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Liv Path > Histopath > Flashcards

Histopath Flashcards

1
Q

Acute vs chronic inflammation - Cells

A

Neutrophil polymorphs = ACUTE inflammation

Lymphocytes = CHRONIC inflammation

Lymphocytes + Neutrophils = ACUTE on CHRONIC

Fibrosis = scarring = CHRONIC disease

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2
Q

Erosion vs Ulcer

A

Erosion: Loss of surface epithelium +/- lamina propria (muscularis intact)

Ulcer: Loss of surface epithelium with depth of tissue loss beyond the muscularis mucosae

Chronic ulcers: have an element of fibrosis Acute ulcers: do not

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3
Q

Metaplasia vs Dysplasia

A

Metaplasia: Change in one mature cell type for another mature cell type (Reversible)

Dysplasia: Cytological and histological features of malignancy but basement membrane intact

  • Mitotic figures
  • Raised nuclear : cytoplasmic ratio
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4
Q

Features of adenocarcinomas

A

Gland forming

Mucin secreting

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5
Q

Features of squamous cell carcinoma

A 
Make keratin (even in non-keratinised tissues)
Inter-cellular bridges
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6
Q

Necrosis

A
  • Represents energy failure
  • Non-energy dependent cell death
  • Cell lysis due to loss of electro-ionic potential
  • Pathological
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7
Q

Apoptosis

A
  • Planned, energy dependent exit strategy

- Cell contents are not released

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8
Q

Epithelial types in the oesophagus

A

Presence of submucosal glands (strict evidence of oesophageal tissue).

Top 2/3 - stratified squamous
Z- line (squamous-columnar junction)
Bottom 1/3 - columnar epithelium

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9
Q

Oesophagitis: Causes, Diseases Process, Complications

A

Caused by:

1) Reflux
2) Corrosives

–> Inflammation –> Ulceration –> Loss of surface epithelium –> Repair –> Replacement of useful cells with myofibroblasts –> Scarring

Inflammation –> Metaplasia –> Metaplasia (+/-with Goblet cells) –> Dysplasia –> Cancer

Complications:

  • Barrett’s Oesophagus: metaplastic columnar lined oesophagus (+/-goblet +ve)
  • Malignancy
  • Stricture
  • Ulceration
  • Perforation
  • Haemorrhage
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10
Q

Barrett’s Oesophagus

A

Columnar-lined oesophagus (intestinal-type)

Two distinct features:

  1. Columnar metaplasia
  2. Columnar metaplasia + Goblet cells = intestinal –type columnar –> Greater risk of malignant transformation

Not all “Barrett’s” carries an equal risk

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11
Q

Oesophageal Malignancy

A 
Mid Oesophagus (lower 2/3): SCC Commonest cause Worldwide 
Smoking and boozing
Histology: keratinised cells with intracellular bridges

Distal Oesophagus (lower 1/3): Adenocarcinoma
Columnar epithelial transformation
Now commonest in UK –
GORD/Oesophagitis -reduced risk with H.Pylori
Histology - glandular epithelium

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12
Q

Liver Cirrhosis

A

Fibrosis of the whole liver with nodules of regenerating hepatocytes and distortion of the vascular architecture

Leads to intra and extra hepatic shunting of blood:

  • blood runs down scar tissue missing the hepatocytes
  • portal anastomoses e.g. oesophageal varices
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13
Q

Oesophageal Varices

A

Result from any cause of portal hypertension

  • Cirrhosis (extra-hepatic shunting)
  • Portal vein thrombosis
  • IVC obstruction

Porto-systemic anastomotic sites - Oesophagus most clinically relevant

Presents with torrential bleeding and melaena

Rx:

  • Resuscitate with blood and crystalloids
  • Terlipressin
  • Score
  • Scope
  • Infuse with PPI
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14
Q

Stomach - Cell Types

A

-Columnar epithelium
Different parts of the stomach have different levels of “specialised cells”

Body and Fundus:

  • Parietal cells - acid
  • P Cells/ Chief cells - pepsin

Pyloric antrum

  • Non-specialised gastric epithelium
  • Neuroendocrine cells - gastrin

GOBLET CELLS ARE NOT SEEN IN THE STOMACH –> Indicates intestinal type metaplasia

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15
Q

Acute Gastritis - Causes

A

Booze, NSAIDs, etc. (H. Pylori), Stress

Stomach is the most sensitive organ in the GI tract to ischaemia

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16
Q

Chronic Gastritis - Causes

A

A: autoimmune (pernicious anaemia)
B: bacteria (H. Pylori)
C: corrosives (bile reflux, NSAIDs, alcohol)
CMV (Renal Transplant Patients) and Crohn’s

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17
Q

Gastritis - Complications

A
  • Ulceration
  • Perforation
  • Haemorrhage
  • Cancer
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18
Q

H.Pylori Infection

A

Gram negative curved rod
Hydrogenase: produce energy by oxidizing molecular H2
+/- Cag pathogenicity island = POORER outcome
Hypothesis about pH, quiescence and infection

Leads to:
Chronic gastritis –> Ulcers and scarring Adenocarcinoma
LYPHOMA

H. Pylori –> Induction of MALT –> Germinal centre + lymphoid follicles (Bacterial causes of lymphoma are rare)

Rx = one week triple therapy

  • PPI
  • Clarythromycin
  • Amoxicillin or metronidazole
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19
Q

Lymphoid follicles

A

Not part of normal structure of MALT
Suggests on-going inflammation
95% of causes will have, or previously had, H.pylori.

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20
Q

Gastric Cancer

A

95% are Adenocarcinomas
5%: SCC, Lymphoma, GIST (GI stromal tumour)

Two main types of adenocarcinoma
1) Intestinal: well-differentiated, mucin producing, gland forming = a classic adenocarcinoma
2) Diffuse: single-cell architecture, no gland formation, contain signet ring cell
(cell appears like a signet ring as mucin has pushed the contents of the cell to the periphery with nucleus at one end)

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21
Q

Duodenum - Cell Types

A

-Intestinal-type epithelium -Villous:crypt ratio >2:1

Change in the ratio

  • Damage to the villi –> shortening or blunting
  • Crypts compensate and undergo hyperplasia –> enlarged crypts

Ratio villous crypts tends to –> 1:1 during inflammatory disease

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22
Q

Duodenal ulcers

A

Most common cause is H.Pylori

Anterior ulcers –> perforation –> peritonitis
Posterior ulcers –> gastroduodenal artery –> Haemorrhage

Cause of major haemorrhage is a posteriorly sited duodenal ulcer

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23
Q

Coeliac

A

Diagnosis:
Anti-endomysial Ab +ve
Anti-TTG +ve
OGD on gluten diet

Changes that occur in malabsorption:

  • Villous atrophy
  • Crypt hyperplasia (and hence reduction in ratio)
  • Increased intraepithelial lymphocytes = CD8+ T Cells (>20: 100 lymphocytes: enterocytes)

Complications: malabsorption, deficiencies, lymphoma EATL (enteropathy associated T cell lymphoma)

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24
Q

Tropical Sprue

A

SAME CHANGES AS COELIAC:

  • Villous atrophy
  • Crypt hyperplasia (and hence reduction in ratio) -Increased intraepithelial lymphocytes = CD8+ T Cells (>20: 100 lymphocytes: enterocytes)

THEY HAVE BEEN TO THE TROPICS i.e. nearish the equator

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25
Q

Lymphocytic Dueodenitis

A

Distinct from coeliac disease but usually a continuum

Increased intraepithelial lymphocytes = CD8+ T Cells (20: 100 lymphocytes: enterocytes)

Architectural villous structure normal = normal villi, normal crypts

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26
Q

Duodenal MALToma

A

Coeliac disease –> chronic inflammation = EATL (Enteropathy associated T-cell lymphoma)

Aggressive lymphoma
Important to stick to gluten-free diet to prevent EATL

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27
Q

Hirschprung’s

A

Congential

Absence of ganglion in myenteric plexus
Nerve fibres ARE present

Distal colon fails to dilate –> obstructing point

  • constipation
  • distension

Histopathology: hypertrophy of the nerve fibres and absence of ganglion

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28
Q

Colitis - Causes

A

Acute:

  • Infection
  • Drugs (notably Abx)
  • Chemotherapy
  • Radiation

Chronic Colitis (acute on chronic picture):

  • Crohn’s
  • UC
  • TB
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29
Q

Ischaemic Colitis - Causes

A

Acute:
Arterial occlusion: Atheroma, Thrombus, Embolism
Venous occlusion: Thrombus,
Hypercoagulable states
Small vessel disease: DM, Vasculitis
Low flow states: CCF, Shock
Obstruction: Hernia, Volvulus, Intussusception

Chronic:

  • PVD
  • Vasculitis
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30
Q

Polyps of the Large Bowel - Types

A

Non-neoplastic:

  • Hyperplastic polyps = folds of mucosa that have grown a bit much
  • Inflammatory pseudo-polyps
  • Hamartomatous polyps

Neoplastic polyps:

  • Tubular adenoma
  • Tubulovillous adenoma
  • Villous adenoma (microscopically different)
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31
Q

Polyps of the Large Bowel - Higher Risk of Cancer

A

Higher risk of cancer:

  • Larger polyps (>4cm)
  • More polyps
  • Higher villous component
  • Dysplastic features

Normal –> Adenoma –> Adenocarcinoma Remove the adenoma–> reduce risk of cancer
98% of colorectal cancers are adenocarcinomas

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32
Q

Renal Stones - Common Sites and Types

A

Aggregates formed in the renal collecting ducts

The most common sites:

  • Pelvi-ureteric (between renal pelvis and ureter)
  • Pelvic brim (where ureter crosses iliac blood vessels)
  • Vesico-ureteric (where ureter inserts into bladder)

The most common stones:

  1. Calcium oxalate 75%
  2. Magnesium ammonium phosphate (struvite) 15%
  3. Uric acid 5%
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33
Q

Calcium Oxalate Stones

A

Precipitated by an increase in the concentration of calcium

Absorptive hypercalciuria (50%) – Vitamin D
Renal hypercalciuria
Hypercalcaemia: primary hyperparathyroidism

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34
Q

Struvite Stones

A

Precipitated by alkaline urine

Infection with proteus species–>urease producing bacteria Cause staghorn calculi

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35
Q

Uric Acid Stones

A

Precipitated by an increase in “uric acid” or cell turn-over
Gout
Chemotherapy (usually for B-cell lymphoma or leukaemia)
Acidic urine

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36
Q

Benign Renal Tumours - Papillary Adenoma

A

<15mm, well-circumscribed
Trisomy 7, Trisomy 17, loss of Y chromosome
Frequent incidental finding in nephrectomies and at autopsy esp in CKD

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37
Q

Benign Renal Tumours - Renal Oncocytoma

A

Pink oncocytic cells. Macrocytically: well circumscribed, Mahogany-brown mass with central scar.
Seen in Birt-Hogg-Dubé syndrome

(note: oncocyte = epithelial cell characterized by an excessive number of mitochondria)

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38
Q

Benign Renal Tumours - Angiomyolipoma

A

Perivascular epitheloid cells (vessel wall, muscle and fat)
Mostly sporadic but can be seen in tuberous sclerosis (with phaeos and hydrocephalus)
Large >4cm
May present with flank pain
May bleed dramatically

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39
Q

Renal Cell Carcinoma - RFs, Presentation and Sub-Types

A

Malignant epithelial kidney tumour

RFs: Smoking, HTN, long-term dialysis, obesity, von Hippel Lindau, PKD

Presentation: painless haematuria, may have flank pain +/- abdo mass, may have weight loss and fever. May be detected incidentally on imaging.

Highly metastatic – lungs, liver and bones

Sub-types:

  • clear cell renal cell carcinoma (70%)
  • papillary renal cell carcinoma (15%)
  • chromophobe renal cell carcinoma (5%)
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40
Q

Renal Cell Carcinoma - Clear Cell Carcinoma

A

Epithelial cell
Golden yellow with haemorrhagic areas
Loss of chromosome 3p

Risk progression index - Leibovich Risk Model

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41
Q

Renal Cell Carcinoma - Papillary Renal Cell Carcinoma

A

Papillary epithelial cell composed of papillae, >15mm in size
Trisomy 7 and 17, and loss of Y chromosome

2 types:

  • type 1 = well defined, classic cytologically
  • type 2 = heterogenous microscopically and cytologically
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42
Q

Renal Cell Carcinoma - Chromophobe Renal Cell Carcinoma

A

Epithelial cell
Sheets of large cells, distinct cell borders, reticular cytoplasm, thick-walled vascular network

Grossly appears as well-circumscribed solid brown tumour

Pale, eosinophilic cells

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43
Q

Urothelial Cell Carcinoma

A

Transitional cell carcinoma

Arise from:

  • Bladder
  • Renal pelvis
  • Ureters

Common RFs: smoking, aromatic amines (dyes)

Most present with haematuria

Three main subtypes

  • Non-Invasive Papillary Urothelial Carcinoma
  • Infiltrating Urothelial Carcinoma
  • Flat Urothelial Carcinoma in-situ
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44
Q

Liver - Blood Supply

A

Dual Blood Supply:

  1. Portal vein
  2. Hepatic artery

Ischaemic disease of the liver is very rare. More commonly Iatrogenic.

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45
Q

Liver - Histology

A

Arranged into portal tracts surround a central vein (6:1)
Blood from portal vein and hepatic artery = portal tract
Trickles down the spaces between strands of hepatocytes into the central vein

Divided into three zones 1, 2, 3
Hepatocytes originate near portal tract in zone 1 –> 2 mature –> 3 Zone 3 hepatocytes are the most metabolically active.
Zone 3 is around central veins where oxygenation is poor.

