STOMACH

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DR. AISHA AKBAR

BLOOD SUPPLY:
a. The left gastric artery b. Right gastric artery c. Right gastro-epiploic artery d. Left gastro-epiploic artery e. Short gastric arteries

The corresponding veins drain into portal system. The lymphatic drainage of the stomach corresponding its blood supply.

Case
45yr old lady took salicylates for 3wks and

developed epigastric pain

ACUTE GASTRITIS
Inflammation of gastric mucosa
Caused by ingestion of strong acids or alkalies, NSAIDs,

cancer chemotherapy, irradiation, alcohol, uremia, severe stress & shock states
Proposed mechanisms: acid production with surface

bicarbonate buffer
Morphology: Mucosal edema, hyperemia, PML infiltration,

erosions (not deeper than muscularis mucosa) & hemorrhages

CASE
48yr old male presented with 3yr history

of heart burn, temporarily relieved by antacids.

CHRONIC GASTRITIS
Chronic mucosal inflammation, leading to mucosal atrophy, intestinal metaplasia & dysplasia. 1)Chronic superficial gastritis -decrease cytoplasmic mucin , nuclear and nucleolar enlargement some increase in foveolar mitosis. 2)Chronic atrophic gastritis Gastric atrophy. thining of mucosa without inflammation.

Clinically: Mild abdominal discomfort, nausea, vomiting; hypochlorhydria, hypergastrinemia & rarely overt pernicious anemia Long-term risk of cancer is 2-4% Two types of metaplastic changes: Pyloric metaplasia -fundic type glands---mucus sec.glands Intestinal metaplasia

Pathogenesis:

Immune gastritis Type A gastritis Non immune gastritis Type B gastritis

Autoimmunity (>10%): Antibodies to parietal cells cause parietal cell destruction Chronic infection by Helicobacter pylori (90%): Elaboration of urease produces ammonia that buffers gastric acid, protecting organism from acid Other diseases associated with H. pylori Infection Peptic ulcer disease Gastric carcinoma Gastric lymphoma

ANTRAL MUCOSA WITH CHRONIC ACTIVE GASTRITIS

SYDNEY SYSTEM
2 from fundic mucosa 2 from antral mucosa 1 from incissura

These should be labelled, assessed and recorded

separately

Special stains are required for

H-Pylori. Giemsa/ Warthin starry Mucin. PAS- neutral mucin

Alcian blue- intestinal mucin

Revised system in 1994

1. Antral- jejunal biopsies to be reported

separately

2. Gastritis to be classified into Acute Chronic Special form 3. Contains gradable non gradable entities non gradable granulomas, eosinophils, intraepithelial lymphocytes, mucin depletion, foveolar hypertrophy, surface erosions, lymphoid follicles

Gradable entities
H-Pylori

not seen Mild..... Occasional Moderate significant Marked almost masses of H-Pylori Chronic inflammation Normal. 2-5/ hpf (40x10) Mild Moderate marked . ( to be graded away from the follicles)

Normal

Neutrophils (Activity)
Normal.. Not seen Mild few Moderate.. Significant number Marked.. Pit abscesses

(recommended term is Active Gastritis or Active Chronic Gastritis)

Atrophy
Mild Moderate Severe

(Thickness of glandular part/ thickness of mucosa difficult in endoscopic bopsies as muscularis mucosae presence is essential)
Intestinal metaplasia
Complete (intestinal) Incomplete (large intestinal) Etiology (if known), topography (cardia,

antrum), morphology all variables

EXAMPLE
Stomach, endoscopic biopsy:
Active Chronic Gastritis, Antral, H-Pylori marked Chronic inflammation marked Activity. moderate Atrophy. moderate Intestinal metaplasia.. incomplete

Other types of gastritis

Acute infectious non bacterial gastroenteritis Hemorrhagic gastritis Collagenous gastritis Lymphocytic gastritis Allergic gastroenteritis Diffuse eosinophilic gastritroentritis Granulomatous gastritis

GUESS THE LESION

Hyperplastic polyp

75% of all Causes: Hypochlorhydria Dec pepsinogen Hypergastrenmia Chronic gastritis Grossly: Small sessile,multiple,smooth contours L/M: elongation, tortous dilated gastric foveolae with mostly pyloric glands in deeper portion.Foamy macrophages
Malignant transformation is accompanied by

increased proliferative activity and P53 expression.

