Transcript GI-neoplasms-(old-M

Neoplasms of the Gastrointestinal Tract
Dr. M Jeffers
Consultant Histopathologist
AMNCH, Tallaght
Objectives: GI tumour pathology
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tumour nomenclature and classification
tumour aetiology and pathogenesis
precursor lesions
mechanisms of carcinogenesis in different tissues
potential points for prevention / modification
tumour growth and behaviour
invasion
metastasis
tumour staging
staging systems
prognostic factors
AMNCH Tallaght
Useful links
http://medstat.med.utah.edu/WebPath/webpath.html
www.bmj.com : collected resources
ABC of colorectal cancer
ABC of the upper gastrointestinal tract: cancer of the stomach and pancreas
AMNCH Tallaght
Neoplasms
Definition
Epidemiology, Aetiology, Pathogenesis
Morphology: Gross / Microscopic
Clinical presentation and outcome
Prognosis
AMNCH Tallaght
Nomenclature and Classification
Nomenclature / Classification by histogenesis:
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Epithelial
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Mesenchymal
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Neuroendocrine
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Haematolymphoid
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Melanocytic
AMNCH Tallaght
Nomenclature and Classification
Epithelial tumours:
Benign: “adenoma”
Malignant: “carcinoma”
Adenocarcinoma Squamous carcinoma
Small cell carcinoma
AMNCH Tallaght
Nomenclature and Classification
Neuroendocrine tumours:
Benign: “carcinoid”
Malignant:
neuroendocrine carcinoma
small cell carcinoma
AMNCH Tallaght
Nomenclature and Classification
Mesenchymal tumours:
Benign: (tissue)oma
lipoma, leiomyoma etc
Malignant: (tissue)sarcoma
liposarcoma, leiomyoma etc
Gastrointestinal stromal tumour (GIST):
benign
low malignant potential
malignant
AMNCH Tallaght
Nomenclature and Classification
Haematolymphoid tumours:
Bone marrow neoplasm (+/- circulating cells):
leukaemia
Lymph node / extranodal lymphoid cell tumour: lymphoma
AMNCH Tallaght
Neoplasms of the Gastrointestinal Tract
Concepts:
Carcinogenesis:
Metaplasia/Dysplasia/Carcinoma sequence
Adenoma/Carcinoma sequence
Differentiation
Invasion and Metastasis
Tumour staging
AMNCH Tallaght
Tumour Aetiology and Pathogenesis: Carcinogenesis
Various mechanisms operative in carcinogenesis in the GI tract:
Intraepithelial neoplasia – Dysplasia – Carcinoma
Metaplasia – Dysplasia - Carcinoma
Adenoma - Carcinoma sequence
Replicator error phenotype
AMNCH Tallaght
Intraepithelial neoplasia – carcinoma sequence
Multistage process of carcinogenesis from
normal through
low grade intra-epithelial neoplasia (dysplasia) (RR 2.2) through
high grade intra-epithelial neoplasia (dysplasia) (RR >60) to
invasive carcinoma.
Progressive development of architectural and cytological abnormality
Progressive increase in relative risk of invasive carcinoma
Useful model is squamous cell carcinoma of oesophagus.
AMNCH Tallaght
Intraepithelial neoplasia – carcinoma sequence:
Oesophageal cancer
Morphologic abnormality in dysplasia –carcinoma sequence in oesophageal mucosa
reflects underlying genetic abnormality.
p53 mutation
low grade
LOH 3p14 (FHIT)
fragile histidine triad, tumour suppressor gene
Cyclin D1 overexpression (11q13), 3p21 LOH
C-myc, EGFR, HST1 overexpression
invasive carcinoma
AMNCH Tallaght
Intraepithelial neoplasia – carcinoma sequence
Normal oesophageal
squamous mucosa
p53 mutation 
High grade squamous dysplasia
(carcinoma in-situ)
FHIT LOH 
CYD1
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Invasive squamous cell
carcinoma
c-myc, EGFR, HST1
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma Sequence
Multistage process of carcinogenesis from
Normal through
Metaplastic columnar epithelium through
Dysplasia in metaplastic epithelium
low grade
high grade
to
Invasive carcinoma
Useful model is adenocarcinoma of oesophagus
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma sequence:
Oesophageal cancer
Barrett’s oesophagus = columnar lined oesophagus
Replacement of the squamous lining of the distal oesophagus by glandular mucosa in response
to injury, most frequently gastro-oesophageal reflux
metaplasia to gastric and intestinal type epithelium
Stepwise progression of dysplasia in metaplastic epithelium leads to invasive malignancy:
architectural and cytological abnormalities develop.
