Royal (Dick) School of Veterinary Studies, University of Edinburgh Hospital for Small Animals, Easter Bush Veterinary Centre
Roslin, Midlothian
The paraneoplastic syndromes represent a complex, diverse set of clinical syndromes resulting from systemic effects of benign, malignant or metastatic neoplasia.
Key points are as follows:
The effects are separate from the effects of invasion, compression or metastatic disease, occurring at sites distant from the tumour and affecting many end-target organs.
Paraneoplastic syndromes include hormonal, metabolic, biochemical, haematological and neurological disorders (Figure 1).
Paraneoplastic syndromes may occur as a result of immune-mediated activity, peptide, protein, ectopic or eutopic hormone secretion, protein hormone precursor or cytokine secretion by the tumour, production of enzymes which interfere with normal metabolic pathways, or by other as yet unspecified biochemical mechanisms.
The classification and detection of paraneoplastic syndromes in dogs and cats is important because they may have:
Diagnostic importance
Therapeutic importance
Prognostic importance
Quality-of-life issues
Clinical indicators
The clinical signs of important paraneoplastic syndromes are referable to the endocrine, haematological, neuromuscular, dermatological, musculoskeletal, renal, gastrointestinal and cardiovascular systems.
The causes of paraneoplastic syndromes are not well known; only a few cases have clearly demonstrated aetiological and pathogenetic factors.
Figure 1. Classification of canine and feline paraneoplastic syndromes.
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|
Paraneoplastic syndrome |
Common associations |
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Metabolic |
Fever |
Lymphomas, leukaemias, histiocytic disease, sarcomas, hepatic, renal, gut tumours and others |
|
Anorexia |
Many tumours |
|
Cachexia |
Many tumours |
|
Endocrine |
Hyperthyroidism |
<20% thyroid carcinomas, common with adenoma/adenomatous hyperplasia |
|
Hyperadrenocorticism |
Pituitary adenoma (dogs), adrenal carcinoma |
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Hypercalcaemia |
Lymphomas, anal gland adenocarcinoma, myeloma, mammary carcinoma, thyroid carcinoma, thymoma, other tumours |
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Acromegaly |
Pituitary adenoma (cats) |
|
Hypoglycaemia |
Insulinoma, hepatic and smooth muscle tumours, some haematopoietic tumours |
|
Feminisation syndrome |
Testicular tumours |
|
Hyperaldosteronism |
Rare |
|
Inappropriate secretion of antidiuretic hormone (ADH) |
Rare |
|
Diabetes insipidus (DI) |
Rarely paraneoplastic |
|
Haematological |
Anaemia |
Many tumours |
|
Erythrocytosis |
Renal and lung tumours, some hepatic tumours |
|
Thrombocytopenia |
Haematopoietic tumours, histiocytic disease, others |
|
Thrombocytosis |
Lung, mammary, gut, reproductive tumours |
|
Leucocytosis
--Neutrophilia
--Eosinophilia |
Lymphomas, lung, mammary, gut tumours Lymphomas, mast cell tumours, thymoma, lymphomatoid granulomatosis |
|
Bleeding diathesis/coagulopathy/ disseminated intravascular coagulation (DIC) |
Haematopoietic, epithelial and mesenchymal tumours, mast cell and histiocytic tumours |
|
Hyperoestrogenism |
Testicular and ovarian tumours |
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Hyperviscosity |
Myeloma, lymphomas, leukaemias |
|
Cutaneous |
Alopecia |
Feline pancreatic adenocarcinoma, biliary carcinoma |
|
Exfoliative dermatitis |
Thymoma (cats) |
|
Nodular dermatofibrosis |
Renal cystadenoma/cystadenocarcinoma (German Shepherd Dog) |
|
Superficial necrolytic dermatitis (rare) |
Glucagonoma, rare |
|
Flushing/erythema (unusual) |
Mast cell tumour, haemangiosarcoma, phaeochromocytoma |
|
Feminisation syndrome |
Testicular tumours |
|
Hypertrichosis |
Insulinoma |
|
Pemphigus complex |
Lymphoma, sarcomas |
|
Renal |
Renal protein loss |
Lymphomas, leukaemias, melanoma, lung, thyroid, gut, mammary, pancreatic tumours, others |
|
Glomerulonephritis, nephrotic syndrome |
Myeloma, lymphomas, leukaemias, polycythaemia vera, renal carcinoma |
|
Neuromuscular |
Myasthenia gravis |
Thymoma, osteosarcoma |
|
Peripheral neuropathy |
Insulinoma, others |
|
Musculoskeletal |
Hypertrophic osteopathy |
Primary lung and other intrathoracic tumours |
|
Polyarthropathy |
Lymphomas, leukaemias, histiocytic disease, gut, prostate and mesenchymal tumours |
|
Polymyositis |
Lymphomas, lung, stomach, breast, uterine tumours |
Investigation
All patients with suspected paraneoplastic disorder warrant comprehensive diagnostic investigation following an algorithm based on presentation and severity of clinical signs (Figure 2).
