Cancer Flashcards
1
Q
Define basal cell carcinoma.
A
The commonest form of skin malignancy.
= rodent ulcer
2
Q
Explain the aetiology / risk factors of basal cell carcinoma.
A
- Prolonged sun exposure or UV radiation
- Photosensitizing pitch
- Tar
- Arsenic
Associated with abnormalities of the patched / hedgehog intracellular signaling cascade as seen in Gorlin’s Syndrome (naevoid basal cell carcinoma syndrome).
3
Q
Summarise the epidemiology of basal cell carcinoma.
A
Common in those with fair skin and areas of high sunlight exposure, elderly, rare before 40 years
Lifetime risk in Caucasians = 1:3
4
Q
Recognise the presenting symptoms of basal cell carcinoma
A
A chronic slowly progressive skin lesion usually on the face but also on the scalp, ears or trunk.
5
Q
Recognise the signs of basal cell carcinoma on physical examination.
A
Nodulo-Ulceractive:
- Small glistening translucent skin over a coloured papule
- Slowly enlarged (early)
- Central ulcer with raised pearly edges
- Fine telangiectatic vessels run over the tumour surface
- Cystic changes in larger, more protuberant lesions
Morphoeic:
- Expanding
- Yellow / white waxy plaque
- Ill-defined edge - more aggressive
Superficial:
- Most often on trunk
- Multiple pink / brown scaly plaques with a fine whipcord edge expanding slowly
- Can grow to more than 10cm in diameter
Pigmented:
- Specks of brown or black pigment
6
Q
Identify appropriate investigations for basal cell carcinoma and interpret the results.
A
Biopsy rarely necessary - diagnosis based on clinical suspicion.
7
Q
Define cholangiocarcinoma.
A
Cancer arising from the bile duct epithelium.
Intrahepatic or extrahepatic.
[Perihilar or distal]
Perihilar - involves bifurcation of the ducts = Klatskin’s tumours.
Slow growing
8
Q
Explain the aetiology / risk factors of cholangiocarcinoma.
A
Causes:
- Flukes
- Caroli’s disease
- Biliary cysts
Risk factors:
- 50 years +
- Cholangitis
- Choledocholithiasis
- Cholecytolithiasis
9
Q
Summarise the epidemiology of cholangiocarcinoma.
A
95%+ are adenocarcinomas.
10
Q
Recognise the presenting symptoms of cholangiocarcinoma.
A
- Abdominal pain - right upper quadrant
- Fever
- Pruritus - itchy skin
- Malaise
11
Q
Recognise the signs of cholangiocarcinoma on physical examination.
A
- Painless jaundice
- Weight loss
- Palpable gallbladder
- Hepatomegaly
12
Q
Identify appropriate investigations for cholangiocarcinoma and interpret the results.
A
- Bloods - bilirubin, AlkPhos, gamma-GT, aminotransferase, PT time
- Abdominal ultrasound
- Abdominal CT, MRI
- MR angiography
- ERCP
13
Q
Define colorectal carcinoma.
A
Malignant adenocarcinoma of the large bowel.
14
Q
Explain the aetiology / risk factors of colorectal carcinoma.
A
Sequence from epithelial dysplasia to adenoma and carcinoma - involves oncogenes (APC, K-ras) and tumour suppressor genes (p53, DCC).
Risk factors:
- Increasing age
- Adenomatous polyposis coli (APC) mutation
- Lynch syndrome - hereditary non-polyposis colorectal cancer
- MYH-associated polyposis
- Chronic bowel inflammation - e.g. IBD
15
Q
Summarise the epidemiology of colorectal carcinoma.
A
60% in rectum and sigmoid colon.
20% in ascending colon
20% in transverse and descending colon
3rd most common cancer in western world.
4th leading cause of cancer deaths in the US.
Rare below 40yrs.
16
Q
Recognise the presenting symptoms of colorectal carcinoma.
A
Depends on locations.
Left-sided colon and rectum:
- Change in bowel habit
- Rectal bleeding
- Blood / mucous in stool
- Tenesmus - sensation of incomplete emptying after defecation
Right-sided colon:
- Later presentation
- Symptoms of anaemia, weight loss and non-specific malaise or lower abdominal pain
17
Q
Recognise the signs of colorectal carcinoma on physical examination.
A
- Anaemia only sign in right-sided lesions
- Abdominal mass
- Low-lying tumours palpable on rectal examination
Metastatic disease:
- Hepatomegaly
- Shifting dullness of ascites
18
Q
Identify appropriate investigations for colorectal carcinoma and interpret the results.
A
- Blood
- Stool
- Endoscopy
- Barium contrast studies
- Abdominal ultrasound scan
Blood
- FBC - for anaemia
- LFT
- Tumour markers - CEA to monitor treatment and reoccurance
Stool
- Occult or frank blood in stool
- Screening
Endoscopy
- Sigmoidoscopy
- Colonoscopy
- Visualisation & biopsy
- If small isolated carcinoma, perform polypectomy
Barium Contrast Studies
- Apple core stricture on barium enema
Abdominal Ultrasound Scan
- For hepatic metastases
- CXR, CT, MRI, endorectal ultrasound
19
Q
Define gastric cancer.
A
Gastric malignancy, most commonly adenocarcinoma, more rarely lymphoma, leiomyosarcoma.
20
Q
Explain the aetiology / risk factors of gastric cancer.
A
Environmental insult in genetically predisposed individuals –> mutation, unregulated cell growth
Risk factors:
- H.pylori infection
- Atrophic gastritis
- Diet high in smoked, processed foods, nitrosamines
- Smoking
- Alcohol
21
Q
Summarise the epidemiology of gastric cancer.
A
Common cause of death worldwide
Highest incidence - Asia, Japan
6th most common cancer in UK
UK annual 15/100,000.
M:F 2:1
Age >50 yrs
Reducing incidence of cancer of antrum/body
Cardia and GI/Oesophageal increasing.
22
Q
Recognise the presenting symptoms of gastric cancer.
A
Early - asymptomatic
- Early satiety
- Epigastric discomfort
- Weight loss
- Anorexia
- N&V
- Haematemesis
- Melaena
- Symptoms of anaemia
- Dysphagia - tumours of the cardia
- Symptoms of metastases - e.g. abdominal swelling, jaundice
23
Q
Recognise the signs of gastric cancer on physical examination.
A
- May be normal
- Epigastric mass
- Abdominal tenderness
- Ascites
- Signs of anaemia
- Virchow’s node/Troisier’s sign - lymphadenopathy in left supraclavicular fossa
- Sister Mary Joseph node - metastatic nodule on umbilicus
- Krukenber’s tumour - ovarian metastases
24
Q
Identify appropriate investigations for gastric cancer and interpret the results.
A
- Upper GI endoscopy - multiquadrant biopsy of gastric ulcers
- Blood - FBC (anaemia), LFT
- CT/MRI - staging of tumour, surgery
- US of Liver - staging of tumour
- Bone scan - staging of tumour
- Endoscopic Ultrasound - assess depth of invasion, lymph node spread
- Laparoscopy - determine if resectable
25
Define hepatocellular carcinoma.
Primary malignancy of hepatocytes, usually occurring in a cirrhotic liver.
26
Explain the aetiology / risk factors of hepatocellular carcinoma.
- Chronic liver disease - e.g. alcoholic liver disease, Hep B/C, autoimmune disease
- Metabolic disease - e.g. haemochromatosis
- Aflatoxins - e.g. Aspergillus flavus fungal toxin on stored grains or biological weapons
Risk factors:
- Cirrhosis
- Chronic Hep B/Hep C
- Chronic heavy alcohol use
27
Summarise the epidemiology of hepatocellular carcinoma.
1-2% of malignancies - common
Less common than secondary liver malignancies
Rare in the west - 1-2 per 100,000/year
Common in HepB/C endemic countries - e.g. Asia and sub-Saharan Africa - 500 per 100,000/year
28
Recognise the presenting symptoms of hepatocellular carcinoma.
Symptoms of malignancy:
- Malaise
- Weight loss
- Loss of appetite
Symptoms of chronic liver disease:
- Abdominal distension
- Jaundice
History of Carcinogen Exposure:
- High alcohol intake
- Hep B/C
- Aflatoxins
29
Recognise the signs of hepatocellular carcinoma on physical examination.
Signs of malignancy:
- Cachexia
- Lymphadenopathy
Hepatomegaly:
- Nodular
- Deep palpation elicits tenderness
- Bruit heard over the liver
Signs of chronic liver disease:
- Jaundice
- Ascites
30
Identify appropriate investigations for hepatocellular carcinoma and interpret the results.
1. Bloods - high AFP, VitB12-binding protein, LFT may show biliary obstruction (poor sensitivity and specificity)
2. Abdominal US - not sensitive if <1cm
3. Duplex scan of liver - demonstrate large vessel invasion
4. CT (thorax, abdomen, pelvis) - define structural lesion and spread
5. Hepatic angiography - using lipiodol
6. Liver biopsy - confirms histology (small risk of tumour seeding along biopsy tract)
7. Staging - CXR, CT (throax, abdomen, pelvis), radionuclide bone scan
8. Screening - AFP, abdominal ultrasound in at-risk individuals
31
Define oesophageal cancer.
Malignant tumour arising in the oesophageal mucosa.
2 major histological types - squamous cell carcinoma and adenocarcinoma.
