information for vets
Mast cell tumours (MCT) are the most commonly diagnosed skin tumours of dogs, with an estimated incidence of 129 per 100 000 dogs, which if extrapolated to the entire dog population of the UK equates to approximately 9,000 new cases a year. MCTs have a wide range of behaviour varying from benign through to extremely aggressive. MCTs are categorised into grades I, II and III, according to their histological characteristics, and histological grade is the most accurate predictor of MCT behaviour. Surgery alone is usually curative for the approximately 30% of dogs with well-differentiated (grade I) MCT. However, the approximately 20% of dogs with poorly differentiated (grade III) MCT, which are treated with surgery alone, usually die due to tumour metastases. The poorly differentiated tumours metastasise to the local lymph node, liver and spleen before causing the death of the animal, typically about 7 months after diagnosis. The dogs that have, or are likely to have, metastatic disease require chemotherapy and have a much more guarded prognosis. Unpredictably, around 10% of the poorly differentiated MCT do not metastasise. Intermediate (grade II) tumours are the most frequently diagnosed grade of MCT (43-59% of cases), and are heterogeneous in behaviour. Approximately 20-30% of the intermediate MCT will go on to metastasise, while the remaining 70-80% are cured by surgery alone, exhibiting a well-differentiated MCT-like behaviour.
Lymphoma (lymphosarcoma, malignant lymphoma) can arise wherever there are lymphocytes that can undergo neoplastic transformation and therefore the clinical presentation can vary enormously, causing a diagnostic challenge for veterinarians. Furthermore, outcome can be difficult to predict. Many cases enjoy sustained remission and even cure with simple chemotherapeutic protocols, whilst other cases respond poorly and have a limited life expectancy. The various presentations of lymphoma may come to be regarded as specific disease entities in their own right (as they have been in man) as more is learnt about the pathogenesis and biology of canine lymphoid neoplasia.
Treatment (note that survival times quoted are for dogs with multicentric lymphoma)
Many lymphoma cases initially partially respond to high dose prednisolone. However they fail within 2 - 3 months (average) due to drug resistance. This drug resistance will extend to many of the other anti-cancer drugs, and if other protocols are then tried a tumour will not respond, or will relapse quickly. Prolonged treatment with prednisolone (> few weeks) will prejudice further attempts at chemotherapy. A basic protocol of cyclophosphamide, vincristine and pred (‘COP’) can achieve remission in 75% of cases with a median survival of 7 - 9 months. Once there is relapse on the COP protocol other protocols can be instituted as rescue protocols. However, for longer and more sustained remission, protocols that include doxorubicin (CHOP protocols) are used as first line, such as the various Madison-Wisconsin protocols. Although these protocols are more involved, more expensive and have some increased toxicity in the short term, they can achieve remission in 85% of dogs, and have been shown to give longer median survival times.
Meningiomas are composed of neoplastic meningothelial cells, and the majority of tumours arise within the intracranial cavity. In humans, 14 meningioma subtypes are recognised (on the basis of histopathological appearance) by the World Health Organisation (WHO) classification, with three grades of malignancy. In dogs, nine grade I meningioma histotypes have been described, including seven that are histologically similar to human subtypes. Microcystic meningioma is not included in the domestic animal classification of meningiomas, but has been described in dogs.
Benign, slowly growing, grade I tumours account for 90% of human meningiomas. The histologically atypical grade II meningiomas have an enhanced capacity for local recurrence in spite of complete resection, and represent 6-8% of meningiomas. Approximately 2-3% of meningiomas are aggressive, rapidly growing anaplastic grade III tumours that exhibit significant histopathological indices of malignant potential. Although the WHO histological grading scheme for human meningiomas has improved the capability to predict tumour behaviour, there remains significant individual variation within each grade category. In dogs, grade II and grade III meningiomas are rarely seen and hence histological grading has little prognostic value. Immunohistochemical staining of canine meningiomasrepresents a means of distinguishing the tumours from central nervous system neoplasms of different origin, and the potential of an immunohistochemistry-based assay of vascular endothelial growth factor expression as a predictor of patient survival has been evaluated. Other potentially prognostic immunohistochemical markers include progesterone receptor expression and the proliferating cell nuclear antigen index.