Morphologic changes reflect underlying molecular genetic / cell cyle regulatory abnormalities
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma sequence:
Oesophageal cancer
Normal
Metaplasia
FHIT alterations, CDKN2A hypermethylation
Dysplasia
rab11 abnormalities
Low grade
Ki67 abnormality
High grade
Invasive carcinoma
APC mutation
p53 mutation (different to scc)
c-erbB2, EGFR
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma sequence:
Oesophageal cancer
Normal oesophageal squamous mucosa
Barrett’s oesophagus: metaplastic columnar and
intestinal mucosa
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma sequence:
Oesophageal cancer
Barrett’s oesophagus: low grade
dysplasia
FHIT
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Barrett’s oesophagus: high grade
dysplasia
Ki67
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p53
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Invasive adenocarcinoma
APC
AMNCH Tallaght
The metaplasia dysplasia sequence: significance
Intestinal metaplasia in the oesophagus is a marker of increased adenocarcinoma risk
Risk of carcinoma is greatest with high grade dysplasia: concurrent carcinoma in up to 50%
Many cases of high grade dysplasia will progress to invasive carcinoma over time
Diagnosis of high grade dysplasia:
Diagnosis of metaplasia:
rebiopsy to exclude invasion
consider surgery
treat underlying conditions (GORD)
surveillance endoscopy to identify dysplasia
aiming to prevent cancers / detect cancer early
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma sequence:
Gastric cancer
Chronic atrophic gastritis is a major risk factor for gastric carcinoma (intestinal type)
Risk of malignant transformation is strongly linked to intestinal metaplasia and intra-epithelial
neoplasia (dysplasia)
Variety of processes may lead to atrophic gastritis:
Helicobacter gastritis
Auto-immune gastritis
Metaplasia – dysplasia sequence acts as a final common pathway in development of
malignancy
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H Pylori infection
Nitrate reductase
Gastritis
iNOS expression
Diet
Nitrite
Acid
NO
N2O 3
Ascorbic acid
Cell damage (DNA, lipids, mitochondria etc)
Apoptosis
Atrophic gastritis
Repair
Metaplasia / dysplasia
Nitrosamines
Mutation
Cancer
AMNCH Tallaght
Metaplasia – Dysplasia – Carcinoma sequence:
Gastric cancer
Chronic gastritis
Intestinal metaplasia
Dysplasia
low grade
high grade
Invasive carcinoma
AMNCH Tallaght
Metaplasia – dysplasia - carcinoma sequence in the stomach
Stomach: normal
Stomach: chronic gastritis
Stomach: atrophy and
intestinal metaplasia
AMNCH Tallaght
Metaplasia – dysplasia - carcinoma sequence in the stomach
Stomach: low grade dysplasia
Stomach: high grade dysplasia
Stomach: invasive adenocarcinoma
AMNCH Tallaght
The metaplasia dysplasia sequence: significance
Most intestinal type gastric cancers develop on a background of atrophy, metaplasia and
dysplasia.
Predisposing factors for atrophy and metaplasia are known:
chronic HP gastritis, auto-immune gastritis etc.
Treatment of predisposing conditions, endoscopic surveillance of patients with documented
metaplasia: strategies to reduce risk, detect cancer early.
AMNCH Tallaght
Colorectal carcinogenesis: the adenoma – carcinoma sequence
Various epidemiological associations in colorectal carcinoma point to the important
role of the adenoma as the precursor lesion of many cancers
Morphological progression in colorectal carcinoma:
Aberrant crypt focus
Adenoma
low grade dysplasia
high grade dysplasia
dysplastic ACF with APC mutation inactivation
proto-oncogene activation: c-myc, ras
suppressor gene inactivation: p53, p21, bax
other abnormalities: BRCA, DCC, E-cad
Carcinoma
AMNCH Tallaght
Methylation
Defect
Normal
Epithelium
Early
Adenoma
APC
Carcinoma
K-Ras
p53
Smad4
??
Intermediate
Late
Adenoma
Adenoma
Mismatch repair defect
TGF, BAX
Metastasis
Carcinoma
MSI +
??