32
Explain the aetiology / risk factors of oesophageal cancer.
Barrett's oesophagus (intestinal metaplasia) can progress to low-grade, high-grade and invasive carcinoma.
Spread is typically initially direct (no serosa on oesophagus) and longitudinal --> via submucosal lymphatics to tracheobronchial, mediastinal, coeliac, gastric or cervical nodes.
Rare oesophageal tumours = lymphoma, melanoma, leiomyosarcoma.
Squamous Cell Carcinoma:
- More common in mid-upper oesophagus
- Alcohol
- Tobacco
- Nutritional deficiency - e.g. vitamines, trace elements
- HPV infection
- Achalasia
- Paterson-Kelly (Plummer-Vinson) Syndrome
- Tylosis (Howel-Evans Syndrome)
- Scleroderma
- Coeliac disease
- Lye stricture
- History of previous thoracic radiotherapy or upper aerodigestive squamous cancer
- Dietary nitrosamines
Adenocarcinoma:
- More common in lower oesophagus or gastro-oesophageal junction
- GORD
- Barrett's oesophagus - intestinal metaplasia of distal oesophageal mucosa
33
Summarise the epidemiology of oesophageal cancer.
8th most common malignancy - UK 7000-8000 per year
M:F 3-4:1
High incidence in northern China, Iran, southern Russia
Adenocarcinoma more common in Westernized countries - 65% cases in UK, increasing by 5-10% per year
Peak incidence 60-70 years
34
Recognise the presenting symptoms of oesophageal cancer.
Early:
- Symptomatic of reflux
Late:
- Dysphagia
- Regurgitation
- Cough
- Choking after food
- Odynophagia
- Weight loss
- Fatigue
- Voice hoarseness (recurrent laryngeal nerve palsy?)
35
Recognise the signs of oesophageal cancer on physical examination.
No physical signs evident
- Weight loss
- Supraclavicular lymphadenopathy
- Hepatomegaly
- Aspiration or direct tracheobronchial involvement --> respiratory signs
36
Identify appropriate investigations for oesophageal cancer and interpret the results.
1. Endoscopy
2. Imaging
3. Other
Endoscopy - tumour location and biopsy, using narrow band imaging or magnification to grade and detect
Imaging - e.g. Barium swallow, CT (chest, abdo, pelvis), PET (metastasis)
Other - Bronchoscopy (if risk of tracheobronchial invasion), bone scan, laparscopy, peritoneal washings, thoracoscopy
37
Define pancreatic cancer.
Malignancy arising from the exocrine or endocrine tissues of the pancreas.
[primary pancreatic ductal adenocarcinoma - 85%+ of pancreatic neoplasms]
38
Explain the aetiology / risk factors of pancreatic cancer.
Unknown cause.
5-10% familial component
- Hereditary syndrome - BRCA2 mutation
- Familial atypical multiple mole melanoma (CDKN2A)
- Peutz-Jeghers (STK11/LKB1)
- Hereditary pancreatitis (PRSS1)
- MEN
- HNPCC
- FAP
- Gardner
- von Hippel-Lindau Syndromes
Precursor lesions - e.g. pancreatic intraductal neoplasia, intraductal pancreatic mucinous neoplasm, mucinous cystic neoplasm
Linear progression from pre-invasive pancreatic intraductal neoplastic lesions to invasive ductal adenocarcinoma.
Risk factors:
- Smoking
- Family history of pancreatic cancer
- Other hereditary cancer syndromes
- Chronic sporadic pancreatitis
39
Summarise the epidemiology of pancreatic cancer.
8-12/100,000
8th cause of cancer deaths worldwide
x2 males
60-80 years (peak age)
40
Recognise the presenting symptoms of pancreatic cancer.
Very non-specific:
- Anorexia
- Nausea
- Malaise
- Weight loss
Later:
- Jaundice
- Epigastric pain
41
Recognise the signs of pancreatic cancer on physical examination.
- Weight loss
- Epigastric tenderness
- Epigastric mass
- Jaundice
- Palpable gallbladder
- Hepatomegaly (metastasis)
- Trousseau's sign (due to superficial thrombophlebitis) - carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes
[Courvoisier's law - palpable gallbladder + painless jaundice isn't gallstones]
42
Identify appropriate investigations for pancreatic cancer and interpret the results.
1. Bloods
2. Imaging
3. Other
Bloods
- Tumour markers CA19-9, CEA elevated
- If jaundiced, high bilirubin, high ALP, deranged clotting
Imaging
- US
- Endoscopic ultrasound
- FNA
- CT
- MRI
- PET
- Laparoscopy
- ERCPY - biopsy, bile cytology, stenting
Other
- Staging laparoscopy
- Intraoperative ultrasound
43
Define breast cancer.
Malignancy arising from breast tissue.
44
Explain the aetiology / risk factors of breast cancer.
Combination of genetic and environmental factors.
Polygenic risk - 5-10% inherited
- BRCA-1 (17q), BRCA-2 (13q) in 2% - 87% risk for carriers
- Li-Fraumeni Snydrome - TP53
- Cowden's Syndrome - PTEN
- Peutz-Jeghers Syndrome - STK11 / LKB1
- Ataxia-telangiectasia - ATM
- Muir-Torre Syndrome - MSH2/ MLH1
Risk Factors:
- Age
- Prolonged exposure to female sex hormones - particularly oestrogen
- Nulliparity
- Early menarche
- Late menopause
- Menopausal hormone replacement therapy
- Obesity
- Alcohol
45
Summarise the epidemiology of breast cancer.
Worldwide, leading cause of cancer death in women - 2nd to lung cancer.
Lifetime risk if 1:9 in the UK.
Peak incidence - 40-70 year olds
Rare in men - <1% of all breast cancers
46
Recognise the presenting symptoms of breast cancer.
Detected from screening
Symptoms of Primary:
- Breast lump
- Painless
- Changes in breast shape
- Nipple discharge
Symptoms of Secondary Spread
- Axillary lump
- Bone pain
- Weight loss
- Paraneoplastic syndromes - e.g. cerebellar syndrome
47
Recognise the signs of breast cancer on physical examination.
Inspection of the breasts with teh patient upright and supine, assessing for asymmetry, peau d'orange appearance of the skin (oedema), dimpling or tethering, nipple scaling or inversion or, in advanced cases, ulceration.
Palpation using clockwise radial technique (for hard, irregular, fixed lumps)
Examination for palpable axillary, supraclavicular lymph nodes, chest abnormalities, hepatomegaly, bony tenderness.
48
Identify appropriate investigations for breast cancer and interpret the results.
Triple Assessment - standardized approach to investigating a breast lump, consisting of clinical examination, imaging (mammography, ultrasound, MRI) and tissue diagnosis (cytology or biopsy)
Mammogram
- Useful screening investigation in women > 35 years
- UK Screening - >50 years
- Craniocaudal and mediolateral oblique views
- Features of malignancy - branching or linear microcalcifications and spiculated lesions
US
- Identify cystic lesions from sinister solid lesions
- More useful in women <35 years
Fine-Needle Aspiration
- Minimally invasive
- Allows cytology of discrete breast lumps and draining of cysts
Core Biopsy
- Can be image-guided, enables histological diagnosis
Sentinal Lymph Node Biopsy
- Radioactive tracer and / or blue dye is injected near the breast lesion
- A nuclear scan identifies the sentinel node
- Node is biopsied to detect spread
Staging
- CT - chest, abdomen, pelvis
- PET or bone scanning for metastases
Bloods
- FBC
- U&E
- Ca2+
- Bone profile
- LFT
- Tumour marker - CA-15-3
Histology
- In situ carcinoma - non-invasive with basement membrane intact - ductal or lobular carcinoma in situ (DCIS, LCIS)
- Invasive - ductal carcinoma (75% of breast cancers)
- Others - lobular (10-15% with Indian filing arrangement of cells), tubular, mucinous, medullary, cribiform, papillary, Paget's disease of the nipple (ductal carcinoma in situ infiltrating the nipple)
Grading:
- Nottingham modification of the Bloom and Richardson grading system
- Tubule formation, nuclear size / pleomorphism and number of mitoses
- Scores used to generate Grades 1 to 3
Staging
- The UICC TNM-staging system
- Tumour size - T1 <2cm, T2 2-5cm, T3 >5cm, T4 - any size with chest wall or skin extension
- Nodes - N1 mobile ipsilateral axillary, N2 fixed ipsilateral axillary, N3 ipsilateral internal mammary nodes
- Metastases - M0 no distant metastases, M1 distant metastases
49
Define deep vein thrombosis (DVT).
Formation of a thrombus within the deep veins - most commonly of the calf or thigh
50
Explain the aetiology / risk factors of deep vein thrombosis (DVT).
As it is has come to be known today, Virchow's triad consists of stasis, vessel damage, and hypercoagulability, and is used to describe the etiology and assess the risk of thrombosis, especially of deep vein thrombosis (DVT.)
Risk factors:
- Medical hospitalisation within the past 2 months
- Major surgery within 3 months
- Active cancer
- Lower-extremity trauma
- Severe trauma
- Increasing age
- Pregnancy
- Factor V Leiden
- Prothrombin gene mutation G20210A
- Protein C or S deficiency
- Anti-thrombin deficiency
- Antiphospholipid antibody syndrome
- Medical comorbidity
- Use of specific drugs
- Smoking
- Obesity
- Recent long-distance air travel
- Family history
51
Summarise the epidemiology of deep vein thrombosis (DVT).
