Tumors of the Skin & Subcutaneous Tissues
INCIDENCE AND RISK FACTORS
In the cat, tumors of the skin and subcutaneous tissue are second in frequency only to tumors of the lymphoid system and account for approximately one quarter of all tumors in the species. Estimates of incidence rates for skin and subcutaneous tumors have been reported to be approximately 120 per 100,000 cats. Many tumor types occur in the skin, and a listing of the 5 most frequent in the cat based on larger North American (U.S.), and United Kingdom (U.K.) surveys are presented in Table 1. Approximately 80% of the cutaneous tumors encountered in the cat are represented in this table. Mast cell tumors represent the second most commonly encountered cutaneous tumor in the cat will be discussed later in this section. Approximately 20 to 30% of primary tumors of the skin and subcutaneous tissues are histologically malignant in the dog, compared to 50 to 65% in the cat. Occasionally, cutaneous tumors in dogs and cats may be secondary metastatic lesions, and should be included as a possibility in the list of differentials.
|Table 1 Frequency (Percentage) of Top Six Cutaneous Neoplasms in the Cat|
Basel Cell Tumor
Mast Cell Tumor
Squamous Cell Carcinoma
Ceruminous Gland Adenocarcinoma
In general, cutaneous tumors occur in older animals and no significant difference in the incidence by sex is noted when all types are considered together. Such differences, where they exist, along with breed predilections, will be discussed under specific tumor types.
Specific etiologies have been proven for only a few tumors in the dog and cat. Several contributing factors in the development of skin tumors include viruses, solar and ionizing radiation, hormones, genetic influences, vaccines, thermal injuries, and immunologic influences.
Long-term exposure to the ionizing effects of sunlight
result in solar dermatosis, leading to documented increases in cutaneous hemangioma,
hemangiosarcoma, and squamous cell carcinoma in beagles as well as squamous cell carcinoma
in the cat. Feline leukemia virus (FeLV) is associated with the development of
cutaneous lymphoma, and the feline sarcoma virus has, under experimental conditions,
produced malignant melanoma in cats. Recently, a vaccine-associated sarcoma of cats
has been associated with aluminum-based adjuvants. Macrophages surrounding some
tumors contained aluminum oxide identified by electron probe microanalysis and imaged by
energy-filtered electron microscopy. Persistence of inflammatory and
immunological reactions associated with aluminum may predispose the cat to a derangement of its fibrous connective tissue
repair response, leading to neoplasia. (Cancer Res 1992 Oct 1;52(19):5391-4 ).
The heterogeneity of cutaneous structures that can be involved in a neoplastic process complicates the issue of classification. Generally, skin tumors are classified histologically according to the tissue of origin (epithelial, mesenchymal, melanotic, or round cell) and individual cell of origin if sufficient differentiation is present. Tumors are further classified as to the degree of malignancy based on several histologic characteristics. In some cases, there is not a clear differentiation between malignant and benign skin tumors.
Clinically, skin tumors are further classified, utilizing
the TNM (tumor-node-metastasis) system devised by the World Health
Organization (J Vet Intern Med 4:242-246, 1990). This system allows the
tumor to be described in exacting detail with regard to its clinical presentation.
Finally, one must consider the tumor location when classifying a skin tumor. Some tumors
behave differently when located in different areas of the body. An example of the
difference in behavior because of location is canine oral melanoma (usually malignant)
versus canine cutaneous melanoma arising from haired skin (usually benign). In addition,
biologic behavior often varies for the same type of tumor in the dog versus the cat.
HISTORY AND CLINICAL SIGNS
The history for an animal with a cutaneous tumor is variable. Commonly, owners will discover a growth while examining or grooming their pets. Benign tumors are more likely to have a history of slow growth from weeks to years. It is not unusual for benign epithelial tumors to be presented for ulceration due to self-trauma or secondary inflammation. Most benign tumors are well circumscribed, nonpainful, and freely movable and incite a minimal inflammatory response. Malignant tumors are often rapidly growing, fixed to underlying structures and ulcerated and will often have ill-defined margins. Invasion into vessels and regional lymphatics is often observed.
