Histopathology Part 3- p167-182- Urological, Renal + Gynae) Flashcards
What type of bacteria are >85% of cystitis caused by?
Gram -ve bacilli that normally reside in intestine- commonest E.coli but also Proteus, Klebsiella, Enterobacter, Strep faecalis
What predisposing factors are there for cystitis?
Female Bladder calculi Urinary obstruction DM Sexually active Instrumentation Cyclophosphamide associated with haemorrhagic cystitis
Clinical features of cystitis?
Suprapubic pain
Low grade fever
Dysuria
Frequency
Complications of cystitis?
Ascending infection causing pyelonephritis
Treatment of cystitis?
Trimethoprim
Nitrofurantoin
What cells are affected in 90% of bladder tumours?
Transitional cell tumours
What are contributing factors to transitional cell tumours?
Cigarette smoking
Industrial exposure to aromatic amines
What are the clinical features of transitional cell tumours?
Painless haematuria
Frequency
Urgency
Pyelonephritis
How are transitional cell tumours diagnosed?
Cystoscopy and biopsy
What is the pathology of benign prostatic hyperplasia (BPH)?
Dihydrotestosterone-mediated hyperplasia of prostatic stromal and epithelial cells, resulting in formation of large nodules
Symptoms of BPH?
Difficulty urinating Retention Frequency Nocturia Overflow dribbling
Treatment of BPH?
TURP
5a reductase inhibitors
What type of cancer is the commonest type of prostate cancer?
Adenocarcinoma
Risk factors for prostate cancer?
Age
Race
FH
Hormonal and environmental influences
Where does prostate cancer spread to?
Bladder locally and spreads to bone haematogenously
How is prostate cancer graded?
Gleason system based on degree of differentiation and glandular patterns
How is prostate cancer diagnosed?
History
Examination
PSA- over 4ng/ml is indicative
What is the most common type of germinal tumour?
Seminoma (Peak age 30s and radiosensitive)
What biomarkers are there for germ cell tumours?
AFP
HCG
LDH
What are the two main categories of testicular cancer?
Germ cell- 95%
Sex cord- stromal- 5%
What is nephrotic syndrome characterised by?
Proteinuria (>3g/24h) + hypoalbuminaemia + oedema (+hyperlipidaemia)
What key words are there for identifying nephrotic syndrome in EMQs?
Swelling- facial in kids and peripheral in adults
‘Frothy’ urine
What are the primary causes of nephrotic syndrome?
Minimal change disease
Membranous glomerular disease
Focal segmental glomerulosclerosis
Who does minimal change disease most commonly affect?
Children (75%)
Second peak in elderly
What do you see on light microscopy for minimal change disease?
No changes
What do you see on electron microscopy for minimal change disease?
Loss of podocyte foot processes
What do you see on immunofluorescence for minimal change disease?
No immune deposits
How does MCD respond to steroids?
Well- 90% respond
What would you see on light microscopy for membranous glomerular disease?
Diffuse glomerular basement membrane thickening
What would you see on electron microscopy for membranous glomerular disease?
Loss of podocyte foot processes, subepithelial deposits- ‘spikey’
What would you see on immunofluorescence for membranous glomerular disease?
Ig and complement in granular deposits along entire GBM
How does membranous glomerular disease respond to steroids?
Poorly
Who does Focal Segmental Glomerulosclerosis commonly affect?
Adults
Most common in Afro-Caribbean people
What would you see on light microscopy for Focal Segmental Glomerulosclerosis?
Focal and segmental glomerular consolidation and scarring
Hyalinosis
What would you see on electron microscopy for Focal Segmental Glomerulosclerosis?
Loss of podocyte foot processes
What would you see on immunofluorescence for Focal Segmental Glomerulosclerosis?
Ig and complement in scarred areas
How does focal segmental glomeruloscerosis respond to steroids?
50%
What would you see in renal histology for diabetes
Diffuse glomerular basement membrane thickening
Mesangial matrix nodules- aka Kimmelstiel Wilson nodules
What stain would you use for amyloidosis in the kidney and what would you see if it was present?
Apple green birefringence with Congo red stain
What is nephritic syndrome characterised by?
PHAROH Proteinuria Haematuria 'coke urine' Azootemia- high urea and creatinine Red cell casts in urine Oliguria HTN
What are the different causes of nephritic syndrome?
Acute post-infectious (post strep) GN IgA Nephropathy- Berger disease Rapidly progressive (crescentic) GN Hereditary nephritis- Alport's syndrome Thin basement membrane disease- benign familial haematuria
When does post-infectious GN occur?
1-3wk after streptococcal throat infection or impetigo (strep pyogenes usually)
What investigation findings would you see in post-infectious GN?
Haematuria- red cell casts Proteinuria Oedema HTN Raised ASOT titre Decreased C3
What would you see in light microscopy in post-infectious GN?
