When confronted with the possibility of a cancer diagnosis, most owners and many veterinary professionals immediately think of the worst case scenario of impending death. Making decisions around the management of cancer in companion animals is often a difficult and complicated process. Differences in attitudes towards and beliefs about the treatment of cancer in people versus pets must be taken into account. Cancer diagnosis and management is an area of practice in which veterinary nurses (VNs) can play an important role in supporting owners and veterinary surgeons (VSs). The aim of this article is to help empower VNs to play a role in oncology by providing information for them to increase their knowledge of the subject.
Cancer in animals
Recent research shows that the lifetime risk of cancer is now 1 in every 2 people born since the early 1960s (Ahmad et al, 2015; Cancer Research UK, 2016). Cancer is estimated to affect up to 1 in every 3 to 4 dogs and 1 in 6 cats during their lifetime (Kidd, 2008; National Canine Cancer Foundation, 2016). The most common cause of death/reason for euthanasia of dogs in the 2004 Kennel Club Purebred Dog Health Survey was cancer, accounting for 27% (4282/15881 dogs) of reported deaths from 1994 to 2003 (Adams et al, 2010). The most commonly reported cancers in cats and dogs are different (Tables 1 and 2). When lumps, bumps and enlarged lymph nodes (LN) are found in a cat, there are more non-cancerous disease possibilities or differential diagnoses than for dogs. As a result of infection or reactive inflammation, cats can develop markedly enlarged lymph nodes. Mast cell tumour (MCT) is the most common type of skin cancer in dogs and the variable clinical behaviour of MCT is thought to be breed related (Murphy et al, 2003; McNeil et al, 2006; Dobson, 2013). Lymphoma is the most frequent life-threatening cancer in dogs, accounting for up to 20% of all malignancies. The various types and sub-types also vary with breed (Edwards et al, 2003; Modiano et al, 2005; Lurie et al, 2008; Pastor et al, 2009; Dobson, 2013) and this breed association is thought to help explain reported differences in survival time and response to therapy (Garrett et al, 2002). Mammary tumours are the most common tumours affecting entire female dogs; ovariohysterecotomy can reduce the risk of this cancer developing although the evidence about age at neutering is weak (Schneider et al, 1969; Rutteman, 1990; Beauvais et al, 2012). Certain breeds have an increased risk of developing particular cancers (Figure 1), such as haemangiosarcoma in German Shepherds, suggesting that there is likely a genetic component or predisposition to cancer (Prymak et al, 1988; Dobson, 2013). Other species of pets are also affected by cancer (Table 3). Mammary neoplasia is common in many small species although the particular type tends to differ: for example, mammary tumours tend to be benign in hamsters and malignant in gerbils, while mammary gland adenocarcinoma is the most common tumour in hedgehogs.
