Cancer Flashcards
Effective screening programme
Affordable for the healthcare system
Acceptable to all social groups
Reduce mortality from cancer
Good discriminatory index between benign and malignant lesions
How do pt with cancer present
Screening programmes
Recent change in symptoms ie wt loss, lump, change in bowel habit
Age > 75y/o common to A/E
Local spread of cancer
Nearby tissue often causes compressive/obstructive problems
Distant spread of cancer
Metastasis from initial to 2ndary site commonly lymph nodes, brain, liver, bones and lung
Lymphatic, haematogenous and transcolemic
Lymphatic spread
Comment route of metastasis can lead to haematogenous spread as the thoracic duct drains into the IVC. Lymphadenopathy can = pain due to obstruction/swelling
- ENT = facial/neck lymphadenopathy
- Gastric, oesophageal and breast to axillary and L supraclavicular
- Testicular and ovarian to paraaortic
- Vulval, scrotal and vaginal to femoral/inguinal
Transcolemic spread
Spreads throughout the peritoneum in the circulating peritoneal fluid. Passes up the L paracolic gutter, across surface of the liver and diaphragm and down the omentum
Haematogenous spread
Via the blood spreads rapidly usually venous flow as narrower walls are easier to penetrate
Government targets for cancer
2wk wait - Any GP can refer suspicious red flag symptoms for investigation
31 day limit - 1st treatment must start within 31 days of agreement with pt
62 day limit - Treatment must begin within 62 days of referral
Common PC of cancer
Ascites - ovarian, gastric, pancreatic, HCC
Change in bowel - CRC, prostate, ovary
Dysphagia - Oesophageal, gastric, lung
#’s = 1 sarcoma, mets from renal,thyroid, lung, prostate and breast
Jaundice - HCC, cholangiocarcinoma,
Cancer of unknown primary
Tumor is able to metastasis before the primary site can be identified. Tends to be aggressive, disseminate early and be unpredictable. 5-10% of all cancers
Cause of CUP
i) Squamous cancer usually arising from head and neck/lung. Usually respond well
ii) Poorly differentiated or anaplastic - high grade lymphomas or germ cell tumours respond well treatment
iii) Adenocarcinomas poor prognosis usually pancreas or lung
CUP Mx
Speak to oncologist. Search for a site! You must rule out potentially curable tumors = germ cell!!
CXR, CT chest abdo pelvis, rectal USS = prostate, mammogram = breast
Use tumor markers, full examination PV and testicular
Poor prognosis of CUP
Adenocarcinoma on histology Hepatic/renal involvement Poor performance status >10% wt loss Supraclavicular lymph node involvement High tumor marker levels
Cytological grading
C1 = inadequate for testing C2 = normal morphology C3 = cells abnormal but likely to benign C4 = highly suspicious of cancer C5 = Cancer cells present
Empyema
pH <7.2, low glucose, high WCC + present on culture/microscopy
Transudate vs Exudate
Transudate = protein <3g/l = cirrhosis, HF, renal failure and meigs syndrome
Exudate = protein >3g/L due to infection, inflammation (RA,SLE), PE or cancer.
Pleural albumin : serum albumin >0.5
Pleural LDH : Serum LDH >0.6
Hypercalcemia
Common complication of malignancy seen in 40% of pt
PC - non specific, renal failure, bone pain, confusion, conspitation
Due to either direct invasion of bones - mets, myeloma or squamous cell producing PTHrp
Confusion in cancer pt
Brain mets, hypercalcemia, constipation - bowel obstruction, infection, opiod OD, metabolic disturbance
Mx CUP
Curative treatment = survival
Palliative = QoL, secondary objective - duration of life
Factors influencing decision = pt choice, age, performance status, organ impairment
Smoking
Linked to 90% of lung cancer. Also increases the incidence of oesophageal, laryngeal, bladder, cervical and breast cancer
Asbestos
Causes malignant mesothelioma, potentiates risk of lung cancer if smoker
Amines in dye/rubber
Bladder cancer
Benzene
Myeloid leukaemia
Ionising radiation
BM, breast and thyroid all very sensitive
BCC vs SCC
BCC = shiny, pearly nodule with rolled edge +/- umbilicate centre and telangiectasia
SCC = hyperkeratotic, crusting ulcerated lesion
Both present @ sites of sun exposure - ears, nose corner of mouth. Only definitive diagnosis is to excise
Xeroderma pigmentosum
Rare autosomal recessive condition at NER DNA mismatch repair gene, unable to repair DNA damaged by UV light
PC: severe sunburn with minimum sunlight often from 6month to 3yrs. Photosensitivity and dry skin. Premature skin ageing, increased risk of BCC,SCC and melanoma.