Endothelial cells are unique
• Do not have a basement membrane
• Discontinuous (no tight junctions)

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46
Q

Acute Hepatitis

A

SPOTTY NECROSIS, foci of inflammation & necrosis, inflammatory infiltrates

Drugs, Hep A&E

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47
Q

Chronic Hepatitis - Causes

A

Viruses not A/E
Drugs
Auto-immune Hepatitis

Primary biliary cholangitis
Primary sclerosing cholangitis (UC)

Haemochromatosis (bronzed diabetes) “Prussian blue”
Wilson’s Disease “Rhodanine”
A1AT Def

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48
Q

Chronic Hepatitis - Stage and Grade

A

Fibrosis = stage
F0 – F4
F4: Compensated cirrhosis

Inflammation = grade

  • Portal inflammation: inflammation confined within limiting plate
  • Interface hepatitis “piecemeal necrosis”: inflammation across the limiting plate
  • Lobular inflammation: inflammation across entire lobule
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49
Q

Liver Inflammation - Histology

A

Changes that occur in liver inflammation –> Fibrosis

-Loss of hepatocyte microvilli
-Loss of fenestration of endothelium
+
-Stellate cell activation and deposition of ECM in space of Disse
-Activation of Kupffer cells

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50
Q

Liver - Cirrhosis - Features and Complications

A

Features: Whole liver fibrosis with nodules of regenerating hepatocytes and distortion of vascular architecture

Structural changes in previous slide lead to –> Intra-hepatic shunting (blood flows straight through sinusoids) –> portal anastomoses e.g. oesophageal varices and haemorrhoids

Complications

  • Hepatic encephalopathy
  • Liver cell cancer
  • Portal hypertension
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51
Q

Alcoholic Hepatitis - Stages

A

1- Fatty Liver - fatty infiltrates
2- Alcoholic hepatitis
3- Cirrhosis - fibrosis, loss of parenchymal tissue

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52
Q

Alcoholic Hepatitis - Histological Features

A
  • Ballooning of cells (accumulation of proteins and water –> swelling)
  • Mallory Denk Bodies (dense pink material within cells - clumping of IFs)
  • Neutrophil polymorphs and scarring
  • Apoptosis
  • Pericellular fibrosis
  • Zone 3 – acetaldehyde highest, and relatively hypoxic

Relatively irreversible

80% of pmts with alcoholic hep are cirrhotic

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53
Q

NAFLD

A

Very similar histological features as alcoholic liver disease

Non-alcoholic fatty liver disease caused by increased IR
-TIIDM
-Obesity
= Metabolic syndrome

–> Non-alcoholic steatohepatitis (equivalence of alcoholic hepatitis) = NASH

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54
Q

Liver Cancers

A

Causes

1) Secondary metastatic disease (commonest)
- Multiple in number
- Discrete

2) Primary tumours
- HCC - AFP tumour marker
- Hepatoblastoma (tumours of primitive hepatocytes)
- Cholangiocarcinoma - associated with PSC, histology - capillary ingrowth
- Haemangiosarcoma

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55
Q

Pancreas - Endocrine and Exocrine Components

A

Endo - Islets of Langerhans: insulin, glucagon, somatostatin

Exocrine- acini: protease, lipase, amylase

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56
Q

Acute Pancreatitis - Causes

A

Aberrant release of pancreatic enzymes
Causes by duct obstruction and reflux + direct acinar injury

Reflux enzymes –> acinar necrosis –> release of more enzymes

Release of lipases –> fat necrosis –> soaponification with calcium

Causes (GETSMASHED):
Duct obstruction: Gallstones (50%) and tumours, trauma
Metabolic / Toxic: Alcohol (33%), drugs, hypercalcaemia/hyperlipidaemia
Ischaemia: Shock
Infection: Mumps
Autoimmune
Idiopathic

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57
Q

Acute Pancreatitis - Patterns of Injury

A

Peri-ductal = Obstructive cause - Acinar cells adjacent to the ducts undergo necrosis

Peri-lobular = Vascular/ischaemic cause -Necrosis at the edges of the lobules (blood supply comes with ducts so periphery most affected)

Pan-lobular: either peri-ductal or peri-lobular injury progressing

Alcohol: spasm/oedema of Sphincter of Oddi and the formation of a protein rich pancreatic fluid which obstructs the pancreatic ducts

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58
Q

Acute Pancreatitis - Complications

A
  • Haemorrhagic pancreatitis (50% mortality)
  • Metabolic disturbances: shock, hypoglycaemia, hypocalcaemia
  • Psuedocyst (lacks epithelial lining - lined by necrotic and granulation tissue) –> may become infected to form abscess
  • Abscess
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59
Q

Acute Pancreatitis - Rx

A

Dx: serum lipase

  • IV fluids (sequestration)
  • ABX not recommended unless necrotising pancreatitis
  • Electrolyte replacement
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60
Q

Chronic Pancreatitis - Causes

A

Relapsing or persistent pancreatitis

Chronic inflammation with parenchymal fibrosis & loss of parenchyma. Islets look bigger as acini disappear. Duct strictures with calcified stones and secondary dilatations.

Causes:
Alcohol (80%)
Gallstones + tumours Haemochromatosis Idiopathic
Autoimmune (IgG4 Disease)

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61
Q

Pancreatic Tumours

A

Carcinomas
• Ductal 85%
• Acinar
Acinar-ductal metaplasia (most originate from acinar –> ductal carcinoma)

Cystic neoplasms
• Serous cystadenoma
• Mucinous cystic neoplasm

Neuroendocrine tumours

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62
Q

Pancreatic Ductal Adenocarcinoma

A

5YSR: 5%

K-ras mutations 95%
Peri-neural invasion very common

Commonest in the head of pancreas (60%), progressively less common moving down to the tail
(Opposite of neuroendocrine tumours)

Pre-malignant Bridges – arise from ductal dysplastic lesions PANcreatic Intraductal Neoplasia = PanIN

Microscopically adenocarcinomas therefore secrete mucin

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63
Q

Pancreatic Neuroendocrine Tumours

A

Contain neuroendocrine markers (e.g. chromogranin, neurosecretory granules – can be measured in blood or used as generic stain for NETs)

Commonest in the tail –> less common in the head

Associated with MEN 1 (pituitary, pancreas, parathyroid)

Most non-secretory (i.e. most common type)

Commonest type of secretory tumour: Insulinoma (beta cells)

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64
Q

Gallstones

A

Incredibly common (20% of all people)

Types:

  1. Cholesterol (>50%; single, radiolucent) – cholesterol solitaires
  2. Pigment (Ca salts of unconjugated bilirubin, multiple, radiopaque)

Complications:
Bile duct obstruction
Acute cholecystitis - neutrophil polymorphs (may be acute on chronic)
Gall bladder cancer - 90% adenocarcinomas Pancreatitis

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65
Q

Chronic Pancreatitis - Complications

A 
Malabsoprtion
Diabetes Mellitus
Pseudocysts
Pancreatic calcifications
Carcinoma of pancreas
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66
Q

Pancreatic Acinar Adenocarcinoma

A

Acinar-ductal metaplasia - most originate from acinar –> ductal carcinoma

Associated with an increase in serum lipase

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67
Q

Chronic Cholecystitis

A
  • Chronic inflammation
  • Fibrosis
  • Diverticula – Rokitansky-Aschoff sinuses
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68
Q

Liver Injury

A
  • Kupfer Cells (macrophages) activate
  • Gaps in the ECs collapse
  • Collagen is deposited
  • Leads to inflammation/fibrosis
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69
Q

Haemochromatosis

A
  • Genetic condition – increased iron absorption
  • FHE Gene mutation on Chr6
  • No special stain required

Damage to organs secondary to iron deposition

  • Pancreas – “bronzed diabetes”
  • Joints – arthritis
  • Heart– arrythmias, cardiomyopathy
  • Liver damage

Rx - venesection

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70
Q

Primary Biliary Cholangitis

A

Progressive autoimmune destruction of intrahepatic bile ducts

Build up of bile and other toxins - cholestasis

AMA positive (anti-mitochondrial antibody)

Histology – destruction of bile ducts associated with CHRONIC INFLAMMATION (with granulomas)

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71
Q

Primary Sclerosing Cholangitis

A

Affects intra and extrahepatic bile ducts

Characterised by bile duct fibrosis and sclerosis

Associated with UC and increased risk of cholangiocarcinoma

Concentric fibrosis – onion skinning fibrosis, chokes off and destroys bile duct. WITHOUT inflammation

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72
Q

Wilson’s Disease

A
  • Accumulation of copper due to failure of excretion
  • Defect of transporter protein from hepatocytes into bile duct
  • Genes on chromosome 13
  • Accumulates in the liver and CNS
  • Kayser Fleicher Rings – slit lamp
  • Rhodanine stain (turns copper golden-brown against blue counter stain)
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73
Q

Benign Liver Tumours

A

Haemangioma - most common, often incidentally picked up

Liver cell adenoma

Bile duct adenoma

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74
Q

Fibrosis

A

Collagen deposition

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75
Q

Breast - Normal Histology

A

Branching ducts ending in terminal-duct lobular units = the functional unit of the breast

Duct-lobular system lined by an inner glandular epithelium and an outer myoepithelium

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76
Q

Duct Ectasia

A

Presents with nipple discharge

Histology shows dilated ducts with peri-ductal inflammation filled with secretions
Cytology shows macrophages and proteinaceous material

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77
Q

Acute Mastitis

A

Presents with painful red breast

Seen in lactating women- stasis of milk/cracked skin
Staphylococci – most common organism
Treatment is usually antibiotics/drainage

Histology shows acute inflammation +/- abscess formation
Cytology shows abundant neutrophils

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78
Q

Fat Necrosis (breast)

A

Presents with firm breast lump

Inflammatory reaction to damaged adipose tissue
Tissue can become fibrosed and calcified
Associated with trauma, surgery and radiotherapy

Cytology shows degenerate fat, foamy macrophages and giant cells

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79
Q

Inflammatory Breast Disease Conditions

A

Duct ectasia
Mastitis
Fat necrosis

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80
Q

Benign Breast Disease Conditions

A 
Fibroadenoma
Fibrocystic change
Phyllodes Tumour
Intraductal papilloma
Radial scar
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81
Q

Fibroadenoma

A

Presents as a mobile breast lump
Benign fibroepithelial tumour of the breast

Histology shows a multinodular mass of expanded
intralobular stroma and compressed slit-like ducts

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82
Q

Fibrocystic change (breast)

A

Cyclical breast lumpiness
Very common – associated with exaggerated hormonal responses

Histology shows cysts, adenosis, mild epithelial and stromal hyperplasia

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83
Q

Phyllodes Tumour

A

Presents as a rapidly enlarging breast mass

  • Group of potentially aggressive fibroepithelial neoplasms of the breast
  • Usually in women > 50
  • Majority are benign – small proportion can be more aggressive

Histology shows overlapping cells (not a monolayer), “leaf like” architecture, stromal overgrowth – particularly next to epithelial components

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84
Q

Intraductal Papilloma (breast)

A

Presents with nipple discharge/mass

  • Benign papillary tumour from the ductal system
  • Lactiferous ducts = central papilloma
  • Terminal ductules = peripheral papillomas

Histology shows a papillary (finger like) mass within a dilated duct lined by epithelium and myoepithelium

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85
Q

Radial Scar (breast)

A

Usually picked up incidentally

  • Benign sclerosing lesion of the breast
  • Usually presents as a stellate mass on mammography

Histology shows a central, fibrous stellate area and proliferation of ducts and acini in the periphery

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86
Q

Malignant Breast Disease

A

Ductal Carcinoma in Situ
Basal Like Carcinoma
Invasive Breast Carcinoma - ductal, lobular, tubular, mucinous

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87
Q

Ductal Carcinoma in Situ (breast)

A

85% present on screening mammography

  • A neoplastic intraductal epithelial proliferation
  • Associated with an inherent, but not inevitable, risk of progression to invasive breast carcinoma

Histology shows ducts filled with atypical epithelial calls – lumen is regular

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88
Q

Basal Like Carcinoma (breast)

A

Recently described type of carcinoma discovered following genetic analysis of breast carcinomas

Immunohistochemically characterised by positivity for “basal” cytokeratins CK5/6 and CK14.

Histologically characterised by sheets of markedly atypical
cells with a prominent lymphocytic infiltrate

This is a dangerous type of breast cancer because it has a propensity for vascular invasion and distant metastatic spread

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89
Q

Invasive Breast Carcinoma

A

Presents with firm breast mass
-Malignant epithelial neoplasms which infiltrate the breast and have the capacity to metastasise

Histological subtypes

1) Ductal carcinoma – cells are big and pleimorphic, invasive cells move to the stroma
2) Lobular carcinoma – linear arrangement with cells of the same size. “Indian file”.
3) Tubular carcinoma – elongated, round tubules of cancerous cells
4) Mucinous carcinoma – empty looking spaces, containing mucin

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90
Q

Endometrial Hyperplasia

A

Hyperplasia results from an increase in both glands and stroma of endometrium

Driven by oestrogen – Persistent oestrogen states:
Perimenopausal
Persistent Anovulation
Polycystic ovaries
Oestrogen only therapy
Granulosa cell ovarian tumours – produce oestrogen

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91
Q

Endometrial Cancer - Type 1

A

80-85% endometrial cancer

  • Low grade tumours which are superficially invasive
  • Often associated with atypical endometrial hyperplasia
  • Subtypes – endometrioid, mucinous and secretory adenocarcinoma
  • Seen in younger patients
  • Associated with PTEN/KRAS mutations
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92
Q

Endometrial Cancer - Type 2

A

15-20%

  • Serous and clear cell carcinomas
  • Seen in older, post menopausal women
  • Not oestrogen dependent
  • More aggressive – higher grade and deeper invasion
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93
Q

Ovarian Epithelial Cysts

A

From the epithelial surface covering the ovary
Can be benign, bordeline or malignant

Type 1 - Less Exciting More Cancers: 
Low- grade serous
Endometriod
Mucinous
Clear Cell

Type 2:
Mostly serous

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94
Q

Serous Ovarian Cyst

A

MOST COMMON
Usually cystic and unilocular
Psammoma bodies seen

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95
Q

Mucinous Ovarian Cyst

A

Mucin secreting tumours
Kruckenburg Tumour – malignancy which
has metastasised from (GI) primary
Mucin producing signet ring cells

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96
Q

Endometrioid Ovarian Cyst

A

Co-existence with endometrioid carcinoma in uterus common
Forms tubular glands
Better prognosis than mucinous/serous

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97
Q

Clear Cell Ovarian Cyst

A

Strong asssociation with endometriosis

Abundant clear cytoplasm

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98
Q

Ovarian Germ Cell Tumours

A

Choriocarcinoma
Teratoma - Mature, Immature
Dysgerminoma
Yolk-Sac Tumours

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99
Q

Choriocarcinoma

A

Malignant

Secretes hCG

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100
Q

Teratoma - Mature

A

Benign, solid/cystic

Mature adult tissue types - teeth/hair common

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101
Q

Teratoma - Immature

A

Malignant, usually solid
Contains immature, embryonal tissue
Secretes AFP

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102
Q

Dysgerminoma

A

No differentiation

Secretes hCG

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103
Q

Yolk-Sac Tumours

A

Most common in children and young women

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104
Q

Ovarian Sex Cord Stromal Tumours

A

Granulosa/Thecal Cell Tumours
Fibromas
Sertoli-Leydig Tumour

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105
Q

Granulosa/Thecal Cell Tumours

A

Produce Oestrogen

Thecomas - benign
Granulosa cell tumours – can recur/progress

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106
Q

Ovarian Fibromas

A

From ovarian stroma
No hormone production
Meig’s Syndrome – ascites, pleural effusion

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107
Q

Sertoli-Leydig Tumour

A

Secretes Androgens

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108
Q

Brain Tumours - Symptoms, Investigations, Management

A 
Symptoms:
Headache
Seizures
Visual disturbances
Focal neurology – weakness and sensory changes

