ESOPHAGUS

DR AISHA AKBAR

 Lamina propria: Loose connective tissue, mucous glands in distal portion (cardiac glands) Muscularis Mucosae: Thicker than other parts of GI tract. Submucosa: Submucosal glands, ducts open in lumen. Muscularis propria: Admixture of striated & smooth muscle in the upper quarter, only smooth muscle in the rest of the organ. No serosal layer, except for the most distal portion. Autonomic nervous system: Meissners plexus in submucosa (sparse); Auerbach (Myenteric) plexus in muscularis propria (denser in the distal portion). Lymphatics: Upper third drains into the cervical nodes, the middle third into the paraesophageal and paratracheal nodes, and lower third into nodes around aorta and celiac axis.

. 45yr old female on anti depressants presented with dysphagia and heartburn

REFLUX ESOPHAGITIS

Inflammation in esophagus due to relux of gastric contents Pathogenesis Alcohol/tobacco Obesity CNS depressants Pregnancy Inc gastric vol/delayed emptying Grossly, severe lesions appear markedly hyperemic. Early microscopic lesions consists of epithelial hyperplasia, infiltration by neutrophils and eosinophils and sometimes by epithelial necrosis. The papillary height of lamina propria and degree of basal cell proliferation are high.

 Dilated and congested venules are seen in top of lengthened papillae . Intraepithelial eosinophils frequently. The short tubular structure distal to the ulcer is seen microscopically to be lined by gastric mucosa and as such it is regarded as an expression of Barrett's esophagus.

Occasionally inflammatory reaction is severe enough to result in a pseudoepitheliomatous

appearance.

60yrs old male, known case of GERD for the last 15yrs now presented with hematemesis

Defined as occurrence of a specialized columnar epithelium lining a segment of distal esophagus above the level of lower esophageal sphincter.

 Adults Genetic predisposition

No Goblets no Barrett's Another more questionable requirement incorporated into definition of Barretts esophagus by Practice Parameters committee of American College of Gastroentrologists is that this change

the biologic significance of intestinal metaplasia of lower esophagus should be the same whether or not the endoscopist was able to recognize it.

can be recognized at endoscopy-

ENDOSCOPIC FEATURES
Barretts
No information of barretts, however biopsy is from GE junction

INTERPRETATION
C/W Barretts
Cardiac mucosa with goblet cells

No site / no endoscopic evidence of barretts

Normal gastric mucosa

Intestinalized mucosa, either barretts mucosa or cardiac mucosa with goblet cells depending on the the endoscopic findings
Hiatal hernia b/c barretts esophagus can never be a normal cardiac mucosa

Important features: Reduplication of muscularis mucosa Long/short segment of barrets MUC2 MUC5AC/MUC6

Main complications include

peptic ulcer, stricture, bleeding development of dysplasia and carcinoma.

 Carcinoma is the most important complication of Barretts esophagus and it is nearly always accompanied by dysplasia.

Dysplasia nearly always arises in an area of incomplete intestinal metaplasia, and should be distinguished from reactive dysplasia secondary to inflammatory injury and graded according to its severity.

Diagnostic criteria according to the 1988 consensus conference for grading dysplasia in Barrett's esophagus

Negative for dysplasia:

Architecture within normal limits

Nuclei do not vary greatly in size or shape and are located basally N/C ratio is not increased. Nuclear envelope is smooth, nucleoli are not markedly enlarged.

Cytoplasmic mucin - may be depleted, progressive inc in mucin content towards surface epithelial cells.

Indefinite for dysplasia (IND):

The architecture may be mildly distorted Nuclear abnormalities are less marked than in dysplasia. Other futures include

more numerous dystrophic Goblet cells, more extensive nuclear stratification diminished or absent mucus production increased cytoplasmic basophilia increased mitoses

 Positive for low-grade dysplasia (LGD) or high grade dysplasia (HGD):

depend on severity of architectural and cytologic criteria that suggest neoplastic transformation of the columanr epithelium.

