Early oesophageal cancer

dr. Nina Zidar

Institute of Pathology

Faculty of Medicine

University of Ljubljana

Slovenia

Early carcinoma of oesophagus = tumor limited

to mucosa or submucosa, not extending into

muscularis propria.

• T1a: tumors invading lamina propria or

muscularis mucosae

• T1b: tumors invading submucosa

AJCC (American Joint Comittee on

Cancer) TNM Classification

Risk of lymph node metastases in 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 and Stolte M. Pathology of the early upper GI 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 = invasion to musc. mucosae

SM1 = invasion of upper third of submucosa

SM2 = invasion of middle thirdof submucosa

SM3 = invasion of lower third ofsubmucosa

• 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

Early carcinoma of oesophagus

Early SCC ≠ early adenocarcinoma!

- epidemiology

- etiology

- behaviour

- prognosis

1. EPIDEMIOLOGY

Epidemiology of oesophageal carcinoma

• 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 oesophageal squamous cell

carcinoma

• tobacco and alcohol

• diet

• genetic factors

• radiation

• achalasia

• inflammatory conditions (gastritis, coeliac

disease, systemic sclerosis, caustic injury)

• history of ca of the upper aerodigestive tract

• infection (aspergillus, candida, HPV)

Etiology of oesophageal squamous 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

• metachronous carcinoma: 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 cell carcinoma of oesophagus

In situ hybr. E6/E7 mRNA

• conflicting results

• prevalence of HVP from 0% to 70%

• HPV may potentially be involved in

oesophageal cancerogenesis

• use proper methods to

demonstrate transcriptionally active

(integrated) virus

p16

Al-Haddad S et al. Infection and esophageal cancer. Ann N Y Acad Sci 2014;

1325: 187-96

Etiology of oesophageal adenocarcinoma

• 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

Rajendra S et al. Transcriptionally active human papillomavirus is strongly associated with

Barrett‘s dysplasia and esophageal adenocarcinoma. Am J Gastroenterol 2013; 108: 1082

HPV may be 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

4. MACROSCOPICAL FEATURES

Carcinoma of oesophagus

• SCC: middle third

• adenocarcinoma: lower

third

Squamous cell carcinoma of oesophagus

pT2pT1 pT3

Adenocarcinoma in Barrett‘s oesophagus

5. MICROSCOPICAL FEATURES

Squamous cell carcinoma of oesophagus

Grade 2Grade 1 Grade 3

Squamous cell carcinoma

Cytokeratin 5/6

Squamous cell carcinoma

p63

Oesophageal squamous cell carcinoma –

differential diagnosis

• dysplasia (intraepithelial neoplasia)

• invasion beyond the basement membrane

• desmoplasia

• no ancillary methods

• serial sections!!

• metastases and direct spread (from lungs)

Adenocarcinoma of oesophagus

Intestinal, well differentiated Intestinal, poorly differentiated

Adenocarcinoma of oesophagus

Diffuse type (signet ring) Mucinous (colloid)

Oesophageal adenocarcinoma –

differential diagnosis

• dysplasia (no nucleoli, no necrosis, no back-

to-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)

Rubio CA, Riddell R. Musculo-fibrous anomaly in

Barrett's mucosa with dysplasia. Am J Surg

Pathol 1988; 12: 885-9

• thickening of muscularismucosae, fibrosis, extension to lamina propria

• similar than in urinary bladdercarcinoma

• specific for Barrett‘s oesophagus(50%-100%)

• not related to dysplasia or carcinoma

• may result in erroneous stagingof carcinoma

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 analysisof 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

Vessels in true submucosaVessels in new layer between layers of

duplicated muscularis mucosae

Staging tumors with duplicated

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

6. PROGNOSIS and TREATMENT

Prognosis of oesophageal 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)

• rarey diagnosed 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!

Low-risk group:

• well- or moderately differentiated carcinoma

• no lymphovascular invasion

• mucosal carcinoma (M1-M3)

• less than 2 cm

High-risk group:

• poorly differentiated carcinoma

• lymphovascular invasion

• submucosal invasion (SM1-SM3)

• larger than 2 cm

Risk stratification in early Barrett‘s adenocarcinoma

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

Thank you for your attention!