Cancer Flashcards
1
Q
What is basal cell carcinoma?
A
Most common type of cancer in the Western world
Related to exposure to sunlight
Clinically presents as a pearly white papulo-nodule or firm plaque
2
Q
What is the aetiology of basal cell carcinoma?
A
Repetitive and frequent sun exposure, as ultraviolet radiation induces DNA damage in keratinocytes
3
Q
What are the characteristics of basal cell carcinomas?
A
Slow-growth and local invasion
Initially a pearly, flesh-coloured papule with telangiectasia
May later ulcerate leaving a central ‘crater’
4
Q
What sites are usually affected in basal cell carcinomas?
A
Sun-exposed sites, especially the head and neck account for the majority of lesions
5
Q
What are the appropriate investigations for basal cell carcinoma?
A
Generally, if a BCC is suspected, a routine referral should be made on the 2WW
Biopsy for dermatohistopathology:
(diagnosis of a cancer is histological)
6
Q
What are some of the management options for basal cell carcinoma?
A
Surgical removal
Curettage
Cryotherapy
Topical cream: imiquimod, fluorouracil
Radiotherapy
7
Q
What is bladder cancer and who does it commonly affect?
A
The second most common urological cancer
It most commonly affects males aged between 50 and 80 years of age
8
Q
What are the two types of bladder cancer?
A
- Urothelial (transitional cell) carcinoma
- Squamous cell carcinoma
9
Q
What is the most common type of bladder cancer?
A
Urothelial carcinoma (previously termed transitional cell carcinoma)
>90%
10
Q
What are the risk factors for urothelial carcinoma of the bladder?
A
- Smoking: most important risk factor in western countries
- Exposure to aniline dyes: for example working in the printing and textile industry e.g. 2-naphthylamine and benzidine
- Rubber manufacture
- Cyclophosphamide
11
Q
What are the risk factors for squamous cell carcinoma of the bladder?
A
Schistosomiasis: causes chronic bladder inflammation
Smoking
12
Q
What are the presenting symptoms of bladder cancer?
A
Most patients (85%) will present with painless, macroscopic haematuria
Others:
Recurrent UTIs
Dysuria: associated with aggressive bladder cancer
Voiding irritability
13
Q
What are the appropriate investigations for bladder cancer?
A
Cystoscopy and biopsies or TURBT: this provides histological diagnosis and information relating to depth of invasion (for staging)
Others:
CT urogram = diagnostic and provides staging
Urinalysis
14
Q
What is TURBT (in context of bladder cancer)?
A
Trans urethral resection of bladder tumour
15
Q
What is the management of bladder cancer?
A
Superficial lesions: TURBT in isolation
Recurrences or higher grade/ risk on histology: intravesical chemotherapy
T2 disease: offered either surgery (radical cystectomy and ileal conduit) or radical radiotherapy
16
Q
What is the staging of bladder cancer?
A
T0 = no evidence of tumour
T1 = Tumour invades sub epithelial connective tissue
T2a = Tumour invades superficial muscularis propria (inner half)
T2b = Tumour invades deep muscularis propria (outer half)
T3 = Tumour extends to perivesical fat
T4 = Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina
a = Invasion of uterus, prostate or bowel
b = Invasion of pelvic sidewall or abdominal wall
Nodal and Metastasis
17
Q
What is the prognosis of bladder cancer?
A
Depends on staging:
T1 = 90%
T2 = 60%
T3 = 35%
T4a = 10-25%
Any T, N1-N2 = 30%
18
Q
What is breast cancer?
A
A malignancy originating in the breast(s) and nodal basins
19
Q
What are some of the predisposing factors for breast cancer?
A
- BRCA1, BRCA2 genes - 40% lifetime risk of breast/ovarian cancer
- 1st degree relative premenopausal relative with breast cancer (e.g. mother)
- Nulliparity, 1st pregnancy > 30 yrs (twice risk of women having 1st child < 25 yrs)
- Oestrogen exposure: early menarche, late menopause
- COCP: (relative risk increase * 1.023/year of use), combined oral contraceptive use
- Past breast cancer
- Not breastfeeding
- Ionising radiation
- p53 gene mutations
- obesity
20
Q
What is the epidemiology of breast cancer?
A
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
21
Q
What are the presenting symptoms of breast cancer?
A
Breast mass (does not have to be a new mass)
Nipple discharge
Skin thickening
Retraction of the nipple
22
Q
What are the signs of breast cancer on physical examination?
A
History of breast mass: tenderness, change in size or character (in relation to menstrual cycle)
Nipple discharge: bloody is more classically associated with neoplasm
Overlying skin changes: Peau d’orange (dimpling of the skin), erythema, ulceration, retraction of nipple (Paget’s?)
Axillary lymphadenopathy: nodal involvement increases in proportion to the size of the tumour
23
Q
What are the appropriate investigations for breast cancer?
A
Triple assessment:
1. Clinical examination
2. Imaging: an irregular spiculated mass, clustered microcalcifications, and linear branching calcifications
3. Core (needle) biopsy: histological findings confirming an invasive ductal carcinoma, invasive lobular carcinoma, medullary carcinoma, mucinous carcinoma, or metaplastic carcinoma
24
Q
What are the different types of breast cancer?
A
Most breast cancers arise from duct tissue followed by lobular tissue, described as ductal or lobular carcinoma respectively
These can be further subdivided as to whether the cancer hasn’t spread beyond the local tissue (described as carcinoma-in-situ) or has spread (described as invasive)
1. Invasive ductal carcinoma (‘No Special Type (NST)’) = MOST COMMON
2. Invasive lobular carcinoma
3. Ductal carcinoma-in-situ (DCIS)
4. Lobular carcinoma-in-situ (LCIS)
25
What is Paget's disease of the nipple?
An eczematoid change of the nipple associated with an underlying breast malignancy (retraction of the nipple)
Present in 1-2% of patients with breast cancer
In half of these patients, it is associated with an underlying mass lesion and 90% of such patients will have an invasive carcinoma
30% of patients without a mass lesion will still be found to have an underlying carcinoma
The remainder will have carcinoma in situ
26
What is the referral pathway for breast cancer?
2WW if:
1. Aged 30 and over and have an unexplained breast lump with or without pain or
2. Aged 50 and over with any of the following symptoms in one nipple only: discharge, retraction or other changes of concern
Consider 2WW if:
1. Skin changes that suggest breast cancer or
2. Aged 30 and over with an unexplained lump in the axilla
Non-urgent referral if: under 30 with an unexplained breast lump with or without pain
27
What are the management options for breast cancer?
Depends on the staging, tumour type and patient background
Ultimately patient's choice!
Options include:
Surgery
Radiotherapy
Hormone therapy
Biological therapy
Chemotherapy
28
What surgical options are available for breast cancer?
Vast majority will be offered surgery
Mastectomy and wide local excision (2/3rds can be WLE)
Prior to surgery: presence/absence of axillary lymphadenopathy?
- if positive then they should have a sentinel node biopsy to assess the nodal burden
- if clinically palpable lymphadenopathy, axillary node clearance is indicated at primary surgery (this may lead to arm lymphedema and functional arm impairment)
29
What are the indications for a mastectomy and wide local excision?
Mastectomy:
Multifocal tumour
Central tumour
Large lesion in small breast
DCIS > 4cm
WLE:
Solitary lesion
Peripheral tumour
Small lesion in large breast
DCIS < 4cm
30
What should all women be offered if they have surgical management of breast cancer?
Regardless of type of surgical treatment, all women should be offered breast reconstruction to achieve a cosmetically suitable result
31
What radiotherapy options are available for breast cancer?
WLE: Whole breast radiotherapy is recommended after WLE (may reduce the risk of recurrence by around two-thirds)
Mastectomy: radiotherapy is offered for T3-T4 tumours and for those with four or more positive axillary nodes
32
What hormonal therapy options are available for breast cancer?
