Paraneoplastic + systematic effect of neoplasia Flashcards
What’s the difference between paraneoplastic syndromes and systemic effects of cancer?
- Paraneoplastic syndromes are a consequence of cancer but not due to the location of cancer cells
- Systemic effects are consequential to the location of the tumour cells
What is cancer cachexia + anorexia? CS? Tx?
- Anaerobic respiration due glucose utilisation and tumoural hypoxia = increased lactate production and altered insulin sensitivity
- Altered metabolism due cancer related cytokines and inflammation
- Poor appetite in some patients
- Clinical signs = Weight loss, reduced fat mass, lean muscle loss = poor treatment tolerance
- Treatment =
- Maintain / intake caloric intake giving low carbohydrate high fat diet
- Omega 3 PUFA may be beneficial in reducing inflammation related changes
What can GI tumours cause? What tumours can produce hormones that damage the GIT?
- GI tumours = gastric or dudodenal ulceration =
- Bleeding can lead to anaemia as a systemic effect.
- Melena or haematoemesis occasionally seen
- Risk of rupture
- Some tumours produce hormones / metabolites = gastric acid = ulceration - PNS
- Dogs with MCT have elevated blood histamine can = GI signs, ulceration and bleeding
- Gastrinoma’s produce gastrin = GI signs, ulceration and bleeding
- Some GI neuroendocrine tumours can cause GI bleeding presumably due to hormone / cytokine production
How does PLE occur? What tumour is it seen with?
- Systemic effect
- Diffuse GI lesions can allow protein loss =
- Typically low TP, globulin and albumin often accompanied by diarrhoea
- Low albumin = ascites
- Myriad of other effects due to loss of proteins binding hormones, clotting factors etc.
- Not specific for cancer but seen particularly with GI lymphoma
What are different mechanisms of haematological effects?
- Loss
- Reduced production
- Destruction
- Cytoses
- Mono-clonal gammopathies
- Coagulation disorders
What is seen with acute blood loss anaemia?
–if no haematemesis or melena more likely splenic than GI
–TP drops before PCV
–Signs of shock
What is seen with chronic blood loss anaemia?
- Main differentials are other GI or oral lesions
- Clinical signs of lethargy, pallor
- Poorly regenerative microcytic hypochromic anaemia due to iron deficiency
- Normal or elevated platelet count
What is reduced production cytopenias?
*Anaemia of chronic inflammatory disease
* Common
* Causes include cancer, but also many other diseases.
* Mild / moderate normochromic normocytic non-regenerative anaemia.
* Anaemia due to -
1. disordered iron storage
2. shortened RBC life span
What are 2 different causes of reduced production cytopenias?
- Myelophthisis =
1. Crowding out of stem cells in the bone marrow by tumour cells
2. Some tumours produce suppressive cytokines - - Tumour types include lymphoma, leukaemias, multiple myeloma, rarely histiocytic sarcoma and mast cell tumour
- One or several cytopenias
- Neutropenia then thrombocytopenia before anaemia
- Non-regenerative normochromic normocytic anaemia
- Diagnosis by bone marrow aspirate
- Hyperoestrogenism =
- testicular tumours - 50% of dogs with Sertoli cell tumours
- Neutrophilia progressing to pancytopenia due to bone marrow hypoplasia
- Other signs are feminisation signs and include symmetrical alopecia, pendulous prepuce, hyperpigmentation, penile atrophy, gynecomastia, prostatic metaplasia
- Castration can reverse many signs but bone marrow changes can be slow to recover or irreversible
What are destruction cytopenias?
*Paraneoplastic immune mediated anaemia and thrombocytopenia
* Secondary to lymphoproliferative tumours and occasionally other tumours
* Must exclude lymphoproliferative disease before treating IMHA or IMTP
* Therapy targeted at tumour will speed resolution of signs
What is a cause of destruction cytopenia?
- Microangiopathic anaemia =
- Systemic effect
- Fragmentation and shearing of RBCs leads to anaemia
- Caused by fibrin networks
- Schistocytosis is a key indicator
What conditions are associated with schistocytosis?
- Disseminated intravascular coagulation
- Haemangiosarcoma
- IMHA
- Metastatic carcinoma
- Microangiopathic anaemia
What is paraneoplastic cytoses?