Viral carcinogens
EBV - Burkitt’s and Hodgkins lymphoma craniopharyingoma,
HBV/HCV - HCC
HPV - cervical and oral cancer
HHV-8 = Kaposi and Castlemans
Parasitic carcinogens
H.pylori - gastric cancer and gastric lymphoma
Bilihartzia - Bladder cancer
Liver flukes - cholangiocarcinoma
Schitsomasis - Bladder cancer
Germline vs Somatic
Germaine present at embryogenesis so all cells in the body possess the mutation. Can be passed on to offspring
Somatic mutations acquired during life. Only affects cells they arose from and their subsequent descendants. Cannot be passed to offspring
Process of carcinogenesis
Proliferation in the absence of growth factors, failure to respond to inhibition to proliferation. Evade apoptosis replicative immunity. Angiogenesis and metastasis.
AD cancer syndromes
50% chance of passing to offspring. Lynch syndrome, BRCA I and II, Peutz Jeghers, von hippel lindau, Rb, NF1, MEN1 and 2, Li fraumeni
Peutz Jeghers
Development of multiple haemartous polyps in the GI tract. These are benign and have a low index of malignancy but increase the risk of intussception and CRC
They also have hyperpigmented macules on lips, oral mucosa and palms/soles
Increased risk of liver, lung, ovarian, breast and testicular cancer
MEN 1
AD mutation in the MEN1 gene which gives risk to pancreatic tumours, parathyroid hyperplasia and pituitary adenoma
MEN 2A and 2B
Gain in function mutation in RET gene
2A = medullary thyroid cancer, parathyroid hyperplasia and phaechromocytoma
2B = medullary thyroid cancer, phaechromocytoma, Marfanoid body habitus and multiple mucosal neuromas @ tongue eyelids
Li Fraumeni
Gene mutation in p53 guardian of the genome leads to leukaemia + lymphoma, premenopausal breast cancer, childhood sarcoma and brain tumour. Penetrance 50% by 50y/o
Ataxia telengestasia
AR mutation in AT gene leading loss of DNA repair. High risk of leukaemia, lymphoma and brain malignancy
PC - ataxia in childhood, slurred speech, telangiectasia over sclera of the eyes, FTT and recurrent URTI
Von hippel lindau
Phaechromocytoma, RCC and hemangioblastomas. Common to have problems with eye sight
NF1
PC 6+ cafe au last spots, freckling in axilla, multiple dermal neurofibrotomas, Lisch nodules in the iris - optic gliomas. Reduced IQ, scoliosis and risk of leukaemia and plexiform neurofibromas
NF2
Rare hearing loss, few cutaneous signs, VIII problems
100% have CNS lesions - bilateral vestibular schwannomas, meningiomas
Sensitivity
Ability to pick up all the people that have the disease, i.e. high power to rule out the condition
- True positive = TP - FN
Specificity
Ability to rule out the disease in all those without disease. Ie is specific to only those with the disease so high power to rule in
- True negative = TN + FP
Breast cancer screening
All women 50-70 y/o invited for 3yrly mammogram. Suspicious feature such as soft tissue density or micro calcification = recall
Breast cancer screening for susceptible
Women with BRCA1/2 yearly MRI from 30y/o
FHx - mammograms from 40y/o
Li-fraumeni - yearly MRI from 20y/o
CRC screening
FOB testing 2 yearly from 60-74y/o. Trial of one off flexisigmoidoscopy @ 55y/o
CRC screening for susceptible
IBD = 10 yearly flexisigmoidoscopy Lynch = 2 yearly colonoscopy from 25y/o or 5 years before age of onset in youngest family member FAP = yearly colonoscopy
Cervical cancer
24-49 = 3yrly, 50-64 = 5yrly. Detection of CIN. Doesn’t detect adenocarcinoma which is responsible for 15% of cervical cancer.