Increased cellularity of glomeruli
What would you see in electron microscopy in post-infectious GN?
Subendothelial humps
What would you see in fluorescence microscopy in post-infectious GN?
Granular deposits of IgG and C3 in GBM
What is the commonest glomerulonephritis worldwide?
IgA nephropathy- Berger disease
What is the pathology of IgA nephropathy?
Deposition of IgA immune complexes in glomeruli
How does IgA nephropathy present?
1-2d after an URTI with frank haematuria or asymptomatic microscopic haematuria
What would you see in fluorescence microscopy in IgA nephropathy?
Granular deposition of IgA and complement in mesangium
What is the most aggressive glomerulonephritis which can cause end stage renal failure in weeks?
Rapidly progressive crescentic GN
How does crescentic GN present?
As a nephritic syndrome but oliguria and renal failure are more pronounced
What are the three types of rapidly progressive (crescentic) GN?
Type 1- Anti-GBM antibody
Type 2- Immune complex
Type 3- Pauci-immune/ANCA-associated
What are rapidly progressive (crescentic) GN all characterised by?
Presence of crescents in glomeruli on light microscopy
What causes type 1 rapidly progressive GN?
Goodpastures syndrome
What would you see in fluorescence microscopy in type 1 rapidly progressive GN?
Linear deposition of IgG in GBM
What other organs are involved in type 1 rapidly progressive GN?
Lungs- pulmonary haemorrhage
What causes type 2 rapidly progressive GN?
SLE
IgA nephropathy
Post-infectious GN
What would you see in fluorescence microscopy in type 2 rapidly progressive GN?
Granular (lumpy bumpy)
IgG immune complex deposition on GBM/mesangium
What causes type 3 rapidly progressive GN?
c-ANCA- Wegener’s granulomatosis
p-ANCA- microscopic polyangiitis
What would you see in fluorescence microscopy in type 3 rapidly progressive GN?
Lack of/scanty significant immune complex deposition
What other organ involvement is there in type 3 rapidly progressive GN?
Vasculitis- skin rashes or pulmonary haemorrhage
What causes hereditary nephritis (Alport’s)?
Mutation in type IV collagen alpha 5 chain
What is the inheritance pattern of hereditary nephritis (Alport’s)?
X linked
What is the presentation of hereditary nephritis (Alport’s)?
Nephritic syndrome + sensorineural deafness + eye disorders
What causes thin basement membrane disease?
Diffuse thinning of GBM caused by mutation in type IV collagen alpha 4 chain
What is the inheritance pattern of thin basement membrane disease?
Autosomal dominant
Which nephritic syndromes cause asymptomatic haematuria?
Thin basement membrane disease
IgA nephropathy- Berger
Alport syndrome
What is the pathology of acute tubular injury (ATI)/necrosis (ATN)
Damage to tubular epithelial cells -> cells shed and block off tubules as casts -> reduced flow and increased haemodynamic pressure in the nephron -> reduced pressure gradient across BM -> acute renal failure -> tubular glomerular feedback reduces blood supply further
What is the most common cause of acute renal failure?
ATI or ATN
What causes ATI/ATN?
Hypovolaemia -> pre-renal ARF -> ischaemia of nephrons
Nephrotoxins- drugs (aminoglycosides, NSAIDs), radiographic contrast agents, myoglobin, heavy metals
What would you see in histopathology of ATI/ATN?
Necrosis of short segments of tubules
What is acute pyelonephritis and what commonly causes it?
Bacterial infection of the kidney, usually a result of ascending infection, most commonly caused by E. coli
How does acute pyelonephritis commonly present?
Fever Chills Sweats Flank pain Renal angle tenderness Leucocytosis \+/- frequency, dysuria + haematuria Leukocytic casts seen in urine
What is chronic pyelonephritis?
Chronic inflammation and scarring of the parenchyma caused by recurrent and persistent bacterial infection
What can cause chronic pyelonephritis?
Chronic obstruction- posterior urethral valves, renal calculi
Urine reflux
What causes acute interstitial nephritis?
A hypersensitivity reaction, usually to a drug (abx, NSAIDs, diuretics)
How does acute interstitial nephritis present?
Fever Skin rash Haematuria Proteinuria Eosinophilia
When is chronic interstitial nephritis seen?
Also known as analgesic nephropathy
Seen in elderly with long term analgesic consumption
Name two thrombotic microangiopathies?
Haemolytic uraemic syndrome (HUS)
Thrombotic thrombocytopenic purpura (TTP)
What are thrombotic microangiopathies characterised by?
Thrombosis (Generally renal in HUS and widespread in TTP)
Triad of MAHA, thrombocytopenia + sometimes renal failure
What is the pathophysiology of thrombotic microangiopathies?
