Cancer Flashcards
Define prostate cancer
A primary malignant tumour/neoplasm of glandular origin situated in the prostate which is commonly seen in older men. Usually an adenocarcinoma.
What is the aetiology/risk factors of prostate cancer?
Aetiology is unknown
Proposed aetiological factors: high fat diet, genetic factors
Risk factors: Age >50 years Black ethnicity North American or Northwest European descent Family history of prostate cancer High fat diet Occupational exposure to cadmium BRCA2 gene
Summarise the epidemiology of prostate cancer
14% of men will develop prostate cancer in their life
Median age of diagnosis is 66 years old
Highest incidence amongst black men
2nd most common cause of cancer death amongst men
What are the presenting symptoms of prostate cancer?
Lower UT obstruction symptoms - FUNDHIPS Frequency Urgency Nocturia Dysuria Haematuria/Hesitancy Incontinence/intermittency Post-micturition dribbling Weak Stream
Metastatic spread: Weight loss Bone pain Lethargy Anorexia Cord compression
What are the signs on physical examination of prostate cancer?
Asymmetrical, nodular prostate on DRE and loss of midline sulcus
Palpable lymph nodes
What are appropriate investigations for prostate cancer?
Bloods:
SERUM PSA - >4micrograms/L however may be elevated in non-malignant conditions (BPH, prostatitis) or normal in those with prostate cancer
Testosterone - normal
LFTs - normal
FBC - normal unless in metastatic disease
DRE
Transrectal USS and Prostate biopsy (12 biopsies) - findings of malignant cells used in diagnosis and staging
Bone scan - check for metastases
X-rays - look for bone metastases
Pelvic CT - enlarged prostate, enlarged pelvic lymph nodes
What is the management of prostate cancer?
Watchful waiting (elderly, comorbid patients)
Active surveillance (low risk low volume)– regular DRE, biopsy
Brachytherapy
External beam radiotherapy
Radical prostatectomy and lymph node dissection
In metastatic disease - Hormonal therapy (shrinks tumour, doesn’t cure)
- LHRH agonists e.g. goserelin
- Anti-androgens e.g. bicalutamide
What are the possible complications of prostate cancer?
Often related to treatment
Radiation induced complications: Dysuria Frequency Rectal bleeding Urinary incontinence Urinary urgency Nocturia Diarrhoea Urinary stricture
Hormone induced complications:
Cognitive impairment
Gynaecomastia
Hot flushes
What is the prognosis of prostate cancer?
Prostate cancer is a curable cancer
Overall survival depends on initial stage at diagnosis
Can be high morbidity from treatment
Gleason score 2-4 on biopsies have minimal risk of death from prostate cancer in 15 years
Define squamous cell carcinoma
Cancer of keratinocytes in the epidermis which can invade local tissue and metastasise.
Explain the aetiology of squamous cell carcinoma
Risk factors:
UV exposure
Family history
Light skin
Actinic keratosis - pre-cancerous condition
Immunosuppression
HPV infection
Genetic predisposition
Carcinogens (e.g. tar derivatives, cigarette smoke)
Chronic skin disease (e.g. lupus) or chronic inflammation
Summarise the epidemiology of squamous cell carcinoma
2nd most common skin cancer
More common in men, individuals with light skin and those over 40 years old
Mainly in MIDDLE AGED and ELDERLY patients
What are the presenting symptoms of squamous cell carcinoma?
Hyperkeratotic (scaly, crusty), ill-defined nodule which may ulcerate Skin lesion Ulcerated Recurrent bleeding Non-healing Rolled, red, erythematous edges
What are the signs on physical examination of squamous cell carcinoma?
Variable appearance - may be ulcerated, hyperkeratotic, crusted or scaly, non-healing
Often on sun-exposed areas
May be local lymphadenopathy
May be neurological signs and symptoms if brain mets are present
What are the appropriate investigations for squamous cell carcinoma?