Cancer prevention
Vaccination - HBV, HCV and HPV
Dietary measures - increased fibre, low red meat, stop smoking, reduced alcohol public health campaigns
Screening programmes
NSAID’s - protective against cancer approx 7% reduced rate, but no survival benefit due to GI bleed
Tamoxifen - preventing of breast cancer but increases risk of endometrial.
Lung Cancer epidemiology
Peak incidence 60-70y/o, smoking and asbestos exposure increase risk, 3x incidence in males, 5x increased risk if +ve FHx
PC lung cancer
Can be asymptomatic and look like a gradual worsening of COPD - crucial to look as these ppl are most @ risk
PC - progressive SOB, chest pain, change in cough - 3wks long = CXR, anorexia, fatigue, wt loss, fever +/- haemoptysis
May have symptoms of extrinsic compression dysphasia, SVC obstruction, hoarseness of voice due to recurrent laryngeal nerve involvement or symptoms of metastasis
O/E lung cancer
Hands - clubbing, tar staining,
Cachexia, wt loss, SOB @ rest
Axillar or supraclavicular lymphadenopathy
Pleural effusion or lung collapse
Lung cancer spread
Spread often along bronchus of origin. Involves lymphatics 1st to ipsilateral peribronchial and hilar nodes then to mediastinal, contralateral hilar and supraclavicular.
Disseminates into blood stream where it often metastases to the brain, bone and liver
Pancoasts syndrome
Caused by a lung cancer @ apex of the lung. It can grow into the chest wall causing compression of structures
Dependent on the extent of growth can =
Horners syndrome a triad of miosis, ptosis and enopthalmus +/- anhydrosis depend of site. This is due to compression of the sympathetic chain
Severe shoulder pain and atrophy of hand muscles if T1 nerve root is compressed
Can also give phrenic palsys, SVC obstruction and recurrent laryngeal damage
Horners syndrome
With or without anhydrosis depends on the site of the lesion
i) Central causes - anhydrosis of the face, arm and trunk = MS, brain tumors, syringomyalyia
ii) Preganglionic - anydrosis of face only = Pancoast, thyroid carcinoma, goitre
iii) Post ganglionic = no anhydrosis = carotid artery dissection, cavernous sinus thrombosis, migraine
PC of pleural effusion
Tachypnoea, pleuritic chest pain, SOB
O/E - dull to percussion, reduced expansion and breathe sounds, vocal resonance reduced
Inv = exudative effusion if cancer, CXR = meniscus fluid level present, Lights analysis
Types of lung cancer
i) Small cell
ii) Non small cell lung cancer (NSCLS)
Adenocarcinoma, Large cell and squamous
Small cell lung cancer
20% of lung cancers. Carry the worst prognosis aggressive, low doubling time and metastasize early.
Arise from neuroendocrine cells therefore give rise to paraneoplastic syndromes such as SIADH, ectopic ACTH and LEMS
Located centrally often with bulky hilar and mediastinal lymphadenopathy
Adenocarcinoma
40% now the most common lung cancer in UK, lowest smoking link, increased in asbestos exposure.
Originates from mucus secreting glandular cells, originates peripherally in the lung so commonly involves the pleura = pleural effusions
Metastasises to pleura, lymph nodes, brain, bone and adrenals
Squamous cell
Central obstructive lesion of the bronchus can cavitate. Grow slowly, spread locally and disseminate late.
Can give paraneoplastic effects of clubbing, PTHrp and HOA
Large cell
Often peripheral mass poorly differentiated. Grow rapidly and metastasise early. Derived from mucus cell most linked to asbestos
Malignant mesothelioma
Caused by light asbestos exposure. CXR shows tumour arising from serosal cells of the pleura. No cure
Inv Lung caner
Stage the extent of the disease - CT thorax, abdo and pelvis
Biopsy is crucial for a tissue diagnosis = define treatment via bronchoscopy
Assess performance status for surgery = pulmonary function tests, echo, vital signs, renal function
Pleural fluid analysis
CXR 1st line, FBC ?anaemia, U+Es, LDH, serum calcium
Poor prognostic factors
Low performance status, any site metastasis, high LDH
SVC obstruction PC
PC = facial swelling and fullness worsened on lying down or bending forward, SOB, arm swelling chest pain.