The precise number of people affected by DVT/PE is unknown, although as many as 900,000 people could be affected (1 to 2 per 1,000) each year in the United States. Estimates suggest that 60,000-100,000 Americans die of DVT/PE (also called venous thromboembolism).
52
Recognise the symptoms of deep vein thrombosis (DVT).
- Calf swelling
- Localised pain along deep venous system
- Asymmetric oedema
- Prominent superficial veins
- Swelling of entire leg
- Phlegmasia cerulea dolens
53
Recognise the signs of deep vein thrombosis (DVT).
- Examine for swelling
- Examine for calf tenderness
- Severe leg oedema and cyanosis (phlegmasia cerulea dolens) is rare
- Respiratory examination for signs of a PE
Use Wells Clinical Prediction Score
54
Identify appropriate investigations for deep vein thrombosis (DVT).
1. Doppler ultrasound
2. Bloods
3. ECG, CXR, ABG - if PE?
Doppler US
- Gold standard
- Good sensitivity for femoral veins
- Less sensitive for calf veins
Bloods
- D-dimers = fibrinogen degradation products - sensitive but non-specific and only useful as a negative predictor in low-risk patinets
- Thrombophilia screen, prior to starting anticoagulation - if recurrent episodes
- FBC - platelet count prior to starting heparin
- U&E
- Clotting
55
Generate a management plan for deep vein thrombosis (DVT).
Anticoagulation:
- Heparin - whilst awaiting therapeutic INR from warfarin anti-coag
- DVT below knee treated with anti-coagulation for 3 months
- DVT above knee treated with anticoagulation for 6 months
- Recurrent DVT - long term warfarin
- If active anticoagulation is contraindicated and/or high risk of embolisation - place IVC filter by IVR to prevent embolus in lungs
Prevention:
- Use of graduated compression stockings
- Mobilisation if possible
- At-risk groups should have prophylactic heparin - e.g. low-molecular weight heparin if no contraindications
56
Identify the possible complications of deep vein thrombosis (DVT) and its management.
Of the disease:
- PE
- Damage to vein valves
- Chornic venous insufficiency of the lower limb (pro-thrombotic syndrome)
- Venous infarction - phlegmasia cerulea dolens
Of the treatment:
- Heparin-induced thrombocytopaenia
- Bleeding
57
Summarise the prognosis for patients with deep vein thrombosis (DVT).
Depends on extent of DVT, below-knee DVTs lower risk of embolus.
More proximal DVTs have higher risk of propagation and embolisation, which if large, may be fatal.
58
Define pulmonary embolism.
Occlusion of pulmonary vessels, most commonly caused by a thrombus that has travelled to the vascular system from another site.
59
Explain the aetiology / risk factors of pulmonary embolism.
- Thrombus
- 95% originate from DVT of lower limbs
- Rarely from right atrium in patients with AF
- Amniotic fluid embolus
- Air embolus
- Fat emboli
- Tumour emboli
- Mycotic emboli from right-sided endocarditis
Risk factors:
- Surgical patients
- Immobility
- Obesity
- OCP
- Heart failure
- Malignancy
60
Summarise the epidemiology of pulmonary embolism.
Fairly common, especially in hospitalized patients
| Occur in 10-20% of those with a confirmed proximal DVT.
61
Recognise the symptoms of pulmonary embolism.
Depends on site and size.
Small - may be asymptomatic
Moderate
- Sudden onset dyspnoea
- Cough
- Haemoptysis
- Pleuritic chest pain
Large
- Sudden onset dyspnoea
- Cough
- Haemoptysis
- Severe pleuritic chest pain
- Shock
- Collapse
- Acute right heart failure
- Sudden death
Multiple Small Recurrent
- Symptoms of pulmonary hypertension
62
Recognise the signs of pulmonary embolism.
Clinical Probability Assessment
- Well's Score - >4 high probability, <3 probability
```
Clinically suspected DVT = 3.0
PE is most likely diagnosis = 3.0
Recent surgery (4 weeks) = 1.5
Immobilization = 1.5
Tachycardia = 1.5
History of DVT or PE = 1.5
Haemoptysis = 1
Malignancy = 1
```
- Raised Geneva Score - >11 high probability, 4-10 intermediate probability, <3 low probability
```
>65 = 1
Recent surgery or fracture (28 days) = 2
Previous DVT / PE = 3
Active maliganancy = 2
Unilateral leg pain = 3
Haemoptysis = 2
Heart Rate > 75-94/min = 3
Heart Rate >85/min = 5
Unilateral leg oedema and tenderness = 4
```
Small
- No clinical signs
- Tachycardia
- Tachypnoea
Moderate
- Tachycardia
- Tachypnoea
- Pleural rub
- Low O2 sats - despite O2 supplementation
Large
- Shock
- Cyanosis
- Signs of right heart strain - e.g. raised JVP, left parasternal heave, accentuated S2 heart sound
Multiple Recurrent PE
- Signs of pulmonary hypertension and right heart failure
63
Identify the appropriate investigations for pulmonary embolism and interpret the results.
Low Probability
- D-dimer blood test - cross-linked fibrin degradation products
- Highly sensitive
- Poor specificity
High Probability
- Requires imaging
Additional:
- Bloods - ABG, thrombophilia screen
- ECG - normal, tachycardia, right axis deviation, RBBB
- CXR - exclude other differentials
NB: Classic Si, QIII, TIII pattern uncommon.
- Spiral CT Pulmonary Angiogram - 1st line, poor sensitivity for small emboli
- Ventilation-Perfusion (VQ) Scan - administration of IV 99mTc macro-aggregated albumin and inhalation of 81 krypton gas to identify areas of ventilation and perfusion mismatch
(If abnormal CXR or co-existing lung disease, do not use due to difficulty in interpretation)
- Pulmonary angiography - gold standard, invasive though
- Doppler USS of lower limb - to examine for VT
- Echocardiogram - right heart strain shown
64
Define lung cancer.
Non-Small Cell
- Primary malignant neoplasm of the lung (80%)
- Squamous cell carcinoma, adenocarcinoma, large cell carcinoma, adenosquamous carcinoma
Small Cell
- Malignant neoplasm of neuroendocrine Kulchitsky cells of the lung with early dissemination
- AKA oat cell carcinoma
65
Explain the aetiology / risk factors of lung cancer.
Non-Small Cell
- Genetic alterations that result in neoplastic transformation
- Mainly in main or lobar bronchi
- Adenocarcinoma = more peripherally
Risk Factors
- Smoking (active or passive)
- Occupational exposure - e.g. polycyclic hydrocarbons, asbestos, nickel, chromium, cadmium, radon
- Atmospheric pollution
Small Cell
- Smoking
- Occupational and environmental exposures
66
Summarise the epidemiology of lung cancer.
Non-Small Cell
- Most common fatal malignancy in the West - 18% of cancer mortality
- 35,000 deaths per year UK
- 3x more common in men, but increasing in women
Small Cell
- 20% of all lung cancers
67
Recognise the symptoms of lung cancer.
Non-Small Cell
- Asymptomatic with radiographic abnormality found (5%)
- Primary = cough, haemoptysis, chest pain, recurrent pneumonia
- Local invasion = e.g. brachial plexus (Pancoast tumour in apex of lung) causing pain in shoulder or arm, left recurrent laryngeal nerve (hoarseness and bovine cough), oesophagus (dysphagia), heart (palpitations / arrhythmias)
- Metastatic or paraneoplastic phenomena = weight loss, fits, bone pain, fractures, neuromyopathies
Small Cell
- Asymptomatic with radiographical abnormality found
- Primary tumour = cough, haemoptysis, dyspnoea, chest pain
- Metastatic disease = weight loss, fatigue, bone pain
- Paraneoplastic Syndrome = weakness, lethargy, seizures, muscle fatiguability
68
Recognise the signs of lung cancer on physical examination.
Non-Small Cell
- No signs
- Fixed monophonic wheeze
- Signs of collapse, consolidation, pleural effusion
- Local Invasion = SVC compression (facial congestion, distension of neck veins, upper limb oedema), Brachial plexus (wasting of small muscles of hand), Sympathetic Chain (Horner's - miosis, ptosis, anhydrosis)
- Metastases = supraclavicular lymphadenopathy, hepatomegaly
- Paraneoplastic Phenomena = hypertrophic osteoarthropathy - e.g. clubbing, painful/swollen wrists/ankles due to periosteal new bone formation, dermatological signs
Small Cell
- No signs or a fixed wheeze on auscultation of the chest
- Signs of lobular collapse or pleural effusion
- Signs of metastases - e.g. supraclavicular lymphadenopathy, hepatomegaly
- Signs of paraneoplastic syndromes
69
Identify appropriate investigations for lung cancer and interpret the results.
