18. Tumours of skin and subcutaneous tissues

Tumours of the skin and subcutaneous tissues are the most common tumours in the dog, accounting for one-third of all neoplasms (Bostock 1986, Brodey 1970, Finnie & Bostock 1979, Rothwell et al 1987). In the cat, skin neoplasms are second in frequency only to lymphoid tumours (Vail & Withrow 2007). Mast cell tumours (MCT) are the most common skin tumour in the dog, and second most common in the cat (Miller et al 1991) (see Chapter 19). Approximately 20–30% of skin tumours in dogs are malignant, compared to 50–65% in the cat (Kaldrymidou et al 2002, Mukaratirwa et al 2005). Generally, cutaneous tumours occur in older animals. Long-term effects of sunlight result in solar dermatosis, leading to documented increases in cutaneous haemangioma, haemangiosarcoma (HSA) and squamous cell carcinoma (SCC) in dogs, and SCC in cats (Dorn et al 1971, Knowles & Hargis 1986, Madewell 1981, Nikula et al 1992).







Clinical signs


The presence of a lump or bump requires investigation. It is important to establish the time the lump has been present and whether or not it has changed or grown in size since it was first noticed, therefore a thorough history and clinical examination are essential in the diagnostic evaluation of any patient with a cutaneous mass.

Three-dimensional calliper measurements give an objective assessment of change and their use should be encouraged. All cutaneous lumps should undergo fine needle aspirate (FNA) as the first diagnostic step, as well as any enlarged lymph nodes. Cytological examination of a lump will help to determine non-neoplastic (hyperplasia, infection or cyst) from neoplastic and in some cases give preliminary identification to a neoplastic growth (e.g. mast cell tumour).






CANINE TUMOURS




Tumour-like lesions


Several types of skin lesions mimic neoplasms, including epidermoid cysts, dermoid and follicular cysts.

Epidermoid cysts (epidermal inclusion cyst, sebaceous cyst) are round to oval, firm to fluctuating, smooth, well-circumscribed lesions that are common in dogs but rare in cats. They are more common on extremities. These masses may contain grey to white-brown cheesy material with bits of hair shafts, usually covered by intact epithelium.

Dermoid cysts are similar, but more complex in that they are often multiple, deeper and can be interconnecting. They appear to be congenital or hereditary in Boxers, Rhodesian Ridgebacks, and Kerry Blue Terriers (Hofmeyer 1963). They are usually found on the dorsal midline, neck and scrotum. Some can extend to the level of the meninges and be continuous with the subarachnoid space. The prognosis is generally excellent with adequate surgery.


Nodular dermatofibrosis (collagenous nevi)


This is an unusual syndrome in German Shepherd (GSD) dogs, characterized by the development of numerous cutaneous nodules. Histologically, they appear as hyperplastic dermal collagen. Almost all cases are associated with multiple bilateral renal cysts that progress to cystadenocarcinomas with metastatic potential. Dogs eventually succumb to renal failure or widespread metastasis. No effective treatment exists (Vail & Withrow 2007).

Tumours of the skin and subcutaneous tissues can be divided into four categories although some overlap may occur:


• tumours of epithelial origin


• round cell tumours


• tumours of mesenchymal origin


• tumours metastatic to skin.


Tumours of epithelial origin



Papillomas


These tumours are common in the dog, very rare in the cat. In young dogs they are associated with a DNA virus that is contagious from dog to dog, and usually spontaneously resolve in a few months. These wart-like lesions often affect the mouth, eyelids, head, and feet. An intact immune system is important for disease regression.

A second type of papilloma is seen in the older dog. This is usually solitary and not thought to be associated with a virus. The prognosis is excellent with surgical excision or cryosurgery (Vail & Withrow 2007).


Squamous cell carcinoma (SCC)


Squamous cell carcinoma usually arises in unpigmented or lightly pigmented skin and is often related to solar exposure (‘actinic SCC’) (Figure 18.1). The most common cutaneous locations in the dog are the nail bed, scrotum, nose, legs and anus. For dogs with lightly pigmented skin, SCC can be seen on the flank and abdomen (Hargis et al 1977). Golden Retrievers appear to be over-represented with SCC of the nose (Bosward et al 2004, Gallegos et al 2007). Treatment depends on size, location and degree of invasiveness of the tumour (also see Chapter 13).


Staging of the patient with SCC requires evaluation of the sentinel node (FNA or excisional biopsy) and thoracic radiographs/CT. In general, the metastatic potential of cutaneous SCC is low, with pulmonary metastases reported infrequently.



Treatment


Small superficial lesions may be amenable to photodynamic therapy (PDT) or cryotherapy (Chapter 8). Large or invasive tumours require surgery, radiotherapy or a combination of the two. Large, locally invasive lesions have a poorer prognosis, due to the likelihood of recurrence. The success of local control or cure of SCC of the canine nasal planum is dependent upon the treatment used and the extent of tumour at the time of diagnosis (Chapter 13).


