Cancer Flashcards
What is basal cell carcinoma?
A common neoplasm, related to exposure to sunlight-clinically presents as a pearly white papulo-nodule or firm plaque
What is the aetiology of basal cell carcinoma?
Repetitive and frequent sun exposure, as ultraviolet (UV) radiation induces DNA damage in keratinocytes
What is the epidemiology of basal cell carcinoma?
The most common malignancy of the skin in fair-skinned adults in the US, Australia, and Europe and its incidence is increasing
The incidence of BCC has been shown to increase markedly after the age of 40 years (incidence in younger people is steadily rising)
What are the presenting symptoms of basal cell carcinoma?
Pearly papules/plaques
Non-healing scabs
What are the signs of basal cell carcinoma on physical examination?
Plaques, nodules and tumours:
- pearly appearance
- rolled borders
- small crusts, non-healing
- associated Telangiectasis (tiny thread like blood vessels)
What are the appropriate investigations for basal cell carcinoma?
*Biopsy for dermatohistopathology:
(diagnosis of a cancer is histological)
-growth of nest(s) of varying size and shape
-either tightly associated with epidermis or follicular opening
-neoplasm composed of basophilic (blue) hyperchromatic cells
-stroma surrounding BCC is hypercellular, fibrous
-separation artefact between nests of neoplastic cells and the stroma (so-called stroma-epithelium split)
What is bladder cancer?
Over 90% of cancers of the urinary bladder are urothelial carcinoma (previously termed transitional cell carcinoma)
What is associated with bladder cancer?
Smoking* Aromatic amines (rubber industry) Chronic cystitis Schistosomiasis (increases risk of squamous cell carcinoma) Pelvic irradiation
What is the aetiology of bladder cancer?
Smoking is the most important causative factor in bladder cancer, increasing the risk two- to fourfold
People with Type 2 DM
Chronic inflammation, Schistosoma infection, and chronic indwelling catheters increase the risk
What is the epidemiology of bladder cancer?
Bladder cancer ranks ninth in worldwide cancer incidence. >90% are transitional cell carcinomas (TCCS) in the UK
M:F is 5:2
What are the presenting symptoms of bladder cancer?
Painless haematuria
Recurrent UTIs
Dysuria: associated with aggressive bladder cancer
Voiding irritability
What are the appropriate investigations for bladder cancer?
Cystoscopy with biopsy is diagnostic* (camera imaging)
Urinalysis: haematuria, microscopy/cytology (cancers may cause sterile pyuria)
Renal and bladder ultrasound: bladder tumours and/or upper tract obstruction may be seen
CT urogram is both diagnostic and provides staging.
Bimanual examination under anaesthetic helps assess spread
MRI or lymphangiography may show involved pelvic nodes
Bloods: FBC (may be mildly anaemic), Alk Phos (may be elevated)
What is breast cancer?
A malignancy originating in the breast(s) and nodal basins
What is the aetiology of breast cancer?
Unknown.
Factors that have a role:
-Genetic: 5% to 10% of breast cancers are linked to inherited genetic mutations- BRCA1 and BRCA2 mutations are the most common inherited genetic mutation found in breast cancer
-Hormonal: increased levels of endogenous sex hormones (oestrogen) increase risk of breast cancer
What is the epidemiology of breast cancer?
Breast cancer is the most common female malignancy
It is most commonly diagnosed in middle-aged or older women (median age at diagnosis is 62 years)
Women are affected 100x more than men
What are the presenting symptoms of breast cancer?
Breast mass (does not have to be a new mass)
Nipple discharge
Skin thickening
Retraction of the nipple
What are the signs of breast cancer on physical examination?
Breast mass:
-Is it tender?
-Are there changes in the size or character of the mass?
-Have the characteristics of the mass have been affected by the menstrual cycle
Nipple discharge:
-May be watery, serous, milky, or bloody
-Bloody discharge is more classically associated with a neoplasm
Axillary lymphadenopathy:
the probability of axillary nodal involvement increases in proportion to the size of the tumour (clinical assessment can be inaccurate- imaging is needed)
Overlying skin changes:
-Peau d’orange (dimpling of the skin)
-Erythema
-Ulceration
*always associated with locally advanced or inflammatory breast cancer
Retraction of the nipple: may be related to Paget’s disease of the breast
What are the appropriate investigations for breast cancer?
