Upper GI Flashcards
What is the IHC profile of HCC vs cholangiocarcinoma
HCC:
Positive: Cam 5.2, HepPar-1, Albumin ISH, AFP (50%), CEA (pattern of positivity specific)
Negative: AE1/AE3neg (an exception to normal rule of carcinomas being positive), CK20/CK7
Cholangio:
Positive: AE1/AE3, cam5.2, CK20/CK7, CEA ( pattern of positivity specific)
Negative: HepPar1, albumin ISH (but positive in intrahepatic cholangio), AFP
What is the epidemiology and risk factors for HCC
Males >. Females
Leading cause of cancer mortality worldwide
Higher incidence in areas with high rates of hep b/c
Risk factors:
Hep b/c infection (80% of cases)
Injected drug use
Liver Cirrhosis
Obesity
Diabetes
Smoking
Alcohol use
Haemochromatosis
What is the typical presentation of HCC
Painless liver mass, without symptoms directly related to cancer
More likely to have signs and symptoms of underlying liver disease
-Cancer related: pain, weight loss, early satiety, diarrhoea, fever, fatigue
-decompensated cirhosis: ascites, encephalopathy, jaundice, variceal bleeding
Associated paraneoplastic syndromes including cutaneous; worse prognosis
What are the typical epidemiological features and risk factors for cholangiocarcinoma
No definite age predisposition
Present age 50-70
Higher rates south east Asia eg Thailand.
Risk factors:
-Primary sclerosing cholangitis (younger age of presentation). Lifetime risk 5-20%
-hepatobiliary lithiasis
-Liver flukes
-cystic fibrosis
-Le Fraumeni
-smoking
-hep b/c
-cirrhosis
-inflammatory bowel disease
-obesity, diabetes (also risk factors for HCC)
What are the microscopic features of cholangiocarcinoma
Usually adenocarcinoma
Significant peritumoural desmoplasia (lower yield of biopsy)
Typically multi focal
High rates of perineural invasion
Polysomy on FISH
What are prognostic factors for cholangiocarcinoma, what is the5yr survival
Age, stage, grade, margin status.
2-30% 5yr OS
What are the most common metastatic sites for cholangiocarcinoma
Liver, lung, peritoneum, bone
What blood tests should be done for a suspected liver cancer
Hep b/c (both, more HCC)
CEA (both)
CA19-9 (CCA)
AFP (HCC)
CBC
Coagulation screen (PT/INR)
Albumin
Liver enzymes, bilirubin
What scoring system is used for liver cirrhosis and what are it’s components?
Child’s Pugh
-total score groups into class A, B, C. C is worst class
-total bilirubin
-serum albumin
-PT or INR
-ascites (absent, moderate, severe)
-encephalopathy
What are the American screening recommendations for HCC
Anyone with chronic hep b infection and/or cirrhosis. Unless Child’s Pugh C and NOT on transplant list (ie prognosis too poor to warrant screening)
6 monthly USSand AFP
What is the microscopic appearance of hepatocellular carcinoma
May be one or several discrete lesions, or diffusely infiltrating the liver
Macroscopically pale or yellow (fatty) or green due to bile. May invade veins
Well/moderately differentiated: cells resembling hepatocytes, marked cellular atypia in poorly differentiated
Thick plates or trabeculae, pseudoglandular structures.
What is a typical presentation of cholangiocarcinoma
Presents early with small tumours due to signs and symptoms of biliary tract obstruction
Intrahepatic can present later, usually in individuals without liver cirrhosis. RUQ pain, weight loss.
