Tumors of the skin and subcutaneous tissues are common in veterinary patients. ^1-5 They are classified as epithelial, mesenchymal, melanocytic, or round cell (discrete cell) in origin. Most are primary tumors, but metastases and cutaneous paraneoplastic conditions are possible. In cats, skin tumors are more likely to be malignant. ^4,5 The most common cutaneous tumors of cats and dogs are listed in TABLE 23-1 and TABLE 23-2 .

Cutaneous tumors are readily identified by inspection and palpation of the skin. In patients with thick haircoats, effort should be made to palpate the skin and part the hair to identify any masses. It is important to examine areas less visible to owners, including lips, ears, ventrum, paws, and the axillary, ventral cervical, inguinal, perianal, and genital regions. Clinicians should look for preneoplastic lesions including non-healing scabs, discolorations, and skin texture changes in lightly pigmented, thin-haired areas susceptible to solar damage. Skin lesions should be documented in the medical record on a body map (included on the website, www.smallanimaloncology.com ) or with a digital photograph. Masses should be measured with calipers, and fine-needle aspirates should be obtained for cytology. Biopsy and histology are indicated for masses that are growing, changing in appearance, or irritating the patient and when cytology does not provide a definitive diagnosis.

The decision of whether incisional or excisional biopsy is appropriate (see Chapter 6 ) is based on the size, location, and suspected diagnosis of the mass. Histology provides important information including diagnosis, assessment of completeness of excision with margin measurements, mitotic index, histologic grade, and identification of vascular/lymphatic invasion. For some tumors, immunohistochemistry or special stains may be required to determine the diagnosis. In addition, assessment of proliferation indices is a valuable prognostic indicator for some tumors.

For most skin tumors, surgical excision is the treatment of choice. The extent of surgery required depends on the tumor type (see Chapter 14 ). Tissues shrink and shift in formalin, ⁶ so small samples should be placed in cassettes; for larger excisions, the subcutaneous tissue should be sutured to the skin. A complete history and description of the mass should be provided for the pathologist. Any resected tissues should be submitted in entirety for histology, even if a benign diagnosis is expected, and the surgical margins should be marked with India ink or the multi-colored Davidson Marking System (Davidson Marking System, Bradley Products, Inc., Bloomington, MN).

SCC appears as solitary or multiple erosive, proliferative, or nodular dermal lesions that may be accompanied by erythema, scale, and concurrent solar-induced tumors (e.g., dermal hemangioma and hemangiosarcoma [HSA]; Figure 23-1 ). In cats, SCC is most commonly seen in white cats on poorly haired areas of the ear tips, preauricular areas, nasal planum, and periocular regions. ^12,13,15 Early lesions are often mistaken for scratches but do not heal.

Multi-centric SCC in situ (MSCCIS) is seen in cats of all colors. Lesions appear as multiple, alopecic, non-healing scabs on the trunk, limbs, and head. ²² Histologically, MSCCIS does not invade the epidermal basement membrane, but in some cases, focal areas of invasive SCC are present. These areas are firm, crusted, crateriforme masses. ²²

Nail bed SCCs are frequently incidental but may be accompanied by lameness, split toenails, and bleeding. ¹⁰ Eighty percent of dogs with digital SCC have radiographic evidence of bone lysis. ^10,11 Multiple digital SCCs are occasionally seen in dogs. ^10,11,20,21 In cats, nail bed carcinomas may represent metastasis from a primary lung carcinoma; most commonly, these cats are evaluated because of lameness, not respiratory signs. ²³

The diagnosis of SCC should be histologically confirmed, since inflammation may confound cytologic diagnosis. Three-view thoracic radiographs and a regional lymph node aspirate should be performed. Biopsy of superficial facial lesions may be accomplished by shaving the lesion with a scalpel blade. Since the resulting biopsy samples are thin and fragile, placement into a tissue cassette prior to submerging in formalin is indicated.

