Canine and feline Oncology

Guillermo Couto NĂŠstor Moreno

Veterinary oncology is a rapidly developing specialty, providing clinicians with an increasing range of treatments for their patients.

However, it also demands a thorough understanding of the subject and constant updating.

To help veterinarians this book explores both the basic knowledge and the latest advances in oncology, presented in a didactic and accessible manner. There is a chapter on the most commonly encountered neoplasms in daily practice with recommendations for their diagnosis and treatment and a chapter with several real-life cases for the reader to test their knowledge on the subject. Finally, it includes an appendix detailing the most commonly used chemotherapeutic protocols for dogs and cats.

Canine and feline oncology

Guillermo Couto NĂŠstor Moreno

FROM THEORY TO PRACTICE

Oncology CANINE AND FELINE

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It is also important to know where the patient lives, whether it travels to other places or has stayed at a dog boarding kennel, where it is usually taken for a walk, where it sleeps, etc.

It is useful to review what the animal does daily with the owners so that they can more easily remember any changes in their animal’s normal behaviour.

Knowing about the pet’s eating habits and whether it shows a loss of appetite, anorexia or difficulties to swallow will help the veterinary surgeon to suspect a tumour.

After gathering information about the animal’s behaviour, it is necessary to ask about any changes the owners may have noticed in every aspect of their pet’s health: digestive or respiratory systems, skin, etc.

The chronicity of the lesion and the information about its evolution through time are indicators of the type of mass and its malignancy. Generally, fast-growing tumours are associated with a worse prognosis.

Figure 2. Evaluation of a dog’s popliteal lymph nodes.

Examination

Physical examination Observing, palpating, or even detecting an unpleasant smell coming from the masses or lesions can help to identify the location, extension and prognosis of a neoplasm.

patient’s lymph nodes (fig. 2), especially those related with the affected zone, in order to detect possible primary neoplasms or metastases.

For example, in superficial tumours, it is very important to detect whether they move when palpating them or remain fixed. This will indicate if they are cutaneous, subcutaneous, or, if on the contrary, they are located in deeper tissues. These observations will provide information to the practitioner about certain characteristics such as the invasiveness of the tumour and the difficulty to extirpate it in case surgery is performed.

X-rays still are particularly useful to locate certain tumours and rule out metastases (figs. 3, 4 and 5).

The shape of the neoplasm is important for its diagnosis, since diffuse and undifferentiated tumours have more complications than those with very welldelimited borders. It is also important to explore the

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Diagnostic imaging techniques

It is a very effective technique in the diagnosis of bone tumours (fig. 6). In the case of a thoracic evaluation, X-rays allow veterinary surgeons to view certain pulmonary patterns that are of particular interest to detect metastases of tumours such as mammary tumours. It should be highlighted that at least three projections (left and right laterolateral and dorsoventral or ventrodorsal) are necessary for a proper examination of the lung area, since on many occasions, lesions may be hidden (figs. 7, 8 and 9).

How to know if a patient has cancer DIAGNOSTIC PROTOCOL

Figure 3.

Osteosarcoma on a patient’s distal radius.

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Figures 4-5.

X-rays of the osteosarcoma shown in figure 3.

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Figure 6. Osteosarcoma in a patient’s distal femur.

Figures 7, 8 and 9. Thoracic X-rays of a patient with osteosarcoma and pulmonary metastases.

VD, LLL and RLL views.

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FROM THEORY TO PRACTICE

Oncology CANINE AND FELINE

Aetiological agents

Monomorphic population: ■■

Neutrophils (suppurative inflammation)

Certain aetiological agents are easy to identify in cytology specimens: Histoplasma, Blastomyces, Cryptococcus, Coccidioides, Aspergillus/Penicillium, Toxoplasma, Leishmania, other rickettsial agents, bacteria and Demodex.

Malignant neoplasms

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A.A(granulomatous inflammation) Macrophages

A.B

Normal cell populations, except those that undergo rapid replication, such as those in the bone marrow, have a homogeneous structure with a normal nuclear-cytoplasmic ratio and nuclei A.C with condensed chromatin.

Malignancy criteria • In neoplastic cells, it is possible to distinguish one or more of these characteristics of malignancy (figs. 26 and 27).

• Regarding the nucleus: B.A • Increase of the nuclear-cytoplasmic ratio.

A.B ■■ Eosinophils (eosinophilic inflammation)

A.C

• Thin chromatin • Presence of nucleoli • Nuclear deformation (compression of a nucleus by a neighbouring one) • Anisokaryosis (nuclei of different sizes)

• Regarding the cell: • Pleomorphism (cells at different stages of development)

B.A A.A A.C

A.B

A.C

• Anisocytosis (cells of different sizes)

Pleomorphic inflammation ■■

Neutrophils and macrophages (pyogranulomatous inflammation)

• Heterotopia (presence of a type of cell where it is not usually found) • Vacuolisation and phagocytic activity (initially in epithelial malignant tumours) • Present of giant cells B.A

.A

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How to know if a patient has cancer DIAGNOSTIC PROTOCOL

In addition to the characteristics of cellular and nuclear malignancy, neoplastic cells usually differ morphologically from the progenitor population.