Triple assessment:
(clinical examination)
-Mammogram: an irregular spiculated mass, clustered microcalcifications, and linear branching calcifications
-Core biopsy: histological findings confirming an invasive ductal carcinoma, invasive lobular carcinoma, medullary carcinoma, mucinous carcinoma, or metaplastic carcinoma
Other imaging:
- Breast ultrasound (adjunct to mammogram): a hypoechoic mass, an irregular mass with internal calcifications, and enlarged axillary lymph nodes
- Breast MRI: more sensitive but less specific, used in screening for patients with positive FH
What are central nervous system tumours?
Primary tumours arising from any of the brain tissue types
What is the aetiology of CNS tumours?
Children: most likely embryonic errors in development
Adults: unknown
What is the pathology of a meningioma?
Benign and most common primary CNS tumour
What is the pathology of a pituitary adenoma?
Benign, space-occupying and endocrine effects
What is the epidemiology of CNS tumours?
Annual incidence of primary tumours 5–9 in 100000 Two peaks of incidence (children and the elderly)
What are the presenting symptoms of CNS tumours?
Headache or vomiting (raised intracranial pressure)
Epilepsy (focal or generalized)
Focal neurological deficits (dysphagia, hemiparesis, ataxia, visual field defects, cognitive impairment)
Personality change
What are the signs of CNS tumours on physical examination?
Papilloedema / false localising signs (raised intracranial pressure)- bilateral hemianopia, anosmia, ophthalmoplegia
Focal neurological deficits (visual field defects, dysphasia, agnosia, hemianopia, hemiparesis,
ataxia, personality change)
What are the appropriate investigations for CNS tumours?
CT-head: Usual initial investigation.
MRI-brain: Higher sensitivity.
Chest X-ray or CT (thorax, abdomen, pelvis): To determine if the lesion is secondary or primary.
Blood: CRP, ESR, consider HIV screen, toxoplasma serology (consider hormone profile-pituitary)
Brain biopsy: Type and grading (degree of differentiation of tumour)
*Lumbar puncture: contraindication if there is evidence of
raised intracranial pressure, may cause coning (herniation).
What are cholangiocarcinomas?
Cancers arising from the bile duct epithelium. These can be divided depending on their location in the biliary tree:
intrahepatic or extrahepatic (perihilar and distal)
What is the aetiology of cholangiocarcinomas?
There is a close association between infection, inflammation, and malignancy
What are the risk factors for cholangiocarcinomas?
Age > 50 years
Cholangitis
Choledocholithiasis (gall stones)
Structural disorders of the biliary tract e.g. bile duct adenoma
Ulcerative colitis
Primary sclerosis cholangitis (high association with UC)
Non-specific cirrhosis, alcoholic liver disease
HIV
Hepatitis B and C
What is the epidemiology of cholangiocarcinomas?
Slight male predominance
Approximately 2/3rds of cholangiocarcinomas occur in patients between 50 and 70 years of age
Highest rates in Thailand and South American Countries
What are the presenting symptoms of cholangiocarcinomas?
Painless jaundice (90% of patients) Others which are less common: -Weight loss -Abdominal pain -Itchiness -Dark urine and pale stools (obstructive jaundice)
What are the signs of cholangiocarcinomas on physical examination?
Jaundice
Triad of: fever, jaundice and right upper quadrant pain (acute cholangitis- 10% of patients)
Palpable gallbladder (RARE)
Hepatomegaly (RARE)
What are the appropriate investigations for cholangiocarcinomas?
Bloods:
-Serum bilirubin: Conjugated bilirubin is elevated in obstructive jaundice
-Serum alkaline phosphate: Suggests obstructive (or cholestatic) pattern of elevated LFTs, along with GGT, AST and ALT
-Serum prothrombin time: increased in prolonged obstruction of the common bile or hepatic duct
Tumour marker: Ca 19-9- elevated in up to 85% of patients with cholangiocarcinoma
Imaging:
-Abdominal ultrasound: intrahepatic cholangiocarcinoma may be seen as a mass lesion
-Abdominal CT: intrahepatic mass lesion, dilated intrahepatic ducts, and localised lymphadenopathy
-Abdominal MRI/angiography: staging tool/extent of tumour
-*ERCP (Endoscopic Retrograde Cholangiopancreatography) : a filling defect or area of narrowing will be seen if a tumour is present- INVASIVE
Others:
MRCP (extent of duct involvement)
Percuatneous transhepatic cathertisation (invasive procedure that is used when the tumour causes complete obstruction of the biliary tree)
What is colorectal cancer?
