Presentation on theme: "Carcinomas of the Alimentary tract"— Presentation transcript:
1Carcinomas of the Alimentary tract 1Viral hepatitisCarcinomas of the Alimentary tractEsophageal Carcinoma (EC)Gastric Carcinoma (GC)Colorectal Carcinoma (CRC)
2Preneoplastic disorders of these three tumors: 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 disorder2chronic esophagitiscarcinoma in situ
3chronic esophagitis Many causes may induce chronic esophagitis Uremia, 3Mild esophagitis: simple hyperemia, with nohistologic abnormality.Uremia,prolonged gastric intubation,ingestion of corrosive or irritant substances, radiation, and so onMany causes may induce chronic esophagitisMorphologic change- on gross:Severe esophagitis: epithelial erosion, or ulcerationinto the submucosa.
4chronic esophagitis ( on microscope) 4chronic esophagitis ( on microscope)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.chronic esophagitis
5Barrett esophagus: Replacement of esophageal squamous-epithelium with gastric epithelium (in book page 218)distal esophagus(pale pink)stomach(more lush light brown)Gastroesophageal junction5(salmon-pink)metaplastic columnargastric epitheliumNormal condition Barrett esophagus
7Preneoplastic disorders CRC 1. Adenoma (villous adenoma)7(in book page 236)(in book page )3. FAP（familial adenomatous polyposis)---2. Ulcerative colitis(in book p237 )
8Adenomas of colon8(in book page 236)villous adenomaBasis 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%)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.
9(ulceroinflammatory disease) 9(in book page )Ulcerative colitis(ulceroinflammatory disease)affect the colonlimite to the mucosa and submucosa(except in the most severe cases)a systemic disorderOn 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.
10Morphology 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/fundusLesser curvature (about 40%) > greater curvature (12%)So, favored location of ～: lesser curvature of the antropyloric regionCRC 50% arise in rectum, and 25% in ascending colon.10Three natural narrow of esophagus
112. 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.11
122. 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-GCDepressed form of E-GCTwo gross patterns: elevated formdepressed formBoth have no obvious tumor massin the mucosa (---)12
132. Gross appearanceGC (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)13
14(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 tothe wall, and lead to narrowing of the lumen)14
15(2.2 ) Endophytic ulcerative mass larger, more surface，significant elevated edges15Gastric ulcerative carcinoma gastric peptic ulcer
16gastric peptic ulcer gastric cancer ulcer Location the lesser curvature the lesser and greater～Size / shape cm, round ＞２cm, irregularBasis of depth deeper more surfaceMargins sharply elevation or beadingSurrounding mucosal folds radiate absentBase of crater clean necrotic grayCut section an eroded artery absentHistologic appearance four zones invasion by malignancyObvious differences between peptic ulcer and cancer ulcer: (list)16peptic ulcerCancer ulcer
172. Gross appearance CRC 17 (1)Exophytic Polypoid or fungating form (2)Endophyticulcerative form(3)Diffuse infiltrative form(4) Mucinous mass with a gel-colloid appearance.(mucinous adenocarcinoma)
18Microscopic appearance : carcinomas arise from superficial epithelium of mucosa or glandEC Squamous cell carcinoma constitute ＞90%Adenocarcinomas: (<10%), arise from dysplastic mucosa in Barrett esophagus.Well moderately poorly-differentiated(Mucin-producing adenocarcinoma)18
19Squamous cell carcinoma (<10%): locate in cardia. GC Adenocarcinoma ＞90%Squamous cell carcinoma (<10%): locate in cardia. Histologic: gastric adenocarcinoma --- two major types: intestinal- type diffuse-typeMicroscopic appearanceThere are some differences between these two types (in book page )WHO Classification Method: well-, moderately-, poorly-differentiated.19Malignant calls form neoplastic glands do not form glandsLike glands of colonic permeate the gastric wall
20Microscopic appearance 20Microscopic appearanceGCsignet-ring cell carcinomaNucleous of tumor cell issqueezed to cell margin,like diamond in married-ring.
21Microscopic appearance CRC Adenocarcinoma ＞90% Signet-ring cell carcinoma:Mucin present in tumor cellsMucinous adenocarcinoam: Mucin is secreted into gland lumina21Squamous cell carcinoma (arising anal zone）Special type: produce mucin
22CPC (clinico-pathological correlation) EC (食道癌)CPC (clinico-pathological correlation)GC (胃癌)CRC (大肠癌)In onset: insidiousIn late stage － dysphagia and obstruction graduallyBleeding-hematemesis or melenaOther: weight loss, anorexia, fatigue,weakness and pain (relate with swallowing)22E-GC: asymptomaticA-GC: abdominal discomfort or weight lossLocate in cardia: dysphagiaLocate in the pyloric canal: obstructive symptomsOther: 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 bloodFaeces like writing brushAlternation of obstruction and diarrhea
23Bleeding: in these three tumors 23Bleeding: in these three tumorsAs blood quickly congeals and turns brown in the acid environment of the stomach lumenVomited blood: coffee grounds in patients with GCbright red blood in ECFaeces: melena (black- faeces) in patients with EC or GCbright red blood in patients with CRC
24Invasion and metastasis (浸润和转移) Spread by direct extension into adjacent structuresFor EC:Upper third larynx, trachea, thyroid (occurred)Middle third bronchusLower third cardia贲门into24
25Invasion and metastasis Spread by direct extension------ 25Invasion and metastasisSpread by direct extension------For GC: spread into greater omentum and pancreasFor CRC: spread into urinary bladder or uterus
26krukenberg tumor (克氏瘤) Invasion and Metastasis2. Metastasis（for EC) Lymphatic pathway: Spread to regional LNlate stage terminal LN - left supraclavicular L（last region）胸导管－左锁骨上LN (Virchow LN)Hematogenous pathway: to distant sitesfavored organs: Lung, liver and bone.Seeding within body cavities:In females , tumor cells of GC seed toboth the ovaries,krukenberg tumor (克氏瘤)26
27Diagnosis 1. Endoscopy biopsy 2. Digital rectal examination : for rectal cancer.Digital rectal examinationDiagnosis27
28Prognosis: 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%， removedat Late stage: 5-y survival rate 10 ～ 15% ，removedSo the only hope for cure of tumor is early detection and surgical remove.28
29Related to gene alterations Many studies indicate: genesis and development of tumor relate to some genes.EC - p53, p16GC - c-met, K-sam, erbCRC - APCDNA repair geneDCC（deleted in colon cancer)p53 K-ras30
30Colorectal 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)30
31Colorectal carcinogenesis: 31Colorectal carcinogenesis:both of these pathways involve the stepwise accumulation of multiple gene’mutations.but the genes involved and the mechanisms are different.
32Mismatch repair pathway (p239, Fig.10-23) APC/β-catenin pathway (p.239,Fig )Normal colonAdenomasCarcinomaMucosal at riskAPC at 5APC/β-cateninK-RAS at 12p12TelomeraseMany other genesP-53 at 17p13LOH at 18q21Sessile serrated adenomaMLH1, MSH2Alteration of second allele by LOH,mutation, or promoter methylationMicrosatellite instabilityMutations ofBAX,TCF-4, et al32