Mainly a CLINICAL DIAGNOSIS
Dermatoscope
Skin biopsy for definitive diagnosis of type
Fine-needle aspiration or lymph node biopsy - if metastasis is suspected
Staging - using CT, MRI or PET
Define basal cell carcinoma
Slow-growing cancer of the keratinocytes in the stratum basale of the epidermis which can show local invasion but rarely metastasise
Summarise the aetiology of basal cell carcinoma
Risk factors: UV light exposure Family history Light skin Immunosuppression History of frequent or severe sunburn in childhood Skin type I (always burns, never tans) Increasing age Male sex Genetic predisposition Photosensitising pitch Toxins: tar, arsenic
Summarise the epidemiology of basal cell carcinoma
Basal cell carcinoma is the most common skin cancer
More common in men
Incidence increases with age
Common in ares of high sunlight exposure
What are the presenting symptoms of basal cell carcinoma?
A chronic slowly progressive skin lesion
Usually found on the face, scalp, ears and trunk
What are the signs on physical examination of basal cell carcinoma?
Nodular/Nodulo-ulcerative (commonest):
Small glistening translucent skin over a coloured papule
Slowly enlarges
CENTRAL ULCER (rodent ulcer) with raised PEARLY EDGES
Fine surface TELANGIECTASIA
ROLLED EDGES
Morphoeic (sclerosing): Expanding Yellow/white waxy plaque with an ill-defined edge More aggressive than nodulo-ulcerative Scar like
Superficial (plaque like):
Most often on trunk
Multiple pink/brown scaly plaques with a fine edge expanding slowly
FLAT
Pigmented:
Dense colour
Looks like squamous cell carcinoma
What are the appropriate investigations for basal cell carcinoma?
Mainly a CLINICAL DIAGNOSIS
Biopsy rarely necessary
Define melanoma and melanocytic lesions
Melanoma is a malignant cancer of the melanocytes in the epidermis which shows local invasion and is very likely to metastasise.
Summarise the aetiology of melanoma
Risk factors: UV exposure Family history Immunosuppression Light skin Genetic predisposition - familial melanoma: CDKN2A gene DNA repair defects (xeroderma pigmentosum) History of moles
Summarise the epidemiology of melanoma
Melanoma is the most aggressive and deadly skin cancer
Most common in Australia
One of the most common cancers in young people
More likely in men and fair-skinned patients
Steadily increasing in incidence
What are the presenting symptoms of melanoma?
Rapidly change in size, shape or colour of a pigmented skin lesion Redness Bleeding Crusting Ulceration
What are the signs on physical examination of melanoma?
ABCDE A - ASYMMETRY B - IRREGULAR BORDER C - PIGMENTED AND COLOUR VARIATION D - DIAMETER >6MM E - RAPID EVOLUTION
Neurological signs and symptoms if metastasises to brain
What are the different types of melanoma and how do you distinguish between them?
Superficial Spreading (70%):
Arises in a pre-existing naevus
Expands in a radial fashion before a vertical growth phase
Common on the lower limbs in young/middle-aged adults
Related to intermittent high-intensity UV exposure
Nodular (15%): Arises de novo AGGRESSIVE NO radial growth phase Common on the trunk RAPID GROWTH Domed shape
Lentigo Maligna (10%): More common in ELDERLY with sun damage Large flat lesions Progresses slowly Usually on the face Related to long-term cumulative UV exposure
Acral Lentiginous (5%):
Arise on palms, soles and subungual areas
Most common type in NON-WHITE populations
Common in elderly and no clear relationship with UV exposure
What are the appropriate investigations for melanoma?
Excisional Biopsy - histological diagnosis and determination of Clark’s Levels and Breslow Thickness (two methods of determining the depth of penetration of a melanoma)
Dermatoscopy
Lymphoscintigraphy - a radioactive compound is injected into the lesion and images are taken over 30 mins to trace the lymph drainage and identify the sentinel nodes
Sentinel Lymph Node Biopsy - check for metastatic involvement
Staging - using ultrasound, CT or MRI, CXR
Bloods - LFTs (because the liver is a common site of metastasis)
Define oesophageal cancer
Malignant tumour arising in the oeseophageal mucosa. There are two main types:
Squamous cell carcinoma (upper 2/3rds of the oesophagus)
Adenocarcinoma (lower 1/3rd of the oesophagus affecting columnar epithelial cells)
Summarise the aetiology of oesophageal cancer
Squamous cell carcinoma: Cigarette smoke Alcohol HPV Hot food/fluids Caustic strictures (stricture following consumption of caustic substances eg bleach) Plummer-Vinson Syndrome (glossitis, cheilosis, oesophageal webs, iron deficiency anaemia) Palmoplantar keratosis Scleroderma Coeliac Disease Nutritional Deficiencies Dietary Toxins (i.e. nitrosamines) Hx Thoracic Radiotherapy
Adenocarcinoma: GORD Barrett's oesophagus (metaplastic change from squamous cell to columnar epithelial) Obesity Male
Risk factors for both:
Age >40
Achalasia
Summarise the epidemiology of oesophageal cancer
Incidence varies based on geography Squamous cell more common worldwide Adenocarcinoma more common in Western countries 8th most common malignancy Incidence increasing More common in men
What are the presenting symptoms of oesophageal cancer?