Figure 2. Investigation of suspected paraneoplastic disorders.
|
Investigation |
Comments |
Findings |
|
Signalment and history |
Species, breed and age |
Disease associations |
|
Duration and progression of signs |
Acute, chronic, insidious |
|
Clinical examination |
Demeanour and physical examination |
Constellation of signs, to rule in/out neoplasia |
|
Complete blood count (CBC), smear examination |
RBC parameters and morphology |
Anaemia of chronic disease, immune-mediated haemolytic anaemia, microangiopathic haemolytic anaemia, iron-deficiency anaemia, erythrocytosis, hyperoestrogenism |
|
WBC parameters and morphology |
Neutrophilia, eosinophilia--differentiate inflammation/infection/neoplasia |
|
Platelet count |
Thrombocytopenia, thrombocytosis, DIC |
|
Comprehensive chemistries |
Renal parameters, calcium, electrolytes, proteins, enzymes |
Hypercalcaemia, gammopathy, hypoglycaemia, renal protein loss, hyperadrenocorticism |
|
Coagulation profile |
Prothrombin time, activated partial thromboplastin time, kaolin cephalin clotting time, fibrinogen, AT-III, D-dimers |
DIC, hyperviscosity |
|
Urinalysis |
Specific gravity, sediment examination, quantify proteinuria with protein:creatinine ratio |
Renal protein loss, nephropathy |
|
Serum/urine/ cerebrospinal fluid (CSF) protein electrophoresis |
Monoclonal or polyclonal gammopathy, nephropathy, neuropathy |
|
|
Serum autoantibodies |
Acetylcholine receptor antibodies |
Myasthenia gravis |
|
Marrow examination |
Cytopenias |
|
|
CSF evaluation |
Neuropathy, pyrexia |
|
|
Imaging |
Survey, local and locoregional radiography, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography--abdomen, mediastinum, neck, masses |
Rule in/out neoplasia, localise primary tumour/metastatic disease |
|
Procedures |
Endoscopy procedures |
Rule in/out/localise neoplasia tissue sampling |
|
Cytology, histology |
Tissue biopsy |
Rule in/out neoplasia |
|
Fine needle aspiration |
Cytological diagnosis |
|
Core/wedge/incision/excision |
Histopathological diagnosis |
|
Exploratory surgery |
Laparotomy, thoracotomy, neck exploration, masses |
Histopathological diagnosis |
Treatment
There are two major management considerations:
Treatment depends on the specific paraneoplastic disorder, its severity and the underlying tumour:
Delay risks increased morbidity, reduced efficacy of specific anti-cancer therapy, treatment failure and death.
Paraneoplastic syndromes may resolve with therapy of the primary tumour.
Treatment of the underlying tumour includes: surgery, chemotherapy, radiotherapy or multimodality therapy as for patients without paraneoplastic syndrome.