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Slide1
Histopathology
Simon Erridge
FY1 – West Middlesex
Slide2Learning Resources
Study material
Lectures
Pathology Guide
Questions
Past paper questions
Meeran’s
questions – quizzes, in-lecture questions
Pathbase
-
https://candidate.speedexam.net/signin.aspx?site=pathbase
Pathology SBAs by
Sukhpreet
Singh
Dubb
Slide3Renal Disease
Slide4Renal Pathology
Functions of the Kidney –
A WET BED
A – Acid-Base Balance
W – Water balance
E –
Erythropoesis
T – Toxin Removal
B – Blood Pressure Control
E – Electrolyte Balance
D –
Vit
D Activation
Slide5The Nephron
Slide6The Nephron
Slide7The Nephron
Slide8Acute Kidney Injury
Definition:
Rapid loss of renal function manifesting as increased serum
creatinine
and urea.
Complications
Metabolic acidosis
Hyperkalaemia
Fluid overload
HTN
Hypocalcaemia
Uraemia
Types:
Pre-renal
Renal
Post-renal
Slide9Acute Kidney Injury
Definition:
Rapid loss of renal function manifesting as increased serum
creatinine
and urea.
Complications
Metabolic acidosis
Hyperkalaemia
Fluid overload
HTN
Hypocalcaemia
Uraemia
Types:
Pre-renal
Renal
Post-renal
Slide10Acute Kidney Injury
Slide11Pre-renal AKI
Slide12Post-renal AKI
Slide13Post-renal AKI
Slide14Renal AKI – Acute Tubular Necrosis
Definition:
AKI resulting from the destruction of tubular epithelial cells.
Aetiology
Ischaemic
Shock
Crush Injury
Non-traumatic
rhabdomyolysis
Mismatched blood transfusion
Toxic
Heavy metal
Aminoglycosides
Ethylene glycol
Myoglobin
Radiographic contrast medium
Slide15Renal AKI – Acute Tubular Necrosis
Slide16Renal AKI – Acute Tubular Necrosis
Slide17Renal AKI – Acute Tubular Necrosis
Slide18Renal AKI – Acute Tubular Necrosis
Slide19Renal AKI – Acute Tubular Necrosis
Slide20Renal AKI – Acute Interstitial Nephritis
Definition:
An inflammatory process of the renal interstitial tissue where there is no primary involvement of glomeruli, tubules or blood vessels.
Aetiology
Infective
Acute/Chronic/
Tuberculous
pyelonephritis
Other infections (viruses/parasites)
Non-infective
Acute hypersensitivity interstitial nephritis
Analgesic abuse nephropathy
Immune (SLE,
Sjogren’s
, Sarcoidosis etc.)
Idiopathic
Slide21Renal AKI – Acute Interstitial Nephritis
Slide22Glomerulonephritis
Definition:
Large and clinically significant group of renal diseases that primarily affect the renal glomeruli.
Classification:
Primary
Secondary
Hereditary Nephritis
Six major syndromes:
Acute nephritic syndrome
Nephrotic syndrome
Acute kidney injury
Chronic kidney disease
Asymptomatic proteinuria
Asymptomatic
haematuria
Slide23Glomerulonephritis
Slide24Glomerulonephritis
Slide25Glomerulonephritis
Slide26Glomerulonephritis
Slide27Glomerulonephritis
Slide28Glomerulonephritis – Nephritic vs
Nephrotic syndrome
Nephrotic syndrome:
HELP
H
ypoalbuminaemia,
O
e
dema
,
L
ipid abnormalities,
P
roteinuria (>3g/24hr)
Nephritic syndrome:
PHAROH
Proteinuria (<3g/24hr), Haematuria, A
zotemia,
R
ed cell casts,
O
liguria,
H
ypertension
Slide29Glomerulonephritis – Nephritic vs
Nephrotic syndrome
Nephrotic syndrome:
HELP
H
ypoalbuminaemia,
O
e
dema
,
L
ipid abnormalities,
P
roteinuria (>3g/24hr)
Nephritic syndrome:
PHAROH
Proteinuria (<3g/24hr), Haematuria, Azotemia, Bed cell casts, O
liguria,
H
ypertension
Slide30Glomerulonephritis – Primary Nephrotic syndrome
Slide31Glomerulonephritis – Primary Nephrotic syndrome
Membranoproliferative
Glomerulonephritis
Age: children & young adults
Histologic features: Increased thickness of
mesangium
+ thickening of
capilary
wall
Type I (70%): Immune complex deposition and associated with systemic immune-complex diseases & malignancy
Type II (30%):
IgG
autoantibody called C3 nephritic factor. Assoc. with partial
lipodystrophy
Type III: Rare and shows feature of Type I and membranous GN with systemic diseases.
