Approach to the Cancer Patient and Paraneoplastic Syndromes Flashcards
What are the odds of canine cancer
1 in 4
50% of dogs > 10 years develop cancer
What organ system is the most common site of tumours in dogs
Skin and soft tissue
What tumour type are Giant /large breeds like Great Dane, Deerhound, lurcher, Rottweiler predisposed to
Osteosarcoma
What tumour type are Bernese Mountain dog, Flat-coated retriever, Rottweiler, Miniature Schnauzer predisposed to
Histiocytic sarcoma
What tumour type are Boxer, G retriever, Lab, Mastiff predisposed to
Lymphoma
What tumour type are Boxer, Pug, SharPei, Weimeraner predisposed to
MCT
What tumour type are Scottish terriers predisposed to
Bladder (TCC)
What tumour type are Boxer, French bull dog, Boston T, G retriever predisposed to
CNS tumours
What tumour type are Dolicocephalic breeds like Labradors, retrievers, collies predisposed to
Nasal tumours
What tumour type are German Shepherd, G retriever predisposed to
Haemangiosarcoma
What tumour type are Cocker (springer) spaniels predisposed to
Anal Sac tumours
What tumour type is most common in cats
Lymphoma
What tumour type is second most common in cats
Leukemia
What is paraneoplastic syndrome
The systemic, metabolic and endocrinological effects associated with some tumour types (Due to secreted peptide / cytokine / hormone)
Presentations of cancer patient
Superficial mass / lump – signalment and history
Non-specific clinical signs as direct effect of internal tumour – eg obstruction, compression
Non-specific clinical signs / medical presentation d/t indirect effect of internal tumour
What is the most common paraneoplastic syndrome sign
Hypercalcaemia
What are the Normal controllers of serum Ca
parathyroid hormone (PTH), calcitonin, and vitamin D.
What is the normal serum calcium level of a dog
2.34-3.0 mmol/l
What is the serum calcium level of a dog for it to be hypercalcaemic
3 mmol/l
What is the normal Ionised calcium level of a dog
1.2 – 1.4 mmol/l
What is the Ionised calcium level of a dog for it to be hypercalcaemic
1.4
Causes of hyperCa (Neoplastic)
Lymphoma /Leukaemia (10-40 % cases; T cell)
Apocrine gland adenocarcinoma of the Anal Sac - (25-55% of cases)
Bone tumours /multiple myeloma (local osteolysis)
Other malignant tumours (mammary, thyroid, lung, thymoma)
Parathyroid adenoma (benign) – PTH induced
Causes of hyperCa (Non-Neoplastic)
Endocrine
Renal
Poisoning - Vit D toxicity – rodenticides, diet
Inflammatory- Infections/ granulomatous inflammatory disorders (osteomyelitis, osteoporosis, blasto or coccidiomycosis)
Lab error
Clinical sign of hypercalcaemia
Renal- PU/PD
Gastrointestinal- Anorexia, vomiting, constipation
Neuromuscular- Muscle weakness, tremors, lethargy
Cardiovascular- Hypovolaemia, Bradycardia, dysrhythmias
Where are the places to hunt for a tumour
Lymphoma – most common cause of HyperCa- Check if lymph nodes enlarged
Apocrine adenocarcinoma of the anal sac- Rectal examination
Parathyroid tumour/adenoma- US neck/PTH gland
Multiple myeloma- Bone pain, ocular changes
Metastatic bone tumours- Bone pain
Diagnostics to hunt for a tumour
Chest radiographs- 3 views – LNs/ lung mets/masses
Abdominal ultrasound- Check internal LNs, organs
Limb & Spine radiographs-Bone lysis/lesions
Routine Bloods- Any clues to organ involvement
Bone Marrow biopsy- Tumour cells
Summarise how PTH regulates calcium levels
When calcium levels in the blood decrease, the parathyroid glands release PTH into the bloodstream. PTH then acts on various organs and tissues in the body to raise calcium levels through several mechanisms:
List mechanisms of how PTCH increases calcium levels
Stimulating Bone Resorption: PTH stimulates osteoclasts, cells responsible for breaking down bone tissue, which releases calcium into the bloodstream.