Non-Small Cell
1. Diagnosis
2. TNM Staging
3. Bloods
4. Pre-Operative
Diagnosis
- CXR - coin lesions, lobar collapse, pleural effusion, features of lymphangitis carcinomatosis
- Sputum cytology
- Bronchoscopy with brushings or biopsy
- CT or US-guided percutaneous biopsy
- Lymph node biopsy
TNM Staging
- Based on tumour size, nodal involvement and metastatic spread
- Use CT chest, CT or MRI head and abdomen or ultrasound, bone scan, PET scan
- Invasive methods - e.g. mediastinoscopy, video-assisted thoracoscopy used
Bloods
- FBC
- U&E
- Ca2+ - hypercalcaemia common
- AlkPhos - high bone metastases
- LFT
Pre-Op
- ABG
- Pulmonary function tests - FEV1 > 80% predicted to tolerate a pneumonectomy
- Lung resection is contraindicated if FEV <30% predicted
- V/Q scan
- ECG
- Echocardiogram
- General anaesthetic assessment
Small Cell
1. Diagnosis - sputum cytology, bronchoscopy with brushings and biopsy, percutaneous biopsy, thoracoscopy
2. Staging - CT of chest, abdomen, head, isotope boen scan
3. Other - lung function tests, FBC, U&E, Ca2+, AlkPhos, LFT
70
Define squamous cell carcinoma.
Malignancy of the epidermal keratoinocytes of the skin.
Marjolin's Ulcer - a squamous cell carcinoma that arises in an area of chronically inflammed or scarred skin.
71
Explain the aetiology / risk factors of squamous cell carcinoma.
Bowen's Disease - intra-epidermal carcinoma in situ
- Proliferation of atypical keratinocytes
- Basement membrane intact
- Solitary or multiple red-brown scaly patches
Squamous Cell Carcinoma
- Malignant keratinocytes invade locally into the dermis
- Spread to local lymph nodes
- Distally metastasies - e.g. lungs, liver
- Staging on TNM
Risk Factor:
- UV radiation from sunlight exposure
- Actinic keratoses - sun-induced precancerous lesions
- Radiation
- Carcinogens - e.g. tar derivatives, cigarette smoke, soot, industrial oils, arsenic
- Chronic skin disease - e.g. lupus, peukoplakia
- Human Papilloma Virus
- Long-term immunosuppression - e.g. transplant recipients, HIV
- DNA repair genetic defects - e.g. xeroderma pigmentosum
72
Recognise the presenting symptoms of squamous cell carcinoma.
- Skin lesion
- Ulcerated
- Recurrent bleeding or non-healing
73
Recognise the signs of squamous cell carcinoma on physical examination.
- Variable appearance
- Ulcerated
- Hyperkeratotic
- Crusted or scaly
- Non-healing lesion
- Often on sun-exposed areas
- Palpate for local lymphadenoapthy
74
Identify appropriate investigations for squamous cell carcinoma and interpret the results.
- Biopsy
- CT body scan
- MRI scan
- PET scan
- FBC with differential
- LFTs
- CXR
- Non-invasive imaging technologies
75
Summarise the epidemiology of squamous cell carcinoma and interpret the results.
2nd most common cutaneous malignancy - 20% of skin cancer
Often occurring in middle-aged and elderly light-skinned individuals.
Incidence 1 in 4000 annually
M:F 2-3:1
76
Define thyroid cancer.
5 Types: Papillary, Follicular, Medullary, Lymphoma and Anaplastic.
1) Papillary
- 60%
- Younger patients
- Spread - lymph nodes, lung (jugulodigastric node)
- Treatment - total thyroidectomy to remove non-obvious tumour +/- node excision +/- radioiodine
- Give levothyroixine to suppress TSH
- Prognosis - better if young and female
2) Follicular
- <25%
- Middle-age
- Spread - via blood to bone and lungs early
- Well-differentiated
- Treatment - total thyroidectoomy + T4 suppression + radioiodine ablation
3) Medullary
- 5%
- Sporadic (80%) or part of MEN Syndrome
- Produce calcitonin which can be used as a tumour marker
- Do not concentrate iodine
- Perform a phaeochromocytoma screen pre-operatively
- Treatment - thyroidectomy + node clearance
- External beam radiotherapy may prevent regional reoccurrence
4) Lymphoma
- 5%
- F:M 3:1
- Present with stridor or dysphagia
- Do full staging pre-treatment - chemoradiotherapy
- Assess histology for mucosa-associated lymphoid tissue (MALT) origin - associated with good prognosis
5) Anaplastic
- Rare
- F:M 3:1
- Elderly, poor response to any treatment
- In absence of unresectable disease, excision and radiotherapy may be tried
77
Explain the aetiology / risk factors of thyroid cancer.
Risk Factors:
- Head and neck irradiation
- Female sex
- Family history of thyroid cancer
78
Summarise the epidemiology of thyroid cancer.
4 types account for 98% of thyroid malignancies.
79
Recognise the presenting symptoms of thyroid cancer.
- Asymptomatic thyroid nodule
- Detected by palpation or US in women in 30s or 40s
- Hoarseness
- Dyspnoea
- Rapid neck enlargement
80
Recognise the signs of thyroid cancer on physical examination.
- Palpable thyroid nodule
- Vocal hoarseness
- Tracheal deviation
- Cervical lymphadenopathy
81
Identify appropriate investigations for thyroid cancer and interpret the results.
1st Line
- TSH - normal
- US neck - nodule number, characteristics, cervical lymph nodes
- Fine needle biopsy
- Laryngoscopy - may show ipsilateral paralyzed vocal cord
- Free T4, T3
- I-123 thyroid scan and uptake
- Core biopsy
- US elastography
- Molecular analysis of cytology specimens
- Sentinel node biopsy
82
Define bladder cancer.
Cancer that forms in tissues of the bladder.
Most are transitional cell carcinomas - inner lining of bladder cells.
83
Explain the aetiology / risk factors of bladder cancer.
Risk factors:
- Tobacco exposure
- Exposure to chemical carcinogens
- Age >55 years
- Pelvic radiation
- Systemic chemotherapy
- Schistosoma infection
- Male sex
- Chronic bladder inflammation
- Positive FHx
- DM Type 2
84
Summarise the epidemiology of bladder cancer.
Ranks ninth in worldwide cancer incidence. Egypt, Western Europe, and North America have the highest incidence rates and Asian countries the lowest rates. More than 90% of new cases occur in people ≥55 years of age.
Over 90% of cancers of the urinary bladder are urothelial carcinoma (previously termed transitional cell carcinoma; UC). Non-muscle-invasive tumours are most common. Low-grade tumours are papillary and generally easy to visualise. High-grade tumours are often flat or in situ, and can be difficult to visualise. If muscle invasion occurs, transurethral resection is insufficient and radical cystoprostatectomy is usually advised.
85
Recognise the presenting symptoms of bladder cancer.
- Presence of risk factors
- Haematuria - gross or microscopic
- Dysuria
- Urinary frequency
86
Recognise the signs of bladder cancer on physical examination.
- Presence of risk factors
- Haematuria - gross or microscopic
- Dysuria
- Urinary frequency
87
Identify appropriate investigations for bladder cancer and interpret the results.
- Urinalysis - red blood cell casts and crenated red cells seen with glomerular bleeding, haematuria, pyuria
- Urine cytology - +ve in 90% of patients with carcinoma or high-grade tumours, <33% of patients with low-grade transitional cell
- Renal and bladder ultrasound - bladder tumours/ upper tract obstruction
- CT urogram - bladder tumours, upper urinary tract tumours, and/or obstruction
- Cystoscopy
- IV urogram - filing defects indicative of bladder tumours
- FBC - normal or mild anaemia
- Chemistry profile (AlkPhos) - normal or elevated AlkPhos (also give bone scan)
- CXR
- CT abdomen and pelvis - rule out stone disease, may reveal primary bladder cancer and/or metastatic disease
- MRI abdomen and pelvis
- MR urogram
- Bone scan - normal or hot spots indicative of bony deposits
- Urinary markers
88
Define renal cell carcinoma.
A malignancy arising from renal parenchyma/ cortex, and accounts for about 85% of kidney cancers.
89
Explain the aetiology / risk factors of renal cell carcinoma.
Risk factors:
- Smoking
- Male sex
- Age over 55 years
- Residence in developed countries
- Black / American-Indian ethnicity
- Obesity
- Hypertension
- Positive family history of RCC
- History of hereditary syndrome
- History of acquired renal cystic disease
Weak risk factors:
- Asbestos/Cadmium
- Obstetric history / oestrogen exposure
- Pelvic radiation
90
Recognise the presenting symptoms of renal cell carcinoma.
TRIAD = Flank pain, Haematuria, Palpable Abdominal Mass.
Can be asymptomatic - indicidental finding (>50%)
- Presence of risk factors
- Haematuria
- Flank pain
Non-specific systemic symptoms:
- Fever
- Weight loss
- Sweats
- Pallor
- Cachexia
- Myoneuropathy
91
Recognise the signs of renal cell carcinoma on physical examination.
- Flank tenderness
- Palpable abdominal mass
- Haematuria
Rare:
- Scrotal varicocele
Signs of hepatic dysfunction:
- Ascites
- Hepatomegaly
- Spider angiomata
Signs of IVC involvement:
- Lower limb oedema
Hereditary Syndromes:
- Dermatological manifestation
- Birt-Hogg-Dube - papules
- Hereditary leimyomatous - skin fibromas
Von Hippel Lindau:
- Vision loss
- Retinal angiomatosis detected on fundoscopy
92
Identify appropriate investigations for renal cell carcinoma and interpret the results.