Architectural abnormalities may include budding, branching, crowded or irregularly shaped glands, papillary extensions into gland lumina and villiform configuration of the mucosal surface. Nuclear features may include marked variation in size and shape, nuclear and/or nucleolar enlargement, increased N/C ratio, hyperchromatism, and increased number of abnormal mitoses.

Architecture Villiform change

Low grade

High grade +/ ++ ++

Crypt budding/branching +/ Crowded (back-to-back) +/ crypts Irregular crypt shapes +/

Intraluminal papilla/ridges

+/

Lamina propria between + glands

+/

Feature Cytology N/C ratio Loss of cell polarity Atypical mitosis

Low Grade

High Grade

+ +/

++ + +

Full-thickness nuclear stratification Decreased goblet cells + (+/ dystrophic) Irregular nuclear + contour Nuclear pleomorphism

+ ( crypts & surface)

++ ++ +

Intramucosal carcinoma:
Carcinoma that has penetrated through the basement membrane of the glands into lamina propria but not yet invaded through the muscularis mucosae into the submucosa. Dysplasia is found in Barretts esophagus absence of carcinoma in 5-10% of cases and in association with carcinoma in 68% to 100% of cases.

ADENOCARCINOMA ARISING IN ESOPHAGUS

Invasive carcinoma arising in Barrett's esophagus is almost always adenocarcinoma. The main feature suggestive of origin of adenocarcinoma from Barretts esophagus is association with dysplastic or non-dysplastic Barretts mucosa and location of more than half of the tumor in the esophagus.

 Unusual types include Adenosquamous carcinoma Squamous cell carcinoma Sarcomatoid carcinoma various type of neuroendocrine carcinoma Choriocarcinoma And yolk sac tumor Sometimes alone and sometimes in association with adenocarcinoma.

Epithelial tumors Squamous cell papilloma Intraepitheilal neoplasia Carcinoma Adeno ca Sq cell ca Verrucous ca Basaloid ca Spindle cell ca Adenosquamous ca mucoepidermoid ca Adenoid cystic ca Small cell ca Undifferentiated ca Other Carcinoid

WHO histologic classification Non epithelial tumors

Leiomyoma Lipoma GIST Rhabdomyosarcoma Kaposi Malignant melanoma

Secondary tumors

A 40 year old male presented with odynophagia and weight loss

HERPES SIMPLEX ESOPHAGITIS

Case
A 60 year old chinese male smoker presented with progressive dysphagia and weight loss

General and clinical features:

Male > 50yrs RISK FACTORS Smoking and alcohol. Association with achlasia lye strictures Plummer Vinson syndrome Diverticula celiac sprue history of irradiation.

Microscopically
Occasionally lack of cohesion of tumor cells results in glandular configuration With extensive search or ultrastructural examination, true glandular or mucus secreting components are found focally in one fifths of the cases. When extensive the tumor is designated as adenosquamous carcinoma.

METASTASIS
High frequency of lymph node metastasis in the periesophageal area, below the diaphragm and upward into the cervical nodes. Metastasis to liver, lung and adrenal gland is common. Tumor may metastasize to submucosa of stomach probably through submucosal lymphatic plexus. Poor prognosis

Prognostic markers: Sex Stage Lymph node metastasis Depth of invasion Microscopic grade Vascular/lymphatic invasion Peritumoral fibrosis/lymphocytic reaction Surgical margins DNA ploidy EGFR P53 Response to therapy

REPORTING ESOPHAGEAL BIOPSY

MACROSCOPIC *Specimen Type *___ Incisional biopsy *___ Excisional biopsy *Tumor Site *Specify, if known: * Not specified *MICROSCOPIC *Histologic Type *Squamous cell carcinoma *___ Adenocarcinoma *___ Adenosquamous carcinoma *___ Small cell carcinoma *___ Undifferentiated carcinoma *___ Other (specify): ____ *___ Carcinoma, type cannot be determined