Adjuvant hormonal therapy is offered if tumours are positive for hormone receptors
Tamoxifen is still used in pre- and peri-menopausal women
In post-menopausal women, aromatase inhibitors such as anastrozole are used for this purpose (aromatisation accounts for the majority of oestrogen production in post-menopausal women and therefore anastrozole is used for ER +ve breast cancer in this group)
*Important side-effects of tamoxifen include an increased risk of endometrial cancer, VTE and menopausal symptoms
33
What chemotherapy options are available for breast cancer?
Cytotoxic therapy may be used either prior to surgery ('neoadjuvanant' chemotherapy) to downstage a primary lesion
Or
After surgery depending on the stage of the tumour e.g. if there is axillary node disease - FEC-D is used in this situation (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel)
34
What biological therapies are available for breast cancer?
The most common type of biological therapy is trastuzumab (Herceptin)
It is only useful in the 20-25% of tumours that are HER2 positive.
*Trastuzumab cannot be used in patients with a history of heart disorders
35
What is the breast cancer screening pathway?
Mammogram offered to women between the ages of 50-70 years every 3 years
> 70 years women may still have mammograms but are 'encouraged to make their own appointments'
36
What are central nervous system tumours?
Primary tumours arising from any of the brain tissue types
37
What is the most common type of brain tumour?
Metastatic brain cancer
Often multiple and not treatable with surgical intervention
Tumours that most commonly spread to the brain include:
- Lung (most common)
- Breast
- Bowel
- Skin (namely melanoma)
- Kidney
38
What is the most common primary brain tumour in adults?
Glioblastoma multiforme
39
What are the features of glioblastomas on imaging?
Solid tumours with central necrosis and a rim that enhances with contrast
Disruption of the blood-brain barrier and therefore are associated with vasogenic oedema
40
What are the histological features of glioblastomas?
Pleomorphic tumour cells border necrotic areas
41
What is the management and prognosis of glioblastomas?
Surgical with postoperative chemotherapy and/or radiotherapy Dexamethasone is used to treat the oedema
Prognosis is poor ~ 1 year
42
What are the second most common primary brain tumours?
Meningiomas
43
What are meningiomas?
Typically BENIGN, extrinsic tumours of the CNS
They arise from the arachnoid cap cells of the meninges and are typically located next to the dura
Cause symptoms by compression rather than invasion
44
What are the histological features of meningiomas?
Spindle cells in concentric whorls and calcified psammoma bodies
45
What is the management plan for a meningioma?
Investigation is with CT (will show contrast enhancement) and MRI
Treatment will involve either observation, radiotherapy or surgical resection
46
What is the most common primary brain tumour in children?
Astrocytoma
47
What are the common CNS tumours?
60% = Glioma and metastatic disease
20% = Meningioma
10% = Pituitary lesions
48
What are some of the common features 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
49
How to symptoms of CNS tumours present depending on site of tumour?
Tumours arising in right temporal and frontal lobe may reach considerable size before becoming symptomatic
Whereas tumours in the speech and visual areas will typically produce early symptoms
50
What is the diagnostic investigation of choice for CNS tumours?
MRI scan - provide best resolution
51
What is the management plan for CNS tumours?
Usually surgery - even if tumour cannot be completely resected conditions such as rising ICP can be addressed with tumour debulking → survival and quality of life prolonged
Curative surgery can usually be undertaken with lesions such as meningiomas
*Gliomas have a marked propensity to invade normal brain and resection of these lesions is nearly always incomplete (hence poor prognosis)
52
What are vestibular schwannomas?
Previously termed acoustic neuroma
Benign tumour arising from the eighth cranial nerve (vestibulocochlear nerve)
Often seen in the cerebellopontine angle
It presents with hearing loss, facial nerve palsy (due to compression of the nearby facial nerve) and tinnitus
53
What are bilateral vestibular schwannomas associated with?
Neurofibromatosis type 2
54
What are cholangiocarcinomas?
Bile duct cancer
55
How can cholangiocarcinomas be divided?
On their location in the biliary tree:
1. Intrahepatic
2. Extrahepatic (perihilar or distal)
56
What is the main risk factor for cholangiocarcinoma?
Primary sclerosing cholangitis
57
What is Primary sclerosing cholangitis?
Biliary disease of unknown aetiology characterised by inflammation and fibrosis of intra and extra-hepatic bile ducts
Closely associated with Ulcerative Colitis
58
What are some other risk factors for Cholangiocarcinoma?
Age > 50 years
Cholangitis
Choledocholithiasis (gall stones)
Structural disorders of the biliary tract e.g. bile duct adenoma
Ulcerative colitis
Non-specific cirrhosis
Alcoholic liver disease
HIV
Hepatitis B and C
59
What are the features of cholangiocarcinoma?
Persistent biliary colic symptoms
Associated with anorexia, jaundice and weight loss
A palpable mass in the right upper quadrant (Courvoisier sign)
Periumbilical lymphadenopathy (Sister Mary Joseph nodes) and left supraclavicular adenopathy (Virchow node) may be seen
Obstructive jaundice = dark urine and pale stools
60
What is the triad seen in Acute Cholangitis?
Fever, jaundice and right upper quadrant pain
61
What are the appropriate investigations for cholangiocarcinomas?
Raised CA 19-9 levels (often used for detecting cholangiocarcinoma in patients with PSC)
Bloods e.g. bilirubin, LFTs
Abdominal USS: intrahepatic cholangiocarcinoma may be seen as a mass lesion
ERCP: filling defect or area of narrowing will be seen if a tumour is present
62
What is the management plan for cholangiocarcinoma?
Surgical resection offers the only potential cure for early-stage disease
Chemotherapy may have a positive effect on overall survival of patients following resection of intrahepatic cholangiocarcinoma
Liver transplant is indicated in a small subset of patients
63
What is colorectal carcinoma?
1. Malignancy of the large bowel
2. The third most common type of cancer in the UK and the second most cause of cancer deaths
64
What is the aetiology of colorectal carcinoma?
Currently thought to be three types:
1. Sporadic (95%)
2. Hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
3. Familial adenomatous polyposis (FAP, <1%)
65
What are the most common risk factors for colorectal carcinoma?
1. Age
2. Genetics (even in sporadic cases, FH is important)
3. Inflammatory bowel disease
4. Lifestyle/ environmental factors
66
What is hereditary non-polyposis colorectal carcinoma (HNPCC)?
1. An autosomal dominant condition: most common form of inherited colon cancer
2. Around 90% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive
3. At risk of other cancers: endometrial cancer
67
What is familial adenomatous polyposis (FAP)?
1. A rare autosomal dominant condition which leads to the formation of hundreds of polyps by the age of 30-40 years
2. Patients inevitably develop carcinoma
3. It is due to a mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5
4. Also at risk from duodenal tumours
5. A variant of FAP called Gardner's syndrome can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin
68
What are the common locations for colorectal carcinomas?
1. Rectal: 40%
2. Sigmoid: 30%
3. Ascending colon and caecum: 15%
4. Transverse colon: 10%
5. Descending colon: 5%
69
What are the features of a left sided colon and rectum carcinoma?
1. Change in bowel habit: increased frequency, looser stools
2. Rectal bleeding or blood/mucous mixed in with stools
3. Rectal masses may also present as tenesmus: sensation of incomplete emptying after defecation
70
What are the features of a right sided colon carcinoma?
Later presentation:
1. Symptoms of anaemia
2. Weight loss and non- specific malaise
2. More rarely, lower abdominal pain
71
How can colorectal carcinoma present in an emergency?
1. 20% of cases
2. Pain and distension caused by large bowel obstruction, haemorrhage or peritonitis as a result of perforation
72
What are the signs of colorectal carcinoma on examination?