Basal Cell Tumors
The basal cell tumors (BCTs) include basal cell epithelioma, basal cell carcinoma, and basiloid tumor. Since the tumor in domestic animals is almost always benign, the preferred nomenclature is basal cell tumor. BCT is the most common skin tumor affecting the cat, representing 15 to 26% of all feline skin tumors. It is less common in the dog, representing 4 to 12% of canine skin tumors. These tumors are generally found in middle-aged dogs (6-9 years) and slightly older cats with a mean age of 10 to 11 years. In the dog, cocker spaniels and poodles have an increased incidence, and in cats, the Siamese were over- represented in one large study, while others have not documented a breed predilection. BCTs are usually solitary, well circumscribed, firm, hairless, dome-shaped elevated masses from 0.5 to 10 cm in diameter. Most BCTs are freely movable and firmly fixed to the overlying skin but rarely invade underlying fascia. These tumors are most commonly located on the head, neck, and shoulders in both the dog and cat. Feline BCTs can be pigmented, cystic, or solid, and are occasionally ulcerated and have a surprisingly high mitotic rate for tumors that are benign. Most BCTs are benign, grow slowly, and may be present for months prior to diagnosis. The treatment of choice for BCTs is surgical excision, which carries a good prognosis. In 124 cases of BCTs in cats treated by surgical excision, none recurred nor metastasized. In another report of 97 BCTs in cats, approximately 10% were classified as histologically malignant; however, only one developed metastasis to regional lymph nodes. Rare recurrences and no metastasis have been reported in the dog. Cryosurgery is an alternative to surgery for smaller (< 1 cm) lesions.
Mast Cell Tumors
The neoplastic proliferation of mast cells referred to as mast cell tumors (histiocytic mastocytoma, mast cell sarcoma) represents the most commonly encountered cutaneous tumor in the dog and the second most common cutaneous tumor in the cat. Systemic forms of the disease are often referred to as mastocytosis. Canine and feline forms of the disease must be considered separately, as many differences exist with regard to histologic type, biologic behavior, therapy, and prognosis.
FELINE MAST CELL TUMORS
Incidence and Risk Factors
MCTs represent the second most commonly encountered cutaneous tumor in the cat, accounting for approximately 20% of cutaneous tumors in this species in the United State. The incidence of MCTs in cats appears to have increased dramaticaly since 1950. MCTs in the United Kingdom appear to occur much less frequently, accounting for only 8% of all cutaneous tumors.' Two distinct forms of cutaneous MCTs in the cat have been reported: (1) the more typical mastocytic MCTs, histologically similar to MCTs in dogs, and (2) the less common histiocytic MCTs, with morphologic features characteristic of histiocytic mast cells. An overall mean age of 8 to 9 years is reported for cats with MCTs; however, the mastocytic and histiocytic forms occur at mean ages of 10 and 2.4 years, respectively. Siamese cats appear to be predisposed to development of MCTs of both histologic types. The distinct histiocytic form of MCTs in cats has been reported to occur primarily in young (< 4 years of age) Siamese cats, including two related litters. In contrast to these reports, Siamese cats have not been found any more likely to develop the histiocytic form of MCTs than the mastocytic form, as reported in another series of cases. This report found only two of seven cases of histiocytic MCTs were from Siamese in their hospital population. Earlier studies reported a male predilection for development of MCTS; however, larger more recent series have failed to confirm such a predilection.
Visceral MCTs appear to be more common in the cat than in
the dog, with up to 50% of MCT cases occurring in visceral sites in some series. A splenic
form (sometimes referred to as lymphoreticular MCT) represents the most common
differential for "splenic disease" in cats, accounting for 15% of submissions in
a series of 455 pathologic specimens. The mean age of affected cats is approximately 10
years and no breed or sex predilection is known. Intestinal MCT is the third most common
primary intestinal tumor in cats after lymphoma and adenocarcinoma. 5 No breed or sex
predilection is known. Older cats appear to be at risk, with a mean age of 13 years;
however, cats as young as 3 years have been reported.
