Viral hepatitis

Carcinomas of the Alimentary tract

Esophageal Carcinoma (EC) Gastric Carcinoma (GC) Colorectal Carcinoma (CRC)

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Barrett esophagus

(precursor of E-adenocarcinoma )

Preneoplastic disorders of these three tumors:EC: >90%-squamous cell carcinomas, <10%-adenocarcinomas. 　　　　　 preceded by chronic esophagitis ---Squamous epithelial dysplasia --- intraepithelial neoplasia (carcinoma in situ)----preneoplastic disorder

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chronic esophagitis carcinoma in situ

chronic esophagitis3

Mild esophagitis: simple hyperemia, with no histologic abnormality.

Uremia,prolonged gastric intubation, ingestion of corrosive or irritant substances, radiation, and so on

Many causes may induce chronic esophagitis

Morphologic change- on gross:

Severe esophagitis: epithelial erosion, or ulceration into the submucosa.

chronic esophagitis ( on microscope)4

chronic esophagitis

three histologic features:

① eosinophils, with or without neutrophils, in the epithelial layer; ② basal zone hyperplasia, ③ elongation of lamina propria papillae.

intraepithelial neutrophils occur in more severe injury.

Barrett esophagus: Replacement of esophageal squamous-epithelium with gastric epithelium (in book page 218)

distal esophagus (pale pink)

stomach(more lush light brown)

Gastroesophageal junction

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(salmon-pink)

metaplastic columnar

gastric epithelium

Normal condition Barrett esophagus

Preneoplastic disorders (precursor lesions)GC1. Atrophic chronic gastritis with mucosal dysplasia

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2. Adenoma : true neoplasm

containing dysplastic epithelium

Preneoplastic disorders

CRC

1. Adenoma (villous adenoma)

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(in book page 236)

(in book page 231-234)

3. FAP （ familial adenomatous polyposis)---

2. Ulcerative colitis

(in book p237 )

Adenomas of colon8

(in book page 236)villous adenoma

Basis on the epithelial architecture, adenomas of colon is divided into three sub-types.

tubular adenomas (most common)tubulovillous adenoma (5-10%), villous adenomas (only 1%)

villous adenoma On gross: sessile, velvety or cauliflower-like masses;

On microscope: frondlike villiform extension of the mucosa is covered by dysplastic epithelium.

Invasive carcinoma is found in up to 40% of these lesions.

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(in book page 231-234)

Ulcerative colitis(ulceroinflammatory disease)

affect the colon limite to the mucosa and submucosa (except in the most severe cases) a systemic disorder

On gross, mucosa hyperemia, edema, and granularity. (with easy bleeding) In severely active cases, broad-based ulceration.

Morphologic features:

Histologic features: mucosal inflammation, ulceration of the mucosa, chronic mucosal damage.

MorphologyMorphology

1. Favored Location:

EC three natural narrow areas

20% of ～ arise in upper third esophagus (5cm)

50% in the middle third esophagus (18cm)

30% in the lower third esophagus (1-2cm)

GC Pylorus and antrum 50~60%;

Cardia 25%; remainder in body/fundus

Lesser curvature (about 40%) > greater curvature (12%)

So, favored location of ～ : lesser curvature of the antropyloric region

CRC 50% arise in rectum, and 25% in ascending colon.

10Three natural narrow of esophagus

2. Three gross pattern –take one of three forms

EC ●Exophytic polypoid or fungating form: mass protrude into the lumen

●Endophytic ulcerative form : ulcerative cancer mass extend deeply

● Diffuse infiltrative form: cancer mass impart thickening and rigidity

to the wall and lead to narrowing of the lumen.

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2. Gross appearance: base on invasive depth-early and advanced ～GC (1) Early Gastric Carcinoma (E-GC) : confined to the mucosa and submucosa, regardless of presence or absence of perigastric lymph node metastases. 　

（ basis on clinical data: 10 ％ of E-GC: lymph node metastases ）

Elevated form of E-GC

Depressed form of E-GC

Two gross patterns: elevated form depressed form

Both have no obvious tumor mass

in the mucosa (---)

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2. Gross appearance

GC (2) Advanced Gastric Carcinoma (A-GC) : tumor mass has extended below the submucosa into the muscular wall. In some cases, perhaps has spread more widely.

A-GC have three gross forms:

(2.1) Exophytic polypoid or fungating mass (form)

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(2.2 ) Endophytic ulcerative form

(2.3 )Diffuse infiltrative mass. This rigid and thickened stomach is called a “leather bottle” stomach— 革囊胃

(cancer mass imparts thickening and rigidity to

the wall, and lead to narrowing of the lumen)

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(2.2 ) Endophytic ulcerative mass

larger, more surface ，significant elevated edges

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Gastric ulcerative carcinoma gastric peptic ulcer

gastric peptic ulcer gastric cancer ulcerLocation the lesser curvature the lesser and greater ～ Size / shape 1-2cm, round ＞２ cm, irregular

Basis of depth deeper more surface

Margins sharply elevation or beading

Surrounding mucosal folds radiate absent

Base of crater clean necrotic gray Cut section an eroded artery absent

Histologic appearance four zones invasion by malignancy

Obvious differences between peptic ulcer and cancer ulcer: (list)16

peptic ulcer

Cancer ulcer

2. Gross appearance

CRC

(1)Exophytic

Polypoid or fungating form

(2)Endophyticulcerative form

(3)Diffuse infiltrative form

(4) Mucinous mass with a gel-colloid appearance.(mucinous adenocarcinoma)

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Microscopic appearance : carcinomas arise from

superficial epithelium of mucosa or gland EC Squamous cell carcinoma constitute ＞ 90%

Adenocarcinomas: (<10%), arise from dysplastic mucosa in Barrett esophagus.

