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com
James Elliott qualified
from the University of
Edinburgh. After a period
in general practice, he
became an intern and then
a resident in oncology at
the University of Liverpool,
where he subsequently
became a lecturer. He is
an European and RCVS
recognised specialist in
veterinary oncology. He
currently works as an
oncologist at Willows
Referral Service.
doi:10.1136/inp.g5826
Elliott .indd 443
Companion Animals
Paraneoplastic syndromes in
dogs and cats
James Elliott
Paraneoplastic syndromes (PNSs) can be described as the indirect effects of tumours,
typically due to tumour production and release of biologically active substances such
as hormones, growth factors and cytokines. PNSs are sometimes the first evidence of
a neoplastic disease; therefore, knowledge of these syndromes and their associated
tumour types can help in early diagnosis. PNSs should resolve with treatment of the
underlying tumour and, conversely, may return with recurrence of the underlying
tumour. In some cases, they cause more significant morbidity than the tumour itself, so
they must be clinically addressed for proper treatment or palliation. A further issue is
that signs caused by PNSs may mimic side effects of treatment such as chemotherapy,
complicating clinical decision making. This article discusses the different types of PNSs
and treatment options for each case.
Endocrine paraneoplastic loss, weakness and vomiting. Bradycardia, obtundation,
syndromes twitching and shaking can occur with severe and
persistent calcium elevations. Cats experience less PUPD
Hypercalcaemia of malignancy and gastrointestinal signs than dogs and about 25 per cent
The most common cause of hypercalcaemia in dogs is an of cats with hypercalcaemia show signs associated with
underlying malignancy, whereas non-neoplastic causes calcium oxalate urolithiasis. Diagnostic evaluation should
predominate in cats. The primary mechanism is the include assaying serum-ionised calcium concentrations,
promotion of bone resorption by osteoclasts, resulting in as this is the biologically active fraction. This can be
release of calcium into the bloodstream. The mechanism done using routinely available ‘bedside’ analysers, such
includes elaborating substances such as parathyroid as the iSTAT. If the ionised calcium is increased, serum
hormone–related peptide (PTHrP), which shares structural may then be submitted for measurement of phosphorus,
homology with parathyroid hormone (PTH). PTHrP binds PTH, and PTHrP concentrations. Typically, dogs and cats
to the PTH receptor with an affinity equal to that of PTH, with HM have increased serum-ionised calcium, normal
resulting in similar biological effects. Other substances or low serum phosphorus, low PTH, and increased
that can cause hypercalcaemia of malignancy (HM) include PTHrP concentrations. Useful diagnostic steps include
interleukin-1β (IL-1β), transforming growth factor-β (TGF- a thorough physical examination that includes rectal
β), and the receptor activator of nuclear factor κ-B ligand palpation (to identify anal sac masses), a complete blood
(RANκL). In dogs, HM is most commonly associated with count (to identify cytopenias and atypical circulating
lymphoma, apocrine gland anal sac adenocarcinoma, lymphoma or leukaemic cells), serum biochemical profile,
multiple myeloma and thymoma, but other tumour types urinalysis, and imaging of the thorax and abdomen.
may cause hypercalcaemia. Dogs with T cell lymphoma, and Thoracic radiographs are paramount given that a very
in particular those with cranial mediastinal masses (which large proportion of animals with HM will have mediastinal
are usually T-cell types), are most likely to develop HM. The lymphoma, and they are also used to identify thymomas.
HM associated with canine multiple myeloma is believed to Abdominal ultrasound is required as opposed to plain
be caused by increased bone resorption in the immediate radiography because of the low sensitivity of the latter for
proximity of neoplastic foci due to widespread, polyostotic detection of lesions, specifically lymphoma.
bone lesions. HM is less common in cats, but has been
associated with lymphoma and a variety of carcinomas. If an animal with hypercalcaemia is unwell, then imaging
should be performed as a priority rather than waiting
HM can have significant deleterious effects on the kidneys, for analysis of ionised calcium (if not readily available
due to altered renal blood flow and mineralisation. The in the practice), and PTH and PTHrP, as HM is a more
distal tubules become less responsive to antidiuretic likely differential in these cases. Also, analysis of PTH
hormone (ADH), leading to polyuria and polydipsia (PUPD). and PTHrP takes time, which may be of major clinical
Dogs with HM are far more frequently azotaemic than significance, particularly in lymphoma patients where
those with primary hyperparathyroidism. time is of the essence.
