Path 2 Flashcards
When do Looser’s zones occur and what are they?
They look like fractures but are not fractures.
caused by severe vitamin D deficiiency
What are brown tumours?
When do you see multinucleatted giant cells in bone histology?
Causes of hilarious lymphadenopathy
lymphoma
TB
sarcoidosis
How does sarcoidosis cause hypercalcaemia?
macrophages in lymph nodes express 1-alpha-hydroxylase
make increased levels of activated vitamin D
this is not controlled by PTH
seasonal hypercalcaemia
Seasonal hypercalcaemia is a feature of sarcoidosis
due to increased levels of sunlight
Management of saarcoidosis
Steroids
-> will normalise calcium and treat the lung problem.
life long condition; have to be careful, higher doses (40/day for a week, taper down) if unwell, if not unwell reassure and observe.
These patients have to be under the resp team.
Sarcoidosis defintion
systemic disease where macrophages express 1-alpha-hydroxylase
affects the lungs (but may also affect other organs, e.g. neurosarcoidosis)
PTHrP - why do we express it?
foetuses express it to make mum release calcium from bone so that they can absorb it
How do you manage hyperCa in 1-HPT and Cancer?
- FLUIDS
in cancer give bisphosphonates.
In primary hyperparathyroidism fo not give bisphosphonates.
What does nutmeg liver indicate?
RHF
(caused by passive venous congestion; blood stays in the liver longer than it would; congested blood vessels)
Causes of splenic enlargement:
Infection: Malaria, EBV
Malignancy: lymphoma, leukemia
Haem:
etc.
When is a fallopian tube most likely to rupture due to ectopic pregnancy?
8-11 weeks
Berry aneurysm
Most aggressive bran tumour?
glioblastoma multiforme
What happens to a brain when it degenerates?
liquefactive necrosis - turns more liquid
What cancers does asbestos predispose you to?
mesothelioma
carcinoma of the lung as well!
Can you put “T1 resp failure’ as cause of death?
not by itself.
Have to add a cause e.g. as a result of asthma
old age on death certificate?
yes, old age is a cause of death that can be on a certificate.
pulmonary oedema on death cert?
not by itself
common causes of sudden death
- stroke
- MI
- ruptured AAA
- oesophageal varices (if people do not know that they had them)
- epilepsy
- illicit drug use
- trauma related to alcohol
What picks up haematoxilin and eosin?
H: nuclei (purple, dark blue)
E: cytoplasm and collagen (pink)
Epidermis - type of epithelium
stratified squamous epithelium
new cells born in the stratum basale, as they go up they lose their nucleus
thickest layer of skin
stratum spinosum
Tissue reaction patterns in dermatology (1-6)
- spongioitic
- lichenoid
- psoriasiform
- vesiculobullous
- granulomatous
- vasculopathic
There is overlap between these patterns
Spongiatic reaction (derm)
- intrtaepidermal oedema (spongiosis)
- can cause vesicles
- superficial perivascular lymphocytic infiltration
example: eczema/dermatitis
Lichenoid inflammation (derm)
- lymphocytes at junction of dermis and epidermis
- attack keratinocytes in the ?epidermis -> kill them -> apoptotic keratinocytes
e.g. lichen planus or erythema multiform or Toxic Epidermal Necrosis (TEN) or SJS
Psoriasiform reaction pattern (derm)
- thickened epidermis
- reddish plaques with silvery scale
- rapid turnover of keratinocytes (e.g. 8 days rather then 30/40ish)
- no time for cells to fully lose nucleus -> stratum corner shows nuclei
- neutrophils in the skin
e.g. psoriasis
psoriasis
silvery, white scale
extensor surfaces (elbows, knees)
psoriasiform reaction pattern
Vesiculobullous reaction pattern (derm)
- antibodes attacking different levels of the epidermis
e.g. pemphigoid, pemphigus
bullous pemphigoid
- IgG autoantibodies attacking the basement membrane
- eosinophils
- bullae are subepidermal
- direct immunofluorescence binding to IgG can show deposit of IgG at the dermal/epidermal junction
pemphigus
- intercellular junctions are attacked
- this leads to epidermolysis
- lethal, can be a very severe disease
pemphigus vs pemphigoif
pemphigus is epidermal
pemphigoid is subepidermal
What exactly is attacked in pemphigus vulgaris?
desmoglycin 3
intraepidermal blistering
Where do bulbar form in pemphigus valgaris?
intraepidermal
Granulomatous skin reaction
x
vasculitis reaction (derm)
How does sun damage show on pathology?
solar elastosis
What is the commonest skin cancer?
basal cell CA
Does basal cell Ca metastasise?
Virtually never metastasises
common mutation in basal cell ca
PTCH (often somatic mutation due to sun exposure, but also you can inherit a mutation that causes BCC)
How to BCCs look under the microscope?
- they are blue tumours
- some artefact
- peripheral nests (cells at periphery of the nests align)
SCC or BCC worse?
SCC is worse
they CAN metastasise and tend to be more aggressive locally
What is Bowen’s disease?
SCC in situ
SCCs colour on histopath
pink
there are keratin pearls
you can have increased mitotic activity and perineurial activity
because of the keratin
Benign naevi on histopath
- maturation with depth
- nests
- well spaced
- …..