Clinically: 50% have nephrotic syndrome, 30% = asymptomatic proteinuria, 20%=nephritic syndrome.
Hypocomplementaemia
is common.
Slide32Glomerulonephritis – Primary Nephrotic syndrome
Focal Proliferative Glomerulonephritis
Histologic features: Pathological changes in <50% of glomeruli with focal proliferation within an otherwise normal glomerulus
Aetiology
: Systemic disease, component of known renal disease or primary idiopathic glomerular disease
Clinical features:
Haematuria
, mild to moderate proteinuria, hypertension uncommon.
Slide33Glomerulonephritis – Primary Nephritic Syndrome
Acute Post-infectious Glomerulonephritis
Post-streptococcal in 70% of cases. Other infections present with worse outcomes
Common in developing countries and children
Onset of disease
1-3 weeks
post infection
ASOT
titre
↑, C3 ↓
Biopsy:
Light microscope (LM): ↑cellularity of glomeruli
Fluorescence Microscope (FM):
granular deposits of
IgG
and C3 in GBM Electron Microscope (EM): Subendothelial humpsClinical: typically nephritic syndrome
Slide34Glomerulonephritis – Rapidly Progressive GN
Rapidly Progressive GN presents with AKI and acute renal failure in weeks – months.
Characterised by ‘crescents’ on inside of Bowman’s capsule which is proliferation of epithelial cells.
Slide35Glomerulonephritis – IgA Nephropathy (Berger’s Disease)
Excessive
mesangial
deposits of IgA, elevated serum IgA and IgA immune complexes in glomerulus.
Activation of C3 and alternative pathway in glomerulus.
Typically occurs 1-2 days after URTI (Think
ig
A
= Acute
)
Clinical picture: Asymptomatic
haematuria
/Nephritic syndrome, occasionally nephrotic syndrome
Slide36Glomerulonephritis – Alport’s
syndrome
Hereditary glomerular disease caused by mutation in
type IV collagen alpha 5 chain
X linked
Nephritic syndrome +
sensorineural
deafness + eye disorder
s (lens dislocation, cataracts)
Presents at 5-20yrs with nephritic syndrome/asymptomatic
haematuria
progressing to ESRF
Slide37Glomerulonephritis – Thin Basement Membrane Disease (Benign familial
haematuria
)
VERY RARELY A CAUSE OF NEPHRITIC SYNDROME – normally exclusively asymptomatic
haematuria
Diffuse thinning of GBM caused by mutation in
type IV collagen alpha 4 chain
Autosomal dominant
Quite common – prevalence is
~5%
Usually
asymptomatic
– incidentally diagnosed with
microscopic
haematuria
Renal function usually normal
Slide38Glomerulonephritis – Diabetic Nephropathy
Diabetic nephropathy: presence of
microalbuminuria
or overt proteinuria in absence of other renal disease
Most common cause of ESRF
Progressive
glomerulosclerosis
Buzzword:
Kimmelstiel
-Wilson nodular
glomerulosclerosis
(15-20%)
More common: diffuse
glomerulosclerosis
Slide39Amyloidosis
Slide40Amyloidosis
Amyloidosis
Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues, disrupting their normal function.
Pathogenesis:
Normal proteins – produced in high quantities
Abnormal proteins – produced in normal amounts
These amyloid proteins/fibrils are
exocytosed
from cells as Beta-pleated sheets.
