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- 1. Primary Lung Tumours In Dogs Louise Martin 23/01/15
- 2. Pip Budd 8 year old, MN Border Collie History Retching/gagging when exercising Chronic right diaphragmatic hernia discovered and repaired Recurrent pleural effusions since surgery Diagnosis of carcinoma from fluid
- 3. Investigations In house Haematology and Biochemistry Thoracic and Abdominal Ultrasound Thoracocentesis: Fluid sent for analysis and cytology CT scan of lungs Differential Diagnosis Chronic Inflammation Pulmonary Carcinoma Mesothelioma
- 5. Pleural Fluid 1 2 3 4
- 6. Canine Lung Tumours Can be primary or secondary Metastatic lung tumours much more common Primary pulmonary tumours rare in dogs Average age of primary tumour diagnosis 11years No sex or breed predilection
- 7. Primary Lung Cancers Majority are malignant Carcinoma predominates 85% bronchoalveolar origin in dogs Multiple routes of metastasis
- 8. Clinical Signs Often none – incidental Coughing, dyspnoea, lethargy, anorexia, weight loss, haemoptysis Dull heart and lung sounds due to pleural effusion Increased lung sounds if extensive mass Lameness – Hypertrophic osteopathy Neurological Signs - Metastasis
- 9. Diagnosis As previously mentioned in Pip’s case Thoracic radiographs Ultrasound guided FNA Bronchoalveolar lavage
- 10. Surgery > Partial lung lobectomy > Complete lung lobectomy Chemotherapy > Systemic > Intra-pleural Palliative Treatment Treatment
- 11. Prognosis A number of factors affect the prognosis of dogs with primary pulmonary disease: Clinical signs Metastasis to lymph nodes Tumour well, moderately or poorly differentiated
- 12. Back to Pip... His owners felt he had been through enough with his previous diaphragmatic hernia surgery so they opted to continue treating him with prednisolone and frusemide and have his chest drained when necessary. Allowing him to have a good quality of life for the time he has left.
- 13. References RS Brodey, PH Craig. Primary pulmonary neoplasms in the dog: a review of 29 cases J Am Vet Med Assoc, 147 (1965), pp. 1628–1643 CR Dorn, DO Taylor, FL Frye, et al. Survey of animal neoplasms in Alameda and Contra Costa Counties, California. I. Methodology and description of cases J Natl Cancer Inst, 40 (1968), pp. 295– 305 DJ Meuten. Tumors in domestic animals (ed 4)Iowa State University Press, Ames, Iowa (2002) FF Hahn, BA Muggenburg, WC Griffith. Primary lung neoplasia in a beagle colony Vet Pathol, 33 (1996), pp. 633–638 JE Moulton, C von Tscharner, R Schneider. Classification of lung carcinomas in the dog and cat Vet Pathol, 18 (1981), pp. 513–528 EA McNiel, GK Ogilvie, BE Powers, et al. Evaluation of prognostic factors for dogs with primary lung tumors: 67 cases (1985-1992) J Am Vet Med Assoc, 211 (1997), pp. 1422–1427 CJ Mehlhaff, CE Leifer, AK Patnaik, et al. Surgical treatment of primary pulmonary neoplasia in 15 dogs J Am Anim Hosp Assoc, 20 (1984), p. 5 GK Ogilvie, WM Haschek, SJ Withrow, et al. Classification of primary lung tumors in dogs: 210 cases (1975-1985) J Am Vet Med Assoc, 195 (1989), pp. 106–108 DC Sorjonen, KG Braund, EJ Hoff. Paraplegia and subclinical neuromyopathy associated with a primary lung tumor in a dog J Am Vet Med Assoc, 180 (1982), pp. 1209–1211 RS Brodey. Hypertrophic osteoarthropathy in the dog: a clinicopathologic survey of 60 cases J Am Vet Med Assoc, 159 (1971), pp. 1242–1256 VT DeVita, TS Lawrence, SA Rosenberg. DeVita, Hellman, and Rosenberg's cancer: principles & practice of oncology (ed 8)Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia (2008) VJ Poirier, KE Burgess, WM Adams, et al. Toxicity, dosage, and efficacy of vinorelbine (Navelbine) in dogs with spontaneous neoplasia J Vet Intern Med, 18 (2004), pp. 536–539 GK Ogilvie, RM Weigel, WM Haschek, et al. Prognostic factors for tumor remission and survival in dogs after surgery for primary lung tumor: 76 cases (1975-1985) AS Moore, C Kirk, A Cardona. Intracavitary cisplatin chemotherapy experience with six dogs J Vet Intern Med, 5 (1991), pp. 227–231 Stephen J. Withrow, David M. Vail, Rodney L. Page (2012). Small Animal Clinical Oncology. 5th ed. Missouri: Elsevier. Stephen J. Ettinger, Edward C. Feldman (2010). Textbook of Veterinary Medicine Diseases of the Dog and Cat. 7th ed. Missouri: Elsevier. p1109-1113.