The etiology for cats with MCTs is unknown. Viruslike particles have been reported in tissue samples from feline MCTs but failed to grow in tissue culture and were not transmissible to other Cats, mice, or hamsters. No association with feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), or feline infectious peritonitis (FIP) has been reported. A genetic predisposition has been proposed because of the high incidence of MCTs in the Siamese breed.
Pathology and Natural History
The granules present in feline MCTs stain blue with giemsa,
and purple with toluidine blue. They tend to appear more eosinophilic than their canine
counterparts, with hematoxylin and eosin stains. As in the canine, granules present in
feline mast cells contain vasoactive substances such as heparin and histamine. In culture,
feline mast cells contain surface-bound immunoglobulins and are capable of secreting
histamine, heparin, and probably other vasoactive compounds when appropriately stimulated.
Complications associated with the degranulation of MCTs can also occur in the cat,
including coagulation disorders, gastrointestinal Ulceration, and anaphylaxis-type type
reactions. Feline mast cells also have phagocytic capability and can endocytize
erythrocytes in both experimental models and in clinical samples.
As previously mentioned, feline cutaneous MCTs occur in two primary histologically distinct forms, referred to as the mastocytic and histiocytic variaties. The mastocytic form can be further subdivided ease. Interestingly, in the face of widespread on histological appearance into two categories, often referred to as compact and diffuse, which metastasis long-term survival following splenectomy is common with splenic MCTs (see Treatmay be of prognostic significance. The com- ment and Prognosis section later). Intestinal pact form, reportedly comprising 50 to 90% of MCT in cats is also associated with widespread cases in several series, are associated with a more dissemination and carries a poor prognosis. It benign behavior. The diffuse form are histologi- more commonly involves the small intestine cally more anaplastic and behaviorally more malignant. The histologic grading system described for canine mast cells provided no prognostic information for the cat in one series. Immunohistochernical studies have also been performed on feline MCTs; all were vimentin positive, and the majority were positive for (a-1 antitrypsin. Metastatic rates for cutaneous MCTs in cats vary considerably, with reported rates of 0%, 14%, and 22%. In two studies in which behavior was separated by compact and diffuse histologies, the relative majority of cases going on to recur or metastasize were of the diffuse type. From this information, in general, it can be stated that the majority of feline cutaneous MCTs are behaviorally benign.
The uncommon histiocytic form of feline MCTs is more challenging to diagnose histologically. Mast cells appear to comprise only 20% of the cells present, with the majority being sheets of histiocytes that lack distinct cytoplasmic granules and are accompanied by randomly scattered lymphoid aggregates and eosinophils. One report, in contrast, readily demonstrated metachromatic granules in seven cases of the histiocytic subtype. They can be initially misdiagnosed as granulomatous nodular panniculitis or deep dermatitis. For those cases in the literature with follow-up information, spontaneous regression of histiocytic MCTs occurred over a period of 4 to 24 months.
With regard to visceral forms of MCTs in the cat (i.e.,
splenic and intestinal), widespread dissemination and metastasis are much more common.
Necropsy data on 30 cats with splenic MCTs revealed dissemination in the following organs
in decreasing order of frequency: liver (90%), visceral lymph nodes (73%), bone marrow
(40%), lung (20%), and intestine (17%). Up to a third of cases have peritoneal and pleural
effusions rich in eosinophils and mast cells. Peripheral blood mastocytosis is present in
as many as 40% of cases. In one clinical report of 43 cases, 23% had bone marrow
involvement. Two gross forms of splenic involvement are possible, a diffuse and smooth
splenomegalic form and a less common nodular form. In one report, 18% of cats with
cutaneous MCTs went on to develop splenic disease. Interestingly, in the face of
widespread metastasis long-term survival following splenectomy is common with
splenic MCTs Intestinal MCT in cats is also associated with widespread dissemination
and carries a poor prognosis. It more commonly involves the small intestine (equally
divided in the duodenum, jejunum, and ileum), with colonic involvement reported in less
than 15% of cases. Lesions can be solitary or multiple. Peritoneal effusion, rich in mast
cells, can occur. Unlike splenic MCTs, peripheral mastocytosis is not associated with
intestinal MCTs, and only two reports exist in the literature of eosinophilia. Metastasis
is common to mesenteric lymph nodes and the liver, followed less commonly by the spleen,
lung, and bone marrow. Most animals either die or are euthanized soon after diagnosis.