| Type of cancer | Predilection site/sub type | Comments |
|---|---|---|
| Lymphoma (Lymphosarcoma) | Alimentary (gastrointestinal) | More common in cats than dogs |
| Cranial mediastinal (chest) | More common in cats than dogs | |
| Extranodal — can occur at any site, including the nose, kidneys and central nervous system | More common in cats than dogs | |
| Multicentric (lymph nodes throughout body) | Fine needle aspirates from lymph nodes are more likely to be diagnostic of lymphoma in dogs | |
| Squamous cell carcinoma | Mouth, nose, ear, eyelid or other skin sites | Non-steroidal anti-inflammatory drugs may help prolong quality of life in both cats and dogs |
| Mammary carcinoma | Mammary glands | Differences in lymphatic drainage |
| Soft tissue sarcoma | Injection sites (FISS) | Less common at injection sites in dogs |
| Other skin sites or under the skin, mouth |
| Type of cancer | Breeds with an elevated risk of developing this cancer |
|---|---|
| Brain tumour (glioma, meningioma) | Golden Retriever, Boxer |
| Haemangiosarcoma (blood vessel tumours) | German Shepherd, Golden Retriever. |
| Lymphoma/leukaemia | Airedale Terrier, Basset Hound, Bouvier des Flandres, Boxer, Bull Mastiff, Labrador Retriever, Saint Bernard, Scottish Terrier |
| Malignant histiocytosis | Bernese mountain dog |
| Mammary tumour | Dachshund, English Setter, German Shepherd, Maltese Terrier, Pointer, Poodles, Puli, Spaniels, Yorkshire Terrier |
| Mast cell tumour | Beagle, Boston Terrier, Boxer, Bulldog, Bullmastiff, Golden Retriever Labrador Retriever, Rhodesian Ridgeback, Staffordshire Bull Terrier, Weimaraner |
| Melanoma | Chow Chow, Cocker Spaniel, Golden Retriever, Pekingese, Poodle, Schnauzer, Scottish Terrier |
| Osteosarcoma (bone cancer) | Borzoi, Doberman, German Shepherd, Golden Retriever, Great Dane, Greyhound, Irish Setter, Irish Wolfhound, Leonberger, Rottweiler, Saint Bernard |
| Soft tissue sarcoma (histiocytic sarcoma) | Flat-coated Retriever |
| Ferrets | Rabbits | Guinea pigs | Rats |
|---|---|---|---|
| Bone tumour — chordoma (B) on tail, chondrosarcoma (M), osteosarcoma (M, rare) | Bone tumour — osteosarcoma (M, rare) | Bone cancer — osteosarcoma (M, rare) | |
| Cutaneous tumour — mast cell tumour (B usually), fibrosarcoma (M, rare but may be injection site sarcoma), squamous cell carcinoma (M) | Cutaneous tumour — various tumours (B) including virus-induced Shope fibroma (B) and papilloma (B), basal cell carcinoma (M), sebaceous gland carcinoma (M), squamous cell carcinoma (M, oral) | Cutaneous tumour — trichoepithelioma (B), basal cell carcinoma (M) | Cutaneous tumour — keratocanthoma (B), squamous cell carcinoma (M) |
| Lymphoma (M) | Lymphoma (M) | Lymphoma (M) | |
| Mammary tumour — adenocarcinoma (M, rare) | Mammary tumour — adenocarcinoma (M) | Mammary tumour — fibroadenoma (B) more common than adenocarcinoma (M) | Mammary tumour — fibroadenoma (B) more common than adenocarcinoma (M) |
| Pancreatic insulinoma (M) | Pituitary adenoma (B) | ||
| Splenic tumour — haemangiosarcoma (M) | Zymbal's gland tumour (B) — sebaceous gland tumour of external ear canal | ||
| Testicular tumour (M) — with cryptorchidism | Testicular tumour | Testicular tumour (most B) | |
| Adrenal carcinoma (M) | Uterine adenocarcinoma (M) | Uterus or bladder (rare) |
Indication of type of neoplasia: B = benign, M = malignant
Frequency of occurrence: most common cancers in bold
Clinical presentation
Cancer can occur in any body part or system and clinical signs are varied as a result. As well, many of the signs are shared by a large range of other diseases. Affected dogs may present with a lump or a mass lesion or non-specific signs that may include lack of appetite, reduced activity and weight loss. Cases present in many different ways depending on the organ(s) affected. Clinical signs may include vomiting, diarrhoea, a palpable mass in the abdomen or on the skin, lameness, unexplained bleeding, an enlarged lymph node or even simply bad breath due to a mass in the mouth.