- Non-specific for cancer or any other diagnosis
- Erythrocytosis =
- Renal tumours via increased EPO, lymphoma, nasal fibrosarcoma, TVT, hepatic tumours
- Clinically significant erythrocytoses include PU/PD, neurological signs and seizures
- Treatment = phlebotomy, removal of inciting cause, hydroxyurea
- Neutrophilia =
- Seen in association with many tumours
- Can be tumour induced or an immune response to the tumour
- Eosinophilia =
- Thought to be due to IL-5 production
- Most commonly associated with T cell lymphoma and MCT
What is mono-clonal gammopathies? CS? Dx? Tx?
- Excess production of a single immunoglobulin (antibody) by tumour cells
- Elevated serum globulins on biochemistry
- Clinical signs due to hyperviscosity (neurological including seizures and coma and cardiac signs), reduced immune function, renal failure, coagulopathies and ocular disorders.
- Dx = Gammopathies detected by electrophoresis of serum and urine (Bence-Jones proteins)
- Treatment by plasmapheresis and tumour directed treatment
What can cause altered coagulation?
- Altered platelet function often seen in association with neoplasia
- Infarcts / thromboembolism can result
** Disseminated intravascular coagulation **
* Syndrome of altered consumptive coagulation
* Thromboembolism in small vessels and bleeding due to consumption of platelets and clotting factors
* Multi-organ failure and death
* Elevated APTT, PT, FDPs / D dimers, low fibrinogen, low platelet count, schistocytes
* Mainly in association with carcinoma and HSA
What tumour is associated with monoclonal gammopathies?
- Myeloma
- Leukaemia
- Lymphoma
What is seen with endocrine problems from tumours?
- Hypercalcaemia
- Hypoglycaemia
- Ectopic ACTH syndrome
- Hyperestrogenism
What can cause hypercalcaemia? Ddx?
- PNS is the cause of 2/3 canine hypercalcaemia and 1/3 feline hypercalcaemia
- Various mechanisms =
- Elevated PTH or PTH related peptide
- IL-1-beta, TGF-beta, RANKL
- Bone lysis
- Ddx = lab error, renal failure, hypervitaminosis D, hypoadenocorticism, granulomatous disease
What are CS of hypercalcaemia?
- PU/PD
- Dehydration
- GI signs – inappetence and vomiting
- Weakness
- Muscle fasiculations
- Calcification of soft tissues (especially kidneys) Ca x P >5
- Arrythmias
- Death
How wound you manage hypercalcaemia?
EMERGENCY
* Initially = Rehydrate with NaCl 0.9% - 3 - 4 x maintenance – also enhances calciuresis
* Then =
- continue fluids
- consider furosemide – increases calciuresis by increase Na loss – moderate effect
- consider bisphosphonates – toxic to osteoclasts therefore slows Ca release from bone
- consider salmon calcitonin – short acting (a few days) but often effective
- consider prednisolone – only when lymphoproliferative disease diagnosed or excluded
** Removal of inciting lesion – only effective long term treatment **
Hypoglycaemia is a PNS seen due to what? non neoplastic Ddx?
- Insulinoma
- Also reported with hepatocellular carcinoma, smooth muscle tumours
- caused by insulin, IFG 1 or 2
- Clinical signs include weakness, disorientation, seizures, coma and death
- Management =
- Emergency – IV glucose + CRI glucose if necessary
- Medical management – prednisolone, diazoxide, octreotide
- Removal of inciting tumour
- Non-neoplastic ddx = sepsis, starvation, liver dysfunction, hypoadrenocorticism, lab error, some toxicities
What is ectopic ACTH syndrome? Dx? Management?
- Rare
- Reported in association with lung tumours
- Clinical signs similar to hyperadrenocorticism
- Dx =
- Positive for hyperadrenocorticism tests
- localisable tumour
- No signs of adrenal associated hyperadrenocorticism
- Management = Excision of primary lesion
What are paraneoplastic syndromes associated with the nervous system?
- Myaesthenia Gravis - secondary immune mediated disease
- Peripheral neuropathy
What are CS of myaesthenia gravis? Dx? Tx?
- CS = Weakness, Exercise intolerance, Dysphagia, Megaoesphagus and regurgitation
- Presumptive diagnosis – +ve ACHr antibodies and a relevant tumour
- Most commonly seen with thymoma
- Also reported wt osteosarcoma and lymphoma
- Tx = remove tumour and consider immunosuppression, manage other problems
What is peripheral neuropathy? tumour causes? Tx?
- Demyelination, myelin globulation and axonal degeneration noted on histology from patients with a variety of malignancies.
- A wide range of tumour types have been reported in association with such findings including:
- lung tumours, insulinoma, lymphoma, MCT, thyroid adenocarcinoma, melanoma
- Mild to moderate and symmetrical – vague signs such as weakness.