1/3 have nodal Mets at diagnosis
What are the typical microscopic features of cholangiocarcinoma
Typically well to moderately differentiated
Adenocarcinoma features
Glandular/tubular structures lined by malignant epithelial cells
Abundant fibrous stroma
LVSI, PNI common
What imaging is used in the work up of hepatocellular carcinoma
MRI or
4 phase CT: pre contrast, hepatic arterial phase, portal venous phase, delayed phase
What are prognostic factors for hepatocellular carcinoma
Child’s Pugh score
Performance status
Stage
Metastatic disease
What does IPMN stand for, and where in the pancreas are they most commonly located. What is its radiological appearance
Intraductal papillary mucinous neoplasm
Head of pancreas, either in the main pancreatic duct or it’s branches
Cystic appearance on imaging (solid more concerning for invasive malignancy)
What are the three subtypes of IPMN
Gastric
Intestinal
Pancreatobiliary
Based on the appearance of the cells
What is the pre invasive lesion that is most commonly a precursor to pancreatic ductal adenocarcinoma
Pancreatic intraepithelial neoplasia (PanIN)
What is the most common pancreatic tumour
Pancreatic ductal adenocarcinoma
Where in the pancreas is pancreatic ductal adenocarcinoma most commonly located
The head of pancreas
What is the typical microscopic appearance of a pancreatic ductal adenocarcinoma
Well to moderately differentiated
Duct-like glandular structures that haphazardly infiltrate
Desmoplasia
PNI in 90%
LVSI in 50%
What does squamous differentiation mean for prognosis of pancreatic ductal adenocarcinoma
Worse prognosis
What four key driver gene mutations are commonly associated with pancreatic ductal adenocarcinoma, which is highly specific
KRAS (>90%)
p53 (50-80%)
p16 (CDKN2A) (95%)
SMAD4 (50%) highly specific
Ie these are molecular tests that can be done
What is the definition of a pancreatic neuroendocrine microadenoma
Well differentiated NET
<5mm
Non-functional
No mitoses
Benign and often incidental
What two inherited genetic syndromes are most associated with pancreatic NETs
MEN1
VHL
What is the prognosis of an unresectable pancreatic ductal adenocarcinoma
<1 year
What are the names of the exocrine cells and endocrine cells of the pancreas
Exocrine: serous actinic cells
Endocrine: islets of langerhans. Alpha cells: glucagon, beta cells: insulin, delta cells: somatostatin
What are the epidemiological patterns of pancreatic cancer
Male 1.3:1
Peak incidence 60-70
What are risk factors for pancreatic cancer
Chronic pancreatitis
Alcohol
Smoking
Red meat
Chronic diabetes
High BMI
Familial:
-hereditary pancreatitis
-PJS
-FAMMM
-BRCA 2
-Lynch
-ataxia telangiectasia
If screening for individuals with hereditary conditions increasing risk of pancreatic cancer, what are the best investigations?
EUS: highest sensitivity
MRI/MRCP
No consensus on management pathway once a lesion is detected, age to initiate/ terminate screening
What is the usual IHC profile of pancreatic cancer
CK7+/CK20-
P53+
Maspin +
S100+
What are the most common types of non-NET malignancies of the pancreas
Ductal adenocarcinoma
Acinar carcinoma
Pancreatoblastoma
What must be present on IHC for the diagnosis of a pancreatic acinar carcinoma
Pancreatic enzymes. Ie, lipase, amylase or elastase
Trypsin and chemo trips in usually positive
What is the epidemiology of pancreatic NETs
1-2% of all pancreatic tumours
M=F
Median age 40-60
No known environmental risk factors
What IHC marker for pancreatic NETs is also commonly measurable in serum
Chromogranin
What is the 5yr OS for resectable vs unresectable pancreatic ductal adenocarcinoma
Unresectable: 5%
Resectable: 25%. 35% local recurrence, 34% metastatic
What proportion of patients presenting with pancreatic cancer are resectable at baseline
20%. But only 70% of these will actually be respected when they proceed to theatre
What cells does GIST arise from
ICC: interstitial cells of Cajal
Pacemaker cells of the gut: regulate smooth muscle
Where does GIST most frequently arise
Stomach, then small bowel.
What is the epidemiological pattern of GIST
Usually sporadic.
M=F.
Median age 50-70
What is the macroscopic appearance of GIST
Well demarcated tumour
Fleshy tan pink
Centred in muscularis propria
average size 6cm at diagnosis
May have haemorrhaged or cystic degenration
What are the microscopic features of GIST
Most commonly spindle cell, but can be epithelioid or mixed
What are the common mutations associated with GIST
Mostly mutually exclusive,
C-kit: activating tyrosine kinase mutation. 75% of tumours
PDGFRa: activating mutation (platelet derived growth factor receptor alpha
SDH mutation: succinct dehydrogenase (syndrome also associated with paraganglioma/phaeochromocytoma and SDH associated RCC)
What are the key prognostic factors for GIST
Main two:
-tumour size
-mitotic rate 5+ per HPF
Others:
-lack of ckit mutation worse prognosis
-R1 resection or tumour spill
-age
What is the IHC profile for GIST
Positive:
DOG1
CD117 (ckit)
CD34 (non specific)
Negative:
-S100 (Schwannoma positive and CD117 neg, multiple others S100 positive)
-Desmin (positive in smooth muscle tumours)
What TKI can be used to target cKIT in GIST
Imatinib (non specific TKI)
How are GISTs graded
Based on mitotic rate only
Low: </=5
High: >5
What are the two types of gastric dysplasia
Gastric type: resembles gastric foveolar cells, tubovillous folds. Apical mucin
Intestinal type: looks like colonic adenoma; tall columnar cells, hyperchromasia nuclei
How is gastric dysplasia graded
Low grade: preserved polarisation (basal nuclei) and preserved architecture
High grade: prominent cytological atypia, high N:C ratio. Loss of polarity
What is the pathway for H pylori causing gastric adenocarcinoma
Chronic infection -> chronic inflammation -> intestinal metaplasia-> dysplasia -> carcinoma
What are the key risk factors for gastric adenocarcinoma
H pylori
EBV
Smoking
Dietary
What are the most common/relevant morphological subtypes of gastric adenocarcinoma (WHO classification)
Tubular: most common
Poorly cohesive: includes signet ring (intracellular mucin) No well formed glands. Second most common
Mucinous: >50% of tumour has malignant cells in extra cellular mucin pools
Gastric adenocarcinoma with lymphoid stroma: often EBV associated.