PUPD is one of the most overt and important clinical Therapy for HM should be focused on re-establishing
indicators of hypercalcaemia. Other common signs of normal calcium levels and treating the underlying
hypercalcaemia include inappetence or anorexia, weight malignancy.
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Companion Animals
Treating hypercalcaemia due to lymphoma or
aggressive lymphoid cancers
The majority of animals that require acute or emergency
treatment of HM, including those that are feeling unwell,
typically have a lymphoproliferative disease, such as
lymphoma (almost always T-cell) or leukaemia. Animals
with azotaemia, significant clinical illness related to their
hypercalcaemia, or those with a marked increase in calcium
should be hospitalised and treated with aggressive fluid
diuresis (eg, three times the maintenance levels, unless
there are contraindications), preferably using a calcium-free
intravenous fluid such as 0.9 per cent saline, but Hartmann’s
solution is also acceptable. Salmon calcitonin injections can
be useful and the author has found this very useful for helping
to reduce serum calcium levels in lymphoma patients in the
short term. Furosemide can be used to promote calciuresis
once hydration is re-established, but this is probably
best avoided for the initial 12 to 24 hours. Prednisone will
decrease serum calcium, but should be reserved for cases
in which the diagnosis has been established, to avoid
masking the diagnosis and potentially reducing the efficacy
of future chemotherapy. Induction chemotherapy should
be started as soon as a diagnosis is achieved, which is why
ill patients with hypercalcaemia should be diagnostically
evaluated as soon as possible.
Treating hyperglycaemia due to anal sac apocrine
gland carcinoma or other solid tumours
Patients with hyperglycaemia associated with anal sac
apocrine gland carcinomas or other solid tumours tend to
be less of an emergency and, in the author’s experience,
are often clinically well, unless very advanced or metastatic
disease is present. These patients can therefore typically
be managed as outpatients, unless their clinical status
dictates otherwise. As with other cases of HM, treatment
of the underlying cause is the initial treatment of choice.
This may involve, for example, surgical removal of the
primary perianal mass and any metastatic sublumbar
lymph nodes. Masses that are surgically excisable should
be removed and this may reverse the HM. Recurrence
of HM typically signifies a return of the tumour and/or
metastasis. A significant number of dogs with anal sac
carcinoma have metastatic lymph nodes (usually medial
iliac) at initial presentation, and these should be evaluated
before surgical removal of the primary tumour, otherwise
there may not be restoration of normocalcaemia.
In some cases where owners decline surgery or the
disease is too advanced or inoperable, medical therapy
of HM may be required, either as the sole therapy or in
addition to palliative anti-cancer therapy. This can still
be successful for a meaningful period in patients with
anal sac carcinoma as, in many cases, the tumour itself
progresses slowly. In this context, the author’s first line
treatment of HM is prednisolone, and this appears to
be safe in conjunction with chemotherapy or tyrosine
kinase inhibitors. Doses typically start at 1 to 2 mg/
kg (or 20 to 40 mg/m2, depending on the size of dog and
the severity of corticosteroid adverse effects), reducing
to the lowest effective dose as maintenance. Doses may
need to be periodically increased as the tumour may
secrete more PTHrP or other HM-promoting factors as it
progresses. In cases that are corticosteroid-refractory,
that require steroid-sparing measures or are intolerant
to corticosteroids, then the author has had some success
with the bisphosphonate pamidronate (Aredia; Ciba) at a
dose of 1 to 2 mg/kg, administered intravenously in 0.9
per cent saline (not calcium-containing fluids) over two
hours every two to three weeks. Zoledronate may also be
444 In Practice  October 2014 | Volume 36 | 443-452
Elliott .indd 444
used. While oral bisphosphonates are available, they have
a very low oral bioavailability and are significantly less
potent. They can also cause more gastrointestinal upset
(eg, oesophagitis). However, they may be worth trying in
cases where alternatives are not possible for financial or
logistical reasons.
