Cancer Flashcards
Learning objectives
Answer
Define basal cell carcinoma
• COMMONEST form of skin malignancy, also known as a rodent ulcer
Explain the aetiology / risk factors of basal cell carcinoma
- MAIN RISK FACTOR: prolonged sun exposure or UV radiation
- Seen in Gorlin’s syndrome
Other risk factors:
o Photosensitising pitch
o Tar
o Arsenic
Summarise the epidemiology of basal cell carcinoma
- COMMON in those with FAIR SKIN
- Common in areas of high sunlight exposure
- Common in the elderly
- Rare before the age of 40 yrs
- Lifetime risk in Caucasians = 1 in 3
Recognise the presenting symptoms of basal cell carcinoma
• A chronic slowly progressive skin lesion • Usually found on the: o FACE o Scalp o Ears o Trunk
Recognise the signs of basal cell carcinoma on physical examination
Nodulo-ulcerative (MOST COMMON)
o Small glistening translucent skin over a coloured papule
o Slowly enlarges
o Central ulcer with raised pearly edges
o Fine telangiectasia over the tumour surface
o Cystic change in larger lesions
Morphoeic
o Expanding
o Yellow/white waxy plaque with an ill-defined edge
o More aggressive than nodulo-ulcerative
Superficial
o Most often on trunk
o Multiple pink/brown scaly plaques with a fine edge expanding slowly
Pigmented
o Specks of brown or black pigment may be present in any BCC
Identify appropriate investigations for basal cell carcinoma and interpret the results
- Biopsy is RARELY necessary
* Diagnosis is mainly on clinical suspicion
Define bladder cancer
• Malignancy of bladder cells
o Most bladder cancers are transitional cell carcinomas
o RARELY, bladder cancers may be squamous cell carcinomas associated with chronic inflammation (e.g. schistosomiasis)
Explain the aetiology / risk factors of bladder cancer
• UNKNOWN • Risk Factors o Smoking o Dye stuffs (naphthylamines and benzidine) o Cyclophosphamide treatment o Pelvic irradiation o Chronic UTIs o Schistosomiasis
Summarise the epidemiology of bladder cancer
- 2% of cancers
- 2nd most common cancer of the genitourinary tract
- 2-3 x more common in MALES
- Peak incidence: 50-70 yrs
Recognise the presenting symptoms of bladder cancer
• Painless macroscopic haematuria • Irritative/storage symptoms o Frequency o Urgency o Nocturia • Recurrent UTIs • Rarely: ureteral obstruction
Recognise the signs of bladder cancer on physical examination
- Often NO SIGNS
* Bimanual examination may be performed as part of disease staging
Identify appropriate investigations for bladder cancer and interpret the results
- Cystoscopy - allows visualisation, biopsy or removal
- Ultrasound
- Intravenous urography
- CT/MRI for staging
Define breast cancer
• Malignancy of breast tissue
o Most common type: invasive ductal carcinoma
Explain the aetiology / risk factors of breast cancer
- Genetics (e.g. BRCA-1 and BRCA-2 genes)
- Environmental factors
Risk Factors o Age o Prolonged exposure to oestrogen • Nulliparity (not having kids) • Early menarche • Late menopause • Obesity • COCP • HRT o Family history of breast cancer
Summarise the epidemiology of breast cancer
- Most common cancer in women (1/9 women in the UK)
* Peak incidence: 40-70 yrs
Recognise the presenting symptoms of breast cancer
• Breast lump (usually painless) • Changes in breast shape • Nipple discharge (may be bloody) • Axillary lump • Symptoms of malignancy: o Weight loss o Bone pain o Paraneoplastic syndromes
Recognise the signs of breast cancer on physical examination
• Breast lump o Firm o Irregular o Fixed to surrounding structures • Peau d'orange • Skin tethering • Fixed to chest wall • Skin ulceration • Nipple inversion
• Paget’s disease of the nipple - eczema-like hardening of the skin on the nipple
o Usually caused by ductal carcinoma in situ infiltrating the nipple
Identify appropriate investigations for breast cancer and interpret the results
TRIPLE ASSESSMENT o Clinical examination o Imaging: • Ultrasound (< 35 yrs) OR • Mammogram (> 35 yrs) o Tissue Diagnosis: • Fine Needle Aspiration OR • Core Biopsy
Sentinel Lymph Node Biopsy
o A radioactive tracer is injected into the tumour and a scan identifies the sentinel lymph node
o This node is then biopsied to check the extend of spread
Staging
o CXR
o Liver ultrasound
o CT (brain/thorax)
Bloods: FBC, U&Es, calcium, bone profile, LFTs, ESR
Define central nervous system (CNS) tumours
- Tumours of the central nervous system.