1. Left sided: abdominal mass, low-lying rectal tumours may be palpable on rectal examination
2. Right sided: anaemia may be only sign
3. Metastatic disease: hepatomegaly, shifting dullness of ascites
73
What are the referral guidelines for colorectal carcinoma for the 2 week pathway?
1. Patients ≥ 40 years with unexplained weight loss AND abdominal pain
2. Patients ≥ 50 years with unexplained rectal bleeding
3. Patients ≥ 60 years with iron deficiency anaemia OR change in bowel habit
74
When else should a patient be referred to the 2WW pathway for colorectal carcinoma?
Tests show occult blood in their faeces (FIT)
75
When should a referral to the 2WW pathway be considered?
1. There is a rectal or abdominal mass
2. There is an unexplained anal mass or anal ulceration
3. Patients < 50 years with rectal bleeding AND any of the following unexplained symptoms/findings:
a. abdominal pain
b. change in bowel habit
c. weight loss
d. iron deficiency anaemia
76
What is the faecal immunochemical test (FIT)?
National screening programme offering screening every 2 years to everyone aged 60 to 74 years in England (if over 74 years may request screening)
1. Eligible patients are sent the tests through the post
2. A type of faecal occult blood (FOB) test which uses antibodies that specifically recognise human haemoglobin (Hb)
3. Used to detect, and can quantify, the amount of human blood in a single stool sample
4. Patients with abnormal results are offered a colonoscopy
77
When is a FIT test recommended to patients outside of the screening programme?
If patients have new symptoms but do not fit the 2WW referral criteria:
1. Patients ≥ 50 years with unexplained abdominal pain OR weight loss
2. Patients < 60 years with changes in their bowel habit OR iron deficiency anaemia
3. Patients ≥ 60 years who have anaemia even in the absence of iron deficiency
78
What is the investigation that all patients with suspected colorectal cancer receive?
Colonoscopy (alongside further blood tests and stool tests
79
What is the sign of colorectal carcinoma on barium enema?
Apple core stricture (stenosing annular carcinoma)
80
What are the staging investigations for colorectal carcinoma?
1. CT of the chest/ abdomen and pelvis: may show colonic wall thickening, enlarged lymph nodes, liver metastases, ascites, lung secondaries
2. The entire colon should have been evaluated with colonoscopy or CT colonography
3. Patients whose tumours lie below the peritoneal reflection should have their mesorectum evaluated with MRI
81
What is the management of colorectal carcinoma?
MDT approach- nearly always treated with surgery:
1. Stents, surgical bypass and diversion stomas may all be used as palliative adjuncts
2. Resectional surgery is the only option for cure in patients with colon cancer
3. When a colonic cancer presents with an obstructing lesion; the options are to either stent it or resect
82
What is the management of rectal cancer?
Tumours located in the rectum can be surgically resected with either an anterior resection or an abdomino-perineal excision of rectum (APER), involvement of the cirumferential resection margin carries a high risk of disease recurrence
83
What are the types of resection for colorectal cancer depending on the site of the tumour?
1. Caecal, ascending or proximal transverse colon:
a. Right hemicolectomy
b. Ileo-colic anastamosis
2. Distal transverse, descending colon:
a. Left hemicolectomy
b. Colo-colon anastamosis
3. Sigmoid colon:
a. High anterior resection
b. Colo-rectal anastamosis
4. Upper rectum:
a. Anterior resection (TME)
b. Colo-rectal anastamosis
5. Low rectum:
a. Anterior resection (Low TME) b. Colo-rectal anastamosis
(+/- Defunctioning stoma)
6. Anal verge:
a. Abdomino-perineal excision of rectu
b. No anastamosis needed
84
What is Hartmann’s procedure and when is it used in the management of colorectal carcinoma?
Defintion: when resection of the sigmoid colon is performed and an end colostomy is fashioned
Indication:
1. In an emergency setting where the bowel has perforated
2. The risk of an anastomosis is much greater, particularly when the anastomosis is colon-colon
3. In this situation, an end colostomy is often safer and can be reversed later
85
What is a colorectal resection?
1. The only option for cure in patients with colon cancer
2. Is tailored to the patient and the tumour location
3. The lymphatic drainage of the colon follows the arterial supply and therefore most resections are tailored around the resection of particular lymphatic chains (e.g. ileo-colic pedicle for right sided tumours)
4. Some patients may have confounding factors that will govern the choice of procedure, e.g. a tumour in a patient from a HNPCC family may be better served with a panproctocolectomy rather than segmental resection
86
What decision must be made following colorectal resection regarding restoration of continuity?
Anastamosis (surgical connection between two structures) or end stoma
87
What are the technical factors regarding anastamosis healing in colorectal resections?
Adequate blood supply, mucosal apposition and no tissue tension
In certain situations (e.g. surrounding sepsis, unstable patients, inexperienced surgeons) it may be better to opt for an end stoma
88
What are stomas?
Involve bringing the lumen or visceral contents onto the skin, most commonly the bowel
89
What stoma should be used for the right side of the abdomen, specifically the RIF?
1. Ileostomy: can be loop or end depending on location
2. Should be spouted so that their irritant contents are not in contact with the skin
3. Output = liquid
90
What stoma should be used for the left side of the abdomen?
1. Colostomy: end or loop, again depends on location and colonic segment used
2. Should be flushed (no need for spouted because contents are less irritant)
3. Output = solid
91
What is important regarding stoma siting?
1. Will ultimately influence the patient's ability to manage their stoma and the risk of leakage
2. Leakage of stoma contents and subsequent maceration of the surrounding skin can rapidly progress into a spiralling loss of control of stoma contents
3. Ideally, the site of the stoma should be discussed with the patient prior to surgery
92
What is Virchow’s triad?
1. Venous stasis
2. Vessel wall injury
3. Blood hypercoagulability
93
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
94
What are the risk factors for DVT?
1. Oral contraceptive pill
2. Surgery
3. Prolonged immobility
4. Long bone fractures
5. Obesity
6. Pregnancy
7. Dehydration
8. Smoking
9. Polycythaemia
10. Anti-phospholipid syndrome
11. Thrombophilia disorders (e.g. protein C deficiency)
12. Active malignancy
95
What is the epidemiology for DVT?
Common, especially in hospitalised patients- yearly incidence of approximately 1 in every 1000 adults
96
What are the presenting symptoms of DVT?
1. Asymptomatic or lower limb swelling or tenderness
2. May present with signs/ symptoms of a pulmonary embolus (sudden onset dyspnoea, chest pain)
97
What are the signs of DVT on physical examination?
Examine for swelling, calf tenderness:
1. Severe leg oedema (usually unilateral)
2. Dilated superficial veins over foot and leg
3. Cyanosis (phlegmasia cerulea dolens) is rare
*Respiratory examination for signs of a pulmonary embolus: Sudden onset dyspnoea, cough, haemoptysis and pleuritic chest pain
98
What should be performed in any patient with suspected DVT?
A two-level DVT Wells score
99
What is the Two-level DVT Wells score?
1. Active cancer (treatment ongoing, within 6 months, or palliative) = 1
2. Paralysis, paresis or recent plaster immobilisation of the lower extremities= 1
3. Recently bedridden for 3 days or more or major surgery within 12 weeks requiring general or regional anaesthesia = 1
4. Localised tenderness along the distribution of the deep venous system = 1
5. Entire leg swollen = 1
6. Calf swelling at least 3 cm larger than asymptomatic side = 1
7. Pitting oedema confined to the symptomatic leg = 1
8. Collateral superficial veins (non-varicose) = 1
9. Previously documented DVT = 1
10. An alternative diagnosis is at least as likely as DVT = -2
100
How is the Two-level DVT Wells score interpreted for DVT likelihood?