Asymptomatic until late stages - early presentation may be symptoms of reflux Progressive dysphagia starting with solids and moving to liquids Odynophagia Heart burn Vomiting Chest and back pain Weight loss Post-prandial cough Hiccups if affects diaphragm Hoarseness of voice
What are the signs on physical examination of oesophageal cancer?
There may be NO PHYSICAL SIGNS – may have signs of weight loss
Metastatic disease may cause: Supraclavicular lymphadenopathy (right) Hepatomegaly Hoarseness Signs of bronchopulmonary involvement (may be due to aspiration or tracheobronchial involvement)
What are the appropriate investigations of oesophageal cancer?
OGD (endoscopy) and biopsy - mucosal lesion with histology showing SCC or adenocarcinoma
Imaging: barium swallow & CXR - see location and complications eg ulcers, stenosis
PET scan - look for metastases and response to chemo
Staging: CT Chest & Abdomen
Bronchoscopy (if risk of tracheobronchial invasion)
Bone Scan
Lung Function Tests (normal/low)
ABG’s
Echo
Define multiple myeloma
A haematological malignancy characterised by excessive proliferation of plasma cells (mature B cells), resulting in excessive monoclonal immunoglobulin production - usually IgG or IgA
Summarise the aetiology of multiple myeloma
No clear aetiology
Genetic inheritance
Association with exposure to ionising radiation or petroleum products, agricultural work or occupational chemical exposure
Possible viral trigger
Summarise the epidemiology of multiple myeloma
Median age of diagnosis is 72y/o
Most common primary tumour in bone in over 50 year olds
Afro-Caribbean > White People > Asians People
What are the presenting symptoms of multiple myeloma?
CRAB Hypercalcaemia symptoms: Nausea Abdominal pain Confusion Depression Bone pain Polyuria Polydipsia Constipation
Renal Failure
Anaemia:
Fatigue
Bone pain - often LOWER BACK PAIN
Recurrent infection - neutropenia
Easy bruising and bleeding - thrombocytopenia
Hyperviscosity symptoms:
Headaches
Visual disturbances
What are the signs on physical examination of multiple myeloma?
Abdominal tenderness Pallor Bruising Hepatosplenomegaly Macroglossia Tachycardia Flow Murmur Signs of Heart Failure Purpura Dehydration Carpal Tunnel Syndrome Peripheral Neuropathies
What are the appropriate investigations for multiple myeloma?
Bloods: Hb - normocytic anaemia FBC - thrombocytopenia, neutropenia Elevated IgG, IgA Creatinine and BUN - elevated due to renal failure Serum calcium - elevated CRP - raised
Chest, Pelvic or Vertebral X-Ray: Osteolytic lesions without surrounding sclerosis, Pathological fractures
Blood film - erythrocytes in rouleux formation, pancytopenia, increased plasma cells, bluish background
Serum or urine electrophoresis - monoclonal proteins, M spike
Bone marrow aspirate - increased plasma cells, atypical cells - DIAGNOSTIC TEST
Bence-Jones proteinuria - monoclonal Ig light chain
Fundoscopy - retinal haemorrhage
Define Hodgkin Lymphoma
A haematological malignancy of lymphocytes, specifically mature B cells which is characterised by Hodgkin cells and Reed-Sternberg cells
Summarise the aetiology of Hodgkin lymphoma
Aetiology is unknown
Association with viruses - HIV, EBV
Genetic predisposition
EBV genome detected in 50% of Hodgkin lymphomas
Summarise the epidemiology of Hodgkin lymphoma
Uncommon
More common in men
Bimodal distribution - peaks at 15-34 years old and over 60
What are the presenting symptoms of Hodgkin lymphoma
Painless cervical lymphadenopathy - usually only one group of lymph nodes affected
Pruritis
B symptoms:
Fever >38 degrees
Weight loss
Night sweats
Pain in lymph nodes following alcohol
Node is enlarging
Mediastinal adenopathy:
Cough, Chest Pain, SOB
Abdominal pain
Tonsillar enlargement (may be indicative of tonsillar lymphoid tissue)
What are the signs on physical examination of Hodgkin lymphoma?