ABCDE and FG of melanoma
AA
B
C
D
E
Firm
Growing
melanoma on histopath
- ## pagetoid spread (melanocytes high up in the epidermis)
stains for melanoma
melan A
…..
main factors in melanoma staging
breslow thickness
ulceration
prognosiit cfactors in melanoma
- breslow thickness
- ulceration
- lymphovascular invasion
- etc.
What mutation do you investigate in melanoma?
BRAF
can use a specific treatment
How is Breslow thickness meaasured?
from granular layer to the deepest melanoma cell
Breslow stage is used to stage which cancer?
melanoma
What is multiple myeloma?
malignancy of bone marrow plasma cells, the terminally differentiated and Ig secreting B cells
Structure of an antiibody
light chain:
heavy chain:
Structure of an antiibody
light chain:
heavy chain:
Somatic hypermutatoin
- ## increases affinity of Ab to Ag
Where does somatic hypermutation occur?
In the germinal centre of lymph nodes
myeloma statistics
- 2nd mostt common heamatological malignancy (f you count lymphoma as 1 )
- 19th n all cancers
- m>f
- less common in asian and Caucasian population
- more common in afrocarribean
- age of onset ~67
- 1% below age 40
- more common in
aetiology of multiple melanoma
Risk factors: obesity, increasing age
Genetics (increased incidence n black population, sporadic cases of familiar myeloma)
Wheat is myeloma preceded by?
MGUS
MGUS
- premalignant condition (before multiple myeloma or lymphoma)
- clonal plasma cells in bone marrow
- no symptoms
Diagnostic criteria for MGUS
MGUS average risk to progression too malignancy
1% per year
IgG and IgA MGUS -> MM
IgM MGUS -> lymphoma
how do you stratify MGUS?
Mayo criteria
Mayo criteria
of RFs
- risk stratification for MGUS
Non-IgG M-spike
M-spke >15g/L
abnormal serum free light chain (FLC) ratio
0 RF -> 2% risk of progression in 20 years
1 RF -> X% risk of progression in 20 years
2 RF -> X% risk of progression in 20 years
3 RF -> X% risk of progression in 20 years
Smouldering myeloma
Definition criteria:
- serum monoclonal protein (IgG or IgA) > 30g/L or urnary monoclonal protein >500mg/24h and/or clonal bone marrow plasma cels 10-60%
- absence of myeloma defining events or amyloidosis
IMWG stratfication
What aree MGRS and MGCS
monoclonal gammopathy of renal/clinical significance
When does myeloma incidence peak?
84-85?
Primary events leading to myeakima
- hyperdploiidy (60%, additional odd number Cir)
- IGH rearrangements (Chr 14q32)
Common secondary events in myeloma pahtogenesis
KRAS, NRRASA
t(8:14) IGH/MYC
etc.
CRAB criteria
- Hyeprcalcaemia (>2.75, no other cause for the high Ca such as HPT)
- Renal impairment
- anaemia
- bone lesions
2014 myeloma defining events (MDE)
- bone marrow plasma cells >60%
- involved:uninvolved FLC ratio >100
- > 1 focal lesion in MRI (>5mm)
What areas of the skeleton are affected by multiple myeloma?
- skull
- spine
- ribs
- pelvis
(proximal skeleton)
Imaging for multiple myeloma
- whole body low-dose CT scan
- CT / FDG-PET scan
- MRI (bone marrow cellularity, active vs treated disease)
Complications of bone disease in multiple myeloma
- cord compression (emergency!) Imaging with MRI
- Hypercalcaemia
Cord compression in MM
- emergency
- Dx and Mx within 24 h
- Ig and FLC studies +/- biopsy
- dexamethasone/radiotherapy
- neurosurgery rarely required
- stabilise unstable spine
- MDT meeting
magin
Hypercalcaemia in MM
- Sx: drowsiness, constipation, etc.
- Mx with fluids, steroids and bisphosphonates
Hypercalcaemia in MM
- Sx: drowsiness, constipation, etc.
- Mx with fluids, steroids and bisphosphonates
Causes of myeloma kidney disease
Causes of myeloma kidney disease
Ix for multiple myelomaa
- Ig studies
- BM biopsy and aspirate
- FISH studies
- other
Staging systems for MM
ISS (international staging system, looks at serum b2-microglobulin level)
R-ISS (revised international staging system, includes genetics)
R2-ISS (revised international staging system, includes genetics and 1q+)
R2-ISS now used!!!
Amyloidosis
- misfolded free light chains aggregate into amyloid fibrils in target organs
- MGUS or myeloma in the background
-
Clinical presentation of amyloidosis
insert
Key histopathological myeloma marker?
CD138
(they often lose markers like CD20)
Stain for Amyloidosis
Congo Red
under polarised light, it has a yellow/green colour
Treatment of myeloma
- monoclonal antibodies
- CAR-T cell therapy
- melphalan
- cyclophhosphamide
- dexamethasone and prednisolone (was first treatment used for myeloma)
- IMiD (lenalidomine, pomalidomide)
- CELMoDs)
Myeloma is not a curable disease.
2 groups of myeloma patients (re treatment)
Transplant-eligible (ft and typically <65/70)
Transplant-ineligible (frail and usually >65/70)
Side effects of CAR-T cells in MM
cytokine release syndrome (CRS)
neurotoxicity
other
Bi-specific antibodies in MM
BiTE
have 2 domains
one recognises CD3 and the other target in the tumour cell)
Bi-specific antibodies in MM
BiTE
have 2 domains
one recognises CD3 and the other target in the tumour cell)
e.g. Teclistamab
