ONCOLOGY - Paraneoplastic Syndromes Flashcards
What are the three clinical presentations of neoplasia?
Superficial mass
Non-specific clinical signs
Paraneoplastic syndrome
Make sure to review your second year notes on the approach to superficial masses
Which dog breeds are predisposed to osteosarcomas?
Great Dane
Deerhound
Lurcher
Rottweiler
Typically giant/large breed dogs
Which dog breeds are predisposed to histiocytic sarcomas?
Bernese Mountain Dogs
Flat coated Retrievers
Rottweilers
Miniture Schnauzers
Which dog breeds are predisposed to lymphoma?
Boxers
Golden Retriever
Labrador
Mastiffs
Which dog breeds are predisposed to mast cell tumours?
Boxers
Pugs
Shar Pei
Weimaraner
Which dog breed is predisposed to bladder transitional cell carcinoma?
Scottish Terrier
Which dog breeds are predisposed to gliomas?
Boxer
French Bulldog
Boston Terrier
Typically seen in brachycephalic breeds
Which dog breeds are predisposed to melangiomas?
Golden Retrievers
Which dog breeds are predisposed to nasal tumours?
Labradors
Golden Retrievers
Flat-coated Retrievers
Collies
Which dog breeds are predisposed to haemangiosarcomas?
German Shepherds
Golden Retriever
Which dog breeds are predisposed to anal sac tumours?
Springer Spaniels
Cocker Spaniels
What is paraneoplastic syndrome?
Paraneoplastic syndrome is the systemic, metabolic and endocrine effects that can be associated with some types of neoplasia
What are the endocrine diseases which result from neoplasia and thus paraneoplastic syndrome?
Hyperthyroidism
Hyperadrenocorticism
Acromegaly
What are some of the other paraneoplastic syndromes seen in small animals?
Hypercalcaemia
Hyperhistaminaemia
Hypoglycaemia
Hyperoestrogenaemia
Hypergastrinaemia (very rare)
Cachexia
Immune-mediated disorders
Hyperviscosity syndrome
Hypertrophic oesteopathy
Dermatological changes (very rare)
What is the most common form of paraneoplastic syndrome?
Hypercalcaemia
What are the three forms of serum calcium?
Ionised calcium
Protein-bound calcium
Complexed calcium
(T/F) Serum calcium levels can be influenced by serum protein levels
TRUE. Serum calcium levels can be influenced by serum protein levels as serum calcium is approximately 50% plasma protein bound
Which three hormones are involved in calcium homeostasis?
Parathyroid hormone (PTH)
1,25 vitamin D3 (calcitriol)
Calcitonin
Describe the process of calcium homeostasis when there is hypocalcaemia
In response to hypocalcaemia, the parathyroid gland will release parathyroid hormone which will act on the kidneys to reabsorb calcium and produce calcitriol which increases calcium absorption by the gastrointestinal tract. Parathyroid hormone also stimulates osteoclasts to mobilise calcium in the bone
Describe the process of calcium homeostasis when there is hypercalcaemia
In response to hypercalcaemia, calcitonin is released from the thyroid gland and acts on the osteoblasts to stimulate calcium storage in the bone, inhibits renal reabsorption of calcium which increases renal excretion of calcium and inhibits calcium absorption in the gastrointestinal tract
When is a patient classfied as hypercalcaemic?
If the total serum calcium is more than 3mmol/l and the ionised calcium is more than 1.4mmol/l, the patient is hypercalcaemic
What are the differential diagnoses for hypercalcaemia?
Neoplasia
Hyperparathyroidism (caused by parathyroid adenoma)
Hypoadrenocorticism
Severe renal failure
Hypervitaminosis D
Feline leukaemia virus (FeLV)
Granulomatous inflammation
Idiopathic hypercalcaemia
Laboratory error
Young animal
What is hypervitamindiosis D?
Hypervitamindiosis D is a toxic state of excess vitamin D within the body
What can cause hypervitamindiosis D?
Nightshade plants
Topical creams
Rodenticides
Which species can get idiopathic hypercalcaemia?
Cats
How do you diagnose idiopathic hypercalcaemia in cats?
Idiopathic hypercalcaemia in cats is a diagnosis of exclusion
How do you manage idiopathic hypercalcaemia in cats?
