Tumor staging and paraneoplastic syndrome Flashcards
Common early Signs of cancer inn pets. (10)
- Unusual swellings that don’t go away or that grow.
- Wounds that won’t heal
- Weight loss
- Loss of appetite
- Bleeding or discharge
- Offensive smell
- Difficulty eating or swallowing
- Reluctance to exercise or low energy level
- Persistent lameness
- Difficulty breathing, urinating, or defecating.
A paraneoplastic syndrome is
a syndrome (a set of signs and symptoms) that is the consequence of cancer in the body but that, unlike mass effect, is not due to the local presence of cancer cells.
Why does paraneoplastic syndrome occur?
- Immune mediated mechanisms
- Peptide, protein, ectopic or eutopic hormone production.
- Protein hormone precursors or cytokine
secretion. - Production of enzymes or other biochemical mechanisms that interfere with normal metabolic pathways.
Name some broad Paraneoplastic syndromes. (7)
- Metabolic syndromes
- Gastrointestinal syndromes
- Endocrinological manifestations
- Cutaneous manifestations
- Renal syndromes
- Neuro-muscular manifestations
- Diverse manifestations (hematologic,
cardiovascular)
Metabolic paraneoplastic syndromes.
Signs
Tx
Diet
- Cancer cachexia and anorexia are more common in humans with cancer than in dogs and cats. Prevalence about 10% in dogs.
- Change in metabolism, reduced food intake. These indicate a guarded prognosis.
- Treatment with IGF-1 increase weight and
reduces cancer cachexia.
The right diet: High quality protein and fat + lowered intake of simple carbohydrates.
Gastrointestinal paraneoplastic syndromes. (2)
Protein losing enteropathy
* Decreased synthesis
* Increased losses
Gastroduodenal ulceration
* Mastocytomas/ mast cell tumors secrete
histamine
* 30% of dogs with MCT have ulcerations in the GI-tract
* Tx with proton pumps inhibitors,
anti-histamines, misoprostol, sucralfate
- Gastrinomas; neoplasia in D-cells in the pancreas most common -> hypersecretion
of gastric juice (“Zollinger-Ellison syndrome” in ppl) causes ulceration.
Endocrine paraneoplastic syndromes (3)
- Hypercalcemia
- Hypoglycemia
- Ectopic ACTH production
Hypercalcemia as a paraneoplastic syndrome.
- Neoplasia is the most common cause of hypercalcemia. Look for the tumor.
- Lymphoma, anal sac carcinoma, multiple
myeloma, tumors in parathyroid glands,
mammary tumors, thymoma. - Less common in cats than in dogs (lymphoma, SCC).
How does neoplasia cause hypercalcemia in PNS?
- Ectopic production of parathyroid hormone (PTH) or parathyroid hormone related peptide (PTH-rp) in the tumor.
- Multifocal lytic metastases to bone also produce osteoclast factors.
- Tumor associated prostaglandins produced.
- Vitamin D can be produced.
- Interleukin-1-β (osteoclast activating
factor)
All of the above may cause bone resorption which lead to increased levels of calcium in the blood.
Hypercalcemia diagnosis in the lab?
Clinical signs?
Use Ionized Ca not protein bound (?) (so the hypercalcemia is
not due to lipemia or hemolysis).
Clinical symptoms:
* PU/PD due to a decreased sensitivity to
ADH
- Ca causes a decrease in blood flow and GFR because of a grave vasoconstriction in the kidney leading to renal toxicity.
Shivering, fatigue, vomiting, bradycardia,
dehydration, coma, death.
Hypercalcemia due to PNS, treatment.
- Treat the tumor!
- Rehydration with NaCl (don’t give anything with extra Ca2+!)
- Diuresis with NaCl, possibly also with furosemide (only when patient is properly
rehydrated), prednisone (when the patient is completely diagnosed and staged).
Grave hypercalcemia:
* Pamidronate 1-1,5mg/kg every 2-3 week (potent inhibitor of bone resorption
(BR) without affecting the calcium reabsorption in renal tubules)
- Calcitonin – inhibits bone resorption
- Mithramycin - blocks osteoclastic function and can be given for severe malignancy-related hypercalcemia. It has significant hepatic, renal, and marrow toxicity.
Hypoglycemia as PNS.