O/E = facial oedema, venous distention of neck veins, cyanosis, plethora of face + oedema of arms
Causes of SVC obstruction
90% due to bronchogenic carcinoma
Lymphoma of 2ndary lymphadenopathy = compression of SVC
Thrombosis - CVC increased risk
Pathophysiology of SVC obstruction
Blockage of the SVC which is responsible for drainage of blood from the brain leads to collateral circulation developing from the internal mammary, lateral thoracic and the oesophageal veins. It can lead to cerebral oedema or lifethreatening laryngeal oedema.
Inv and Mx of SVC obstruction
CXR/CT may show superior mediastinal enlargement, R hilar mass
Mx = steroids to reduce swelling, stenting of SVC if severe. treat cause!
Brain mets PC
PC new onset headache, confusion, seizures +/- neurological defects parathesia, hemiparesis
Causes of brain mets
Lung, breast, CUP, prostate and myeloma
Mx of Brain mets
Supportive - corticosteroid to reduce cerebral oedema - improves survival in 50% - relieve headache and cognitive dysfunction. Anticonvulsants to reduce seizure risk.
Surgery is only favourable if one discrete lesion which is accessible, Chemo doesn’t work due to inability to cross BBB. Radiotherapy may increase survival.
Hypercalcemia due to PTHrp
PTHrp 100x more potent than PTH acts at the PTH receptor to stimulate increased bone reabsorption and distal tubular Ca2+ reabsorption. Doesnt increase intestinal Ca2+ reabsorption
Produced by NSCLC, RCC, ENT cancer and SCC of oesophagus
PC hypercalcemia
Confusion, dehydration, constipation, polyuria, polydyspia, muscle weakness and cardiac arrthymias.
High Ca2+ leads to reduced membrane permeability to Na+ ion movement. This leads to hypotonicity of smooth and striated muscle.
Inv and Mx hypercalemia
Serum calcium, undetectable or low PTH, high urinary Ca2+. Mx = IV bisphosphanates stat, fluid resus
Ectopic ACTH PC
PC Cushing syndrome truncal obesity, hypertension, fatigue, weakness, hirsutism, high Na+, low K+
Causes of ectopic ACTH
SCLC, pancreatic islet cell tumours, medullary thyroid ca, phaechromocytoma, carcinoid tumours
Inv and Mx ectopic ACTH
24hr urinary cortisol, high ACTH, no response to high dose dexamethasone suppression test. CT for site. Chemotherapy to treat.
SIADH PC
PC confusion, lethargy, HTN, tremor, hyponatremia, cerebral oedema. Increased ADH leads to water retention and low Na+. This causes a low serum osmolality due to dilution of the extracellular space and a high urine osmolality as high levels of Na+ are excreted
Causes of SIADH
SCLC, prostate, pancreatic
Inv and Mx SIADH
hyponatremia < 130, high urine Na+,
urine osmolality > serum osmolality
non surpressed ADH
Mx = fluid restrict, demoxycycline
Lambert eaton myaesthenic syndrome
AI reaction with autoantibodies forming against presynaptic voltage gates Ca2+ channels. This leads to reduced influx of Ca2+ to the nerve ending reducing act release. 60% due to underlying malignancy = SCLC/breast
PC = proximal weakness of arms and legs. No affect on bulbar muscles. Constipation, blurred vision, dry mouth
O/E = increased strength with use. Lambert sign is increased power on grip
Gonadotrophins
Secreted by pituitary tumors, germ cell and gestationaltrophoblastic tumors. Can = gynecomastia in males
High BhcG (can cross react causing hyperthyroidism)
Medullary thyroid cancer
Calcitonin secreting tumors can lead to hypocalcemia. Calcitonin is a polypeptide produced by C-cells of the thyroid prevents Ca2+ release from the bone and increases renal excretion
PC = tetany, diarrhoea, twitches and spasms
Hypertrophic pulmonary osteodystrophy
Combination of clubbing and thickening of periostum and long bones. This classicaly presents with joint stiffness, pain @ wrists and ankles. Linked to squamous cell cancer
Encephalomyopathies
Perivascular inflammation and selective neuronal degeneration can affect the limbic system, brainstem and spinal cord. Autoantibodies present on the tumor surface cross react with other tissues
PC - slow progressive onset, loss of STM, personality, hallucinations and fits
Inv - high IgG in CSF, autoantibody in serum
Neutropenic sepsis definition
Pyrexia one off reading >38.3 or >38 for 1hr
Symptoms of rigors, unexplained hypotension or tachycardia
Neutrophil count <1.0x106
PC neutropenic sepsis
Have low suspicion, this is deadly in cancer its
PC = vomiting, drowsiness, fatigue, diarrhoea, fever may not always be present
O/E - hypotension, oliguria, tachycardia
Mx neutropenic sepsis
Sepsis six. Broad spectrum Abx IV within 1hr !
