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Canine and feline skin tumors (Part 2)

 Mast cell tumors
The presentation and behavior of mast cell tumors (MCT) differs between the cat and dog.
 
 
Canine MCT
These are one of the most common cutaneous neoplasms, representing up to 20% of all canine skin tumors (6). They tend to affect older animals (mean age 8 years) but may occur at any age. Several breeds of dog including the boxer, Staffordshire bull terrier, and possibly the Labrador and golden retriever appear to be predisposed. The tumors show tremendous diversity in gross appearance, clinical behavior, rate of metastasis and response to treatment, as a result of which they present considerable prognostic and therapeutic problems. The following is a short review; readers are advised to refer to the extensive literature available.

Figure 4 and 5
Presentation/clinical signs
The gross appearance can mimic any other cutaneous tumor (Figures 4,5). Low grade, well differentiated tumors usually present as a solitary slowly growing, dermal nodule. Some tumors ulcerate through the skin and in some cases local release of histamine from tumor cells may cause the lesion to fluctuate in size and become red and ‘angry’ looking. More aggressive MCTs may present as large, ill-defined soft tissue masses and some may be surrounded by satellite nodules as the tumor spreads through surrounding cutaneous lymphatic vessels (Figure 6).

 
Behavior
MCTs can vary in behavior, from slowly growing, low grade tumors which follow a benign course to rapidly growing, invasive, highly malignant tumors. Histological grading based upon the degree of cellular differentiation, the mitotic index and invasion of adjacent tissue has been shown to be of prognostic value (7-9). Behavior, suggested treatments and prognosis of MCTs are discussed in Table 2.
Malignant MCTs may metastasize either by the lymphatic route or via the blood. In most cases the first sign of metastasis is enlargement of the local lymph node. Discrete pulmonary metastases are rare; disseminated MCTs more commonly metastasize to the spleen, liver, kidneys and the skin.

Figure 6
Paraneoplastic Syndromes
Both solitary and metastatic MCTs can have local or systemic effects via the release of histamine and other vasoactive amines from the tumor cells. This can cause local edema and erythema of the adjacent tissues and distant gastro-duodenal ulceration leading to anorexia, vomiting, melena, anemia and, in some cases, perforation.

 
Diagnostic Investigations
Hematological assessment may indicate anemia due to blood loss from a bleeding intestinal ulcer. Circulating mast cells (mastocytosis) are rare but eosinophilia may be present.

Mast cells can be readily identified by FNA cytology and this simple technique should be performed prior to surgical removal of any cutaneous lesion. MCT cannot be graded accurately on cytology alone, although some indication of the degree of differentiation of the tumor cells may be possible. Excisional samples should therefore be submitted for histological grading and assessment of the margins of excision.

Local and regional lymph nodes should always be evaluated by palpation, radiography/ultrasound (as appropriate) and cytology. Ultrasound evaluation of liver, spleen and kidneys is also valuable. Pulmonary metastasis is rare but skin is a common site for MCT metastasis and skin nodules should be investigated by FNA or biopsy. Dogs presenting with multiple low/intermediate grade MCT have separate de novo tumor development rather than metastatic disease, and each should be dealt with as a separate tumor. Survival time in these animals is not less than dogs with a single MCT (10).

 
Treatment
Surgical resection is undoubtedly the treatment of choice for any well differentiated MCT. Wide surgical resection is not as important as previously thought and 2 cm margins should be adequate for all grade I & II tumors < 5 cm diameter, but not the most aggressive tumors (11). The most common cause of treatment failure is poorly executed or planned surgery, leading to inadequate resection of the primary tumor and subsequent local recurrence. The first surgical attempt stands most chance of success and cure rates for subsequent surgical excisions or adjunctive therapies are low. It is vitally important to identify a MCT (cytologically or histopathologically) prior to any attempt at treatment so that appropriate surgical margins can be planned and achieved at the first attempt.

Radiotherapy may be beneficial as a post-surgical treatment in cases of intermediate tumors where complete surgical resection is not feasible (12) and, on occasions, may be used in conjunction with chemotherapy for the treatment of tumors which cannot be surgically excised due to their site (13). There is no good evidence for the use of radiotherapy as a sole treatment.

For grade II tumors with a high mitotic index and grade III tumors chemotherapy is used to prevent or slow metastatic spread (14). Short term responses have been achieved with protocols involving vinblastine, chlorambucil and prednisone, or lomustine (CCNU). Two tyrosine kinase inhibitors, masitinib and toceranib, are licensed in some countries for use in unresectable or recurrent intermediate and high grade canine MCT; although experience is lacking, they show promising efficacy (15,16). It should be remembered that surgery is still the treatment of choice and a judgment of unresectable should be made by a specialist surgeon.