Mammary tumours are the most common tumour in female dogs, and are most frequent in dogs that are not spayed prior to the age of two. The average age at diagnosis is 10 - 11 years. Approximately 50% (some authorities suggest that 70% is a more realistic figure) of mammary tumours are benign, and low grade carcinomas also follow a relatively benign course and do not metastasise. Up to 50% of bitches may present with multiple tumours affecting different glands, and these tumours can be of different histological types. The majority of mammary tumours (regardless of whether they are benign or malignant) carry a favourable prognosis as long as they have been removed with an appropriate surgery.
Oral tumours are the most frequent melanomas (56% of melanomas) and the most malignant with metastases in 80% of the cases. A primary tumour will grow and becomes an increasing problem in the mouth, such that within 4 - 6 months euthanasia is required. Secondary spread is extremely common with >80% dead within 12 months due to secondary tumours.
Treatment: Surgery (mandibulectomy or maxillectomy) can remove the primary tumour, but has no effect on secondary rate; however, surgery is extensive. Radiotherapy can reduce the primary tumour in about 80% of cases, with long term remissions in 60% of dogs, which then die of their secondary tumours. Radiation has few side effects and is very well tolerated by the dog.
Palliation with non steroidal anti inflammatories and antibiotics will also improve a dog’s quality of life for a period.
Cutaneous tumours represent around 11% of canine melanomas. The melanomas can be benign (>50%) or malignant, and metastases occur in
10 to 15% of cases (in part dependent upon stage and treatment.). Malignant and non-malignant cutaneous melanomas (melanocytomas) occur within the same breeds, which are typically black coated breeds.
Ungual melanomas constitute approximately 8% of melanomas, with metastases in 58% of cases.
Uveal melanomas and ocular melanosis
Ocular melanomas are the least frequent (2%) of canine melanomas, with uveal melanomas being the most common of these. Uveal melanomas arise most commonly from the anterior uvea [iris & ciliary body - canine anterior uveal melanoma (CAUM)], and occasionally within the choroid
- Clinically these tumours usually present as heavily pigmented, slowly progressive, intra-ocular (IO) lesions which may be associated with secondary IO signs (uveitis, haemorrhage, glaucoma)
- Local extension may be a feature of CAUM (cornea, choroid, sclera and extrascleral) and may occur with both benign and malignant disease
- Uveal melanoma is most common in older dogs (8 -10 years)
- There is some evidence to support inheritance of CAUM in Labrador & Golden Retrievers
- Diagnosis may be facilitated by ultrasonography (if opaque media obscure IO examination), gonioscopy (to help differentiate CAUM from limbal melanoma) & transillumination (distinguish CAUM from uveal cysts)
- Ancillary investigations may help establish the stage of the tumour & include ultrasonography (abdominal), radiography (abdominal & thoracic) & FNABs of enlarged lymph nodes
- Definitive diagnosis relies on histopathology and should be performed on all enucleated eyes. CAUMs and choroidal melanoma may be classified as benign or potentially malignant based on the cytological indices used as indicators of malignant potential (mitotic index, nuclear pleomorphism, nuclear: cytoplasmic ratio), which may be of prognostic value. FNABs of IO masses are not routinely used in veterinary ophthalmology.
- Management of CAUM and choroidal melanoma is difficult due to the inability to predict the tumours biological behaviour
- In the majority of cases this is apparently benign and many ophthalmologists choose to monitor CAUMs and choroidal melanoma for progression & secondary IO complications rather than remove a visual eye.
- Enucleation and orbital exenteration may provide a definitive cure in cases of malignant CAUM and choroidal melanoma which have not metastasised.
Ocular melanosis (also known as melanocytosis and pigmentary glaucoma) is an inherited eye disease that generally affects both eyes
- In the early stages of onset, characterised by pigmented scleral patches and thickened iris roots
- Consequence of a build up of pigmented melanocytes is fluid accumulation and enlargement of the anterior cavity, and secondary glaucoma
- Occurs predominantly in the Cairn Terrier (in which it may be bilateral), but also in other breeds including German Shepherd Dogs and Boxers
- Onset of visible changes occurs between 7 to 12 years of age
- Definitive diagnosis by histopathology, although discrimination from diffuse or circumferential CAUM can be difficult particularly for breeds other than the Cairn Terrier
- Enucleation often required to alleviate pain caused by build up of pressure
- Early diagnosis and instigation of prophylactic antiglaucoma therapy could slow the onset of glaucoma and therefore visual deficits