Anisokaryosis

Nucleoli

Neoplastic cells can also be classified depending on their characteristics and on those of the tissue of origin, in carcinomas (epithelial cells), sarcomas (mesenchymatous cells) or round cells tumors.

Vacuolisation Figure 26. Malignancy criteria.

Anisokaryosis and nuclear deformation

Increase of the nucleus/ cytoplasm relation

Vacuolisation

Pleomorphism

Anisocytosis

Figure 27. Malignancy criteria. Sample from an alpaca.

Carcinomas Most carcinomas contain round or polygonal cells that form groups (cell-to-cell interaction). They have a dark blue cytoplasm and the nuclei are large with thin chromatin and evident nucleoli (fig. 28).

There are evident vacuoles in most adenocarcinomas. In squamous cell carcinomas, the cells appear isolated and are sometimes accompanied by phagocytosed leukocytes.

Figure 28. Apocrine gland carcinoma in a dog.

Monomorphic cell population without definite limits.

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FROM THEORY TO PRACTICE

Oncology CANINE AND FELINE

Figure 34. FNA sample of a mesenteric lymph node in a cat with diarrhoea: large granular lymphocyte lymphoma.

Figure 35. FNA sample of a dermoepidermic mass in a 5-year-old Newfoundland: plasmocytoma or plasma cell tumour.

Figure 36. FNA sample of an oral mass in a 12-year-old Schnauzer: melanoma.

Figure 37. Osteosarcoma.

When reacting to the different stimuli, lymph nodes show different patterns:

Evaluation of the lymph nodes ■■

• Normal lymph node.

• Reactive or hyperplastic lymphadenopathy.

• Lymphadenitis.

• Neoplasia.

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Normal lymph node: small lymph node in a proportion of 75 to 90% are usually observed. Lymphocytes have a diameter which is 1 to 1.5 times as large as that of an erythrocyte and a dense chromatin pattern with no nucleoli. The rest of the cells in the sample are lymphoblasts, macrophages, plasma cells, etc.

Reactive or hyperplastic lymphadenopathy: it occurs in lymphoid tissues that have reacted to an antigenic stimulus. Cytologically, they have small,

How to know if a patient has cancer DIAGNOSTIC PROTOCOL

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medium and large lymphocytes, lymphoblasts, plasma cells and macrophages.

The presence of cells at different stages of develop­ment indicates an antigenic response to various antigens.

Feline lymph nodes do not usually have plasma cells but they have numerous blasts, which can lead to confusions when it comes to differentiating them from a lymphoma.

Lymphadenitis: they are reactive lymph nodes with a cytological aspect that is similar to that of a reactive lymphadenopathy. Inflammatory cells are abundant and there are degenerative changes in most cell lines. It is also sometimes possible to detect the aetiological agents that trigger the disease.

Neoplasia: the metastatic neoplastic cells can reach the lymph node by lymphatic route or through blood; or they can come from primary conditions that affect those structures (lymphomas).

Biopsies provide tissue samples for a histopathological analysis and generally, although now always, lead to a definitive diagnosis.

Techniques Incisional biopsy and excisional biopsy In an incisional biopsy, the clinician obtains a portion of the mass, while in an excisional biopsy, the entire mass is sent to the laboratory (figs 38 and 39).

The cytology specimens of metastatic lesions have reactive patterns with a presence of neoplastic cells.

In the most advanced metastatic invasions, neoplastic cells can represent almost all the cells present in the specimen.

In the case of primary lymphomas, homogeneous populations of large and immature lymphoid cells with a low nuclear-cytoplasmic ratio, large chromatin and nucleoli are detected.

Figure 38. Incisional biopsy.

Biopsy If a cytology specimen does not give a definitive ans­ wer regarding the diagnosis of a mass or tumour, it is necessary to perform a biopsy. This is important as a high percentage of malignant neoplasms are not treated surgically, but with radiotherapy or chemotherapy, so it will not be possible to carry out a histopathological analysis after their excision. In addition, when the tumour requires surgical treatment, knowing the type of neoplasm before the surgery often helps to plan the surgical and medical procedure, and usually gives a better prognosis to the patient.

Figure 39. Excisional biopsy.

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FROM THEORY TO PRACTICE

Oncology CANINE AND FELINE

Caso 1 Case

Gastrinoma in a Chihuahua

Clinical history Trixie is a 10-year-old non-spayed female Chihuahua, weighing 3 kg.