Beta-pleated sheets are deposited in extracellular spaces
Damage is either systemic or
localised
Slide41AL Amyloidosis
AL Amyloidosis
A = amyloid
L = light chain from
Ig
Aetiology
Plasma cell disorders (
eg
multiple myeloma)
Light chain production > heavy chain
Ix = free serum light chains in serum and urine (
Bence
Jones) and high bone marrow plasma cells
Biopsies show apple green birefringence with
congo
red stain under
polarised
light
Slide42AA Amyloidosis
AA Amyloidosis
A = amyloid
A = serum amyloid A
An acute phase reactant
Aetiology
In chronic
inflamation
increased serum Amyloid A
Amyloid A
misfolds
AA amyloid
AA
amylid
accumulates in tissues
Biopsies show apple green birefringence with
congo
red stain under
polarised
light
Slide43Systemic Amyloidosis
Kidney
Amyloid deposits in basement membrane of glomerulus
Causes
podocyte
damage
Results in proteinuria and nephrotic syndrome
Spleen
Splenomegaly
Liver
Deposits between hepatocytes and endothelial cells
Eventually liver cells become replaced by amyloid
Liver function in tact even in advanced stage
Heart
Deposition results in ventricular stiffening, restrictive cardiomyopathy and diastolic heart failure
Can also result in arrhythmias
Intestines
Damage to intestinal villi resulting in malformation
Tongue
Macroglossia
Peripheral/autonomic neuropathy incl. carpal tunnel.
Slide44Sarcoidosis
Slide45Sarcoidosis
Sarcoidosis
A
multisystem disease
of unknown cause, commonly affecting young adults, characterized by
non-
caseating
granulomas
in many tissues
Histopathology: non-
caseating
granulomas;
Schaumann
and asteroid bodies (protein and calcium inclusions)
Afro-
Caribbeans
= more severe disease
F>MLungs most common organ involvement
Stage of lung involvement:
Stage 1: BHL alone
Stage 2: BHL with pulmonary infiltrate
Stage 3: Pulmonary infiltrates without BHL
Stage 4: fibrosis
Slide46Sarcoidosis
Extrapulmonary
manifestations:
SKIN: erythema
nodosum
, lupus
pernio
, skin nodules
LNs: lymphadenopathy, painless and rubbery
JOINTS: arthritis, bone cysts
EYES: anterior uveitis → misting of vision and painful red eye; posterior uveitis → progressive visual loss;
uveoparotid
fever = bilateral uveitis, parotid enlargement +/- facial nerve palsy (
Heerfordt’s
Syndrome);
keratoconjunctivitis
, lacrimal gland enlargement
LIVER/SPLEEN: HepatosplenomegalyBLOOD:
Leukopaenia
/
anaemia
Hypercalcaemia/hypercalciuria → renal calculi +
nephrocalcinosis
HEART→ dysrhythmias, cardiomyopathy, conduction defects
CNS involvement
CONSTITUTIONAL SX: malaise, fever,
wt
loss, night sweats
Investigations:
High calcium, high ESR, high ACE
Slide47Cerebral Disease
Slide48Strokes
Slide49Strokes – Weber’s syndrome
Midbrain infarction caused by occlusion of the
paramedian
branches of the posterior cerebral artery or of basilar perforating arteries
Damaged Structure
Effect
Substantia
Nigra
Contralateral Parkinsonism as projections to basal ganglia innervate
ipsilateral
motor cortex
Corticospinal
fibers
Contralateral hemiparesis (pre-
decussation
) and typical
UMN findings.