Histologically, the mast cells from intestinal lesions appear less well differentiated
than those of skin tumors, and cytoplasmic granules are harder to find. A cranial
mediastinal form of MCT in cats has also been described.
History and Clinical Signs
The typical feline cutaneous MCT is a solitary, raised, firm, well-circumscribed, hairless, dermal nodule between 0.5 and 3 cm in diameter. It is often white in appearance, although a pink erythematous form is occasionally encountered. Approximately 20% are multiple, although one report from the United Kingdom found the majority to present as multiple lesions. Ulceration is present in approximately one fourth of cases. Two other clinical forms have been described: one a flat pruritic plaquelike lesion similar in appearance to eosinophilic plaques and the other a discrete subcutaneous nodule.
Unlike the dog, the head and neck are the most common site for MCTs in the cat, followed by the trunk, limbs, and miscellaneous sites. Those on the head often involve the pinnae near the base of the ear. They rarely occur in the oral cavity. Intermittent itching and redness are common, and self-trauma or vascular compromise may result in ulceration. Darier's sign, the erythema and wheal formation following mechanical manipulation of the tumor, has been reported in the cat. Affected cats are usually otherwise healthy.
The spontaneously regressing histiocytic form of cutaneous MCTs are usually multiple, nonpruritic, firm, hairless, pink, and sometimes ulcerated subcutaneous nodules. Affected animals are otherwise healthy.
Cats with disseminated forms of MCTs may present with signs
of systemic illness. Depression, anorexia, weight loss, and intermittent vomiting are most
commonly associated with splenic and intestinal MCTs. Abdominal palpation reveals massive
splenornegaly in the majority of cases, and occasionally the presence of peritoneal
effusion is suggested with splenic MCTs. Intestinal MCTs can often be palpated as well.
Diarrhea with or without bloody stools is commonly seen with the intestinal form, and
fever may be present. Affected cats usually have been ill for a number of months. The
signs related to the release of vasoactive components of mast cell granules, including
gastrointestinal ulceration, uncontrollable hemorrhage, altered smooth muscle tone,
hypotensive shock, and labored breathing, are more likely to be observed with systemic
forms. The signs related to vasoactive arnines are often episodic in nature. Labored
breathing may also occur secondary to pleural effusion or anemia, which is present in
approximately one third of disseminated MCTs in cats.
The diagnosis and staging of MCTs in cats is similar to those in the dog. Fine-needle aspiration (FNA) cytology is usually diagnostic. This includes FNA of cutaneous lesions as well as splenic aspirates and thoraco- and abdominocentesis in the case of pleural and peritoneal effusions. Less frequently, intestinal mass aspirates are diagnostic. Tissue biopsy and histologic assessment is typically required for the histiocytic form of MCTs, because FNA is only rarely diagnostic.
In cases in which disseminated (e.g., splenic or intestinal) disease is suspected, CBC, buffy coat smear, bone marrow aspirate, coagulation profile, and serum biochemistry profile will be helpful. One third of cats with visceral disease will be anemic, and up to 50% of cats with splenic MCTs will have evidence of bone marrow and buffy coat involvement. Peripheral mastocytosis can be striking; peripheral mast cell counts up to 32,000 cell/µ have been reported. Unlike the splenic form, intestinal MCT is not associated with peripheral mastocytosis, though eosinophilia has been reported on two occasions. In one report of 43 cats with splenic MCTs, 90% had abnormalities on coagulation assessment, and while this was rarely of clinical significance, knowledge of its presence should allow preoperative precautions to be taken if surgery is contemplated. Hvperglobulinemia has also been reported in cats with splenic MCTs, the cause of which remains unknown. Other common differential diagnoses for splenornegaly in the cat include lymphoma, myeloproliferative disease, accessory spleen, hemangiosarcoma, hyperplastic nodules, and splenitis. The two most common differential diagnoses for intestinal masses in aged cats are lymphoma and adenocarcinoma.