Enhancing Calcium Reabsorption: PTH acts on the kidneys to increase the reabsorption of calcium from the urine, reducing calcium loss in the urine and preserving it in the bloodstream.
Stimulating Calcium Absorption in the Intestines: PTH indirectly increases the absorption of calcium from the intestines by stimulating the production of active vitamin D (calcitriol), which enhances calcium absorption.
Suppressing Phosphate Reabsorption: PTH inhibits the reabsorption of phosphate in the kidneys, leading to decreased serum phosphate levels.
Summarise how PTHrp regulates calcium levels
PTHrP, or Parathyroid Hormone-related Protein, is a protein that shares structural similarities with PTH and acts on the same receptors as PTH. While PTH primarily regulates calcium levels, PTHrP has a broader range of functions
How does cancer affect PTHrp (Parathyroid Hormone-related Protein)
PTHrP can contribute to hypercalcemia (elevated calcium levels) by acting similarly to PTH, leading to increased calcium release from bones and decreased excretion of calcium by the kidneys.
What levels of Calcium, PTH and PTHrp will you typically see in a cancer patient
Calcium: High
PTH: Low
PTHrp:High
What levels of Calcium, PTH and PTHrp will you typically see in a hyper PTH patient ( no cancer)
Calcium: High
PTH: High
PTHrp: Low
Signs of hypoglycaemia
Episodic collapse/weakness
Low blood glucose
Tumour causes of hypoglycaemia
Insulinoma (high insulin)
Hepatic neoplasia (altered glucose metabolism, consumption)
Non-tumour causes of hypoglycaemia
Sepsis, Pregnancy toxaemia
Liver diseases –shunts, cirrhosis, storage diseases
Hypoadrenocorticism
Signs of Hyperestrogenaemia
Gynaecomastia
Bilaterally symmetrical alopecia
Reduced libido
Pendulous prepuce
Tumour causes of hyperestrogenaemia
Estrogen producing tumour
Sertoli cell tumour
Cachexia
Muscle Wasting
Tumour causes of cachexia
Lymphoma, any extensive/ systemic or metastatic tumour
Hypertrophic pulmonary osteopathy (Marie’s disease)
primary lung mass or metastatic disease
Periosteal new bone growth -long bones
Painful limbs, lameness
Myasthenia gravis
neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. Immune mediated
List two ways to diagnose a tumour
Biopsy and FNA
What is the most accurate way to diagnose a tumour
Biopsy
List advantages of Biopsy of tumour
Provides tissue architecture, and tumour grade
Most accurate and definitive diagnosis
List disadvantages of Biopsy of tumour
Sedation/local or GA needed, more expensive, time-consuming
List advantages of FNA of tumour
Quick, easy, cheap, no GA
Inflammatory /neoplastic
Sarcoma, carcinoma, LSA, MCT
List disadvantages of FNA of tumour
No tissue architecture (no grade)
Can be unrepresentative?