Corticobulbar
Tract
Difficulty with contralateral facial muscles and hypoglossal nerve functions
Oculomotor
nerve fiber
Ipsilateral
oculomotor
nerve palsy leading
to diplopia
Slide50Strokes – Medial pontine
syndrome
Medial Pontine infarction due to occlusion of
paramedian
branches of the basilar artery
Damaged Structure
Effect
Corticospinal
tract
Contralateral UMN hemiparesis
Medial
Lemniscus
Contralateral loss of fine touch, proprioception and vibration
Abducens
nerve
Strabismus (
Ipsilateral
lateral rectus muscle paralysis)
Slide51Strokes – Lateral pontine
syndrome
Lateral Pontine infarction due to occlusion anterior inferior cerebellar artery or
circumfrential
arteries
Damaged Structure
Effect
Lateral
spinothalamic
tract
Contralateral loss of temperature and pain
Facial
nucleus
Ipsilateral
paralysis of face (LMN), loss
of lacrimation and salivation, loss of taste from ant. 2/3rds of tongue, corneal reflex (eff. limb)
Spinal trigeminal nucleus
Ipsilateral
loss of pain and temperature of the face
Vestibular nuclei
Nystagmus
, nausea, vomiting,
vertigo
Cochlear nuclei
Ipsilateral
central deafness
Middle and inferior cerebellar peduncle
Ipsilateral
ataxia
Descending sympathetic tract
Ipsilateral
horner’s
syndrome
Slide52Strokes – Medial Medullary syndrome
Medial medulla infarction due to occlusion of anterior spinal artery
Damaged Structure
Effect
Hypoglossal nerve
Deviation of tongue towards lesion
Medullary pyramid (
corticospinal
tract)
Contralateral hemiplegia
Medial
leminiscus
Contralateral loss of fine touch, vibration and proprioception
Slide53Strokes – Lateral Medullary syndrome
Lateral medulla infarction due to occlusion of posterior inferior cerebellar artery
Damaged Structure
Effect
Vestibular nuclei
Nystagmus
,
vertigo, nausea
Inferior cerebellar peduncle
Ipsilateral
cerebellar signs
Central tegmental tract
Palatal myoclonus
Lateral
spinothalamic
tract
Contralateral deficit in pain and temperature sensation
Spinal trigeminal nucleus
Ipsilateral
deficits in pain and temperature sensation of face
Nucleus
ambiguus
Ipsilateral
laryngeal/pharyngeal
/absent gag reflex
Descending sympathetic
fibres
Ipsilateral
Horner’s syndrome
Slide54Brain tumours
Slide55Brain tumours
Slide56Parkinson’s
Definition
: A movement disorder caused by degeneration of dopaminergic pathways in the
substantia
nigra
resulting in
TRAP
Tremor (Resting, asymmetrical, ‘pill-rolling’ UL>jaw>LL>head)
Rigidity
Akinesia
/
Bradykinesia
Postural instability
α-
synucleinopathy
:
α-synuclein accumulates in Lewy bodies and causes neurotoxicity in substantia nigra
Slide57Multiple Sclerosis
Definition
: A chronic inflammatory disease of the CNS characterized by relapsing remitting, or progressive neurologic symptoms due to inflammation, demyelination, and axonal degeneration
Buzzwords –
Myelin Basic Protein
and
Proteo
-lipid protein
Characterised
by multifocal demyelination, loss of
oligodendrocytes
and
astrogliosis
Slide58Neoplastic Bone Disease
Slide59Primary Bone Tumours
Slide60Primary Bone Tumours
Slide61Primary Bone Tumours
Slide62Bone Forming Tumours
- Benign
Osteoma
:
Rare, benign, slow-growing lesion.
May occur following trauma.
Restricted to flat bones of skull and face
Microscopically = mature lamellar bone
Osteoid
Osteoma
:
Children and young adults
Small (<1cm) and painful
Cortex of long bone
Radiographically
= radiolucent
nidus
with surrounding sclerotic bone (‘Bull’s Eye’)
Osteoblastoma
Larger(>1cm) and painless
Medullary, commonly in vertebrae, ribs,
ilac
crest
Absence of reactive bone formation
Slide63Bone Forming Tumours
- Malignant
Cortical Osteosarcoma:
Most common primary bone malignancy
10-20
yrs
old
M>F
Metaphysis of long bones
Lower 1/3
rd
of femur and Upper 1/3
rd
of tibia (most common site)
Primary - assoc. with
RB
gene mutation
Secondary – following underlying bone disease (eg Paget’s) – more aggressive.
Presents with pain obvious swelling, high ALP
Agressively
metastatic
Medullary Osteosarcoma:
Arises centrally in metaphysis
Breaks through
cotex
leading to
periosteum
reaction
Codman’s triangle/Sunburst appearance.