Investigations:
CT/MRI head
Stereotactic or intraoperative biopsy
Genetic sequencing

Management:
Tumour debulking
Chemotherapy
Radiotherapy 
Palliative care
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109
Q

Tumours that metastasise to the brain

A

Mets are the most common cause of brain tumour

Melanoma, breast, lung (also large bowel and prostate)

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110
Q

Pilocytic Astrocytoma

A
  • Benign (WHO grade I)
  • Most common brain tumour in children (20% of CNS tumours <14)
  • Common in neurofibromatosis 1
  • Usually cerebellar
  • MRI: well circumscribed, cystic, enhancing lesion
  • Cystic and piloid ‘hairy’ cell, often Rosenthal fibres & granular bodies
  • Slow growing - low mitotic activity
  • BRAF mutation (KIAA1549-BRAF fusion) in 70% of PA (better prognosis)
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111
Q

Meningioma

A
  • 25-30% primary tumours - 2nd after gliomas
  • Common in elderly (rare in pts <40)
  • Attached to meninges
  • Calcified with psammoma bodies
  • MRI: extraxial, isodense, contrast-enhancing

80% Grade I: benign, recurrence <25%
20% Grade II: atypical, recurrence 25-50%
1% Grade III: malignant, recurrence 50-90%

May get psuedoinvasion along the Virchows-Robin Space

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112
Q

Glioblastoma

A
  • Malignant
  • Lethal tumour with dismal prognosis (WHO grade 4)
  • Most pts >50
  • Spontaneous (90%) or transforms from more indolent astrocytomas (10%)
  • MRI - heterogeneous, enhancing post-contrast
  • Multiple mitotic figures, microvascular proliferation and necrosis
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113
Q

Medulloblastoma

A
  • WHO grade 4
  • Most common malignant brain tumour in children (but still rare)
  • Usually cerebellar
  • Homer-Wright Rosettes
  • EMBRYONAL TUMOUR: originates from neuroepithelial precursors of the cerebellum/dorsal brainstem
  • Outcome considerably improved with chemo/radiotherapy

Small round blue cell tumour: high grade, poorly differentiated

Molecular classification: WNT-activated, SHH-activated, group 3, group 4

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114
Q

Anterior Ischaemic Stroke

A

Supplies:

  • Superior motor and sensory cortices
  • Frontal lobe

Stroke deficits:

  • Contralateral paralysis and sensory loss of leg and foot
  • Frontal lobe symptoms e.g. personality change and urinary incontinence
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115
Q

Middle Ischaemic Stroke

A

Supplies:

  • Bulk of cerebral hemispheres
  • Broca’s area (speech production)
  • Wernicke’s area (speech comprehension)

Stroke deficits:

  • Contralateral paralysis and sensory loss of face and arm
  • Aphasia
  • Facial droop
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116
Q

Posterior Ischaemic Stroke

A

Supplies:
- Occipital lobe, visual cortices and cerebellum

Stroke deficits:

  • Contralateral visual loss
  • Faceblindness
  • Ataxia if cerebellar
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117
Q

Extradural Haemorrhage

A

Rupture of arteries between dura and skull

Common after pterion trauma –> middle meningeal artery rupture

Convex white region on CT

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118
Q

Subdural Haemorrhage

A

Rupture of veins between dura and arachnoid mater

Common after falls in the elderly

White, crescent shaped region on CT

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119
Q

Subarachnoid Haemorrhage

A

Spontaneous rupture of berry aneurysms in the subarachnoid space (present in 1% of population)

80 % - internal carotid artery bifurcation, 20% occur within the vertebro-basilar circulation

30% of patients have multiple aneurysms

Greatest risk of rupture when 6-10mm diameter

Present with sudden onset of severe headache - thunderclap, vomiting, loss of consciousness

Endovascular treatments - coils

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120
Q

Alzheimer’s

A

Loss of neurons, synapses and glia result from deposition of amyloid-β and tau in Alzheimer’s

Pathology starts in the temporal lobe (hippocampus) and progressively spreads to the occipital lobe and throughout the cortices

Key histopathology: amyloid-β plaques and tau neurofibrillary tangles (also Cerebral amyloid angiopathy (CAA, thickening of the vessels) and neuronal loss (cerebral atrophy))

Staging of tau pathology- Braak stages

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121
Q

Parkinson’s

A

Loss of dopaminergic neurons in the substantia nigra impairs basal ganglia function in Parkinson’s

Pathology starts in the brainstem and spreads upwards into the cortices

Key histopathology: Lewy bodies (neuronal inclusions of α-Synuclein)

Staging - Braak staging

Key differentials to rule out on autopsy:
Multiple system atrophy
Progressive supranuclear palsy
Corticobasal degeneration

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122
Q

Frontotemporal Dementia

A

Selective atrophy of the frontal lobes –> personality changes, and the temporal lobes –> impaired memory

2 main subtypes – Pick’s disease and TDP-43 positive FTD (linked with ALS), also TDP-17 syndromes

Can differentiate the different tauopathies based on their molecular characteristics - 3R/4R (microtubule binding sites)

Key histopathology: Pick bodies (tau) or TDP-43 inclusions

Pick's disease:
Fronto-temporal atrophy
Marked gliosis and neuronal loss
Balloon neurons
Tau positive Pick bodies
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123
Q

COPD

A

Obstructive lung disorders characterised by decreased exercise tolerance, infective exacerbations and mucus plugging

  • 2 components – bronchitis and emphysema
  • Neutrophilic infiltration into airways
  • Loss of alveoli, elastic fibres and lung parenchyma
  • COPD in a non-smoker + cirrhosis = alpha-1 antitrypsin deficiency
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124
Q

Asthma

A

Obstructive lung disorders characterised by decreased exercise tolerance, infective exacerbations and mucus plugging

Airway remodelling with smooth muscle hypertrophy, goblet cell hyperplasia and an eosinophilia in severe cases.

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125
Q

Cystic Fibrosis

A
  • Autosomal recessive mutation in CFTR gene on chromosome 7
  • Viscous mucus secretion leads to recurrent lung infections, pancreatic insufficiency and malabsorption
  • Mucus clogged airways and inflammatory cell infiltration
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126
Q

Bronchiectasis

A
  • Pathological airway dilation secondary to recurrent infections
  • Cystic fibrosis is a major risk factor
  • Dilated, fibrotic airways with mucus plugging
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127
Q

Adenocarcinoma of the Lung

A
  • Non-small cell lung cancer
  • Most common lung cancer in non-smokers
  • Tend to be located peripherally compared to other lung tumours –> originate from type II pneumocytes in alveolar walls
  • Atypical adenomatous hyperplasia eventually becomes invasive
  • Mutations in KRAS and EGFR
  • Extrathoracic metastases common and early

Histology:

  • Histology shows evidence of glandular differentiation
  • Papillae
  • Mucin
  • Variety patterns relate underlying molecular abnormalities and prognosis
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128
Q

Squamous Cell Carcinoma of the Lung

A
  • Non-small cell lung cancer
  • Lung cancer with the strongest correlation with smoking
  • Originate from the bronchi (also increasing number of peripheral)
  • Mutations in p53 are the most common
  • Local spread, metastasise late
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129
Q

Lung Cancer - Paraneoplastic Syndromes

A

SIADH - Small cell lung cancer secretes ectopic ADH –> euvolemic hyponatraemia

CUSHINGS - Small cell lung cancer secretes ectopic ACTH –> Cushing’s syndrome (does not suppress with high dose dexamethasone)

LAMBERT-EATON - Small cell lung cancer secretes anti-VGCC abs –> acts on presynaptic membrane –> muscle fatiguability that improves with activity
(unlike myasthenia gravis)

HYPERCALCAEMIA OF MALIGNANCY - Squamous cell lung cancer secretes PTHrp –> hypercalcaemia and hypophosphatemia (& suppression of endogenous PTH)

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130
Q

Small Cell Lung Cancer

A
  • Thought to arise from bronchial neuroendocrine cells
  • Mutations in p53 and retinoblastoma protein (RB1)
  • Very strong smoking association
  • Highly malignant and has a high rate of metastasis - 80% present with advanced disease
  • Commonly spreads to brain, ribs and spinal column
  • Very chen-sensitive but abysmal prognosis
  • ‘Oat cells’ on microscopy
  • Small, poorly differentiated cells on histology
  • High incidence of paraneoplastic syndromes
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131
Q

Atheroma Formation

A
  • Endothelial injury
  • Cholesterol deposition and oxidation
  • Macrophage recruitment
  • Phagocytosis of lipids –> foam cell formation
  • Foam cell deposition and fibrous cap formation
  • Fibrous cap thinning and rupture
  • Thrombous formation and artery occlusion
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132
Q

Myocardial Ischaemia - Histopathology

A
  • First 24 hours - loss of cell nuclei and necrosis
  • 1-4 days: neutrophilic infiltration
  • 5-10 days: macrophages recruit debris
  • Weeks-months: granulation tissue and fibrosis
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133
Q

Cardiac Post-Ischaemic Complications

A

VENTRICULAR RUPTURE

  • Damaged ventricle splits open following myocardial infarction and a cardiac tamponade forms
  • Chest pain, signs of shock and haemodynamic instability quickly develop

DRESSLER’S SYNDROME

  • Myocardial infarction followed by pericarditis
  • Release of myocardial proteins during cell necrosis triggers an autoimmune reaction
  • Pan-ST elevation on ECG
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134
Q

Infective Endocarditis

A

Acute or subacute bacterial infection of the inner lining of the heart (endocardium)

RFs:
IVDU - Staph aureus or epidermidis
Dental surgery- Strep viridans
Immunocompromise e.g. alcohol or HIV

Strep viridans infections present subacutely (>2 weeks) with splenomegaly and clubbing

Vegetations eats into heart valves leading to regurgitation

Any new murmur + fever must be investigated with a transthoracic echocardiogram

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135
Q

Stenosis and Regurgitation

A

All 4 heart valves can become stenosed or can regurgitate following rheumatic fever

STENOSIS:

  • Most common valve affected is the aortic valve
  • Advancing age is the single biggest risk factor –> calcification of the valve
  • Other risk factors include rheumatic fever and a bicuspid valve
  • Aortic stenosis presents with chest pain, syncope and an ejection systolic murmur

REGURGITATION:

  • Most common valves affected are mitral and aortic
  • Infective endocarditis is a massive risk factor –> vegetations eat into valve
  • Connective tissue disease e.g. Marfan’s and Ehlers-Danlos can also predispose
  • Mitral regurgitation presents with shortness of breath, syncope and a pansystolic murmur
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136
Q

Cardiomyopathies

A

Hypertrophic - thick walls
Dilated - thin walls
Restrictive - stiff walls (most common cause is amyloidosis)

Causes:
Genetic
Chemo
Acromegaly
Haemochromatosis
Amyloidosis
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137
Q

Neutrophil

A

Appearance: Multilobed nuclei with granules

Significance: Acute inflammation

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138
Q

Lymphocyte/plasma cell

A

Appearance: Little cytoplasm with big nucleus

Significance: Chronic inflammation, lymphoma

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139
Q

Eosinophil

A

Appearance: Bi-lobed nucleus with red granules

Significance: Allergic, parasites, Hodgkin lymphoma

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140
Q

Mast Cell

A

Appearance: Large and heavily granular

Significance: Allergy (e.g. urticaria)

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141
Q

Macrophage

A

Appearance: Large with lots of cytoplasm

Significance: Late acute inflammation, chronic inflammation (inc granuloma)

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142
Q

Squamous Cell Carcinoma- General

A

Histological features:
Keratin production
Intercellular bridges

Sites of origin: Lung, skin, oesophagus, head&neck, anus, cervix, vagina

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143
Q

Adenocarcinoma - General

A

Histological features:
Mucin production - stain turns mucin blue
Glands

Sites: Lung, breast, colon, pancreas, cervix, stomach

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144
Q

Transitional Cell Carcinoma - General

A

Sites: bladder, ureter, urethra

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145
Q

Sarcoma - General

A

Histological features:
Arises from mesenchymal cell
Sites: Bone, cartilage, fat, vascular

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146
Q

Stains - Histochemical vs Immunohistochemical

A

Histochemical:

  • Chemical reaction between stain and a specific component of the tissue
  • e.g. H&E - everyday stain, Prussian Blue - Iron (haemochromatosis), Congo Red - Amyloid

Immunohistochemical:

  • Antibodies bind to specific antigen in the tissue –> immunofluorescence/immunoperoxidase
  • e.g. cytokeratin ab - epithelial cells, CD45 - lymphoid marker
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147
Q

Stellate cells in Liver

A

Store vitamin A

Become activated to my-fibroblasts (lay down collagen)

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148
Q

Cirrhosis - Micronodular vs Macronodular

A

Micronodular tends to be associated with alcoholism.

Macronodular tends to be associated with viral infections

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149
Q

Haemosiderosis

A

Caused by iron overload

Accumulation of iron in macrophages
Usually occurs after blood transfusions

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150
Q

Autoimmune hepatitis

A
  • Very active form of hepatitis with lots of plasma cells
  • Anti-smooth muscle antibodies (ASMA)
  • Responds to steroids
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151
Q

Alpha-1 Antitrypsin Deficiency

A

Failure to secrete alpha-1 antitrypsin

Misfolded protein cannot exit hepatocytes leading to accumulation
Leads to emphysema and cirrhosis

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152
Q

Causes of hepatic granulomas

A

PBC
Drugs
TB
Sarcoidosis

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153
Q

How does alcohol cause pancreatitis?

A

Alcohol affects the protein content of the pancreatic duct fluid which predisposes to obstruction as the thickened fluid condenses out

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154
Q

Calcium in pancreatitis

A

HypERcalcaemia can cause acute pancreatitis but acute pancreatitis can cause hypOcalcaemia

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155
Q

Type of gland in the oesophagus

A

Submucosal

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156
Q

Pseudomembranous Colitis

A

Px: explosive watery diarrhoea, usually after a course of abx

Ix: C. diff stool toxin assay

Rx: metronidazole or vancomycin

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157
Q

Ischaemic Colitis

A

Definition: inflammation and injury of the large intestine caused by an inadequate blood supply

Watershed: area between the supply of the SMA and IMA –> splenic flexure

Causes:
Arterial (e.g. thrombus)
Venous (e.g. hypercoagulable)
Small vessel disease (e.g. DM)
Low flow (e.g. shock)
Obstruction (e.g. hernia)
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158
Q

Familial Adenomatous Polyposis

A

AD
Mutation of APC tumour suppressor gene
Large numbers of polyps, pretty much everyone gets cancer

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159
Q

Gardner Syndrome

A

Same features as FAP

Extra-intestinal manifestations:
Osteomas
Desmoid tumours - connective tissue tumour
Dental caries 
Supernumerary teeth
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160
Q

Hereditary Non-Polyposis Colorectal Cancer

A

AD
Mutation in DNA mismatch repair genes
High risk of cancer, no polyps

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161
Q

Cervical Cancer

A

Risk Factors

  • HPV 16 and 18
  • Multiple sexual partners
  • Smoking
  • Immunosuppression

Tumourigenesis
HPV 16 and 18 encode two proteins that inactivate tumour suppressor genes. E6 - p53, and E7 - retinoblastoma.