DVT likely: 2 points or more
DVT unlikely: 1 point or less
101
What is the next step in management for a patient who scored 1 point or less on the two-level DVT Wells score?
DVT ‘unlikely’:
1. Perform a D dimer score within 4 hours
2. If not, interim therapeutic anticoagulation should be given until the result is available, but still performed within 24 hours
102
What should be the next step in management if a D dimer result is negative in a suspected DVT?
Then DVT is unlikely and alternative diagnoses should be considered
103
What should be the next step in management if a D dimer result is positive in a suspected DVT?
A proximal leg vein ultrasound scan should be carried out within 4 hours (if delayed then give interim therapeutic anticoagulation)
104
What are d-dimer tests in the investigation of DVTs?
1. NICE recommend either a point-of-care (finger prick) or laboratory-based test
2. Age-adjusted cut-offs should be used for patients > 50 years old
105
What is the next step in management for a patient who scored 2 points or more on the two-level DVT Wells score?
DVT is ‘likely’:
1. A proximal leg vein ultrasound scan should be carried out within 4 hours
2. If not, interim therapeutic anticoagulation should be given until the result is available, but still performed within 24 hours
106
What should be the next step in management if a proximal leg vein ultrasound is positive in a suspected DVT?
Then a diagnosis of DVT is made and anticoagulant treatment should start
107
What should be the next step in management if a proximal leg vein ultrasound is negative in a suspected DVT?
A D-dimer test should be arranged: a negative scan and negative D-dimer makes the diagnosis unlikely and alternative diagnoses should be considered
108
What should be the next step in management if a proximal leg vein ultrasound is negative in a suspected DVT but the D dimer is positive?
1. Stop interim therapeutic anticoagulation
2. Offer a repeat proximal leg vein ultrasound scan 6 to 8 days later
109
What is meant by interim therapeutic anticoagulation in suspected DVT?
Used to be LMWH, now a direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban
110
What is the management of a confirmed DVT?
1. NICE now advocate using a DOAC once a diagnosis is suspected, with this continued if the diagnosis is confirmed
2. All patients should have anticoagulation for at least 3 months
3. Then if the VTE was provoked, the treatment can be stopped
4. If the VTE was unprovoked, then treatment is typically continued for up to 3 further months (i.e. 6 months in total)
111
What is the ORBIT score used for?
To help assess the risk of bleeding in a patient on anticoagulation
112
In what group of patients are DOACs recommended as first line for the management of DVTs?
Essentially all patients including those with active cancer unless contraindicated
Not to be used in patients with:
1. Renal impairment (< 15/min) then LMWH, unfractionated heparin or LMWH followed by a VKA
2. Antiphospholipid syndrome then LMWH followed by a VKA should be used
113
How can VTEs be prevented?
1. Use of graduated compression stockings
2. Mobilisation if possible (physical activity)
3. At-risk groups (immobilised hospital patients) should have prophylactic heparin, e.g. LMWH if no contraindications
114
What are the complications of DVT?
Of the disease:
1. PE
2. Damage to vein valves and chronic venous insufficiency of the lower limb (post-thrombotic syndrome)
3. Rare: Venous infarction (phlegmasia cerulea dolens)
Of the treatment:
1. Heparin-induced thrombocytopaenia
2. Bleeding
115
What is the prognosis of DVT?
Depends on the location of DVT:
1. Below-knee DVTs lower risk of embolus
2. More proximal DVTs have higher risk of propagation and embolisation, which, if large, may be fatal
116
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
117
What is the epidemiology of gastric cancer?
1. Accounts for around 2% of all cancer diagnoses in the developed world
2. Much less common than colorectal and slightly less common than oesophageal cancer
3. It is a cancer of older people (half of patients are > 75 years) are has a male predominance (2:1)
118
What are the risk factors for gastric cancer?
1. Helicobacter pylori
2. Atrophic gastritis
3. Lifestyle: diet and smoking
119
How does Helicobacter pylori increase the risk of gastric cancer?
1. Triggers inflammation of the mucosa
2. Leads to atrophy and intestinal metaplasia
120
What are the symptoms of gastric cancer in the early stages?
Often asymptomatic
121
What are the features of gastric cancer?
1. Abdominal pain: typically vague, epigastric pain, may present as dyspepsia
2. Weight loss and anorexia
3. Nausea and vomiting
4. Dysphagia: particularly if the cancer arises in the proximal stomach
5. Overt upper gastrointestinal bleeding is seen only in a minority of patients
122
What are the features of lymphatic spread in gastric cancer?
1. Left supraclavicular lymph node: Virchow's node
2. Periumbilical nodule: Sister Mary Joseph's node
123
What is the investigation of choice to diagnose gastric cancer?
Oesophago-gastro-duodenoscopy with biopsy
124
What are the findings of gastric cancer on biopsy?
Signet ring cells:
1. They contain a large vacuole of mucin which displaces the nucleus to one side
2. Higher numbers of signet ring cells are associated with a worse prognosis
125
What investigation is used for staging in gastric cancer?
CT
126
What is the management of gastric cancer?
1. Surgery: options depend on the extent and site but include:
a. Endoscopic mucosal resection
b. Partial gastrectomy
c. Total gastrectomy
2. Chemotherapy
127
What is a gastric MALT lymphoma?
1. Associated with H. pylori infection in 95% of cases
2. Good prognosis
3. If low grade then 80% respond to H. pylori eradication
128
What is H. pylori eradication therapy?
A 7-day course of:
1. A proton pump inhibitor + amoxicillin + (clarithromycin OR metronidazole)
2. If penicillin-allergic: a proton pump inhibitor + metronidazole + clarithromycin
129
What is head and neck cancer?
An umbrella term, includes:
1. Oral cavity cancers
2. Cancers of the pharynx (including the oropharynx, hypopharynx and nasopharynx)
3. Cancers of the larynx
130
What are the features of head and neck cancer?
1. Neck lump
2. Hoarseness (voice change)
3. Persistent sore throat
4. Persistent mouth ulcer
131
What is laryngeal cancer?
Form of cancer that is frequently associated with smoking and alcohol use
132
What are the features of laryngeal cancer?
Hoarseness
Dysphonia
Sore throat
Difficulty swallowing
Referred otalgia
133
What is the NICE (2WW) referral pathway criteria for laryngeal cancer?
In people aged 45 and over with:
1. Persistent unexplained hoarseness or
2. An unexplained lump in the neck
134
What is the management for laryngeal cancer?
Dictated by TNM stage
Modalities include surgical resection, radiotherapy, chemotherapy, or any combination of these
Goals of therapy are eradication of cancer with organ preservation
Speech therapy is appropriate after treatment
135
What is the prognosis of laryngeal cancer?
Overall mortality has not changed in nearly 30 years, but the rate of organ preservation has significantly improved
136
What is oropharyngeal cancer (carcinoma)?
Cancer of the oropharynx strongly associated with tobacco and alcohol use
Also strongly implicated with human papilloma virus (HPV) infection in people not exposed to smoking and alcohol use
(Betel nut chewing in developing countries)
137
What are the features of oropharyngeal cancer?
Sore throat
Referred oral pain
Dysphagia
Trismus (muscle spasms in jaw = tightness)
Weight loss and neck mass can be the first signs of otherwise asymptomatic oropharyngeal cancer
138
What is the NICE referral pathway (2ww) for suspected oral cancer?
Consider a 2ww referral in people with either:
1. Unexplained ulceration in the oral cavity lasting for more than 3 weeks or
2. Persistent and unexplained lump in the neck.
Consider an urgent 2ww referral for assessment by a dentist in people who have either:
1. A lump on the lip or in the oral cavity or
2. A red or red and white patch in the oral cavity consistent with erythroplakia or erythroleukoplakia
139
What is the management of oropharyngeal cancer?