In dogs and cats with nail bed SCC, radiographs of the affected digit(s), three-view thoracic radiographs, and a regional lymph node aspirate are indicated to evaluate the patient for bony lysis of the digit and pulmonary metastasis or a primary bronchogenic carcinoma (cats). ^10,11,23

Cutaneous SCC is locally invasive. Metastasis to regional lymph nodes is uncommon and pulmonary metastasis is rare. In a study of cats with planum SCC, 6 of 15 (40%) of necropsied cats had regional lymph node metastasis, and 1 (6%) had pulmonary metastasis. ¹³ Only 3% to 13% of dogs with nail bed SCC have radiographic evidence of pulmonary metastasis at the time of diagnosis, ^10,11 and, in one study, 29% eventually developed metastasis. ¹⁰

For dogs with solitary or multiple dermal SCC, surgical excision and behavioral modification to avoid sun exposure are recommended. When multiple lesions are present, topical imiquimod cream (Aldara, 3M Pharmaceuticals, St. Paul, MN) may slow the progression of dermal SCC and other skin lesions. ²⁴ Although the extent of disease in most patients limits its use, electron beam radiation therapy could be considered for localized SCC. Anecdotally, laser removal ²⁵ and oral COX-2 inhibitors have been used to control SCC lesions. Oral and topical retinoids are uncommonly used for multiple SCC in dogs because of cost, potential for serious side effects, and questionable efficacy. ²⁶

For cats with SCC lesions on the face, treatment options are limited by the size and invasiveness of the tumor, so early treatment is best. Untreated SCC invades normal tissues, resulting in disfigurement and loss of function. ¹⁵ Pinnectomy and nosectomy can be effective in controlling the disease. ¹⁵ Tumor control is better for cats with tumors amenable to surgical excision when compared with external beam radiation therapy, and cryotherapy is associated with shorter control times when compared with either of these modalities. ¹⁵

Strontium-90 beta radiation ( ⁹⁰ Sr) is effective for lesions < 2 mm in depth and incompletely excised small lesions ( Figure 23-2 ). ^{27,28 90} Sr is effective for superficial SCC, with nearly 90% of cats tumor free at 1 year and 80% tumor free at 2 years after therapy. ²⁷ In a study of 90 cats with nasal planum SCC treated with external beam radiation therapy, 1- and 5-year progression-free rates were 60% and 10%, respectively. Cats with tumors < 2 cm had a better prognosis than those with tumors > 3 cm in diameter. ¹³ For more advanced local disease, external beam radiation therapy may provide long-term tumor control. ^13,15 Intratumoral administration of carboplatin (Paraplatin, Bristol-Myers Squibb Co., Princeton, NJ), ²⁹ photodynamic therapy, ^30,31 and cryotherapy ¹⁵ have also been used for superficial lesions but are associated with shorter control times. SCC is poorly responsive to systemic chemotherapy. ¹⁵ In one study, none of the feline cutaneous SCC tested expressed COX-2, suggesting that COX-2 inhibition is unlikely to be useful in this species. ³²

Client education about SCC prevention is essential. Techniques to minimize sun exposure in dogs and cats include limiting access to the outdoors and windows during peak sun hours and the use of topical sunscreen or protective clothing.

Surgical excision can provide local control of MSCCIS lesions; however, cats frequently develop lesions at other sites. ²² In a recent report of 12 cats with MSCCIS treated with imiquimod, all cats showed improvement in lesions. ³³ Observed toxicities included local erythema, gastrointestinal signs, elevated liver enzymes, and neutropenia. ⁹⁰ Sr may also be useful for lesions < 2 mm in depth. ³⁴ In cats with MSCCIS, local recurrence following surgical excision is rare; however, long-term monitoring is required because of the multifocal nature of the disease. ²² Long survival times are observed. ³³

For dogs with nail bed SCC, wide amputation with disarticulation of the first phalanx or metacarpal/metatarsal bone is the treatment of choice. Radiation therapy and chemotherapy may be indicated for incompletely excised or metastatic tumors. ¹⁰ In one study of dogs with nail bed SCC, the 1- and 2-year survival rates were 95% and 74%, respectively, for subungual SCC, and 60% and 44% for SCC from other parts of the digit. ¹¹ A more recent study showed a 1-year survival rate of 50% and a 2-year survival rate of 18%. ¹⁰ Only 15% had metastasis at the time of death or last follow-up, and dogs treated with surgery survived longer than those not treated.