*Histologic Grade *___ Not applicable *___ GX: Cannot be assessed *___ G1: Well differentiated *___ G2: Moderately differentiated *___ G3: Poorly differentiated *___ G4: Undifferentiated *Extent of Invasion *___ Cannot be assessed *___ Epithelium only (no invasion) *___ Lamina propria *___ Submucosa *___ Muscularis propria *Additional Pathologic Findings (check all that apply) *___ None identified *___ Intestinal metaplasia *___ Dysplasia *___ Esophagitis (type): _________________________ *___ Other (specify): __________________________

*Comment(s)

 ESOPHAGEAL RESECTION: MACROSCOPIC Specimen Type ___ Esophageal resection ___ Esophagogastrectomy ___ Other (specify): ___ Not specified Tumor Site Specify, if known: ___ Not specified Tumor Size Greatest dimension: ___ cm *Additional dimensions: ___ x ___ cm ___ Cannot be determined (see Comment)

MICROSCOPIC Histologic Type ___ Squamous cell carcinoma ___ Adenocarcinoma ___ Adenosquamous carcinoma ___ Small cell carcinoma ___ Undifferentiated carcinoma ___ Other (specify): _ ___ Carcinoma, type cannot be determined Histologic Grade ___ Not applicable ___ GX: Cannot be assessed ___ G1: Well differentiated ___ G2: Moderately differentiated ___ G3: Poorly differentiated ___ G4: Undifferentiated

Pathologic Staging (pTNM) Primary Tumor (pT) ___ pTX: Cannot be assessed ___ pT0: No evidence of primary tumor ___ pTis: Carcinoma in situ ___ pT1: Tumor invades lamina propria or submucosa *___ pT1a: Tumor invades lamina propria *___ pT1b: Tumor invades submucosa ___ pT2: Tumor invades muscularis propria ___ pT3: Tumor invades adventitia ___ pT4: Tumor invades adjacent structures Regional Lymph Nodes (pN) ___ pNX: Cannot be assessed ___ pN0: No regional lymph node metastasis ___ pN1: Regional lymph node metastasis *___ pN1a: 1 to 3 nodes involved *___ pN1b: 4 to 7 nodes involved *___ pN1c: More than 7 nodes involved Specify: Number examined: ___ Number involved: ___ Distant Metastasis (pM) ___ pMX: Cannot be assessed ___ pM1: Distant metastasis, cannot further subclassify ___ pM1a: Lower thoracic esophagus: metastasis in celiac lymph nodes; Mid-thoracic esophagus: not applicable; Upper thoracic esophagus: metastasis in cervical nodes ___ pM1b: Lower thoracic esophagus: other distant metastasis; Mid-thoracic esophagus: nonregional lymph nodes and/or other distant metastasis; Upper thoracic esophagus: other distant metastasis Specify location of other distant metastases, if possible:

Margins (check all that apply)

Proximal Margin ___ Cannot be assessed ___ Uninvolved by invasive carcinoma ___ Involved by invasive carcinoma ___ Carcinoma in situ absent at proximal margin ___ Carcinoma in situ present at proximal margin
Distal Margin ___ Cannot be assessed ___ Uninvolved by invasive carcinoma ___ Involved by invasive carcinoma ___ Carcinoma in situ absent at distal margin ___ Carcinoma in situ present at distal margin Circumferential (Adventitial) Margin ___ Cannot be assessed ___ Uninvolved by invasive carcinoma ___ Involved by invasive carcinoma If all margins uninvolved by invasive carcinoma: Distance of invasive carcinoma from closest margin: ___ mm Specify margin: __________________________

Venous (Large Vessel) Invasion (V) *___ Absent *___ Present *___ Indeterminate

*Lymphatic (Small Vessel) Invasion (L) *___ Absent *___ Present *___ Indeterminate
*Additional Pathologic Findings (check all that apply) *___ None identified *___ Intestinal metaplasia *___ Dysplasia *___ Esophagitis (type): ___________________________ *___ Gastritis (type): ___________________________ *___ Other (specify): ___________________________

*Comment(s)