Hyperplastic polyp

Adenomas
Antral Sessile or pedunculated L/M: dystrophic glands with pseudostratified

epithelium, nuclear abnormalities, increase mitosis Gastric type Intestinal type

Mixed(hyperplastic and adenomatous)

Fundic gland polyp

Causes: Sporadic ZollingerEllison syndrome proton pump inhibitors familial adenomatous polyposis Grossly : Multiple, small, polypoidal mass in fundus or body L/M: microcysts lined by fundic epithelium, including oxyphilic cells; the overlying foveolae are usually shortened.There is also an increase in the smooth muscle content, often in a pericystic distribution

CASE
Patient presented with: Epigastric pain 1-3 hours

after meals & worse at night; nausea; vomiting; belching & occult blood in the stools

ULCERS
Ulcer - a breach in mucosa & extends thru muscularis mucosae into submucosa or

deeper
1) Acute Gastric Ulcers:
acute erosive gastritis = erosions ABOVE the muscularis mucosa

Caused by Severe stress (= Stress Ulcers)

Shock, extensive burns (Curlings ulcers) Severe head injuries (Cushings ulcers) NSAIDs.

2) CHRONIC GARSTRIC ULCER:

Ratio of duodenal : gastric = 4 : 1

Age-50 years
Morphology:
Surrounding mucosa shows chronic gastritis & radial convergence of rugal folds

towards the ulcer niche (unlike malignant ulcer) Active, well devepled ch.peptic ulcer show 4 distinct layers:
Surface coat of purulent exudate,bacteria,necrotic debris Fibrinoid necrosis Granulation tissue Fibrosis replacing muscle wall extend into subserosa

CASE
A 40 year old female, presented with epigastric pain and malena ENDOSCOPIC FINDINGS Multiple ulcers in small intestine and stomach

HYPERTROPHIC GASTROPATHY
Characterized by Giant enlargement of the gastric rugal folds Caused by hyperplasia of epithelial cells ( not due to inflammation ) risk of cancer
Includes 3 variants Zollinger - Ellison Syndrome

Caused by Gastrinoma of Pancreas secreting gastrin elevated serum

gastrin levels multiple peptic ulcerations in stomach, duodenum, jejunum Hypertrophic rugal folds & Parietal cell hyperplasia and hypertrophy excess gastric acid production Fundic glands may be cystically dilated-reminiscent of fundic gland polyps.

HYPERTROPHIC GASTROPATHY
Menetriers disease
Hyperplasia of surface mucous cells (foveolar hyperplasia) glandular atrophy excessive loss of proteins in gastric secretion (protein-losing Gastropathy)

Hypersecretory Gastropathy
Hyperplasia of parietal and chief cells Secondary to excessive gastrin stimulation.

Regenerative hyperplasia
occurs most often in areas of mucosal injury

Simple hyperplasia, the cells are immature, with

basophilic cytoplasm, hyperchromatic nuclei, and reduced or absent mucus secretion. Uniform in size and shape, with basally or centrally located nuclei arranged in a row pseudostratification is slight or absent. Maturation and differentiation toward the surface are present Glandular dilation and some degree of intraglandular papillary growth.

Atypical hyperplasia >pseudostratification and

compression and less maturation and differentiation inflammatory reaction, sometimes intense, and focal erosive changes are common.

Dysplasia
Increased cell proliferation accompanied by

abnormalities in cell size, configuration, and orientation.

Mucus secretion is reduced or absent increase in the nucleocytoplasmic ratio, loss of nuclear polarity, and pseudostratification. Mitoses are

numerous, and some of them are atypical

Architectural derangement of the glands, cellular crowding,

intraluminal folding, and glandular budding and branching.