Thoracic and abdominal radiographs will confirm the presence of pleural and peritoneal effusions, present in up to one third of cats with splenic MCT. Abdominal ultrasound may be required to determine the extent of intestinal involvement and indicate the presence of visceral dissemination. While most intestinal MCTs are either palpable or visible on abdominal radiographs or ultrasound, exploratory celeotomy may ultimately be required for definitive diagnosis.
Treatment and Prognosis
Surgery is the treatment of choice for the mastocytic form of cutaneous MCTs in the cat. As previously discussed, most are behaviorally benign, and wide surgical margins may not be as critical as in the dog. This is fortunate, as most occur on the head, where such margins would be difficult to achieve. Frequency of local recurrence and systemic spread vary widely in the literature. Local recurrence rates of 0%, 19%, and 24% have been reported following surgical excision. The frequency of systemic spread following surgical excision also varies, from 0%, 14%, and 22%. Recurrence, should it take place, is usually noted within 6 months. For histologically anaplastic (i.e., diffuse) mastocytic tumors, a more aggressive approach similar to that for the dog may be prudent, because higher rates of recurrence and metastasis are associated with this type. Following biopsy confirmation, conservative resection or a wait-and-see approach may be taken with the histiocytic form in young cats with multiple masses, because the majority are reported to regress spontaneously.
Little is known about the effectiveness of adjunctive therapy for cutaneous MCTs in the cat. Efficacy trials for corticosteroids, chemotherapeutics, and radiotherapy do not exist in the veterinary literature. Response to steroids in cats with the histiocytic form is equivocal.
Cats with splenic MCTs will usually benefit from splenectomy. Surprisingly, even in the face of significant bone marrow and peripheral blood involvement, long-term survival with good quality of life is the norm following splenectomy, with median survivals from 12 to 19 months reported. Anorexia, significant weight loss, and the male sex have been associated with a worsening prognosis. Frequent re-evaluation and buffy coat smears are used to follow response in such cases. Rarely does the peripheral mastocytosis resolve, but it will significantly decline, and its subsequent rise can serve as a marker of progression. Adjunctive therapy with various chemotherapy protocols, including prednisone, vincristine, cyclophosphamide, and methotrexate, have been attempted in a limited number of cases but do not appear to increase survival times. Ancillary drugs to combat the effect of vasoactive amines (see discussion under canine MCTs) may transiently abate clinical signs.
The intestinal form of feline MCTs carries a poor prognosis. Metastasis at the time of diagnosis is common, and most cats either die or are euthanized soon after. If surgery is possible, wide surgical margins, including 5 to 10 cm of normal bowel on either side of the lesion are recommended, because tumor often extends histologically well beyond visible gross disease.
COMPARATIVE ASPECTS OF MAST CELL TUMORS
Mast cell cancer is rare in humans. As is the case in dogs and cats, a wide range of syndromes exist from hyperplastic syndromes to malignant visceral forms and mast cell leukemia. The most common human mast cell neoplasm is a multiple cutaneous form occurring in infancy, known as urticaria pigmentosa. It is similar to mast cell disease described in kittens and an immature puppy in that it arises during infancy and regresses spontaneously at the onset of puberty. It is not, however, associated with a histiocytic histology as in the kitten. Other forms of MCTs in humans include benign systemic mastocytosis, malignant mastocytosis, and mast cell leukemia. Approximately one third of patients with urticaria pigmentosa will go on to develop malignant mastocytosis, a uniformly fatal disease. Many human patients are, like our veterinary patients, susceptible to systemic symptoms resulting from vasoactive substances released during degranulation of neoplastic mast cells. They will often benefic symptomatically from H1 and H2 blocking therapy. Because of the rarity of this condition, no standard treatment protocols are available for malignant mast cell disease in humans. The response to various chemotherapeutics has been disappointing.