- NOTE: brain tumours cannot be truly differentiated into benign and malignant because supposedly ‘benign’ tumours can cause significant morbidity and mortality
Instead they are differentiated into:
High-Grade = a tumour that grows rapidly and aggressively
• Glioma and glioblastoma multiforme
• Primary cerebral lymphoma
• Medulloblastoma
Low-Grade = a tumour that grows slowly and may or may not be successfully treated • Meningioma • Acoustic neuroma • Neurofibroma • Pituitary tumour • Craniopharyngeoma • Pineal tumour
Brain metastases commonly arise from: • Lung • Breast • Stomach • Prostate • Thyroid • Colorectal
Explain the aetiology / risk factors of central nervous system (CNS) tumours
• Can arise from any of the cells in the CNS (e.g. glial cells, ependymal cells, oligodendrocytes)
• Risk Factors
o Ionising radiation
o Immunosuppression (e.g. HIV)
o Inherited syndromes (e.g. neurofibromatosis, tuberous sclerosis)
Summarise the epidemiology of central nervous system (CNS) tumours
- Primary brain tumours = 2% of tumours diagnosed in the UK
- AIDS patients have an increased risk of developing CNS tumours
- Can develop at any age but are more common between 50-70 yrs
Recognise the presenting symptoms & signs of central nervous system (CNS) tumours
- Presentation depends on the size and location of the tumour
- Headache (worse in the morning and when lying down)
- Nausea and vomiting
- Seizures
- Progressive focal neurological deficits
- Cognitive and behavioural symptoms
- Papilloedema
Identify appropriate investigations for central nervous system (CNS) tumours and interpret the results
- Bloods - check CRP/ESR to eliminate other causes (e.g. temporal arteritis)
- CT/MRI
- Biopsy and tumour removal
- Magnetic resonance angiography - define changing size and blood supply of the tumour
- PET
- NOTE: distant metastases are RARE with primary CNS tumours
Define cholangiocarcinoma
• Primary adenocarcinoma of the biliary tree
Explain the aetiology / risk factors of cholangiocarcinoma
• UNKNOWN
• Risk Factors
o Ulcerative colitis + primary sclerosing cholangitis
o Choledochal cyst (congenital conditions involving cystic dilatations of bile ducts)
o Caroli disease (rare genetic condition in which you get dilatation of intrahepatic bile ducts)
o Parasitic infection of biliary tract
Summarise the epidemiology of cholangiocarcinoma
- VERY RARE
* More common in the developing world due to the increased prevalence of parasitic infections
Recognise the presenting symptoms of cholangiocarcinoma
Obstructive jaundice symptoms o Yellow sclera o Pale stools o Dark urine o Pruritus
Abdominal pain or fullness
Systemic symptoms of malignancy: weight loss, malaise, anorexia
Recognise the signs of cholangiocarcinoma on physical examination
• Jaundice • Palpable gallbladder o NOTE: Courvoisier's Law - in the presence of jaundice, a palpable gallbladder (that is non-tender) is unlikely to be due to gallstones (i.e. cancer of the pancreas or biliary tree is more likely) • Epigastric/RUQ mass • There may be hepatomegaly
Identify appropriate investigations for cholangiocarcinoma and interpret the results
Bloods o FBC o U&Es o LFTs (high ALP + GGT) o Clotting screen o Tumour markers • CA19-9 is a marker of pancreatic cancer and cholangiocarcinoma
Endoscopy
o ERCP will allow bile cytology and tumour biopsy
Ultrasound
CT, MRI, Bone Scan - for staging
Define colorectal carcinoma
• Malignant adenocarcinoma of the large bowel o Distribution: • 60% - rectum and sigmoid • 30% - descending colon • 10% - rest of colon
Explain the aetiology / risk factors of colorectal carcinoma
• Environmental and genetic • There is a sequence of genetic changes that go from normal bowel epithelium to cancer (e.g. APC, K-Ras) • Risk Factors o Western diet (e.g. red meat, alcohol) o Colorectal polyps o Previous colorectal cancer o Family history o IBD
Summarise the epidemiology of colorectal carcinoma
- SECOND MOST COMMON cause of cancer death in the West
- UK: 20,000 deaths per year
- Average age of diagnosis: 60-65 yrs
Recognise the presenting symptoms of colorectal carcinoma
• Depends on the size and location of the tumour
Left-Sided Colon and Rectum
o Change in bowel habit
o Rectal bleeding (blood or mucus mixed with the stools)
o Tenesmus (due to a space-occupying tumour in the rectum)
Right-Sided Colon o Presents later o Anaemia symptoms (lethargy) o Weight loss o Non-specific malaise o Lower abdominal pain (rare)
IMPORTANT: 20% of tumours will present as an EMERGENCY with pain and distension due to:
o Large bowel obstruction
o Haemorrhage or peritonitis due to perforation
Recognise the signs of colorectal carcinoma on physical examination
- Anaemia
- Abdominal mass
If metastatic:
o Hepatomegaly
o Ascites (shifting dullness)
• Low-lying rectal tumours may be palpable on DRE
Identify appropriate investigations for colorectal carcinoma and interpret the results
Bloods
o FBC - anaemia
o LFTs
o Tumour markers (CEA)
Stools
o FOBT - used as a screening test
Endoscopy
o Sigmoidoscopy
o Colonoscopy
o This can be used to biopsy the tumour
Double-Contrast Barium Enema
o May show ‘apple core’ strictures
Contrast CT
o For staging (Duke’s staging)
Define deep vein thrombosis (DVT)
• Formation of a thrombus within the deep veins (most commonly in the calf or thigh)
Explain the aetiology / risk factors of deep vein thrombosis (DVT)
• Deep veins in the legs are more prone to blood stasis, hence clots are more likely to form (look up Virchow’s triad)
Risk Factors o COCP o Post-surgery o Prolonged immobility o Obesity o Pregnancy o Dehydration o Smoking o Polycythaemia o Thrombophilia (e.g. protein C deficiency) o Malignancy
Summarise the epidemiology of deep vein thrombosis (DVT)
- VERY COMMON
* Especially in hospitalised patients
Recognise the presenting symptoms of deep vein thrombosis (DVT)
- Swollen limb
* May be painless
Recognise the signs of deep vein thrombosis (DVT) on physical examination
Examination of the Leg
o Local erythema, warmth and swelling
o Measure the leg circumference
o Varicosities (swollen/tortuous vessels)
o Skin colour changes
o NOTE: Homan’s Sign - forced passive dorsiflexion of the ankle causes deep calf pain
Risk is stratified using the WELLS CRITERIA (NOTE: this is different from the PE Wells criteria)
o Score 2 or more = high risk