Slide64Cartilage Forming
Tumours
- Benign
Osteochondroma
Not a true
tumour
and is a disorder of growth in adolescence
Can be solitary or multiple cartilage – capped, mushroom-shaped
‘
exostoses
’ (aka bone spurs) enclosing well-formed cortical bone
Arise from metaphysis of long bones
M>F
Asymptomatic until so big to cause pain
Malignant transformation rare
Hereditary multiple
osteochondroma
= assoc. with bony abnormalities and short stature
Enchondroma
Benign cartilage-forming
tumour
that develops from medulla
Lesion is similar in microscopic features to
osteochondroma
Common locations = short tubular bones of hands and feet
M=F
Asymptomatic/pathological fractures
Malignant transformation rare
Multiple
enchondroma’s
=
Ollier’s
disease (non-hereditary)
Slide65Cartilage Forming Tumours
- Malignant
Chondrosarcoma
Malignant
tumour
of
chondroblasts
2
nd
most common primary malignancy
Slow growing
Central
More common
Arises in medulla of diaphysis or metaphysis
Peripheral
Arises form cortex of metaphysis
May be primary or due to secondary transformation of
osteochondromas
60
yrs
+
M>F
Typically in central skeleton
Radiographically
=
osteolytic
growth with foci of calcification
Histologically = invasive nature and lobules of anaplastic cartilage cells
Slide66Giant Cell Tumours
Giant Cell
Tumours
Arises from epiphysis of long bones
Most common sites = lower end of femur and upper end of tibia
Young adults
M=F
Clinical presentation = pain on weight bearing, swelling, pathological fracture
Radiologically
– lobulated and
osteolytic
lesion at end of long bone – ‘Soap Bubble’ appearance
Behave as low grade malignant
tumours
. 40-60% of them recur following initial resection.
4% result in distant
mets
.
Mets are
histologicaly
benign
Slide67Ewing’s Sarcoma
Ewing’s Sarcoma
Highly malignant small round cell
tumour
/small blue cell
tumour
5-20yrs old
F>M
Originated from cells of neural origin
Common cytogenetic translocation t(11; 22) (q24; q12)
Arises in medullar canal of diaphysis or metaphysis of long bones
Common sites = femur, tibia,
humerus
, fibula
Clinical features = pain, tenderness, swelling and fever
Ix =
leucocytosis
and elevated ESR.
X-Ray =
osteolytic
lesion with
subperiosteal
reactive bone formation – ‘onion skin reaction’
Slide68Breast Disease
Slide69Mastitis/Breast Abscess
Disease
Mastitis - Inflammation of the breast with or without infection.
Types:
Lactational
(puerperal)/non-
lactational
(e.g., duct
ectasia
)/granulomatous.
Age
Women of childbearing age
Incidence
Lactating women: 1-10%
Non-lactating women: 5-9%
Abscesses develop in 3-11% of women with mastitis
Sex
100% females
Slide70Mastitis/Breast Abscess
Geography
No known difference due
to geography
Macroscopic Path
Inflammatory changes of breast
Aetiology
Infectious: Milk stasis + Skin
commensals
Non-infectious: Duct
ectasia
, foreign
materia
(
eg
nipple piercing)
Granulomatous: unknown
Microscopic Path
Infectious: Staphylococcus
Aureus
most common, 40%
polymicrobial
Granuloma
= Collection of macrophages
Slide71Mastitis/Breast Abscess
Symptoms
and Signs
Flu-like
sx
Breast Pain
Milk Stasis
Inflammatory changes*
Discharge
Ipsilateral
lymphadenopathy
Treatment
Supportive +
Antibiotics
Lactational
: Milk expression
Granulomatous: Corticosteroids
Breast Abscess: antibiotics + aspiration/incision and drainage
Investigations
Ultrasound
± aspiration
Culture and sensitivities of discharge
Pregnancy test
Blood cultures
Prognosis
Most will resolve in 2-3 days
Recurrence rate is high in granulomatous
Complications: Sepsis, scaring, fistulas
Slide72Duct Ectasia
Disease