- Insulinoma (tumor in pancreatic β-cells) can cause such severe hypoglycemia they can bring on seizures and look like epilepsy.
- Also tumors outside the pancreas that cause hypoglycemia due to increased glucose consumption, decreased
gluconeogenesis or glycogenolysis in the liver. - Liver tumors, pancreatic tumors,
leiomyomas/leiomyosarcomas, plasma cell tumors, lymphoma, mammary tumor.
Symptoms of hypoglycemia.
- Polyphagia
- Fatigue
- Seizures (consume GLU)
- Important to differentiate from other conditions (xylitol toxicosis, plain epileptic seizures).
Diagnostics for hypoglycemia.
- Insulin measurement from blood: more than one sample as variations occur normally.
- Fructosamine
– Normal in hypoglycemia due to e.g. seizures
– Low in insulinoma - Diagnostic imaging
– Ultrasound
– CT - contrast - Biopsy
Hypoglycemia treatment.
- Slow adjustment of blood glucose, no big boluses. Glucose infusion will likely lead to rebound effect and lowering of blood glucose even more.
- Use steroids for slow GLU increase,they initiate glycogenolysis and are anti-insulinogenic (cause insulin resistance).
- Slow release carbohydrates and fat don’t trigger such an abrupt release of insulin.
- Many smaller portions per day to
avoid triggering excessive insulin release. - Insulinomas are deficient in negative feed-back regulations due to lower blood glucose level.
- Glucagon injection – works like
steroids.
ACTH producing tumors are usually
primary lung tumors which produce
steroids from the adrenals and thus Cushing like syndrome.
Hematological PNSs. (5)
- Hypergammaglobulinemia
- Anemia
- Neutrophilia
- Thrombocytopenia, coagulopathies, DIC
Hypergammaglobulinemia as PNS.
- Multiple myeloma
- Lymphoma
- Increased production of monoclonal antibodies from plasma cells or lymphocytes.
- Gel electrophoresis, gamma globulin peak
- Sometimes Bence-Jones proteins in urine
- Hyper viscosity
- Hypoxia in tissue
- Bleeding (due to antibodies coating thrombocytes), bleeding in eyes (hyphema due to retinal detachment due to blood clotting in retinal vessels due to the antibodies attaching to platelets)
Reasons for anemia as PNS. (6)
- Cancer is a chronic disease (dysregulated iron storage and metabolism, shortened red cell lifespan, decreased bone marrow response).
- IMHA can be triggered by the tumor
- Blood loss (intestine, abdomen, urine, skin)
- Microangiopathic hemolytic anemia (often due to tumor induced DIC or red blood cell shearing (hemangiomas)).
- Tumor invaded bone marrow (leukemias) resulting in anemia.
- Bone marrow suppression due to estrogen producing tumors (sertoli cell tumors, granulosa cell tumors).
Erythrocytosis as a PNS.
- Quite uncommon. Caused by erythropoietin producing tumors.
- Renal tumors, lymphomas (renal),
lung tumors, liver tumors, leiomyomas in
caecum, nasal fibrosarcomas and transmissible venereal tumors.
Don’t forget heart failure as a ddx!
Thrombocytopenia as a PNS.
- 36% of veterinary oncology cases have it aka 1/3.
- 58% of patients with thrombocytopenia have a lymphoproliferative neoplasia aka hematological cancer like splenic hemangiosarcoma, leukemias/lymphomas.
- Increased consumption, decreased production, shortened lifespan, immune mediated thrombocytopenia.
Cutaneous manifestations as a PNS. (5)
- Alopecia
- Cutaneous flushing
- Nodular dermatofibrosis
- Necrolytic migratory erythema
- Paraneoplastic Pemphigus vulgaris
Alopecia as PNS in cats. What type of neoplasms?
- Cats with pancreatic carcinomas and liver metastases (bilateral, symmetric ventral,
shimmering) - Cats with bile duct carcinoma
Cutaneous flushing as PNS.
- Skin turns red episodically because of
vasodilatation in the superficial vessels. - E.g. in Pheochromocytoma
- Primary lung tumor combined with
intrathoracal MCT - Plain MCT
Describe Nodular dermatofibrosis as a PNS.