BLOODS
- FBC - paraneoplastic syndrome (reduced Hb or elevated RBC) symptoms such as anaemia of chronic disease, erythrocytosis
- LDH - >1.5 upper limit
- Corrected calcium - >2.5mmol/L (>10mg/dL)
- LFTs - metastatic disease / paraneoplastic syndrome= abnormal
Transaminitis (elevated liver transaminases, aspartate aminotransferase/alanine aminotransferase) and/or poor liver function may be indicative of metastatic lesions.
In the absence of liver metastases, cholestasis (elevated bilirubin, alk phos, gamma-GT), with concomitant elevated prothrombin time, thrombocytosis, and hepatosplenomegaly, is a paraneoplastic presentation of RCC known as Stauffer syndrome.
- Coagulation - elevated PT in paraneoplastic syndrome
In the absence of liver metastases, cholestasis (elevated bilirubin, alk phos, gamma-GT), with concomitant elevated prothrombin time (PT), thrombocytosis, and hepatosplenomegaly, is a paraneoplastic presentation of RCC known as Stauffer syndrome
- Creatinine - elevated with reduced creatinine clearance indicating chronic renal insufficiency either preceding or due to RCC (know baseline function)
URINALYSIS
- Haematuria
- Proteinuria - seen in CKD and HTN which are risk factors for RCC
IMAGING
- Abdominal / pelvic US Scan - cyst / mass, lymphadenopathy
- CT CAP - renal mass, lymphadenopathy, bone or visceral metastases
- MRI CAP - renal mass, lymphadenopathy, bone or visceral metastases
- Bone scan - uptake in bone site consistent with metastases (if bone pain or elevated AlkPhos)
93
Define tumour lysis syndrome.
An oncological emergency characterised by metabolic and electrolyte abnormalities that can occur after the initiation of any cancer treatment, but can also occur spontaneously.
94
Explain the aetiology / risk factors of tumour lysis syndrome.
It is caused by rapid breakdown of large numbers of cancer cells and subsequent release of large amounts of intracellular content into the bloodstream, which overwhelms normal homeostatic mechanisms.
Can lead to:
- AKI
- Cardiac arrhythmias
- Seizures
- Neuromuscular dysfunction
- Death
- Compromise clinical management of cancer patients
Risk factors:
- Haematological malignancy
- Large tumour burden
- Chemosensitive tumours
- Recent chemotherapy
- Pre-existing renal impairment
- Dehydration
- Volume depletion
- Nephrotoxic medication
- Advanced age
95
Summarise the epidemiology of tumour lysis syndrome.
Most commonly associated with highly proliferative, bulky, chemosensitive haematological malignancies, particularly high-grade B-cell lymphoid malignancies (e.g. acute lymphocytic leukaemia and Burkitt's lymphoma).
96
Recognise the presenting symptoms of tumour lysis syndrome.
- Syncope
- Chest pain
- Dyspnoea
- Seizures
- Nausea & Vomiting
- Anorexia
- Diarrhoea
- Muscle weakness
- Muscle cramps
- Lethargy
- Paraesthesia
97
Recognise the signs of tumour lysis syndrome on physical examination.
Laboratory TLS (2 or more):
- Hyperuricaemia
- Hyperphosphataemia
- Hyperkalaemia
- Hypocalcaemia
Clinical TLS (one or more):
- AKI
- Cardiac arrhytmia
- Seizure
- Sudden death
Other signs:
- Haematological malignancy
- Pre-existing renal impairment
- Lymphadenopathy
- Splenomegaly
- Hypertenison / hypotension
- Oliguria / anuria / Haematuria
98
Identify appropriate investigations for tumour lysis syndrome and interpret the results.
- Serum uric acid - >476 micromol/L (>8mg/dL) or 25% increase from baseline
- Serum phosphate - high previous levels increase likelihood, adults >1.45mmol/L (4.5mg/dL) or 25% increase from baseline
- Serum potassium - >6.0 mmol/L (>6mg/L) or 25% increase from baseline
- Serum calcium - <1.75mmol/L (<7mg/dL) or 25% decrease from baseline
- FBC - elevated WBC levels, increase risk of TLS
- Lactate dehydrogenase - elevated
- Serum creatinine - >1.5x upper limit of normal
- Serum urea - elevated with renal impairment, acute kidney injury, dehydration
- Urine pH - <5
- ECG - arrhythmia
Hyperkalaemia = peaked T waves, long PR and QRS intervals, flat P waves --> AV conduction blocks, VFib, Asystole
Hypocalcaemia = long QT --> ventricular arrhythmias
Biochemistry should be performed at first presentation prior to initiation of cancer treatment, and for 2-3 days after initiation of treatment.
99
Define neutropenic sepsis.
It is defined as a temperature of greater than 38°C or any symptoms and/or signs of sepsis, in a person with an absolute neutrophil count of 0.5 x 10^9/L or lower.
100
Explain the aetiology / risk factors of neutropenic sepsis.
Causes:
- Cytotoxic chemotherapy - temporary reduction in production of blood cells (5-10 days after chemotherapy neutrophils are at their lowest, recover 5 days later)
- Drugs - azathioprine, methotrexate, sulfasalazine, adalimumab, infliximab
- Stem cell transplantation
- Infections
- Bone marrow disorders such as aplastic anaemia and myelodysplastic syndromes
- Nutritional deficiencies
- Autoimmune
Risk factors:
- People receiving high-intensity chemotherapy regimens
- People undergoing haematopoietic stem cell transplantations
- Age - >60yrs
- Chemotherapy
- Corticosteroids
- Antibiotics
- Advanced maliganncy
- History of previous febrile neutropenia
- Prolonged hospital admission
- Previous surgery
- DM
- Liver disease
- Renal disease
- Poor nutritional status
- CV access device
- TPN - risk of invasive fungal infection
101
Summarise the epidemiology of neutropenic sepsis.
Rate of increase of deaths is higher for 15-24 year old age group, lower for >80 age group.
102
Recognise the presenting symptoms of neutropenic sepsis.
- Neutrophil count <0.5 x 10^9/L
- Temperature >38 degrees
- Chills and shvering
- Tachycardia
- Tachypnoea
- Clammy
- Cold
- Pale or mottled skin
- Dizziness
- Confusion
- Disorientation
- Slurred speech
- Diarrhoea
- N&V
103
Recognise the signs of neutropenic sepsis on physical examination.
- Neutrophil count <0.5 x 10^9/L
- Temperature >38 degrees
- Chills and shvering
- Tachycardia
- Tachypnoea
- Clammy
- Cold
- Pale or mottled skin
- Dizziness
- Confusion
- Disorientation
- Slurred speech
- Diarrhoea
- N&V
104
Identify appropriate investigations for neutropenic sepsis and interpret the results.
Take blood tests and microbiology samples including:
- Blood gas including glucose and lactate measurement — hypoglycaemia may result from depleted glycogen stores; hyperglycaemia may result from the stress response to sepsis; hyperlactataemia is a non-specific indicator of cellular or metabolic stress and is a marker of illness severity, with a higher level predictive of higher mortality rates.
- Blood culture — ideally done before antibiotic administration.
- Full blood count — white cell count may be high or low; thrombocytopenia may indicate disseminated intravascular coagulation (DIC), but may also be chemotherapy- or tumour-related.
- C-reactive protein (CRP) — may indicate infection and/or inflammation.
- Creatinine, urea and electrolytes — may indicate dehydration and/or acute kidney injury.
- Liver function tests — increased bilirubin or alanine aminotransferase (ALT) levels may indicate cholestasis or other liver dysfunction, and may be chemotherapy-induced.
- Clotting screen — if abnormal may indicate coagulopathy/DIC.
- Urine analysis and culture, sputum microscopy and culture, chest X-ray, and additional investigations such as chest CT or bronchoalveolar lavage may be indicated if there is severe or prolonged neutropenia. This may allow identification of the source of infection, pathogen(s) and sensitivities, and subsequent tailoring and/or de-escalation of antibiotic therapy if appropriate. Source control to eliminate a focus of infection may be possible, such as abscess drainage, debridement of infected tissue, removal of infected devices or foreign bodies, or surgery.
105
Define testicular cancer.
Cancer that forms in tissues of one or both testicles. Testicular cancer is most common in young or middle-aged men. Most testicular cancers begin in germ cells (cells that make sperm) and are called testicular germ cell tumors.
106
Explain the aetiology / risk factors of testicular cancer.
Risk factors:
- Cryptorchidism
- Gonadal dysgenesis
- Family history of testicular cancer
- Personal history of testicular cancer
- Testicular atrophy
- White ethnicity
- HIV infection
- Chemical carcinogens and low sperm count
- Rural residence
- Higher socioeconomic status
- Inguinal hernia
- Genetic abnormality
107
Summarise the epidemiology of testicular cancer.
The most common malignancy in young adult men (20 to 34 years of age), and highly curable when diagnosed early.
108
Recognise the presenting symptoms of testicular cancer.
- Presence of risk factors
- Age 20-34 years
- Testicular mass - 55% on right side, 2% bilateral, 85% painless, 10% acute pain
- Extratesticular manifestation - e.g. bone pain, extremity swelling (venous occlusion), supraclavicular lymph nodes, hyperthyroidism, gynaecomastia
109
Recognise the signs of testicular cancer on physical examination.
- Presence of risk factors
- Age 20-34 years
- Testicular mass - 55% on right side, 2% bilateral, 85% painless, 10% acute pain
- Extratesticular manifestation - e.g. bone pain, extremity swelling (venous occlusion), supraclavicular lymph nodes, hyperthyroidism, gynaecomastia
110
Identify appropriate investigations for testicular cancer and interpret the results.