Dilation of ducts assoc. with
periductal
inflammation
Age
30-70 years
Incidence
5.5-25%
Sex
Female
Slide73Duct Ectasia
Geography
No known effect of ethnicity of geography
Macroscopic Path
Dilation of duct
fills with secretions irritates surroundings inflammation fibrosis
‘slit-like’ nipple
retration
Aetiology
Smoking + biggest risk factor
Hyperprolactinaemia
Intraductal
metaplasia
Microscopic Path
Inflammatory
reaction
Slide74Duct Ectasia
Symptoms
and Signs
Nipple discharge (Typically green/brown
, c
an be bloody)
Subareolar
mass
Abscess
Fistula
Nipple retraction
Treatment
Stop smoking
Treat mastitis
Surgery:
excision of all major ducts
Investigations
Clinical Diagnosis
If mass
Triple assessment
Prognosis
Very difficult to treat
Surgery is curative
Slide75Breast Cysts
Disease
Cyst
= fluid-filled, epithelium lined mass
Age
35-50 = peak incidence
Less common post-menopause
Can
be found at all ages post-puberty however
Incidence
37.5% of women in lifetime
Sex
Female
Slide76Breast Cysts
Geography
No change
Macroscopic Path
Distension and obstruction
of terminal duct lobular unit
Clear/yellow fluid filled
Aetiology
Higher premenopausal women
HRT increases risk
Microscopic Path
Epithelial lining of cuboidal cells
Serous
fluid
Slide77Breast Cysts
Symptoms
and Signs
Mass
(may be solitary,
muliple
or small clusters)
Smooth, firm, discrete, oft. Tender, tense, occ. fluctuant
Acute enlargement may cause pain
Pain may start prior to menses
Treatment
Aspiration = investigation and therapeutic
If malignant features on cytology
core biopsy
Investigations
Triple
Assessment
Prognosis
Small risk of recurrence
Risk of breast cancer is not increased for simple cysts
Slide78Fibroadenoma
Disease
Benign breast
tumour
Age
Typically <30
Incidence
V. common cause of breast lumps
Sex
Female
Slide79Fibroadenoma
Geography
Multiple/giant
fibroadenomas
more common in Afro-
Carribean
patients
Macroscopic Path
Normally <3cm in diameter
Aetiology
Increasing
oestrogen
– i.e. contraceptive pill
Microscopic Path
Mix of stromal and epithelial
Slide80Fibroadenoma
Symptoms
and Signs
Nodules
Firm,
rubbery, discrete, well circumscribed, non-tender, mobile
Hormone dependent
Treatment
Watch and wait
Surgery
Cryoablation
Investigations
Triple Assessment – needle aspiration yields no fluid
± core biopsy
Prognosis
Surgery, usually curative, but patient may
still develop more in life.
Slide81Phyllodes
Tumour
Disease
Fast-growing masses that form from the
periductal
stromal cells of the breast
Spectrum of
fibroepithelial
disease of breast
Fibroadenoma
benign
phyllodes
malignant
phyllodes
sarcoma
Age
Median age of diagnosis = 5
th
decade
(
peri
-menopausal)
Incidence
Rare
1% of breast
tumours
85-90% benign
10-15% malignant
Sex
Rare in men
Slide82Phyllodes
Tumour
Geography
More common in Latin America
Presents at earlier age in Asians
Macroscopic Path
Smooth, sharply demarcated
, typically freely movable.
Benign – do no
metastasise
but grow aggressively and local recurrence
Malignant –
haematogenous
mets
Aetiology
A
fibroepithelial
tumour
that arises from
intralobular
stroma
Microscopic Path
Fibroblasts
Benign
vs
borderline
vs
malignant
Features of malignancy = increased nuclear
material (mitotic figures), loss of differentiation
Slide83Phyllodes
Tumour
Symptoms
and Signs
Firm palpable mass
Mobile on chest wall
Fast-growing
Treatment
Surgical – wide local
excision
Post-operative radiotherapy
Investigations
Triple assessment
Core needle biopsy
Prognosis
High risk of recurrence
Increased risk if any
of the following:
atypia
, high mitotic index, stromal overgrowth, incomplete surgical margin.