Fever
Non-tender firm rubbery lymphadenopathy (may be cervical, axillary or inguinal)
Splenomegaly
Skin excoriations
Signs of intrathoracic disease (e.g. pleural effusion, SVC obstruction)
What are the appropriate investigations for Hodgkin lymphoma?
FBC: Anaemia of Chronic Disease, increased neutrophils and eosinophils, lymphopenia in advanced disease
LFTs: (increased LDH, increased transaminase if the liver is involved)
High ESR and CRP
Lymph Node Biopsy
Bone Marrow Aspirate and Trephine Biopsy
Blood film - Hodgkin cell (large mononucleated cells) and Reed Sternberg cells (bilobed nuclei)
Imaging:
CXR - may show mediastinal adenopathy
CT (thorax, abdo & pelvis) - show enlarged lymph nodes - used for staging
Gallium Scan, PET - show bright at affected areas
Define non-Hodgkin’s lymphoma
Neoplasm of lymphoid cells originating in lymph nodes involving both T and B cells. There is no presence of reed-sternberg or Hodgkin cells.
They are most commonly B cell lymphomas - 85%
15% T cell and NK cell forms
Summarise the aetiology of non-Hogdkin lymphoma
Associated with viral infection eg EBV
Associated with autoimmune conditions eg rheumatoid arthritis, coeliac disaease
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)
What are the risk factors for non-Hodgkin lymphoma?
Age >50 years Male Immunocompromised Radiotherapy Immunosuppressive agents Chemotherapy Infection: HIV, HBV, HCV Connective tissue disease (e.g. SLE) Auto-Immune diseases (Sjogren’s)
Summarise the epidemiology of non-Hodgkin lymphoma
More common in men
More common in white patients
Incidence increases with age - more common >50 years old
More common in the Western world
What are the presenting symptoms of non-Hodgkin lymphoma?
Painless lymphadenopathy with enlarging mass in neck, axilla or groin
B symptoms:
Fever
Weight loss
Night sweats
Bowel extra-nodal involvement:
Bowel obstruction - constipation
Spinal cord extra-nodal involvement:
Weakness
Loss of sensation in legs
Bone marrow extra-nodal involvement:
Fatigue
Easy bruising
Recurrent infections
Other extra-nodal symptoms: Skin rashes Headache Sore throat Abdominal discomfort Testicular swelling Cough Shortness of breath
What are the signs on physical examination of non-Hodgkin lymphoma?
Painless firm rubbery lymphadenopathy
Skin rashes: Mycosis fungoides (cutaneous T-cell lymphoma)
Hepatosplenomegaly
Signs of bone marrow involvement:
Pallor (due to anaemia)
Infections
Purpura (due to thrombocytopenia)
What are the appropriate investigations for non-Hodgkin lymphoma?
Bloods: FBC: anaemia, neutropenia, thrombocytopenia, leukopenia High ESR and CRP Calcium may be raised HIV, HBV and HCV serology
Blood Film: 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
Define renal cell carcinoma
A primary renal tumour of the parenchyma/cortex, particularly the epithelial cells of the proximal convoluted tubule.