Transformation zone is most common site.

162
Q

CIN and CGIN

A

Cervical Intraepithelial Neoplasia (CIN)
Dysplastic changes within the epithelium with an intact basement membrane.
Progress to SCC

CGIN: cervical glandular intraepithelial neoplasia progresses to adenocarcinoma (20%)

163
Q

Polycystic Kidney Disease

A
  • Autosomal dominant
  • Flank pain and haematuria + recurrent pyelonephritis and hypertension
  • Associated with liver cysts + berry aneurysms in the Circle of Willis –> subarachnoid haemorrhage
  • End-stage renal failure by age 40-60
  • PKD1, PDK2 -genes
164
Q

Alport’s Syndrome

A
  • X-linked deficiency of type 4 collagen
  • Sensorineural hearing loss from an early age with macroscopic haematuria
  • End-stage kidney disease and cataracts develop as the disease progresses
165
Q

AKI - Causes

A 
PRE-RENAL:
Hypoperfusion
- Dehydration
- Shock
- Renal artery stenosis
RENAL:
Interstial or tubular damage 
- NSAIDs
- Gentamycin
- ACE inhibitors
- Contrast
POST-RENAL:
Outflow obstruction
- Stones
- Tumours
- BPH
166
Q

AKI - Clinical Picture

A

Hyperkalaemia
Uraemia
Metabolic acidosis

167
Q

CKD - Clinical Picture

A 
Normocytic anaemia (decreased EPO)
Vitamin D deficiency (decreased 1aOHase)

Association with ischaemic heart disease- Hypertension, hyperlipidaemia, calcification of blood vessels

Association with calcium and phosphate metabolic derangement- Hyperparathyroidism, osteomalacia, osteoporosis

168
Q

IgA Nephropathy

A

Up to 2 days post-URTI

Presents with abdominal pain and haematuria

Associated with IgA vasculitis (Henoch-Schonlein purpura)

IgA predominant mesangial immune complex deposition

30% develop end stage renal failure

Oxford classification (MEST-C)

169
Q

Post-Streptococcal Glomerulonephritis

A

Up to 2 weeks post-strep throat

Associated with Streptococcus pyogenes

Presents with haematuria and oliguria - “coca cola urine”

170
Q

Goodpasture’s

A

Autoimmune crescentic glomerulonephritis

  • Antibody production against type 4 collagen
  • Anti-glomerular basement membrane abs detectable with serology
  • Linear deposition of IgG demonstrable on the glomerular basement membrane
  • Haemoptysis and progressive renal failure
  • Post-renal transplant in Alport’s
171
Q

Wegner’s/Churg-Strauss

A

Pauci-immune crescentic glomerulonephritis - trigger neutrophil activation and glomerular necrosis

Vasculitis

Wegner’s:

  • granulomatosis with polyangiitis
  • c-ANCA
  • ENT problems - (‘saddle nose’) + renal failure

Churg-Strauss:

  • eosinophilic granulomatosis with polyangiitis
  • p-ANCA
  • Atopic background + renal failure
172
Q

Nephrotic Syndrome- Criteria and Complications

A

4 Key Criteria:

  • Proteinuria >3.5g per day
  • Hypoalbuminemia <2.5g/dl
  • Oedema
  • Hyperlipidaemia

Complications:

  • Loss of anti-thrombin III –> thrombophilia
  • Loss of immunoglobulins –> infections
  • Pulmonary oedema
173
Q

Minimal Change Glomerulonephritis

A
  • Primary glomerular disease, non-immune complex mediated
  • Most common cause of nephrotic syndrome in children
  • Normal histology on light microscopy
  • Effacement of podocyte foot processes on electron microscopy
  • Need biopsy to confirm
  • General responds to immunosuppression
174
Q

Focal Segmental Glomerulonephritis/Glomerulosclerosis

A
  • Primary glomerular disease, non-immune complex mediated
  • Most common cause of nephrotic syndrome in adults
  • Visible sclerosis of podocytes and bowman’s capsule
  • Associated with chronic glomerulonephritis e.g. SLE or vasculitis
  • Need biopsy to confirm
175
Q

Membranous Glomerulonephritis

A
  • Primary renal disease, immune complex mediated
  • Common cause of nephrotic syndrome in adults
  • Common as a
    paraneoplastic or co-morbid phenomenon
  • Associated with immune deposits on outside of glomerular basement membrane (subepithelial)
  • Production of anti-phospholipase A2 type M receptor (PLA2R) antibodies against podocytes in 75% of cases
  • Need biopsy to confirm
176
Q

Diabetic Nephropathy

A
  • 30-40% of diabetics
  • High glucose levels thought to be directly injurious
  • Typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome- Mesangial thickening followed by Kimmelstiel-Wilson nodule formation
  • Albumin: creatinine ratio is measured to monitor the severity of nephropathy
  • All diabetic patients should receive an ACEi (nephroprotective)

Nodular Glomerulosclerosis
Stage 1 – Thickening of basement membrane on EM
Stage 2 – Increase in mesangial matrix, without nodules
Stage 3 – Nodular lesions / Kimmelstiel-Wilson
Stage 4 – Advanced glomerulosclerosis

177
Q

Lupus Nephritis

A
  • Renal disease in SLE progresses from glomerulonephritis to nephrotic syndrome
  • ‘Wire-loop glomeruli’ indicate antibody complex deposition
  • A high anti-dsDNA titre and low complement indicate an active lupus flare
  • ISM/RPS classification
178
Q

Bladder Cancer - Transitional Cell Carcinoma

A
  • The ureters and bladder are lined by transitional epithelium –> most common type of bladder cancer
  • Associated strongly with smoking and exposure to chemicals e.g. dyes–>always ask about occupation
  • Macroscopic haematuria –> all haematuria is malignancy until proven otherwise
  • Diagnosis is with cystoscopy and tumour excision or cystectomy
179
Q

Bladder Cancer - Squamous Cell Carcinoma

A
  • Much rarer subtype of bladder cancer
  • Develops at junction between bladder and urethra
  • Strongly associated with chronic parasitic worm infections e.g. schistosomiasis
  • Much more common in developing countries without access to anti-parasite medication
180
Q

Bengin Prostatic Hyperplasia

A

Concentric hyperplasia of the prostate secondary to prolonged testosterone exposure. Stromal proliferation.

Storage sx- frequency, nocturne, urgency
Voiding sx - hesitancy, poor stream, incomplete emptying

Rx:

  • Alpha blockers e.g. tamsulosin
  • 5-alpha reductase inhibitors e.g. finasteride
  • Transurethral Resection of the Prostate (TURP)
181
Q

Prostate Cancer

A
  • Total incidence - 1:8, Afro-Caribbean males – 1:4
  • Similar storage and voiding symptoms as BPH
  • Red Flags: haematuria and back pain – don’t miss Cauda Equina!

Vast majority are adenocarcinomas – most peripheral glands proliferate first

Arises from Prostatic Intraepithelial Neoplasia
Mutations in PTEN, AMACR, GST-pi, p27 and more…
Gleason grading system – score up to 10. The higher the score, the greater the malignancy and the worse the prognosis.

182
Q

Varicocele

A
  • Dilated scrotal venous plexus
  • Heaviness in testicle and soft lump
  • ‘Bag of worms’ on palpation and scrotal ultrasound to confirm
183
Q

Hydrocele

A
  • Smooth, symmetrical mass secondary to fluid accumulation
  • Due to intact embryological tract or failure of fluid resorption
  • Transilluminates
184
Q

Testicular Tumours

A

Vast majority are germ cell tumours (95%) – arising from spermatocyte precursors. Amplification of i12p.

Typically present in men aged 20-45

RFs: undescended testes, low birth weight/SGA

Symptoms include a painless, craggy, fixed mass on the testicle and back pain if metastasised

Seminomas are the most common germ cell tumour (also embryonal carcinoma, post pubertal teratoma, yolk sac tumour, choriocarcinoma)

Non-germ cell tumours include Lymphoma (highly aggressive, older men), Sertoli and Leydig cell malignancies (usually benign)

Investigation and treatment is with ultrasound, biopsy and orchidectomy. Germ cell tumours highly sensitive to platinum-based chemo.

Germ cell - 98% 5YSR

185
Q

Prussian Blue Stain

A

Iron - haemachromatosis

186
Q

Congo red stain

A

Amyloid

Apple green birefringence under polarised light

187
Q

.

A

.

188
Q

Fontana stain

A

Melanin

189
Q

Post-Mortem - Approach

A

Inspection and Evisceration

Do an examination of the body first:

  • Hands – clubbing, scars, splinter haemorrhages
  • Scar from median sternotomy – measure it and document (indicates CABG)
  • Look at the legs for vein harvest scar – measure and document
  • Hip replacement
  • Any operations on neck, any cyanosis on face

Check name tag and identification of patient

Make an incision from Adams apple to pubis to examine organs –> must remove chest plate on top of heart and lungs

Cut through ribs (pericardium adheres to chest plate)

Cut through trachea and great vessels in neck –> Remove heart and lungs in one block. Detach back of aorta.

Detach large intestine

Take out liver, spleen, pancreas, small bowel in another block

Kidneys, bladder, ureters, prostate come out (also look at vessels for ruptured aneurysms)

Genitals (&hernia)
Organs go back in body in plastic bag. All sown up with suture material and can be buried and cremated. Can take swabs or samples of collections to the lab.

190
Q

Normal weight of male heart

A

350g

191
Q

Colour of normal lung on fixation

A

Black

192
Q

Ischamic bowel appearance (on Post-mortem)

A

black and necrotic

193
Q

Infarcted kidney appearance (on Post-mortem)

A

Wedge shaped white spaces

194
Q

Kidney cortex with HTN appearance (on Post-mortem)

A

Thinning cortex

195
Q

Medical certificate cause of death sections

A

Section 1a, b, c – deals with cause of death:
A: immediate
B: led to A
C: led to B

Section 2:
Contributory factor
Did not directly cause death

Example:

1a) MI
1b) coronary artery atheroma
2) Diabetes, hypertension

196
Q

Tumours of the CNS

A

Brain and spinal cord

197
Q

Tumours of the PNS

A

Any organ

Intracranial: vestibular schwannoma (acoustic neuroma)

198
Q

Extra-axial CNS Tumours

A

Tumours of the “coverings” - bone, cranial soft tissue, meninges, nerves, metastatic deposits

Astrocytes - astrocytoma
Oligodendrocytes - oligodendroglioma
Ependyma – ependymoma
Neurons - neurocytoma
Embryonal cells – medulloblastoma
199
Q

Intra-Axial CNS tumours

A

Tumours of the parenchyma

Derived from the normal cell populations of the CNS - glia, neurons, vessels, connective tissue..

Derived from other cells types - metastases, lymphomas, germ cell tumours

Meningothelial cells – meningioma
Schwann cells – schwannoma

200
Q

Aetiology of CNS Tumours

A

LARGELY UNKNOWN

Radiation to head and neck: meningiomas, rarely gliomas
Neurocarcinogens?
Genetic predisposition <5% of primary brain tumours- Familiarity, Familial syndromes

201
Q

Genetic Predisposition to CNS Tumours

A

NF1: NEUROFIBROMA, PILOCYTIC ASTROCYTOMA

NF2: SCHWANNOMA, MENINGIOMA

TS: HAMARTOMAS, SEGA

VHL: HEMANGIOBLASTOMA

(neurofibromatosis, tubers sclerosis, von hippel lindau)

202
Q

WHO Classification of CNS Tumours

A

Tumour type: putative cell of origin

Tumour grade: tumour differentiation

A subset of tumours are defined by diagnostic mutations: genetic profile

INTEGRATED HISTOLOGICAL AND MOLECULAR DIAGNOSIS

No staging (like TNM)

203
Q

WHO CNS Tumour Grading

A 
4  tier system:
Grade I - benign - long-term survival 
Grade II – more than 5 yrs 
Grade III – less than 5 yrs 
Grade IV – less than 1yr

Grade guides treatment!

Some tumour types have only one possible grade, some have 2 or 3, and some have all 4

204
Q

Glial Tumours - Genetics

A

DIFFUSE GLIOMAS
IDH1/2 mutations
Positive prognostic factor

CIRCUMSCRIBED GLIOMAS
MAPK pathway mutations (BRAF)

205
Q

Mitotic Activity and Grading of CNS Tumours

A 
Mitotic activity is crucial: determines grade
mitoses / 10HPF (0.16mm2):
<4 = grade I
4-20 = grade II
> 20 = grade III
206
Q

Diffuse Astrocytoma

A
  • WHO grade 2
  • Patients usually 20-40 years
  • Cerebral hemispheres most common site
  • MRI: T1 hypointense, T2 hyperintense, non-enhancing lesion. Low choline / creatinine ratio at MRSpec.
  • Low to moderate cellularity. Mitotic activity is negligible or absent. Vascular proliferation and necrosis are absent
  • Mutation of IDH1/2: in >80% of cases
  • Progression to higher grade is the rule: astrocytomas (grade II-III) become eventually glioblastoma (grade IV)
207
Q

Oligodendrioma

A
  • WHO grade 2-3
  • 5% of all primary brain tumours
  • Patients usually 20-40 years
  • Presents with long history of neurological signs – seizure
  • MRI: no or patchy contrast enhancement; MRI and MRSpec are not predictive of transformation
  • Round cells with clear cytoplasm (“fried eggs”)
  • Mutation of IDH1/2 + codeletion 1p/19q: almost 100%

Better prognosis than astrocytomas
Slow growth – resection is important
Better response to chemo and radiotherapy

208
Q

Cerebral Oedema

A

Excess accumulation of fluid in the brain parenchyma

Two main types:
Vasogenic – disruption of the blood brain barrier
Cytotoxic – secondary to cellular injury e.g. hypoxia/ischaemia

Result is raised intracranial pressure

CT - area of lucency or hypodense or hypoattenuation

209
Q

Hydrocephalus

A

Increased volume of CSF in the ventricular system

Non-communicating involves obstruction of flow of CSF

Communicating involves no obstruction but problems with reabsorption of CSF into venous sinuses

210
Q

Raised ICP

A
  • ICP is measured in mmHg and, at rest, is normally 7–15mmHg for a supine adult
  • Enclosed bony box- pressure can increase because of localised (space occupying) lesions, oedema or both
  • Increased pressure forces brain against unyielding bony wall of skull and inflexible dural folds
  • This results in herniation of brain structures where space is available –> subfalcine, transtentorial, tonsillar herniation
211
Q

Stroke Definition

A

Rapidly developing clinical symptoms and/or signs of focal, and at times global loss of cerebral function, with symptoms lasting more than 24 hours, with no apparent cause other than that of vascular origin

Includes stroke due to: cerebral infarction, primary intracerebral haemorrhage, intraventricular haemorrhage and most cases of subarachnoid haemorrhage

Excludes: subdural haemorrhage, epidural haemorrhage, intracerebral haemorrhage (ICH) or infarction caused by infection or tumour

212
Q

TIA

A

TIA is a warning stroke that should be taken very seriously
TIA is caused by a clot; the blockage is temporary
Most TIAs last less than five minutes; the average is about a minute. Unlike a stroke, when a TIA is over, there is usually no permanent injury to the brain
1/3 of those with TIA get significant infarct within 5 years
REMEMBER: TIA important predictor of future infarct

213
Q

Non-Traumatic Intra-Parenchymal Haemorrhage

A
  • Haemorrhage into the substance of the brain - rupture of a small intraparenchymal vessel
  • Most common in basal ganglia
  • Hypertension in > 50% of bleeds
  • Presentation with severe headache, vomiting, rapid loss of consciousness, focal neurological signs
214
Q

Cerebral Arteriovenous Malformations

A
  • Occur anywhere in the CNS
  • Become symptomatic between 2nd and 5th decade (mean age 31.2 years)
  • Present with haemorrhage, seizures, headache, focal neurological deficits
  • High pressure – MASSIVE BLEEDING!!!
  • Seen on angiography
  • Morbidity after rupture 53-81% - high in eloquent areas
  • Mortality 10-17.6%
  • Treatment: surgery, embolization, radiosurgery

Blood passes quickly from artery to vein, bypassing the capillary network.