Cats with cancer may present similarly with a mass lesion or nonspecific signs which may include hypo/anorexia, reduced activity and weight loss. When considering mass lesions and lymphadenopathy in cats, there are more non-neoplastic differentials than for dogs. Cats can develop marked lymphadenopathy due to infectious or reactive causes. Unfortunately, many cats present with advanced disease and not always because of the primary tumour. An example of this is when a cat with a primary lung tumour(s) presents with secondary lesions of the digits (usually multiple) due to metastasis of bronchial or bronchioalveolar adenocarcinoma. Clinical signs of digital metastatic lesions include swelling and reddening of the digit with purulent discharge from the nail bed and dysplasia or fixed exsheathment of the nail. While these signs may be suggestive of infection, radiographic evidence of extensive bony lysis of the distal phalanx raises the index of clinical suspicion for metastasis of a primary pulmonary tumour. Thoracic radiography is recommended prior to any surgery as the prognosis is generally grave for cats with this syndrome (Goldfinch and Argyle, 2012).
Diagnosis
A thorough history and physical examination are always an essential part of the diagnostic process as it will determine which further tests will be required. VNs can play an important role in questioning the owner about their animal's history and current complaint at the start of a veterinary consultation. Complete blood cell counts and biochemistry tests can help to reveal which organs are involved and whether there is any concurrent disease. Various imaging modalities, including radiographs, ultrasound studies and sometimes also computed tomography (CT) or magnetic resonance imaging (MRI) scans may be helpful in determining the extent of the disease.
Biopsy, biopsy, biopsy
A diagnosis of cancer is usually based on histopathological examination of a sample that is obtained by a fine needle aspirate (FNA) or a biopsy. While cytology can be very useful, it has limitations in that the presence of dysplastic epithelial or mesenchymal cells may mimic neoplastic change. This is especially true when there is inflammation present as well. Also, a FNA may be non-diagnostic due to low cell yield, particularly with sarcomas. When there is any doubt, a biopsy is the next step. If an infectious cause is suspected when performing a biopsy, it is important not to fix all tissue so that bacterial, fungal or mycobacterial cultures can be performed, particularly in cats (Blackwood, 2015). Once the diagnosis of tumour type is made, further pathological evaluation may be recommended to help establish the grade of the tumour and possibly the sub-type as this can affect prognosis and treatment options.
A VN can help support owners through the process of diagnosis and decision making about treatment. Before starting treatment, an owner may want another opinion about the diagnosis and treatment plan. A second opinion is usually sought when there is doubt about the diagnosis whereas a referral is usually to seek specialist management of the case. Specialists who treat cancer include surgeons, medical oncologists and radiation oncologists. VNs can support owners in understanding that there are options available so that they can make an informed decision. VNs can play a role as a facilitator in the communication that occurs between VSs and owner(s). For example, reminding owners why an accurate diagnosis is essential and why this requires a biopsy. While it may be appropriate to monitor a lump in some situations, VNs can also question VSs about why and when it might be appropriate to play ‘let's wait and see’.
Types of biopsies
While it is sometimes difficult to influence the work of VSs, there is an opportunity for VNs to discuss which might be the best type of biopsy to obtain based on what type of cancer is suspected. VNs can broach this subject while preparing the patient and equipment for the biopsy procedure. The type of biopsy largely depends on the location of the tumour (Blackwood, 2015). Grab biopsies via endoscopy are most often used for intestinal or nasal tumour biopsies. A cut-off urinary catheter or sharp bone curette may be used to obtain a sample from nasal tumours. The instrument should not be introduced any further than the marked measurement of the distance from the external nares to the medial canthus to avoid the risk of penetrating the brain cavity. Gastrointestinal endoscopic grab biopsy specimens tend to be small, superficial and composed mainly of mucosa, making them less useful. When the major differentials are inflammatory bowel disease or lymphoma, multiple full-thickness biopsies are most useful and samples should be taken from both the duodenum and ileum. Any exploratory laparotomy should contribute to tumour staging by taking specimens from multiple tissues. Excision or wedge biopsies are recommended for LNs.