Summarise the aetiology of renal cell carcinoma
Renal clear cell carcinoma (80%): UNKNOWN CAUSE Papillary carcinoma (10%): UNKNOWN CAUSE
Risk Factors: Smoking (most established modifiable risk factor) Family history of renal cell cancer Polycystic Kidney Disease Chronic Dialysis Male Sex Hypertension Obesity Increasing age Pelvic radiation exposure
Associated with certain inherited conditions: von Hippel-Lindau disease - autosomal dominant mutation in VHL on chromosome 3 - headaches, dizziness, limb weakness, increased BP Tuberous sclerosis (rare genetic condition causing growth of benign tumours)
Inherited RCC:
Bilateral
Affects younger men and women
Sporadic:
Unilateral
Usually upper pole
Old men
Summarise the epidemiology of renal cell carcinoma
Most common type of malignant kidney cancer in adults
6th-8th most common malignancy in adults
More common in men
Peak incidence = 55-84 years old
What are the presenting symptoms of renal cell carcinoma?
Usually asymptomatic and presents late
Pain in flank or hip Haematuria Palpable abdominal/lower back mass if in lower zone Fever Weight loss
Symptoms of paraneoplastic syndrome:
Erythropoeitin - symptoms of polycythaemia eg headache, visual disturbance
PTHrp - symptoms of hypercalcaemia (stone, moans, bones, abdominal groans)
ACTH - symptoms of Cushing’s
What are the signs on physical examination of renal cell carcinoma?
Weight loss
Abdominal mass
Signs of Hepatic Dysfunction: ascites, hepatomegaly, spider Naevi
Left Sided Scrotal Varicocele: obstruction of left testicular vein as it joins renal vein by left RCC
Paraneoplastic syndrome signs:
Renin secretion - hypertension
What are the appropriate investigations of renal cell carcinoma?
Urinalysis: Haematuria and/or proteinuria, cytology
FBC - shows signs of paraneoplastic syndrome, elevated RBC
Calcium - elevated if paraneoplastic PTHrp secretion
LFTs
U&Es - increased creatinine with reduced clearance
ESR - increased in 75% of patients
Abdominal Ultrasound: can distinguish between SOLID MASSES and CYSTIC STRUCTURES
CT/MRI: useful for staging – use the Robson Staging System
Define testicular cancer
A malignant tumour of the testes, most common in young adult men.
Seminomas: MOST COMMON - 50%
Non-seminomatous germ-cell tumours and teratomas: 30%
RARE: Gonadal Stromal Tumours (Sertoli and Leydig cell tumours), Non-Hodgkin’s lymphoma
Summarise the aetiology of testicular cancer and risk factors
Aetiology is UKNOWN
Thought to be due to a precancerous lesion that will lead to malignant growth
Environment factors eg trauma, atrophy, hormones
Genetic predisposition
Risk factors: FHx Previous testicular cancer Kleinfelter's syndrome Cryptorchidism - failure of descent of testes Ectopic Testes Atrophic Testes HIV White Ethnicity Inguinal Hernia
Summarise the epidemiology of testicular cancer
Highest incidence in 25-35 year olds
Highest incidence in white men
Most common solid tumour in men aged 20-35
RARE - only accounts for 1% of cancers
What are the presenting symptoms of testicular cancer?
Painless, hard lump in testicle
May have sharp or dull pain in testicle or abdomen
Swelling or discomfort of the testes
Lung metastases:
Dyspnoea
Haemoptysis
Skeletal metastases:
Bone Pain
Lumbar Back Pain (involvement of Psoas Muscles and Nerve roots)
What are the signs on physical examination of testicular cancer?
Hard, painless, firm lump in testicle
Lump non trans-illuminable
Gynaecomastia - due to hCG release
Lymphadenopathy (e.g. supraclavicular, para-aortic)
Lower extremity swelling (venous occlusion)
Signs of hyperthyroidism
What are the appropriate investigations for testicular cancer?