- Due to Bilateral renal cysts/cystadenomas
- Genetic disease
- Often middle aged German shepherds
- Often slow-growing
- Unknown pathogenesis
Cutaneous manifestations
* Necrolytic migratoric
erythema
* In human and dog
* Erosions, erythemas
* Glucagonoma
(pancreas)
* Paraneoplastic
pemphigus vulgaris
* Intraepidermal bullae,
erosions in skin and
mucosa.
* Mediastinal lymphoma,
sarcomas in spleen
* Circulating IgG
antibodies?
Cutaneous manifestations
* Necrolytic migratoric
erythema
* In human and dog
* Erosions, erythemas
* Glucagonoma
(pancreas)
* Paraneoplastic
pemphigus vulgaris
* Intraepidermal bullae,
erosions in skin and
mucosa.
* Mediastinal lymphoma,
sarcomas in spleen
* Circulating IgG
antibodies?
Neuro-muscular PNS. (2)
Myastenia gravis
* Antibodies against acetylcholine receptors
* Can be caused by thymomas
* Osteosarcomas, lymphomas, bile-duct carcinomas
Peripheral neuropathies
* Different types of changes in peripheral nerves (demyelination, degeneration of axons)
* Difficult to differentiate neuro-muscular PNS from other causes to these diseases.
* Quite unusual in clinic
Hypertrophic osteopathy as PNS.
- Periosteal proliferation of bone along the shafts of the long bones. Typical look on X-rays.
- Primary lung tumors, but also in pulmonary metastatic disease (osteosarcoma).
- Lameness, warm and swollen legs
- Probably is stimulation of afferent nerves a part of the etiology?
NB (HO can also be seen in
a lot of non-neoplastic diseases)
Fever as a PNS?
- Many different tumor types
- About 1/3 of the human patients where the cause of the fever is unknown are
later diagnosed with a tumor. - Excessive production of interleukins IL-1, IL-6, TNF-α, interferons.
Why do we need a diagnosis?
- To know where and how we should search for metastases. Different tumor types have different patterns of spread.
+ To know if we have to evaluate the patient in a special way differing from the standard data base. For example ionized Ca in patients with lymphoma/leukemia or electrophoresis in dogs with plasma cell tumors.
+ To be able to present a prognosis and a
treatment plan for the owner after we have
done the right staging!
+ To plan the surgery. The first time you do surgery is the time when you have the
best opportunities to get a good result of your surgery. The extent of the tumor is easier to see and the tissue layers are intact.
Most commonly, skin tumors spread to local lymph nodes and lungs.
MCTs are an exception, they mainly spread to local lymph nodes and abdomen (spleen, liver, kidneys, lnns).
- Some tumors are not so prone to spread but can cause local problems (infiltrative lipomas, hemangiopericytomas).
- Some patients need special preparation before surgery (antihistamines/steroids in patients with MCT).
Staging cancer.
- Clinical Stage is crucial for the prognosis in almost all tumor types.
- Use WHO:s TNM system
- T extent of primary tumor
N involvement of local lymph node
M distant metastasis - Different schedules for staging the different types of tumors.
Subgroups a or b
Explain WHO:s TNM system.
A system to describe the amount and spread of cancer in a patient’s body, using TNM.
T describes the size of the tumor and any spread of cancer into nearby tissue;
N describes spread of cancer to nearby lymph nodes; and
M describes metastasis (spread of cancer to other parts of the body).
Skin tumors in dogs and cats,
TNM-Staging.
Staging for multicentric disease such as
lymphoproliferative disorders often present as a disseminated form and thus the TNM classification is
not appropriate.
The disease has to be staged according to the different organ systems involved.
Stage is NOT the same as
grade.
- Stage is the amount of tumor burden and
localization of tumor(s). - Grade is the tumor phenotype and
characteristics, diagnosed with different
pathological examinations (e.g. histopathology, immunohistochemistry, cytology, PCR etc.).
Stage vs grade
A cancer’s stage explains how large the primary tumor is and how far the cancer has spread in the patient’s body.
A grade describes the appearance of cancer cells and tissue especially histopathologically.
Staging is done using what tools? (11)
- X-rays (contrast)
- Ultrasound
- Blood samples, tumor markers
- CT
- MRI
- Endoscopy
- Laparotomy
- Bone marrow aspirate
- Lymph node aspirate
- Scintigraphy
- PET-scan