- 14. Any Questions? Special thanks to Mike in oncology!
Editor's Notes
- I am going to present to you today a little bit about primary lung tumours in dogs. This is something we hear a lot about in humans, however is mentioned less in animals. It’s something that wasn’t really covered in our clinical lectures, so I felt this was a good opportunity to learn a little bit more about it.
- Pip is an 8 year old male neutered border collie. He presented to the Oncology service on Tuesday the 13th of January for investigation into what could be causing his recurrent pleural effusion. He had a complex history, in November 2014 he was taken to the vet following gagging/retching episodes when out walking. They admitted him a few days later for examination under anaesthesia to investigate this. His breathing deteriorated under sedation. Radiographs were taken and 100ml of fluid was drained from his thorax. He was diagnosed with a chronic right diaphragmatic hernia, with the spleen, liver, intestines and omentum all in the thoracic cavity, Pip underwent surgery on 25/11/14 to repair this and there were extensive attachments present. A chest drain was placed, however he pulled this out. Following the surgery Pip required to have his chest drained 3 times, the largest volume of fluid drained was 1200ml, this was just before Christmas and Pip was very unwell at this point, a sample of this pleural fluid was sent off for analysis and came back as Carcinoma. He was receiving injections of dexadresson from his vet, this slowed down the formation of the fluid and made Pip feel better. He was referred to GUVS for confirmation of diagnosis of carcinoma.
- After taking the history we had three main differentials on our list: Chronic inflammation following the surgery to repair the diaphragmatic hernia because mesothelial cells (the cells lining the thoracic cavity) can look like neoplastic cells when they are highly proliferative when there is an inflammatory response. This was optimistic but it was the diagnosis we were hoping for. The second was of course carcinoma of the lung as the previous fluid analysis had come back with carcinoma cells present. And finally the third was mesothelioma, these tumours produce extensive effusions, the most common clinical sign when an animal has this type of tumour in the thorax is dyspnoea caused by pleural effusion. We carried out a number of investigations on Pip: In house haematology and biochemistry: to check overall health and organ function. Thoracic and abdominal ultrasound: This showed a significant volume of fluid in both sides of the thoracic cavity, the pleurae were thickened. On abdominal ultrasound the liver was large, with rounded edges and bright, this is consistent with steroid administration. On the rest of the abdominal ultrasound, aside from things being slightly out of place there were no other abnormalities detected. Thoracocentesis: Due to the large amount of fluid in Pip’s pleural space, a chest drain was placed. When it was initially drained 750ml of straw coloured/blood stained fluid was removed from the cavity. Some of this was sent to the lab for analysis. Finally a CT of his lungs was taken. See next slide.
- Again everything was a bit out of place on the CT taken of Pip, due to the correction of the diaphragmatic hernia. These are two images from Pip’s lungs on the scan. The top one shows the difference in the size of the lungs and also how the heart is sitting over to the right hand side. This would normally be over on the left. This decrease in the lung lobes could be hypoplasia related to the chronic diaphragmatic hernia. The second image shows a focal area of lung consolidation around the right cranial bronchus, this could be consistent with a neoplastic process. Even when the lung was manually inflated this area didn’t change. Also seen in the CT was a moderate enlargement in the sternal LNs (~11mm), the appearance was consistent with reactive lymphadenopathy, however, neoplastic infiltration could not be ruled out. The discovery of this consolidated/mass-like area in his right cranial lung lobe was concerning for Pip.