Patient: Trixie

An appropriate vaccine protocol and external and internal antiparasitic treatment have been followed. She has been treated with praziquantel and fenbendazole every three months and wears an antiparasitic collar.

Trixie’s owners have come to the practice because their dog has not eaten since the day before. During the anamnesis, the practitioner comes to the conclusion that the animal does not eat her food or extra food or rewards she is offered by her owners, a situation they feel very worried about. In addition, she spends a lot of time lying down and does not to walk or move, except to urinate or defecate in the street. On the other hand, the owners have not observed any vomiting, diarrhoea, coughing, sneezing or nasal secretion.

Physical examination After examining the patient, the following observations can be made: ■■ Her general aspect is that of a thin dog. Her ribs, spine and pelvic bones can be seen and she has very little abdominal fat. A body condition score of 2 out of 5 is determined.

■■ Her rectal temperature is 38.5 ºC. ■■ She shows signs of mild pain during abdominal palpation.

■■ The mucosae are slightly pale but have a normal capillary refill time.

■■ After carrying out a skinfold test, her hydration level is considered appropriate.

■■ Pulmonary and heart auscultation is normal, except for a mild tachycardia.

■■ The femoral pulse is within the normal range.

■■ At the moment, no more alterations can be seen in the patient.

Once the physical examination has been done, what tests should be performed to guide the diagnosis?

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File number: 0042054 Breed: Chihuahua Age: 10 years old Sex: female Weight: 3kg Reason for consultation: Anorexia and exercise intolerance

Complementary diagnostic tests In this case, blood analyses are carried out first: complete blood count and biochemical analysis: ■■ The parameters of the biochemical analysis are within the normal range, except blood urea nitrogen, which is slightly high.

■■ The complete blood count parameters are the following: Red cells Ht. (%)

38-53

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Hb (g/dL)

14.2-19.2

5

MCV (fl)

65-80

38

MCHC (g/dL)

32-36

28.1

Reticulocytes

< 1.5

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How would you evaluate this complete blood count?

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A haematocrit value of 18% indicates that the patient is suffering from severe anaemia.

The concentration of haemoglobin is 5, which means that this is a case of hypochromic anaemia.

CLINICAL CLINICAL CASES CASES CASE 1. Gastrinoma in a Chihuahua

Other complementary tests ■■

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An MCV value of 38 indicates that it is a microcytic anaemia.

A number of reticulocytes of 12 shows that there is blood regeneration.

The following diagram is a reminder of the classification of anaemias: Anaemia

Regenerative

Semi-regenerative

Non-regenerative

Macrocytic Hypochromic

Microcytic Hypochromic

Normocytic Normochromic

Therefore, if the diagram is applied, the patient presents with a type of anaemia that can be classified as semi-regenerative anaemia. The main cause of this type of anaemias is iron deficiency.

It is useful to remember the four typical signs of haematological alterations shown by dogs with anaemia caused by an iron deficiency: ■■ Microcytosis ■■ Hypocromasia ■■ Mild regeneration ■■ Thrombocytosis The anaemias due to iron deficiency are usually caused by chronic blood losses. In this case, a flea or tick infestation is ruled out, since the dog has not been in direct contact with ectoparasites lately and has followed the external antiparasitic treatment given by the veterinary surgeon.

White blood cells Leukocytes (U/dL) Segmented cells (%) Lymphocytes/Monocytes Platelets (1000/dL)

6,000-19,000

21,500

55-70

90

1,100-6,300

2,200

175-500

921

After considering some initial diagnostic tests, it is decided to carry out more tests in order to reach a definitive diagnosis of the disease.

■■ Blood culture: positive result. Although the dog has not shown high temperature yet.

■■ Abdominal ultrasound scan: this test is carried out so as to find possible internal haemorrhages. A gastric mass as well as an area of the pancreas with a different echotexture are detected. No other alterations or free liquid are observed in the rest of the abdomen.

■■ Endoscopy: the purpose of this test is to evaluate the gastric mass that has been detected on ultrasound scan. During the endoscopy, a mass with a diameter of approximately 1.5 cm that protrudes from the mucosa (fig. 1) is observed. An active haemorrhage is also observed (fig. 2).

■■ Cytology: thanks to this test, the lesion is defined as hypertrophic gastropathy.

■■ Measurement of the level of gastrin: 262 ng/ml (normal range 65-190 ng/ml).

Figure 1. Gastric mass that protrudes from the digestive mucosa.

Figure 2. Active haemorrhage.

Why does this dog present with hypertrophic gastropathy? Can we reach a definitive diagnosis with these data?

The high gastrin levels together with the symptoms observed help to focus the diagnosis. It is very likely that the hypertrophic gastropathy of this patient is secondary to a gastrinoma located in the pancreas (Zollinger-Ellison syndrome), which is in turn associated with a semi-regenerative anaemia caused by iron deficiency.

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