Well- moderately- poorly-differentiated

(Mucin-producing adenocarcinoma)

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GC Adenocarcinoma ＞ 90%

Squamous cell carcinoma (<10%): locate in cardia.

　 Histologic: gastric adenocarcinoma --- two major types:

　　　　 intestinal- type diffuse-type

Microscopic appearanceMicroscopic appearance

There are some differences between these two types (in book page 226-227)

WHO Classification Method: well-, moderately-, poorly-differentiated.

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Malignant calls form neoplastic glands do not form glandsLike glands of colonic-- permeate the gastric wall

Microscopic appearanceMicroscopic appearance

GC

signet-ring cell carcinoma

Nucleous of tumor cell is

squeezed to cell margin,

like diamond in married-ring.

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Microscopic appearanceMicroscopic appearance

CRC

Adenocarcinoma ＞ 90%

Signet-ring cell carcinoma: Mucin present in tumor cells

Mucinous adenocarcinoam: Mucin is secreted into gland lumina

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Squamous cell carcinoma (arising anal zone ）

Special type: produce mucin

EC ( 食道癌 )

CPC (clinico-pathological correlation)

GC ( 胃癌 )

CRC ( 大肠癌 )

In onset: insidiousIn late stage －　dysphagia and obstruction gradually Bleeding-hematemesis or melena Other: weight loss, anorexia, fatigue, weakness and pain (relate with swallowing)

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E-GC: asymptomaticA-GC: abdominal discomfort or weight loss Locate in cardia: dysphagia Locate in the pyloric canal: obstructive symptoms Other: melena, fatigue, weekness--

Most cases: remain asymptomatic for yearsTo see doctor: Faeces with bright red blood, change in bowel habit, and abdominal discomfortSignificant clinical features: Faeces with bright red blood Faeces like writing brush Alternation of obstruction and diarrhea

Bleeding: in these three tumors

As blood quickly congeals and turns brown in the acid environment of the stomach lumen

Vomited blood: coffee grounds in patients with GC bright red blood in EC

Faeces: melena (black- faeces) in patients with EC or GC bright red blood in patients with CRC

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Invasion and metastasis ( 浸润和转移 )

Spread by direct extension into adjacent structures

For EC:

Upper third larynx, trachea, thyroid (occurred)

Middle third bronchus

Lower third cardia贲门

into

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Invasion and metastasis

Spread by direct extension------

For GC: spread into greater omentum and pancreas

For CRC: spread into urinary bladder or uterus

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Invasion and Metastasis

2. Metastasis （ for EC) Lymphatic pathway: Spread to regional LN

late stage terminal LN - left supraclavicular L

　　　　　　　 （ last region ）胸导管－左锁骨上 LN (Virchow LN)

Hematogenous pathway: to distant sites

favored organs: Lung, liver and bone. Seeding within body cavities: In females , tumor cells of GC seed to both the ovaries,

krukenberg tumor ( 克氏瘤 )

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1. Endoscopy biopsy

2. Digital rectal examination : for rectal cancer.

Digital rectal examination

Diagnosis27

Prognosis: for all tumors

The most important prognostic indicator is the tumor stage at the time of resection.

at Early stage: 5-y survival rate 90 ～ 95% ，　removed

at Late stage: 5-y survival rate 10 ～ 15% ， removed

So the only hope for cure of tumor is early detection and surgical remove.

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Related to gene alterations

Many studies indicate: genesis and development of tumor relate to some genes.

EC - p53, p16

GC - c-met, K-sam, erb

CRC - APC

DNA repair gene

DCC （ deleted in colon cancer)

p53 K-ras

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Colorectal carcinogenesis: two pathogenetically distinct pathways for the development of colon cancer.

APC/β-catenin pathway

(adenoma-carcinoma sequence, or chromosome instability)

Mismatch repair pathway

(microsatellite instability)

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Colorectal carcinogenesis:

both of these pathways involve the stepwise accumulation of multiple gene’mutations.

but the genes involved and the mechanisms are different.

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Mismatch repair pathway (p239, Fig.10-23)

APC/β-catenin pathway (p.239,Fig. 10-22)

Normal colonAdenomas

Carcinoma

Mucosal at risk

APC at 5 APC/β-catenin K-RAS at 12p12 TelomeraseMany other genesP-53 at 17p13

LOH at 18q21

Normal colon CarcinomaSessile serrated adenoma

MLH1, MSH2

Alteration of second allele by LOH, mutation, or promoter methylation

Microsatellite instability

Mutations of BAX,TCF-4, et al

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