Genetic Model for Sporadic Colorectal Carcinogenesis
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Adenomatous polyps of the colon
Neoplastic polyps, precursors of carcinoma
Architectural patterns:
Tubular/Villous/Tubulovillous
Gross presentation:
sessile/pedunculated/flat adenoma
Risk of malignancy
size (ras), architecture, dysplasia
AMNCH Tallaght
Colon: tubular adenoma
AMNCH Tallaght
normal epithelium
adenomatous epithelium
AMNCH Tallaght
Colon: villous adenoma
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Colon: villous adenoma
AMNCH Tallaght
Polyposis syndromes
Sydromes characterised by multiple polyps in colorectum +/- elsewhere in GIT
FAP:5q21 defect, multiple polyps, 100% lifetime risk of carcinoma
HNPCC:
MSH gene defect, fewer polyps,
typical pattern of tumours
Gardner:
variant of FAP with skin and other lesions
Turcot:
association with CNS neoplasms
AMNCH Tallaght
Table 1. Intestinal polyposis syndromes
Location
Location of
Type(s) of polyp
Location of
of polyp
Gl cancer
extraintestinal tumors
AD
lymphoid
Adenoma;
FGP,
C, SI, ST
C, SI
AD
AD
Adenoma
Hamartoma
C
C,SI,ST
C
C,SI,ST
AD
Juvenile
C,SI,ST
C,SI,ST
Lipoma; fibroma; desmoid
tumor; dental cysts;
osteoma; carcinoma of
thyroid and adrenal glands
Central nervous system tumors
Cancers of the breast,
ovary, uterus, and testis
None
Syndrome
Inheritance
Gardner’s
Turcot’s*
Peutz-Jeghers
Familial polyposis
coli (familial
adenomatous
polyposis)
Juvenile polyposis
(one-third of cases)
Cowden’s
AD
AD
Cronkite-Canada
Adenoma, FGP C, SI, ST
C, SI
None
Hamartoma;
C,SI
inflammatory;
ganglioneuroma;
lipoma; lymphoid
None
Juvenile-like
None
C,SI,ST
Colon (rare)
Facial trichilemomas;
oral mucosal papillomas;
carcinoma of thyroid
gland and breast
None
C,SI,ST
C,SI,ST
None
C,SI,ST
C,SI,ST
None
C
Skin cancer: basal cell;
squamous cell; sebaceous
carcinoma
None
Attenuated
familial
polyposis coli**
Hereditary flat
Adenoma
syndrome**
Muir Torre syndrome
AD
Adenoma;
FGP
AD
Adenoma;
AD
Adenoma
Hereditary mixed
polyposis syndrome
AD
Adenoma; juvenile;
hyperplastic
FGP
C
C
C
GI, gastrointestinal, AD, autosomal dominant, FGP, fundic gland polyp; C, colon; SI, small intestine; ST, stomach.
*Some cases of Turcot’s syndrome have mutations in APC gene, Some cases of Turcot’s syndrome have germline mutations in mismatch repair genes
(hMLH1 and hPMS2).
**Attenuated familial polyposis coli and hereditary flat adenoma syndrome most likely are the same disorder, but they are listed separately in this table.
Attenuated familial polyposis coli and hereditary flat adenoma syndrome are considered variants of familial polyposis coli.
AMNCH Tallaght
Familial adenomatous polyposis (FAP)
Autosomal dominant condition characterised by numerous adenomatous polyps and
high risk of progression to adenocarcinoma
Germline mutation in APC gene (5q21-22) which encodes a 2843 aa polypeptide
which acts as a negative regulator in the Wnt signalling pathway, regulates
cellular -catenin concentration
Lack of functional APC leads to accumulation of -catenin and consititutive
expression of c-myc and cyclin D1
AMNCH Tallaght
Colon: familial adenomatous polyposis
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Adenoma carcinoma sequence: significance and implications
Mechanism underlying most colorectal carcinomas
Identifiable precursor lesions in many cases: early detection of precursor lesions has
obvious implications for early treatment and prevention of invasive disease
Identification of families with germ-line mutations and significant polyposis
syndromes offers significant preventive opportunities
Tumour pathogenesis has direct implications on cancer management and prevention
AMNCH Tallaght
Colorectal carcinogenesis: the mismatch repair defect pathway
Mechanism of carcinogenesis distinct from the adenoma – carcinoma sequence
Tumours characterised by extensive nucleotide insertions / deletions in repeated
sequences in tumour DNA: microsatellite instability (MSI) / DNA replication error (RER)
Tumours with MSI are classified as MSI high-frequency (MSI-H) or