Reporting of gastric biopsies

Negative for dysplasia Indefinite for dysplasia Low grade dysplasia High grade dysplasia Intramucosal carcinoma Invasive carcinoma

Intestinal (adenomatous, type 1), gastric (foveolar, type 2) combined (hybrid) subtypes, low-grade and high-grade High-grade dysplasia is regarded as

synonymous with carcinoma in situ (CIS) and must be distinguished from intramucosal carcinoma, in which the process has broken through the basement membrane

CASE
A 60 year old male

presented with weight loss and malena.

CARCINOMA
Age: > 50yr

Etiology:
chronic atrophic gastritis with intestinal metaplasia and

preceded by dysplasia, CIS and superficial Ca

Hypochlorhydria85-90% H.pylori Gastric polyps, Menetriers disease Peptic gastric ulcer and gastric stump Radio and chemotherapy for other maligancies

Gastric Cancer Dietary/Lifestyle Factors

Carl-McGrath S, et al. Cancer Therapy

Sequence of events:
Normal Chronic gastritis Mucosa l atrophy Intestin al metapla sia Dysplas Intestinaltype ia carcinoma

Increasing risk

CLASSIFICATION
Bormann, 1926
Type I (polypoid) Type II (fungating) Type III (ulcerated) Type IV (infiltrative) Fungating Penetrating Spreading Superficial spreading Linitis plastica No special type

Lauren 1965 Ming, 1977

Intestinal Diffuse

Stout, 1953

Japanese society for gastric

Expanding Infiltrative

cancer, 1981 Papillary Tubular Poorly differentiated Mucinous Signet ring

CLASSIFICATION
WHO, 2000 Adenocarcinoma Intestinal Diffuse Papillary adenocarcinoma Tubular adenocarcinoma Mucinous adenocarcinoma Signet ring adenocarcinoma Adenosquamous carcinoma Squamous cell carcinoma Small cell carcinoma Undifferentiated carcinoma others

CARCINOMA
GROSS: Fungating, flat, ulcerating or deeply invasive tumor growing through wall of stomach Fleshy, fibrous or gelatinous Site: Fundic Casubmucosal invasion likely than pyloric Ca Multicentricity6% Adjacent non neoplastic mucosa thickened
L/M: 1 of 4 cell types: foveolar, mucopeptide, intestinal

columnar or goblet cells

CARCINOMA TYPES
1. INTESTINAL TYPE: .Arise from metaplastic epithelium .Maybe extremely well differentiated, D/D: intestinal

metaplasia

.Mucin is variable, calcification, metaplastic ossification .Neutrophil or histiocytic infiltrate in stroma .Poorly differentiatedsolid pattern

2.DIFFUSE TYPE: (linitis plastica, signet ring Ca)

young prepyloric area pyloric obstruction submucosal fibrosis, mucosal ulceration, muscle

hypertrophy

L/M: diffuse pattern of growth Transmural or intramucosal Gland formation rare, individual tumor cellsmostly Intracytoplasmic mucinsignet ring appearance Extracellular mucin pools Presence of signet ring cellstumor categorized as

signet ring Ca rather than mucinous adenocarcinoma

MUC1 for the intestinal type, MUC5AC for the diffuse type, MUC2 for the mucinous type MUC5B for the unclassified type Reactivity of gastric adenocarcinoma cells for

keratin, epithelial membrane antigen, and CEA is the rule

The keratins present are usually of the simple

epithelial type (low molecular weight), but sometimes those seen in normal squamous epithelia (such as CK13 and 16) are also detected.

CK7/CK20 expression patterns of gastric ca

vary
In some cases (particularly of the diffuse

type) there is coexpression of keratin and vimentin.