For cats with nail bed tumors resulting from metastasis of primary bronchogenic carcinomas, surgical resection of the digit is rarely palliative because of the poor prognosis associated with this syndrome. ²³ In one study, the mean survival time for these cats was 58 days from diagnosis, regardless of treatment. ²³

Papilloma ( Table 23-3 )

Sebaceous adenoma, ductal adenoma, and epithelioma are benign tumors that are common in dogs and rare in cats. Sebaceous carcinoma is uncommon. ^46,47 Sebaceous tumors are most common in middle-aged to older dogs and cats. Predisposed breeds include English cocker spaniel, cocker spaniel, Samoyed, Siberian husky, cock-a-poo, Alaskan malamute, West Highland white terrier, cairn terrier, dachshund, miniature poodle, toy poodle, shih tzu, and Persian cats. ⁴⁶

Sebaceous tumors may be solitary or multiple. Common sites are the head and dorsum. Sebaceous tumors present as elevated alopecic nodules that may contain keratin or may have a wart-like appearance. Sebaceous epitheliomas may be pigmented. ^46-48

Cytology may be suggestive of the diagnosis, and biopsy is needed for definitive diagnosis. Regional lymph node aspiration and three-view thoracic radiographs are indicated for sebaceous carcinomas.

Sebaceous carcinomas are locally invasive. Rarely, sebaceous carcinomas and epitheliomas metastasize to local lymph nodes or other sites. ^46-48

Wide surgical resection is curative for most sebaceous tumors. Rarely, sebaceous carcinomas and epitheliomas metastasize. ^46-48

Benign apocrine tumors, including apocrine cyst, cystadenoma, ductular adenoma, and secretory adenoma, are common in the dog and uncommon in the cat. Cutaneous apocrine gland carcinomas are uncommon. ^49,50 Apocrine tumors are most common in middle-aged to older dogs. Predisposed breeds for adenomas include Lhasa apso, Old English sheepdog, collie, shih tzu, great Pyrenees, chow chow, malamute, and Irish setter; for carcinomas, they include the Old English Sheepdog, shih tzu, German shepherd, cocker spaniel, Coonhound, Norwegian Elkhound, and Siamese cats. ^49,50

Apocrine tumors usually present as solitary masses on the head (cats and dogs) and legs (dogs). ^49,50 Multiple masses are also possible. ⁵¹ Tumors may be freely movable or invasive.

Cytology may be suggestive of the diagnosis, and biopsy is needed for definitive diagnosis. Regional lymph node aspiration and three-view thoracic radiographs are indicated for apocrine carcinomas.

The growth rate of apocrine carcinomas is variable and metastasis is uncommon, usually to lymph nodes and lungs. Inflammatory carcinomas are associated with rapid growth and metastasis. ⁴⁹

Surgical resection is curative for most apocrine tumors. ^51,52 In a study of 25 dogs with apocrine gland carcinomas treated with surgery, only 1 dog was euthanized for tumor-related causes and the median survival time (MST) was 30 months (17 dogs still alive). ⁵¹ Occasionally, lymphatic and distant metastasis may be seen. Metastasis is predicted by vascular invasion and tumor grade. ^50,51 For incompletely excised carcinomas or those with vascular/lymphatic invasion or regional lymph node metastasis, adjunctive therapy with radiation or chemotherapy is indicated. Protocols for these tumors are not well described, but protocols effective for anal sac gland adenocarcinoma (see Section G ) or mammary adenocarcinomas ( Chapter 22, Section F ) would be logical choices.