- Ultrasound with colour Doppler of testis - testicular mass
- CXR - mediastinal and lung mass suggestive of metastasis
- CT Scan (AP) - enlarged retroperitoneal lymph nodes
- Serum beta-hCG - >0.7 IU/L - elevated in all choriocarcinomas, 5-10% of seminomas
- Serum AFP - >25microgram / L - elevated by embryonal carcinoma, yolk sac tumours, combined tumours but NOT choriocarcinomas and seminomas
- Serum LDH - only elevated marker in 10% of non-seminomas, elevated in 50% of all cases
- Histological examination of testicular mass post-rochiectomy
- Serum placenta AlkPhos - elevated in 40% patients with advanced disease
- Serum gamma-GT - >85 U/L in 1/3 cases of seminoma
- MRI AP - staging tool
- CT Chest - show metastatic lesions
111
Define prostate cancer.
A malignant tumour of glandular origin, situated in the prostate.
112
Explain the aetiology / risk factors of prostate cancer.
Risk factors:
- Age >50 years
- Black ethnicity
- North American or Northwest European descent
- Family history of prostate cancer
- High levels of dietary fat
113
Summarise the epidemiology of prostate cancer.
Prostate cancer is the second leading cause of cancer mortality in men in the US.
Uncommon in men aged under 50 years.
114
Recognise the presenting symptoms of prostate cancer.
- Presence of risk factors
- Nocturia
- Urinary frequency
- Urinary hesitancy
- Dysuria
- Haematuria
- Weight loss/anorexia
- Lethargy
- Bone pain
115
Recognise the signs of prostate cancer on physical examination.
- Elevated PSA
- Abnormal digital rectal exam
- Palpable lymph nodes
- Haematuria
116
Identify appropriate investigations for prostate cancer and interpret the results.
1st Line:
- Serum PSA - >4 micrograms / L
- Testosterone - baseline test for patients in whom androgen deprivation is considered
- LFTs - check for risk of hepatitis when giving androgen deprivation
- FBC - normal except for advanced metastatic disease
- Renal function - normal except for locally advanced disease causing obstruction
- Prostate biopsy - malignant cells detected (grade 1-5)
Consider:
- Bone scan
- Plain X-rays
- Pelvic CT scan
- Pelvic MRI / endorectal MRI
117
Define CNS tumours - Meningioma, Acoustic neuroma, Medulloblastoma, Astrocytic brain tumour, Craniopharyngioma, Primary CNS lymphoma, Non-functional pituitary adenoma, Acromegaly, Cushing's, Prolactinoma.
A brain tumour is an abnormal growth occuring in any tissue contained within the cranium, including the brain, cranial nerves, meninges, skull, pituitary gland and pineal gland.
May be benign or malignant and originate from within the cranium (primary) or from a metastatic tumour found elsewhere (secondary).
Present with signs of raised ICP and gait abnormality.
Meningioma:
- Primary tumour of cranial and spinal compartments
```
Acoustic Neuroma (Vesticular Schwannoma):
- Benign, slow-growing cerebellopontine angle tumour that grows from the superior vestibular component of the vestibulocochlear nerve
```
Medulloblastoma:
- Malignant, invasive brain tumour arising from cerebellar vermis
Astrocytic Brain Tumours:
- Primary tumour of the brain arising from astrocytes, which are an important part of the blood-brain barrier
- A neuroepithelial type tumour categorised by histological type and grade with each subtype having different age-adjusted incidence rate, behaviour and clinical course
Craniopharyngioma:
- Benign extra-axial non-glial epithelial tumours of the CNS
Acromegaly:
- Due to pituitary somatotroph adenoma in 99% of cases
Cushing's Disease :
- Hypercortisolism caused by an ACTH-secreting pituitary adenoma
Prolactinoma:
- Benign, prolactin-expressing and secreting pituitary adenoma
118
Explain the aetiology / risk factors of CNS tumours - Meningioma, Acoustic neuroma, Medulloblastoma, Astrocytic brain tumour, Craniopharyngioma, Primary CNS lymphoma, Non-functional pituitary adenoma, Acromegaly, Cushing's, Prolactinoma.
```
Acoustic Neuroma (Vesticular Schwannoma):
- Neurofibromatosis Type 2 - autosomal dominant
```
Craniopharyngioma:
- Arise within the sellar / suprasellar space
Primary CNS lymphoma:
- Immunosuppression
- HIV infection
- EBV infection
Non-functional pituitary adenoma:
- Multiple endocrine neoplasia Type 1 (MEN-1)
Acromegaly:
- Pituitary somatotroph adenomas chronically secrete excessive GH
- Stimulates IGF-1 production
119
Summarise the epidemiology of CNS tumours - Meningioma, Acoustic neuroma, Medulloblastoma, Astrocytic brain tumour, Craniopharyngioma, Primary CNS lymphoma, Non-functional pituitary adenoma, Acromegaly, Cushing's, Prolactinoma.
Meningioma:
- Represent over 36% of primary brain tumours, 53.5% of all non-malignant tumours
- More common in women and usually benign
Medulloblastoma:
- Usually in first 2 decades of life
- Common brain tumours of childhood
Astrocytic Brain Tumours:
- Common in industrial countries
- White males
Craniopharyngioma:
- Both children and adults
- Presents at any age
- Bimodal age distribution - peak between 5-14 years and 50-70 years
Primary CNS lymphoma:
- <1% of all non-Hodgkin's lymphoma
- Uncommon
Prolactinoma:
- Women during childbearing years
120
Recognise the presenting symptoms of CNS tumours - Meningioma, Acoustic neuroma, Medulloblastoma, Astrocytic brain tumour, Craniopharyngioma, Primary CNS lymphoma, Non-functional pituitary adenoma, Acromegaly, Cushing's, Prolactinoma.
Meningioma:
- Neurological deficit
- Progressive, focal or general headaches in large tumours
- Visible bony growth
Acoustic Neuroma (Vesticular Schwannoma):
- Unilateral sensorineural hearing loss
- Found on routine hearing examinations
- Progressive dizziness
- Unilateral facial numbness
Medulloblastoma:
- Due to mass effect from tumour or due to obstructive hydrocephalus
- Morning headaches
- Nausea
- Vomiting (relieving headaches)
- Diplopia - 6th nerve palsy
- Ataxia
Astrocytic Brain Tumours:
- Focal neurological defecits according to location
- Signs of raised ICP
Craniopharyngioma:
- Mass effect symptoms
- Visual loss
- Symptoms of ICP
- Pituitary dysfunction
- Children - growth failure
- Adults - diabetes insipidus and sexual dysfunction
Non-functional pituitary adenoma:
- Features of hormonal insufficiency
- Longstanding and progress slowly
Prolactinoma:
- Hyperprolactinaemia
- Hypogonadism
- Sexual dysfunction
- Galactorrhoea
- Hypopituitarism
- Osteoporosis
121
Recognise the signs of CNS tumours on physical examination, including pituitary mass, acute headache, ataxia, hyperprolactinaemia, short stature assessments.
PITUITARY MASS ASSESSMENT
- 2 type
- Clinically Non-functional Adenoma (CNFA) - no hypersecretion of hormone
- Functional Adenoma - hypersecretion of hormone
Functional:
- Acromegaly
- Cushing's disease
- Prolactinoma
Compression of adjacent structures:
- Visual disturbances
- Ophthalmoplegia
- Headaches
ACUTE HEADACHE ASSESSMENT:
- Most with a benign diagnosis
- HIgh index of suspicion
- Brain tumours causing headaches seen on non-enhancing contrast CT
- 0.7-1.3% of all paeds emergency visits
- 62% of patients with childhood brain tumours have a headache, 98% have 1 neurological symptom on exam
ATAXIA ASSESSMENT:
- Hereditary or acquired
- Cerebellar, sensory or vestibular
- Extensive list of acquired causes - e.g. vascular, demyelinating, neoplastic, autoimmune, toxic, degenerative, compressive, infectious aetiologies
HYPERPROLACTINAEMIA
- Prolactinomas - micro or macroadenomas
- Acromegaly
- Interruption of the hypothalamic-pituitary axis
SHORT STATURE
- Craniopharyngioma
- Cushing's syndrome during childhood
- Symptoms of Craniopharyngioma: Diplopia, vision loss, headache, short stature
122
Identify appropriate investigations for CNS tumours and interpret the results - Meningioma, Acoustic neuroma, Medulloblastoma, Astrocytic brain tumour, Craniopharyngioma, Primary CNS lymphoma, Non-functional pituitary adenoma, Acromegaly, Cushing's, Prolactinoma.
Meningioma:
- MRI with and without contrast enhancement
- Asymptomatic lesions followed up with serial observation
```
Acoustic Neuroma (Vesticular Schwannoma):
- Gadolinium-enhanced MRI
```
Medulloblastoma:
- Cranial CT and MRI
Astrocytic Brain Tumours:
- Cranial imaging with surgical biopsy
Craniopharyngioma:
- Crania CT / MRI
- Full endocrine evaluation
Primary CNS lymphoma:
- Cranial CT
- Clinical history
- LP & CSF analysis
Non-functional pituitary adenoma:
- Endocrine evaluation
- Cranial imaging
Acromegaly:
- IGF-1 hypersecretion biochemical confirmation
Cushing's Disease :
- Demonstration of unsuppressed ACTH
- Cranial MRI
Prolactinoma:
- Assessment of serum prolactin levels
- Cranial imaging
123
Define multiple myeloma.