Ultimately, effective treatment of the underlying
malignancy is essential for sustained resolution of HM.
Hypoglycaemia
Hypoglycaemia, particularly severe and symptomatic, is
most commonly associated with insulinoma. However,
it can also occur secondary to intestinal smooth-muscle
tumours, hepatocellular carcinoma and lymphoma.
Tumour production of insulin, insulin-like growth factor
1 (IGF1) and insulin-like growth factor 2 (IGF2), and
somatomedins have all been implicated. In addition,
upregulation of insulin receptors, decreased glycogenolysis
or gluconeogenesis, excess tumour utilisation of glucose,
and binding of insulin by M proteins in myeloma may
contribute to paraneoplastic hypoglycaemia.
Ideally, hypoglycaemia is treated via surgical removal of
the neoplasm; however, management before surgery may
be necessary. In an emergency situation, intravenous
glucose products may be required, but only in a strictly
controlled hospitalised environment as there is a possible
risk of rebound hypoglycaemia, particularly in insulinoma,
where intravenous glucose can stimulate a surge of insulin
release (Fig 1). If emergency management is needed at
home, owners can apply honey or Glucogel to their pet’s
gums and then follow this with solid food containing
complex carbohydrates. In insulinoma cases, resolution
of hypoglycaemia for a period of time is the norm with
surgery, but it invariably recurs. When insulinomas are
unresectable or the tumour recurs, medical management
of hypoglycaemia with dietary and pharmacological
intervention (eg, prednisone, diazoxide or glucagon) may
reduce the severity of clinical signs.
Ectopic adrenocorticotropic hormone
syndrome
Although reported with a number of malignancies in
people, ectopic production of adrenocorticotropic hormone
(ACTH) is extremely rare in animals. It has been reported
in patients with an abdominal neuroendocrine tumour,
hepatic carcinoid tumours, and in dogs with primary lung
tumours, but it has not, to the author’s knowledge, been
reported in cats. Clinical signs can resolve with surgical
removal of the primary tumour.
Syndrome of inappropriate ADH secretion
Syndrome of inappropriate ADH secretion (SIADH) is
characterised by hyponatraemia, serum hypo-osmolality,
and urine hyper-osmolality in the absence of renal or
adrenal dysfunction. Although widely recognised in
humans, it has not been reported in animals. Symptoms in
people relate to the effects of hyponatraemia on the CNS.
Drug-related SIADH can also occur.
Hyperoestrogenism
The most common neoplastic cause of hyperoestrogenism
is the presence of a Sertoli cell tumour. As well as a 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.
Hyperoestrogenism results in bone marrow suppression
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Fig 1: Intravenous glucose products may be required in the treatment of hypoglycaemia
associated with a tumour. These should only be given in a strictly controlled hospital
environment, as there is a risk of rebound hypoglycaemia
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. Effective treatment
relies on surgical excision of the tumour. Preoperative
supportive care of animals with pancytopenia should
include administration of broad-spectrum antibiotics for
neutropenia and blood or red cell transfusions as required.
There is a significant surgical risk due to bleeding diathesis
and anaemia. Once surgically removed, bone marrow
may take weeks to months to recover. In the author’s
experience, clinical recovery from severe pancytopenia is
rare and the prognosis is very poor.
Haematological paraneoplastic
syndromes
Anaemia
Anaemia is one of the most common PNSs in dogs and cats,
occurring with a wide variety of tumours and mechanisms,
such as blood loss and haemolysis.
For blood-loss anaemia to be considered paraneoplastic,
it must occur distant from the primary tumour. Examples
include blood loss due to gastrointestinal ulceration that
occurs with mast cell tumours (due to histamine release)
and gastrinomas (due to gastrin secretion). This type of
anaemia is usually regenerative early in the course of the
disease, but later becomes non-regenerative, microcytic,
and hypochromic due to iron-deficiency. Treatment is
by eradication of the primary tumour and supportive
measures, including gastrointestinal protectants.
