Earlyoesophagealcancer dr. Nina Zidar Institute of Pathology Faculty ofmedicine University of Ljubljana Slovenia
Early carcinoma of oesophagus = tumor limited to mucosa or submucosa, not extending into muscularispropria.
AJCC (American Joint Comittee on Cancer) TNM Classification T1a:tumorsinvadinglamina propriaor muscularis mucosae T1b: tumors invading submucosa
Riskof lymphnodemetastasesin GI tract depending on the depth of invasion Depth of infiltration Colon Stomach Oesophagus Mucosa 0 2 4 % 2 3 % Submucosa 3 18 % 12 27 % 30 52 % Vieth M andstoltem. Pathologyof theearly uppergi cancer. Best Pract Res Clin Gastroenterol 2005; 19: 857-69
Staging T1 carcinoma of oesophagus M1= in situ carcinoma M2 = invasion of lamina propria M3= invasionto musc. mucosae SM1= invasionof upper thirdof submucosa SM2= invasionof middlethird of submucosa SM3= invasionof lowerthirdof submucosa Endo M and Kawano T. Detection and classification of early esophageal squamous cell cancer. Dis Esophagus 1997; 10: 155-8 Eguchi T et al. Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer. Mod Pathol 2006; 19: 475-80
Earlycarcinomaof oesophagus
EarlySCC early adenocarcinoma! -epidemiology -etiology -behaviour -prognosis
1. EPIDEMIOLOGY
Epidemiology of oesophagealcarcinoma worldwide SCC predominates Western world: adenocarcinoma replaced SCC 6-fold increase in incidence of adenocarcinoma mild decline of SCC adenocarcinoma: the most rapidly increasing ca SCC rarely diagnosed at early stage adenocarcinoma may be detected early (endoscopic surveillance of Barrett s)
2. ETIOPATHOGENESIS
Etiology of oesophagealsquamous cell tobacco and alcohol diet genetic factors radiation achalasia carcinoma inflammatory conditions (gastritis, coeliac disease, systemic sclerosis, caustic injury) history of ca of the upper aerodigestive tract infection (aspergillus, candida, HPV)
Etiology of oesophagealsquamous cell carcinoma extensive genetic damage - field cancerization high risk for developing a second primary tumor (prevalence of 9%) synchronous carcinoma: diagnosed within 6 months after the index tumor metachronouscarcinoma: diagnosed more than 6 months after the index tumor pharyngeal or oral SCC risk for esophageal SCC Slaughter et al.»field cancerization«in oral stratified squamous epithelium: clinical implication of multicentric origin. Cancer 1953; 6: 963-8
HPV in squamous cellcarcinoma of oesophagus conflicting results prevalenceof HVP from 0% to 70% HPV may potentiallybeinvolved in oesophageal cancerogenesis useproper methodsto demonstrate transcriptionally active (integrated) virus p16 In situ hybr. E6/E7 mrna Al-HaddadS et al. Infection andesophagealcancer. Ann N Y AcadSci 2014; 1325: 187-96
Etiology of oesophagealadenocarcinoma Barrett oesophagus (95% of adenocarcinomas) gastro-oesophageal reflux disease (GERB) tobacco and alcohol obesity dietary factors inversely associated with H pylori gastritis HPV? rarely from submucosal glands and gastric heterotopia
HPV in adenocarcinoma of oesophagus HPV maybe involved in oesophageal adenocarcinoma: p16, PCR, E6/E7 mrna: high viral load in Barrett with dysplasia or carcinoma, but not in Barrett without dysplasia and in controls Rajendra S et al. Transcriptionally active human papillomavirus is strongly associated with Barrett s dysplasia and esophageal adenocarcinoma. Am J Gastroenterol 2013; 108: 1082
4. MACROSCOPICAL FEATURES
Carcinomaof oesophagus SCC: middle third adenocarcinoma: lower third
Squamous cell carcinoma of oesophagus pt1 pt2 pt3
Adenocarcinoma in Barrett s oesophagus
5. MICROSCOPICAL FEATURES