Tumour markers - elevated hCG, AFP, LDH
USS colour doppler of testes - see solid mass
CT/MRI chest and abdomen - stage and see metastases, retroperitoneal lymph node enlargement
CXR - mediastinal and lung metastases
Staging System: Royal Marsden Hospital Staging
Urine Pregnancy Test - will be positive if the tumour produces β-hCG
Define bladder cancer
Common form of cancer developing from the lining of the bladder
Most often these are transitional cell carcinomas however rarely they can be squamous cell carcinoma or adenocarcinoma associated with chronic bladder inflammation due to Schistosoma infection
Summarise the aetiology of bladder cancer
Squamous cell carcinoma:
Chronic irritation eg recurrent UTI, kidney stones
Schistosoma infection
Adenocarcinoma:
Schistosoma
90% are transitional cell carcinomas: SMOKING Alcohol Phenacitin Analine dye Cyclophosphamide Increasing age Extended dwell time p53 mutation Pelvic irradiation Chronic Bladder Inflammation i.e. UTIs Kidney and bladder stones Schistosomiasis Family history Male Age >55 Type 2 diabetes
p53 dependent tumours are flat and invasive
Non-p53 tumours are papillary
Summarise the epidemiology of bladder cancer
9th in worldwide cancer incidence
Egypt, Western Europe and North America have highest incidence
Asia has lowest incidence
Incidence increases with age - 70% are >65
2% of cancers (2nd commonest cancer of the genitourinary tract)
2-3 times more common in males
Peak incidence: 50-70 years
What are the presenting symptoms of bladder cancer?
Painless haematuria!!! - usually gross haematuria
Mucusuria in adenocarcinoma
Bladder irritation/storage problems - Frequency, Urgency, Nocturia
Recurrent UTIs
Rarely: ureteral obstruction
Advanced:
Pelvis or bone pain
What are the signs on physical examination of bladder cancer?
Often no signs
What are the appropriate investigations for bladder cancer?
Cystoscopy and biopsy - allows visualisation of tumour and histology to diagnose type
Urinalysis - haematuria with no casts or crystals
Ultrasound (renal & bladder): visualisation of tumours and/or upper tract obstruction CT (preferred) or Intravenous urogram CT/MRI for staging Bone scan FBC - may show mild anaemia
Define pancreatic cancer
Malignancy arising from the exocrine or endocrine tissue of the pancreas, often characterised by painless obstructive jaundice and weight loss.
Summarise the aetiology and risk factors of pancreatic cancer
Aetiology unknown
5-10% are hereditary
Risk factors: Smoking Obesity Increased age Male Family history - BRCA2 gene Increased red meat diet
Associated with: Diabetes Chronic pancreatitis Liver cirrhosis Alcohol
Summarise the epidemiology of pancreatic cancer
Most common aged 65-75 years old
Most common in men
What are the presenting symptoms of pancreatic cancer?
Initial symptoms non-specific
Fatigue
Nausea and vomiting
Weight loss - anorexia or due to malabsorption
Greasy smelly stool (obstruction of CBD)
Mid epigastric pain radiating to back and worse on lying down
Swelling, erythema and tenderness at extremities
Feel small lumps under skin
Pruritis
Abdominal, non-tender mass
Dark urine
Symptoms of DM: thirst, polyuria, nocturia
What are the signs on physical examination of pancreatic cancer?
Painless jaundice
Courvoisier’s sign - enlarged, palpable, non-tender gallbladder with painless jaundice (unlikely due to gallstones)
Trousseau sign - blood clots felt under the skin as small lumps
Epigastric tenderness and/or mass
Hepatomegaly (if hepatic involvement)
What are the appropriate investigations for pancreatic cancer?
CEA - elevated
CA19-9 - elevated
Obstructive jaundice - raised bilirubin, ALP, transaminases
Serum amylase and lipase - elevated
Deranged clotting - prolonged PT
FBC - anaemia if GI bleeding, thrombocytopenia if DIC
Abdo USS - pancreatic mass, dilated bile ducts, liver mets
CT with/without guided biopsy
Staging Laparoscopy OR Intraoperative Ultrasound
Define thyroid cancer
A malignancy arising in the thyroid gland. There are four main types:
Differentiated - papillary (most common type of thyroid cancer) and follicular (2nd most common type of thyroid cancer)
Medullary - associated with MEN 2A and 2B
Anaplastic
Summarise the aetiology and risk factors of thyroid cancer
Genetic mutations
Papillary - BRAF mutation
Medullary - RET mutation leading to oncogene
Risk factors:
Age >65
Previous radiation therapy to the head or neck
Age <20
Family history
Medullary thyroid cancers may be familial and are associated with MEN 2A or 2B
Lymphoma is associated with Hashimoto’s thyroiditis
Summarise the epidemiology of thyroid cancer
Most common type of endocrinological malignancy
More common in women
Often diagnosed between 45 and 54 years old
Papillary: 20-40 years
Follicular: 40-50 years
Anaplastic: more common in the ELDERLY
What are the presenting symptoms of thyroid cancer?