Dictated through staging (via CT or MRI with contrast and ultrasound-guided fine needle aspiration cytology, followed by triple endoscopy (nasolaryngopharyngoscopy, oesophagoscopy, and bronchoscopy), positron emission tomography (PET), or CT-PET.
Treatment involves surgery, chemotherapy, radiotherapy, and monoclonal antibodies (in combination with radiotherapy)
Patients should be managed by an MDT in specialised head and neck centres to optimise outcome
140
What is the NICE referral criteria (2ww) for suspected thyroid cancer?
People with an unexplained thyroid lump
141
What is hepatocellular carcinoma?
Primary malignancy of hepatocytes, usually occurring in a cirrhotic liver
142
What is the epidemiology of hepatocellular carcinoma?
The third most common cause of cancer worldwide
143
What are the most common causes of hepatocellular carcinoma?
1. Chronic hepatitis B is the most common cause worldwide
2. Chronic hepatitis C is the most common cause in Europe
144
What is the main risk factor for developing hepatocellular cancer?
Liver cirrhosis
145
What are the most common causes of liver cirrhosis?
Secondary to:
1. Hepatitis B and C
2. Alcohol
3. Haemochromatosis
4. Primary biliary cirrhosis
146
What are some of the risk factors of hepatocellular cancer?
1. Alpha-1 antitrypsin deficiency
2. Glycogen storage disease
3. Drugs: OCP, anabolic steroids
4. Porphyria cutanea tarda
5. Diabetes mellitus, metabolic syndrome
6. Male sex
7. Aflatoxins: Aspergillus flavus fungal toxin found on grains or biological weapons
147
What are the features of hepatocellular cancer?
1. Tends to present late, features of liver failure:
a. Jaundice
b. Ascites
c. RUQ pain,
d. Hepatosplenomegaly
e. Pruritus
2. Possibly present as decompensated chronic liver disease: encephalopathy, asterixis, spider naevi
148
What is the tumour marker for hepatocellular carcinoma?
AFP: alpha-fetoprotein, will be raised, has high sensitivity
149
What is the screening for hepatocellular carcinoma?
Ultrasound ± AFP in high risk groups:
1. Patients with liver cirrhosis secondary to Hep B and C, haemochromatosis
2. Men with liver cirrhosis secondary to alcohol
150
What is the management of hepatocellular carcinoma?
1. In early disease: surgical resection
2. Definitive management: liver transplantation
3. Radiofrequency ablation
4. Transarterial chemoembolisation
5. Sorafenib: a multikinase inhibitor
151
What is the prognosis of hepatocellular carcinoma?
A very aggressive type of cancer, depends upon stage and overall functional status of the liver
152
What is the difference between acute and chronic leukaemia?
1. Acute leukemia: occurs when leucocytes are less mature and fast-developing and become dysfunctional cells called blasts as they leave the bone marrow
2. By contrast, chronic leukemia occurs when leucocytes develop more slowly, potentially taking years to cause symptoms
153
What is the most common cause of acute leukaemia in children and in adults?
1. Acute lymphoblastic leukaemia (ALL): most common malignancy affecting children and accounts for 80% of childhood leukaemias
2. Acute myeloid luekaemia (AML): the more common form of acute leukaemia in adults
154
What is acute myeloid leukaemia?
1. AML is the more common form of acute leukaemia in adults
2. It may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder
155
What is the aetiology of AML?
1. Myeloblasts, arrest at an early stage of development, with varying cyto-genetic abnormalities (e.g. gene mutations and chromosome translocations)
2. Myeloblasts then undergo malignant transformation and proliferation, with subsequent replacement of normal marrow elements
3. Resulting in bone marrow failure
156
What are the features of AML?
Largely related to bone marrow failure:
1. Anaemia: pallor, lethargy, weakness
2. Neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc
3. Thrombocytopenia: bleeding
4. Splenomegaly
5. Bone pain
157
What are the investigations for AML?
1. Bloods: reduced Hb, reduced platelets, variable WCC
2. Blood film: AML blasts may show cytoplasmic granules or Auer rods
3. Bone marrow aspirate or biopsy:
Hypercellular with >30 % blasts (immature cells)
4. Cytogenetics: diagnostic and prognostic information
158
What are the poor prognostic features of AML?
1. > 60 years
2. > 20% blasts after first course of chemo
3. Cytogenetics: deletions of chromosome 5 or 7
159
What is Acute promyelocytic leukaemia?
1. A rare subtype of AML
2. Associated with t(15;17)
3. usion of PML and RAR-alpha genes
4. Presents younger than other types of AML (average = 25 years old)
5. Auer rods (seen with myeloperoxidase stain)
6. DIC or thrombocytopenia often at presentation
7. Good prognosis
160
What is acute lymphoblastic leukaemia (ALL)?
1. Malignancy of the bone marrow and blood characterized by the proliferation of lymphoblasts (primitive lymphoid cells)
2. Most common malignancy affecting children and accounts for 80% of childhood leukaemias
161
What is the epidemiology of ALL?
Peak incidence is at around 2-5 years of age and boys are affected slightly more commonly than girls
162
What is the aetiology of ALL?
1. Lymphoblasts, arrest at an early stage of development, with varying cytogenetic abnormalities (e.g. gene mutations and chromosome translocations)
2. Lymphoblasts then undergo malignant transformation and proliferation, with subsequent replacement of normal marrow elements
3. Resulting in bone marrow failure and infiltration into other tissues
163
What are the risk factors/associations of ALL?
1. Environmental: radiation, viruses
2. Genetic: e.g. Down’s syndrome, neurofibromatosis type 1, increased risk in siblings
164
What are the main features of ALL?
Bone marrow failure:
1. Anaemia: lethargy and pallor
2. Neutropaenia: frequent or severe infections
3. Thrombocytopenia: easy bruising, petechiae
165
What are some of the other features of ALL?
1. Bone pain (secondary to bone marrow infiltration)
2. Splenomegaly
3. Hepatomegaly
4. Fever is present in up to 50% of new cases (representing infection or constitutional symptom)
5. Testicular swelling
166
What are the investigations for ALL?
1. Bloods: FBC (normochromic normocytic anaemia, reduced platelets, variable WCC)
2. Blood film: Lymphoblasts evident
3. Bone marrow aspirate or trephine biopsy:
a. Hypercellular with >30 % lymphoblasts
b. Immunophenotyping: Using antibodies for cell surface antigens e.g. CD20
167
What are the classifications for ALL?
Morphologic classification(French–American–British classification):
L1: Small lymphoblasts, scanty cytoplasm
L2: Larger, heterogenous lymphoblasts
L3: Large lymphoblasts with blue or vacuolated cytoplasm
168
What are the poor prognostic factors for ALL?
1. Age < 2 years or > 10 years
2. WBC > 20 * 109/l at diagnosis
3. T or B cell surface markers
4. Non-Caucasian
5. Male sex
169
What is Chronic Myeloid Leukaemia (CML)?
1. A malignant clonal disease characterized by proliferation of granulocyte precursors in the bone marrow and blood
2. Distinguished from AML by its SLOWER progression
170
What is the aetiology of CML?
Malignant proliferation of stem cells, three stages:
1. Relatively stable chronic phase of variable duration (average of 4–6 years)
2. Accelerated phase (3–9 months)
3. Acute leukaemia phase (blast transformation)
171
What is the epidemiology of CML?
1. Incidence increases with age, mean 40–60 years
2. More common in men
172
What chromosome is present in CML?
Philadelphia chromosome:
1. This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22
2. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal
173
What is the presentation of CML?
1. Usually at 60-70 years
2. Anaemia: lethargy
3. Weight loss and sweating are common
4. Splenomegaly may be marked → abdo discomfort
5. An increase in granulocytes at different stages of maturation +/- thrombocytosis
6. Decreased leukocyte alkaline phosphatase
7. May undergo blast transformation (AML in 80%, ALL in 20%)
174
What are the investigations for CML?