Malignancy of the large bowel - the majority of colorectal cancers are adenocarcinomas derived from epithelial cells
What is the aetiology of colorectal cancer?
Colorectal cancer represents a complex interaction of genetic and environmental factors:
Genetic: next to age, FH is the most common risk factor
*Family cancer syndromes: familial adenomatous polyposis (FAP) and Lynch syndrome
Environmental: Obesity, high energy intake, and physical inactivity are synergistic risk factors (low fibre diet)
Also: inflammatory bowel disease, acromegaly
What is the epidemiology of colorectal cancer?
Second most common cause of cancer death in the West
Average age at diagnosis 60–65 years.
What are the presenting symptoms of colorectal cancer?
Left-sided colon and rectum:
- Change in bowel habit (increased frequency, looser stools)
- Rectal bleeding or blood/mucous mixed in with stools
- Rectal masses may also present as tenesmus (sensation of incomplete emptying after defecation)
Right-sided colon:
-Later presentation, with symptoms of anaemia, weight loss and non- specific malaise or, more rarely, lower abdominal pain
Up to 20% of tumours will present as an emergency with pain and distension caused by large bowel obstruction, haemorrhage or peritonitis as a result of perforation
What are the signs of colorectal cancer on physical examination?
Anaemia may be only sign, particularly in right-sided lesions
Abdominal mass, low-lying rectal tumours may be palpable on rectal examination
Metastatic disease: Hepatomegaly, shifting dullness of ascites
What are the appropriate investigations for colorectal cancer?
Blood: FBC (for anaemia), LFT (often normal), tumour markers (CEA to monitor treatment response or disease recurrence)
Stool: Occult or frank blood in stool (screening test)
Endoscopy:
-Sigmoidoscopy, colonoscopy: may see ulcerating or exophytic (growing outward) mucosal lesion that may narrow the bowel lumen
-Allows visualization and biopsy. Polypectomy can also be performed if isolated small carcinoma in situ
Barium contrast studies: Apple core stricture on barium enema
Abdominal ultrasound scan for hepatic metastases
Other staging investigations include:
-CXR
-CT: colonic wall thickening, enlarged lymph nodes, liver metastases, ascites, lung secondaries
-MRI, endorectal ultrasound
What is deep vein thrombosis (DVT)?
Formation of a thrombus within the deep veins (most commonly of the calf or thigh) which may result in impaired venous blood flow and consequent leg swelling and pain
What are the risk factors for DVT?
Oral contraceptive pill Surgery Prolonged immobility Long bone fractures Obesity Pregnancy Dehydration Smoking Polycythaemia Anti-phospholipid syndrome Thrombophilia disorders (e.g. protein C deficiency) Active malignancy
What is Virchow’s triad?
Venous stasis
Vessel wall injury
Blood hypercoagulability
What is the epidemiology for DVT?
Common, especially in hospitalised patients- yearly incidence of approximately 1 in every 1000 adults
Long-term complications of DVT (venous insufficiency, ulceration) affect 0.5% population
Incidence increases with age (increased medical co-morbidities, declining mobility, and perhaps age-related changes in coagulation)
What are the presenting symptoms of DVT?
Asymptomatic or lower limb swelling or tenderness
May present with signs/ symptoms of a pulmonary embolus (sudden onset dyspnoea, chest pain)
What are the signs of DVT on physical examination?
Examine for swelling, calf tenderness:
Severe leg oedema (usually unilateral)
Dilated superficial veins over foot and leg
Cyanosis (phlegmasia cerulea dolens) is rare
*Respiratory examination for signs of a pulmonary embolus (Sudden onset dyspnoea, cough, haemoptysis and pleuritic chest pain)
What are the appropriate investigations for DVT?
*Doppler ultrasound: gold standard
-Good sensitivity for femoral veins; less sensitive for calf veins (reduced/absent spontaneous blood flow)
Bloods:
-D-dimers (fibrinogen degradation products) are sensitive but very non-specific and only useful as a negative predictor in low-risk patients
-If indicated (e.g. recurrent episodes), a thrombophilia screen should be sent, prior to starting anticoagulation
-FBC (platelet count prior to starting heparin)
-U&E and clotting
ECG, CXR and ABG: If there is suggestion that there might be PE
What is the Well’s system for DVT?
