The Case Of The Abnormal Mammogram + The Case Of The Unfair Diagnosis Flashcards
example of an inherited oncogene mutation
RET mutation
what disease does RET mutation give you
multiple endocrine neoplasia type 2
multiple endocrine neoplasia type 2
Medullary carcinoma of thyroid, pheochromocytoma, hyperparathyroidism due to parathyroid adenoma
when to suspect MEN2?
2 or more endocrine tumours in a person
symptoms of medullary thyroid cancer (3)
nodule
hoarseness
dysphagia
Symptoms of phaeochromocytoma (3)
anxiety
hypertension
sweating
Symptoms of parathyroid adenoma (4)
Hypercalcaemia so abdo cramps, constipation, thirst, weakness
treating medullary thyroid cancer (2)
total thyroidectomy
levothyroxine
Treating phaeochromocytoma (2)
drugs for BP
unilateral adrenalectomy
screening for MEN2 involves what tests? (6)
calcitonin TFTs neck imaging metanephrines blood pressure calcium levels
example of a cancer caused by tumour suppressor gene mutation
retinoblastoma
Mutations in retinoblastoma
RB1 autosomal dominant mutation
then a 2nd somatic mutation
(2 hit hypothesis)
age of retinoblastoma diagnosis?
age of retinoblastoma diagnosis
usually children under 5
sign of retinoblastoma?
absence of red reflex
white reflex instead
most common eye tumour?
retinoblastoma
prevalence of unilateral vs bilateral retinoblastoma
60% unilateral
40% bilateral
Treating Retinoblastoma if found early? (2)
cryotherapy
laser eye surgery
treating retinoblastoma if found later? (2)
chemotherapy
enucleation
enucleation is…
surgical removal of the eyeball
Prevalence of breast cancer?
1 in 8 women
prevalence of BRCA mutations in breast cancer?
5-10% of breast cancers have these genes
How much does having a BRCA mutation increase your risk of breast cancer
goes up to 80% in women
history suggestive of BRCA mutation?
several family members with breast or ovarian cancer
diagnosed at younger ages
men with breast cancer in families with lots of women with breast cancer
types of genetic testing?
-Diagnostic Testing
-Predictive Testing
can look for specific faulty genes or rarely sequence whole genome
unregulated cell growth that can invade and spread from primary site around the body =
Cancer
epithelial cell tumours
carcinomas
mesodermal tumour?
sarcoma
glandular cell tumours?
adenocarcinomas
general risk factors for cancer
radiation ageing pollution radon gas diseases e.g. COPD family hx occupation asbestos smoking
causes of lung cancer (5)
smoking, passive smoking, air pollution, asbestos, occupational
2 tests for lung cancer
bronchoscopy and biopsy
2 types of cancer mutations?
germ line
somatic
oncogenes are..
genes that can cause cancer by dysregulating cell division
proto-oncogenes are….
the corresponding normal cellular genes that are responsible for normal cell growth and division
Tumour suppressor genes
Genes in normal cells that suppress uncontrolled cell proliferation, can get loss of function mutations causing cancer
mutation for proto-oncogenes has what dominance?
dominant allele
mutation for tumour suppressor has what dominance?
recessive allele so need 2
why does ageing increase cancer risk?
often need many mutations over time to cause cancer, longer life increases the risk
Hallmarks of Cancer
avoiding destruction unlimited replication Evading growth suppressors tumour promoting inflammation invasion and metastasis reprogramming energy metabolism growth signal autonomy angiogenesis Resisting cell death genomic instability
how do cancer cells avoid immune destruction?
how do cancer cells avoid immune destruction?
hide from immune surveillance e.g. by not replicating
Why can cancer cells replicate forever?
hold onto telomeres so they don’t shorten
how does angiogenesis help tumours?
blood supply needed for growth
why is genomic instability useful for cancers?
the more alterations the more likely cancer is
how does cancer evade cell death?
doesn’t respond to apoptotic signals
how can cancer cells reprogram energy metabolism?
can do glycolysis even if oxygen present
PD-L1 mutation
a mutation which helps cancer evade immune system, present in many cancers
EGFR
epidermal growth factor receptor, can mutate in some cancers
afatinib is..
EGFR inhibitor/tyrosine kinase inhibitor
side effects of afatinib (2)
rashes
paronychia
types of drugs that could combat cancer (4)
glycolysis inhibitors
EGFR inhibitors
telomerase inhibitors
VEGF signal inhibitors
T790M mutation
mutation in EGFR receptors that enables resistance to TKIs
Osimertinib
EGFR inhibitor used 2nd line after T790M mutations
frequency of breast screening in the UK?
every 3 years once in the age range
2 views of mammogram
mediolateral oblique
craniocaudal
Mediolateral oblique view
Breast compression from medial to lateral, use of a 30-60 degree angle, divided into superior and inferior breast
craniocaudal view
Breast compression from superior to inferior, divided into outer and inner breast
where is most breast tissue within the breast?
upper outer quadrants
why is it important to get axilla in your MLO view?
some breast tissue in and near axilla
what are you looking for on mammogram?
Masses
calcification
Coarse calcifications in breast are usually what?
more likely to be benign
described as teacupping
fine calcifications in breast usually indicate?
worrying for malignancy
branching micro calcification in a segmental pattern is suggestive of which cancer?
ductal carcinoma in situ
when should you do a true lateral mammogram?
if abnormality on initial views, may allow you to get a better view of an invasive element
What does in situ mean?
still within the basement membrane
stereotactic breast biopsy
technique that combines mammography and computer-assisted biopsy to obtain tissue from a breast lesion
spiculated mass
centrally dense lesion with sharp lines radiating from the margins
is a benign mass usually mobile or tethered?
mobile
is a malignant mass usually mobile or tethered?
tethered
above what age would you biopsy a benign mass just in case?