Squamous cell carcinoma of oesophagus Grade 1 Grade 2 Grade 3
Squamouscellcarcinoma Cytokeratin 5/6
Squamouscellcarcinoma p63
Oesophageal squamous cell carcinoma differential diagnosis dysplasia(intraepithelial neoplasia) invasion beyond the basement membrane desmoplasia no ancillary methods serial sections!! metastasesanddirect spread(from lungs)
Adenocarcinomaof oesophagus Intestinal, well differentiated Intestinal, poorly differentiated
Adenocarcinomaof oesophagus Diffuse type(signet ring) Mucinous(colloid)
Oesophageal adenocarcinoma differential diagnosis dysplasia(no nucleoli, no necrosis, no backto-back glands) stomach carcinoma infiltrating oesophagus CK7+ CK20±, CDX2±, mostly TTF1 - metastases and direct spread from lungs (TTF1+)
Duplicated muscularis mucosae in Barrett s oesophagus
Duplicated muscularis mucosae (musculo-fibrous anomaly) thickening of muscularis mucosae, fibrosis, extensionto lamina propria similar than in urinary bladder carcinoma specific for Barrett s oesophagus (50%-100%) not relatedto dysplasia or carcinoma may result in erroneous staging of carcinoma RubioCA, RiddellR. Musculo-fibrousanomalyin Barrett's mucosa with dysplasia. Am J Surg Pathol 1988; 12: 885-9
Duplicated muscularis mucosae in Barrett s oesophagus
Duplicated muscularis mucosae in Barrett s oesophagus Smoothelin
Duplicated muscularis mucosae in Barrett s oesophagus superficial/new muscularis mucosae new layer of lamina propria deep/true muscularis mucosae Vieth M et al. Histological analysis of endoscopic resection specimens from 326 patients with Barretts s esophagus and earyl neoplasia. Endoscopy 2004; 36: 776-81
Duplicated muscularis mucosae in Barrett s oesophagus Vesselsin newlayerbetweenlayersof duplicated muscularis mucosae Vessels in true submucosa
Staging tumors with duplicated muscularis mucosae Vieth M et al. Histological analysisofendoscopic resection specimens from 326 patients with Barretts s esophagus and earyl neoplasia. Endoscopy 2004; 36: 776-81
6. PROGNOSIS andtreatment
Prognosis ofoesophageal carcinoma Stein HJ et al. Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection. Ann Surg 2005; 242: 566-73
Clinical behaviour in early oesophageal carcinoma SCC: nodal metastases in 10% of M3 tumors, and 50% of submucosal tumors (SM1-SM3) rareydiagnosed in M1 and M2 stage Adenocarcinoma: no nodal metastases in M1-M3 tumors nodal metastases in 10% of SM1 tumors and in 35% of SM3 tumors
Therapy of early oesophageal carcinoma Radical surgery: significant morbidity and mortality removal of lymph nodes Endoscopic resection: less morbidity, negligible mortality incomplete removal continuous endoscopic surveillance!
Risk stratification in early Barrett s adenocarcinoma Low-risk group: well- or moderately differentiated carcinoma no lymphovascular invasion mucosal carcinoma(m1-m3) lessthan2 cm High-risk group: poorly differentiated carcinoma lymphovascular invasion submucosal invasion (SM1-SM3) largerthan2 cm
Endoscopic mucosal resection for early carcinoma in Barett s oesophagus
Handling endoscopic mucosal resection specimens resected en bloc oriented pinned on cork or styrofoam mark deep (!) and lateral margins deep margin more important serial sections
Conclusions Differences between SCC and adenocarcinoma In adenocarcinoma, lymphatic spread occurs later and less frequently. SCC rarely diagnosed in early stage radical surgery needed in the majority of patients Intramucosal adenocarcinoma suitable for endoscopic resection Important correct histopathologic examination of EMR specimens
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