Often asymptomatic and found incidentally
Firm, non-tender, immobile thyroid nodule
Hoarse voice
Dysphagia
Lump in neck slow-growing
What are the signs on physical examination of thyroid cancer?
Tracheal deviation
Unilateral, solitary, firm thyroid nodule which is immobile and non-tender
Cervical lymphadenopathy
Patient usually EUTHYROID as often non-functional therefore no hyperthyroid signs
What are the appropriate investigations of thyroid cancer?
Thyroid USS - visualise nodules and evaluate size, consistency, borders etc
Tumour markers:
Thyroglobulin tumour marker in papillary and follicular cancers
Serum calcitonin - increased in medullary thyroid cancer
Radioiodine uptake scan - cold nodule (white circle) suggests a malignant nodule
TSH, T3/T4 - normal as usually non-functional so EUTHYROID
FNA of thyroid nodule - histological diagnosis
Excision Lymph Node Biopsy: If there is cervical lymphadenopathy
Define acute leukaemia
ALL:
Malignant clonal disease of the bone marrow and blood caused by uncontrolled division of lymphoid precursor cells, often in children.
AML:
Malignant clonal disease of the bone marrow and blood caused by uncontrolled division of myeloid precursor cells, often in older adults.
Summarise the aetiology of acute leukaemia
ALL:
Lymphoblasts undergo malignancy transformation and proliferation, replacing normal marrow elements, leading to bone marrow failure and infiltration into other tissues.
Risk Factors: Radiation, Smoking, Viral Infection, Genetic (Down’s syndrome, Neurofibromatosis type 1, Fanconi’s anaemia, Xeroderma Pigmentosum), Age < 6 or mid-late 30s/mid 80s, Family history, History of malignancy
AML:
Risk Factors:
Age > 65
Family history
Radiation Exposure
Benzene Exposure
History of chemotherapy
Constitutional Karyotype Abnormalities (i.e. Down’s Syndrome, Klinefelter’s)
Genetic Conditions (i.e. Fanconi’s anaemia)
Hx Haematological disorders - aplastic anaemia, myelodysplastic sydnrome
Summarise the epidemiology of acute leukaemia
ALL:
Most common malignancy in children
75% of cases children under 6
AML:
More common in elderly - median age 65 years old
More common in men
Incidence increases with age
What are the presenting symptoms of acute leukaemia?
Symptoms of anaemia: Fatigue Pallor Weakness Dyspnoea Palpitations Dizziness
Symptoms of thrombocytopenia:
Easy bruising/bleeding, epistaxis, menorrhagia
Symptoms of leukopenia:
Recurrent infections
FLAWS
ALL - symptoms of organ infiltration:
Testicular enlargement
Painless lympahdenopathy
Bone pain
AML:
Gum enlargement due to monocytic infiltration
CNS involvement (headaches, nausea, diplopia)
Lymphadenopathy
What are the signs on physical examination of acute leukaemia?
Signs of anemia - pallor, tachypnoea
Signs of thrombocytopenia - bruises, purpura, ecchymoses
ALL - organ infiltration: Lymphadenopathy Hepatosplenomegaly Painless unilateral testicular enlargement Renal enlargement Mediastinal/abdominal mass - T cell ALL
AML:
Skin rashes i.e. Pyoderma Gangrenosum (characterised by presence of ulcers on leg)
Gum hypertrophy (gingival enlargement)
Deposit of leukemic blasts in the eye, tongue and bone (RARE)
Lymphadenopathy
What are the appropriate investigations for acute leukaemia?