- The following day the cytology came back from the fluid taken from his effusion: In the background were a population of inflammatory cells, non-degenerate neutrophils, some mature lymphocytes and a few RBCs. Image 1: The round cells present with the scalloped edges are typical of reactive mesothelial cells, these can be present due to chronic inflammation in the thorax. However, the very large round cell with 3 nuclei present increases suspicion of something nasty going on here. Image 2: Hyperchromatic round cell population with marked anisocytosis and anisokaryosis. Image 3:Active macrophages, but nuclei all consistent, similar sizes, faint chromatin pattern in nuclei. Active, vacuolated cytoplasm. Image 4: Very nasty looking cells, multinucleate with marked anisokaryosis and anisonucleolosis within the cell. Also cells with karyomegaly present. Nuclear and cytoplasmic anisochromasia present also. Many cells present in cohesive sheets or ‘grape bunch’ appearance, commonly seen in epithelial tumours. Many criteria of malignancy present. Unfortunately this confirmed the diagnosis of carcinoma.
- So if we think about lung tumours in the dog, these can be primary or secondary. Secondary, metastatic disease is much more common. Where cancer has spread from another distant site and a new tumour has grown in the lung. Primary lung tumours are much less common, only making up around 1% of all tumours diagnosed in dogs. The number has increased in recent years, however this could be due to our patients having longer lifespans, therefore more and more are diagnosed and also increasing ability of vets to make the diagnosis due to available tests. On average the age of onset of primary lung cancer is 10.5-11years old. There doesn’t appear to be any strong breed predispositions, however some breeds are overrepresented e.g. boxer, doberman, irish setter and bernese mountain dog. In humans, lung cancer is one of the commonest causes of cancer-related death, and there are a number of risk factors including smoking that are linked with causing it. However, in dogs there is no clear evidence of definitive risk factors.
- 80% of primary lung tumours are malignant. Carcinoma is the predominant tumour type in the lungs, these can form from any of the tissues making up the lungs, however, they are most commonly derived from the epithelium of the airways or from the parenchyma of the lung. Parenchymal tumours tend to be more peripherally located and tumours derived from epithelium of large airways tend to be found around the hilus. 85% of primary lung tumours in dogs are bronchoalveolar carcinoma, adenocarcinoma, adenosquamous carcinoma and squamous cell carcinoma make up the other 15%. Lung tumours have good ability to metastasise, either via local spread to other lung lobes or to thoracic LNs (tracheobronchial or sternal) or via a haematogenous or lymphatic route where they will commonly invade bone or the brain. In Pip’s case, due to the number of carcinomatous cells present in the pleural effusion, the chance of seeding tumour cells and therefore lots of small metastases throughout the thorax was likely in his case (e.g. on the pleurae, pericardium, diaphragm). However, the rate of metastasis for bronchoalveolar carcinoma (the most common type) is less than that or the rarer tumour types: SCC and anaplastic carcinoma (50% and 90% respectively).
- Many primary lung tumours (30%) are an incidental finding in older dogs who are seeing their Vet for another reason, they are not showing any signs of respiratory disease. However, the most common clinical sign seen in dogs is coughing this is present in 52-93% of dogs with primary lung tumours. Other signs include dyspnoea, lethargy, anorexia, weight loss and haemoptysis (coughing up blood). Clinical examination findings are also important in this disease, auscultation of the thorax can raise suspicion. For example the heart and lung sounds can be dull or muffled due to a pleural effusion produced by the tumour. Image of radiograph above shows what the appearance of a pleural effusion on radiograph looks like. The lung lobes have sharp clear borders and are elevated off of the sternum and the cardiac shadow is not obvious as the fluid is of soft tissue opacity. Or if there is a large tumour burden in the lungs there may be increased breath sounds. Some animals may just present with lameness and no other signs. This is due to a paraneoplastic syndrome called Hypertrophic osteopathy (Marie’s disease). This causes periosteal new bone growth, long bones are most affected by this. As seen in the picture above. This condition is secondary to masses in the thoracic cavity, however these do not have to be neoplastic, they can have other causes e.g. infectious. Finally, some dogs can present with neurological abnormalities on clinical examination, this can be due to metastasis of the lung tumour to the CNS, this has been reported in a number of cases.