Subungual SCC


This is a common tumour in the dog and deserves special mention as they can often be misdiagnosed, along with the other common subungual tumour, melanoma, as infection. SCC is the most common subungual neoplasm and accounts for between 30 and 50% of all subungual tumours (Henry et al 2005, Marino et al 1995, O’Brien et al 1992, Wobeser et al 2007) and typically presents as a nail bed (paronychia) infection that does not respond to antibiotic therapy. It is seen most frequently in large breed dogs (~75%), with black dogs accounting for two-thirds of the cases (Vail & Withrow 2007). It arises from the subungual epithelium and often causes lysis of third phalanx (Figure 18.2).



Typically SCC is locally invasive but the majority of these tumours do not metastasize (Marino et al 1995). Multiple digits can be involved and unfortunately if digital amputation is not possible, this warrants a poor prognosis. Liptak et al (2005) reported good function and tumour control with amputation of both central weight-bearing digits (digits 2 and 3). In the authors’ experience, small dogs can function with amputation of most digits on a single limb.

The role of chemotherapy has not been established in the management of canine SCC and is currently not recommended. For superficial solar-induced and pre-neoplastic skin lesions, retinoids (etretinate) have been used (Marks et al 1992). Etretinate is a valid option for treatment of solar-induced pre-neoplastic lesions; however, the cost of treatment can be considerable. It may be considered for multifocal superficial disease not easily managed by other means of local therapy. PDT should be considered for canine patients with superficial disease (see Chapter 8).


Basal cell tumours (including basal cell carcinomas, basal cell epitheliomas and basaloid tumours)


These tumours are almost always benign and the most common locations are found on the head, neck and shoulder regions. They are solitary, well-circumscribed, firm, hairless, dome-shaped masses and can be pigmented, cystic, solid or ulcerated. Surgical excision is almost always curative. In patients where complete surgical excision cannot be guaranteed, radiotherapy is effective in local control.


Sebaceous gland tumours


These are frequently seen in older dogs and should be distinguished from sebaceous gland hyperplasia. The most common sebaceous gland diagnosis is hyperplasia, likely forming a continuum with eventual transformation to sebaceous adenoma and finally adenocarcinomas (Vail & Withrow 2007).


Sebaceous gland adenomas


These are benign tumours commonly seen in Cocker Spaniels and Poodles. They appear wart-like and are often pedunculated and frequently occur in multiples. If traumatized, they should be surgically excised; the prognosis is excellent.


Sebaceous gland adenocarcinomas


These are relatively uncommon malignant tumours of sebaceous gland origin. They are locally invasive, but with low metastatic potential. The treatment of choice is surgical excision with clean margins; in patients where this cannot be guaranteed, radiotherapy is indicated. The efficacy of chemotherapy has not been proven.


Sweat gland tumours


These uncommon tumours of epithelial origin arise from either the apocrine sweat glands that make up the majority of the tubular skin glands or eccrine sweat glands that are found in the footpad. Cysts of apocrine sweat glands are benign lesions and are common. Adenomas and adenocarcinomas are rare, with adenocarcinomas being more frequently seen. With timely, adequate local treatment, the distant metastatic rate is low, despite fairly common local tumour invasion, particularly into local lymphatics (Kalaher et al 1990, Simko et al 2003).

Post-excisional median survival of dogs with apocrine sweat gland adenocarcinomas was 30 months at the time of survey, and intravascular invasion may be an important indicator of potential systemic metastases (Simko et al 2003).

The treatment of choice is surgical excision with adequate margins. In patients where complete excision cannot be guaranteed, radiotherapy is indicated and is usually necessary in patients with eccrine tumours to prevent local recurrence. The efficacy of chemotherapy has not been proven.


Hepatoid gland tumours (perianal gland tumours)


These tumours arise from the circumanal glands and are modified sebaceous glands. They are discussed in Chapter 15.


Ceruminous gland tumours


These tumours arise from the modified apocrine sweat glands found in the external ear canal. For a full discussion of these tumours, see Chapter 13.


Anal sac adenocarcinoma


These tumours arise from the apocrine glands of the anal region. For a full discussion of these tumours, see Chapter 15.


Intracutaneous cornifying epithelioma (keratoacanthoma)


This is a benign epithelial proliferation arising from between hair follicles that is seen only in the dog. It usually affects dogs less than 5 years old and is more commonly seen in males than females. Predisposed breeds include Norwegian Elkhound, Keeshond and GSD. Surgical excision offers an excellent prognosis for solitary tumours. Multiple small lesions can be treated with cryosurgery. Long-term treatment with synthetic retinoids may be successful (Vail & Withrow 2007).