Squamous Cell Carcinoma
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 crusting lesion 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
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.
Solar-Induced Squamous Cell Carcinoma in Cats
Fibrosarcomas , Fibromas and Spindle Cell Tumors
Neoplasms originating in the fibroblasts are common in
cats, where they comprise 24 to 33 percent of all tumors of the skin and subcutis.
Approximately 75 percent of the cutaneous mesenchymal neoplasms are malignant.
Fibromas occur predominantly in adult cats, with a mean age at presentation of 11 years (range 3 to 17 years) They usually appear as subcutaneous or dermoepidermal/subcutaneous oval masses with smooth surface, and their consistency varies from soft (fibroma molle) to extremely firm (fibroma durum). Alopecia overlying these masses is rare, and there is no predilection for any specific anatomic site. Complete surgical excision of fibromas is curative.
Fibrosarcomas and spindle cell tumors are the malignant counterpart of fibromas. Fibrosarcomas are the third most common skin tumor in cats. There is no sex or breed predisposition, but aged cats appear to be predisposed. Fibrosarcomas in cats can be caused by a virus, be associated with vaccination injection sites, or develop spontaneously. Virus-induced fibrosarcomas contain C-type retroviral particles and occur in kittens younger than 4 months of age that are positive for FeLV. Cats older than 4 months of age are resistant to the oncogenic effects of the feline sarcoma virus and usually do not develop tumors or they develop tumors that regress spontaneously. Viral-induced fibrosarcomas tend to be multiple rapidly growing truncal masses.
Fibrosarcomas and spindle cell tumors occur in one of two clinical forms of presentation: a solitary form common in older cats, and a multicentric form common in cats tinder 5 years of age. The solitary form resembles its canine counterpart in that these neoplasms are usually infiltrative and originate in either the dermis or the subcutis. Solitary cutaneous fibrosarcomas and spindle cell tumors in the cat are predominantly locally invasive and appear to have a relatively low metastatic potential on first presentation. Solitary cutaneous fibrosarcomas are not associated with the feline sarcoma virus. Fibrosarcomas have developed at vaccine injection sites in cats. In a recent study of 44 cats with the solitary form, approximately 50 pervent of tumors occurred on the limbs and 25 percent on the head and neck. Survival following surgery was directly related to the anatomic location, since the mean survival was more than 36 weeks for cats with tumors of the pinnae and the flank, and 30 weeks for cats with tilmors in other sites. The 3-year recurrence rate for the first group of tumors was 0 percent, while it was 71 percent for the latter. These findings may reflect the fact that tumors in the flank and pinnea can usually be completely excised, while tumors in other location, such as the limbs, cannot be completely excised unless aggressive surgery (i.e., limb amputation) is perforined. In addition, the mitotic rate of these tumors could be used as a prognostic factor; when fibrosarcomas were evaluated according to their mitotic indexes (i.e., the sum of mitotic figures in 10 high-power fields), it was found that cats in which the mitotic index was under 6 had a median survival of 128 weeks, while the survival was 16 weeks in tumors with a mitotic index greater than 6. In the same study, only 11 percent of cats had evidence of metastatic disease.
Nonviral spontaneous or vaccine-induced fibrosarcomas are usually solitary, variable in size, irregular to nodular in shape, poorly circumscribed, firm or fleshy with soft friable areas, fixed to the overlying skin, and frequently ulcerated. Vaccination-site fibrosarcomas are seen most commonly over the dorsal scapular area or at the site of intramuscular rabies vaccination. Fibrosarcomas developing at the site of previous administration of vaccines are being recognized with increasing frequency. The tumors develop months to years after injection and have not been definitively linked with any particular vaccine or formulation. To date, infectious agents have not been identified in any of the vaccines reportedly associated with the development of these tumors. It is possible that the tumor development may be initiated by the presence of an inert material or adjuvant in the vaccine. However, the incidence of vaccine-induced sarcomas is extremely low, 20-30 in 100,000 vaccines administered. At our present level of understanding this very complex problem, it is clear that for most cats, the benefits of vaccination far outweigh the risk of tumor development.