MSI low frequency (MSI-L)
These tumours arise through defects in the DNA mismatch repair mechanism, defects
which may be sporadic or inherited
Some sporadic tumours are MSI-H but most MSI-H tumours characteristic of hereditary
non-polyposis colorectal carcinoma (HNPCC)
AMNCH Tallaght
HNPCC
HNPCC: a syndrome characterised by inherited defects in DNA repair due to
germline mutations of the relevant genes: (hMLH1, hMSH2)
High frequency of colorectal carcinoma
Extracolonic tumours in endometrium, stomach, ovary, brain, skin, small bowel
Criteria for classification as HNPCC: Amsterdam criteria (+ revisions)
Classical tumour characteristics: right sided, large, mucinous, low stage
AMNCH Tallaght
Hereditary Non-polyposis Colorectal Cancer
Criteria:
At least 3 relatives with a HNPCC associated cancer (colorectum/endometrium/small
bowel/ureter/renal pelvis)
Ones should be first degree relative of other two
At least 2 successive generations involved
At least one tumour diagnosed before 50 yrs of age
Familial adenomatous polyposis should be excluded
Tumours should be verified by histopathological examination
AMNCH Tallaght
MSI in colorectal cancer: diagnosis
hMSH2: normal
Normal tissue: hMSH2 expression
hMSH2: tumour
Loss of expression in MSI-H tumour
AMNCH Tallaght
Replicator error phenotype: implications
Identification of MSI-H tumours confers a high probability of an inherited cancer
Cancers can be screened for MSI status, confirmation of germ-line status required
for definition of syndrome
Careful family history combined with tumour characteristics can identify at-risk
groups
Early intervention and prevention opportunities
Tumour pathogenesis impacts directly on patient management and prognosis.
AMNCH Tallaght
Carcinogenesis: review of mechanisms
Various mechanisms operative in carcinogenesis in the GI tract:
Intraepithelial neoplasia – Dysplasia – Carcinoma
Metaplasia – Dysplasia - Carcinoma
Adenoma - Carcinoma sequence
Replicator error phenotype
Various mechanisms implicated at different sites
Significance in terms of identification of precursor lesions, treatment and prevention of cancer
AMNCH Tallaght
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Differentiation
Differentiation refers to the degree of maturation of tumour cells / tissues:
what cell type / tissue type does the tumour grow in ?
how closely does the tumour reproduce normal tissue architecture ?
Tumours are described as:
well differentiated
moderately differentiated
poorly differentiated
Differentiation is closely related to tumour grade:
well differentiated – low grade
poorly differentiated – high grade
AMNCH Tallaght
Differentiation: colorectal carcinoma
well differentiated
moderately differentiated
poorly differentiated
AMNCH Tallaght
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Neoplasms of the Gastrointestinal Tract
Classification of tumours:
Anatomical Location
Origin (Primary/Secondary)
Behaviour (benign/uncertain/malignant)
Histogenesis (epithelial/stromal/lymphoid etc)
AMNCH Tallaght
Tumours of the oesophagus
Benign tumours rare:
Leiomyoma
Most are malignant and most are carcinomas
Squamous cell carcinoma
Adenocarcinoma
AMNCH Tallaght
Oesophageal carcinoma
Approx 6% of GIT cancers
1996 Irish Cancer Registry data:
299 cases (1.4% of all cancers)
303 deaths (4.1% of all cancer deaths)
AMNCH Tallaght
Oesophageal carcinoma
Histological types:
Squamous cell carcinoma
Adenocarcinoma (a/w Barrett’s oesophagus)
Others
Relative proportion of squamous and adenocarcinoma varies with geography
Adenocarcinoma increasing incidence
AMNCH Tallaght
Oesophageal carcinoma
Squamous carcinoma:
Alcohol, Tobacco, Food, HPV
Arise on background of dysplasia / in-situ carcinoma
Varying differentiation
well - poorly differentiated
AMNCH Tallaght
AMNCH Tallaght
Normal Oesphagus
AMNCH Tallaght
Oesophageal squamous carcinoma
AMNCH Tallaght
Squamous cell carcinoma
AMNCH Tallaght
Oesophageal carcinoma
Adenocarcinoma:
Majority arise on a background of Barrett’s oesophagus.