1. Bloods:
a. FBC: grossly raised WCC, low Hb, raised basophils /eosinophils/ neutrophils, variable platelets
b. Raised uric acid, low neutrophil alkaline phosphatase
2. Blood film: Shows immature granulocytes in peripheral blood
3. Bone marrow aspirate or biopsy:
Hypercellular with raised myeloid–erythroid ratio
175
What is the first line management for CML?
Imatinib:
1. Inhibitor of the tyrosine kinase associated with the BCR-ABL defect
2. Very high response rate in chronic phase CML
176
What else can be given in the management of CML?
1. Imatinib
2. Hydroxyurea
3. Interferon-alpha
4. Allogenic bone marrow transplant
177
What is Chronic lymphocytic leukaemia (CLL)?
1. Characterized by progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin
2. There is an overlap between CLL and non- Hodgkin’s lymphomas
178
What is the aetiology of CLL?
Caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
179
What is the epidemiology of CLL?
The most common form of leukaemia seen in adults
180
What are the features of CLL?
1. Often none: may be picked up by an incidental finding of lymphocytosis
2. Constitutional: anorexia, weight loss
3. Bleeding, infections
4. Lymphadenopathy more marked than chronic myeloid leukaemia (non-tender)
181
What are the investigations for CLL?
1. Bloods:
a. lymphocytosis
b. anaemia: may occur either due to bone marrow replacement on autoimmune hemolytic anaemia (AIHA)
c. thrombocytopenia: may occur either due to bone marrow replacement on immune thrombocytopenia (AIHA)
2. Blood film: smudge cells/ smear cells
3. Immunophenotyping: (key investigation)
a. a panel of antibodies specific for CD5, CD19, CD20 and CD23
182
What are the complications of CLL?
1. Anaemia
2. Hypogammaglobulinaemia leading to recurrent infections
3. Warm autoimmune haemolytic anaemia in 10-15% of patients
4. Transformation to high-grade lymphoma (Richter's transformation)
183
What is Richter's transformation from CLL?
1. Occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin's lymphoma
2. Patients often become unwell very suddenly:
a. lymph node swelling
b. fever without infection
c. weight loss
d. night sweats
e. nausea
f. abdominal pain
184
What are the two broad types of lung cancer?
Histologically classified into:
1. Small cell lung cancer (SCLC) = 15%
2. Non-small cell lung cancer (NSCLC) = 85%
185
Which class of lung cancer carries a worse prognosis?
Small cell lung cancer
186
What are the different types of non-small cell lung cancer?
1. Adenocarcinoma (most common)
2. Squamous
3. Large cell
4. Alveolar cell carcinoma
5. Bronchial adenoma
187
What is adenocarcinoma lung cancer?
1. A subtype of non-small cell lung cancer
2. Most common type of lung cancer
3. Often seen in non-smokers
188
What are the features of lung cancer?
1. Persistent cough
2. Haemoptysis
3. Dyspnoea
4. Chest pain
5. Weight loss and anorexia
6. Hoarseness (Pancoast tumours pressing on the recurrent laryngeal nerve)
7. Superior vena cava syndrome: oncological emergency due to compression of SVC
189
What are the findings of lung cancer on examination?
1. Fixed, monophonic wheeze may be noted
2. Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
3. Clubbing
190
What is superior vena cava syndrome?
An oncological emergency due to compression of the SVC- most commonly seen in lung cancer
191
What are the features of superior vena cava syndrome?
1. Dyspnoea (most common symptom)
2. Swelling of the face, neck and arms - conjunctival and periorbital oedema may be seen
3. Headache: often worse in the mornings
4. Visual disturbance
5. Pulseless jugular venous distension
192
What is the management of superior vena cava syndrome?
1. Dependent on the individual patient and their malignancy (or cause)
2. Endovascular stenting is often treatment of choice: provides symptom relief
193
When should an urgent chest x-ray be considered within 2 weeks to assess for lung cancer?
Over 40 years of age and any of the following:
1. Persistent or recurrent chest infections
2. Finger clubbing
3. Supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
4. Chest signs consistent with lung cancer
5. Thrombocytosis
194
When should an urgent chest x-ray be offered within 2 weeks to assess for lung cancer?
Over 40 years of age if they have 2 or more of the following unexplained symptoms, or if they have ever smoked and have 1 or more of the following unexplained symptoms:
1. Cough
2. Fatigue
3. Shortness of breath
4. Chest pain
5. Weight loss
6. Appetite loss
195
When should someone be referred on the suspected lung cancer pathway (appointment within 2 weeks)?
1. Have chest x-ray findings that suggest lung cancer
2. Are aged over 40 years with unexplained haemoptysis
196
What is squamous cell cancer of the lung?
1. Type of NSCLC
2. Typically central
3. Associated with parathyroid hormone-related protein secretion causing hypercalaemia
4. Strongly associated with finger clubbing
5. Cavitating lesions
6. Hypertrophic pulmonary oestoarthropathy (HPOA)
197
What is adenocarcinoma of the lung?
1. Type of NSCLC
2. Typically peripheral
3. Most common type of lung cancer in non-smokers (but majority of patients who develop these are smokers)
198
What is large cell lung carcinoma?
1. Type of NSCLC
2. Typically peripheral
3. Anaplastic, poorly differentiated tumours
4. Poor prognosis
5. May secrete b-hCG
199
What are the features of small cell lung cancer?
1. Usually central
2. Associated with ectopic ADH and ACTH secretion
a. ADH: hyponatraemia
b. ACTH: Cushing's syndrome
3. ACTH secretion can cause bilateral adrenal hyperplasia: hypokalaemic acidosis
200
What is Lambert-Eaton syndrome in small cell lung cancer?
Antibodies to voltage gated calcium channels causing myasthenic like syndrome
201
What are the investigations for lung cancer?
1. Chest x-ray (often the first test)
2. CT = investigation of choice
3. Bronchoscopy (for biopsy)
4. PET scanning: typically for NSCLC
5. Bloods: raised platelets
202
What is the investigation of choice for suspected lung cancer?
CT scan
203
What is the role of bronchoscopy in the diagnosis of lung cancer?
1. Allows a biopsy to be taken to obtain a histological diagnosis
2. Sometimes aided by an endobronchial ultrasound
204
What is the role of PET scanning in the diagnosis of non-small cell lung cancer?
1. To establish eligibility for curative treatment
2. Uses 18-fluorodeoxygenase which is preferentially taken up by neoplastic tissue
3. Has been shown to improve diagnostic sensitivity of both location and distant metastasis spread in NSCLC
205
What is the management for non-small cell lung cancer?
1. Only 20% are suitable for surgery
2. Can be offered curative or palliative radiotherapy
3. Has poor response to chemotherapy
206
What needs to be performed prior to surgery for NSCLC?
1. Mediastinoscopy
2. This is because CT does not always show mediastinal lymph node involvement
207
What are the contraindications for surgery in the management of NSCLC?
1. Assess general health
2. Staged 3b or 4 = metastases present
3. FEV1 < 1.5 L for lobectomy
4. Malignant pleural effusion
5. Tumour near hilum
6. Vocal cord paralysis
7. SVC obstruction
208
What is the management for small cell lung cancer?
1. Usually metastatic disease by the time of diagnosis
2. Patients with very early stage disease are now considered for surgery (T1-2a, N0, M0)
3. Most patients with early/ limited disease receive a combination of chemotherapy and radiotherapy
4. Patients with more extensive disease are offered palliative chemotherapy
209
Which type of lung cancer generally carries a worse prognosis?
Small cell lung cancer
210
What are the paraneoplastic features of small cell lung cancer?