Markers indicative of specific gastric

TNM: most important clinical prognostic factor

Gastric Cancer Staging Systems

http://www.hopkinshttp://www.medscape.com/viewarticle/543 gi.org

OTHER TYPES
ADENOSQUAMOUS AND SQUAMOUS CELL CA:
<1% of gastric Ca Ca should be surrounded

HEPATOID ADENOCARCINOMA:
Glands+ hepatocellular

all around by gastric mucosa Those involving lower 1/3rd of esophagus regarded as primary esophageal Ca Behaviordetermined by differentiation MUCINOUS CA:

differentiation Tubulopapillary pattern, clear cells Nodular growth, cytoplasmic glycogen or hyaline globules Extensive venous congestion IHC: CEA+, Hep-Par1+, AFP+ D/D: typical gastric

OTHER TYPES
PARIETAL GLAND (ONCOCYTIC) CA:

Glandular or solid pattern Abundant oncocytic

cytoplasm PTAH and Luxol fast blue+ E/M: abundant mitochondria, tubulovesicles, intracellular canaliculi and intercellular lumina

LYMPHOEPITHELIOMA LIKE CA: Resembles homonymous tumor in resp tract EBV related SARCOMATOID CA: Epithelialglands+ sarcoma like spindle cells Heterologousbone and skeletal muscle Neuroendocrine cells

Prognostic factors
Age Tumor stage/lymph node involvement Location in the stomach Tumor margins/surgical margins/type of

surgery Tumor size Microscopic type/grading Inflammatory reaction Perineural invasion DNA ploidy/p53/c-ERB2 EBV expression

NEUROENDOCRINE DIFFERENTIATION
1. Well differentiated neuroendocrine tumors
.Well differentiated, slow growing -Neuroendocrine cells

(carcinoid):

of gastric mucosa

.Grossly,: gastric WDNETs are small,

sharply outlined, and covered by a flattened mucosa..

.May resemble gastric polyps. .L/M: predominant pattern of growth may

be microglandular, trabecular, or insular

Carcinoid

NEUROENDOCRINE DIFFERENTIATION 2. Atypical carcinoid/ neuroendocrine carcinoma/

.Tumors with obvious morphological features of

large cell neuroendocrine ca

neuroendocrine differentiation but obvious atypia .Trabaculae, rosettes, insulae; dense core secretory granules, NSE+ .Atypiainvasiveness, necrosis, mitosis

3. Small cell carcinoma: .Analogous to pulmonary counterpart .Aggressive behavior

4. Otherwise typical adenocarcinoma of diffuse or

intestinal type having cells with argyrophilia or neuroendocrine differentiation

SPREAD OF TUMOR

CASE
63 yr old male presented with abdominal mass

grossly exophytic type Markers: c-Kit +ve CD34 ve Actin-ve

GASTRO INTESTINAL STROMAL TUMOR (GIST)

Most common mesenchymal tumors of the GIT. A relationship to the interstitial cells of Cajal (ICCs) has been proposed, and expressionof CD117 GISTs are most common in the stomach (70%), small intestine (20%), colon ,rectum (5%) esophagus (<5%). GISTs commonly have activating mutations in exon 11 of the KIT gene that encodes a TK receptor for the stem cell factor or mast cell growth factor. The only absolute criterion for malignancy is tumor spread beyond the organ of origin at the time of diagnosis..

Smooth muscle differentiation Sma

Caldesmon/myosin- frequently Could arise from muscularis propria,mucosa

or vessel. Spindle tumor cells with acidophilic fibrillary cytoplasm and the presence of cytoplasmic vacuoles at both ends of the nucleus should suggest smooth muscle differentiation An epithelioid appearance is also more likely to be associated with evidence of smooth muscle differentiation- round to polygonal cells with a central nucleus and a usually abundant acidophilic or clear cytoplasm

Neural differentiation
Neural filaments Chromogranin Synaptophysin Neuron specific enolase+ve Leu 7 S-10 composed of spindle (but sometimes

epithelioid) cells growing in the form of fascicles, palisades, and whorls. Deposition of amorphous eosinophilic extracellular collections of abnormal collagen (immunoreactive for type VI) referred to as skenoid fibers is generally associated with