25
Fibroadenoma
a round, firm, rubbery mass that arises from excess growth of glandular and connective tissue in the breast
very common
breast cyst
fluid-filled sac in breast tissue - smooth, easily movable
very common
sometimes painful
treating breast cysts
conservative
aspirate if painful
most common solid mass in women?
most common solid mass in women
fibroadenoma
most common mass in female breast?
most common solid mass in women
fibroadenoma
Breast Abscess - define
localized collection of pus in the breast tissue
common when breastfeeding
what 2 organisms commonly cause breast abscess?
staph aureus
pseudomonas aeruginosa
Treatment of breast abscess?
incision and drainage
Gynaecomastia
Benign enlargement of tissue in the male breast, either ductal or glandular
treating gynaecomastia?
locate underlying cause and treat
maybe surgical excision if psychological stress
triple assessment for breast cancer
clinical examination
imaging
biopsy
Categories in breast cancer biopsy
category 1 in breast cancer biopsy
normal tissue
category 2 in breast cancer biopsy
benign tissue
category 3 in breast cancer biopsy
uncertain tissue
category 4 in breast cancer biopsy
suspicious of malignancy
category 5a in breast cancer biopsy
intra-epithelial, needs excision
category 5b in breast cancer biopsy
invasive, needs excision and sentinel lymph node biopsy
Comedo necrosis
central necrosis of cancer cells within involved ducts
how does cancer calcify in breast tissue?
central necrosis of cancer cells within involved ducts
what does B5 warrant treatment wise?
wide local excision
dissect specimen to investigate margins
how to grade breast cancer neoplasms?
based on cell differentiation, how much mitosis there is and whether glands are still forming
E-cadherin
an intercellular adhesion molecule, which some malignant cells lose
does ductal neoplasia still have e-cadherin?
yes so shows up on staining
does lobular neoplasia have e-cadherin
no
helps differentiate from glandular
E-cadherin
an intercellular adhesion molecule, which some malignant cells lose
Which has it still, ductal neoplasia or lobular neoplasia?
does ductal neoplasia still have e-cadherin?
yes so shows up on staining
what receptors can breast tumours express? (3)
oestrogen
progesterone
HER2/neu
HER2/neu
growth factor gene highly activated in cells of certain types of breast cancer
treatment for Her2 positive breast cancer?
Trastuzumab/Herceptin
treating oestrogen receptor positive breast cancer
anti-oestrogen therapy
molecular subtypes of breast cancer?
Luminal A
Luminal B
Triple negative/basal-like
HER2 rich
which subtypes of breast cancer more likely to have BRCA mutations?
basal-like
HER2 rich
significance of BRCA mutations
women with these have a high risk of breast and ovarian cancer
how do we identify lymph-vascular invasion?
fluorescent dye injected
identify first lymph node that drains an area
remove it, dissect it and see whether cancerous
drug for oestrogen receptor positive breast cancer
tamoxifen
Luminal A breast cancer
hormone receptor positive
HER2 negative
low Ki-67
good prognosis
Luminal B breast cancer
hormone receptor positive
either HER2 positive or negative
high Ki-67
Triple negative breast cancer
dont express ER, PR, or Her2, very hard to treat, more common in women with BRCA1 mutations
HER2 enriched breast cancer
HER2 positive, hormone receptor negative
grow fast
endobrachial ultrasound (EBUS)
performed during bronchoscopy to diagnose and stage lung cancer
transbronchial needle aspiration through endoscope
2 main divisions of lung cancer
non-small cell lung carcinoma
small cell/neuroendocrine carcinoma
Types of NSCLC (4)
Adenocarcinoma
Squamous cell carcinoma
Mesothelioma
Large cell carcinoma
Types of small cell carcinoma
carcinoid
atypical carcinoid
small cell neuroendocrine
large cell endocrine
where is lung adenocarcinoma often located?
Types of small cell carcinoma
4 molecular mutations in lung cancer
EGFR
ALK
PD-L1
ROS1
markers for lung adenocarcinoma (2)
TTF-1
Napsin A
Which tumours commonly metastasise to bone?
lung
breast
prostate
ovary
which tumours commonly metastasise anywhere?
melanoma
kidney
thyroid
most common areas of bone metastasis
spine pelvis femur humerus ribs skull
Where in the lung is Squamous cell carcinoma found?
centrally
markers for squamous cell carcinoma of the lung? (3)
p40
p63
CK5/6
markers for small cell neuroendocrine carcinoma (2)
CD56
Chromogranin
Markers for mesothelioma (2)
WT-1
calretinin
characteristics of small cell neuroendocrine carcinoma
highly cellular
very large nuclei
pleural effusion in cancer
can be … or ….
can be reactive or malignant
malignant pleural effusion
malignant pleural effusion
cancerous cells increase production of pleural fluid
sign of worse prognosis and progression
treating malignant pleural effusion
3
pleural taps
tunnel drains
pleurodesis
pleurodesis - what is this?
Infusion of a sterile, irritating substance into the pleural space, causing the pleural linings to fuse to one another by developing scar tissue
Risk in draining pleural effusion too quickly?
can get re-expansion pleural oedema
rare malignant tumor arising in the pleura associated with asbestos exposure?
mesothelioma
mesothelioma
rare malignant tumor arising in the pleura associated with asbestos exposure
differential for mesothelioma
(Rare malignant tumor arising in the pleura associated with asbestos exposure)
adenocarcinoma with pleural thickening
what do metastasis look like on imaging
multiple and bilateral
sharply outlined
necrotic
how to decide if a tumour is primary or metastasis using immunohistochemistry
look at markers to identify cancer
which cancer metastasises to bone the most?
prostate