Bone marrow infiltration and myelophthisis (eg, with
lymphoma, leukaemia, myeloma and histiocytic sarcoma)
can lead to decreased red blood cell production and
resultant anaemia, but some clinicians do not consider this
truly paraneoplastic. However, cytopenias are not just the
result of ‘over-crowding’ of normal haematopoietic tissue,
and neoplastic cells can release cytokines which suppress
myelopoiesis.
Elliott .indd 447
Companion Animals
Anaemia of chronic disease (ACD) occurs with many
different neoplastic diseases. It is typically very mild, and
is characterised as normocytic, normochromic and non-
regenerative. The exact cause is unknown, but it may be
partly due to abnormal iron metabolism. Resolution can
be anticipated once the primary tumour is addressed,
although ACD may persist if aggressive treatment such as
chemotherapy is undertaken.
Immune-mediated haemolytic anaemia (IMHA) can occur
as a PNS associated with haematopoietic and (rarely)
solid tumours. It is a secondary IMHA, in which antibodies
directed against tumour-associated antigens cross-react
with erythrocytes. The anaemia can be acute or chronic,
mild or severe. Clinical signs include lethargy, weakness,
tachycardia, pallor, icterus, hepatosplenomegaly,
haemoglobinuria and anorexia, depending on the severity
of the anaemia and how acutely haemolysis occurs.
Diagnostic tests may include identification of spherocytes
(Fig 2), other signs of haemolysis, or a positive Coombs’
test. Drugs used in the treatment of primary IMHA,
including corticosteroids, azathioprine, ciclosporin,
mycophenolate, intravenous γ-globulin and liposome-
encapsulated clodronate, have not been fully assessed for
their value in treating secondary IMHA. Optimal therapy
requires elimination of the underlying malignancy as the
most important factor, although specific treatment with
one or more of the above agents may be necessary.
Microangiopathic haemolytic anaemia is 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.
Thrombocytopenia
Thrombocytopenia occurs as a PNS with a wide range of
tumours, most commonly lymphoma, HSA and melanoma.
Mechanisms include increased platelet utilisation, platelet
destruction, or decreased platelet production. Platelet
counts are significantly lower in dogs with HSA that present
with a splenic mass and haemoabdomen, compared to
dogs with non-HSA. As with anaemia, immune-mediated
destruction of platelets can be seen with lymphoma or
multiple myeloma, and decreased platelet production can
occur secondary to myelophthisis induced by marrow-
infiltrating malignancies. Clinical signs are typically not
evident until platelet counts decrease below 30 x 10 9/litre,
when findings may include petechiation and haemorrhage.
Interestingly, however, with severe thrombocytopenia in
canine lymphoma patients, spontaneous haemorrhage
appears to be unusual. Treatment varies depending
upon the severity of the thrombocytopenia and the
underlying cause, although resolution of the primary
tumour is the ideal outcome. Fresh whole blood may be
indicated before surgery, or red cell transfusion may be
required if secondary significant anaemia has ensued. In
the case of immune-mediated thrombocytopenia (ITP),
immunosuppressive drugs may be required along with
chemotherapy to treat the tumour.
Erythrocytosis
Erythrocytosis (or polycythaemia) is an uncommon PNS
that is 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),
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Companion Animals
Fig 2: Identification of spherocytes can be used as a diagnostic test of immune-mediated
haemolytic anaemia
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.
Clinical findings include erythema of the mucous
membranes, polydipsia, and neurologic signs such
as disorientation, ataxia, and seizures secondary to
hyperviscosity or hypervolaemia. Polycythaemia is readily
apparent on haematology. Subsequent diagnostics include
chemistry profile, thoracic radiographs and abdominal
ultrasound, arterial blood gas, echocardiography and
possibly measurement of serum EPO concentrations. As
primary and secondary polycythaemias are principally
classified based on EPO levels, it would appear that
measurement of serum EPO concentration may be helpful,
but only an increased EPO value is helpful clinically.
Although an increased serum EPO level is diagnostic
for secondary polycythaemia, a low or normal serum
EPO value can also be found in animals with secondary
polycythaemia. Contrary to popular belief, examination of
bone marrow aspirates and core biopsy cannot distinguish
causes of primary and secondary polycythaemia, and
hence is generally not helpful. In either case, erythroid
hyperplasia with complete maturation is observed.
