Histopathology - GI Disease Flashcards
What is normal oesophageal histology?
Squamous stratified epithelium (NO GOBLET CELLS), separated from columnar epithelium of the stomach via squamo-columnar junction/Z-line
What are the charcteristics, complications and treatment of Reflux oesophagitis/GORD?
- Commonest cause of oesophagitis
- Los Angeles Classification of Severity
- Cx: Ulceration, Haemorrhage (leads to haematemesis/meleana), Barrett’s oesoophagus, strictures, perforation
- Tx: Lifestyle changes (stop smoking, weight loss), PPI/H2 receptor antagonists
What is Barrett’s Oesphagus, it’s characteristics and complications?
Intestinal metaplasia of squamous mucosa to columnar epithelium (have goblet cells) following chronic GORD - upwards migation of the squamo-columnar junction
- 10% of symptomatic GORD pts
- Cx: Adenocarcinoma (metaplasia -> dysplasia -> Cancer)
What confers a higher risk of developing cancer in a patient with Barrett’s oesophagus?
Presence of goblet cells (Intestinal metaplasia)
Where is oesophageal adenocarcinoma most commoly seen, and its risk factors?
Distal 1/3 Oesophagus (due to Barrett’s oesophagus)
RFs:
- Barrett’s oesophagus
- Smoking
- Obesity
- Prev. radiation therapy
- Caucasian
- M»F
What are some RFs of Squamous cell oesophageal carcinoma?
Ethanol use + smoking
- Achalasia of cardia
- Plummer-Vinson syndrome
- Nutritional deficiencies
- Nitrosamines
- HPV
- Afro-caribbean
- M>F
Where is squamous cell oesophageal carcinoma most commonly found?
- Middle 1/3 = 50%
- Upper 1/3 = 20%
- Lower 1/3 = 30%
What is the presentation of squamous cell oesophageal carcinoma?
- Progressive dysphasia
- Odynophagia (pain)
- Anorexia
- Severe weight loss
What are varices, its presentation and treatment?
Engorged dilated veins, usually due to portal HTN (back pressure)
- Sx: Pt vomits large volumes of blood
- Tx: Emergency endoscopy = sclerotherapy/banding
What is the spread of squamous cell oesophageal carcinoma?
- Rapid growth
- Early spread to LNs, liver, + proximal structures (results in palliative care)
- Invades mucosa and creates keratin + intracellular bridges
What is the normal histology of the stomach?
Lined by gastric mucosa (NO GOBLET CELLS), columnar epithelium (mucin secreting) + glands
What are some causes of acute gastritis?
- Aspirin
- NSAIDs
- Corrosives (bleach)
- Acute H. pylori
- Severe stress
What are some causes of chronic gastritis?
- H-pylori (Antral)
- Autoimmune (e.g. pernicious anaemia)
- Ethanol
- Smoking
What are some complications of gastritis?
- Chronic –> Gastric ulcer formation
- Chronic from H. pylori may induce lymphoid tissue in stomach + increase future risk of mucosa associated lymphoid tissue (MALT) Lymphoma
- Intestinal metaplasia –> Dysplasia –> Cancer
What is a gastric ulcer and its symptoms?
Breach through muscularis mucosa into submucosa (deoth of tissue loss goes beyond mucosa)
- Epigastric pain +/- weight loss
- Pain worse with food + relieved by antacids
What are some RFs, Ix and Cx for gastric ulcer?
RFs:
- H. pylori
- Smoking
- NSAIDs
- Stress
- Delayed gastric emptying
- Elderly
Ix:
- Biopsy (Punched out lesion with rolled margins)
Cx:
- Anaemia - IDA (massive haemorrhage)
- Perforation (erect CXR)
- Malignancy
What are some charactertistics of gastric cancer?
- Highest incidence: Japan/China (more fermented/pickled foods eaten)
- > 95% = adenocarcinomas
- Intestinal or diffuse
What are the histological differences between intestinal and diffuse gastric cancers?
Intestinal:
- Well differentiated
- Goblet cells present following intestinal metaplasia
Diffuse:
- Poorly differentiated
- No gland formation
- Includes signet ring cell carcinoma
What is gastric lymphoma (MALT) and it’s treatment?
Chronic inflammation + B-lymphocyte driven
- Caused by H.pylori
Tx: Remove cause
- H. pylor = triple therapy (PPI, clarythromycin + amoxicillin)
What are some features of a duodenal ulcer, its RFs and complications?
- 4x more common than gastric ulcer
- Epigastric pain, worse at night
- Pain relieved by food + milk
- Occurs in younger adults
RFs:
- H. pylori
- Drugs
- Aspirin
- NSAIDs
- Steroids
- Smoking
- Increased drug use
- Acid secretion
Cx:
- IDA
- Perforation (CXR)
What is coelia diseaase + its presentation?
T-cell mediated autoimmune disease (DQ2, DQ8 HLA status)
Presentation:
- Young children (paeds) + irish women
What are some symptoms of coeliac disease (malabsorption)
- Steatorrhoea
- Abdo pain
- Bloating
- N+V
- Weight loss
- Fatigue
- IDA
- Failure to thrive
- Rash (dermatitis herpetiformis)
- Hyposplenism
What are some complications of coeliac disease?