Metaplasia - Dysplasia - Carcinoma sequence
Sequential acquisition of genetic abnormalities, oncogene activation, TSG
inactivation
Majority are intestinal type adenocarcinoma
AMNCH Tallaght
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Oesophageal carcinoma
Invasion through submucosa, muscularis and into soft tissue
Metastasis to regional nodes, distant sites
Most are advanced at diagnosis
5 year survival is poor (<30%)
Early diagnosis improves outcome
AMNCH Tallaght
Tumours of the stomach
Benign tumours are rare:
Leiomyomas etc
Malignant tumours:
carcinoma
>> lymphoma, stromal tumours, carcinoid tumours
AMNCH Tallaght
Gastric carcinoma
Irish Cancer Registry Data 1996:
482 cases (2.3% of total cancers)
399 deaths (5.4% of total cancer deaths)
Male : female 1.5:1
18 lymphomas in same time period
AMNCH Tallaght
Gastric carcinoma
Pathogenesis:
Chronic gastritis - metaplasia - dysplasia
(H Pylori)
Dietary factors, smoking
Genetic factors (HNPCC)
Dysplasia is a final common pathway in intestinal type tumours
AMNCH Tallaght
Gastric carcinoma
Tumour pathology: 2 major types:
Intestinal: Bulky masses / ulcers,
glandular pattern
Diffuse: infiltrative lesions,
“signet-ring” cells
AMNCH Tallaght
Gastric tumour
AMNCH Tallaght
Gastric cancer: Linitis Plastica
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Normal stomach mucosa
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Gastric adenocarcinoma: diffuse type
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Gastric adenocarcinoma: signet ring cells
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Gastric carcinoma
Late presentation is typical
6% present in stage I, 30% stage IV
(of those staged)
Prognosis is poor:
Cumulative probability of survival
34% @ 1yr
20% @5yrs
AMNCH Tallaght
Gastric carcinoma
Importance of Pathologic Staging:
Early gastric carcinoma is disease limited to mucosa and submucosa,
irrespective of nodal involvement
5ys is >90% with surgical resection
Advanced gastric carcinoma is disease which invades the muscularis propria
5ys is <20% regardless of treatment
AMNCH Tallaght
Gastric carcinoma
Patterns of disease spread:
Direct invasion: stomach wall, adjacent structures
local/regional/distant nodal metastases: lesser/greater curve, porta hepatis
haematogenous dissemination: liver, lungs
peritoneal spread
(Krukenberg tumour of ovaries)
AMNCH Tallaght
Adenocarcinoma of the oesophago-gastric junction
Adenocarcinoma which crosses the junction of oesophagus and stomach, regardless
of where the tumour bulk lies
(entirely above ogj: oesophageal carcinoma
entirely below ogj: gastric carcinoma)
Typically a tumour of older males
Increasing in frequency (gastric carcinoma decreasing)
Principal predisposing factor is GERD (not diet or HP gastritis)
Typically present late
AMNCH Tallaght
Other tumours of the stomach
Lymphoma:
Low grade B cell MALT lymphoma
clonal B cell process related to chronic H Pylori infection
High grade B cell lymphoma
Carcinoid tumours
Stromal neoplasms
tumours of muscle/nerve/vascular etc phenotype
Metastases
AMNCH Tallaght
Stomach: large B cell lymphoma
AMNCH Tallaght
Carcinoid tumours of stomach
1. Atrophic gastritis / Pernicious anaemia
hypochlorhydria, antral G cell hyperplasia, Gastrin , ECL cell 
2. Sporadic (G cell or ECL) not a/w hypochlorhdyria
3. Fundic ECL tumours in patients with Zollinger-Ellison syndrome
4. Poorly differentiated small cell carcinoma
AMNCH Tallaght
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Tumours of the small intestine
Small bowel:
75% of GIT, 6% of GIT tumours
Adenomas:
majority occur in region of ampulla of Vater
precursor of carcinoma in this location
AMNCH Tallaght
Tumours of the small intestine: Carcinoma
Adenocarcinoma:
Most occur in duodenum and jejunum
Most probably arise from precursor adenoma
Typical intestinal type adenocarcinomas
May obstruct/perforate/bleed/spread
AMNCH Tallaght
Ampullary carcinoma
AMNCH Tallaght
Tumours of the small intestine: Carcinoid Tumour
Carcinoid tumour:
origin from endocrine (APUD/Kultchitsky cells)
cells are neuroendocrine type, contain neurosecretory granules
may produce hormone and cause carcinoid syndrome
behaviour depends on depth of infiltration
intra-mural: good prognosis,
peritoneal involvement: poor prognosis
AMNCH Tallaght
Small intestinal carcinoid tumour
AMNCH Tallaght
Carcinoid tumour
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Tumours of the small intestine: Lymphoma
Lymphoma:
B cell lymphoma may be of MALT type or non-MALT
T cell lymphoma associated with enteropathy (coeliac disease)
AMNCH Tallaght
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Tumours of the small intestine: Stromal tumours
Stromal tumours:
Tumours derived from mesenchymal structures: muscle ,nerve, interstitial cells etc.