Lower limb trauma or surgery or immobilisation in a plaster cast (+1)
Bedridden for >3 days or surgery within the last 4 weeks (+1)
Tenderness along deep venous system (+1)
Entire limb swollen (+1)
Calf >3 cm bigger circumference; 10 cm below tibial tuberosity (+1)
Pitting oedema (+1)
Dilated collateral superficial veins (non-varicose) (+1)
Malignancy (including treatment up to 6 months previously) (+1)
Alternative diagnosis more likely than DVT (-2)
Clinical probability of DVT:
High >3
Moderate 1–2
Low <1
What is the management for DVT?
Anticoagulation:
- Patients should be treated with heparin while awaiting therapeutic INR from warfarin anticoagulation
- DVTs not extending above the knee treated with anticoagulation for 3 months, while those extending beyond the knee require anticoagulation for 6 months
- Recurrent DVTs may require long-term warfarin*
- If active anticoagulation is contraindicated and/or high risk of embolisation, placement of an IVC filter, e.g. Greenfield filter, by interventional radiology is indicated to prevent embolus to the lungs
Prevention:
- Use of graduated compression stockings
- Mobilisation if possible (physical activity)
- At-risk groups (immobilised hospital patients) should have prophylactic heparin, e.g. low molecular weight heparin if no contraindications
What are the complications of DVT?
Of the disease:
-Pulmonary embolus
-Damage to vein valves and chronic venous insufficiency of the lower limb (post-thrombotic syndrome)
*Rare: Venous infarction (phlegmasia cerulea dolens)
Of the treatment:
-Heparin-induced thrombocytopaenia
-Bleeding
What is the prognosis of 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
What is gastric cancer?
A neoplasm that can develop in any portion of the stomach and may spread to the lymph nodes and other organs, most commonly adenocarcinoma, more rarely lymphoma, leiomyosarcoma
What is the aetiology of gastric cancer?
Most cases are probably caused by environmental insults in genetically predisposed individuals that lead to mutation and subsequent unregulated cell growth
Risk factors include:
-Helicobacter pylori infection
-Atrophic gastritis
-Diet high in smoked, processed foods and nitrosamines
-Smoking
-Alcohol
What is the epidemiology of gastric cancer?
Common cause of cancer death worldwide, with highest incidence in Asia, especially Japan
Sixth most common cancer in UK (annual incidence is 15 in 100000)
M: W is 2:1
Age>50 years
*Cancer of the antrum/body is becoming less common, while that of the cardia and gastro- oesophageal junction is increasing
What are the presenting symptoms of gastric cancer?
In the early phases, it is often asymptomatic
Early satiety or epigastric discomfort
Weight loss, anorexia, nausea and vomiting
Haematemesis, melaena, symptoms of anaemia
Dysphagia (tumours of the cardia)
Symptoms of metastases, particularly abdominal swelling (ascites) or jaundice (liver involvement)
What are the signs of gastric cancer on physical examination?
Physical examination may be normal Epigastric mass Abdominal tenderness Ascites Signs of anaemia Many eponymous signs: **Virchows node/Troisiers sign: Lymphadenopathy in left supraclavicular fossa Sister Mary Joseph node: Metastatic nodule on umbilicus Krukenbergs tumour: Ovarian metastases
What are the appropriate investigations for gastric cancer?
*Upper gastrointestinal endoscopy with biopsy: ulcer or mass or mucosal changes
Bloods: FBC (for anaemia), LFT
CT/MRI: Staging of tumour and planning of surgery (metastatic lesions)
Ultrasound of liver: Staging of tumour (metastatic lesions)
Bone scan: Staging of tumour (metastatic lesions)
Endoscopic ultrasound: Assesses depth of invasion and lymph node spread (determines clinical tumour (T) and node (N) stage)
Laparoscopy: May be needed to determine if tumour is resectable
What is hepatocellular carcinoma?
Primary malignancy of hepatocytes, usually occurring in a cirrhotic liver
What is the aetiology of hepatocellular carcinoma?
- Chronic liver damage e.g. alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disease
- Metabolic disease e.g. haemochromatosis (inherited condition where iron levels accumulate)
- Aflatoxins: Aspergillus flavus fungal toxin found on stored grains or biological weapons
What is the epidemiology of hepatocellular carcinoma?
Worldwide, HCC is the sixth most common cause of cancer and the second leading cause of cancer-related death
Rare in West (1–2 in 100 000/year)
Very common malignancy in areas where Hepatitis B and C are endemic, i.e. Asia and sub-Saharan Africa
What are the presenting symptoms of hepatocellular carcinoma?