Dietary modification
Prednisolone
What is the most common differential diagnosis for hypercalcaemia?
Neoplasia
How can neoplasia can hypercalcaemia?
Tumours can secrete parathyroid hormone (PTH)
Tumours can secrete parathyroid hormone related peptide (PTHrP)
Cytokines
Which cytokines can stimulate hypercalcaemia?
IL-1
IL-6
TNF
Which neoplasms can cause hypercalcaemia?
Lymphoma
Leukaemia
Anal sac adenocarcinoma
Bone tumours
Multiple myeloma
Parathyroid adenoma (causes hyperparathyroidism)
How does lymphoma cause hypercalcaemia?
Lymphoma releases parathyroid hormone related peptide (PTHrP)
How does anal sac adenocarcinoma cause hypercalcaemia?
Anal sac adenocarcinoma releases parathyroid hormone related peptide (PTHrP)
How do bone tumours cause hypercalcaemia?
Bone tumours cause disruption of and breakdown of bone which results in excess mobilisation of calcium
How does multiple myeloma cause hypercalcaemia?
Multiple myeloma releases parathyroid hormone related peptide (PTHrP)
What are the clinical signs of hypercalcaemia?
PUPD
Anorexia
Vomiting
Constipation
Muscle weakness
Tremors
Lethargy
Hypovolaemia
Bradycardia
How should you approach the investigation of causes of hypercalcaemia?
Determine if it is a true hypercalcaemia
Rule out non-neoplastic causes of hypercalcaemia
Investigate for neoplasia
How can you determine if a patient is presenting with a true hypercalcaemia?
Patients presenting clinical signs are much more likely to have a true hypercalcaemia, however sometimes hypercalcaemia can be detected on hypercalcaemia without clinical signs and thus it is important to determine if this is a true hypercalcaemia. Repeat the bloods to rule out laboratory error, check the ionised calcium levels as well as the total serum calcium levels and assess the age of the patient - if they are young and growing, this could account for the hypercalcaemia
How can you rule out non-neoplastic causes of hypercalcaemia?
History
Clinical examination
Haematology and biochemistry
Urinalysis
ACTH stimulation test
Test FeLV in cats
How should you approach investigation of neoplastic causes of hypercalcaemia?
Clinical examination
Radiography
Ultrasound
FNA/biopsy
PTH and PTHrP assays
Bone marrow biopsy
Which factors should you play close attention too during a clinical exam to investigate neoplastic causes of hypercalcaemia?
Palpate lymph nodes
Rectal examination
Assess for lameness/bone pain
Assess for ocular changes (can be caused by multiple myeloma)
Palpate the parathyroid gland (very challenging so may require ultrasound)
What is the indicator for PTH and PTHrP assays?
PTH and PTHrP assays are indicated only if there is no obvious indicator of hypercalcaemia, as they are expensive tests to run and provide delayed results
How do you treat hypercalcaemia?
Intravenous fluid therapy
Diuretics
Bisphosphonates
Corticosteroids
Calcitonin
Treat underlying disease
What are the purposes of intravenous fluid therapy when managing hypercalcaemia?
Replace fluid deficits
Maintenance fluids
Replenish ongoing losses
Support the kidneys
Promote further calcium excretion
Correct potassium deficits
Which type of fluid should you use when treating hypercalcaemia?
0.9% NaCl at two or three times maintenance
Which diuretic should you use when treating hypercalcaemia?
Only use diuretics when the patient iss rehydrated
Frusemide
What are bisphosphonates?
Bisphosphantes prevent further loss of bone density by inhibiting osteoclast-mediated bone resorption
List three examples of biphosphonates
Pamidronate
Zoledronate
Oral alendronate (used in cats)
What should you be aware of when administering pamidronate?
Pamidronate is nephrotoxic and thus should be administered along side IV fluid therapy
When are corticosteroids indicated in the treatment of hypercalcaemia?
Corticosteroids are indicated when there is a definitive diagnosis of the cause of hypercalcaemia as corticosteroids have a cytotoxic effect on lymphoma and thus can obscure the diagnosis
What are the benefits of corticosteroids in the treatment of hypercalcaemia?