How is it determined if a GOJ tumour is staged as oesophageal or gastric
Sievert
Oesophageal: tumour crosses the GOJ and epicentre is within 2cm of GOJ
Gastric: tumour doesn’t cross the GOJ or if it does the epicentre of tumour is >2cm into stomach from GOJ
What are the two types of lymphoma that most commonly affect the stomach
Extranodal DLBCL: similar molecular/IHC profile to nodal DLBCL. Still determine if germinal centre type or activated. Less aggressive than nodal DLBCL
MALToma: h pylori associated, may be cured with H pylori triple therapy. Extranodal Marginal zone lymphoma
What cancers of the stomach is H pylori associated with
gastric MALToma
Gastric adenocarcinoma
What translocation commonly renders gastric MALToma resistant to triple therapy
t(11:18)
Invasion of what layer of the stomach wall distinguishes between early and advanced gastric cancer
The muscularis propria
What is the IHC pattern of gastric MALToma and gastric DLBCL
MALT: CD20, Pax5 positive (b cell markers), CD34. H pylori positive
DLBCL: EBV negative, CD20, CD19, Pax5, CD79a positive. Check for MYC and BCL2 alterations
What were the subtypes of gastric adenocarcinoma under the old Lauren classification
Intestinal type: well differentiated
Diffuse type: poorly differentiated. Basically signet ring/ e cadherin loss. Associated with worse prognosis, early lymphatic dissemination, peritoneal carcinomatosis, highly metastatic.
What are the Siewart classification of GOJ tumours (adenocarcinoma)
Class 1: arise from metaplasia 1-5cm above GOJ, but still involves GOJ.
Class 2: arise 1cm above GOJ to 2cm below
Class 3: arise 2-5cm below GOJ, but still involves GOJ
Class 1 and 2 treated as oesophageal cancer. Class 3 treated as Gastric
What is the cellular process occurring in Barrett’s oesophagus
Metaplasia from squamous epithelium to gastric type intestinal epithelium. Columnar cells with presence of goblet cells.
What are risk factors for Barrett’s oesophagus
GORD
Smoking
Obesity
Male gender
H pylori
What is the pathogenesis to Barrett’s leading to oesophageal adenocarcinoma
Acid/bile reflux ->
Intestinal metaplasia ->
Mutations ->
Low grade dysplasia ->
TP53 mutations ->
High grade dysplasia ->
DNA/chromosomal instability ->
Cancer
What is the microscopic appearance of Barrett’s oesophagus without dysplasia
Columnar cells with apical mucin, moderate cytoplasm, basal nuclei. Wild type p53 IHC staining
Invasion of what layer of the oesophagus wall defines invasive carcinoma
Invasion through basement membrane
What are patterns of growth of oesophageal adenocarcinoma
Tubular
Papillary
Signet ring
Mucinous
(Often mixed, note that these are mostly the same as gastric except for papillary)
What are the IHC patterns of oesophageal adenocarcinoma vs SqCC
Adenocarcinoma: CK7+, mucin +. P63, p40, CK5/6-
SqCC: opposite to above
What are the cytological and architectural features of oesophageal squamous dysplasia
Cytological: nuclear enlargement, pleomorphism, hyperchromasia, loss of polarity, overlapping nuclei
Architecture: loss of maturation
How are low and high grade oesophageal squamous dysplasia distinguished
Low grade: only lower half of epithelial layer involved AND mild atypia only
What are risk factors for oesophageal SqCC
Smoking
Alcohol
Very hot beverages
Achalasia
Caustic ingestion
Most prevalent SE Asia
HPV infection often present, but not thought to be contributing to malignancy.
What are subtypes of oesophageal SqCC
Verrucous- exceedingly well differentiated
Spindle cell- high grade spindle cell component
Basaloid. Solid or nested growth of Basaloid cells. (No HPV associated unlike the oropharynx equivalent
What is the annual risk of oesophageal malignancy associated with each of; Barrett’s oesophagus, LG dysplasia, HG dysplasia
Barrett’s: 0.2-0.5% per year
LG: 0.7% per year
HG: 7% per year
What is the pathogenesis of hepatitis b vs hep c in HCC
Both:
-acute infection -> chronic infection -> chronic liver disease/inflammation -> cirrhosis -> increased hepatocyte division -> HCC
Hep C
- RNA virus that does not integrate in host DNA, so no direct carcinogenic effect
Hep B
-DNA virus that integrates into host DNA, causing genomic instability which causes activation of oncogenes and loss of tumour suppressors -> HCC
What percentage of pancreatic cancer over expresses HER-2
50%
What is the prognosis of pancreatic adenocarcinoma
90% die within 1 year
5yr OS 5%