Rates of metastases or tumor-related death in GISTs grouped by tumor location, tumor size and mitotic rate
TUMOR PARAMETERS PERCENT OF PATIENTS WITH PROGRESSIVE DISEASE DURING LONG-TERM FOLLOW-UP AND CHARACTERIZATION OF RISK (IN PARENTHESES) FOR METASTASIS Jejunal and ileal Duodenal GISTs Rectal GISTs GISTs 0% (none) 0% (none) 8.3% (low) 0% (none) 8.5% (low)

Group 1 2 3a 3b 4 5 6a 6b

Tumor size =2 cm

Mitotic rate =5/50-HPFs

Gastric GISTs 0% (none)

>2 cm to =5 cm=5/50-HPFs >5 cm to =10 cm >10 cm =2 cm =5/50-HPFs =5/50-HPFs >5/50 HPFs

1.9% (very low) 4.3% (low) 3.6% (low) 24% (moderate)

34% (high)[b] 12% (moderate) 52% (high) 0%[a] 50%[a] [c] 50% (high)

57% (high)[b]

54% (high) 52% (high)

>2 cm to =5 cm>5/50 HPFs >5 cm to =10 cm >10 cm >5/50 HPFs >5/50 HPFs

16% (moderate) 73% (high) 55% (high) 86% (high) 85% (high)

86% (high) 90% (high)

71% (high)[b]

Differentials
SFT Fibromatosis Inflammatory fibroid polyp Glomus tumor Schwanomma Leiomyoma/sarcoma Malignant lymphoma/ca

CASE
A 40 year old male presented with dyspepsia

and epigastric pain.

MALTOMA

Extranodal marginal zone lymphoma of

mucosa-associated lymphoid tissue-3rd most common non-Hodgkin lymphoma subtype 68% of all non-Hodgkin lymphomas in the West.
clinically indolent, typically chronic, requiring

long-term clinical surveillance and, often, repeated biopsies.

H pylori is critical for lymphomagenesis and

also creates a microenvironment favouring the growth of neoplastic B cells, probably through

Grading system indicating the degree of certainty of the diagnosis of MALT-type lymphoma
Grade 0 (Normal) Scattered plasma cells in lamina propria. No lymphoid follicles. Small clusters of lymphocytes in lamina propria. No lymphoid follicles. No lymphoepithelial lesions. Prominent lymphoid follicles with surrounding mantle zone and plasma cells. No lymphoepithelial lesions. Lymphoid follicles surrounded by small lymphocytes that infiltrate diffusely in lamina propria and occasionally into epithelium.

Grade 1 (Chronic active gastritis)

Grade 2 (Chronic active gastritis with florid lymphoid follicle formation)

Grade 3 (Suspicious lymphoid infiltrate in lamina propria, probably reactive)

Grade 4 (Suspicious lymphoid infiltrate in lamina propria, probably lymphoma)

Lymphoid follicles surrounded by centrocytelike cells that infiltrate diffusely in lamina propria and into epithelium in small groups.

Presence of dense diffuse infiltrate of Grade 5 (Low-grade B-cell lymphoma of MALT) centrocyte-like cells in lamina propria with prominent lymphoepithelial lesions

LARGE CELL LYMPHOMA

LARGE CELL LYMPHOMA

heterogeneous category transformed MALT lymphomas 75%de novo lymphomas A high proportion of large cell lymphomas of

the stomach express BCL6 (in contrast to lowgrade lymphomas), whether they are thought to be related to MALT lymphoma or not EBV+

large lobulated (sometimes polypoid) mass.

Superficial or deep ulceration is common

Gastric large B-cell lymphoma are composed

of cells resembling large noncleaved cells (centroblasts) but with a slightly more abundant cytoplasm, sometimes resulting in a plasmablastic or immunoblastic appearance

D/D-Undifferentiation carcinoma lack of continuity between epithelium and

tumor cells lack of suggestion of an acinar pattern preservation of muscularis mucosae fibers

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