215
Q

Cavernous Angioma

A
  • “Well-defined malformative lesion composed of closely packed vessels with no parenchyma interposed between vascular spaces”
  • Can be found anywhere in the CNS, usually symptomatic after age 50
  • Pathogenesis unknown
  • Present with headache, seizures, focal deficits, haemorrhage
  • Low pressure – recurrent bleeds
  • Treatment: surgery
  • Target sign on T2 MRI
216
Q

Ischaemic Stroke - General

A
  • 70-80% stroke
  • Worse atherosclerosis in larger vessels
  • Often near carotid bifurcation or in basilar artery
  • Other cause - emboli (intracerebral arteries)
  • Usually from heart or atherosclerotic plaques
  • Embolic occlusion usually in middle cerebral artery branches
217
Q

Stroke - Differentiating Infarct vs Haemorrhage

A 
Infarct:
Tissue necrosis (stains)
Rarely haemorrhagic
Permanent damage in the affected area
No recovery
Haemorrhage:
Bleeding
Dissection of parenchyma
Fewer macrophages
Limited tissue damage (periphery)
Partial recovery
218
Q

Traumatic Brain Injury - Epidemiology

A

Trauma single largest cause of death in people under 45

9 deaths from head injury per 100,000

Account for 25% of all trauma deaths

High morbidity:
19% vegetative or severely disabled
31% good recovery

219
Q

TBI - General

A

Non-missile vs missle (missle = penetrating e.g. gun shot –> rare in this country)
Non-missile by far most common –> most common cause of this is acceleration/deceleration in RTAs, falls and assaults

If it’s rotational - tends to focus all of the damage on midline structures

Result can be focal (fractures, contusions) or diffuse

220
Q

TBI - Fractures

A
  • Fissure fractures often extend into base of skull
  • May pass through middle ear or anterior cranial fossa - may get CSF leakage –> Otorrhea or rhinorrhea
  • Infection risk

Battle sign and periorbital haemorrhages (racoon eyes)

221
Q

TBI - Contusions

A
  • Brain in collision with skull
  • Surface “bruising”
  • If pia mater torn then becomes laceration
  • Some regions for susceptible than others due to bone on brain action - Lateral surfaces of hemispheres, inferior surfaces of frontal and temporal lobes
  • Coup or contrecoup injuries - RTA, rapid deceleration –> brain hits front of the skull, then there’s a rebound and it hits the back of the skull
222
Q

TBI - Diffuse Axonal Injury

A
  • Occurs at moment of injury (but also secondary phase where axons become more susceptible to damage later on)
  • Shear & tensile forces affecting axons
  • Commonest cause of coma (when no bleed)
  • Midline structures particularly affected e.g. corpus callosum, rostral brainstem and septum pellucidum

Research that there may be evidence of cognitive decline a while after TBI

223
Q

Prion Diseases - General

A
  • Rapidly progressive neurodegenerative disease – death within about a year
  • A series of diseases with common molecular pathology
  • Transmissible factor
  • No DNA or RNA involved
  • Prion (proteinaceous infectious only) - Purely protein – protein interaction which causes the problem
224
Q

Kuru

A

“The shake”, motor/brain disease in Papua New Ginuea.

Caused/perpetated by endocanabolism – tradition in the tribe to eat your deceased relatives. Largely ended in the 70s but has a long incubation period – still some new cases.

225
Q

Human Prion Diseases

A

Creutzfeldt-Jakob disease
Gerstmann-Straüssler-Sheinker syndrome (GSSS) - genetic
Kuru
Fatal familial insomnia - genetic (north america and italy), massive psychiatric consequences

226
Q

Prion Diseases - Histopathological Changes

A

Spongiform encephalopathies – brain full of holes on post-mortum due to vacuolization – holes formed in the tissue due to the disease process.

Prion proteins - cause plaques – lumps of prion protein sitting in brain substance.

Transmission entirely dependent on interaction with host protein. Abnormal protein interacts with normal host protein and converts it to pathological protein.
Normal prion protein unfolds from a helical structure and refolds into beta pleated sheet (same formation as amyloid). –> prion protein plaque deposits –> at some point this becomes irreversible.

227
Q

New Variant CJD (vCJD)

A
  • Sporadic neuropsychiatric disorder
  • Patients <45 yrs old
  • Cerebellar ataxia
  • Dementia
  • Longer duration than CJD
  • Linked to BSE - same protein found in mad cow disease
  • Diagnosed at autopsy since 1990
228
Q

Histopathology of Parkinsons Differentials

A

Multiple system atrophy (MSA) – a synuclein gone wrong but in the glial cells, not the neurons so much (it’s an oligodendroglial pathology)

PSP and CBD – tauopathies (different protein to parkinsons)

  • Corticobasal degeneration (CBD) – astrocytic plaques with abnormal tau protein (hyperphosphorylated)
  • Progressive Supernuclear Palsy (PSP) – tufted astrocytes and oligoinclusions (pat lantos bodies)- tau
229
Q

In the stomach, importantly, there are no

A

Goblet cells

230
Q

Another term for Barrett’s Oesophagus

A

Columnar Lined Oesophagus

231
Q

Why are the numbers of diagnoses of Barrett’s different in the US and UK?

A

US - has to be INTESTINAL metaplasia i.e. columnar AND goblet cells
UK - diagnose with just gastric metaplasia i.e. columnar, no goblet cells

232
Q

Oesophageal cancer prognosis

A

Poor

Diagnosis of pre-invasive stage important

233
Q

Oesophageal varcies risk of mortality

A

50% per bleed/rebleed

234
Q

Most common part of stomach to have H.pylori

A

Antrum

235
Q

H.pylori MALToma

A

Treat early - lymphoma will go away, if you leave it too long then it won’t

236
Q

H.pylori - The Carcinogen

A
  • Helicobacter infection is associated with an 8x increased risk of (non-cardia) gastric cancer
  • cag-A-positive H.pylori have a needle like appendage that injects toxin into intercellular junctions allowing the bacteria to attach more easily.–> most damaging form
  • This strain is associated with more chronic inflammation.
  • Treatment of the infection with antibiotics drastically reduces the risk of cancer.
237
Q

Key difference between acute and chronic ulcers

A

Chronic ulcers are fibrosed

238
Q

Diffuse Gastric Cancer Prognosis

A

Worse than intestinal. Signet ring cells tend to spread everywhere throughout the stomach.

Lauren classification –> Different aeitiologies, pathways of development and clinical implications

239
Q

Gastric Cancer Overall Survival Rate

A

15%

240
Q

Duodenal ulcers cause

A

H pylori is the cause of almost all duodenal ulcers –> get acid in the duodenum which is is completely not used to –> gastric metaplasia (if you see this, you know there has been increased acid)

Others:
Immunosuppressed 
CMV
Cryptosporidiosis 
Giardia lamblia infection
Whipple’s disease -Tropheryma whippelii.
241
Q

Chronic Pancreatitis Pathology - AXR, Macroscopically and Histopathologically

A

Pancreatic calcifications are diagnostic on AXR

Macroscopically - fat, fibrosis, strictures and duct dilatation

Histo: no acini - replaced by fibrosis. Appear to have more islets of langerhans.

242
Q

Pancreatic pseudocyst contents

A

Pancreatic enzymes
Necrotic material

Connect with pancreatic ducts
May resolve, compress adjacent structures, become infected or perforate

243
Q

IgG4 Related Disease(Autoimmune pancreatitis)

A

Characterised by large numbers of IgG4 positive plasma cells.

May involve the pancreas, bile ducts and almost any other part of the body.

Brown stain for IgG4

244
Q

Microscopic Appearance of Pancreatic Ductal Adenocarcinoma

A

Mucin secreting glands set in desmoplastic (fibrous) stroma - makes them “gritty” and hard to cut out

245
Q

Perineural invasion is very characteristic of

A

pancreatic cancer

246
Q

Duct carcinoma - venous thrombosis

A

“migratory thrombophlebitis”

Secrete mucin –> activates clotting cascade

247
Q

Cystic diseases of the kidney

A

Cysts commonly develop in patients with end stage renal disease who are on dialysis- multiple, bilateral, Cortical and Medullary

Increased risk of development of malignancy - 7% risk at 10 years. Papillary renal cell carcinoma.

248
Q

AKI - Acute Tubular Injury

A

Failure of Glomerular Filtration

Blockage of tubules by casts –> Leakage of tubules to interstitial space –> Secondary haemodynamic changes

249
Q

AKI - Acute Tubule-Interstitial Nephritis

A

Immune injury to tubules and interstitium

Can also be due to infection and drugs:
NSAIDs
Antibiotics
Diuretics
Allopurinol
Proton Pump Inhibitors

Heavy interstitial inflammatory infiltrate with tubular injury - can see eosinophils, granulomas

250
Q

Acute Glomerulonephritis

A
  • Acute inflammation of glomeruli
  • Presents with oliguria with urine casts containing erythrocytes and leucocytes
  • When sufficient to cause acute renal failure, there are almost always crescents (proliferation of cells within Bowman’s space).
251
Q

Amyloidosis - Renal

A

Deposition of extracellular proteinaceous material exhibiting β-sheet structure

Commonest forms in kidney are:

  • AA, derived from serum amyloid associated protein (SAA), an acute phase protein; patients tend to have a chronic inflammatory state
  • AL, derived from immunoglobin light chains; 80% of patients have multiple myeloma
252
Q

CKD - Causes

A 
Diabetes – 27.5%
Glomerulonephritis – 14.1%
Polycystic Kidney Disease – 7.4%
Pyelonephritis – 6.5%
Hypertension – 6.8%
Renal Vascular Disease – 5.9%
Other / Uncertain – 31.7%
253
Q

Hypertensive Nephropathy

A

Pathophysiology is not fully understood

  • Narrowing of arteries and arterioles leading to scarring and ischaemia of glomeruli
  • Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring

Shrunken kidneys with granular cortices

Histopathology may show “nephrosclerosis” –> Arteriolar hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis

254
Q

Nephroblastoma

A
  • Wilm’s tumour
  • Malignant triphasic kidney tumour of childhood - Blastema (small round blue cells), Epithelial, Stromal
  • Typically presents as an abdominal mass in children aged 2-5 years old
  • 1 in 8,000 – second most common childhood malignancy
  • 95% of cases show favourable histological features with excellent prognosis
255
Q

Non-Invasive Papillary Urothelial Carcinoma

A
  • Appear as frond-like growths
  • Divided into low grade and high grade (WHO 2004) based on nuclear atypia
  • Low grade tumours have a low risk of progression to invasive disease (<5%)
  • High grade tumours carry a higher risk of progression to invasive disease–> Unstable, carry a number of genetic aberrations including in RB and TP53
256
Q

Infiltrating Urothelial Carcinoma

A

Urothelial tumour displaying invasive behaviour

Wide range of subtypes

Treatment based on depth of invasion- Lamina propria, Muscularis propria

257
Q

Flat Urothelial Carcinoma In-Situ

A

May be invisible or appear as a reddish area

Flat urothelial lesion with unequivocal high grade features- High risk of progression

258
Q

Penile Disorders

A

Lichen Sclerosus / Balanitis Xerotica Obliterans- Inflammatory condition that causes phimosis

Zoon’s balanitis - Inflammatory condition that causes red areas

Condylomas - HPV 6 and 11 –> warts

Peyronie’s Disease - Scarring , inflammation, thickening of corpus cavernosa –> erectile issue (curvature)

Penile carcinoma - Rare, elderly men
Smoking, HPV, chronic Lichen Sclerosus are risk factors

259
Q

Urethral Diseases

A

Urethritis - N. gonorrhoeae, C. trachomatis

Prostatic Urethral Polyp - Papillary lesion in prostatic urethra

Urethral Caruncle - Common lesion at urethral meatus in women

Urethral Carcinoma - Rare, more common in women, usually squamous cell carcinoma

Malignant Melanoma - Rare

260
Q

Scrotal Diseases

A

Epidermoid Cyst- Common

Scrotal Calcinosis- Rare; may be related to old epidermoid cysts

Angiokeratomas- Benign vascular lesions

Fournier’s Gangrene -Necrotising fasciitis; mortality of 15-20%

Scrotal squamous cell carcinoma - Very rare, Historical interest; chimney sweep

261
Q

Pituitary Adenomas

A

10% of intracranial tumours that come to clinical attention
Discovered incidentally in up to 25% of autopsies
Adults. Peak 4th - 6th decade
Microadenomas if < 1cm

262
Q

Thyroid parafollicular cells secrete

A

Calcitonin –> promotes absorption of calcium by the skeletal system

263
Q

Non-toxic goitre

A
  • Common if there is impaired synthesis of thyroid hormone - most often due to iodine deficiency
  • Endemic in areas where iodine in the soil and water is low (‘Derbyshire neck’)
  • May be seen at puberty particularly in females
  • May be due to ingestion of substances that interfere with thyroid hormone synthesis e.g. brassicas
  • May be due to hereditary enzyme defects
264
Q

Niche causes of thyrotoxicosis

A

Struma ovarii (ovarian teratoma with ectopic thyroid)

Factitious thyrotoxicosis (exogenous thyroid intake)

265
Q

Clues to the nature of thyroid nodules

A
  • Solitary nodules more often neoplastic than multiple nodules
  • Solid nodules more likely to be neoplastic than cystic nodules
  • Nodules in younger patients more likely to be neoplastic than in older patients
  • Nodules in males more likely to be neoplastic than those in females
  • Nodules that do not take up radioactive iodine (cold nodules) more commonly neoplastic than ‘hot’ nodules
266
Q

Causes of acute primary adrenal sufficiency

A
  • Sudden withdrawal of corticosteroid therapy
  • Haemorrhage (neonates)
  • Sepsis with DIC (Waterhouse-Friderichson syndrome)
267
Q

Adrenocortical neoplasms

A

Adenomas:
most non-functional
May be associated with Cushing’s syndrome or Conn’s syndrome

Carcinomas:
Rare
Usually large
More commonly associated with virilizing syndrome than adenoma

268
Q

Phaeos - rule of 10s

A
  • 10% arise in association with a familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome
  • 10% are bilateral
  • 10% are malignant
  • In addition 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas)
269
Q

HIV - CMV oesophagitis

A

Macroscopically - ulceration of the oesophagus

Coin-like nuclear inclusion (CMV inclusion) in epithelial cells. IHC for CMV stains brown.