1. ADH: hyponatraemia
2. ACTH: not typical, HTN and hyperglycaemia, hypokalaemia alkalosis and muscle weakness
3. Lambert- Eaton syndrome
211
What are the paraneoplastic features of squamous cell lung cancer?
1. Parathyroid hormone-related protein secretion: causes hypercalcaemia and clubbing
2. Hypertrophic pulmonary osteoarthropathy
3. Hyperthyroidism due to ectopic TSH
212
What are Lymphomas?
Neoplasms of lymphoid cells, originating in lymph nodes or other lymphoid tissues
213
What are the different types of lymphoma?
1. Hodgkin's
2. Non-Hodgkin's
3. Burkitt's
4. Gastric MALT lymphoma
214
What is Hodgkin's lymphoma?
A malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell
215
What is the epidemiology of Hodgkin's lymphoma?
Bimodal age distributions being most common in the third and seventh decades
216
What are the two risk factors for Hodgkin's lymphoma?
1. HIV
2. Epstein-Barr virus
217
What is the main presenting symptom of Hodgkin's lymphoma?
Lymphadenopathy (75%):
1. Most commonly in the neck (cervical/supraclavicular) > axillary > inguinal
2. Usually painless, non-tender, asymmetrical
3. Alcohol-induced lymph node pain is characteristic of Hodgkin's lymphoma but is seen in less than 10% of patients
218
What are the other symptoms of Hodgkin's lymphoma aside from lymphadenopathy?
1. Systemic - 'B symptoms' (25%):
a. weight loss
b. pruritus
c. night sweats
d. fever (Pel-Ebstein)
2. Mediastinal mass: may be symptomatic (e.g. cough) or found incidentally on a chest x-ray
219
What investigation is diagnostic for Hodgkin's lymphoma?
Lymph node biopsy: Reed-Sternberg cells are diagnostic: these are large cells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an 'owl's eye' appearance)
220
What are the investigations for Hodgkin's lymphoma?
1. Bloods:
a. Normocytic anaemia: may be multifactorial e.g. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia
b. Eosinophilia: caused by the production of cytokines e.g. IL-5
c. LDH raised
2. Lymph node biopsy: Reed-Sternberg cells
3. Imaging:
a. CXR: mediastinal mass, large mediastinal adenopathy
b. CT of thorax, abdomen and pelvis: may show enlarged lymph nodes and other sites of disease
221
What are the different histological types of Hodgkin's lymphoma?
1. Nodular sclerosing:
a. Most common (around 70%)
b. Good prognosis
c. More common in women
d. Associated with lacunar cells
2. Mixed cellularity:
a. Around 20%
b. Good prognosis
c. Associated with a large number of Reed-Sternberg cells
3. Lymphocyte predominant
a. Around 5%
b. Best prognosis
4. Lymphocyte depleted
a. Rare
b. Worst prognosis
222
What is the staging system for Hodgkin's lymphoma?
Ann-Arbor staging:
I: single lymph node
II: 2 or more lymph nodes/regions on the same side of the diaphragm
III: nodes on both sides of the diaphragm
IV: spread beyond lymph nodes
Each stage may be subdivided into A or B:
A = no systemic symptoms other than pruritus
B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)
223
What is the management of Hodgkin's lymphoma?
1. Chemotherapy (mainstay of treatment): Two combinations may be used
a. ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine): considered the standard regime
b. BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone): better remission rates but higher toxicity
2. Radiotherapy
3. Combined modality therapy (CMT): chemotherapy followed by radiotherapy
4. Hematopoietic cell transplantation
may be used for relapsed or refractory classic Hodgkin lymphoma
224
What are the complications of treatment of Hodgkin's lymphoma?
1. Most patients now achieve long-term survival free of Hodgkin's lymphoma with modern therapy
2. Complications of treatment are therefore more of an issue for these patients (e.g. chemotherapy)
3. Secondary malignancies are a risk, in particular solid tumours: breast and lung
225
What is non-Hodgkin's lymphoma?
Malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs, every other type of lymphoma that is not Hodgkin's lymphoma
226
What is the epidemiology of Non-Hodgkin's lymphoma?
1. The 6th most common cause of cancer in the UK
2. Much more common than Hodgkin's lymphoma
3. While different subtypes can affect different ages, it typically affects the elderly with one-third of cases occurring in those over 75 years of age
227
What are the risk factors for NHL?
1. Elderly
2. Caucasians
3. History of viral infection (specifically Epstein-Barr virus)
4. Family history
5. Certain chemical agents (pesticides, solvents)
6. History of chemotherapy or radiotherapy
7. Immunodeficiency (transplant, HIV, diabetes mellitus)
7. Autoimmune disease (SLE, Sjogren's, coeliac disease)
228
What are the symptoms of NHL?
1. Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
2. Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
3. Extranodal Disease:
a. gastric (dyspepsia, dysphagia, weight loss, abdominal pain)
b. bone marrow (pancytopenia, bone pain)
c. lungs
d. skin
e. central nervous system (nerve palsies)
229
What are the differences in presentation between Hodgkin's and NHL?
1. Lymphadenopathy in Hodgkin's lymphoma can experience alcohol-induced pain in the node
2. 'B' symptoms typically occur earlier in Hodgkin's lymphoma and later in non-Hodgkin's lymphoma
3. Extra-nodal disease is much more common in non-Hodgkin's lymphoma than in Hodgkin's lymphoma
230
What are the signs of NHL?
1. Signs of weight loss
2. Lymphadenopathy (typically in the cervical, axillary or inguinal region)
3. Palpable abdominal mass - hepatomegaly, splenomegaly, lymph nodes
4. Testicular mass
5. Fever
231
What is the investigation of choice for NHL?
Excisional node biopsy: certain subtypes will have a classical appearance on biopsy such as Burkitt's lymphoma having a 'starry sky' appearance
232
What are the investigations for NHL?
1. Excisional node biopsy
2. CT chest, abdomen and pelvis (to assess staging)
3. HIV test (often performed as this is a risk factor for non-Hodgkin's lymphoma)
4. FBC and blood film (normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)
5. ESR (useful as a prognostic indicator)
6. LDH (a marker of cell turnover, useful as a prognostic indicator)
7. Other investigations can be ordered as the clinical picture indicates (LFT's if liver metastasis suspected, PET CT or bone marrow biopsy to look for bone involvement, LP if neurological symptoms)
233
How is NHL staged?
1. Ann Arbor system:
Stage 1 - One node affected
Stage 2 - More than one node affected on the same side of the diaphragm
Stage 3 - Nodes affected on both sides of the diaphragm
Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
2. The stage is combined with the letter A or B to indicate the presence of 'B' symptoms
234
What is the management of NHL?
1. Dependent on the specific sub-type of non-Hodgkin's lymphoma and will typically take the form of watchful waiting, chemotherapy or radiotherapy
2. All patients will receive flu/pneumococcal vaccines
3. Patients with neutropenia may require antibiotic prophylaxis
235
What are the complications of NHL?
1. Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
2. Superior vena cava obstruction
3. Metastasis
4. Spinal cord compression
5. Complications related to treatment e.g. Side effects of chemotherapy
236
What is the prognosis of NHL?
1. Low-grade non-Hodgkin's lymphoma has a better prognosis
2. High-grade non-Hodgkin's lymphoma has a worse prognosis but a higher cure rate
237
What is Burkitt's lymphoma?
1. A type of NHL
2. A high-grade B-cell neoplasm with two major forms: endemic (African) or sporadic
238
What are the microscopy findings of Burkitt's lymphoma from excisional node biopsy?
'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
239
What is the management of Burkitt's lymphoma?
Chemotherapy: tends to produce a rapid response which may cause 'tumour lysis syndrome'
Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin) is often given before the chemotherapy to reduce the risk of this occurring
240
What is multiple myeloma?