The presence of a renal mass with concurrent
erythrocytosis is, in the author’s opinion, sufficient
evidence of paraneoplastic polycythaemia, such that
additional diagnostics are rarely necessary, other than
staging of the tumour. Nephrectomy is generally effective
in resolving paraneoplastic polycythaemia related to renal
neoplasia, provided that metastasis has not yet occurred,
although medical management may be required initially.
For other aetiologies, hydroxyurea, phlebotomy and
treatment of the underlying cause are the cornerstones of
therapy.
Neutrophilic leukocytosis
An increase in the number of mature neutrophils in the
absence of infection or leukaemia and has been reported
in various histologies. The underlying aetiology is tumour
448 In Practice  October 2014 | Volume 36 | 443-452
Elliott .indd 448
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.
Eosinophilia
Paraneoplastic eosinophilia is a 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.
Thrombocytosis
Thrombocytosis may be an incidental finding in dogs
and cats with neoplastic disease, but it is rarely of
clinical concern, and the aetiology is unknown. Although
thrombocytosis theoretically puts animals at risk of
thrombotic events, these appear to be extremely rare. The
diagnosis is one of exclusion, once other causes have been
excluded. Treatment is generally not necessary, although
resolution of the underlying malignancy can be expected to
cause a normalisation of the platelet count.
Platelet hyperactivity and
hypercoagulability
Changes in platelet function have been demonstrated in
dogs with cancer. 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.
Disseminated intravascular coagulation
DIC is a clinical alteration of coagulation frequently seen
in dogs and cats with cancer. The cancers most often
implicated are HSA, mammary carcinoma and lung
carcinoma, but various others have been implicated.
Interestingly, the incidence of DIC in dogs with
haematopoietic malignancies appears to be less than that
seen in people, with DIC predominating in solid canine
malignancies. Animals with paraneoplastic DIC have a
poor prognosis, unless the underlying tumour can be
completely eradicated.
Hyperglobulinaemia
Hyperglobulinaemia occurs 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. Production of normal immunoglobulins
may be inhibited, leading to infections (so called ‘immune
cripples’). Other significant clinical sequelae may include
hyperviscosity syndrome and associated hypertension
and tissue hypoxia. Related clinical findings, such as
cardiomegaly, renal failure, ocular disorders including
retinopathies and papilloedema, and various neurologic
abnormalities may develop, and these are the primary
concern of owners. Bleeding tendencies are also common
with hyperglobulinaemia and relate to decreased
adhesion of platelets to damaged endothelial surfaces,
coating of platelets with immunoglobulins, and release
of platelet factor 3. Confirmation of paraneoplastic
hyperglobulinaemia is via serum or urine electrophoresis,
where a monoclonal gammopathy indicates a likely
neoplastic cause and a polyclonal gammopathy indicates
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a likely infectious or inflammatory cause. Successful
treatment relies on resolution of the underlying tumour,
usually with chemotherapy in the case of myeloma or
lymphoma. Plasmapheresis may be necessary for patients
with serum hyperviscosity.
Cutaneous paraneoplastic syndromes
Feline paraneoplastic alopecia
A unique PNS of alopecia occurs in 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.
Superficial necrolytic dermatitis
Superficial necrolytic dermatitis (SND) is a rare PNS
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. There
are reported classical histological findings. Although not
entirely understood, plasma amino acid concentrations
are typically markedly decreased in affected dogs. Dogs
and cats with paraneoplastic SND have a guarded to poor
prognosis, depending on the severity of their underlying
neoplastic disease. Surgical removal of pancreatic
tumours has been associated with resolution of SND, as
has administration of somatostatin analogues.
Nodular dermatofibrosis
Nodular dermatofibrosis is a rare cutaneous PNS
affecting dogs, typically German shepherd dogs, that have
bilateral renal cystadenocarcinoma. The genetic mutation
associated with this disorder has been mapped to exon
7 of the Birt-Hogg-Dubé locus of canine chromosome 5.
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.