Keep platelets >20x109
Radiation pneumonitis
Acute manifestation of radiation induced lung disease
PC = 4-12 wks post radiation exposure
cough oedema and pleuritic pain
CXR = ground glass opacities
Pathology of radiation pneumonitis
Degenerative - loss of type 1 pneumocytes, deposition of fibrin in aveoli leading to increased permeability can interstitial and pulmonary oedema
Regenerative - proliferation of connective tissue in parenchyma
Breast cancer epidemiology
100x more likely in females, lifetime risk of 1/9
10% = familial breast cancer, 3% due to BRCA and p53
Risk factors for breast cancer
Non modifable - age, female gender, FHx, BRCA/p53 mutations, early menarche late menopause,
Modifiable - nulliparity, late 1st child, HRT, smoking, obesity, breast tissue irradiation
Familial breast cancer
Relative risk with one 1st degree family relative = 1.7x, if premenopausal onset = 3x, bilateral disease = 5x
BRCA 2
lower risk of breast cancer (40-70%) and ovarian (15%)
Increased risk of prostate cancer and pancreatic (7%)
Male breast cancer
BRCA 2
lower risk of breast cancer (40-70%) and ovarian (15%)
Increased risk of prostate cancer and pancreatic (7%)
Male breast cancer
PC breast cancer
80% of women detect a lump
Breast enlargement, pain, nipple retraction and discharge are rare. Wt loss, fatigue and malaise.
O/E supraclavicular or axillary lymphadenopathy, discolouration of skin, puckering, peau d’orange, skin thickening or ulceration
Comparison of breasts is crucial
Paget’s disease of the breast
Linked to intraducal carcinoma involving the terminal ducts of the breast.
PC eczematous erythematous keratotic patch over areolar area +/- discharge or mass
Breast cancer metastasis
Bone, lung, liver and brain
Triple assessment
2wk wait involves radiologist, surgeon and oncologist. Clinical exam, imaging -mammogram/MRI, biopsy - FNA/core
Breast cancer tumour marker
CA15.3
Mammogram findings suggestive of maligancy
asymmetrical mass, microcalification, distorted architecture
Cystic mass
USS to determine if cystic. FNA to drain cyst. Biopsy if need if bloody aspirate, incomplete resolution or recurrence
Solid mass
Mammogram and core biopsy. +ve gives architectural and cellular characteristics
Non palpable mass
Breast MRI + wire guided or excision biopsy
Receptors in breast cancer
All breast cancers are tested for oestrogen, progesterone and herceptin receptors. Triple -ve = poorer prognosis
ER - tamoxifen oestrogen antagonist or aromatase inhibitors
HER2 - monoclonal Ab - trastuzumab
Bone metastasis
5 main causes = breast, lung, renal, thyroid, prostate and myeloma. Average survival is 2 yrs from 1st lesion discovered
PC bone metastasis and Mx
Severe boring bone pain, pathological #, hypercalcemia, MSCC, reduced mobility and QoL
Mx = bisphosphanates - zolendronate, pain relief
MSCC
Needs rapid diagnosis to prevent permeant paralysis