Examine for PE
o Check respiratory rate, pulse oximetry and pulse rate
Identify appropriate investigations for deep vein thrombosis (DVT) and interpret the results
Doppler Ultrasound - GOLD STANDARD
Impedance Plethysmography - changes in blood volume results in changes of electrical resistance
Bloods
o D-dimer: can be used as a negative predictor
o Thrombophilia screen if indicated
If PE suspected
o ECG
o CXR
o ABG
Generate a management plan for deep vein thrombosis (DVT)
ANTICOAGULATION
o Heparin whilst waiting for warfarin to increase INR to the target range of 2-3
o DVTs that do NOT extend above the knee may be observed and anticoagulated for 3 months
o DVTs extending beyond the knee require anticoagulation for 6 months
o Recurrent DVTs require long-term warfarin
IVC Filter
o May be used if anticoagulation is contraindicated and there is a risk of embolisation
Prevention
o Graduated compression stockings
o Mobilisation
o Prophylactic heparin (if high risk e.g. hospitalised patients)
Identify the possible complications of deep vein thrombosis (DVT) and its management
- PE
- Venous infarction (phlegmasia cerulea dolens)
- Thrombophlebitis (results from recurrent DVT)
- Chronic venous insufficiency
Summarise the prognosis for patients with deep vein thrombosis (DVT)
- Depends on extent of DVT
- Below-knee DVTs have a GOOD prognosis
- Proximal DVTs have a greater risk of embolisation
Define gastric cancer
• Cancer of the stomach. Most commonly adenocarcinoma
Rarer causes of gastric cancer:
• Lymphoma
• Leiomyosarcoma
• Stromal tumours
Explain the aetiology / risk factors of gastric cancer
- UNKNOWN
- Environment and genetics
Risk Factors o Smoked and processed foods o Smoking o Alcohol o Helicobacter pylori infection o Atrophic gastritis o Pernicious anaemia o Partial gastrectomy o Gastric polyps
Summarise the epidemiology of gastric cancer
- COMMON cause of cancer death worldwide
- Highest incidence in JAPAN (and Asia in general)
- 6th most common cancer in the UK
- Usual age of presentation: > 50 yrs
Recognise the presenting symptoms of gastric cancer
- Often asymptomatic early
- Early satiety
- Epigastric discomfort
- Systemic symptoms: weight loss, anorexia, nausea/vomiting
- Dysphagia (in tumours of the gastric cardia)
- Symptoms of metastases (e.g. ascites, jaundice)
Recognise the signs of gastric cancer on physical examination
- Epigastric mass
- Abdominal tenderness
- Ascites
- Signs of anaemia
- Virchow’s Node (aka Troisier’s sign)
- Sister Mary Joseph’s Nodule (metastatic node on the umbilicus)
- Krukenberg’s Tumour (ovarian metastases)
Identify appropriate investigations for gastric cancer and interpret the results
- Upper GI endoscopy
- Bloods - FBC (check for anaemia), LFTs
- CT/MRI - for staging
- Endoscopic USS - assess depth of gastric invasion and lymph node involvement
Define hepatocellular carcinoma
• Primary malignancy of the liver parenchyma
Explain the aetiology / risk factors of hepatocellular carcinoma
Associated with:
Chronic liver damage
• Alcoholic liver disease
• Hepatitis C
• Autoimmune disease
Metabolic disease
• E.g. haemochromatosis
Aflatoxins
• E.g. cereals contaminated with fungi
Summarise the epidemiology of hepatocellular carcinoma
- COMMON
- 1-2% of all malignancies
- LESS common than liver metastases
- High incidence in regions where hepatitis B and C are endemic
Recognise the presenting symptoms of hepatocellular carcinoma
Symptoms of Malignancy
o Malaise
o Weight loss
o Loss of appetite
History of Exposure to Carcinogens
o High alcohol intake
o Hepatitis B or C (e.g. sexual activity, IV drug use)
o Aflatoxins
Abdominal distention
Jaundice
Recognise the signs of hepatocellular carcinoma on physical examination
Signs of Malignancy
o Cachexia
o Lymphadenopathy
- Hepatomegaly (may be nodular)
- Jaundice
- Ascites
- Bruit over the liver
Identify appropriate investigations for hepatocellular carcinoma and interpret the results
Bloods o FBC o ESR o LFTs o Clotting o a-fetoprotein - tumour marker for liver cancer o Hepatitis serology
Imaging
o Abdominal US
o CT/MRI - GOLD STANDARD for staging
Histology/Cytology
o Ascitic tap my be sent for cytological analysis
Staging
o CT scan (chest/abdo/pelvis)
Define ALL
• Malignancy of the bone marrow and blood characterised by the proliferation of lymphoblasts (primitive lymphoid cells)
Explain the aetiology / risk factors of ALL
- Lymphoblasts undergo malignancy transformation and proliferation
- This leads to the replacement of normal marrow elements, leading to bone marrow failure and infiltration into other tissues
Risk Factors: o Environmental (radiation, viruses) o Genetic (Down's syndrome, Neurofibromatosis type 1, Fanconi's anaemia, xeroderma pigmentosum)
Summarise the epidemiology of ALL
- MOST COMMON malignancy of CHILDHOOD
- Peak incidence: 2-5 yrs old
- There is a second peak in incidence in the elderly
- Annual UK incidence: 1/70,000
Recognise the presenting symptoms of ALL
Symptoms of Bone Marrow Failure:
o Anaemia (fatigue, dyspnoea)
o Bleeding (spontaneous bruising, bleeding gums, menorrhagia)
o Opportunistic infections
Symptoms of Organ Infiltration: o Tender bones o Enlarged lymph nodes o Mediastinal compression o Meningeal involvement (headache, visual disturbances, nausea)
Recognise the signs of ALL on physical examination
Signs of Bone Marrow Failure: o Pallor o Bruising o Bleeding o Infection
Signs of Organ Infiltration: o Lymphadenopathy o Hepatosplenomegaly o Cranial nerve palsies o Retinal haemorrhage o Papilloedema on fundoscopy o Leukaemic infiltration of the anterior chamber of the eye o Testicular swelling
Identify appropriate investigations for ALL and interpret the results
Bloods o FBC - normochromic normocytic anaemia, low platelets, variable WCC o High uric acid o High LDH o Clotting screen
Blood Film
o Abundant lymphoblasts
Bone Marrow Aspirate or Trephine Biopsy
o Hypercellular with > 20% lymphoblasts
Immunophenotyping - using antibodies to recognise cell surface antigens
Cytogenetic - karyotyping to look for chromosomal abnormalities or translocations
Cytochemistry
Lumbar Puncture - check for CNS involvement
CXR - may show mediastinal lymphadenopathy, lytic bone lesions
Bone Radiographs - mottled appearance with punched out lesions due to leukaemic infiltration
Define AML
• Malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the bone marrow and blood
o Classified using the FAB (French-American-British) System into EIGHT morphological variants
Explain the aetiology / risk factors of AML
- Myeloblasts undergo malignant transformation and proliferation
- This leads to replacement of normal marrow and bone marrow failure
Summarise the epidemiology of AML
- MOST COMMON acute leukaemia in ADULTS
* Incidence INCREASES with age
Recognise the presenting symptoms of AML
Symptoms of Bone Marrow Failure:
o Anaemia (lethargy, dyspnoea)
o Bleeding (due to thrombocytopaenia or DIC)
o Opportunistic or recurrent infections
Symptoms of Tissue Infiltration:
o Gum swelling or bleeding
o CNS involvement (headaches, nausea, diplopia)
Recognise the signs of AML on physical examination
Signs of Bone Marrow Failure: o Pallor o Cardiac flow murmur o Ecchymosis o Bleeding o Opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections)
Signs of Tissue Infiltration:
o Skin rashes
o Gum hypertrophy
o Deposit of leukaemic blasts in the eye, tongue and bone (RARE)
Identify appropriate investigations for AML and interpret the results
Bloods
o FBC - low Hb, low platelets, variable WCC
o High uric acid
o High LDH
o Clotting studies, fibrinogen and D-dimers (to check for DIC)
Blood Film
o Myeloblasts
Bone Marrow Aspirate or Biopsy
o Hypercellular with > 20% blasts
Immunophenotyping
o Antibodies against surface antigens used to classify the lineage of the abnormal clones
Cytogenetics
Immunocytochemistry
Define CLL
• Characterised by progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin. There is an overlap between CLL and non-Hodgkin’s lymphoma
Explain the aetiology / risk factors of CLL
• Malignant cells may accumulate as a result of their inability to undergo apoptosis
The most common chromosomal changes include:
o Trisomy 12
o 11q and 13q deletions
Summarise the epidemiology of CLL
- 90% are > 50 yrs
- More common in MALES
- Rare in Asians
Recognise the presenting symptoms of CLL
Asymptomatic - 40-50% of cases are diagnosed following routine blood tests
Systemic Symptoms:
o Lethargy
o Malaise
o Night sweats
Symptoms of Bone Marrow Failure:
o Recurrent infections
o Herpes zoster infection
o Easy bruising or bleeding
Recognise the signs of CLL on physical examination
- Non-tender lymphadenopathy
- Hepatomegaly
- Splenomegaly
LATE STAGE signs of bone marrow failure:
o Pallor
o Cardiac flow murmur
o Purpura/ecchymosis
Identify appropriate investigations for CLL and interpret the results
• NOTE: CLL may be associated with autoimmune phenomena such as haemolytic anaemia (warm agglutinins) or thrombocytopaenia
Bloods o FBC • Lymphocytosis • Low Hb - Could be due to bone marrow infiltration, hypersplenism or autoimmune haemolysis • Low platelets • Low serum Ig
Blood Film
o Small lymphocytes with thin rims of cytoplasm
o Smudge cells
Bone Marrow Aspirate or Biopsy
o Lymphocytic replacement of normal marrow
Cytogenetics
Define CML
• Chronic myeloblastic leukaemia is a malignant clonal disease characterised by proliferation of granulocyte precursors in the bone marrow and blood, distinguished from AML by its slower progression
Explain the aetiology / risk factors of CML
Malignant proliferation of stem cells
95% of cases have a chromosomal translocation between chromosomes 9 and 22 to form the Philadelphia chromosome
Variants of CML include:
o Ph-negative CML
o Chronic neutrophilic leukaemia
o Eosinophilic leukaemia
Pathogenesis
o The Philadelphia chromosome results in the formation of the BCR-ABL fusion gene
o The product of this gene enhances tyrosine kinase activity and drives cell replication
THREE phases of CML
o Relatively stable chronic phase (4-6 yr duration)
o Accelerated phase (3-9 months)
o Acute leukaemia phase - blast transformation
Summarise the epidemiology of CML
- Incidence increases with age
- Mean age of diagnosis: 40-60 yrs
- 4 x more common in MALES
Recognise the presenting symptoms of CML
ASYMPTOMATIC in 40-50% of cases - diagnosed on routine blood count
Hypermetabolic Symptoms:
o Weight loss
o Malaise
o Sweating
Bone Marrow Failure Symptoms: o Lethargy o Dyspnoea o Easy bruising o Epistaxis o Abdominal discomfort and early satiety o Rare symptoms: • Gout • Hyperviscosity symptoms (visual disturbance, headaches, priapism) o May present during a blast crisis with symptoms of AML and ALL
Recognise the signs of CML on physical examination
• SPLENOMEGALY - most common physical finding (90% of cases) • Signs of bone marrow failure: o Pallor o Bleeding o Ecchymosis
Identify appropriate investigations for CML and interpret the results
Bloods o FBC • High WCC • Low Hb • High basophils/neutrophils/eosinophils • High/normal/low platelets • High uric acid • High B12 and transcobalamin I
Blood Film
o Immature granulocytes
Bone Marrow Aspirate or Biopsy
o Hypercellular with raised myeloid-erythroid ratio
Cytogenetics
o Show the Philadelphia chromosome
Define lung cancer
• Primary malignant neoplasm of the lung
o WHO classification of bronchocarcinoma:
• Small Cell Lung Cancer - 20%
• Non-Small Cell Lung Cancer - 80%
Explain the aetiology / risk factors of lung cancer
- Smoking
- Asbestos exposure
- Other occupational exposure: polycyclic hydrocarbons, nickel, radon
- Atmospheric pollution
Summarise the epidemiology of lung cancer
- Most common FATAL cancer in the west (18% of cancer mortality worldwide)
- 3 x more common in MALES
Recognise the presenting symptoms of lung cancer
• May be ASYMPTOMATIC
Symptoms due to primary o Cough o Haemoptysis o Chest pain o Recurrent pneumonia
Symptoms due to local invasion
o Brachial plexus invasion –> shoulder/arm pain
o Left recurrent laryngeal nerve invasion –> hoarse voice and bovine cough
o Dysphagia
o Arrhythmias
o Horner’s syndrome
Symptoms due to metastatic disease or paraneoplastic phenomenon o Weight loss o Fatigue o Fractures o Bone pain
Recognise the signs of lung cancer on physical examination
- May be NO SIGNS
- Fixed monophonic wheeze (suggesting that there is a single obstruction)
- Signs of lobar collapse or pleural effusion
- Signs of metastases (e.g. supraclavicular lymphadenopathy or hepatomegaly)
Identify appropriate investigations for lung cancer and interpret the results
Diagnosis o CXR o Sputum cytology o Bronchoscopy with brushings or biopsy o CT/US-guided percutaneous biopsy o Lymph node biopsy