Widespread fibrin deposition in vessels associated with ADAMTS3 (platelet surface protein) -> formation of platelet-fibrin thrombi which damage passing platelets and RBCs -> platelet and RBC destruction (thrombocytopenia and MAHA)
Who does HUS usually affect?
Children
Who does TTP usually affect?
Adults
What is HUS associated with?
Diarrhoea caused by E.Coli O157:H7- ‘Children visiting petting zoos’
Non-diarrhoea associated– abnormal proteins in complement pathway/endothelium
Where are the thrombi found in HUS?
Kidneys
Where are the thrombi found in TTP?
Throughout circulation esp in CNS- headaches, LOC, seizures, comas)
What are the signs and symptoms of thrombotic microangiopathies?
Decreased platelets -> bleeding (petechiae, haematemesis, melaena)
MAHA -> pallor and jaundice
How are thrombotic microangiopathies diagnosed?
Decreased Hb and Plts
Signs of haemolysis- increased bilirubin, reticulocytes and LDH
Fragmented RBCs on blood smear
Coomb’s test negative (as not AIHA)
What is acute renal failure?
A rapid loss of renal function manifesting as an increased serum creatinine and urea
What are the complications of acute renal failure?
Metabolic acidosis Hyperkalaemia Fluid overload HTN Decreased calcium Uraemia
What are the different causes of acute renal failure?
Pre-renal- caused by renal hypoperfusion e.g. hypovolaemia, sepsis, burns, acute pancreatitis and renal artery stenosis
Renal- ATN, acute glomerulonephritis, thrombotic microangiopathy
Post-renal- obstruction to urine flow as a result of stones, tumours, prostatic hypertrophy + retroperitoneal fibrosis
What are the commonest causes of chronic renal failure in the UK?
Diabetes Glomerulonephritis HTN + vasc disease Reflux nephropathy Polycystic kidney disease
How is chronic renal failure classified?
Stage 1- GFR>90 Stage 2- mild- GFR 60-89 Stage 3- moderately- GFR 30-59 Stage 4- severely- GFR 15-29 Stage 5- Renal failure- GFR<15
What causes adult polycystic kidney disease (APCKD)?
Autosomal dominant inheritance- 85% due to mutations in PKD1 on chromosome 16 (encoding polysystin-1), remainder in PKD2 on chromsome 4 (encoding polycystin-2)
What are the pathological features of APCKD?
Large multicystic kidneys with destroyed renal parenchyma, liver cysts and berry aneurysms
What are the clinical features of APCKD?
Haematuria
Flank pain
UTI
Features are often due to cyst complications- rupture, infection and haemorrhage
Different types of renal cell carcinoma?
Clear cell carcinoma- well differentiated
Papillary carcinoma- dialysis-associated
Chromophobe renal carcinoma- pale, eosinophilic
RFs for renal cell carcinoma?
Smoking Obesity HTN Unopposed oestrogen Heavy metals CKD
Clinical features of renal cell carcinoma?
Costovertebral pain
Palpable pain
Haematuria
Paraneoplastic syndrome- polycythaemia, hypercalcaemia, HTN, Cushing’s, amyloidosis
What is pelvic inflammatory disease?
Infection ascending from vagina and cervix up to uterus and tubes, leading to inflammation (endometritis, salpingitis) and formation of adhesions
Most common organisms causing PID in UK?
Chlamydia trachomatis
Neisseria gonorrhoea
Clinical features of PID?
Lower abdo pain Dyspareunia Vaginal bleeding/discharge Fever Adnexal tenderness Cervical excitation
Complications of PID?
Fitz Hugh Curtis syndrome- RUQ from peri-hepatitis + violin string peri-hepatic adhesions Infertility Risk of ectopic pregnancy Tubo-ovarian abscess Chronic pelvic pain Peritonitis
What is endometriosis?
Presence of endometrial glands or stroma in abnormal locations outside the uterus e.g. ovaries, uterine ligaments, rectovaginal septum, Pouch of Douglas, pelvic peritoneum
How does endometriosis present clinically?
Pelvic pain Dysmenorrhoea Deep dyspareunia Decreased fertility Cyclical PR bleeding Haematuria Umbilical bleeding Nodules/tenderness in vagina, posterior fornix or uterus
What does endometriosis macroscopically present as?
Red-blue to brown nodules- ‘powder burns’
‘Chocolate cysts’ in ovaries
What does endometriosis microscopically present as?
Endometrial glands and stroma
What is adenomyosis?
Presence of ectopic endometrial tissue deep within the myometrium
How does adenomyosis present clinically?
Heavy menstrual bleeding
Dysmenorrhoea
Deep dyspareunia
Globular uterus
What is a leiomyoma (fibroid)?
A benign tumour of smooth muscle origin
What is the most common tumour of the female genital tract?
Leiomyoma/fibroid (20% of women >35)
What has a strong influence over leiomyoma size?