Biopsy procedures
Excisional biopsy (removal of the mass) is feasible if the mass is small (<3 cm in diameter), freely moveable and there is no adjacent tissue invasion. The sample taken must contain a complete margin of normal tissue, otherwise the tumour may be spread from the biopsy site and may be more difficult to resect later. Excisional biopsies should be considered a therapeutic procedure only when complete tumour removal is histologically verified and the tumour is benign or of low grade malignancy. In other situations, excisional biopsy should be used to consider a more definitive treatment recommendation. Excisional biopsy is indicated for LNs, small cutaneous nodules with ample surrounding normal tissue, most mammary gland tumours, tumours of the central nervous system (to provide decompression) and solitary masses of the lungs or intestines found during a thoracotomy or laparotomy where re-excision is unlikely. Inappropriate excisional biopsy can jeopardise future treatment as it is often stated that the first surgery has the best chance of success. This is especially important in soft tissue sarcomas and excisional biopsy is generally not recommended for feline skin tumours. Incisional biopsy where a piece of tissue is removed is recommended if a definitive diagnosis or histologic grade will influence subsequent decisions. For example, histologic grade of soft tissue sarcomas and MCT are prognostic factors that can be helpful in treatment planning.
Biopsy results may suggest the degree of surgical resection necessary for definitive control or indicate that additional types of therapy may be beneficial. Ideally, any sample obtained for histopathology should contain a representative portion of the entire tumour. Superficial tumours should be sampled away from regions of ulceration, necrosis or inflammation. Deep biopsies (> 1 cm) may be necessary to avoid sampling only overlying tissue. Biopsy at the tumour margin can be undesirable in certain deepseated tumours if it disrupts and thereby extends the tumour margin. This can necessitate wider resection or a larger radiation field for adequate treatment. Biopsy needles are preferred for deep-seated tumours. The biopsy incision or needle tract for every biopsy should be pre-planned since it is a potentially contaminated region, and should be removed at the time of the definitive procedure or included in the radiation treatment field.
Paraneoplastic disease
Paraneoplastic disease (PND) is the result of indirect effects of tumours. PND is usually due to the production and release of biologically active substances such as hormones, peptides, growth factors and cytokines. PND may be the first sign of a neoplastic disease; knowledge about the various paraneoplastic syndromes and their associated tumour types can help in early diagnosis. PND occurs distant to the tumour and may involve stimulation of immune responses leading to auto-immunity. Examples of PND in dogs include hypercalcaemia, hypoglycaemia, anaemia, thrombocytopenia, polycythaemia, neurologic problems such as megaoesophagus, hypertrophic osteopathy and cancer cachexia. Cats do not commonly present with PND although paraneoplastic alopecia and exfoliative dermatitis are dramatic when they do occur. Treatment of the underlying tumour results in resolution of PND although the signs may return with recurrence of the underlying tumour. In some cases, the PND may cause more significant morbidity than the tumour itself, so they must be clinically addressed for proper treatment or palliation. The clinical signs of PND may also mimic side effects of treatment such as chemotherapy and this may further complicate clinical decision making.
Staging
Once a diagnosis of cancer has been established, the cancer should be staged. Staging is the process that determines to what extent the cancer has spread throughout the animal's body. The degree of spread will affect prognosis and may affect treatment options. Clinical staging using the TNM system to assess the primary tumour (T), including involvement of adjacent structures, metastasis to local and regional lymph nodes (N) and distant sites (M) should be carried out, as indicated by the biological behaviour of the tumour (Table 4).
