymphatic and vascular channels as opposed to the caudal tongue, whose richer
Squamous Cell Carcinoma - Nasal Planum
INCIDENCE AND RISK FACTORS
Cancer of the nasal planum is rare in the dog and fairly common in the cat. The development of squamous cell carcinoma (SCC) has been correlated with ultraviolet light exposure and lack of protective pigment. It is classically seen in older, lightly pigmented cats.
PATHOLOGY AND NATURAL BEHAVIOR
By far the most common cancer is SCC. Depending on the timing of biopsy, these tumors may be reported as carcinoma in situ, superficial SCC, or deeply infiltrative SCC. They may be very locally invasive but only rarely metastasize.
Other cancers reported in this site are lymphoma, fibrosarcoma, hemangiomas, melanoma, mast cell tumors, fibromas, and eosinophilic granulomas. Immune-mediated disease may present as erosive or crusty lesions on the nose but are rarely proliferative and usually have other sites on the body affected.
HISTORY AND CLINICAL SIGNSInvasive SCC is usually preceded by a protracted course of disease (months to years) that progresses through the following stages: crusting and erythema, superficial erosions and ulcers (carcinoma in situ or early SCC), and finally deeply invasive and erosive lesions. Associated eyelid and ear pinna lesions may be seen if these sites lack pigment. Patients have often been treated with corticosteroids or topical ointments with little response.
DIAGNOSTIC TECHNIQUES AND WORKUP
Erosive or proliferative lesions should have a deep wedge biopsy to determine the degree of invasion and histologic type of disease. These biopsies will require a brief general anesthetic because of sensitivity of the nasal planum. Hemorrhage can be profuse and will usually require one or two sutures to appose the edges. Rarely, dilute epinephrine (1 : 10,000) can be injected or topically applied to arrest capillary oozing. Cytologic scrapings or superficial biopsies are of little value, since they only reveal the inflammation that may accompany both cancer and noncancerous conditions. Lymph nodes are rarely involved except in very advanced disease, and thoracic radiographs are invariably negative for metastasis.
It may be possible to prevent or arrest the course of the preneoplastic disease by limiting exposure to the sun or tattooing to add pigment protection. topical sunscreens are readily licked off and rarely help. When inflammation and ulceration are present, it is very difficult to maintain the tattoo, since it is rapidly removed by macrophages. Even under the best of circumstances, tattooing will have to be repeated at regular intervals. Attempts to increase epithelial differentiation with synthetic derivatives of vitamin A generally have been unsuccessful for advanced disease but may be of help in reversing or limiting the growth of preneoplastic lesions.
SCC, and probably other neoplasms as well, fall into two general categories: (1) superficial minimally invasive disease and (2) deeply infiltrating disease. Superficial cancers can be managed effectively by almost any method, including cryosurgery, phototherapy, hyperthermia, or irradiation. A distinct disadvantage with these techniques is the inability to get a surgical margin to document the adequacy of the treatment. Deeply invasive cancer, on the other hand, is generally resistant to these treatments. In particular, radiation therapy, which would have the greatest chance of preserving the cosmetic appearance of the nose, has had poor local control rates for bigger and more invasive SCC in the dog and the cat. The expectations for radiation with other tumor types would have to be extrapolated from the radiation results achieved in more conventional sites.
Complete excision of invasive cancer of the nasal planum can be performed in the cat with an acceptable cosmetic result. The nasal planum is completely removed with a 360-degree skin incision that also transects the underlying turbinates