Tumours of the hair follicles: trichoblastomas, trichoepithelioma and pilomatrixoma


Trichoblastomas arise from the primitive hair germ epithelium; trichoepitheliomas arise from the follicular sheath and are more common; pilomatrixomas arise from the hair matrix. All generally have an excellent prognosis following surgery. However, metastasis can occur from malignant pilomatrixoma and from clear cell adnexal carcinoma/follicular stem cell carcinoma.


Round cell (discrete cell) tumours (round cell cytological appearance but varying histogenesis)


Round cell tumours are so called because they appear to be individually oriented, round cells with no association to other cells on the slide. The round cell tumours include lymphoma, plasmacytoma, MCT, histiocytoma, transmissible venereal tumours (TVT) and neuroendocrine tumours. Melanomas and basal cell tumours can appear to be discrete cell tumours.


Cutaneous plasma cell tumours



In general, the prognosis is excellent and the treatment of choice depends on the size, location and availability of treatment. Surgical excision is usually recommended; however, for a very small tumour on the end of the nose or adjacent to the footpad, surgery would be disfiguring so other options include chemotherapy (cyclophosphamide/melphalan and prednisolone) or radiotherapy. The former is effective on small lesions; however, if a complete response is not achieved, then it may shrink the tumour prior to surgery. Radiotherapy provides excellent control for tumours not amenable to surgery and for large intra-oral tumours will shrink them, allowing a smaller surgery to be performed.


Cutaneous lymphoma



Non-epitheliotrophic lymphoma


Cutaneous lymphoma has always presented a treatment challenge because of the general poor response to standard chemotherapy protocols. The poorest responses were seen in patients with cutaneous T-cell lymphoma (CTCL). Immunophenotyping is recommended for all malignant cutaneous round cell tumours because it can be difficult to distinguish lymphomas from histiocytic tumours based on morphology alone, and with lymphoma immunophenotype is a prognostic indicator. CCNU is the drug of choice for cutaneous lymphomas. It will induce good partial to complete remission in many cases, although the response is transient with progression of disease inevitable (Figure 18.3). For a full discussion of lymphoma, see Chapter 22.



Epitheliotropic lymphoma (ELSA)


ELSA, although an uncommon clinical disease, is the most common variant of CTCL. Historically it has been referred to as ‘mycosis fungoides’ (MF) because of its similarities to MF in humans. CTCL typically expresses the T-cell markers CD3 and CD8, and ELSA is characterized by lymphocyte epitheliotropism throughout all stages of the disease.

The clinical presentation and progression of ELSA can be extremely variable. In some patients the diagnosis of ELSA may take many months as the patients present with ‘dandruff’ and are treated with medicated baths for dry skin. Eventually, these may progress to solitary patches (Figure 18.4), plaques or nodules, generalized erythema and scaling with mucocutaneous involvement. Most dogs affected with ELSA will become extremely pruritic. Rarely, patients may present with solitary oral lesions.


In patients with these clinical signs a biopsy is required for diagnosis. The histopathological changes seen in a biopsy are characteristic for ELSA and distinct from other cutaneous lymphomas. The unique characteristic of ELSA is the presence of Pautrier’s microabscesses (collections of neoplastic lymphocytes around cutaneous dendritic cells); the neoplastic cells are confined to the epidermis and show tropism for the hair follicles and apocrine sweat glands. Advanced disease is characterized by lymphadenopathy or circulating T cells in the peripheral blood (Sézary syndrome); the latter is extremely uncommon.


Other topical treatments for ELSA have been used that include nitrogen mustard (however, this requires repeated application by the client with the associated risk of exposure to the chemotherapeutic agent by others in addition to the patient), and methoxsalen combined with UV light. Prednisolone is beneficial in the early stages of the disease and reduces pruritus for patients with more advanced disease.

For those patients with more significant disease and not suitable for localized treatment, a number of approaches have been tried and although the gold standard of treatment has not been established, CCNU is currently the drug of choice. To compare CCNU with other treatment options a number of studies have evaluated this drug (Risbon et al 2006, Williams et al 2006). In these studies the response rate was from 78 to 83% compared to <50% with other earlier treatments including retinoids (White et al 1993), ciclosporin, fatty acids, dacarbazine, PEG l-asparaginase and pegylated doxorubicin (Vail & Young 2007). The duration of response was variable, as were the number of cycles of drug required to induce and maintain the response. The authors currently recommend three cycles at 3-weekly intervals at a dose of 60 mg/m2 (this may need to be adjusted depending on the degree of myelosuppression). After three cycles the patient is evaluated and treatment modified according to response.


Histiocytomas and cutaneous manifestations of histiocytic disease


For a more detailed discussion of histiocytic cell derivation, see Chapter 20. Briefly, canine histiocytic disease complex can be divided into a number of categories and in some cases it can be difficult to distinguish between them:
Sep 11, 2016 | Posted by in SMALL ANIMAL | Comments Off on 18. Tumours of skin and subcutaneous tissues

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