| T | = | Tumour size and/or extent | Example | Oral cavity tumours in cats and dogs |
| Tis | Tumour in situ* | Tis | Pre-invasive tumour (carcinoma in situ)* | |
| T0 | No evidence of tumour | T0 | No evidence of tumour | |
| T1 | Specific categories designated for each tumour type | T1 | Tumour < 2 cm in diameter | |
| T2 | T2 | Tumour 2–4 cm in diameter | ||
| T3 | T3 | Tumour 3 cm in diameter sub-classification: | ||
| T4 | ± | a = no bone invasion or b = bone invasion | ||
| N | = | Regional lymph Node (LN) involvement | ||
| N0 | No evidence of LN involvement | N0 | No evidence of LN involvement | |
| N1 | Describes regional LN characteristics such as number of nodes enlarged, tissue adhesion, and presence or absence of neoplasia | N1 | Moveable ipsilateral nodes enlarged | |
| N2 | N2 | Moveable contralateral/bilateral nodes enlarged | ||
| N3 | N3 | Fixed nodes | ||
| ± a | ||||
| ± b | ||||
| M | = | Distant Metastasis | ||
| M0 | Absence of distant metastasis | M0 | No distant metastasis detected | |
| M1 | Presence of distant metastasis | M1 | Distant metastasis detected |
The aim of staging is to ensure the best treatment possible is offered and to give a more accurate prognosis (or expected outcome). Carcinomas, including mammary cancer, and MCT mainly undergo metastasis (spread) via the lymphatic system. Bone cancer tends to spread to the lungs. Blood tests, imaging scans, bone marrow and/or lymph node biopsies may be necessary procedures in staging. The importance of the staging in helping to determine feasibility of therapy and overall prognosis cannot be emphasised enough (Box 1).
Other staging systems may consider factors such as the presence or absence of clinical signs such as in lymphoma, the degree of malignancy based on microscopic examination of a MCT or other tumour(s) which may occur at the same site such as with squamous cell carcinoma of mouth, tonsil, ear or digit. For many cancers, the TNM combination will correspond to one of these five alternative clinical stages (Table 5), although the criteria for stages tend to vary for different types of cancer.
| Stage | Definition |
|---|---|
| 0 | Carcinoma in situ |
| I | Higher numbers indicate more extensive disease: larger tumour size and/or spread of the cancer beyond the organ in which it first developed to nearby lymph nodes and/or tissues or organs adjacent to the primary tumour |
| II | |
| III | |
| IV | The cancer has spread to distant tissues or organs |
| V | And there are clinical signs of ill health |
A cancer is always referred to by the stage it was given at diagnosis, even if it gets worse or spreads. Additional information about how a cancer is changing over time is added to the original stage designation. The cancer stage does not change even though the cancer itself might change. This is due to the fact that survival statistics and information on treatment by stage for specific cancer types are normally based on the original cancer stage at diagnosis. It is important to note that there is a difference between the clinical stage and the true pathological stage of disease as it is often impossible to detect microscopic tumour extensions or deposits.
Accurate staging requires an understanding of the expected biologic behaviour of the different tumour types and sub-types as well as a thorough diagnostic evaluation, including tumour measurement, lymph node assessments and imaging of the region or whole body if indicated. Location of the tumour and histological type and grade are also important in determining prognosis. Carcinomas and MCT mainly undergo metastasis via the lymphatic system. Osteosarcomas tend to spread to the lungs. Cats develop classical well defined ‘cannon ball’ pulmonary metastases much less commonly than dogs. Lung metastases in cats tend to appear as ill-defined mass lesions or diffuse alveolar, interstitial or mixed patterns. Blood tests, imaging scans, bone marrow and/or lymph node biopsies may be necessary procedures in staging.
Conclusion
Once the cancer type has been determined along with an assessment of the grade and stage, the expected prognosis and proposed management plan must be discussed with the owner so that an informed decision can be made about treatment, taking into account the patient's general health and age. Sometimes the goal of treatment is not to cure the cancer but to maintain as normal a quality of life as possible for as long as possible. In this case, the goal is to control the disease or to reduce clinical signs associated with the cancer for as long as possible. The next article will discuss the different types of treatment available for cancer in companion animals. A treatment plan depends mainly on the type of cancer and the stage of the disease and it may change over time. Further details on the diagnosis and management of specific types of cancer are available on the Animal Cancer Trust website at www.animalcancer-trust.co.uk.