270
Q

Kaposi Sarcoma

A
  • The dermis is expanded by a solid tumour.
  • Fascicles of relatively monomorphic spindled cells, with slit-like vascular channels containing erythrocytes.
  • The nuclei of the tumour cells demonstrate immunoreactivity for HHV-8.
271
Q

CNS lymphoma in HIV

A

Lymphoma may show fewer lymphocytes and the person is immunosuppressed and the nature of that is having fewer lymphocytes

272
Q

Mycobacteria

A

Caeseating granulomas

Stain +ve for acid-fast bacilli

273
Q

Sarcoid

A

Non-caseating granulomas

Diagnosis of exclusion

274
Q

IgG4 related disease

A
  • Inflammation dominated by IgG4 antibody producing plasma cells
  • Fibrosis, obliteration of veins

Plasma cell rich, inflammatory infiltrate
Immunohistochemistry for IgG4

  • Salivary and lacrimal glands: Mikulicz syndrome
  • Thyroid: Riedel thyroiditis
  • Peritoneum: Retroperitoneal fibrosis
  • Liver: Biliary obstruction
  • Pancreas: Autoimmune pancreatitis
  • Mass lesions: Inflammatory pseudotumour
275
Q

Amyloidosis

A
  • Deposition of an abnormal proteinaceous substance in non branching fibrils, 7.5-10nm diameter
  • Always contains P component
  • Beta-pleated sheet structure
  • A variety of proteins can take on this conformation
    Resistant to enzymic degradation

AA - derived from serum amyloid A e.g. Crohn’s Disease, Rheumatoid arthritis
AL - derived from light chains e.g. multiple myeloma, B Cell lymphoma

Another classification:

  • Transthyretin e.g. mutation
  • Beta2-macroglobulin – peritoneal dialysis
  • Abeta2 protein - Alzheimer’s
  • Insulin, calcitonin – endocrine tumours
276
Q

Amyloid - Clinical Presentations

A 
Proteinuria, renal failure
Restrictive cardiomyopathy, arrhythmias
Autonomic neuropathy
Carpal tunnel syndrome
Macroglossia
Bleeding on injury
Also deposited in blood vessels, endocrine organs, liver, spleen
277
Q

Composition of bone

A

65% inorganic salts - Ca and PO4

35% organic - 30-40% collagen (Type 1 mostly with some type V) 10-20% water and ~5% non-collagenous protein & carbohydrate.

I know the percentages don’t add up but just know the vibe lol

278
Q

Cortical Bone

A 
Long bones
80% of skeleton
Appendicular (limbs)
80-90% calcified
mainly mechanical and protective
279
Q

Cancellous Bone

A 
Vertebrae &amp; pelvis
20% of skeleton
Axial
15-25% calcified
mainly metabolic
Large surface
280
Q

Cortical bone microanatomy

A

Circumferential lamellae
Concentric lamellae
Interstitial lamellae
Trabecular lamellae

281
Q

Bone Cell Types

A
  1. Osteoblasts - build bone by laying down osteoid
  2. Osteoclasts - multinucleate cells of macrophage family resorb or chew bone
  3. Osteocytes - osteoblast like cells which sit in lacunae
282
Q

Osteoclast Differentiation

A

Increased osteoclast activity - RANK/RANKL
Decreased osteoclast activity - OPG binds RANKL

Osteoclasts are derived from the same mononuclear cells that differentiate into macrophages. Osteoblast/stromal cell membrane-associated RANKL binds to its receptor RANK located on the cell surface of osteoclast precursors. This interaction in the background of macrophage colony-stimulating factor (M-CSF) causes the precursor cells to produce functional osteoclasts. Stromal cells also secrete osteoprotegerin (OPG), which acts as a “decoy” receptor for RANKL, preventing it from binding the RANK receptor on osteoclast precursors. Consequently, OPG prevents bone resorption by inhibiting osteoclast differentiation.

283
Q

Metabolic Bone Diseases - Investigations

A

Histology requires bone biopsy from iliac crest,
processed un-decalcified for histomorphometry

‘Static’ parameters include:

  • cortical thickness & porosity
  • trabecular bone volume
  • thickness, number & separation of trabeculae

Bone mineralisation is studied using osteoid parameters –> orange= unmineralised osteoid, green = mineralised osteoid

‘Histodynamic parameters’ are obtained from fluorescent tetracycline labelling

284
Q

Osteoporosis - General

A

Aetiology – 90% cases due to insufficient Ca intake and post-menopausal oestrogen deficiency:
1º - age, post-menopause
2º - drugs, systemic disease

‘High turnover’ OP results from ↑ bone resorption
‘Low turnover’ OP results from ↓ bone formation

Fracture Pathogenesis – low initial bone mass or accelerated bone loss can reduce bone mass below the fracture threshold

Incidence: 1/3 women; 1/12 men >50
£1.7bn / yr = Cost of Rx 310k fractures
50% fracture patients cannot live independently post fracture; 20% die

285
Q

Osteoporosis RFs

A 
Advanced age
Female sex 
Smoking
Excess Alcohol 
Early menopause
Long-term immobility 
Low body mass index 
Poor diet ↓vit D, ↓Ca2+ 
Malabsorption
Thyroid disease
Low testosterone
Chronic renal disease
Steroids
286
Q

Effects of glucocorticoids on bone cells

A

Osteoclasts:

  • Decreased osteoclastogenesis
  • Early transient increase in osteoclast survival, cancellous osteoclasts, bone resorption

Osteocytes:

  • Increased apoptosis
  • Decreased canceller circulation
  • Decreased bone quality

Osteoblasts:

  • Decreased osteoblastogenesis
  • Increased apoptosis
  • Early and continual decrease in cancellous osteoblasts, synthetic ability, bone formation
287
Q

Osteoporosis - Fractures

A

Patients commonly present with back pain and #

wrist (Colles’), hip (NOF and intertrochanteric) & pelvis may be the first sign of disease

> 60% vertebral # are asymptomatic
Compression # usually in T11-L2 distribution

288
Q

Osteoporosis - Lab Ix, Imaging and Bone Densitometry

A

Lab:
Serum calcium, phosphorous & alk phos (usually N)
Urinary calcium
Collagen breakdown products

Imaging - XR fractures

Bone Densitometry

  • T score between 1 & 2.5 SD below normal peak bone mass= osteopaenia
  • T score >2.5 SD below normal peak bone mass = osteoporosis
289
Q

Bone in osteomalacia

A

More orange than green i.e. more osteoid than mineralised bone

Risk of horizontal fracture in Looser’s zone

290
Q

Renal osteodystrophy

A

Comprises all the skeletal changes of chronic renal disease:-
Increased bone resorption (osteitis fibrosa cystica)
Osteomalacia
Osteosclerosis
Growth retardation
Osteoporosis

291
Q

Osteitis fibrosa cystica

A
  • Lytic lesions

- hyperparathyroidism –> brown cell tumour

292
Q

Renal Osteodystrophy

A

Comprises all the skeletal changes of chronic renal disease:-

  • Increased bone resorption (osteitis fibrosa cystica)
  • Osteomalacia
  • Osteosclerosis (abnormal hardening of bone and an elevation in bone density)
  • Growth retardation
  • Osteoporosis
293
Q

Subtypes of Paget’s

A
  1. Osteolytic
  2. Osteolytic-osteosclerotic
  3. Quiescent osteosclerotic
294
Q

Paget’s - Epidemiology

A 
Onset > 40y
M=F
Rare in Asians and Africans
Mono-ostotic 15% (one bone affected)
Remainder polyostotic

Aetiology is unknown
Familial cases show autosomal pattern of inheritance with incomplete penetrance (mutation 5q35-qter - sequestosome 1 gene)
Parvomyxovirus type particles have been seen on EM in Pagetic bone

295
Q

Pagets - Clinical Presentation

A
  • pain
  • microfractures
  • nerve compression (incl. Spinal N and cord)
  • skull changes may put medulla at risk
  • +/- haemodynamic changes, cardiac failure
  • Development of sarcoma in area of involvement 1%
296
Q

Pagets - Ix and Histo

A

Only ALP raised

Gross - Thickening of cortex and coarse/irregular/thickened trabeculae

Histo- thickened bony trabeculae with characteristic mosaic pattern and osteoclastic and osteoblastic activity

297
Q

Types of Fracture

A

Simple - a fracture of the bone only, without damage to the surrounding tissues or breaking of the skin

Compound - extends through skin

Greenstick - the cortex is broken, but only on one side, more common in children

Comminuted- more than two parts (i.e. bone broken into multiple bits)

Impacted- broken ends of the bone are jammed together by the force of the injury

298
Q

Natural Process of Fracture Repair

A
  1. Organisation of haematoma at # site (pro-callus)
  2. Formation of fibrocartilaginous callus
  3. Mineralisation of fibrocartilaginous callus
  4. Remodelling of bone along weight-bearing lines
299
Q

Histology of Fracture Callus

A

Disorganised mixture of bone and cartilage and vascular fibrous tissue.

Could be mistaken for osteosarcoma by non specialist pathologists with insufficient clinical information.

300
Q

Factors Influencing Fracture Healing

A
  • Type of fracture
  • Presence of infection
  • Pre-existing systemic condition :-Neoplasm, Metabolic disorder, Drugs, Vitamin deficiency
301
Q

Osteomyelitis - Common Sites

A
  • Vertebrae
  • Jaw (2º to dental abscess)
  • Toe (2º to diabetic skin ulcer) (>3mm)
  • Long bones (usually metaphysis)
302
Q

Osteomyelitis - Presentation

A

Clinical features

  • General - malaise, fever , chills , leucocytosis
  • Local - pain, swelling and redness

60% positive blood cultures

X-ray - mixed picture; eventually lytic

303
Q

Osteomyelitis - Routes of Infection and Causative Organisms

A

Almost always bacterial, rarely fungal

Routes of infection:

a) haematogenous (blood borne)
b) direct extension (from nearby soft tissue infection)
c) traumatic (inc surgery)

Organisms - general:
Staph Aureus(90%)
E. Coli
Klebsiella
Salmonella (associated with sickle cell disease)
Pseudomonas (IVDA)

Organisms - neonates:
Haemophilus influenzae
Group B Streptococcus
Occasionally enterobacter

304
Q

Osteomyelitis - X-Ray Changes

A

Usually appear 10 days or so post onset

Mottled rarefaction and lifting of periosteum

> 1week - irregular sub-periosteal new bone formation called involucrum

Later - irregular lytic destruction (takes 10-14days)

Some areas of necrotic cortex may become detached called sequestra (takes 3-6 weeks)

305
Q

TB Osteomyelitis

A

3-5% cases of extra-pulmonary TB

Affects immunocompromised patients

More destructive and resistant to control

Spinal disease (50% cases) may result in psoas abscess and severe skeletal deformity (Pott’s disease)

Systemic amyloidosis may result in protracted cases

Presence of Langhans-type Giant cells

306
Q

Syphilis Osteomyelitis

A

Another rare cause of OM (Treponema pallidum)

May be congenital or acquired
Congenital skeletal lesions:-
- Osteochondritis
- Osteoperiostitis
- Diaphyseal osteomyelitis

Aquired – late skeletal lesions:-

  • Non-gummatous periostitis
  • gummatous inflammation of bone and joints
  • Neuropathic joints (Tabes Dorsalis)
  • Neuropathic shaft fractures
307
Q

Lyme Disease - Definition

A

Definition:-

  • Inflammatory arthropathy as part of a complex multisystem illness resulting from tick bite.
  • It is the most prevalent vector bone disease in temperate Northern hemisphere

Organism:-
Borrelia burgdorferi

Tick Species:-
Ixodes dammini

Associated tic bite - ‘erythema chronicum migrans’ (targetoid)

308
Q

Lyme Disease - Disease Progression

A

Early localised

  • Characterised by rash (90%) usually within 7-10 days and between 1 & 50cm diameter.
  • Often thigh, groin, axilla (earlobe in children)

Early Disseminated
- Affects many organs, musculoskeletal, heart, nervous system.

Late, persistent
- Dominated by arthritis.

309
Q

Lyme Disease - Treatment

A 
Treatment is based on prevention.
Vaccines are available.
Antibiotics for proven disease.
No effective prophylaxis.
Diagnosis is clinical. No specific histological features.
310
Q

Osteoarthritis

A

Degenerative joint disease
Primary- age related
Secondary - any age, previously damaged or congenitally abnormal joint

Aetiology: ?biomechanical factors, ?biochemical factors, ?aging, ?genetic

Result in:

  • Cartilage degeneration
  • Fissuring
  • Abnormal matrix calcification
  • Osteophytes

Sites:
Main sites vertebrae hips and knees
+/-DIPJ PIPJ of the hand
+/- carpometacarpal and metatarsophalangeal joints

311
Q

Rheumatiod Arthritis - General

A
  • Severe chronic relapsing synovitis
  • Unpredictable course
  • Incidence 1% world population
  • 3F:1M, Age 30-40y

Aetiology: likely autoimmune, genetic predisposition (risk alleles TNFA1P3, STAT4)

80% pts rheumatoid factor +ve - mostly IgM, forms immunocomplexes with IgG (these may underlie extra-articular disease)

312
Q

Rheumatiod Arthritis - Presentation

A 
Clinical features:
Mild anaemia
Raised ESR
RF+ve(80%)
\+/- rheumatoid nodules (25%)
*can be multisystem disease

Sites:

  • Small joints, hands and feet, sparing DIPJ
  • Wrists elbows ankles and knees

Characteristic Deformities:

  • Radial deviation of wrist
  • Ulnar deviation of fingers
  • ‘Swan neck’ & ‘Boutonniere’ deformity of fingers
  • ‘Z’ shaped thumb
313
Q

Rheumatoid Arthritis - Histology

A

Proliferative synovitis with

  1. Thickening of synovial membranes ( villous)
  2. Hyperplasia of surface synoviocytes
  3. Intense inflammatory cell infiltrate
  4. Fibrin deposition and necrosis

Pannus (abnormal layer of fibrovascular tissue or granulation tissue) formation with exuberant inflamed synovium
overlying the articular surface.