Ceruminous and Apocrine Sweat
Gland Neoplasms (Adnexal Tumors)
Ceruminous and apocrine sweat gland neoplasms are relatively common in cats, representing approximately 13 percent of all skin neoplasms. As opposed to dogs, anal and perianal neoplasms appear to be rare in cats. Most sweat gland neoplasms occur on the head and neck, while cerurminous gland neoplasms affect the external and middle ear canal. Most adnexal tumors in cats are malignant (i.e., adenocarcinomas) and are characterized by locally invasive behavior with rare metastases to regional lymphs nodes. A sweat gland adenocarcinoma with ocular metastases was reported in a 15-year-old cat.
The treatment of choice for sweat gland and ceruminous gland adenocarcinomas is complete surgical excision. In the case of neoplasms involving the ear canal, complete ear ablation may be necessary. If the margins of the incision are free of tumor cells, as determined by histologic evaluation, no further therapy is required. If surgical excision is not possible, or if complete excision cannot be achieved, radiation therapy is recommended, since most of these tumors are radiosensitive.' In one report, all three cats with ceruminous gland adenocarcinomas treated with external beam radiotherapy (45 Cy) were tumor free at 2 years.
In one cat treated with metastatic sweat gland adenocarcinoma using a combination of doxorubicin (20 to 30 Mg/M2 BSA IV) on day I of a 28-day cycle, cyclophospbamide (200 ing/m 2 BSA PO) on days 15 and 16 of the cycle, and vincristine (0.5 nig/m2 BSA IV) on days 8, 15, and 22 of the cycle, the cat experienced complete remission and survived longer than I year.
Sebaceous Gland Tumors
Sebaceous gland tumors represent a complex array of growths that can be divided into four groups based on histologic appearance. These are, in decreasing frequency, sebaceous hyperplasia, sebaceous epithelioma, sebaceous adenoma, and
sebaceous adenocarcinoma. Sebaceous gland tumors are among the most common skin tumors in the dog, accounting for 6.8 to 7.9% of all skin tumors. Sebaceous gland tumors are less common in the cat, accounting for 2.3 to 4.4% of all skin tumors. Modified sebaccous glands are found in a variety of locations and may give rise to neoplastic growths, including eyelid meibomian gland tumors and perianal gland tumors .
Sebaceous hyperplasia accounts for the majority of sebaceous gland tumors in the dog. They are characterized histologically by an accumulation of nearly mature sebaceous glands. Most are solitary; however, multiple lesions can occur. They are found on older animals (mean 9.1 years), and miniature schnauzers, beagles, poodles, and cocker spaniels appear to be over-represented. They can occur anywhere on the body but most are found on the limbs, trunk and eyelids. Most are less than 1 cm in diameter, wartlike or cauliflowerlike, and can become ulcerated because of trauma. In a compilation of 92 cases in the dog, only one recurred following excision; however, nearly 10% of cases developed new lesions at other body sites. Sebaceous hyperplasia is often found peripheral to and phasing into sebaceous adenomas or adenocarcinomas and is likely a precursor to their development. In the cat, sebaceous hyperplasia is typically a solitary lesion more common on the head, with a male predisposition. Lesions may be present for many years. Recurrence has not been reported following excision.
Sebaceous epithelioma, occurs primarily on the head (especially the eyelid) as a solitary lesion, however, generalized cases have been reported. These lesions are nearly identical in appearance to sebaceous hyperplasia and the treatment of choice is excision. They are more likely to recur than sebaceous hyperplasia or adenoma, though the recurrence rate is still low, at approximately 6%.
Sebaceous adenomas are relatively uncommon sebaceous gland tumors, similar in appearance and behavior to hyperplastic lesions. Sebaceous adenocarcinomas are rare in the cat and dog and appear to have a low potential for metastasis and recurrence. They are characterized by ulceration and inflammation of surrounding tissues. More aggressive surgical excision is indicated fot these tumors.