- MALT
- Hyposplenism
- Osteoporosis
- Subfertility
- IDA
What is a differential diagnosis for coeliac disease?
Tropical sprue
What are the serological tests + results for coeliac disease?
- Anti-endomysial Ab (Best sensitvity + specificity)
- Anti-Tissue transglutaminase (IgA)
- Anti-gliadin (poor marker of disease control)
What is the gold standard investigation for coeliac disease and what is seen on histology?
- Upper GI endoscopy + duodenal biopsy (while eating gluten)
- Villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes
What is a normal villous:crypt ratio?
2:1
What is the treatment for coeliac disease?
Gluten-free diet
What are some congenital GI diseases?
- Atresia
- Stenosis
- Duplication
- Imperforate anus
- Hirschsprung’s disease
What is the most common congenital GI abnormality?
Hirschsrprung’s disease
What is Hirschsrpung’s disease and how does it present?
An absence of ganglion cells in myenteric plexus
- Sx + signs of obstruction in young babies (constipation, abdominal distension, overflow diarrhoea)
- Mostly male
- Failure to pass meconium within first 48hrs
What are some RFs for Hirschprung’s disease?
- Down’s syndrome (2%)
- Males
- RET proto-oncogene Cr10+ (genetics)
What is the gold-standard investigation and treatment for Hirschprung’s disease?
Ix:
- Full thickness biopsy of affected segment
- Hypertrophied nerve fibres, no ganglia
Tx:
- Insufflation
- Resection of affected segment + pull-through of normal functioning bowel
What are some causes of an obstruction?
- Constipation
- Diverticular disease
- Adhesions
- Herniation
- External mass
- Volvulus
- Intussusception
What is a volvulus?
The complete twisting of bowel loop at mesenteric base around vascular pedicle
- Small bowel (infants)
- Caecum (elderly)
What are some inflammatory bowel diseases?
Acute colitis:
- Infection
- Drug/toxin
- Chemo/radiotherapy
Chronic colitis:
- IBD
- TB
What is a Clostridium difficle infection, its causes, diagnosis + treatment?
Pseudomembrane formation
- Causes: (4C’s) Ciprofloxacilin, Cephalosporins, Clindamycin, Co-amoxiclav
- Dx: Exotoxins (toxin stool assay)
- Tx: Side room + vancomycin + metronidazole
What are some causes of ischaemic colitis?
- Arterial or venous occlusion
- Small vessel disease (DM / Vasculitides)
- Low flow rates (hypovolaemic shock -> hypoperfusion)
- Obstruction
What is the epidemiology and aetiology of Crohn’s disease?
Epi:
- Western populations
- Peak onset = 20s
- F>M
- White 2-5x > non-white
- Smoking worsen Sx
Aetiology:
- Unknown
- MZ twin concordance 50%
What is the pathophysiology of Crohn’s disease?
Distribution, nature of lesions, bowel + first lesion
Distribution:
- Affects whole GI tract (mouth to anus)
- Terminal ileum + caecum
- SKIP LESIONS
- COBBLESTONE APPEARNCE (areas of healthy mucosa lie above diseased mucosa)
Nature of lesions:
- TRANSMURAL INFLAMMATION
- Non-caseating granulomas
Bowel:
- Thick bowel wall
- Narrow lumen
First lesion = aphthous ulcer
- Ulcers, fissures + abscesses
What is the epidemiology + aetiology of Ulcerative colitis?
Epi:
- More common than Crohn’s
- White > non-white
- Peak age = 20-25yrs
- Smoking is protective factor
Aetiology:
- Unknown
- MZ twin concordance = 15%
What is the pathophysiology of Ulcerative Colitis?
Distribution, nature of lesions + bowel
Distribution:
- Proximal extension from rectum + colon
- CONTINUOUS involvement of mucosa
- BACKWASH ILEITIS
Nature of lesions:
- Inflammation of superficial
- Confined to mucosa
- Shallow ulcers
Bowel:
- Normal bowel thickness
- Pseudopolyps
What are the clinical featuers of Crohn’s + Ulcerative colitis?
Crohn’s
- Intermittent diarrhoea
- Pain
- Fever
Ulcerative Colitis:
- Bloody diarrhoea
- Mucus
- Crampy abdominal pain, relieved by defecation
General:
- Angular stomatitis
- Anterior uveitis
- Erythema nodosum
- Pyoderma gangrenosum
- Arthritis
What are some complications, investigations and management options for Crohn’s disease?
Cx:
- Strictures
- Fistulae
- Abscess formation
- Perforation
Ix:
- Systemic markers of inflammation
- ESR/CRP, Barium contrast, Endoscopy
Tx:
- Prednisolone (Mild attack)
- IV hydrocortisone + metronidazole (Severe attacks)
- Azathioprine, methotrexate, infliximab (additional)
What are some complications, investigations + management options for ulcerative colitis?