314
Q

Gout

A
  • Affects any joint but great toe in 90%
  • Usually limited to lower extremities
  • Precipitate of needle shaped crystals into joint
  • Tophus is the pathognomic lesion
315
Q

Pseudogout

A

Usual age > 50y
Crystals of:
- Calcium pyrophosphate - mainly knees or
- Calcium phosphates (hydroxyapatite) - knees and shoulders

Subsets:
Sporadic
Metabolic
Hereditary (autosomal dominant)
Traumatic
316
Q

Gout vs Pseudo Crystals

A

Pseudo: positively birefringent rhomboid crystals
Gout: negatively birefringent needle-like crystals

317
Q

Mets to Bone - Adults

A

Thyroid, breast, lung, kidney, prostate

318
Q

Mets to Bone - Children

A

Neuroblastoma, Wilm’s tumour, osteosarcoma, ewings, rhabdomyosarcoma

319
Q

Primary Malignant Bone Tumours

A

Osteosarcoma
Chondrosarcoma
Ewing’s sarcoma/PNET (primitive peripheral neuroectodermal tumour)

320
Q

Osteosarcoma

A

Commonest primary bone sarcoma

Age: peak in adolescence (75% patients are <20y)

Site: 60% occur around the knee

X-ray: usually metaphyseal, lytic, permeative, elevated periosteum (Codman’s Triangle)

Histo: malignant mesenchymal cells +/- bone and cartilage formation

Prognosis: poor- 60% 5 year survival. Treatment is usually chemo and limb salvage surgery

321
Q

Chondrosarcoma

A

Malignant cartilage producing tumour

Age: 40y and over

Site: pelvis, axial skeleton, prox femur, prox tibia

X-ray: lytic with fluffy calcification

Histo: malignant chondrocytes +/- chondroid matrix may dedifferentiate to high grade sarcoma

Prognosis: 70% 5y survival (depends on grade & size)

322
Q

Ewing’s Sarcoma/PPNET

A

Highly malignant small round cell tumour

Age: usually < 20y (80%)

Site: diaphysis/metaphysis of long bones, pelvis

X-ray: onion skinning of periosteum, lytic +/- sclerosis

Histo: sheets of small round cells

Prognosis : - 75% 5y survival 50% longterm

Specific chromosome translocation 11:22 (EWS/Fli1)

323
Q

Normal Skin Layers

A

epidermis (keratinocytes, squamous epithelial cells), dermis (collagen, elastic fibres, adenexal structures) subcutaneous fat

324
Q

Bullous Pemphigoid

A
  • Vesiculobullous inflammatory reaction pattern
  • Reasonably high morbidity rate –> need to be admitted
  • Tense bullae that tend to present in the flexural surfaces
  • Autoimmune – complement attacks the way in which the keratinocytes sit on the basement membrane.
  • Complement attracts eosinophils which then release elastase –> fluid build up.
  • Subepidermal - the whole epidermis lifts up
  • Immunofluorescence IgG and C3- dermoepidermal junction (along the basement membrane zone)
325
Q

Pemphigus Vulgaris

A
  • Vesiculobullous inflammatory reaction pattern
  • Flaccid looking blisters
  • Antigens against proteins that keep the keratinocytes stuck together so you get splitting WITHIN the epidermis
  • Autoimmune – IgG related –> immunofluorescence
326
Q

Pemphigus foliaceus

A
  • Vesiculobullous inflammatory reaction pattern - but don’t really see bullae as they are very thin and often come off after a period of time (leaving excoriated looking area)
  • Rare
  • Loss of top layer of epidermis - stratum corneum
  • IgG related –> immunofluorescence key for making diagnosis
327
Q

Discoid Eczema

A
  • Spongiotic inflammatory reaction pattern
  • Atopic/contact dermatitis
  • Scaly while plaques on flexural surfaces
  • Itchy
  • Spongiosis –> oedema between the keratinocytes
  • Eosinophil recruitment
  • Thickening of the epidermis over time
328
Q

Plaque Psoriasis

A
  • Psorisaform inflammatory reaction pattern
  • Extensor surfaces
  • Silvery white plaques
  • Rapid shedding of skin - Normal Stem cell to keratinocyte = 56 days. 7 days in this. Thickening of the epidermis as a result.
  • Lose some normal layers of epidermis.
  • Munro micro abscesses –> little accumulations of neutrophils.
329
Q

Lichen Planus

A
  • Lichenoid inflammatory reaction pattern
  • Itchy purple/red patches/plaques
  • Extensor surfaces
  • Wickham striae – white lines in mouth
  • Histologically can’t see where the epidermis stops and the dermis starts –> T lymphocytes damage bottom layer of keratinocytes in the epithelium. They die and you get “band-like” inflammation
330
Q

Pyoderma Gangrenosum

A

Ulcer

Manifestation of many underlying diseases

331
Q

Seborrhoeic Keratosis

A 
Cauliflower shape
Pigmented 
Completely harmless 
Keratinocytes proliferating upwards in an orderly fashion
Keratin horn cysts – gaps
332
Q

Sebaceous Cyst

A

Central punctum, smooth, round, well circumscribed

Epidermis invaginates the dermis  produce keratin  get caseous stuff coming out

333
Q

Basal Cell Carcinoma

A

Sun exposed areas in the elderly
Ulcerated, pearly rim, ‘rodent ulcer’
Tumour cells infiltrate into the dermis (beyond BM)
Don’t metastasise but are locally invasive

334
Q

Bowen’s Disease

A

Big keratin horn
Pre-cancerous/Full thickness dysplasia - Keratinocytes, bigger, pleiomorphic, hyperpigmented but haven’t broken basement membrane

335
Q

Squamous Cell Carcinoma- Skin

A

Can be poorly or well differentiated

Can wrap round nerve –> perineurial invasion. Risk of recurrence greater with this.

336
Q

Benign Junctional Naevus
Compound Naevus
Intradermal Naevi

A

Melanocytes sit on basement layer of epidermis –> make naevi when they accumulate/proliferate

Junctional - group of melanocytes creating nests in epidermis.
Compound - nests within epidermis and nests within dermis
Intradermal - within the dermis

Melanocytes allowed to break through basement membrane without being cancer.

337
Q

Malignant Melanoma

A

Irregular outline, variable pigmentation, bleeding, itchy, growing.

Junctional melanocytes moving up through the epidermis- upward migration/pagetoid spread (usually will drop down to dermis). Cells are bigger than expected in epidermis.

In dermis- melanocytes should get smaller as they mature and move downwards, here they are all the same size so aren’t maturing and also there is increased mitosis (shouldn’t see mitotic figures in melanocytes in the dermis except in pregnancy).

Graded by depth in mm

338
Q

SLE

A

Presentation: Skin (malar rash, discoid rash, raynaud’s “even gangrene”), Oral ulcers, Joints, Neurological, Serositis (pleuritic chest pain, abdo pain etc), Renal, Haemotogical (can have pancytopenia), Immunological

ANA - anti-nuclear antibodies - immunoflurosence screening test

Specific antigens:
Anti-dsDNA (Crithidia luciliae protozoan with lots of dsDNA - yellow, ELISA)
Anti-smith (against ribonucleoproteins) - most specific but not v sensitive
Anti-histone (drug related e.g. hydralazine)

339
Q

SLE- Skin Histo

A

Lymphocyte infiltration in the upper dermis
Vacuolization of the basal layer of epidermis
RBCs extravasated into the upper dermis (which are the reasons for the rash)

Immunofluorescence staining (antibody to IgG showing evidence for immune complexes at the dermal-epidermal junction)

340
Q

SLE - Renal Histo

A

Thickened pink glomerular capillary loops (‘wire loops’) due to immune complex deposition

Deposits of IgG and complement in the basement membrane - Immunofluorescence

Electron dense deposit within the glomerular basement membrane - electron microscopy

341
Q

SLE - Libman-sacks

A

Non-infective endocarditis

Strands of fibrin, neutrophils, lymphocytes, histiocytes

342
Q

Scleroderma (Systemic Sclerosis)

A

Tight skin
Fibrosis & excess collagen (localised form is called morphoea in the skin)

Tight skin over trunk = diffuse form
No tight skin over trunk = limited form

Diffuse form: Antibodies to DNA topoisomerase (Scl70)
Limited form (CREST): Anticentromere antibody
Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly 
Telagiectasia
Nailfold capillary dilatation
Microstomia
343
Q

Scleroderma - Histo

A

Nucleolar pattern immunofluorescence
Increased dermal collagen resulting in reduced skin elasticity
‘Onion skin’ intimal thickening of small arteries

344
Q

Polymyositis/Dermatomyositis

A

Proximal myopathy
High CK
Speckled pattern of ANA test

Dermato- Gottron’s papules: erythematous rash over knuckles & dorsal aspect of hand

345
Q

Sarcoid - Presentation

A

Pres: Joints, Skin (nodules/papules, lupus pernio, erythema nodosum), Lungs, Lymphadenopathy, Heart, Eyes, Neuro, Liver

Skin: Lupus pernio, erythema nodosum
CNS: Meningitis, cranial nerve lesions
Eyes: Uveitis, keratoconjunctivitis
Parotids: Bilateral enlargement
Lungs: BHL (bilateral hilar lymphadenopathy), fibrosis, lymphocytosis (CD4+ in BAL)
Liver: Hepatitis, cholestasis & cirrhosis

346
Q

Sarcoid - Histo

A

Non-caseating granulomas- histiocytes (epithelioid cells), multinucleated giant cells of Langhans (peripheral nuclei) and lymphocytes.

Hypergammaglobulinaemia
Raised ACE
Hypercalcaemia - Vit D hydroxylation by activated macrophages

347
Q

Polyarteritis nodosa

A 
Necrotising arteritis
Polymorphs, lymphocytes, eosinophils
Arteritis is focal and sharply demarcated
Heals by fibrosis
More often renal and mesenteric arteries

Nodular appearance on angiography (small aneurysms)

Associated with hep B

348
Q

Characteristic rash for vasculitis

A

Palpable purpuric rash

349
Q

Temporal arteritis

A

Steroids
ESR
Biopsy - Chronic lymphocytic inflammation in the media, giant cells, narrowing of the lumen

350
Q

Granulomatosis with polyangiitis (Wegners)

A

Small vessel vasculitis

ENT
Lung
Kidneys

C-ANCA (cytoplasmic ANCA) directed against proteinase 3

351
Q

Eosinophilic Granulomatosis with polyangiitis (Churg Strauss)

A

Small vessel vasculitis

Asthma
Eosinophilia
Vasculitis

P-ANCA (perinuclear ANCA) directed against myeloperoxidase

352
Q

Breast Lump cytology coding

A 
C1 = inadequate
C2 = benign
C3 = atypia, probably benign
C4 = suspicious of malignancy
C5 = malignant
353
Q

Radial scar >1 cm are sometimes called

A

“complex sclerosing lesions”

354
Q

Breast - Usual epithelial hyperplasia

A

Not considered a direct precursor lesion to invasive breast carcinoma but is a marker for a slightly increased risk (relative risk of 1.5-2.0) for subsequent invasive carcinoma.

355
Q

Breast - Flat epithelial atypia/Atypical ductal carcinoma

A

Emerging genetic data suggests FEA may represent the earliest morphological precursor to low grade ductal carcinoma in situ.

4 times relative risk of developing cancer.

356
Q

Breast - In situ lobular neoplasia

A

Current evidence suggests that in situ lobular neoplasia is a risk factor for subsequent invasive breast carcinoma in either breast in a minority of women.

The relative risk is quoted as between 7-12 times that expected in women without lobular neoplasia.

357
Q

Breast - Ductal Carcinoma in Situ

A

A neoplastic intraductal epithelial proliferation in the breast with an inherent, but not inevitable, risk of progression to invasive breast carcinoma.
Common.

Incidence has markedly increased since the introduction of breast screening programmes.

  • 85% are detected on mammography as areas of microcalcification.
  • 10% produce clinical findings such as a lump, nipple discharge, or eczematous change of the nipple (Paget’s disease of the nipple).
  • 5% are diagnosed incidentally in breast specimens removed for other reasons.
  • Subclassified histologically into low, intermediate and high grade.

Complete excision with clear margins is curative.
Recurrence is more likely with extensive disease and high grade DCIS.

358
Q

Chromosomal loss show in low grade breast carcinomas

A

16q

359
Q

Breast Cancer - Histological Grading

A

All invasive breast cancers are graded histologically by assessing 1) tubule formation 2) nuclear pleomorphism, and 3)mitotic activity.

Each parameter is scored from 1-3 and the three values are added together to produce total scores from 3-9.
3-5 points = grade 1 (well differentiated).
6-7 points = grade 2 (moderately differentiated).
8-9 points = grade 3 (poorly differentiated).

360
Q

Breast Cancer Receptor Status

A

All invasive breast carcinomas are assessed for oestrogen receptor (ER), progesterone receptor (PR) and Her2 status.
Low grade tumours tend to be ER/PR positive and Her2 negative.
High grade tumours tend to be ER/PR negative and Her2 positive.
Basal-like carcinomas are often ER/PR/Her2 negative (“triple negative”).

361
Q

Breast Cancer - Prognosis

A

The single most important prognostic factor is the status of the axillary lymph nodes.
Other important factors include tumour size, histological type, and histological grade.

362
Q

Breast Cancer - Screening

A

Women aged 47-73 are invited for screening every three years.
The screening test is a mammogram which looks for abnormal areas of calcification or a mass within the breast.
About 5% of women have an abnormal mammogram and are recalled to an assessment clinic for further investigation.

Core biopsies taken from the breast as part of the screening programme are given a B code from 1-5.
B1 = normal breast tissue.
B2 = benign abnormality.
B3 = lesion of uncertain malignant potential.
B4 = suspicious of malignancy.
B5 = malignant (B5a = DCIS, B5b = invasive carcinoma).

363
Q

Gynaecomastia

A

Enlargement of the male breast.
Pubertal boys and older men aged over 50.
Idiopathic or associated with drugs (both therapeutic and recreational).
Histologically the breast ducts show epithelial hyperplasia with typical finger-like projections extending into the duct lumen. The periductal stroma is often cellular and oedematous.
Benign, no risk of malignancy.