A plasma cell dyscrasia characterized by terminally differentiated plasma cells, infiltration of bone marrow by plasma cells and the presence of monoclonal immunoglobulin (or immunoglobulin fragment) in serum and/or urine.
124
Explain the aetiology / risk factors of multiple myeloma.
Risk factors:
- Osteolytic bone disease
- Anaemia
- Renal failure
- Abnormal free light-chain ratio
- Monoclonal gammopathy of undetermined significance (MGUS)
- Family history
- Radiation exposure
- Petroleum products exposure
125
Summarise the epidemiology of multiple myeloma.
Myeloma incidence rates are projected to rise by 11% in the UK between 2014 and 2035, to 12 cases per 100,000 people by 2035. [1] This includes a larger increase for males than for females. It is projected that 8,888 cases of myeloma (5,229 in males, 3,659 in females) will be diagnosed in the UK in 2035.
126
Recognise the presenting symptoms of multiple myeloma.
- Anaemia
- Bone pain
- Monoclonal gammopathy of undetermined significance (MGUS)
- Infections
- Fatigue
- Renal impairment
127
Recognise the signs of multiple myeloma on physical examination.
- Anaemia
- Bone pain
- Monoclonal gammopathy of undetermined significance (MGUS)
- Infections
- Fatigue
- Renal impairment
128
Identify appropriate investigations for multiple myeloma and interpret the results.
1st Line:
- Serum / urine electrophoresis - paraprotein spike, hypogammaglobulinaemia
(IgG >35g/L or IgA >20g/L and light chain urinary excretion >1g/day)
- Skeletal survey - osteopenia, osteolytic lesions, pathological fractures
- Whole-body, low-dose computed tomography (WBLD-CT) - osteolytic lesions (>5mm in diameter), pathological fractures
- Serum-free light-chain assay - increased concentrations of free light chain in serum
- Bone marrow aspirate and biopsy - monoclonal plasma cel infiltration in bone marrow >10%
- Serum calcium - hypercalcaemia
- FBC - anaemia
- Creatinine, urea - renal impairment (creatinin >176 mmol/L)
- Serum beta-2-microglobulin - correlates with clinical stages, <3.5mgd/dL (stage 1), >5.5mgL (Stage 3)
- Serum albumin - prognostic significance - >35g/L (stage I)
Consider:
- Whole body MRI - >1 focal lesions on MRI study, bone marrow infiltration
- 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) - bone disease, bone marrow infiltration
- CRP - high or increasing
- LDH - higher = more extensive disease
- Cytogenetics & fluorescence in situ hybridisation analysis - chromosomal trisomies or monosomies
129
Define Hodgkin's lymphoma.
An uncommon haematological malignancy arising from mature B cells.
130
Explain the aetiology / risk factors of Hodgkin's lymphoma.
Characterized by the presence of Hodgkin's cells and Reed-Sternberg cells.
Risk factors:
- History of EBV infection
- Family history
- Young adults from higher socio-economic class
- HLA types
- Jewish ancestry
131
Summarise the epidemiology of Hodgkin's lymphoma.
Hodgkin's lymphoma is a rare cancer of the lymphatic system that affects the B-lymphocytes and leaves a patient susceptible to infection. Estimates suggest that around 1 in 25,000 people are affected by this cancer every year and the condition accounts for just under 1% of all cancers that occur worldwide.
132
Recognise the presenting symptoms of Hodgkin's lymphoma.
B-Symptoms:
- Fevers
- Night sweats
- Weight loss
Common presentation:
- Painless
- Cervical and/or supraclavicular lymphadenopathy
- Young adult
Uncommon factors:
- Unexplained fevers
- Night sweats
- Weight loss
- Dyspnoea
- Cough
- Chest pain
- SVC syndrome - due to extensive mediastinal adenopathy causing dyspnoea, cough, orthopnoea, facial and upper extremity oedema and dilated neck veins
- Abdominal pain
- Generalised pruritus
- Alcohol-induced pain at involved sites
- Hepatomegaly and / or splenomegaly
- Tonsillar enlargement
133
Recognize the signs of Hodgkin's lymphoma on physical examination.
B-Symptoms:
- Fevers
- Night sweats
- Weight loss
Common presentation:
- Painless
- Cervical and/or supraclavicular lymphadenopathy
- Young adult
Uncommon factors:
- Unexplained fevers
- Night sweats
- Weight loss
- Dyspnoea
- Cough
- Chest pain
- SVC syndrome - due to extensive mediastinal adenopathy causing dyspnoea, cough, orthopnoea, facial and upper extremity oedema and dilated neck veins
- Abdominal pain
- Generalised pruritus
- Alcohol-induced pain at involved sites
- Hepatomegaly and / or splenomegaly
- Tonsillar enlargement
134
Identify appropriate investigations for Hodgkin's lymphoma and interpret the results.
- FBC - low Hb and platelets, WBC may be high or low
- Metabolic panel - normal
- ESR - elevated
- CXR - mediastinal mass, large mediastinal adenopathy (negative prognostic factor)
- PET-CT scan - involved sites appear FDG-avid (bright)
- Gallium scan - bright involved sites
- Contrast CT neck, chest and AP - enlarged lymph nodes
- Excisional lymph node biopsy - Hodgkin's cells
- Immunohistochemical studies - CD30-positive, CD15-positive, CD45-negative, CD20 positive
Investigations to consider:
- Bone marrow biopsy - Hodgkin's cells
- TFTs - abnormal in patients who receive radiotherapy to neck
- Echo or multi-gated acquisition (MUGA) scan
- Pulmonary function tests
135
Define non-Hodgkin's lymphoma.
A heterogeneous group of malignancies of the lymphoid system.
136
Explain the aetiology / risk factors of non-Hodgkin's lymphoma.
- Malignant lymphoid cells retain many qualities of their normal counterparts - e.g. defending organism from external and internal (neoplastic) threats
- Boundaries between leukaemias and lymphomas are blurred - e.g. acute alymphocytic leukaemia and acute lymphoblastic lymphoma, chronic lymphocytic leukaemia and small lymphocytic lymphoma
- Depends on relative presence of solid phase (lymphoma) versus circulating phase (leukaemia)
Risk factors:
- Age > 50 years
- Male
- Immunocompromised host
- Epstein-Barr virus (EBV)
- HTLV-1 virus
- Herpes Virus-8
- H.pylori
- Coeliac disease
- HIV
- Hepatitis C virus
- Sjogren's syndrome
- Wiskott-Aldrich Syndrome
- Ataxia - Telangiectasia
- Organ transplant
- Borrelia burgdoferi
- Rheumatoid arthritis
- SLE
- Common veriable immunodeficiency
- Chediak-Higashi syndrome
- Klinefelter's syndrome
- Pesticides
- Phenoxyherbicides
- Breast implants
137
Summarise the epidemiology of non-Hodgkin's lymphoma.
- 4% of total cancer cases
- 80-84 years peak rate
- Increase by 39% incidence rate since 1990s
138
Recognise the presenting symptoms of non-Hodgkin's lymphoma.
- Night sweats
- Weight loss
- Fatigue / malaise
- Fever
- Shortness of breath
- Cough
- Abdominal discomfort
- Headache
- Change in mental status
- Dizziness
- Ataxia
- Chest pain
- Bone pain
- Back pain
- Jaundice
- Pallor
- Purpura
- Skin lesions
139
Recognise the signs of non-Hodgkin's lymphoma on physical examination.
- Fever
- Lymphadenopathy
- Splenomegaly
- Hepatomegaly
- Abdominal discomfort
- Change in mental status
- Jaundice
- Pallor
- Purpura
- Skin lesions
- Neuological abnormalities on examination
140
Identify appropriate investigations for non-Hodgkin's lymphoma and interpret the results.
1st Line:
- FBC - thrombocytopenia, pancytopenia, lymphocytosis from bone-marrow / liver involvement
- Blood smear - nucleated red blood cells, left shift
- Lymph node biopsy - positive
- Skin biopsy - positive
- Bone marrow biopsy - positive
- Basic metabolic panel - normal or deranged kidney, electorlyte and glucose function
- LFTs - elevated due to liver involvement
- LDH - elevated
Consider:
- Flow cytometry - tumour surface markers determined, type of lymphoma
- Immunohistochemistry - tumour surface markers determined, type of lymphoma
- PCR for tumor markers - BCL1 and BLC2, TCR
- Ig gene rearrangement studies - detection of rearrnaged genes
- Cytogenetics studies with or without FISH - chromosomal translocations
- Hep B and C serology - negative, if positive then risk of reatcivation, need to determine prior to chemo
- HIV - positive or negative
- LP - presence of abnormal cells, low glucose, high protein, high pressure (for Burkitt's lymphoma, primary CNS lymphoma, AIDS-related B-cell lymphoma, CNS relapse risk high)
- Colonoscopy - micropolyps
- CT - staging tool
- Multiple-gated acquisition scan - cardiac baseline function
- Echo - cardiac baseline function
- PET scan - involved sites brightness
141
Define acute myeloid leukaemia.
The clonal expansion of myeloid blasts in the bone marrow, peripheral blood or extramedullar tissue.