Melanoma is common in dogs ^4,53,54 and the second most common tumor of the digit in this species. ^{10,11,53,55,56} Melanoma is rare in cats. ^4,5,53,56 The most common pigmented tumor in cats is basal cell tumor (trichoblastoma). Melanomas are more common in purebred dogs. ⁵⁷ Genetic predisposition is suggested by increased prevalence in standard and miniature schnauzers, Doberman pinschers, Scottish terriers, Boston terriers, boxers, Airedale terriers, Irish and Gordon setters, cocker and Springer spaniels, and Golden retrievers. ⁵⁸ More recently, for melanoma of the haired skin, Labrador retrievers, miniature schnauzers, and Rottweilers were overrepresented and for melanoma of the digit, Labrador retrievers, Golden retrievers, and Rottweilers were overrepresented. ⁵⁹

Although melanomas are typically pigmented dermal masses, some are amelanotic.

Cytology may be suggestive of the diagnosis, but melanoma is diagnosed with biopsy and histology. Immunohistochemical stains (S100 and MelanA) for proteins expressed by melanomas may be required for diagnosing anaplastic tumors. ⁶⁰ For dogs with negative prognostic indicators (i.e., digital or mucocutaneous junction location, malignant histologic appearance, high mitotic index, or vascular/lymphatic invasion), cytology of regional lymph nodes, and three-view thoracic radiographs are indicated. Abdominal ultrasound should also be considered. Because the behavior of cutaneous melanomas in cats is less predictable, these tests are recommended routinely.

Cutaneous melanoma is typically behaviorally benign in dogs. ^61,62 Malignant melanoma metastasizes via lymphatics to lymph nodes, lungs, and other sites. The behavior of cutaneous melanomas in cats is less predictable. In cats, melanomas are often slow growing and some are cured with surgical excision, but others recur locally or spread to lymph nodes, lungs, and other sites, including viscera or bone. ^63,64

Adjunctive therapies may be indicated for patients with malignant melanoma. Radiation therapy is effective for malignant oral melanomas in dogs ( Chapter 20, Section A ) and may be useful for control of incompletely excised malignant cutaneous melanomas and involved regional lymph nodes. Chemotherapy with carboplatin may be helpful for slowing local progression and metastasis. One study demonstrated a 28% response rate of measurable malignant melanomas to this drug. ⁶⁵ In addition, because melanomas are highly immunogenic, there has been great interest in developing immunotherapy as a treatment for these tumors. ^57,66,67 A xenogenic DNA canine melanoma vaccine is currently commercially available (Canine Melanoma Vaccine, Merial Limited, Duluth, GA). Plasmid DNA encoding human tyrosinase (a melanocytic protein) is injected into the muscles of the medial thigh. Canine myocytes express the DNA, and the resultant human tyrosinase induces an immune response. Human and canine tyrosinase are similar enough that the immune response can cross over to be directed at canine melanocytic cells. ^66,68 This vaccine has been demonstrated to be safe and active in phase 1 and 2 clinical trials in dogs and survival times > 1 year have been described. It is recommended that this vaccine be used as adjunctive therapy once locoregional tumor control has been achieved. Currently, the canine melanoma vaccine is licensed for use by veterinary oncologists only.

The behavior of cutaneous melanomas in cats is much less predictable, and even histologic diagnosis as benign or malignant may not predict behavior. ⁶³ In one study of cats with cutaneous melanoma treated with surgery with or without adjuvant therapies, survival times ranged from 0 to 1003 days, with 5 of 19 cats dying of melanoma. ⁶³ Another study described 45 cats with cutaneous melanoma treated with surgery ⁶⁴ ; 22 of 37 cats that died during the study had local recurrence. Sixteen of these 37 cats were necropsied and all had metastasis.