Patients with systemic and/or gastrointestinal signs must be treated appropriately with agents such as H2 antagonists, cimetiidine or ranitiidine. Sucralfate is also of benefit.
Table 2
 
Feline MCT
In the cat MCTs are less common than in the dog and also less of a diagnostic problem. Two forms are recognized: cutaneous and visceral. Most cutaneous MCTs are benign solitary cutaneous/ dermal nodules. Uncommonly, a cat may be affected by multiple skin nodules, or a solitary lesion may be invasive. Histological grading of feline cutaneous MCTs has not been shown to be clinically useful. Surgical resection is the treatment of choice and the prognosis is usually good (17). In cats with multiple tumors corticosteroids may be of palliative value. Invasive or incompletely excised tumors may be treated with adjunctive radiotherapy.
A variant of feline MCT has been reported mostly affecting Siamese cats (18). This tumor, which may be multicentric, is characterized histologically by sheets of histiocyte-like mast cells with scattered lymphoid aggregates and eosinophils. These tumors may regress spontaneously without therapy.

 
Plasmacytoma
Plasmacytomas are common in dogs but rare in cats. They typically affect older dogs with no breed predilection and usually present as a solitary skin or mucocutaneous tumor; the oral cavity (including gingiva), feet, trunk and ears are the most common sites. The gross appearance is usually of a raised red or ulcerated, quite well-defined mass, rarely more than 2-5 cm in size. Plasma cells are derived from _-lymphocytes; histological diagnosis can be difficult if the tumor cells are lacking clear differentiation, and special staining techniques may be required to differentiate plasmacytoma from poorly differentiated sarcoma and other round cell tumors. Potentially a plasmacytoma could represent a metastasis from the systemic form of plasma cell malignancy, multiple myeloma; this has been reported in the cat but not the dog (19). Both cutaneous and oral forms of plasmacytomaare usually benign and are rarely associated with systemic signs. Surgical resection is usually curative and prognosis is good.

 
Histiocytic skin conditions
Several reactive and malignant neoplastic histiocytic diseases have been described. The most common is canine cutaneous histiocytoma (CCH), a benign cutaneous tumor unique to the skin of the dog and representing up to 10% of all caninecutaneous tumors. CCH is most common in young dogs with 50% occurring in animals < 2 years old. The tumor typically arises on the head, the limbs, feet or trunk, and presents as a rapidly growing, intradermal lesion. The surface may become alopecic and ulcerated. The boxer, dachshund and the flat-coated retriever are reported to be predisposed to CCH. Histological sections show infiltration of the epidermis and dermis by neoplastic histiocytic cells; numerous mitotic figures and an indistinct boundary give this lesion the appearance of a highly malignant neoplasm. However, CCH is a benign tumor which usually regresses spontaneously. Regression is associated with infiltration of the tumor by cytotoxic T-cells and lymphocytic infiltration is often described in histological reports. Surgical excision - if necessary - is usually curative and the prognosis is good.

 
 
Multifocal/diffuse cutaneous neoplasia
Although MCT and metastases from both carcinomas and sarcomas can present as multiple nodular skin lesions, the tumors most commonly associated with multifocal or diffuse skin lesions are lymphoid neoplasms.

 
Cutaneous Lymphoma
Usually of T-cell origin, primary cutaneous lymphoma may be classified as either epitheliotrophic (epidermal) or non-epitheliotrophic (dermal) on histology.
Epitheliotrophic lymphoma (Mycosis fungoides) is more common in dogs. Histological sections show a diffuse infiltration of the epidermis by neoplastic memory T-lymphocytes and other inflammatory cells, Pautrier’s microabscesses and a tropism for adnexal structures (Figure 7). In the advanced stages of the disease the tumor cells invade into deeper layers of the dermis, heralding systemic dissemination.

In the early stage a dog may present with an erythematous, exfoliative or seborrheic skin condition, which is often very pruritic; lesions can heal in one region and then erupt in another. This gradually progresses with the development of plaques, nodules and ulceration of the skin. At mucocutaneous junctions infiltration, depigmentation, and ulceration are typical. Terminally there is rapid progression, culminating in widespread dissemination to other organs. The mucous membranes of the mouth, eyes and genitalia may be affected at all stages (Figure 8).

Non-epitheliotrophic lymphoma is a very aggressive tumor that usually presents with multiple cutaneous nodules, plaques or erythroderma. Histologically there is an infiltration of the dermis and subcutis with malignant lymphoid cells, usually of T-cell origin. The disease usually has a rapid course and quickly disseminates to involve other organs such as the liver, spleen and bone marrow. This form of cutaneous lymphoma is more common (although still rare) in the cat.

The prognosis for non-epitheliotrophic lymphoma is poor, with a rapid course and survival times rarely exceeding 2-3 months. Epitheliotrophic lymphoma carries a longer disease course and treatment may be more successful. Response of the lesions to systemic chemotherapy is variable but some improvement can be achieved. Single agent Lomustine (CCNU) has reportedly good but often short-lived remission rates (80%) whilst retinoids, L-asparaginase and Interferon alpha, as well as radiotherapy, have been tried and show some efficacy (20).
Topical treatment with nitrogen mustard is not recommended.