1. Haematological malignancy characterised by plasma cell proliferation in the bone marrow
2. This results in bone lesions and production of a monoclonal immunoglobulin in the serum and/or urine
241
What is the aetiology of multiple myeloma?
Arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells
242
What is the epidemiology of multiple myeloma?
The median age at presentation is 70 years old
243
How can multiple myeloma present?
Asymptomatic: incidental finding on routine blood tests
244
What are the features of multiple myeloma?
1.CRABBI:
a. Calcium
b. Renal
c. Anaemia
d. Bleeding
e. Bones
f. Infection
2. Amyloidosis e.g. macroglossia
3. Carpal tunnel syndrome
4. Neuropathy
5. Hyperviscosity
245
What does the C stand for in 'CRABBI' for multiple myeloma?
Calcium- hypercalcaemia:
1. Primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
2. Much less common contributing factors:
a. impaired renal function
b. increased renal tubular calcium reabsorption and elevated PTH-rP levels
3. This leads to constipation, nausea, anorexia and confusion
246
What does the R stand for in 'CRABBI' for multiple myeloma?
Renal impairment:
1. Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
2. This causes renal damage which presents as dehydration and increasing thirst
3. Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
247
What does the A stand for in 'CRABBI' for multiple myeloma?
Anaemia:
1. Bone marrow crowding suppresses erythropoiesis leading to anaemia
2. This causes fatigue and pallor
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What do the two B's stand for in 'CRABBI' in multiple myeloma?
1. Bleeding
a. Bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
2. Bones
a. Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
b. This may present as pain (especially in the back) and increases the risk of pathological fractures
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What does the I stand for in 'CRABBI' for multiple myeloma?
Infection: a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
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What are the investigations for multiple myeloma?
1. Bloods
2. Protein electrophoresis
3. Bone marrow aspiration
4. Imaging: whole-body MRI
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What are the blood findings for multiple myeloma?
1. Full blood count: anaemia
2. Peripheral blood film: rouleaux formation
3. Urea and electrolytes: renal failure
4. Bone profile: hypercalcaemia
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What are the findings on protein electrophoresis for multiple myeloma?
1. Raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
2. In the urine, they are known as Bence Jones proteins
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What will be the bone marrow aspirate findings for multiple myeloma?
Confirms the diagnosis if the number of plasma cells is significantly raised
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What imaging is recommended in multiple myeloma?
1. Whole-body MRI: now recommended in the 2016 NICE guidelines
2. X-rays: 'rain-drop skull' (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots)
a. Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull'
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What is the diagnostic criteria for multiple myeloma?
Requires:
a. one major and one minor criteria or
b. Three minor criteria in an individual who has signs or symptoms of multiple myeloma
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What is the major criteria for multiple myeloma?
1. Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
2. 30% plasma cells in a bone marrow sample
3. Elevated levels of M protein in the blood or urine
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What is the minor criteria for multiple myeloma?
1. 10% to 30% plasma cells in a bone marrow sample
2. Minor elevations in the level of M protein in the blood or urine.
3. Osteolytic lesions (as demonstrated on imaging studies)
4. Low levels of antibodies (not produced by the cancer cells) in the blood
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What is neutropenic sepsis?
1. A relatively common complication of cancer therapy, usually as a consequence of chemotherapy
2. It most commonly occurs 7-14 days after chemotherapy
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How can neutropenic sepsis be defined?
Neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
a. a temperature higher than 38ºC or
2. other signs or symptoms consistent with clinically significant sepsis
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What is the most common causative organism for neutropenic sepsis?
Gram-positive bacteria, particularly Staphylococcus epidermidis: this is probably due to the use of indwelling lines in patients with cancer
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What antibiotic can be given prophylactically in patients who are having chemotherapy to prevent neutropenic sepsis?
A fluoroquinolone
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What is the management of neutropenic sepsis?
1. Antibiotics must be started immediately, do not wait for the WBC
a. NICE: empirical antibiotic therapy with piperacillin with tazobactam (Tazocin) immediately
2. Following this patients are usually assessed by a specialist and risk-stratified to see if they may be able to have outpatient treatment
3. If patients are still febrile and unwell after 48 hours an alternative antibiotic such as meropenem is often prescribed +/- vancomycin
4. If patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly
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What is squamous cell carcinoma?
1. The proliferation of atypical, transformed epidermal keratinocytes in the skin with malignant behaviour
2. A common variant of skin cancer
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What are the risk factors for squamous cell carcinoma?
1. Eexcessive exposure to sunlight / psoralen UVA therapy
2. Actinic keratoses and Bowen's disease
3. Immunosuppression e.g. following renal transplant, HIV
4. moking
5. Long-standing leg ulcers (Marjolin's ulcer)
6. Genetic conditions e.g. xeroderma pigmentosum, oculocutaneous albinism
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What are the features if squamous cell carcinoma?
1. Typically on sun-exposed sites such as the head and neck or dorsum of the hands and arms
2. Rapidly expanding painless, ulcerate nodules
3. May have a cauliflower-like appearance
4. There may be areas of bleeding
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What are the signs of squamous cell carcinoma of the skin on physical examination?
Variable appearance:
1. Ulcerated
2. Hyperkeratotic
3. Crusted or scaly
4. Non-healing lesion
Often on sun-exposed areas
5. Palpate for local lymphadenopathy: metastatic disease (2-5%)
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What are the investigations for squamous cell carcinoma of the skin?
1. Skin biopsy: Confirms malignancy (full thickness keratinocyte atypia) and distinguishes it from other skin lesions
2. Fine-needle aspiration or lymph node biopsy: Only necessary if suspicion of metastasis
3. Staging: CT and/or MRI, PET scanning: lymphadenopathy and/or visceral nodules
4. Bloods: normal unless metastasis
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What are the differences between Basal Cell Carcinoma and Squamous Cell Carcinoma?
1. SCC are fast growing, penetrate deeper
2. BCC are slow growing, rarely metastasise
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What is the management of squamous cell carcinoma?
1. Surgical excision:
a. With 4mm margins if lesion <20mm in diameter
b. If tumour >20mm then margins should be 6mm
2. Mohs micrographic surgery may be used in high-risk patients and in cosmetically important sites
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What is the prognosis of squamous cell carcinoma?
1. Good prognosis:
a. Well differentiated
b. <20 mm diameter
c. <2mm deep
d. No associated diseases
2. Poor prognosis:
a. Poorly differentiated
b. >20 mm diameter
c. >4mm deep
d. If immunosuppressed
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What is tumour lysis syndrome?
1. A potentially deadly condition related to the treatment of high-grade lymphomas and leukaemias
2. It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy (can be steroids alone)
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What is the aetiology of tumour lysis syndrome?
1. Occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell
2. It leads to a high potassium and high phosphate level in the presence of a low calcium
2. It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level
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What are the two types of tumour lysis syndrome?
1. Laboratory
2. Clinical
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How is laboratory tumour lysis syndrome graded?
Cairo-Bishop scoring system: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy:
1. uric acid > 475umol/l or 25% increase
2. potassium > 6 mmol/l or 25% increase
3. phosphate > 1.125mmol/l or 25% increase
4. calcium < 1.75mmol/l or 25% decrease
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How is clinical tumour lysis syndrome diagnosed?
Laboratory tumour lysis syndrome plus one or more of the following:
1. Increased serum creatinine (1.5 times upper limit of normal)
2. Cardiac arrhythmia or sudden death
3. Seizure
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What should patients who are at high and low risk of tumour lysis syndrome receive?
1. High risk: IV allopurinol or IV rasburicase immediately prior to and during the first days of chemotherapy (should not be given together)
2. Low risk: should be given oral allopurinol during chemotherapy cycles in an attempt to avoid the condition
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What is IV rasburicase in the prophylaxis management of tumour lysis syndrome?
1. A recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin
2. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys
