Paraneoplastic Syndromes Flashcards by Brittany Jermalovic

What are Paraneoplastic Syndromes?

Systemic effects of cancer
May involve hormones/other factors
Usually unrelated to the tissue of origin 
May be more detrimental than the tumor
May be the first symptom

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What is Cancer Cachexia?

Profound state of malnutrition and weight loss despite adequate nutrition

A paraneoplastic syndrome

More common in cats

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Clinical Significance of Cancer Cachexia

Decreased QOL
Decreased response to treatment
Decreased survival time

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Cancer Cachexia Mechanism

Cancer stealing all energy!
Glucose is preferred substrate for cancer cells
Tumor cells incomplete glucose metabolism; molecules of ATP
Lactate is produced as an end product
Energy expended converting lactate back to glucose
Gluconeogenesis increases; net energy loss by host –> protein degradation (muscle wasting, decreased immune function, decreased wound healing)
Lipolysis occurs to provide energy for host

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Cancer Cachexia

Treatment

Provide 30-50% of non-protein calories as fat vs. CHO

Provide adequate calories (1.5 to 3 times that of normal animals)

Cannot decrease intake because cancer will cause hypoglycemia

Best to stick to regular diet and give them more of the food

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What is Hills N/d

Cancer diet

Actually caused diarrhea in dogs; malabsorption

Not shown to improve outcome or maintain weight

Only tested on dogs with lymphoma (stage III)

Not shown to starve cancer

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What is a common labwork abnormality in both dogs and cats with cancer?

Hypercalcemia

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Ectopic hormone production
Hypercalcemia
Tumor types

Lymphosarcoma
Anal sac Apocrine gland adenocarcinoma

Multiple myeloma
Thymoma
Parathyroid gland adenomas
Mammary carcinomas
SCC

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Ectopic hormone production
Hypercalcemia
Mechanisms

Ectopic tumor produced parathomone like peptides (PTHrp)

True hyperparathyroidism (PTH)

Vitamin D like factors

Tumor production of osteoclast activating factor

Direct bone lysis (rare)

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Ectopic hormone production
Hypercalcemia
Clinical Signs

Anorexia
Vomiting
PU/PD
Muscle weakness

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Ectopic hormone production
Hypercalcemia
Diagnosis

Can be difficult if concurrent disease (renal)
Careful search for potential neoplasia
Assays for PTH, PTHrp
Avoid symptomatic therapy that may interfere with diagnosis (glucocorticoids)

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Primary hyperparathyroidism
Serum Calcium
Serum Phos

Ca: slightly high
Ph: low

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Vitamin D Toxicosis
Serum Calcium
Serum Phos

Ca: High to very high
Ph: High

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Malignant humoral hypercalcemia
Serum Calcium
Serum Phos

Ca: High to very high
Ph: Normal or low

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Bone lysis
Serum Calcium
Serum Phos

Ca: High
Ph: Normal or high

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Ectopic hormone production
Hypercalcemia
Treatment Goals

Increase renal excretion of calcium (diuresis)
Inhibit bone reabsorption
Prevent calcium deposition in tissue
Promote external loss of Ca

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Ectopic hormone production
Hypercalcemia
Treatment

Treat underlying disease!

Saline diuresis
Furosemide (inhibits reabsorption at loop of Henle)
Glucocorticoids

Bisphosphonates

Bisphosphonates
Example
What they do

Pyrophosphate analogues (Pamidronate)

Keeps Ca in the bone
Helps patient when hypercalcemia is making them clinically ill

Ectopic hormone production
Hypoglycemia
Causes

Insulinoma
Hepatic tumors (not making glucose)
Leiomyoma/Leiomyosarcoma
Oral melenoma
Lymphosarcoma

Hypoglycemia

Clinical Signs

Weakness
Tremors
Seizures

Ectopic hormone production
Hypoglycemia
Treatment

Feed frequently; high protein better than high CHO but avoid giving too much sugar (hepatic overload)

Glucose IV or orally (careful with insulinoma)

Glucocorticoids; increase hepatic gluconeogenesis (okay to do this prior to diagnosis)

Eventually need to address tumor; stabilize first

Ectopic hormone production

Treatment of Insulinoma

Causes hypoglycemia

Remove the underlying problem/tumor (prognosis; 14 months)

Streptozotocin; antineoplastic agent with affinity for pancreatic islet cells (nephrotoxic, must administer with fluids); could induce diabetes mellitus

+/-Tocernib (Palladia)

Ectopic Hormone Production
Erythropoietin
Tumor examples

Causes polycythemia

Renal cell tumors
Lymphosarcoma
Hepatic tumors
Nasal fibrosarcoma

Ectopic Hormone Production
Erythropoietin
Clinical Signs

Polycythemia

Neurologic; motor or sensory depression, dullness, lethargy, seizures

Hemorrhage (epitaxis, hyphema)

Ectopic Hormone Production Erythropoietin Treatment

Polycythemia Phelbotomy (bleed them) Remove or treat primary tumor Hydroxyurea (suppresses bone marrow; decreases RBC production)

Hypertrophic Osteopathy | What is it?

Pain, reluctance to move, "swollen legs or swollen joints" -- very painful Periosteal proliferation of new bone along the shafts of long bones

Hypertrophic Osteopathy | Radiographic findings

Thickening of long bones; proliferative bone Associated with large thoracic or abdominal cavity mass (unknown mechanism)

Hypertrophic Osteopathy | Treatment

Treat or remove primary tumor Corticosteroids NSAIDs; has been proven to help Bisphosphonates

Fever and Neoplasia

Cancer is always a DfDx for fever of unknown origin Possible cytokine release by tumor or macrophages responding to tumor (IL-1, IL-2, IL-6, TNF-alpha)

Cancer Hematologic Abnormalities (broad)

Failure of production Loss Sequestration (tumor or spleen) Destruction

Cancer Hematologic Abnormalities | Anemia

``` Chronic inflammation Blood loss Microangiopathic hemolytic anemia (HSA0 IMHA Chemotherapeutic drugs Bone marrow infiltration with tumor Hyperestrogenism (sertoli cell tumor) ```

Cancer Hematologic Abnormalities | WBC

Leukocytosis Common Granulopoietic factors Inflammation Chronic inflammation Note: rebound after chemotherapy leukopenia or anemia

Cancer Hematologic Abnormalities | Platelets

Thrombocytopenia 35% of dogs with tumors Mechanism: decreased production, sequestration, increased consumption, increased destruction Thrombocytosis Chronic inflammation

Cancer Hematologic Abnormalities | Globulins

Hypergammaglobulinemia: PU/PD, neurologic signs, bleeding, more signs secondary to tumor Monoclonal gammopathy Single clone of Ig-producing cells

Cancer Hematologic Abnormalities Globulins Tumor types

Plasma cell tumors (sky high globulins) Lymphoma Leukemia

Cancer: Neurologic Syndromes (3)

Myasthenia gravis Peripheral neuropathies Chemo related neurologic toxicity

What causes Myasthenia gravis (cancer wise)

Thymoma Anti-Ach receptor antibody

Drug that should be avoided in cats

5 Flurouracil Seizures and death

Cancer Dermatologic Syndromes (3 main)

Cutaneous flushing Nodular dermatofibrosis in German Shepherds Alopeica

Cancer Dermatologic Syndromes | What causes cutaneous flushing

Pheochromocytoma | Mast cell tumors (degranulation)

Cancer Dermatologic Syndromes | Nodular dermatofibrosis

Rare German Shepherds! Autosomal dominant inheritance Lumps and bumps everywhere Linked to renal cysts or cystadenocarcinomas

Cancer Dermatologic Syndromes | What causes alopecia

Pancreatic carcinomas in cats -- pathopneumonic