Who grades tumours after biopsy
Pathologist
What soft tissue sarcoma has high malignancy and increased risk of metastasis
Haemangiosarcoma
Describe criteria for a tumour to be classified as low grade (grade 1)
low chance of metastasis so surgery usually sufficient
Describe criteria for a tumour to be classified as high grade (grade 3)
high chance of local recurrence and metastasis, so needs aggressive treatment and chemotherapy
Describe criteria for a tumour to be classified as Intermediate grade (grade 2)
Intermediate risk of local recurrence and possibly metastasis so local treatment ± chemotherapy
Summarise MCT grading Patnaik scheme
Based on histopathology NOT cytology
3 Tier system published in 1984
Most commonly used historically
What is Grading criteria for dermal tumours based on
Cell morphology and differentiation
Mitotic index/count
Extent of tissue involvement
Cellularity and Stromal reaction
Describe characteristics of a Grade 1 MCT
Well differentiated mast cells
No tissue invasion (dermis only)
No mitotic figures
Minimal stromal reaction
Low histol grade / benign nature
Low risk of metastasis
Prognosis following surgery good
> 90% have long term survival
Describe characteristics of an Intermediate grade MCT (Grade II)
Moderately differentiated /pleiomorphic mast cells
Some local tissue invasion – lower dermis, subcutis and occ deeper
0-2 mitoses per hpf
Some areas of oedema, necrosis
Variable behaviour
40 - 75 % long term survival
Prognosis variable
Good (wide) surgery improves prognosis
Describe characteristics of a Poorly diff MCT (Grade III)
Poorly diff, pleomorphic mast cells (few /no granules), binucleate or multinucleated cells
Very cellular
3-6 mitoses per hpf
Extend into subcutis and tissues
Haemorrhage, oedema, necrosis
Aggressive, locally invasive tumours
High rate of distant metastasis
Poor prognosis, v few long term survivors (>6 months)
what does HPF mean
HPF stands for High Power Field, a term used in microscopy, particularly in pathology and cytology. It refers to the area visible under a high-power microscope objective lens and is used as a unit of measurement when counting cells or assessing cellular features. HPF provides a standardized way to quantify observations made under the microscope, aiding in consistent comparisons between different samples or observers.
What was the patnaik scheme problematic
Pathologists found it difficult to apply
>50% of MCT - called Grade 2 tumours
Grade 2 tumours have 50:50 chance of long survival so not helpful!
What is Kiupel scheme
2 Tier classification system - LOW and HIGH grade only for MCT
What is the high grade criteria for the Kiupel scheme
At least 7 mitotic figures in 10hpf
At least 3 multinucleated cells in 10hpf
At least 3 bizarre nuclei in 10hpf
Karyomegaly- Enlargement of nucleus
What is tumour staging
Defining the anatomical extent of the tumour in terms of primary site and distant spread (anatomical staging) -determined by a clinician = clinical assessment
What system does tumour staging use
TNM system
Primary tumour T
Node N
Metastasis M
Approach to Primary tumour-T in tumour staging
Measure its dimensions with a ruler or calipers
for staging scheme and tumour response
Assess whether there is local invasion
Physical examination - palpation
Radiography
Ultrasonography
CT/MRI
Approach to Local lymph nodes-N in tumour staging
Assess the sentinel LNs/anatomical drainage LNs to see if they are enlarged d/t tumour infiltration
Palpate
Image
Aspirate
Biopsy /excise
Approach to Metastasis-M in tumour staging
Physical examination- for external mets - eg skin lesions
Imaging- for internal mets – Xray/CT chest, US abdomen
Laboratory evaluation – organ function may be altered
FNA/biopsy if possible to confirm suspicious lesions
Why do staging
To decide whether treatment / what treatment is feasible (combined with grade information)
Helps predict clinical behaviour/prognosis (see clinical staging/group staging)
Provides a precise record of the tumour extent in the body at that time (anatomical staging)
To monitor how tumour changes with time (response to treatment – shrinks [CR/PR], progresses [PD], static [SD])
What are the two types of staging systems
Anatomical staging and clinical staging
Outline anatomical staging
Purely the clinical anatomical extent
More disease usually means worse prognosis
Other factors may also influence prognosis
Outline clinical staging
Use of anatomical (TNM) staging and
Knowledge of their established clinical behaviour (tumour histological type/ grade, location)
Higher clinical stage worsens prognosis for several tumour types
Summarise lymphoma staging
I- Single node or lymphoid tissue in a single organ (excluding bone marrow)
II- Several nodes in regional area
III-Generalised LN involvement (both sides of diaphragm)
IV- Liver and spleen (+/- stage III)
V- Bone marrow and /or other organ systems (extranodal)(+/- stages I-IV)
Summarise MCT staging
0- Incompletely excised tumour from dermis with no LN involvement
I- Single tumour in dermis without LN involvement
II- Single tumour in dermis with LN involvement
III-Multiple dermal tumours Large infiltrating tumours ± LN involvement
IV- Any tumour with distant metastasis, blood or BM involvement
