SA paraneoplastic & systemic effects of neoplasia

What is the difference between paraneopalstic syndromes?

• Paraneoplastic syndrome: consequence of cancer but not due to location

• Systemic effects: consequential to location of the tumour

What are the three main paraneoplastic syndromes related to the GI tract?

• Cachexia and anorexia

• Gastroduodenal ulceration

• Protein losign enteropathy

Explain how cancer can cause cachexia and anorexia

1. Anaerobic resp due to glucose utilisation and tumoural hypoxia leads to inc lactate prod and altered insulin sensitivity

2. Altered metabolism due to cancer related cytokines and inflm

3. Poor appetite in some patient

How can you treat cancer cachexia and anorexia?

• Maintain/ increase caloric intake giving low carb high fat diet

• Omega 3 PUFA (may be beneficial)

How can gastroduodenal ulceration occur 2° to cancer?

• GI tumour

• Some tumours prod hormones/ metabolites that cuase ulceration

  • MCT produce histamine

  • Gastrinoma's produce gastin

  • GI neuroendocrine tumours

How can protein losing enteropathy occur 2° to cancer?

• Damage to gut wall

  • Typically low TP, globlin, albumin often accompanied by diarrhoea

  • Low albumin -> ascited

• Seen partciularly with GI lymphoma

What are the mechanism of haeamatological effects 2° to cancer?

• Loss

• Reduced production

• Destruction

• Cytoses

• Mono-clonal gammopathies

• Coagulation disorders

What does acute vs chronic blood loss anaemia suggest? How do they present?

Acute: if no haematemesis or melaenia more likely splenic than GI

Chronic: many differentials are other GI or oral lesions

• Poorly regenerative microcytic hypochromic anaemia due to iron deficiency

What are reduced production cytopenias?

• Anaemia of chronic inflammatory disease (not just cancer)

  • Common

  • Mild-mod normochromic normocytic non-regen anaemia

    • Due to disordered iron storage

    • Shortened RBC life span

What does myelopthisis cause?

• One or several cytopenias

  • Neutropenia then thrombocytopenia then anaemia

    • Non regen, normochormic, normocytic

What tumour can cause hyperestrogenism?

Testicular tumours

(50% of dogs with Sertoli cell tumour)

What cytopenia do testicular tumours cause?

Pancytopenia due to bone marrow hypoplasia

What cancer does paraneoplastic IMHA and thrombocytopenia occur 2° to?

• Lymphoproliferative tumours (occassionally others)

What are the features of microangiopathic anaemia secondary to cancer?

• Systemic effect

• Fragmentation and shearing of RBCs leads to anaemia

• Caused by fibrin networks

What is a key indicator of microangiopathic anaemia?

Schistocytosis

Which of the following conditions have been associated with schistocytosis

• DIC

• Lymphoma

• MCT

• Haemangiosarcoma

• STS

• Hyperadrenocorticism

• IMHA

• Metastatic carcinoma

DIC

Haemangiosarcoma

IMHA

(+ Metastatic carcinoma)

When can cause a paraneoplastic cytoses?

• Erythrocytosis

  • Renal tumours via inc EPO, lymphoma, nasal fibrosarc, TVT, hepatic tumours

    • PUPD, neuro signs, seizures

• Neutrophilia

  • Seen with many tumours

• Eosinophilia

  • Due to IL-5 production

  • Most common with T cell lymphoma and MCT

What causes a paraneoplastic mono clonal gammopathy?

Excess production of single immunoglobulin by tumour cells

• Elevated serum globulins on biochem

What are the clinical signs, diagnosis and treatment for a paraneoplastic monoclonal gammopathy?

• Clinical signs due to hyperviscosity (neurological including seizures and coma and cardiac signs), reduced immune function, renal failure, coagulopathies and ocular disorders.

• Dx: Electrophoresis of serum and urine (Bence-Jones proteins)

  

• Tx: plasmapheresis and tumour directed treatment

Which of the following are commonly associated wiht monoclonal gammopathies?

• Melanoma

• Myeloma

• Leukaemia

• Carcinoma

• Lymphoma

• Myeloma

• Leukaemia

• Lymphoma

How can coagulation be affected by neoplasms? What can these cause?

• Altered coagulation- altered platelet function

  • Infarct/ thromboembolism

• DIC

  • Multi-organ failure and death

What are the main tumours associated with DIC?

Carcinoma and HSA

What endocrine alterations can occur paraneoplastically?

• Hypercalcaemia

• Hypoglycaemia

• Ectopic ACTH syndrome

• Hyperestrogenism (see haematological section)

What mechanisms can cause paraneoplastic hypercalcaemia?

• Elevated PTH or PTH related peptide

• IL-1 beta, TGF beta, RANKL

• Bone lysis

What are some non neoplastic differentials for hypercalcaemia?

lab error, renal failure, hypervitaminosis D, hypoadrenocorticism, granulomatous disease

What are the clinical signs of hypercalcaemia?

• PU/PD

• Dehydration

• GI signs – inappetence and vomiting

• Weakness

• Muscle fasciculations

• Calcification of soft tissues (especially kidneys) Ca x P >5

• Arrythmias

• Death

How do you treat hypercalcaemia? (urgent)

• Rehydrate with NaCl (3-4x maintenance)

• Then:

  • Continue fluids

  • Consider:

    • Furosemide

    • Bisphosphonates

    • Salmon calcitonin

    • Prednisolone (if lymphoprolif disease diagnosed or exluded)

• Remove inciting cause is only real tx

How would you work up a hypercalcaemia case?

• Assess tCa and iCa, also consider phosphate

• Ensure rectal exam negative for anal gland tumours

• Assess and aspirate LN

• Check history for diet and toxin exposure

• Imaging of thorax and abdomen and ultrasound neck esp. if iCa ↑ and Phos ↓

• PTH / PTHrp / vitamin D if appropriate history of exposure

  • Reference interval PTH is abnormal in a hypercalcaemic animal

• Bone marrow biopsy

• Consider ACTH stim if other signs are consistent with hypoadrenocorticism

What is the main neoplasm causing hypoglycaemia?

Insulinoma

• (Also hepatocellular carcinoma, smooth muscle tumorus and number of others)

• Caused by insulin, IGF or 2

How do you manage a paraneoplastic hypoglycaemia?

• Emergency – IV glucose + CRI glucose if necessary

• Medical management – prednisolone, diazoxide, octreotide

• Removal of inciting tumour

What are the non neoplastic ddxs for hypoglycaemia?

• Sepsis,

• Starvation,

• Liver dysfunction,

• Hypoadrenocorticism,

• Lab error

• Some toxicities

What are the features of ectopic ACTH syndrome?

• Rare

• Reported in association with lung tumours

• Clinical signs similar to hyperadrenocorticism

• Diagnosis

  • Positive for hyperadrenocorticism tests

  • + localisable tumour

  • No signs of adrenal associated hyperadrenocorticism

• Management

  • Excision of primary lesion

What paraneoplastic neurological effects can you get?

• Systemic effects of neurological mass lesion

• PNS

  • Myaesthenia Gravis

  • Peripheral neuropathy

How does myaesthenia gravis present as a paraneoplastic syndrome?

• Immune mediated disease

• Most commonly seen with thyomoma

How does a peripheral neuropathy present?

• Wide range of tumour types associated

• Not very common

List the possible 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 are the features of feline paraneoplastic alopecia?

• Alopecia

  • Symmetrical- Initially ventral abdo then limbs

• Glistening skin

  • Alopecic, skin inelastic and thin, smooth shiny appearance

• Footpad lesions

  • Concentric scale, crusting and painful fissure affecting FPs

• Malassezia dermatitis

What is pancreatic panniculitis?

Inflammation and hydrolysis of adipose tissue due to pancreatitis and pancreatic carcinoma and adenocarcinoma

What is Superficial necrolytic dermatitis (SND) aka hepatocutaneous syndrome?

=hepatocutanoues syndrome

• Cause by hepatic disease and pancreatic neoplasia

• Red white and blue histo

• Footpad hyperkeratosis and crusting dermatits

What is paraneoplastic pemphigus?

• Very rare cutaneous PNS

• Autoimmune-induced ulceration of the mucosae and mucocutaneous junctions

• Lymphoma, thymoma, splenic sarcoma, metastatic thymic mass

• Oral and mucocutaneous ulceration

  • Vesicles, severe oral ulceration

What is Feline Thymoma-Associated Exfoliative Dermatitis (FTAED)?

• Generalised exfoliative dermatitis

• Most cases associated with thymoma

• Exfoliative dermatitis, keratosebaceous accumulations, crusting and ulceration

What is cutaneous flushhing?

• 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

Recall what hypertrophic osteopathy is

• Periosteal proliferation along shaft of long bones

• 2° to pulmonary (or abdo) tumours

• Inc blood flow to limbs

How is hypertrophic osteopathy treated?

• Remove inciting cause

• Prednisolone

• Pain relief

• Bisphosponates

What causes paraneoplastic fever? What tumours is it seen with?

• Expression of inflammatory cytokines by or in response to the tumour.

• Seen with a variety of tumours especially lymphoma, renal cancers and hepatic tumours.

• Can lead to anorexia and malaise.

What is a common systemic cardioresp effect due to tumour exudation or bleeding?

Effusions

• Pleural

• Pericardial