Acute promyelocytic leukaemia (APML) - form of AML with normal WBC, bi-lobed nuclei, hypergranulated blasts, bundles of Auer rods.
142
Define acute lymphocytic leukaemia.
A malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered through somatic changes and undergoes uncontrolled proliferation.
143
Define chronic myeloid leukaemia.
The malignant clonal disorder of haematopoietic stem cell that results in marked myeloid hyperplasia of the bone marrow.
144
Define chronic lymphocytic leukaemia.
NB: The main difference between lymphocytic leukemias and lymphomas is that in leukemia, the cancer cells are mainly in the bone marrow and blood, while in lymphoma they tend to be in lymph nodes and other tissues.
Chronic lymphocytic leukaemia:
An indolent lymphoproliferative disorder in which monoclonal B lymphocytes are found in peripheral blood.
(if found in lymph nodes = small lymphocytic lymphoma).
145
Summarise the epidemiology leukaemia (AML, ALL, CML, CLL).
Leukaemia incidence rates are projected to rise by 5% in the UK between 2014 and 2035, to 19 cases per 100,000 people by 2035. [1] This includes an increase for males and a drop for females. It is projected that 13,758 cases of leukaemia (8,714 in males, 5,044 in females) will be diagnosed in the UK in 2035.
146
Recognize the presenting symptoms of acute myeloid leukaemia.
- Pallor
- Ecchymoses or petechiae
- Fatigue
- Dizziness
- Palpitations
- Dyspnoea
- Infections or fever
- Lymphadenopathy
- Hepatosplenomegaly
- Mucosal bleeding
147
Explain the aetiology / risk factors of chronic myeloid leukaemia.
Dysregulation of haematopoiesis due to BCR-ABL fusion gene.
Abnormal expansion of myeloid cells in bone marrow and peripheral blood.
Chronic phase may transform to accelerated or blast phase in 5-10% of patients despite tyrosine kinase inhibitor treatment = acute myeloid or acute lymphoblastic leukaemia.
Risk factors:
- Age 65-74 years
- Ionising radiation exposure
- Male
148
Explain the aetiology / risk factors of chronic lymphocytic leukaemia.
Risk factors:
- Age over 60 years
- Male sex
- White ethnicity
- Family history of CLL
149
Identfiy appropriate investigations for leukaemia (AML, ALL, CML and CLL) and interpret the results.
AML:
- FBC - anaemia, macrocytosis, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - blasts on blood film, presence of Auer rods
- Coagulation panel - if abnormal = DIC
- Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid
- Renal function - elevated urea
- LFTs - normal or elevated
- Serum lactic dehydrogenase - elevated
- Bone marrow biopsy or aspiration - hypercellularity, infiltration
- Immunophenotyping and molecular studies - specific lineage of blasts
- Lumbar puncture- malignant cells
- HLA antigen typing
- CXR - consolidation, pulmonary infiltrates, cardiomegaly due to leukostasis
- Echocardiogram
- Multi-gated acquisition scan
ALL:
- FBC - anaemia, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - leukaemic lymphoblasts
- Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid
- Renal function - elevated or normal urea
- Liver function - elevated or normal
- Lactic dehydrogenase - elevated
- Coagulation profile
- Bone marrow aspiration and trephine biopsy - hypercellularity, lymphoblastic infiltration
- Immunophenotyping
- TPMT phenotype -
- Cytogenetics
- Molecules studies - Philadelphia chromosome?
- HLA-typing
- CXR - mediastinal mass, pleural effusion, LRTI
- LP - leukaemic lymphoblasts
- Pleural tap - leukaemic lymphoblasts
- CT / MRI brain
- CT
- Minimal residual disease molecular samples
150
Recognise the presenting symptoms of chronic myeloid leukaemia.
- Presence of risk factors
- Splenomegaly
- Shortness of breath
- Left upper quadrant discomfort or fullness
- Epistaxis
- Arthralgia
- Sternal tenderness
- Weight loss
- Excessive sweating
- Fever
- Pallor
- Bruising
- Retinal haemorrhages
151
Identfiy appropriate investigations for leukaemia (AML, ALL, CML and CLL) and interpret the results.
AML:
- FBC - anaemia, macrocytosis, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - blasts on blood film, presence of Auer rods
- Coagulation panel - if abnormal = DIC
- Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid
- Renal function - elevated urea
- LFTs - normal or elevated
- Serum lactic dehydrogenase - elevated
- Bone marrow biopsy or aspiration - hypercellularity, infiltration
- Immunophenotyping and molecular studies - specific lineage of blasts
- Lumbar puncture- malignant cells
- HLA antigen typing
- CXR - consolidation, pulmonary infiltrates, cardiomegaly due to leukostasis
- Echocardiogram
- Multi-gated acquisition scan
ALL:
- FBC - anaemia, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - leukaemic lymphoblasts
- Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid
- Renal function - elevated or normal urea
- Liver function - elevated or normal
- Lactic dehydrogenase - elevated
- Coagulation profile
- Bone marrow aspiration and trephine biopsy - hypercellularity, lymphoblastic infiltration
- Immunophenotyping
- TPMT phenotype -
- Cytogenetics
- Molecules studies - Philadelphia chromosome?
- HLA-typing
- CXR - mediastinal mass, pleural effusion, LRTI
- LP - leukaemic lymphoblasts
- Pleural tap - leukaemic lymphoblasts
- CT / MRI brain
- CT
- Minimal residual disease molecular samples
CML:
- FBC - high WCC, anaemina, normal platelets, thrombocytosis (chronic, accelerated), thrombocytopenia (accelerated or blast crisis)
- Complete metabolic profile - elevated potassium, LDH, uric acid
- Peripheral blood smear - mature or maturing myeloid cells, elevated basophils and eosinophils
- Bone marrow biopsy - granulocytic hyperplasia
- Cytogenetics - Philadelphia chromosome positive (t9,22)
- qRT-PCR - detection of BCR-ABL fusion
- FISH - t(9,22) positive
152
Recognise the presenting symptoms of chronic myeloid leukaemia.
- Presence of risk factors
- Splenomegaly
- Shortness of breath
- Left upper quadrant discomfort or fullness
- Epistaxis
- Arthralgia
- Sternal tenderness
- Weight loss
- Excessive sweating
- Fever
- Pallor
- Bruising
- Retinal hemorrhages
153
Recognise the presenting symptoms of chronic lymphocytic leukaemia.
- Shortness of breath and fatigue
- Lymphadenopathy
- Splenomegaly
- Hepatomegaly
- Presence of risk factors
- B-symptoms
- Recurrent infections
- Petechiae
154
Identfiy appropriate investigations for leukaemia (AML, ALL, CML and CLL) and interpret the results.
AML:
- FBC - anaemia, macrocytosis, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - blasts on blood film, presence of Auer rods
- Coagulation panel - if abnormal = DIC
- Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid
- Renal function - elevated urea
- LFTs - normal or elevated
- Serum lactic dehydrogenase - elevated
- Bone marrow biopsy or aspiration - hypercellularity, infiltration
- Immunophenotyping and molecular studies - specific lineage of blasts
- Lumbar puncture- malignant cells
- HLA antigen typing
- CXR - consolidation, pulmonary infiltrates, cardiomegaly due to leukostasis
- Echocardiogram
- Multi-gated acquisition scan
ALL:
- FBC - anaemia, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - leukaemic lymphoblasts
- Serum electrolytes - elevated calcium, potassium, phosphorus, uric acid, lactic acid
- Renal function - elevated or normal urea
- Liver function - elevated or normal
- Lactic dehydrogenase - elevated
- Coagulation profile
- Bone marrow aspiration and trephine biopsy - hypercellularity, lymphoblastic infiltration
- Immunophenotyping
- TPMT phenotype -
- Cytogenetics
- Molecules studies - Philadelphia chromosome?
- HLA-typing
- CXR - mediastinal mass, pleural effusion, LRTI
- LP - leukaemic lymphoblasts
- Pleural tap - leukaemic lymphoblasts
- CT / MRI brain
- CT
- Minimal residual disease molecular samples
CML:
- FBC - high WCC, anaemina, normal platelets, thrombocytosis (chronic, accelerated), thrombocytopenia (accelerated or blast crisis)
- Complete metabolic profile - elevated potassium, LDH, uric acid
- Peripheral blood smear - mature or maturing myeloid cells, elevated basophils and eosinophils
- Bone marrow biopsy - granulocytic hyperplasia
- Cytogenetics - Philadelphia chromosome positive (t9,22)
- qRT-PCR - detection of BCR-ABL fusion
- FISH - t(9,22) positive
CLL:
- WBC - elevated with absolute lymphocytosis (>5 x 10^9/L)
- Blood film - smudge / smear cells, spherocytes, polychromasia
- Haemoglobin - Hb < 110g/L (anaemia)
- Platelet count - thrombocytopenia (<100 x 10^9/L)
- Flow cytometry - CD5, CD19, CD20, CD23, CD38, CD49d, ZAP-70
- FISH - cytogenic abnormalities
- Molecular genetic analysis - mutations with IgVH or TP 53
- DAT - positive = autoimmune haemolytic anaemia
- Ig Levels - hypo-gammaglobulinaemia
- Bone marrow aspirate and trephine biopsy - infiltration by leukaemic cells, reduction in haematopoetic precursor compartment
- CT scan - may show hepatosplenomegaly; retroperitoneal or mediastinal adenopathy