- As previously mentioned, in Pip’s case we carried out a number of diagnostic tests: Haem/bio, thoracic & abdominal ultrasound, thoracocentesis and chest CT. There are some other diagnostic tests which can be carried out: Most pulmonary tumours are diagnosed with thoracic radiographs, especially in first opinion practice this will probably be the only imaging available to you without referral. Ultrasound can be used to get an FNA of the tumour to confirm the diagnosis, this wasn’t necessary in this case because the cells present in the effusion gave us this information. BAL may be used to diagnose pulmonary neoplasia as it may yield neoplastic cells. This is an uncommon method of diagnosis.
- Surgery is the preferred treatment of primary lung tumours. This can be done in a number of ways depending on the site and size of the tumour and the surgeon’s preferences. (lateral thoracotomy or median sternotomy, thoracoscopic lobectomy if peripheral mass) The goal of surgery is to get rid of all gross disease, a complete lung lobectomy is best in general. However, if the mass is very peripherally located and small then a partial lobectomy may be possible. It is still important to try to achieve wide margins if possible. (Generally performed with suturing material or a surgical stapler, crushing forceps are placed proximal to the lesion, suture then placed proximal to the clamp, pulm artery and vein individually tied off). If the tumour is very extensive throughout one lung a pneumonectomy (removal of whole lung) may be performed. Chemotherapy: there is not a lot of evidence suggesting which chemotherapy agents are best in canine primary lung tumours. However, it is clear that chemotherapy is not very effective against gross disease, therefore attempting chemotherapy without surgery may be unrewarding. Cisplatin based protocols are used as standard in human medicine. In one study the chemotherapy agent vinorelbine was used for bronchoalveolar carcinoma and it induced partial responses in 2 out of 7 dogs. Three more dogs were treated with this for microscopic disease, and it increased their survival time markedly. At the moment, based on human protocols and the minimal research done in dogs cisplatin of vinorelbine based protocols seem to have the best outcome. Systemic chemotherapy is not the only option in lung cancer, it is also possible to carry out intrapleural chemotherapy and especially in the case of malignant pleural effusions (as in Pip’s case) a combination of both of these methods can be successful in treatment of the effusion, however, this is more of a palliative measure. This results in a reduction in clinical signs and helps to improve quality of life. Carboplatin and Cisplatin have both been successful in reducing malignant pleural effusions. Tyrosine kinase inhibitors, such as Palladia (tocanerib) have shown to be beneficial in some human cases on lung cancer, this is an area which requires much more research in dogs.
- There are a number of factors which can affect the prognosis of primary lung tumours in dogs, even though 80% are malignant some patients can have a relatively good survival depending on the following: Whether clinical signs were present at the time of diagnosis or the tumour was an incidental finding. One study showed that dogs without clinical signs at diagnosis had a mean survival time of around 18months compared to 8 months for those with clinical signs already present. Similarly dogs with lymph node metastasis had a severely shortened mean survival time of 1 month compared to those without who survived an average of 15 months. Whether the tumour is well-differentiated, moderately or poorly differentiated also has a large bearing on the survival time, the MST being 2 years, 9 months and 1 week respectively. Finally in dogs where all gross tumour was removed during surgery the MST was 1 year. This shows that there can be successful outcomes with good survival times in primary pulmonary neoplasia, however when deciding on a treatment plan it is important to look at all the above factors and decide what is best based on the prognostic factors.
- Pip’s owners decided that he had been through enough already with the previous diaphragmatic hernia surgery, so they have opted to treat him with frusemide to try to reduce/slow the formation of the pleural effusion and also prednisolone to decrease inflammation. Also to have his chest drained as necessary, to give him the best quality of life for the time he has left.