Staging - requires CT/MRI of head, chest and abdomen. PET scans may also be useful
Bloods o FBC o U&Es o Calcium (hypercalcaemia is a common feature) o ALP (raised with bone metastases) o LFTs
Pre-Op - ABG and pulmonary function tests
Define lymphoma (Hodgkin’s)
• Lymphomas are neoplasms of lymphoid cells, originating in the lymph nodes or other lymphoid tissues. Hodgkin’s lymphoma (15% of all lymphomas) is diagnosed histopathologically by the presence of Reed-Sternberg Cells (binucleate lymphocytes)
Explain the aetiology / risk factors of lymphoma (Hodgkin’s)
- UNKNOWN
- Likely to be an environmental trigger in a genetically susceptible individual
- EBV genome has been detected in 50% of Hodgkin’s lymphomas
Summarise the epidemiology of lymphoma (Hodgkin’s)
- Bimodal age distribution with peaks at 20-30 yrs and > 50 yrs
- More common in MALES
Recognise the presenting symptoms of lymphoma (Hodgkin’s)
Painless enlarging mass
o Most commonly in the neck
o Can also be in the axilla or groin
The mass may become painful after alcohol ingestion
B symptoms of Lymphoma
o Fever > 38 degrees
• If this is cyclical it is referred to as Pel-Ebstein fever
o Night sweats
o Weight loss > 10% body weight in the past 6 months
Other symptoms
o Pruritis
o Cough
o Dyspnoea
Recognise the signs of lymphoma (Hodgkin’s) on physical examination
- Non-tender firm rubbery lymphadenopathy (may be cervical, axillary or inguinal)
- Splenomegaly (or sometimes, hepatosplenomegaly)
- Skin excoriations
- Signs of intrathoracic disease (e.g. pleural effusion, superior vena cava obstruction)
Identify appropriate investigations for lymphoma (Hodgkin’s) and interpret the results
Bloods o FBC • Anaemia of chronic disease • Leucocytosis • High neutrophils • High eosinophils • Lymphopaenia in advanced disease o High ESR and CRP
Lymph Node Biopsy
Bone Marrow Aspirate and Trephine Biopsy
Imaging - CXR, CT, PET
Ann Arbor Staging o I = single lymph node region o II = 2+ lymph node regions on one side of the diaphragm o III = lymph node regions on both sides of the diaphragm o IV = extranodal involvement o A = absence of B symptoms o B = presence of B symptoms o E = localised extranodal extension o S = involvement of spleen
Define lymphoma (non-Hodgkin’s)
• Lymphomas are malignancies of lymphoid cells originating in lymph nodes or other lymphoid tissues. Non-Hodgkin’s lymphomas are a diverse group consisting of:
o 85% B cell
o 15% T cell and NK cell forms
• It can range from stable, indolent disease to aggressive disease
Explain the aetiology / risk factors of lymphoma (non-Hodgkin’s)
• Complex process involving the accumulation of multiple genetic lesions • The changes in the genome in certain lymphoma subtypes have been associated with the introduction of foreign genes via oncogenic viruses (e.g. EBV and Burkitt's lymphoma) • Other risk factors: o Radiotherapy o Immunosuppressive agents o Chemotherapy o HIV, HBV, HCV o Connective tissue disease (e.g. SLE)
Summarise the epidemiology of lymphoma (non-Hodgkin’s)
- Incidence increases with age
- More common in MALES
- More common in the WESTERN WORLD
Recognise the presenting symptoms of lymphoma (non-Hodgkin’s)
Painless enlarging mass (in neck, axilla or groin)
Systemic Symptoms (occurs less frequently than in Hodkin's): o Fever o Night sweats o Weight loss > 10% body weight o Symptoms of hypercalcaemia
Symptoms related to organ involvement o Extranodal disease is MORE COMMON in NHL than in Hodgkin's lymphoma o Skin rashes o Headache o Sore throat o Abdominal discomfort o Testicular swelling
Recognise the signs of lymphoma (non-Hodgkin’s) on physical examination
• Painless firm rubbery lymphadenopathy Skin rashes o Mycosis fungoides - looks like a fungal infection but is in fact a cutaneous T-cell lymphoma) • Abdominal mass • Hepatosplenomegaly
Signs of bone marrow involvement:
o Anaemia
o Infections
o Purpura
Identify appropriate investigations for lymphoma (non-Hodgkin’s) and interpret the results
Bloods o FBC • Anaemia • Neutropaenia • Thrombocytopaenia o High ESR and CRP o Calcium may be raised o HIV, HBV and HCV serology Blood Film o Lymphoma cells may be visible in some patients Bone Marrow Aspiration and Biopsy Imaging - CXR, CT, PET Lymph Node Biopsy - allows histopathological evaluation, immunophenotyping and cytogenetics Staging - Ann-Arbor
Define multiple myeloma
• Haematological malignancy characterised by proliferation of plasma cells resulting in bone lesions and the production of a monoclonal immunoglobulin (paraprotein, usually IgG or IgA)
Explain the aetiology / risk factors of multiple myeloma
- UNKNOWN
- Possible viral trigger
- Chromosomal aberrations are frequent
- Associated with ionising radiation, agricultural work or occupational chemical exposures
Summarise the epidemiology of multiple myeloma
- Annual incidence: 4/100,000
- Peak incidence: 70 yrs
- Afro-Caribbean > White People > Asians
Recognise the presenting symptoms of multiple myeloma
• May be an INCIDENTAL finding on routine blood tests
Bone Pain
o Usually in the back and ribs
o Sudden and severe bone pain may be caused by a pathological fracture
Infections - often recurrent
General o Tiredness o Thirst o Polyuria o Nausea o Constipation o Mental change (due to hypercalcaemia)
Hyperviscosity
o Bleeding
o Headaches
o Visual disturbance
Recognise the signs of multiple myeloma on physical examination
- Pallor
- Tachycardia
- Flow murmur
- Signs of heart failure
- Dehydration
- Purpura
- Hepatosplenomegaly
- Macroglossia
- Carpal tunnel syndrome
- Peripheral neuropathies
Identify appropriate investigations for multiple myeloma and interpret the results
Bloods o FBC - low Hb, normochromic normocytic o High ESR (and possible high CRP) o U&Es - high creatinine, high Ca2+ o Normal ALP
Blood Film
o Rouleaux formation with bluish background (suggests high protein)
Serum or Urine Electrophoresis
o Serum paraprotein
o Bence-Jones protein (monoclonal immunoglobulin light chain that’s found in the urine and suggests multiple myeloma)
Bone Marrow Aspirate and Trephine
o High plasma cells (usually > 20%)
Chest, Pelvic or Vertebral X-Ray
o Osteolytic lesions without surrounding sclerosis
o Pathological fractures
Define neutropenic sepsis
• The development of sepsis in a patient with neutropenia.