HSAs and hemangiomas are tumors of vascular endothelium. They occur more frequently in dogs than any other species but are uncommon in the skin of dogs and less common in cats. ^69,70 In dogs, cutaneous hemangioma is more common than HSA. Cutaneous HSA is more common in older animals. Predisposed breeds include the Italian greyhound, greyhound, whippet, Dalmatian, pit bull, boxer, and Basset hound. ^69-71 Solar radiation induces dermal hemangiomas and HSA in dogs with short hair and lightly pigmented skin. ⁷¹ Subcutaneous HSA is not solar induced. The identification of pairs of affected sibling Italian greyhounds and whippets suggests a possible genetic predisposition. ^70,71

Dermal hemangiomas and HSAs appear as red or purple discolorations or raised masses, and lesions may be solitary or multiple. Dermal HSA frequently occurs in lightly haired and unpigmented areas, including the ventral abdomen, limbs, neck, dorsum, and head. ^69-72 Subcutaneous lesions are firm or soft masses that often appear bruised and have no site predilection.

Diagnosis of HSA is accomplished with biopsy and histology. For anaplastic tumors, immunohistochemical staining for Factor VIII–related antigen (von Willebrand factor), and CD31 can be used to confirm the diagnosis. ^73,74 Solar-induced changes such as dermal elastosis and actinic keratosis may be observed in the skin surrounding dermal HSA. Because HSA of the skin can metastasize or may represent metastasis from visceral HSA, further staging tests are indicated. A CBC, serum chemistry profile, urinalysis, thoracic and abdominal radiographs, abdominal ultrasound, cytology of local lymph node, and echocardiogram are recommended, particularly for subcutaneous lesions, multiple lesions, or lesions not consistent with solar etiology. A staging scheme has been described for canine cutaneous HSA: stage I is a primary tumor confined to the dermis, stage II is a primary tumor involving the hypodermis, and stage III is a primary tumor with underlying muscular involvement. ⁶⁹

For subcutaneous tumors or those with vascular/lymphatic invasion or metastasis, adjunctive chemotherapy may improve survival time. Treatment protocols are those used for splenic HSA ( Chapter 22, Section D ) and should include doxorubicin. In a study evaluating vincristine (Vincasar, SICOR Pharmaceuticals, Irvine, CA), doxorubicin, and cyclophosphamide (Cytoxan, Mead Johnson Oncology Products, Princeton, NJ) chemotherapy for dogs with HSA, an MST of 425 days was reported for 6 dogs with subcutaneous HSA, ⁷⁹ and in a study evaluating doxorubicin and cyclophosphamide for dogs with HSA, survival times ranged from 183 to 704 days for four dogs with subcutaneous HSA. ⁸⁰ In one study of 17 dogs with subcutaneous HSA treated with doxorubicin chemotherapy with or without radiation therapy, the median survival was 1189 days. ⁷⁷ The role of continuous low-dose oral chemotherapy for subcutaneous HSA has not been defined, but a preliminary study of cyclophosphamide, etoposide (Etoposide, Gensia Sicor Pharmaceuticals, Irvine, CA), and piroxicam (Feldene, Pfizer Incorporated, New York, NY) administered in this fashion after splenectomy to dogs with splenic HSA demonstrated a similar MST (6 months) to dogs treated with doxorubicin. ⁸¹ There is much interest in immunotherapy and antiangiogenic therapy for HSA, ^82,83 but these therapies are not readily available at this time.

In cats, subcutaneous HSA is more likely to recur or metastasize than cutaneous HSA, but complete excision can be associated with long survival. ^72,76 In one study, 10 cats treated with surgery for subcutaneous HSA lived 13 to >112 weeks. ⁸⁴ In another study of 18 cats with cutaneous HSA, the MST was 912 days (range, 4–1460; 5 cats still alive at 120–1186 days), and cats treated with surgery lived significantly longer than those not treated with surgery. ⁷² For incompletely excised HSA, radiation therapy should be considered. There is little information regarding adjuvant chemotherapy for HSA in cats, but doxorubicin (as a single agent or in combination with vincristine and cyclophosphamide), carboplatin, and a combination of mitoxantrone (Novantrone, Immunex Corp, Seattle,WA) and cyclophosphamide have been used. ^72,76,85

Plasmacytomas appear as raised, hairless, pink dermal nodules and are typically found on the face, ears, or feet ( Figure 23-4 ). ^86,87 In dogs, they are usually solitary, but multiple PCTs are possible.