30% of malignant
pts
die of disease
Slide84Fibroadenoma
vs
Phyllodes
Tumour
Fibroadenoma
Younger
(<30yr)
Slower progression
Recurrence less common
Smaller
Mammography – round density with smooth borders
Ultrasound – cystic spaces
Cytology – same as low grade
phyllodes
Histology – low mitotic
index, mixture of stromal and epithelial cells (similar to low grade
phyllodes
)
Phyllodes
Older (40-50
yr
)
Rapid growth
Recurrence common
Large,
bosselated
Mammography – round density with smooth borders
Ultrasound – cystic spaces
Cytology – malignant
type = higher cellularity
Histology – higher mitotic index, higher
atypia
, loss of differentiation (malignant)
Slide85Fibrocystic Changes/Fibroadenosis
Disease
Combination about
localised
fibrosis, inflammation, cyst formation and hormone-drive chest pain
Age
Almost exclusively between menarche and menopause
Incidence
Affects >60% of women in their lifetimes
Sex
Female
Slide86Fibrocystic Changes
Geography
More common in Caucasian females
Macroscopic Path
Oestrogen
/Progesterone
/Prolactin cause cells to grow and multiply
small cysts and fibrosis
Aetiology
Associated with hormonal
imbalance (increased
oestrogen:progesterone
ratio)
Microscopic Path
Primarily affects terminal duct lobular unit
Slide87Fibrocystic Changes
Symptoms
and Signs
Cyclical pain – peaking in days before menses and decreasing afterwards
Swelling, ‘lumpy breasts’, cobblestone
texture
Lumps often in upper outer section
Treatment
Provide adequate support
caffeine
Medications – evening primrose oil, NSAIDs,
Danazol
,
Tamoxifen
/OCP
Investigations
Triple assessment
Prognosis
Often long-lasting
Relapsing-remitting course
Hormonal event
spontaneous remission
Slide88Fat Necrosis
Disease
Unregulated
cell death of fat cells following direct or indirect violence.
Age
Typically middle aged women
V. rarely in neonates
following traumatic delivery
Incidence
Common
Sex
Female
Slide89Fat Necrosis
Geography
More
common in Western countries
Macroscopic Path
May mimic carcinoma with skin puckering
Aetiology
Most common in obese patients
Assoc. with trauma (can present 10 years later)
Inc. surgery, radiotherapy, contraction
of
pectoralis
muscles
Increased if on anti-
coag
Microscopic Path
Trauma to breast causes
haemorrhage
Blood and tissue lipases
cause adipose cell necrosis
Foam cells and multinucleated giant cells are classic
Slide90Fat Necrosis
Symptoms
and Signs
Variable presentation
Lump – single/multiple/smooth/round/firm/irregular
Skin tethering
Nipple retraction
Treatment
Conservative
Surgery – very rare as high risk for recurrence at surgery sight.
Investigations
Triple Assessment ± core needle biopsy
±MRI
Prognosis
Difficult
to treat
Slide91Breast Cancer
Disease
Malignant neoplasm of the breast
Age
≥50yrs – 375 per 100,000 females
<50yrs
– 42.5 per 100,000 females
Incidence
V. common
Sex
Most common female
malignancy
Slide92Breast Cancer
Geography
≤35yrs – higher incidence in Afro-Caribbean
Caucasians have substantially higher incidence at all other ages
Macroscopic Path
Locally invasive mass
Aetiology
Age,
Personal
or family
hx
High breast density,
nulliparity
, 1
st
pregnancy >30yrs, menarche <12yrs, menopause >55yrs.
BRCA1 + 2
>5yrs HRT, >10yrs OCP
Microscopic Path
Invasive
ductal carcinoma – 55%
Ductal carcinoma in situ – 13%
Invasive lobular carcinoma – 5%
Rarer: lobular carcinoma in situ, malignant
Phyllodes
, sarcoma, lymphoma
Slide93Breast Cancer
Symptoms
and Signs
Progressive
in size.
Upper Outer Quadrant (most com.)
Skin thickening,
discolouration
,
peau
d’orange
Axillary lymphadenopathy
Retraction of nipple/Paget’s/discharge
Treatment
Surgery – breast conserving
vs
mastectomy
Chemotherapy – FAC/
FEC±taxane
Radiotherapy – T3/4 or axillary disease
Endocrine Therapy – SERMS
vs
AI
Investigations
Triple Assessment
Mammogram (>40) – irregular
spiculated
mass
(calcification)
USS (<40) –
hypoechoic
mass with internal calcifications
FNA/Core biopsy + Receptor status
Prognosis
TMN
Adjuvant!
Surgery –
lymphoedema
/
angiosarcoma
/cancer-
encuirasse
Chemo
–
Neutropaenia
/peripheral neuropathy/cardiomyopathy
Endocrine – menopausal/VTE
Slide94Gynaecology Disease
Slide95Endometrial Cancer
Disease
Malignant neoplasm of the endometrium
Age
Mean
age of diagnosis = 60 years
Incidence
Most
common
gynaecological
malignancy
2-3% of women
devlop
in their lifetime
Sex
4
th
most common cancer in women
Slide96Endometrial Cancer
Geography
Most common in US and Eastern Europe
Uncommon in Asia (cervical cancer is most common
gynae
malignancy here)
Macroscopic Path
Type 1 =
endometrioid
(80%)
Type
2 = non-
endometrioid
(20%)
Aetiology
General: increasing age + family
Hx
Type I: excess
oestrogen
(Obesity, PCOS, unbalanced HRT,
nulliparity
, late menopause
Type
II not
oestrogen
related: assoc. with
tamoxifen
Microscopic Path
Type 1 are mainly adenocarcinoma,
but may show squamous differentiation
Type 2 are more aggressive (papillary, serous and clear cell)
Slide97Endometrial Cancer
Symptoms
and Signs
Postmenopausal bleeding is endometrial carcinoma
until proven otherwise!
Potentially bulky uterus if advanced
Ca
Treatment
Surgical: Hysterectomy/bilateral
salpingo-oophrectomy
± pelvic and aortic LN dissection ±
omentectomy
Adjuvant Chemo/
radiotherap
Hormonal:
progestins
used in recurrent disease.
Investigations
Endometrial biopsy
(
pipelle
/dilation and
curretage
)
Pelvic ultrasound
Prognosis
According to FIGO staging
Slide98Ovarian Tumours
Leading cause of death from
gynaecological
malignancy
In women >50
yrs
, more than 50% are malignant
Risk factors
Excess
oestrogen
Age
Family history of breast, colon, endometrial and ovarian cancer (BRCA1/2/Lynch syndrome/
Peutz-Jeghers
Caucasian
Protective factors
OCP
Pregnancy/breastfeeding
Salpingectomy
BSO
Slide99Ovarian Tumours
Slide100Ovarian Tumours
Slide101Ovarian Tumours
–
dermoid
cyst
Slide102Ovarian Tumours
Slide103Cervical Intraepithelial Neoplasia (CIN) and Cervical cancer
Normal cervical histology:
Outer cervix covered by squamous epithelium;
endocervical
canal lined by columnar glandular epithelium. The
squamocolumnar
junction (SCJ) separates them.
Transformation zone (TZ)
: the area where columnar epithelium transforms into squamous cells (=squamous metaplasia). This is a normal physiological process. This area is susceptible to malignant change
CIN:
Dysplasia at the TZ as a result of infection by HPV 16 & 18.
Graded mild, moderate or severe
dyskaryosis
on cytology, but graded CIN 1-3 on histology (from biopsy).
CIN 1 = dysplasia confined to lower 1/3 of epithelium
CIN 2 = lower 2/3CIN 3 = full thickness, but basement membrane intact, equivalent to carcinoma in situ
Schiller’s test – used to
dtect
glycogen in cells – low levels of
glygogen
in CIN cells.
Slide104Cervical Intraepithelial Neoplasia (CIN) and Cervical cancer
Slide105Cervical Intraepithelial Neoplasia (CIN) and Cervical cancer
Slide106Cervical Intraepithelial Neoplasia (CIN) and Cervical cancer
Previous most common
gynaecological
cancer worldwide
95% are squamous cell carcinomas, 5% adenocarcinoma
Invasion through the basement membrane marks the change from CIN to carcinoma
Clinically: post-coital bleeding,
intermenstrual
bleeding, postmenopausal bleeding, discharge, pain. Staged using FIGO system
Stage 0: CIN
Stage I: limited to cervix (80-95%)
Stage II: extended beyond uterus but not to pelvic side wall or lower 1/3 vagina (75%)
Stage III: extension to pelvic side wall and/or lower 1/3 vagina (50%)
Stage IV: extension beyond true pelvis or involvement of bladder/bowel mucosa (20-30%)