364
Q

Male Breast Cancer

A

Carcinoma of the male breast is rare (0.2% of all cancers).
Median age at diagnosis 65 years old.
Most present with a palpable lump.
Histologically the tumours show similar features to female breast cancers.

365
Q

2 distinct biological states of HPV infection

A

Non-productive/latent phase:
HPV DNA continues to reside in the basal cells
Infectious virions are not produced
Replication of viral DNA is coupled to replication of the epithelial cells occurring in concert with replication of the host DNA
Complete viral particles are not produced
The cellular effects of HPV infection are not seen
Infection can only be identified by molecular methods

Productive Viral Infection
Viral DNA replication occurs independently of host chromosomal DNA synthesis.
Large numbers of viral DNA are produced and results in infectious virions.
Characteristic cytological and histological features are seen.

366
Q

Genetics of Type 1 Endometrial Carcinoma

A

Develop through the accumulation of mutations of at least 4 different genes:

  • PTEN (10q23; 37-61%)
  • PI3KCA (39%) (mainly codons 9 and 20)
  • K-ras (10-30%)
  • CTNNB1 (14%-44%)
  • FGFR2 (16%)
  • P53 (10%)
367
Q

Genetics of Type 2 Endometrial Carcinoma

A

Endometrial serous carcinoma

  • P53 mutations in 90%
  • PI3KCA mutations in 15% Her-2 amplification

Clear cell carcinoma

  • PTEN mutation
  • CTNNB1 mutation
  • Her-2 amplification
368
Q

FIGO Staging of Endometrial Carcinoma

A

Stage 1 – confined to uterus
Stage 2 – spread to cervix
Stage 3 – spread to adnexae, vagina, local lymph nodes (pelvic or para-aortic)
Stage 4 – other pelvic organs distant spread inc any other distant lymph node groups

369
Q

Complete vs Partial Mole Progression

A
  • None of partial and only 2.5% of complete moles progress to malignancy
  • 10% of complete moles develop into invasive moles – locally destructive
  • Complete moles may persist or recur
  • Chromosomal abnormalities play an important role in development of moles.
370
Q

Choriocarcinoma

A 
1 in 20,000 to 30,000  pregnancies
Rapidly invasive, widely metastasising (lung, vagina, brain, liver, kidney)
Responds well to chemotherapy
50% arise in moles
25% arise in previous abortion
22% arise in normal pregnancy
371
Q

Incidence of ovarian cancer by tumour type

A

Epithelial tumours make up 65% of all ovarian tumours & 95% of malignant ovarian tumours

Epithelial tumours: 50% found in 45-65 age group

Germ cell tumours have bimodal distribution; one peak 15-21 year olds and one peak at 65-69.

Sex cord tumours most common in post-menopausal women but some sub-types peak in 25-30 year age group

372
Q

Type I Ovarian Tumours (20%)

A

Low grade, relatively indolent, arise from well characterised precursors (BOT) and endometriosis

Usually present as large stage I tumours

Mutations in K-ras, BRAF, PI3KCA and HER2, PTEN and beta–catenin

Usually have precursors

Include low grade serous, low grade endometrioid, mucinous and tentatively CCC.

(CCC is high grade, but molecular changes are more like type I and also having endometriosis as precursor lesion

373
Q

Type 2 Ovarian Carcinoma

A

High grade mostly of serous type
Aggressive
More than 75% have p53 mutations
No precursor lesions

374
Q

Immature Teratoma

A
  • Indicates presence of embryonic elements
  • Neural tissue particularly conspicuous
  • A malignant neoplasm that grows rapidly, penetrates the capsule and forms adhesions to the surrounding structures
  • Spreads in the peritoneal cavity by implantation
  • Mets to lymph nodes, lung, liver and other organs
  • Three grading system according to amount of primitive elements
375
Q

Mature cystic teratoma with malignant transformation

A

Malignant transformation is rare occurring in 2% of cases, usually in post menopausal women

Most frequently SCC

Also carcinoid, thyroid ca, BCC, malignant melanoma, intestinal adenocarcinoma, leiomyosarcoma, chondrosarcoma and hemangiosarcoma

376
Q

Heredity and Ovarian Cancer

A

Up to 10% of epithelial ovarian cancer cases are familial

10% of women with ovarian carcinoma are carries of a breast/ovarian ca susceptibility gene

3 familial syndromes: All are transmitted in an autosomal dominant fashion
familial breast-ovarian cancer syndrome
site-specific ovarian cancer
cancer family syndrome (Lynch type II)

Familial breast-ovarian cancer and site-specific ovarian cancer syndromes both associated with mutations of the BRCA1 suppressor gene; account for 90% of familial ovarian cancers

Hereditary ovarian cancer occurs at a younger age than sporadic

Carriers have 15 fold increase risk of ovarian carcinoma to non-carriers Multiple cases of early onset breast cancer

377
Q

Vulval Lesions

A 
Benign tumours: Papillary Hidradenoma
Malignancy:3% of female genital tract tumours
SCC: 85% 
HPV or lichen sclerosus
VIN: vulval intraepithelial  neoplasia
Paget’s disease: (adenocarcinoma-in-situ) rarely associated with invasive adenocarcinoma 
Adenocarcinoma
Malignant melanoma
Basal cell carcinoma
378
Q

Vaginal Lesions

A

Congenital anomalies: Absence or atresia
Tumours: 1% of female genital tract tumours
Carcinoma: squamous cell carcinoma
Adenocarcinoma: Clear cell adenocarcinoma if mother was treated during pregnancy by Diethyl stilbosterol for threatened abortion
Rhabdomyosarcoma

379
Q

Pulmonary oedema - histopath

A

Heavy watery lungs, intra-alveolar fluid on histology. Iron laden macrophages - stain blue.

Fluid in alveoli leads to reduced gas exchange.

380
Q

Acute lung injury/diffuse alveolar damage

A

Important cause of rapid onset respiratory failure

Pathogenesis: acute damage to endothelium and/or alveolar epithelium leading to exudative inflammatory reaction. Get diffuse alveolar damage - lungs expanded and firm, plum coloured, airless, often weight >1kg.

Exudative phase –> hyaline membranes –> Organising phase = fibrosis of the exudates

Adults – Acute respiratory distress syndrome “shock lung”

Neonates - Hyaline membrane disease of newborn (surfactant deficiency)

Outcomes: death (40%), superimposed infection, resolution (lung returns to normal), residual fibrous scarring of lung (chronic resp impairment).

381
Q

Asthma - Pathophysiology and Histology

A

Widespread narrowing of the airways that changes in severity over short periods of time.

Acute change:
Bronchospasm, oedema, hyperaemia, inflammation

Chronic change:
Muscular hypertrophy
Airway narrowing
Mucus plugging
Overinflated lungs

Histology:
Lots of eosiniophils. Lots of goblet cells producing mucus. Thickened airway and dilated blood vessels.

382
Q

COPD - Pathology

A

Dilated airways
Mucus gland hyperplasia
Goblet cell hyperplasia
Mild inflammation

383
Q

Emphysema - Pathology

A

Permanent loss of the alveolar parenchyma distal to the terminal bronchiole

Pathogenesis
Inflammation –> neutrophil and macrophage activation
This leads to an increase in proteases (e.g. elastase) –> tissue damage

SMOKING: Loss centred on bronchiole - CENTRILOBULAR

ALPHA 1 ANTITRYPSIN DEF - Diffuse loss of alveolae - PANACINAR

384
Q

Bronchiectasis - Pathology

A

Permanent abnormal dilatation of bronchi with inflammation and fibrosis extending into adjacent parenchyma.

Can be inflammatory or congenital. Most commonly associated with infection (especially in children with CF), also in ciliary dyskinesia (primary = kartagener’s)

385
Q

Bacterial Pneumonia - Causes and Patterns

A

Community acquired: streptococcus pneumoniae, haemophilis influenzae, mycoplasma

Hospital acquired: gram –ve (klebsiella, pseudomonas)

Aspiration: Mixed aerobic and anaerobic

Variety of patterns of lung involvement depending upon organism and other co-factors

  • Bronchopneumonia
  • Lobar pneumonia
  • Abscess formation
  • Granulomatous inflammation
386
Q

Bronchopneumonia

A

Compromised host defense - Elderly

Often low virulence organisms - Staphylococcus, Haemophilius, Streptococcus, Pneumococcus,

Pathology - Patchy bronchial and peribronchial distribution, often lower lobes

Histopathology- Peribronchial distribution. Acute inflammation surrounding airways and within alveoli.

387
Q

Lobar Pneumonia

A

Acute bacterial infection of a large portion of a lobe or entire lobe.
Infrequent with advent of antibiotics
90-95% pneumococci (S. pneumoniae)
Widespread fibrinosuppurative consolidation

Histopath:
1. Congestion - Hyperaemia, Intra-alveolar fluid
2. Red hepatization- Hyperaemia, Intra-alveolar neutrophils
3. Grey hepatization- Intra-alveolar connective tissue
4. Resolution
Restoration normal architecture. Scarring in some pts.

388
Q

Atypical Pneumonias

A

Mycoplasma, viruses (e.g. CMV, influenza), Coxiella, Chlamydia

Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells

Chronic inflammatory cells within alveolar septa with oedema +/- viral inclusions

389
Q

Sarcoid lung path

A

Discrete epithelioid and giant cell granulomas, preferential distribution in upper zones with tendency to be perilymphatic, peribronchial

Advanced disease may be fibrotic and cystic

Diagnosis:

  • Biopsy (Bronchial/OLB) - Non-necrotising granulomas, either singly or coalescent. May undergo fibrosis.
  • Elevated serum Angiotensin Converting Enzyme (ACE)
390
Q

Other causes of non-infectious granulomas

A

Intravascular talc granulomas in an intravenous drug abuser

Aspirated material

391
Q

Idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis

A

Macro – Basal and peripheral fibrosis and cyst formation
Micro - interstitial fibrosis at varying stages

Diagnosis by HRCT +/- biopsy.
Progressive disease
Over 50% die in 2-3 years

392
Q

Asbestosis - Histopath

A

Fine subpleural basal fibrosis with asbestos bodies in tissue.

May also see pleural disease - fibrosis, pleural plaques.

Increased risk of lung cancer in the presence of asbestosis.

393
Q

Causes of pulmonary hypertension

A

PHBP = mean pulmonary arterial pressure > 25mmHg at rest

Precapillary:
VASOCONSTRICTIVE
- Chronic hypoxia
- Hyperkinetic congenital heart disease
- Unknown (primary pulmonary HTN)
- Chronic liver disease, HIV, connective tissue disease

EMBOLIC

  • Thromboembolic
  • Parasitic (schistosomal)
  • Tumour emboli

Capillary:
- Widespread pulmonary fibrosis - mechanical vascular distortion and chronic hypoxia

Postcapillary:

  • Veno-occlusive disease
  • Left sided heart disease
394
Q

Chronic Hypoxia - Histopath

A

Normal response of lung is to reduce blood supply to hypoxic areas of lung and divert it to aerated zones

Chronic hypoxia results in chronic vasoconstriction pulmonary arterioles (COPD, Fibrosing lung disease)

Morphological changes in vessels:

  • Eccentric intimal fibrosis
  • Thickening muscle wall
395
Q

Pulmonary Embolism

A

Common site formation in deep veins of leg (95%)

Thrombus formation- Virchows triad:

  • factors promoting blood stasis
  • damage to endothelium
  • increased coagulation

SMALL EMBOLI

  • Small peripheral pulmonary arterial occlusion
  • Haemorrhagic infarct
  • Repeated emboli cause increasing occlusion of pulmonary vascular bed and pulmonary hypertension
  • Patients present with pleuritic chest pain or chronic progressive shortness of breath

LARGE EMBOLI

  • Large emboli can occlude the main pulmonary trunk (saddle embolus)
  • Sudden death, acute right heart failure, or cardiovascular shock occurs in 5% of cases when >60% of pulmonary bed is occluded
  • If patient survives, the embolus usually resolves
  • 30% develop second or more emboli
NON-THROMBOTIC EMBOLI
Bone marrow
Amniotic fluid
Trophoblast
Tumour
Foreign body
Air
396
Q

Pulmonary Veno-Occlusive Disease

A

Fibrotic occlusion of pulmonary veins

Collagenous occlusion of vein (pink stains
Collagen, black stains elastic lamina
of vein).

397
Q

Complications of Pulmonary HTN

A

Right sided heart failure

  • Venous congestion of visceral organs – “nutmeg liver”
  • Peripheral oedema
  • Pleural effusions and ascites
  • Poor lung perfusion and hypoxia
398
Q

Pulmonary Vasculitis

A

Uncommon

Present as life threatening haemorrhage, chronic haemoptysis, mass lesion, interstitial lung disease

Variety of patterns from granulomatous vasculitis involving small-medium sized vessels (GPA) through to a leukocytoclastic vasculitis involving capillaries (e.g with Rheumatoid arthritis)

399
Q

Large Cell Lung Carcinoma

A

Peripheral or central 10% of tumours

Poorly differentiated tumours composed of large cells

No histological evidence of glandular or squamous differentiation

BUT on electron microscopy many show some evidence of glandular, squamous or neuroendocrine differentiation
i.e are probably very poorly differentiated adeno/squamous cell carcinomas

Poorer prognosis

400
Q

Lung Cancer - Rx and Prognosis by Histological Type

A

Small cell lung carcinoma:
Survival 2-4 months untreated
10-20 months with current therapy
chemoradiotherapy (surgery very rarely undertaken as most have spread at time of diagnosis)

Non-small cell lung carcinoma:
Early Stage 1: 60% 5 yr survival
Late Stage 4: 5% 5 yr survival
20-30% have early stage tumours suitable for surgical resection. 
Less chemosensitive

Adenocarcinoma vs squamous cell carcinoma:
Some adenocarcinomas show a variety molecular changes which can be targeted by specific therapies. (EFGR, ALK, Ros1)
In contrast some patients with squamous cell carcinoma develop fatal haemorrhage with some drugs (Bevacizumab)

Pathologists frequently need to sub-type small biopsy material/cytology material to guide diagnosis.

401
Q

Molecular Testing and Targeted Therapy for Lung Cancer

A

(Adenocarcinomas)
EGFR- Cetuximab, Gefitinib, Erlotinib. Tyrosine kinase inhibitor therapy.

ALK translocation and Ros1 translocation respond to crizotinib.

402
Q

Immunotherapy for Lung Cancer

A

High levels of PD1 or PDL1
protein expression (IHC) may inhibit
Immune response.

Cytotoxic T cells express PD-1
Tumour cells express PD L1 – binds PD-1, inhibits t cells from killing tumour cells, escape immune response

Other cells also express PD L1, dendritic cells, macrophages, fibroblasts which may also modulate cytotoxic t cell activity.

Liv Path (24 decks)

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