• Diagnostic criteria:
o Temperature > 38 degrees
o Neutrophil count < 0.5 x 109 /L
• CAUTION: patients can have neutropenic sepsis without a fever because they may be on anti-pyretic medications or steroids
Explain the aetiology / risk factors of neutropenic sepsis
• Incidental Neutropenia
o Congenital - ethnic variation, cyclical neutropenia in children (all VERY RARE)
o Acquired
• Decreased/ineffective neutrophil production: bone marrow infiltration, aplastic anaemia, B12/folate deficiency, chemotherapy, radiotherapy
• Accelerated turnover: Felty’s syndrome, hypersplenism, malaria
• Others: toxoplasmosis, dengue fever
• Febrile Neutropenia
o DEFINITION: temperature > 38.5 or two consecutive readings of > 38 for two hours and an absolute neutrophil count < 0.5 x 109 /L
Summarise the epidemiology of neutropenic sepsis
• Most common in patients with cytotoxic chemotherapy
Recognise the presenting symptoms & signs of neutropenic sepsis
• Check history for: o High-risk features: active cancer, recent chemotherapy, use of immunosuppressants or immunosuppressive illness (e.g. HIV) o Chronic kidney disease o Recent blood products o Intravascular devices (e.g. central line) • Examination findings: o Signs of infection may be minimal o Pyrexia o Features of infective endocarditis o Lymphadenopathy o Skin rashes
Identify appropriate investigations for neutropenic sepsis and interpret the results
- FBC (check neutrophil level)
- Blood cultures (check for sepsis)
- Others - blood film, D-dimer (for DIC), U&Es, creatinine, LFTs
Define oesophageal cancer
• Malignant tumour arising in the oesophagus. There are TWO major histological types:
o Squamous cell carcinoma
o Adenocarcinoma
Explain the aetiology / risk factors of oesophageal cancer
• Squamous Cell Carcinoma o Alcohol o Tumour o Plummer-Vinson syndrome o Achalasia o Scleroderma o Coeliac disease o Nutritional deficiencies o Dietary toxins (e.g. nitrosamines) • Adenocarcinoma o GORD o Barrett's oesophagus
Summarise the epidemiology of oesophageal cancer
- 8th most common cancer
- 3 x more common in MALES
- Squamous cell carcinoma is more common in DEVELOPING COUNTRIES
- Adenocarcinoma is more prevalent in the WESTERN WORLD
Recognise the presenting symptoms of oesophageal cancer
- Often ASYMPTOMATIC
- Progressive dysphagia (initially worse for solids)
- Regurgitation
- Cough
- Choking after food
- Voice hoarseness
- Odynophagia (painful swallowing)
- Weight loss
- Fatigue (due to iron deficiency anaemia)
Recognise the signs of oesophageal cancer on physical examination
• There may be NO SIGNS • Metastatic disease may cause: o Supraclavicular lymphadenopathy o Hepatomegaly o Hoarseness o Signs of bronchopulmonary involvement
Identify appropriate investigations for oesophageal cancer and interpret the results
- Endoscopy - brushings and biopsy
- Imaging - barium swallow and CXR
- Staging - CT chest and abdomen
- Other - bronchoscopy, lung function tests and ABGs
Define pancreatic cancer
• Malignancy arising from the exocrine or endocrine tissues of the pancreas
Explain the aetiology/risk factors of pancreatic cancer
• UNKNOWN • 5-10% are hereditary (e.g. MEN, HNPCC, FAP, Von-Hippel Lindau syndrome) • Risk Factors o Age o Smoking o Diabetes mellitus o Chronic pancreatitis o Dietary (low intake of fresh fruit and vegetables)
Summarise the epidemiology of pancreatic cancer
- Increasing incidence
- 2 x more common in MALES
- Peak age: 60-80 yrs
Recognise the presenting symptoms of pancreatic cancer
- Initial symptoms are often NON-SPECIFIC
- Anorexia
- Malaise
- Nausea
- Epigastric pain
- Weight loss
- Diabetes mellitus
- Jaundice
Recognise the signs of pancreatic cancer on physical examination
- Weight loss
- Epigastric tenderness or mass
- Jaundice and a palpable gallbladder (Courvoisier’s law - a palpable gallbladder with painless jaundice is unlikely to be due to gallstones)
- If metastatic spread –> hepatomegaly
- Trousseau’s Sign of Malignancy - superficial thrombophlebitis
Identify appropriate investigations for pancreatic cancer
• Bloods o CA 19-9 o CEA is also elevated o Obstructive jaundice features: • High bilirubin • High ALP • Deranged clotting • Imaging o Ultrasound o CT with/without guided biopsy o MRI/MRCP o ERCP - may allow biopsy, bile cytology and stenting
Define prostate cancer
• Primary malignant neoplasm of the prostate gland
Explain the aetiology/risk factors of pancreatic cancer
• UNKNOWN • Risk Factors o Age o Afro-Caribbean o Family history o Dietary factors o Occupational exposure to cadmium
Summarise the epidemiology of prostate cancer
- COMMON
* 2nd most common cause of male cancer deaths
Recognise the presenting symptoms of prostate cancer
• Often ASYMPTOMATIC • Lower Urinary Tract Obstruction o Frequency o Hesitancy o Poor stream o Terminal dribbling o Nocturia • Metastatic Spread o Bone pain o Cord compression o Systemic symptoms: malaise, anorexia, weight loss o Paraneoplastic syndromes (e.g. hypercalcaemia)
Recognise the signs of prostate cancer on physical examination
- Asymmetrical hard nodular prostate
* Loss of midline sulcus
Identify appropriate investigations for prostate cancer
• Bloods
o FBC
o U&Es
o PSA
• NOTE: not a very specific test for prostate cancer
o Acid phosphatase
o LFTs
o Bone profile
• CT/MRI Scan
o Assesses extent of local invasion and lymph node involvement
• Transrectal Ultrasound and Needle Biopsy