Symptoms of malignancy: -Malaise -Weight loss -Loss of appetite Symptoms of chronic liver disease: -Abdominal distension -Jaundice -Right upper quadrant pain History of carcinogen exposure: -High alcohol intake -PMH of Hepatitis B or C or Aflatoxins
What are the signs of hepatocellular carcinoma on physical examination?
Signs of malignancy: -Cachexia -Lymphadenopathy Hepatomegaly: -Nodular (but may be smooth) Deep palpation may elicit tenderness *There may be bruit heard over the liver Signs of chronic liver disease: -Jaundice -Ascites -Palmar erythema Others: -Splenomegaly: indicative of portal hypertension secondary to cirrhosis of the liver -Decompensated cirrhosis- hepatic encephalopathy: asterixis, spider naevi
What are the appropriate investigations for hepatocellular carcinoma?
Blood:
-*Raised AFP (tumour marker with high sensitivity): elevated in 60% of patients with HCC
-Vitamin B12-binding protein is a marker of fibrolamellar hepatocellular carcinoma
-LFT has poor specificity and sensitivity but may show biliary obstruction (elevated aminotransferases, alkaline phosphatase, and bilirubin; low albumin)
-Prothrombin time: normal or elevated
Abdominal ultrasound:
-Poorly defined margins and coarse, irregular internal echoes
-Not sensitive for tumours <1 cm
Duplex scan of liver:
-May be used to demonstrate large vessel invasion (e.g. into hepatic or portal veins)
*CT (thorax, abdomen, pelvis) with contrast:
-Typical hypervascular pattern
-To define structural lesion and spread
-Hepatic angiography: Using lipiodol (an iodized oil).
Liver biopsy:
-Confirms histology of tumour: well-differentiated to poorly differentiated hepatocytes with large multinucleated giant cells having central necrosis
-Small risk of tumour seeding along biopsy tract
Staging:
-CXR
-Radionuclide bone scan: “hot” spots- bone mets
*Screening: AFP and abdominal ultrasound in at-risk individuals
What is Leukaemia, acute myeloblastic (AML)?
Malignancy of primitive myeloid lineage WBCs (myeloblasts) with proliferation in the bone marrow and blood
What is the aetiology of Leukaemia, acute myeloblastic (AML)?
- Myeloblasts, arrest at an early stage of development, with varying cyto-genetic abnormalities (e.g. gene mutations and chromosome translocations)
- Myeloblasts then undergo malignant transformation and proliferation, with subsequent replacement of normal marrow elements
- Resulting in bone marrow failure
What is the epidemiology of Leukaemia, acute myeloblastic (AML)?
*Most common acute leukaemia in adults
Incidence increases with age.
What are the presenting symptoms of Leukaemia, acute myeloblastic (AML)?
Symptoms of bone marrow failure:
-Anaemia (lethargy, dyspnoea)
-Bleeding (thrombocytopaenia) or DIC(Disseminated intravascular coagulation-blood clots form throughout the body)
-Opportunistic or recurrent infections
Symptoms of tissue infiltration:
-Gum swelling or bleeding
-CNS involvement (headaches, nausea, diplopia-double vision): especially with particular variants
What are the signs of Leukaemia, acute myeloblastic (AML) on physical examination?
Signs of bone marrow failure:
-Pallor
-Cardiac flow murmur
-Ecchymoses (discolouration of skin from bleeding underneath)
-Bleeding
-Opportunistic or recurrent infections (e.g. fever, mouth ulcers, skin infections, Pneumocytis Pneumonia- PCP)
Signs of tissue infiltration:
-Skin rashes
-Gum hypertrophy
-Deposits of leukaemic blasts may rarely be seen in the eye (chloroma), tongue and bone – in the latter may cause fractures
What are the appropriate investigations for Leukaemia, acute myeloblastic (AML)?
Bloods:
-FBC (reduced Hb, reduced platelets, variable WCC)
-Raised Uric acid
-Raised LDH
-Others: clotting studies, fibrinogen and D-dimers (when DIC is suspected)
*Blood film: AML blasts may show cytoplasmic granules or Auer rods
*Bone marrow aspirate or biopsy:
-Hypercellular with >30 % blasts (immature cells)
Immunophenotyping: Antibodies against surface antigens to classify lineage of abnormal clones
Immunocytochemistry: Myeloblasts granules are positive
[Cytogenetics: For diagnostic and prognostic information]