PC = bilateral UMN, paralysis of limbs and reduced sensation below level of lesion. +/- incontience
Inv = MRI stat Mx = IV steroids stat - may need surgery or chemo. Call oncologist
Mx breast cancer
Staging by TMN. Anyone with tumor >5cm, >3 lymph nodes effected or clinical suspicion should have a CXR and a bone scan to hunt for mets
Senital node biopsy and radioactive labelled isotope to stage lymphocytic spread
Surgery breast cancer
Partial mastectomy = tumor and surrounding tissue removed with some lymph nodes removed to check for spread
Modified radial mastectomy = Whole breast and underarm lymph nodes removed. Chest wall left intact
Adjuvant to surgery
Radiotherapy - mandatory for those with lumpectomy, wide local excision, >5cm tumor or 4+ lymph nodes. Reduces risk of local recurrence
Endocrine therapy - only in those ER,PR or HER2 +ve
- Tamoxifen or Aromatase inhibitor (Only in post-menopausal otherwise causes ovarian failure)
Trastuzumab for HER2. HER2 causes cellular growth and division in the absence of growth factors
Tamoxifen
Reduced risk = DCIS and invasive cancer
Increased risk of DVT, PE, endometrial cancer
Ovarian Cancer epidemiology
White female, developed country, increased risk in BRCA1/2, Lynch syndrome and ashkanazi jews
PC ovarian cancer
Asymptomatic, abdo bloating and pain, change in bowel habit, frequency and urge urination due to mass effect compressing bladder/colon
In advanced disease = ascites, ovarian torsion, PV/PR bleeding, hydronephrosis 2ndary to uteric obstruction, pleural effusion
Sister mary nodules
Ovarian cancer metastasis to umbilicus
Risk factors for ovarian cancer
Non modifable = BRCA1/2, age, early menarche + late menopause, Lynch syndrome
Modifiable = nulliparity, IVF, obesity, PCOS
Protective for ovarian cancer
COCP, multiparity, breast feeding
Risk of malignancy index
CA125 x menopausal status x USS score
premenopausal = -1, postmenopausal = 3
USS score = 1+ for ascites, bilateral, mulitlocular, metastasis
> 200 = stat referral to specialist centre
CA125
Ovarian cancer. Raised in SLE,IBD, endometriosis, pregnancy, fibroids and menstruation
Serial rise >25% accurate method in predicting progression. 2x increase from upper limit 100% specificity for relapse of disease
AFP
HCC and germ cell
CA19.9
Cholangiocarcioma and pancreatic cancer. Chronic inflammatory conditions such as PSC, PBC, and gallstones will raise.
Calcitonin
Medullary thyroid cancer
PSA
Prostate cancer
CEA
CRC, lung, ovarian, breast
Inv of ovarian cancer
Explorative laparotomy is crucial aim to reduce tumour size, obtain histological sample and stage the disease
- FNA not done due to risk of seeding tumour through abdominal wall
Pathology of ovarian cancer
90% epithelial in origin
- Serous begin in fallopian tubes, fluid filled cysts
- Mucinous large multiloculated mucus filled cyst derived from GI or endocervical epithelium
- Endometrial - blood filled chocolate cysts
- Transitional cell found on bladder rare !