Cx:
- Toxic megacolon
- Severe haemorrhage
- Adenocarcinoma (20-30x risk)
Ix:
- Rectal biopsy
- Flexible sigmoidoscopy
- AXR
- Stool Culture
Tx:
- Prednisolone + Mesalazine (Mild)
- Prednisolone + 5-ASA + Steroid enema BD (Moderate)
- Admit + NBM + IV fluids + IV hydrocortisone + rectal steroids (severe)
- 5-ASA first-line OR azathioprine second-line (remission)
What are some features of diverticular disease?
- High incidence in west (low fibre diet)
- 90% = left colon
- Asymptomatic +/- PR bleed
- Presence of diverticulae = diverticulosis
- Barium enema CT/endoscopy = BOWEL OUTPOUCHINGS (at weak points of bowel)
What are some complications fo diverticular disease?
- Divertculitis: Fever + peritonism
- Gross perforation
- Fistula
- Obstruction
What is carcinoid syndrome?
- Diverse group of tumours of enterochromaffin cell origin
- Produce 5-HT (serotonin)
- Commonly found in bowel
- Slow growing
What symptoms are characteristic of carcinoid syndrome versus a carcinoid crisis?
Syndrome:
- Bronchoconstriction
- Flushing
- Diarrhoea
Crisis:
- Life threatening vasodilation
- Hypotension
- Tachycardia
- Bronchoconstriction
- Hyperglycaemia
What are the investigations and management for carcinoid syndrome?
Ix:
- 24hr urine 5-HIAA (main metabolite of serotonin)
Tx:
- Octreotide (somatostatin analogue)
What is the classification for gastric (neoplastic polyps) adenomas and their occurrence?
- Tubular appearance (>75%)
- Tubulovillous (25-75%)
- Villous (>75%)
What are some features of gastric adenomas?
- Benign dysplastic lesions
- Precursors to most adenocarcinomas
- 50% of >50yrs in Western world
- Mostly asymptomatic
What are RFs for malignancy in a gastric adenoma?
- Large size (>3.4cm)
- Degree of dysplasia
- Increased villous components
- No. of polyps
What proto-oncogenes require activation for the transformation of gastric adenomas to carcinomas?
- KRAS
- LOF mutations (p53)
What are some non-neoplastic polyps?
- Hamartomatous polyp
- Hyperplastic polyp
- Inflammatory
What is the epidemiology + aetiology of colorectal cancer?
Epi:
- 2nd most common cause of cancer deaths in UK
- 60-79yrs
- IF <50yrs consider familial syndrome
- Western population
- 98% adenocarcinomas
- 45% in rectum
Aetiology:
- Diet (reduced fibre, increased fat)
- Lack of exercise
- Obesity
- Chronic IBD
- Familial syndromes
What are protective against the development of colorectal cancer?
NSAIDs
What are some clinical features and investigations for colorectal cancer?
Right sided tumours:
- IDA
- Weight loss
Left-sided tumours:
- Change in bowel habit
- Crampy LLQ pain
Ix:
- Proctoscopy/sigmoidoscopy/colonoscopy
- Barium enema
- Bloods
What is used to monitor disease + response to therapy in colorectal cancer?
Carcinoembryonic antigen (CEA)
What staging system is used in Colorectal cancer and what are the different types?
Duke’s Staging
- A: Confined to mucosa
- B1: Extends into muscularis propria
- B2: Transmural invasion
- C1: Extends to muscularis propria with LN metastasis
- C2: Transmural invasion with LN metastasis
- D: Distant metastasis
What is the management of colorectal cancer?
SURGERY
- Rectal cancer/low sigmoid cancer <1-2cm above anal sphincter = abdomino-perineal resection
- Rectal cancer/low sigmoid cancer >1-2cm above anal sphincter = anterior resection
- Sigmoid cancer = sigmoid colectomy
- Descending colon = Left hemicolectomy
- Ascending colon = Right hemicolectomy
- Transverse colon = Extended right hemicolectomy
RADIOTHERAPY
CHEMOTHERAPY (in palliation): 5-FU - fluorouracil
What is familial adnemomatous polyposis and its features?
- Lots of polps ~1000
- 70% AD mutation in adenomatous polyposis coli (APC) gene
- 30% AR mutation in DNA mismatch repair genes
- 100% will get cancer (adenocarcinoma) in 10-15yrs
Where is the APC gene found and what type of gene is it?
- Adenomatous Polyposis Coli
- C5q1
- Tumour suppressor gene
What is Gardners syndome and its features?
- Subtype of FAP (familial adenomatous polyposis)
- AD
- Has extra-intestinal features (e.g. osteomas of skull, dental caries, epidermoid cysts, desmoid tumours, unerupted supernumary teeth)
What is Hereditary Non-Polyposis Colorectal Cancer/Lynch Syndrome (HNPCC) + its features?
- AD mutation in DNA mismatch repair genes
- Carcinomas usually in right colon
- Fast progression to malignancy
- Onset <50yrs
- A/w extra-colonic cancers: Endometrial, Ovarian, Small bowel, stomach etc.
- Fewer polyps than FAP
What is the general treatment for familial syndromes causing colorectal cancer?
- Regular monitoring
- Total colectomy (eventually)