Cytology is often diagnostic and histology provides a definitive diagnosis. For more anaplastic tumors, immunohistochemical staining may be required to definitively differentiate PCT from lymphoma or MCT. For most dogs, a CBC, serum biochemical profile, urinalysis, and regional lymph node aspirate provide complete staging information. For dogs with multiple tumors, lymph node metastasis, or hyperglobulinemia, serum and urine protein electrophoresis or immunoelectrophoresis, thoracic and abdominal radiographs (including axial skeleton), abdominal ultrasound, and bone marrow aspirate are indicated. Because of the systemic nature of PCT in cats, all of the staging tests listed are recommended.

Most cutaneous PCTs in dogs are primary tumors. ^86,87 Rarely, canine cutaneous PCT may be associated with multiple myeloma and/or paraneoplastic syndromes (including hyperglobulinemia and hypercalcemia). ^86,87 In contrast, in cats PCT may be more commonly associated with metastasis or multiple myeloma. ^88,89

Most cutaneous PCTs in dogs are benign and are cured with surgical excision. ^86,87 In one study of 57 dogs with cutaneous PCT, 46 had no recurrence at 1 to 62 months after surgery, and 4 were euthanized for systemic disease related to the tumor. ⁸⁷ Histologic grading of canine PCT does not predict behavior. ⁹⁰ Rarely, dogs develop multiple cutaneous PCTs or lymph node metastasis. These dogs may enjoy long survival times with chemotherapy. A chemotherapy protocol for multiple myeloma (combination of melphalan [Alkeran, Cardinal Health for GlaxoSmithKline, Albuquerque, NM] and prednisone; see Chapter 25, Section C ) is indicated for cats and for dogs with metastatic disease or multiple PCTs. Radiation therapy can provide long-term control for tumors in locations not amenable to surgery. There is little information describing the prognosis for PCT in cats, but association with systemic disease would suggest a poorer prognosis. ⁸⁸

Histiocytic proliferative disorders (HPDs) of dogs include cutaneous histiocytoma, reactive histiocytosis (cutaneous and systemic histiocytosis [believed to be an immunoregulatory disorder]), and malignant histiocytosis (localized and disseminated histiocytic sarcoma [HS] [ Section F ]. These diseases are distinguished by histologic appearance, immunophenotype, and varying clinical presentations/courses. ^91-94 Histiocytomas are benign tumors of Langerhans’ cells (antigen-presenting cells of the epidermis). They are most common in young, purebred dogs but can be seen in any dog. ⁹⁵ Breeds at risk include Scottish terriers, boxers, Doberman pinschers, Labrador retrievers, cocker spaniels, Rottweilers, and miniature schnauzers. ⁹⁵ They are extremely rare in cats.

Histiocytomas are hairless, raised, and white, pink, or red dermal nodules that can become inflamed and ulcerated, especially when regressing ( Figure 23-5 ). Most commonly they occur on the head or limbs.

Cytology is usually diagnostic for histiocytoma. Because of the possibility of misdiagnosis of cutaneous lymphoma or another round cell tumor, in cases with an atypical presentation (old dog, multiple lesions, not regressing), biopsy and histologic confirmation of diagnosis are indicated. Rarely, immunophenotyping ^91-93 may be necessary to rule out other diagnoses and confirm that a mass is a histiocytoma.

Histiocytomas are usually solitary and do not metastasize; however, multiple regressing cutaneous histiocytomas have been reported. Langerhans cell histiocytosis (LCH) is a syndrome of multiple cutaneous histiocytomas that may be slow to regress, wax and wane for a period, or progress to organ involvement. ^96,97 LCH is seen in children and has been reported in young dogs.

Most canine histiocytomas regress spontaneously within 2 to 4 months, and recurrence or development of additional lesions is rare. If a histiocytoma does not resolve, is irritating to the patient, or has an atypical presentation, surgical resection and histology are indicated.

^k Alkeran®, Cardinal Health for GlaxoSmithKline, Albuquerque, NM.