• Isotope Bone Scan - check for bone metastases
Define pulmonary embolism
Occlusion of pulmonary vessels, most commonly by a thrombus that has travelled to the pulmonary vascular system from another site
Explain the aetiology / risk factors of pulmonary embolism
Thrombus 95% arise from DVT in the lower limbs Rarely arises in the right atrium (in AF patients) Other causes of embolus: Amniotic fluid Air Fat Tumour Mycotic
Risk Factors Surgical patients Immobility Obesity OCP Heart failure Malignanc
Summarise the epidemiology of pulmonary embolism
Relatively COMMON (especially in hospitalised patients) Occur in 10 - 20% of patients with confirmed proximal DVT
Recognise the presenting symptoms of pulmonary embolism
Depends on the SITE and SIZE of the embolus
Small
may be ASYMPTOMATIC
Moderate Sudden onset SOB Cough Haemoptysis Pleuritic chest pain
Large (or proximal) As above and: Severe central pleuritic chest pain Shock Collapse Acute right heart failure Sudden death Multiple Small Recurrent Symptoms of pulmonary hypertension
Recognise the signs of pulmonary embolism on physical examination
Severity of PE can be assessed based on associated signs:
Small
often no clinical signs. There may be some tachycardia and tachypnoea
Moderate Tachypnoea Tachycardia Pleural rub Low O2 saturation ( despite O2 supplementation)
Massive PE Shock Cyanosis Signs of right heart strain Raised JVP Left parasternal heave Accentuated S2 heart sound
Multiple Recurrent PE
Signs of pulmonary hypertension
Signs of right heart failure
Identify appropriate investigations for pulmonary embolism and interpret the results
The Well's Score is used to determine the best investigation for PE Low Probability (Wells 4 or less) - use D dimer High Probability (Wells > 4) required imaging (CTPA)
Additional investigations:
Bloods - ABG, thrombophilia screen
ECG
May be normal
May show tachycardia, right axis deviation or RBBB
May show S1Q3T3 pattern
CXR
often NORMAL
but helps exclude other diagnoses
Spiral CT Pulmonary Angiogram FIRST LINE INVESTIGATION Poor sensitivity for small emboli VERY sensitive for medium to large emboli
Ventilation - Perfusion (VQ) Scan
Identifies areas of ventilation and perfusion mismatch, which would indicate an area of infarcted lung
Pulmonary Angiography
Invasive
Rarely necessary
Doppler US of Lower Limb
allows assessment of venous thromboembolism
Echocardiography
may show right heart strain
Generate a management plan for pulmonary embolism
Primary Prevention
Compression stockings
Heparin prophylaxis for those at risk
Good mobilisation and adequate hydration
If haemodynamically stable O2 Anticoagulation with heparin or LMWH Switch over to oral warfarin for at least 3 months Maintain INR 2 - 3 Analgesia
If haemodynamically UNSTABLE (massive PE)
Resuscitate
O2
IV fluids
Thrombolysis with tPA may be considered if cardiac arrest is imminent
Surgical or radiological
Embolectomy
IVC filters
sometimes used for recurrent PEs despite adequate anticoagulation or
when anticoagulation is contraindicated
Identify the possible complications of pulmonary embolism and its management
Death
Pulmonary infarction
Pulmonary hypertension
Right heart failure
Summarise the prognosis for patients with pulmonary embolism
30% mortality in those left untreated
8% mortality with treatment
Increased risk of future thromboembolic disease
Define renal cell carcinoma
• Primary malignancy of the kidneys
Explain the aetiology / risk factors of renal cell carcinoma
• Renal clear cell carcinoma (80%) - UNKNOWN CAUSE
• Papillary carcinoma (10%) - UNKNOWN CAUSE
• Transitional cell carcinoma (10%)
o NOTE: these occur at the renal pelvis
• Risk Factors
o Associated with certain inherited conditions:
• von Hippel-Lindau disease
Mutation in the von Hippel-Lindau protein, which causes headaches, balance issues, dizziness, limb weakness, vision problems and high blood pressure
• Tuberous sclerosis
A rare genetic disease that causes benign tumours to grow in the brain and other organs (e.g. skin, kidneys, lungs, eyes)
• Polycystic kidney disease
• Familial renal cell cancer
• Smoking
• Chronic dialysis
o NOTE: renal cell cancer can cause abnormal LFTs in the absence of liver metastases = Strauffer’s Syndrome
Summarise the epidemiology of renal cell carcinoma
- UNCOMMON
- 3% of all adult malignancies
- Peak incidence: 40-60 yrs
Recognise the presenting symptoms of renal cell carcinoma
• Renal Cell Carcinoma o Usually present LATE o Asymptomatic in 90% o Triad of Symptoms: • Haematuria • Flank pain • Abdominal mass • Transitional Cell Carcinoma o Presents EARLIER with haematuria • Systemic Signs of Malignancy o Weight loss o Malaise o Paraneoplastic syndromes (e.g. fever, hypercalcaemia, polycythaemia)
Recognise the signs of renal cell carcinoma on physical examination
- Palpable renal mass
- Hypertension
- Plethora
- Anaemia
- A left-sided tumour can obstruct the left testicular vein as it joins the left renal vein, and cause a left-sided varicocoele
Identify appropriate investigations for renal cell carcinoma and interpret the results
• Urinalysis o Haematuria o Cytology • Bloods o FBC o U&Es o Calcium o LFTs o High ESR (in 75%) • Abdominal Ultrasound
o Best first-line investigation o Can distinguish between solid masses and cystic structures • CT/MRI o Useful for staging • Staging system: Robson Staging
Define squamous cell carcinoma
• Malignancy of epidermal keratinocytes of the skin.