Decrease bone reabsoption
Decrease gastrointestinal absorption of calcium
Increase renal excretion of calcium
Cytotoxic to lymphoma
(T/F) Calcitonin can only be administered to hospitalised patients
TRUE. Calcitonin requires regular subcutaneous injections and thus can only be done in hospitalised patients
What are the differential diagnoses for hypoglycaemia?
Neoplasia
Insulin overdose
Hypoadrenocorticism
Severe hepatic failure
Xylitol toxicity
Inflammation
Infection
Laboratory error
What is the clinical presentation of hypoglycaemia?
Episodic collapse
Weakness
Hypoglycaemia on biochemistry
What are the neoplastic causes of hypoglycaemia?
Insulinoma
Hepatic neoplasia
What are the clinical signs of hyperoestrogenism?
Gynaecomastia
Bilateral symmetrical, non-pruritic, alopecia
Decreased libido
Pendulous prepuce
Attractive to other males
Hyperpigmentation of the skin/scrotum
Bone marrow hypoplasia (pancytopenia)
What is gynaecomastia?
Gynaecomastia is enlargement of the mammary chain
Which tumour causes hyperoestrogenism in male dogs?
Sertoli cell tumour (produces oestrogen)
What are sertoli cell tumours often associated with?
Sertolic cell tumours are often associated with retained testicles however they can be seen in normal testicles, with one often being much larger than the other due to atrophy of the non-neoplastic testicle
What is the most serious complication of sertoli cell tumours?
Sertoli cell tumours cause bone marrow suppression resulting in anaemia, thrombocytopenia and leukopenia
What is hypertrophic osteopathy?
Hypertrophic osteopathy is a diffuse periosteal proliferative condition of the long bones
Which tumours is hypertrophic osteopathy most commonly associated with?
Primary lung tumours or pulmonary metastases
Which immune-mediated syndromes can be seen as a result of neoplasia?
Immune-mediated neuropathies
Myasthenia gravis
Immune-mediated haemolytic anaemia (IMHA)
Immune-mediated thrombocytopenia (IMTP)
Which tumours can cause myasthenia gravis?
Thymomas can produce antibodies against acetylcholine receptors resulting in myasthenia gravis
What is hyperviscosity syndrome?
Hyperviscosity syndrome is where the blood is very thick and viscous
What are the main causes of hyperviscosity syndrome?
Polycythaemia
Excessive serum proteins
What are the two classifications of polycythaemia?
Polycythaemia vera (primary neoplasia)
Secondary polycythaemia
How can neoplasia cause excessive serum protein production and hyperviscosity syndrome?
B-lymphocyte/plasma cell tumours can cause excessive production of immunoglobulins resulting in hyperviscosity syndrome
What is tumour grading?
Tumour grading is the assessment of the degree of malignancy
Who carries out tumour grading?
Tumour grading is carried out by pathologists
Which factors are assessed by pathologists to determine tumour grading?
Cellular differentiation
Cellular pleomorphism
Mitotic index
Invasiveness
Necrosis
Inflammation
Overall cellularity
Stromal reaction
How should you treat low grade (grade I) tumours?
Low grade tumours have a low change of metastasis so local surgery should be sufficient treatment
How should you treat intermediate grade (grade II) tumours?
Intermediate grade tumours have an intermediate risk of local recurrence and metastasis so local surgery with or without chemotherapy should be sufficient treatment
How should you treat high grade (grade III) tumours?
High grade tumours have a high risk of local recurrence and metastasis, so require aggressive treatment and chemotherapy
What are soft tissue sarcomas?
Soft tissue sarcomas are a heterogenous group of tumours of different cell lineages but with similar histopathology
List the different soft tissue sarcomas in order of increasing malignancy and risk of metastasis
Haemangiopericytoma
Peripheral nerve sheath tumour
Fibrosarcoma
Myxosarcoma
Liposarcoma
Lymphangiosarcoma
Leiomyosarcoma
Synovial sarcoma
Histiocytic sarcoma
Haemangiosarcoma
Which specific factors are assessed when grading a soft tissue sarcoma?
Cellular differentiation
Mitotic index
Necrosis
Which specific factors are assessed when grading a dermal mast cell tumour?