 
Secondary cutaneous lymphoma
Systemic lymphoma can disseminate to the skin. This is more commonly of β-cell origin, reflecting the original tumor. Prognosis is poor as these animals have frequently received extensive chemotherapy and have multi-drug resistance. Radiotherapy may assist with treatment of problematic lesions.
Figure 7 and 8
Metastatic cutaneous tumors
Cutaneous metastases may be seen with any malignancy. Lesions can be very variable in appearance, but usually the presence of a primary malignancy will be known. Biopsy or FNA is usually diagnostic and the prognosis is typically grave. Worthy of particular mention is the lung-digit syndrome seen in cats; this is characterized by metastatic tumors of the digits attributable to a primary lung tumor (SCC, bronchogenic carcinoma, pulmonary carcinoma). Affected cats are typically lame, with pain due to swelling and ulceration of one or more digits; the nail may be lost (21). Prognosis is hopeless.

 
 
Conclusion
Tumors of the skin are a daily occurrence in small animal practice and whilst the majority of such lesion in dogs are benign and carry a favourable prognosis, it is important to be familiar with the more common malignant tumors in order that they be diagnosed and managed appropriately. This article has sought to provide an overview of the more common skin tumors of the cat and dog for this purpose. The reader is referred to further literature as the subject of cutaneous neoplasia is a vast and complex issue to cover comprehensively.

 
 
If you missed Part 1 CLICK HERE to read it now...
 
 
 
REFERENCES
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2. Bexfield NH, Stell AJ, Gear RN, et al. Photodynamic therapy of superficial nasal planum squamous cell carcinomas in cats: 55 cases. J Vet Int Med 2008;22:1385-1389.
3. Baer KE, Helton K. Multicentric squamous cell carcinoma in situ resembling Bowen's Disease in cats. Vet Path 1993;30:535-543.
4. Paradis M, Scott DW, Breton L. Squamous cell carcinoma of the nail-bed in three related giant schnauzers. Vet Rec 1989;125:322-324.
5. Bergman PJ, Camps-Palau MA, McKnight JA, et al. Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006;24(21):4582-5.
6. Bostock DE. Neoplasms of the skin and subcutaneous tissues in dogs and cats. Br Vet J 1986;142:1-18.
7. Patnaik AK, Ehler AJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Path 1984;21: 469-474.
8. Romansik EM, Reilly CM, Kass PH, et al. Mitotic index is predictive for survival for canine cutaneous mast cell tumors. Vet Path 2007;44:335-34.
9. Kiupel M, Webster JD, Bailey KL, et al. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Vet Path 2011;48:147-155.
10. Murphy S, Sparkes AH, Blunden AS, et al. Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours. Vet Rec 2006;158:287-291.
11. Simpson AM, Ludwig LL, Newman SJ, et al. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc 2004;224:236-240.
12. Al-Sarraf R, Maudlin GN, Patnaik AK, et al. Prospective study of radiation therapy for the treatment of Grade 2 mast cell tumors in 32 dogs. J Vet Int Med 1996;10:376-378.
13. Dobson J, Cohen S, Gould S. Treatment of canine mast cell tumours with prednisolone and radiotherapy. Vet and Comp Oncology 2004;2:132-141.
14. Hayes A, Adams V, Smith K, et al. Vinblastine and prednisolone chemotherapy for surgically excised grade III canine cutaneous mast cell tumours. Vet and Comp Oncology 2007;5:168-176.
15. Hahn KA, Legendre AM, Shaw NG, et al. Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors. Am J Vet Res 2010;71(11):1354-1361.
16. London CA, Malpas PB, Wood-Follis SL, et al. Multi-center, placebo controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res 2009;15:3856-3865.
17. Molander-McCrary H, Henry CJ, Potter K, et al. Cutaneous mast cell tumours in cats: 32 cases (1991-1994). J Am An Hosp Assoc 1998;34:281-28.
18. Chastain CB, Turk MAM, O'Brien D. Benign cutaneous mastocytomas in two litters of Siamese kittens. J Am Vet Med Assoc 1988;193:959-960.
19. Mellor PJ, Haugland S, Smith KC et al. Histopathologic, immunohistochemical, and cytologic analysis of feline myeloma-related disorders: further evidence for primary extramedullary development in the cat. Vet Path 2008;45(2):159-73.
20. Fontaine J, Bovens C, Bettenay S, et al. Canine cutaneous epitheliotropic Tcell lymphoma: a review. Vet and Comp Oncol 2009;7:1-14.
21. Scott-Moncrieff JC, Elliott GS, Radovsky A, et al. Pulmonary squamous cell carcinoma with multiple digital metastases in a cat. J Small Anim Pract 1989;30:696-699.
This article was kindly provided by Royal Canin, makers of a range of veterinary diets for dogs and cats. For the full range please visit www.RoyalCanin.co.uk or speak to your Veterinary Business Manager:

This article was first published in 2012.

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