Spectrum from benign-indeterminate-malignant
Usually present as bulky masses with perforation / obstruction / haemorrhage
Criteria for malignancy include size, necrosis, proliferation
Most are Gastrointestinal Stromal Tumours (GIST)
probably of interstitial cell origin
c-kit (CD117) mutation
AMNCH Tallaght
Tumours of the appendix
Carcinoid tumour:
small, often at tip of appendix
typical carcinoid / goblet cell carcinoid
Mucinous neoplasms:
mucinous cystadenoma
mucinous cystadenocarcinoma
May be associated with Pseudomyxoma Peritoneii
AMNCH Tallaght
Colorectal Tumours
Polyps:
Hyperplastic (metaplastic)
Inflammatory, Juvenile, Hamartomatous
Adenomatous
Sporadic / Hereditary syndromes
AMNCH Tallaght
Colorectal cancer
Risk factors / associations:
Geography: industrialised societies
Obesity, inactivity
Diet: meat and refined carbohydrates
family history
adenomatous polyps (sporadic/familial syndromes)
ulcerative colitis
AMNCH Tallaght
Colorectal Carcinoma
>70% arise from adenomas
adenoma incidence is ~ 30 -40%
immediate family of affected patient: risk x 2-3
~ 2% arise on a background of ulcerative colitis
different genetic pathways to neoplasia:
(1) adenoma - carcinoma sequence
(2) hereditary non-polyposis mechanism
(3) UC associated neoplasia
AMNCH Tallaght
Adenomatous polyps of the colon
Neoplastic polyps, precursors of carcinoma
Architectural patterns:
Tubular/Villous/Tubulovillous
Gross presentation:
sessile/pedunculated/flat adenoma
Risk of malignancy
size (ras), architecture, dysplasia
AMNCH Tallaght
Colon: tubular adenoma
AMNCH Tallaght
Colon: adenomatous epithelium
AMNCH Tallaght
Colon: villous adenoma
AMNCH Tallaght
Colon: villous adenoma
AMNCH Tallaght
Colitis-associated neoplasia
UC increases risk x 2-8
Risk increased with
- duration of disease
- extent of disease
- presence of dysplasia
neoplasm evolves from dysplasia rather than adenoma
bcl-2 overexpression less frequent in UCAN
APC gene mutations much less frequent in UCAN
E-cadherin mutations more frequent in UCAN
AMNCH Tallaght
Colorectal carcinoma: Pathology
Virtually all are adenocarcinomas
Irish Cancer Registry 1996:
1784 cases (8.6% of all cancers, largest group apart from skin cancer), close to
European average
Crude incidence 40% > in males
Age standardised incidence 75%> in males
AMNCH Tallaght
Colorectal carcinoma
Left > right side
Left side tend to be annular obstructing lesions
Right side tend to be polypoid exophytic
Intestinal type adenocarcinomas, range of differentiation: well- moderate –poor
+/- mucinous, neuroendocrine differentiation
Mucinous differentiation more common in right sided tumours, HNPCC
association
AMNCH Tallaght
Colon: carcinoma
AMNCH Tallaght
Colon: carcinoma
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Colon: carcinoma
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Colon: adenocarcinoma
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Colorectal carcinoma
Infiltrate into and through wall
metastasize to regional nodes
disseminate through blood to liver, distant sites
prognosis is primarily dependent on stage
Staging: Dukes’ A B C
Dukes’ variants
TNM
Accurate staging depends on pathological examination of resected specimen in conjunction with clinical and
radiological information
AMNCH Tallaght
Dukes’ A
Dukes’ B
Colon cancer: staging
AMNCH Tallaght
Dukes’ C
Colon cancer: staging
AMNCH Tallaght
Colorectal carcinoma
Stage at diagnosis:
Stage 1: <20%
Stage 4 >20%
Cumulative survival probability: 1 yr 69%, 3yrs 51%
1yr: stage 1 90%, stage 4 30%
3yr: stage 1 80%, stage 4 10%
AMNCH Tallaght
Objectives: GI tumour pathology




tumour nomenclature and classification
tumour aetiology and pathogenesis
precursor lesions
mechanisms of carcinogenesis in different tissues
potential points for prevention / modification
tumour growth and behaviour
invasion
metastasis
tumour staging
staging systems
prognostic factors
AMNCH Tallaght