Cellular differentiation
Cellular pleomorphism
Mitotic index
Invasiveness
Cellularity
Stromal reaction
What is the patnaik grading system for dermal mast cell tumours?
The patnaik grading system is a three tier grading system which classifies dermal mask cell tumours as low grade (grade I), intermediate grade (grade II) and high grade (grade III)
What are the features of a grade I dermal mast cell tumour using the Patnaik scheme?
Well differentiated mast cells
No tissue invasion
No mitotic figures
Minimal stromal reaction
What is the prognosis for a grade I dermal mast cell tumour using the Patnaik scheme?
Over 90% of patients with a grade I dermal mast cell tumour have a long lifespan
What are the features of a grade II dermal mast cell tumour using the Patnaik scheme?
Moderately differentiated cells
Pleomorphic cells
Some local tissue invasion
0 to 2 mitotic figures in a high power view
Some areas of oedema and necrosis
What is the prognosis for a grade II dermal mast cell tumour using the Patnaik scheme?
Variable prognosis
What are the features of a grade III dermal mast cell tumour using the Patnaik scheme?
Poorly differentiated cells
Binucleate/multinucleate cells
3 - 4 mitotic figures per high power view
Invasion into surrounding tissues
Haemorrhage
Oedema
Necrosis
What is the prognosis for a grade III dermal mast cell tumour using the Patnaik scheme?
Poor prognosis, survival of approximately 6 months
What is the kiupel grading scheme for dermal mast cell tumours?
The kiupel grading scheme is a two tier classification system with a low and high grade only
What is the criteria for a high grade dermal mast cell tumour using the kiupel scheme?
At least 7 mitotic figures in 10 high power views
At least 3 multinucleated cells in 10 high power views
At least 3 bizarre nuclei in 10 high power views
Karyomegaly
How should you grade dermal mast cell tumours?
Dermal mast cell tumours should be graded on both the patnaik and kiupel system
What is tumour staging?
Tumour staging is the assessment of the anatomical extent of the tumour within the body in terms of the primary site and any metastases
Who carries out tumour staging?
Tumour staging is carried out by clinicians
What are the purposes of tumour staging?
To determine the extent of treatment required
To help to determine prognosis
Provides a precise record of tumour extent at that period of time
Monitor how to tumour changes over time
What is the TNM classification system used for tumour staging?
The TNM system is a system used to descibe the extent and spread of neoplasia throughout the body. T describes the size and extent of the primary tumour; N describes the extend of the spread of neoplasia to nearby lymph nodes; and M describes metastasis
What do you use to determine the size of the primary tumour for tumour staging?
Calipers
Rulers
How do you determine the invasiveness of the primary tumour for tumour staging?
Assess the primary tumour for local invasion using palpation and diagnostic imaging such as radiography, ultrasound, CT and MRI
How should you investigate for neoplasia in nearby lymph nodes for tumour staging?
Palpate lymph nodes
Diagnostic imaging
Fine needle aspirate (FNA)
Biopsy
What is the best diagnostic imaging technique to visualise lymph nodes?
CT
What are sentinel lymph nodes?
Sentinel lymph nodes is a term used to describe the local lymph nodes most likely to drain the primary tumour and this the most likely to become neoplastic
What should you do if the sentinel lymph nodes are neoplastic?
If the sentinel lymph nodes are neoplastic, surgically remove the lymph node and begin more aggressive treatment
How should you investigate for external metastasis for tumour staging?
Clinical examination
How should you investigate for internal metastasis for tumour staging?
Diagnostic imaging such as endoscopy, radiography, ultrasound, CT and/or MRI
Which techniques can be used to confirm metastasis?
Fine needle aspirate (FNA)
Biopsy
What is the most useful technique for determining the prognosis for neoplasia?
Clinical staging
What is clinical staging?
Clinical staging groups tumours according to their likely prognosis using the TNM staging system and the clinical behaviour of the tumour type, grade and location
Which tumours have their own clinical staging systems?
Oral tumours
Lymphoma
Mast cell tumours
Thymomas
How do you clinically stage oral tumours?
Clinical stage I: Primary tumour is less than 2cm
Clinical stage II: Primary tumour is between 2-4cm
Clinical stage III: Primary tumour is over 4cm, or, there is lymph nodes metastasis
Clinical stage IV: There is metastasis