Gastrointestinal paraneoplastic
syndromes
Cancer cachexia
Cancer cachexia is a complex syndrome that includes
weight loss and loss of lean body mass with or without
anorexia. It is not very common in veterinary practice
and, indeed canine cancer patients are more likely to be
overweight than cachectic; however, cats may be more
Elliott .indd 451
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affected. Cancer cachexia appears to be more often
associated with lymphoma than with solid tumours in dogs
and cats.
Metabolic alterations are complex with altered cytokine
profiles, hyperlactataemia, and changes in responsiveness
to insulin. Clinical signs include weight loss, reduced fat
mass, and muscle wasting, often despite a good appetite.
In addition to treatment of the underlying malignancy,
aggressive nutritional support is necessary, via an enteral
route if possible. Attention should be paid to conditions
related to the primary tumour or its treatment which
may affect food intake. In truly cachectic cancer patients,
foods high in fat (including polyunsaturated omega-3 fatty
acids) and low in carbohydrates have been recommended,
although dietary modification must be tailored to each
individual cancer patient.
Gastrointestinal ulceration
Paraneoplastic gastrointestinal ulceration 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.
Neurological paraneoplastic
syndromes
Myasthenia gravis
Myasthenia gravis (MG) is an uncommon PNS that 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. Diagnosis is aided by
detection of circulating auto-antibodies against the AchR
or by the edrophonium (tensilon) test and electromyography
with repetitive nerve stimulation. Anticholinesterase
agents such as pyridostigmine bromide may improve
signs of muscle weakness. Use of immunosuppressive
agents such as prednisone is controversial, and may
be contraindicated if aspiration pneumonia is present.
Elevating food and water bowls may decrease the risk
of aspiration with megaoesophagus. When feasible,
resection of the primary tumour is recommended and
may eliminate clinical signs. However, owners must be
forewarned that MG may not resolve and may require
specific therapy longer term.
Peripheral neuropathy
Peripheral neuropathy is associated with several tumour
types in dogs, including 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.
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Renal paraneoplastic syndromes
Glomerulonephritis and nephropathy
Glomerular disorders 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.
Other paraneoplastic syndromes
Hypertrophic osteopathy
Hypertrophic osteopathy (HO) is a well-characterised PNS
that is 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. Resolution of signs in some
patients following vagotomy supports this hypothesis.
Presenting complaints include shifting leg lameness or
reluctance to move, and affected limbs are typically warm
and can be oedematous. Radiographs of the affected limbs
452 In Practice October 2014 | Volume 36 | 443-452
Elliott .indd 452
reveal a characteristic periosteal reaction. Successful
treatment of the primary mass should lead to resolution
of HO. When this is not feasible, pain management with
anti-infl ammatory doses of steroids or NSAIDs is advised.
Vagotomy may lead to resolution of HO, but is not commonly
employed in the management of HO in dogs, because of the
poor prognosis associated with an unresectable primary
tumour.
Fever
True paraneoplastic fever occurs secondary to release of
pyrogenic cytokines, either by the tumour or by the host
immune response to the tumour, which act as endogenous
pyrogens on the thermoregulatory centre of the anterior
hypothalamus. Therapy is dependent upon the underlying
cause of the fever, although symptomatic therapy with
NSAIDs or paracetamol may provide some palliation if the
underlying cancer cannot be eliminated.
Conclusion
Ultimately, the recognition of PNSs may lead to the more
timely diagnosis and treatment of neoplastic disorders
and may help optimise therapy. An understanding of the
aetiology and pathogenesis of these disorders can lead to
an improved patient approach and better care of the whole
patient.
Further reading
BERGMAN, P. (2013) Paraneoplastic syndromes. In Withrow &
MacEwen’s Small Animal Clinical Oncology. 5th edn. pp 83-92
HENRY, C. (2010) Paraneoplastic syndromes. In Textbook of
Veterinary Internal Medicine. 7th edn, vol 2. pp 2213-2218
02/10/2014 16:38
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Paraneoplastic syndromes in dogs and cats

James Elliott

In Practice 2014 36: 443-452

doi: 10.1136/inp.g5826

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