Paraneoplastic syndromes

Question 1

What are the most common tumours causing hypercalcaemia of malignancy?

Answer 1

Dogs - lymphoma, apocrine gland anal sac adenocarcinoma, multiple myeloma and thymoma, but other tumour types may cause hypercalcaemia. Dogs with T cell lymphoma, and in particular those with cranial mediastinal masses (which are usually T‐cell types), are most likely to develop HM

Cats - lymphoma and carcinomas

Question 2

How does hypercalcaemia affect the kidneys?

Answer 2

altered renal blood flow and mineralisation. The distal tubules become less responsive to antidiuretic hormone (ADH), leading to polyuria and polydipsia (PUPD). Dogs with HM are far more frequently azotaemic than those with primary hyperparathyroidism.

Question 3

What are the clinical signs of hypercalcaemia?

Answer 3

PUPD, inappetence or anorexia, weight loss, weakness and vomiting. Bradycardia, obtundation, twitching and shaking can occur with severe and persistent calcium elevations. Cats experience less PUPD and gastrointestinal signs than dogs and about 25 per cent of cats with hypercalcaemia show signs associated with calcium oxalate urolithiasis

Question 4

What would you expect to see with hypercalcaemia of malignancy on bloods?

Answer 4

increased serum‐ionised calcium, normal or low serum phosphorus, low PTH, and increased PTHrP concentrations

Question 5

Which tumours are associated with hypoglycaemia?

Answer 5

insulinoma, intestinal smooth‐muscle tumours, hepatocellular carcinoma and lymphoma

Question 6

How can you medically manage hypoglycaemia from insulinoma

Answer 6

dietary and pharmacological intervention (eg, prednisone, diazoxide or glucagon)

Question 7

What are the clinical signs of hyperoestrogenism?

Answer 7

possible mass, signs include non‐pruritic symmetrical alopecia, hyperpigmentation, gynaecomastia, a pendulous prepuce, and a symmetrically enlarged prostate. Owners of male dogs with this condition have observed that their dog will attract intact male dogs and may start to squat to urinate

Question 8

What may you find on bloods with hyperoestrogenism?

Answer 8

bone marrow suppression and resultant pancytopenia with subsequent signs of anaemia and/or neutropenia and/or thrombocytopenia. Haematology will demonstrate any cytopenias, and bone marrow biopsy reveals hypocellularity.

Question 9

What is microangiopathic haemolytic anaemia?

Answer 9

erythrocyte fragmentation resulting from intravascular fibrin formed in disseminated intravascular coagulation (DIC). It may be a result of other causes, such as abnormal vascularity within a tumour. It is most often associated with the vascular splenic haemangiosarcoma (HSA), but can occur with any tumour that leads to DIC. Resolution of the underlying malignancy is considered the only effective treatment.

Question 10

When is paraneoplastic IMTP most commonly seen?

Answer 10

lymphoma or multiple myeloma, and decreased platelet production can occur secondary to myelophthisis induced by marrow‐infiltrating malignancies.

Question 11

Outline paraneoplastic erythrocytosis

Answer 11

most often associated with renal cancer, although various other neoplasms have been implicated. It is a form of secondary erythrocytosis in which the underlying mechanism is an increased level of erythropoietin (EPO), rather than a bone marrow disorder. EPO may be produced ectopically by the tumour itself, or it may be produced in excess by the kidney, either in direct response to renal hypoxia caused by tumour compression or through the action of hypoxia‐inducible transcription factors, which stimulate EPO production.

Question 12

What are the clinical signs of erythrocytosis?

Answer 12

erythema of the mucous membranes, polydipsia, and neurologic signs such as disorientation, ataxia, and seizures secondary to hyperviscosity or hypervolaemia

Question 13

Outline paraneoplastic neutrophilic leukocytosis

Answer 13

mature neutrophils in the absence of infection or leukaemia and has been reported in various histologies. The underlying aetiology is tumour production of colony‐stimulating factors (CSFs). It is usually an incidental finding and should resolve with successful treatment of the underlying tumour. The elevation in neutrophil count can be very marked.

Question 14

Outline paraneoplastic eosinophilia

Answer 14

rare manifestation of cancer, but seems to primarily occur in cases of T‐cell lymphoma and mast cell tumours (MCTs), due to tumour production of IL‐5. However, it is insensitive and non‐specific for the diagnosis of neoplasia.

Question 15

Outline Platelet hyperactivity and hypercoagulability

Answer 15

Mechanisms may include an increase in serum factors that induce platelet aggregation, a change in the lipid composition of plasma membranes, and an increase in the number of newer platelets that have a higher activity. It is of clinical relevance in that it may predispose affected animals to thromboembolism.

Question 16

When is DIC most often seen?

Answer 16

The cancers most often implicated are HSA, mammary carcinoma and lung carcinoma, but various others have been implicated.