- Treatment is removal of inciting tumour
What are examples of cutaneous paraneoplastic syndrome?
- Alopecia and Malassezzia associated dermatitis
- Pancreatic associated panniculitis
- Superficial necrolytic dermatitis (SND)
- Paraneoplastic immune mediated disease – Pemphigus and Erythema multiforme
- Feline Thymoma-Associated Exfoliative Dermatitis (FTAED)
- Cutaneous flushing
- Nodular dermatofibrosis
What is seen with feline paraneoplastic alopecia?
- Alopecia
- Glistening skin
- Footpad lesion
- Malassezia dermatitis
What are Ddx for feline paraneoplastic alopecia?
- DDx =
-dermatophytosis - demodicosis
- SIA (pruritus, psychogenic)
- telogen
- defluxion
- endocrinopathies
- SND (superficial necrolytic dermatitis)
What is pancreatic panniculitis?
- Inflammation and hydrolysis of adipose tissue
- No age, breed or sex predilection
- Pancreatitis and pancreatic carcinoma and adenocarcinoma
- Pancreatic enzymes (lipase, amylase, trypsin)
What is superficial necrolytic dermatitis?
- Aka necrolytic migratory erythema, hepatocutaneous syndrome
- Dogs and cats
- Hepatic disease and pancreatic neoplasia
- Associated amino acid deficiency
- Distinctive histo and U/S
CS of SND?
- Footpad hyperkeratosis
- Crusting dermatitis
- Early stages none
- Lethargy
- Inappetance
- Systemic signs associated with hepatic / pancreatic disease or rarely glucagonoma
- Some cases develop diabetes mellitus in association with hepatic disease
What is paraneoplastic pemphigus? Aetiopathogenesis?
- Very rare cutaneous PNS
- Autoimmune-induced ulceration of the mucosae and mucocutaneous junctions
- Aetiopathogenesis =
- Lymphoma, thymoma, splenic sarcoma, metastatic thymic mass
- Primary immune mediated pemphigus also seen
- exact pathomechanism unknown
- antibodies against tumour antigens cross-react with self-antigens
What are cutaneous markers of paraneoplastic pemphigus?
- Oral and mucocutaneous ulceration =
– vesicles (rapidly rupture)
– severe ulceration of oral cavity and mucocutaneous junctions
– lesions often bilaterally symmetrical
– clawbeds and pressure points may be affected
What is feline thymoma-associated exfoliative dermatitis?
- Generalised exfoliative dermatitis
- Most cases associated with thymoma
- Some may be idiopathic
- Older cats, no sex or breed predilection
What are cutaneous markers of feline thymoma-associated exfoliative dermatitis?
- Exfoliative dermatitis =
– non-pruritic
– diffuse erythema and skin exfoliation/scaling
– alopecia
– head and pinnae, and then generalised - Kerato-sebaceous accumulations =
– brown, keratosebaceous debris interdigital skin, claw beds and ear canals
– some cases associated with Malassezia dermatitis - Crusting and ulceration
What is cutaneous flushing? Ddx?
- Periodic release of vasoactive substances by tumours leads to skin colour changes
- Rarely reported but reported with pheochromocytoma, lung tumours and MCT
- Ddx = Demodicosis, drug reactions and systemic lupus erythematosus
What is nodular dermatofibrosis?
- Nodules of well differentiated collagenous nevi mainly on limbs but also heads and trunk
- Seen in middle aged GSDs with bilateral renal cysts or cyst adenocarcinoma
- Inherited in autosomal dominant fashion
- Due to mutated Birt-Hogge-Dube gene leading to production of novel protein
What is hypertrophic osteopathy? CS?
- Palisading periosteal proliferation along the shafts of long bones.
- Pulmonary (or occasionally abdominal) tumours
- none neoplastic causes also reported.
- Cause unknown =
- Increased blood flow to limbs due to afferent neurological stimulation
- In humans vagotomy can lead to resolution
- CS = Shifting lameness, Swelling / oedema, Limbs feel warm and are uncomfortable to touch
Dx OF hypertrophic osteopathy? Tx?
*Diagnosis =
- Clinical signs and radiography of long bones and pelvis
*Treatment =
- Remove inciting cause
- Prednisolone
- Pain relief
- Bisphosponates
How is PN pyrexia treated?
- Removal of tumour
- NSAIDs / paracetamol
What are cardiorespiratory syndromes of tumours?
- Pleural = Tachypnea and dyspnea and restricted breathing pattern
- Pericardial = Signs of right side hear failure, collapse, pulsus paradoxus and electrical alternans