o Marjolin’s ulcer is a squamous cell carcinoma that arises in an area of chronically inflamed skin
Explain the aetiology / risk factors of squamous cell carcinoma
- Main risk factor = UV RADIATION
- Sun exposure can lead to actinic keratosis (sun-induced precancerous lesion)
• Other risk factors:
o Radiation
o Carcinogens (e.g. tar derivatives, cigarette smoke)
o Chronic skin disease (e.g. lupus)
o HPV
o Long-term immunosuppression
o Defects in DNA repair (xeroderma pigmentosum)
Summarise the epidemiology of squamous cell carcinoma
- SECOND most common cutaneous malignancy (20% of all skin cancers)
- Occurs mainly in MIDDLE-AGED and ELDERLY people
- LIGHT-SKINNED individuals are at higher risk
- 2-3 x more common in MALES
Recognise the presenting symptoms of squamous cell carcinoma
- Skin lesion
- Ulcerated
- Recurrent bleeding
- Non-healing
Recognise the signs of squamous cell carcinoma on physical examination
- Variable appearance - may be ulcerated, hyperkeratotic, crusted or scaly, non-healing
- Often on sun-exposed areas
- Palpate for local lymphadenopathy
Identify appropriate investigations for squamous cell carcinoma and interpret the results
- Skin Biopsy - confirm malignancy and specific type
- Fine-needle aspiration or lymph node biopsy - if metastasis is suspected
- Staging - using CT, MRI or PET
Define testicular cancer
• Malignant tumour of the testes
• Types:
o Seminomas - 50%
o Non-seminomatous germ-cell tumours and teratomas - 30%
o RARE: gonadal stromal tumours (Sertoli and Leydig cell tumours) and non-Hodgkin’s lymphoma
Explain the aetiology / risk factors of testicular cancer
• UNKNOWN • Risk Factors o Maldescended testes o Ectopic testes o Atrophic tests
Summarise the epidemiology of testicular cancer
- UNCOMMON
- 1% of male malignancies
- Common age of onset: 18-35 yrs
Recognise the presenting symptoms of testicular cancer
- Swelling or discomfort of the testes
- Backache due to para-aortic lymph node enlargement
- Lung metastases –> SOB, haemoptysis
Recognise the signs of testicular cancer on physical examination
- Painless, hard testicular mass
- There may be a secondary hydrocoele
- Lymphadenopathy (e.g. supraclavicular, para-aortic)
- Gynaecomastia (tumour produces hCG)
Identify appropriate investigations for testicular cancer and interpret the results
• Bloods o FBC o U&Es o LFTs o Tumour Markers • a-fetoprotein • b-hCG • LDH • Urine Pregnancy Test - will be positive if the tumour produces -hCG • CXR - show lung metastases • Testicular Ultrasound o Allows visualisation of the tumour o Can see associated hydrocoele • CT Abdomen and Thorax - allows staging o Staging System: Royal Marsden Hospital Staging
Define thyroid cancer
• Malignancy arising in the thyroid gland. Types include: o Papillary o Follicular o Medullary o Anaplastic
Explain the aetiology / risk factors of thyroid cancer
• UNKNOWN
• Risk Factors
o Childhood exposure to radiation
o Medullary thyroid cancers may be familial and are associated with MEN IIa or IIb
o Lymphoma is associated with Hashimoto’s thyroiditis
Summarise the epidemiology of thyroid cancer
- RARE
- More common in FEMALES
- Papillary: 20-40 yrs
- Follicular: 40-50 yrs
- Anaplastic: more common in the ELDERLY
Recognise the presenting symptoms of thyroid cancer
- Slow-growing neck lump
- Discomfort swallowing
- Hoarse voice
Recognise the signs of thyroid cancer on physical examination
- Palpable nodules or diffuse enlargement of thyroid gland
- Cervical lymphadenopathy –> suspect malignancy
- NOTE: the patient is usually euthyroid
Identify appropriate investigations for thyroid cancer and interpret the results
• Bloods o TFTs o Bone profile o Tumour Markers • Thyroglobulin - papillary and follicular • Calcitonin - medullary • Fine-Needle Aspiration Cytology (FNA) o Allows histological diagnosis • Excision Lymph Node Biopsy o If there is cervical lymphadenopathy • Isotope Scan o If the cause of the thyroid lump is unclear • CT/MRI - for staging
Define tumour lysis syndrome
• A group of metabolic abnormalities that can occur as a complication during treatment of cancer, where large amounts of tumour cells are lysed at the same time by treatment, releasing their contents into the bloodstream.
Explain the aetiology / risk factors of tumour lysis syndrome
• It is caused by the sudden lysis of many tumour cells, which release their toxic contents into the blood stream
• Occurs most commonly after treatment of lymphomas and leukaemias
• Risk Factors
o Tumour Characteristics - high cell turnover rate, rapid growth rate, high tumour bulk
o Patient Characteristics - baseline serum creatinine, renal insufficiency, dehydration
o Chemotherapy Characteristics - chemo-sensitive tumours (e.g. lymphoma) tends to have a higher risk
Summarise the epidemiology of tumour lysis syndrome
• Tends to occur most commonly in patients with poorly differentiated lymphomas and leukaemias
Recognise the presenting symptoms & signs of tumour lysis syndrome
• Hyperkalaemia o K+ is mainly an intracellular ion o Symptoms: • Arrhythmias • Severe muscle weakness and paralysis • Hyperphosphataemia o Causes acute kidney failure because of deposition of calcium phosphate crystals in the kidney parenchyma • Hypocalcaemia o Calcium precipitates to form calcium phosphate, so serum calcium drops o Symptoms: • Tetany • Parkinsonism • Myopathy • Sudden mental incapacity • Hyperuricaemia o Leads to gout • Lactic Acidosis
Identify appropriate investigations for tumour lysis syndrome and interpret the results
• Check the levels of all the metabolites that are deranged: o Potassium o Phosphate o Calcium o Uric acid • Monitor for symptoms: o Increased serum creatinine o Arrhythmia o Seizure