Question 17

Outline hyperglobulinaemia

Answer 17

most commonly in association with multiple myeloma, although other neoplastic diseases (typically lymphoid), including lymphoma, chronic lymphocytic leukaemia and plasmacytoma are also reported causes. The mechanism is excess production of monoclonal (or, rarely, bi‐ or oligoclonal) immunoglobulins by plasma cells or neoplastic lymphocytes. Most animals with multiple myeloma have an IgG or IgA monoclonal gammopathy.

Question 18

How do you confirm if hyperglobulinaemia is paraneoplastic?

Answer 18

serum or urine electrophoresis, where a monoclonal gammopathy indicates a likely neoplastic cause and a polyclonal gammopathy indicates a likely infectious or inflammatory cause

Question 19

Outline paraneoplastic alopecia

Answer 19

some cats with pancreatic and biliary carcinoma. The underlying mechanism is unclear, but an association with Malassezia species yeast has been suggested and leads to pruritus. Acute, progressive, non‐pruritic symmetrical alopecia occurs, with lesions characterised by easily epilated hair and underlying smooth, shiny skin. Resolution has been reported after removal of the primary pancreatic mass, with recurrence coinciding with developing metastases.

Question 20

What is superficial necrolytic dermatitis?

Answer 20

mainly associated with glucagonoma in dogs and pancreatic carcinoma in cats, although it has been reported with insulinoma. SND caused by hepatopathy, often with a history of phenobarbital therapy is more common, hence the term hepatocutaneous syndrome. Other terms previously used to describe this disorder are necrolytic migratory erythema (NME), metabolic epidermal necrosis, and diabetic dermatopathy. Hypoaminoacidaemia is a characteristic feature and may be central to the aetiology. The cutaneous lesions are characterised by erythema, crusting, exudation, ulceration, and non‐pruritic alopecia. Lesions affect the face, anogenital region, and pressure points on the trunk and extremities. The footpads are also often affected, with severe crusting, fissures, ulceration, and secondary infections with yeast, bacteria or dermatophytes

Question 21

What is nodular dermatofibrosis

Answer 21

Nodular dermatofibrosis is a rare cutaneous PNS affecting dogs, typically German shepherd dogs, that have bilateral renal cystadenocarcinoma.
Involves a genetic mutation
It is characterised by small, firm skin nodules located in the subcutaneous tissues of the limbs and head. The nodules are composed of well‐differentiated, densely packed collagen. Uterine leiomyomas may occur in a large percentage of affected intact females. Given the progressive nature of the disease and the degree of renal impairment that can occur with bilateral disease, the overall prognosis for affected dogs is poor.

Question 22

Outline paraneoplastic gastric ulceration

Answer 22

occurs indirectly as a result of an ulcerogenic substance being released from the primary tumour. Examples include release of histamine from an MCT and gastrin from a gastrinoma. Both substances bind to receptors on the parietal cells and stimulate increased gastric acid secretion and subsequent gastrointestinal ulceration. Therapy is aimed at resolution of the primary tumour and treatment for gastrointestinal ulceration with proton‐pump inhibitors, H2‐receptor blockers and sucralfate.

Question 23

Outline paraneoplastic myasthenia gravis

Answer 23

most often occurs with thymoma, but has also been reported with other tumours. The cause of paraneoplastic MG is production of antibodies to the nicotinic acetylcholine receptors (AChRs) by the tumour. A rare disorder of MG development after thymectomy for thymoma has also been described. Clinical signs include muscle weakness, dysphagia, regurgitation, and aspiration pneumonia secondary to megaoesophagus

Question 24

Outline paraneoplastic peripheral neuropathy

Answer 24

lymphoma, multiple myeloma, insulinoma, and various carcinomas and sarcomas. The likely aetiology is production of antibodies targeting antigens that are shared between the tumour and the peripheral nerves. This PNS is characterised by focal or whole‐body weakness. Electromyography and motor‐nerve conduction studies are helpful in confirming the diagnosis. This may be difficult to distinguish from drug‐induced neuropathy, a rare adverse effect associated with the use of some chemotherapeutic agents, such as vincristine.

Question 25

Outline paraneoplastic glomerulopathy and nephropathy

Answer 25

may occur in cancer patients secondary to tumour‐related immune complexes being deposited in the renal glomeruli. As such, neoplasia should be considered in the differential diagnosis list for dogs and cats that have protein‐losing renal disease. Treatment involves elimination of the underlying tumour, with careful attention to fluid and electrolyte needs and avoidance of drugs that may exacerbate renal damage. Therapy for proteinuria may involve ACE inhibitors.

Question 26

Outline hypertrophic osteopathy

Answer 26

uncommon in dogs and is rarely seen in cats. It is most often associated with primary intrathoracic masses, although non‐neoplastic space‐occupying lesions within the thoracic or abdominal cavities, including abscesses and granulomas, foreign bodies and parasites, may induce HO. The disorder is characterised by progressive periosteal proliferation along the shafts of long bones of distal extremities and occasionally along other bones of the appendicular skeleton. The aetiology is not completely understood, but one mechanism is thought to involve stimulation of the vagus nerve, resulting in increased blood flow to the distal extremities.