FBC - thrombocytopenia, leukopenia, normocytic anaemia
Peripheral blood smear - increased blast cells, ALL = increased lymphoblasts, AML = increased myeloblasts, Auer rods
Bone marrow biopsy - >20% blasts
Lactate Dehydrogenase - increased
U&E’s - increased Ca2+, K+, Uric Acid, Lactic Acid
Immunophenotyping: using antibodies to recognise cell surface antigens
Cytogenetic: karyotyping to look for chromosomal abnormalities or translocations
CXR: may show mediastinal lymphadenopathy, pleural effusion, lytic bone lesions
Bone Radiographs: mottled appearance with punched out lesions due to leukaemic infiltration
AML:
Clotting studies, fibrinogen and D-dimers - if abnormal suspect DIC due to promyelocytic leukaemia
Define chronic leukaemia
CLL:
Progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin. Cells are normally differentiated but excess proliferation
CML:
Malignant clonal disorder of the haematopoietic stem cell that results in marked myeloid hyperplasia of the bone marrow
Summarise the aetiology of chronic leukaemia
CLL:
Aetiology is UNKNOWN - may be a result of multiple genetic events affecting oncogenes and Tumour Suppressor Genes - leads to increased cell survival and resistance to apoptosis
Risk Factors:
Age > 60 (median age at diagnosis is 70), Male, white ethnicity, Family history
CML:
Most often have translocation between chromosome 9 and 22 - Philadelphia chromosome forming BCR-ABL fusion protein which enhances tyrosine kinase activity
Summarise the epidemiology of chronic leukaemia
CLL:
Most COMMON leukaemia in western world
90% are > 50 years old
More common in men
CML:
Incidence peaks between 65 and 74 years old
Increases with age
More common in men
What are the presenting symptoms of chronic leukaemia?
May be asymptomatic
Symptoms of anaemia - fatigue, dizziness, dyspnoea, palpitations
Symptoms of thrombocytopenia - easy bruising and bleeding, epistaxis, menorrhagia
FLAWS
CLL:
Enlarged lymph nodes
What are the signs on physical examination of chronic leukaemia?
Pallor, dyspnoea
Bruises, ecchymosis, purpura
HepatoSplenomegaly
Lymphadenopathy
CLL:
Cardiac flow murmur
What are the appropriate investigations of chronic leukaemia?
FBC - thrombocytopenia, anaemia, lymphocytosis
Peripheral blood smear - increased mature leukocyte cells, CLL - smudge cells
Bone marrow biopsy - lymphocytic replacement of normal marrow
CML:
FBC - Elevated basophils/neutrophils/eosinophils
Elevated uric acid
Decreased neutrophil alkaline phosphatase
Elevated B12 and transcobalamin I (B12 binding protein)
Cytogenetics - find Philadelphia chromosome
Define tumour lysis syndrome
Metabolic or electrolyte derangement due to excessive lysis of cells often in patients with haematological malignancies, following start of chemotherapy treatment or suddenly
Summarise the aetiology of tumour lysis syndrome
Sudden lysis of cells causes the release of their toxic contents resulting in: Hyperkalaemia Hyperphosphataemia Hyperuricaemia Hypocalcaemia
This is common following the initiation of cytotoxic medications in patients with high proliferating rate: non-Hodgkin lymphoma and ALL
Summarise the epidemiology of tumour lysis syndrome
More prevalent in malignancies with high proliferative rates
More likely in increasing age
What are the presenting symptoms and signs on physical examination of tumour lysis syndrome?
Hyperkalaemia:
Arrhythmias - chest pain, syncope, dyspnoea
Severe muscle weakness and paralysis
Paraesthesia
Hyperphosphatemia:
Acute kidney failure due to deposition of calcium phosphate crystals in the kidney
Peripheral oedema
Oliguria/anuria/haematuria
Hypocalcaemia:
Tetany
Parkinsonism
Myopathy
Sudden mental incapacity
Trousseau - inflating BP cuff on upper arm causes carpopedal spasm
Chvostek sign - tapping facial nerve anterior to ear causes facial twitch
Hyperuricaemia: Leads to gout
Splenomegaly, Lymphadenopathy, Lethargy, Diarrhoea, Nausea & Vomiting, Anorexia
What are the appropriate investigations of tumour lysis syndrome?
Check levels of all the deranged metabolites: Potassium, Phosphate, Calcium, Uric Acid
Bloods: FBC, Serum Urea, Creatinine, Lactate Dehydrogenase
ECG: arrhythmia due to hyperkalaemia