Oestrogen
Grow during pregnancy and regress post-menopause
What do leiomyomas look like macroscopically?
Sharply circumscribed, discrete, round, firm, gray-white tumours
What do leiomyomas look like microscopically?
Bundles of smooth muscle cells
How do leiomyomas present clinically?
Heavy menstrual bleeding
Dysmenorrhoea
Pressure effects (urinary freq, tenesmus)
Sub fertility
What complications are associated with leiomyomas in pregnancy?
Red degeneration of fibroids- haemorrhagic infarction -> severe abdo pain
Post-partum torsion
What is postmenopausal bleeding until proven otherwise?
Endometrial cancer (10% with PMB have malignancy)
How is endometrial cancer staged?
FIGO system
What are the two types of endometrial cancer?
Endometrioid- 80% (look like normal endometrial glands and mainly adenocarcinomas)
Non-endometrioid- 20% (include papillary, serous and clear cell)
What is the pathophysiology of endometrioid endometrial cancer?
Related to oestrogen excess- peri-menopausal women
Risk factors for endometrioid endometrial cancer?
E2 excess- obesity, anovulatory amenorrhoea (PCOS), nulliparity, early menarche, late menopause, tamoxifen
DM, HTN
What is the pathophysiology of non-endometrioid endometrial cancer?
Unrelated to oestrogen excess- elderly women with endometrial atrophy
What is normal vulval histology?
Squamous epithelium
What is vulval intraepithelial neoplasia (VIN) associated with?
HPV-16
How does the usual type of VIN present?
Warty and basaloid in women 35-55y
What is the main type of vulval carcinoma?
Squamous cell carcinoma- can arise from VIN or from other skin abnormalities
What is the leading cause of death from gynae malignancy in the UK?
Ovarian carcinoma
What is the main cell type in ovarian carcinoma?
Epithelial- 70%
At what age group is the peak incidence of ovarian cancer?
75-84
Subtypes of epithelial ovarian cancer?
Serous cystadenoma- most common (Psammoma bodies common) Mucinous cystadenoma (No psammoma and in younger women) Endometrioid Clear cell (hobnail appearance)
How do germ cell tumours usually differ in severity between children and adults?
Children- malignant
Adults- benign
What is treatment for dysgerminoma?
Radiotherapy
What are the different types of teratoma and how do they differ?
Mature (95%)- e.g. dermoid cyst, benign
Immature- malignant, solid, can secrete AFP
What can choriocarcinomas secrete?
hCG
What are the different types of ovarian germ cell tumours?
Dysgerminoma
Teratoma
Choriocarcinoma
What are the three main cell types of ovarian cancer?
Epithelial- 70%
Germ cell- 20%
Sex cord/stroma- 10%
Three different types of sex cord/stroma tumour and how do they differ in production?
Fibroma- no hormone production and 50% associated with Meig’s syndrome (ascites+pleural effusion)
Granulosa-theca cell tumour- produce E2 (oestrogenic effects)
Sertoli-Leydig cell tumour- secrete androgens- look for defeminisation and virilisation
What staging system is used for ovarian cancer?
FIGO
What are the different stages of FIGO?
1- limited to ovaries
2- limited to pelvis
3- limited to abdo including regional LN metastases
4- Distance metastases outside abdo cavity
What is normal cervical histology? (outer and endocervical canal)
Outer cervix covered by squamous epithelium
Endocervical canal lined by columnar glandular epithelium
Squamocolumnar junction separates them
What is the transformation zone?
Area where columnar epithelium transforms into squamous cells (squamous metaplasia). Normal physiological process. This area is susceptible to malignant change.
What is cervical intraepithelial neoplasia (CIN)?
Dysplasia at TZ as result of infection by HPV 16 + 18
How is CIN graded on both cytology and histology?
Cytology: mild, moderate or severe dyskaryosis
Histology-
CIN 1- dysplasia confined to lower 1/3 of epithelium
CIN2- lower 2/3
CIN 3- Full thickness but basement membrane intact
What percentage of CIN1 reverts to normal over 10-23m?
60-90%
What percentage of CIN3 progresses to cervical cancer over 10yrs?
30%
What are the risk factors for CIN?
Early age at first intercourse Multiple partners Multiparity Smoking HIV Immunosuppression
What is the second most common cancer in women worldwide?
Cervical carcinoma
Which age groups are at most risk of cervical carcinoma?
2 peaks
30-39
>70
RF for cervical cancer?
Early exposure to HPV
COCP + high parity
Smoking
Immunosuppression
Most common type of cervical cancer?
Squamous (70-80%)
What marks the change from CIN to carcinoma?
Invasion through the basement membrane
Clinical presentation of cervical cancer?
PCB Intermenstrual bleeding PMB Discharge Pain
How is cervical cancer staged?
FIGO