Germ cell
Sex cord stromal - highly aggressive and unilateral lead to increased oestrogen production due to follicle cell development PC = pv bleed, breast tenderness
Thyroglobulin
Follicular and papillary thyroid cancer
Miegs syndrome
Benign ovarian fibroma, ascites and pleural effusion often R sided
Malignant ascites
Collection of intraperitoneal fluid may be due to serial implants in the peritoneal membrane. 10% of ascites are due to malignancy
Lymphedema
Collection of lymphatic fluid due to obstruction in lymphatic vessels. If not removed inflammatory reaction from high levels of protein and debris will lead to fibrosis of tissue in effected limb. Can be a complication of treatment
Inflammatory myopathies
Polymyositis = Pain @ neck, torso and hips due to inflammatory breakdown of muscle, low grade pyrexia
- Endomysium of muscles
Dermatomyositis = skin involvement gottrans papules = erythematous heliotrope rash over extensor tendons, proximal muscle weakness, arthralgia
Both are heavily linked to malignancy 40%. NSCLC, SCLC, breast, ovary and upper 1/3rd GI tract
Inv and Mx polymyositis and dermatomyositis
high CK, LDH
EMG = erratic, high frequency signals
Anti-Jo abs, ANA +ve
Muscle biopsy = diagnostic
Mx = look for cancer!! If found often will remit if cancer treated. Steriods
Trousseau’s sign of malignancy
Episodes of vessel inflammation due to blood clots. Hyper coagulability leads to increased risk of DVT/PE
Mx ovarian cancer
Surgery to reduce tumour bulk - if post menopausal bilateral oophoro salpingohysterectomy
Adjuvant carboplatin and paxitel chemo = increased survival
If cancer recurs it is considered platinum resistant based on the length of time it was in remission
Germ cell cancer
Testicular germ cell most common cancer in males 18-35y/o. Only account for 2% of total cancers. Rapid doubling time, highly sensitive to chemotherapy
5yr survival of 98.5%
PC of testicular germ cell cancer
Testicular enlargement, painless solid unilateral mass, 10% back pain due to paraaortic lymphadenopathy, gynecomastia if tumor BhcG secreting.
Invx of germ cell cancer
aFP and LDH both hugely elevated
BhcG - glycoprotein found in syncytitrophoblast of placenta found grossly elevated in trophoblastic disease and germ cell cancer. May = thyrotoxicosis due to cross reaction
USS of ovary/testicles. CXR and CT for staging
Risk factors for testicular germ cell cancer
FHx = 10x, testicular maldescent, Downs and Kleinfelters
Differential diagnosis of cannonball metastasis
RCC, thyroid cancer, melanoma, osteosarcoma, testicular cancer
Poor prognosis testicular cancer
AFP>10,000 BhcG >500,000
Mediastenial or non pulmonary mets
Only NSGCT have poor prognosis 48% @ 5yrs
Seminomas
Metastasis via para aortic lymph nodes to pelvic to mediastinal. Locally invades the rete testis. Very radio and chemosensitive
NSGCT
Commonly metastasises to lung via blood, rarely to brain and bones. Variable lymphatic spread with skip node functions
Tumour lysis syndrome PC
PC hyperkalemia, hyperphosphatemia, hyperuremia and secondary hypocalcemia due to high phosphate levels.
Occurs due to break down of large tumour bulk over short period of time. AKI due to urate nephropathy, cardiac arrhythmias from high K+ and low Ca2+, DIC
Risks of tumour lysis syndrome
Male <25y/o, renal impairment, large volume sensitive tumour i.e. lymphoma, leukaemia or germ cell
Prevention of tumour lysis
Hydration, allopurinol a xanthine oxidase inhibitor to reduce urate levels,
Stop ACEi and NSAID’s
If serious/high risk = Rasburicase and dialysis on standby
Mx germ cell cancer
Orchidectomy - sperm banking and prosthesis offered
Seminoma = surveillance with BhcG and aFP monitoring, adjuvant radiotherapy of para-aortic strip, single dose carboplatin if rate testis > 4cm
NSGCT - surveillance relapse rate 30%, increased if lymph/blood involvement
Surveillance of germ cell
Months clinic appt, exam and tumour markers for 1st year,
CT @ 3,12 and 24 months
Mx of metastasis germ cell
High intensity chemotherapy
i) Bleomycin - 10% fibrosis so crucial to do pul function tests, TLCO and KCO before each cycle
ii) Cisplatin = 18% have reduction in eGFR permanently, loss of high range hearing, neuropathy. Small risk of severe vascular toxicity
Complications of Mx
Tumor lysis syndrome
CVD and fibrosis risk
Psychosexual issues - depression, anxiety
Infertility
ALP (Especially with high Ca2+ and low PTH)
Represents osteoblast activity. Osteosarcoma, bone mets.
Myeloma presents with high Ca2+, low PTH and a low ALP due to IL-1 and IL-6 acting as strong osteoclast stimulating factors
PSA
Prostate cancer
Ca-15-3
Breast
Tumour markers aren’t used for diagnosis
Low sensitivity and specificity
Change in Bowel habit >60
Urgent 2wk wait colonoscopy to exclude malignancy
