Difference between revisions of "Stomach"

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**''Helicobacter heilmannii''.
**''Helicobacter heilmannii''.


Epidemiologic associations:
Epidemiologic associations - ''Helicobacter'' infections are associated with:<ref>{{Ref PBoD|814}}</ref>
Helicobacter infections are associated with:<ref>{{Ref PBoD|814}}</ref>
*Gastritis.
*Gastritis.
*Peptic ulcers.
*Peptic ulcers.
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*[http://commons.wikimedia.org/wiki/Category:Helicobacter_gastritis Set of images - HP gastritis (WC)].
*[http://commons.wikimedia.org/wiki/Category:Helicobacter_gastritis Set of images - HP gastritis (WC)].
*[http://gut.bmj.com/content/58/12/1669/F2.large.jpg Helicobacter heilmannii (bmj.com)].<ref>URL: [http://gut.bmj.com/content/58/12/1669.extract http://gut.bmj.com/content/58/12/1669.extract]. Accessed on: 2 March 2012.</ref>
*[http://gut.bmj.com/content/58/12/1669/F2.large.jpg Helicobacter heilmannii (bmj.com)].<ref>URL: [http://gut.bmj.com/content/58/12/1669.extract http://gut.bmj.com/content/58/12/1669.extract]. Accessed on: 2 March 2012.</ref>


===Stains===
===Stains===

Revision as of 03:26, 3 March 2012

Stomach is an important organ for pathologists. It is often inflamed and may be a site that cancer arises from. Gastroenterologists often biopsy the organ. Surgeon take-out the organ. It connects the esophagus to the duodenum. An introduction to gastrointestinal pathology is in the gastrointestinal pathology article.

Normal

Gross anatomy

  • Cardia - first part of the stomach; joins with esophagus.
  • Fundus - superior portion - not attached directly to the esophagus.
  • Body - contains parietal cells.
  • Pylorus - distal (think pyloric stenosis); it joins with the duodenum.

Image: Stomach anatomy (WP).

Microscopic

Foveolar cells vs. intestinal goblet cells

  • Intestinal goblet cells - clear mucin.
  • Foveolar cells - eosinophilic contents.

Stomach vs. intestine[1]

Intestine Stomach
Spacing Goblets cell - spaced Foveolar cells - beside one another
Morphology of epithelial cells columnar tall columnar (Champagne flute)
Vesicle at luminal surface touching/small opening wide open
PAS-D -ve (???) +ve (???)
Villin stain[2] +ve -ve
Images Tubular adenoma - goblet
cells on right of image (WC)
Gastric biopsy (microscopy-uk.org.uk)

Notes:

  • Intraepithelial lymphocytes in the gastric mucosa have a clear halo around 'em.[3]
  • Memory device: Folveolar cells have friends, i.e. they are close to other foveolar cells.

Ref.

  • PMID 11984877.

Gastric antrum vs. gastric body

Body Antrum Histology Image
Parietal cells abundant few or none parietal cells: intensely
eosinophilic cytoplasm
[1], [2]
Chief cells present absent chief cells: basophilic cytoplasm,
IHC: +ve for pepsinogen I
[3]
G cells absent present fried egg appearance (clear cytoplasm,
round nucleus); look at high power -
usu. middle 1/3 of gland,[4]
IHC: +ve for gastrin.
[4]
Surface flat blunted villi antrum is somewhat
duodenum-like
body - flat
Gastric glands
/ mucosa
thick thin not so useful for
discrimination
body - thick, body & antrum

Notes:

  • G cells may superficially resemble intraepithelial lymphocytes.
    • G cell nucleus is usu. perfectly round and slightly larger (diameter of 12 micrometers?) than a lymphocyte nucleus (diameter ~ 9-10 micrometers?).

Introduction

Useful stains for stomach

  • Cresyl violet stain[5] - used to find H. pylori.[6]
  • Alcian blue - used to find mucin[7] which is present in intestinal metaplasia
    • Other mucins stains:[8] mucicarmine, PAS, PASD (doesn't stain glycogen)

Things to look for...

  • Parietal cells (indicate you're in the body of the stomach) - pink (eosinophilic) cytoplasm.
    • Lack of parietal cells -- DDx: Bx of antrum (pylorus), Bx of cardia, pernicious anemia.
  • Goblet cells = intestinal metaplasia.
  • Architectural distortion of gastric glands - suspect cancer.
  • Signet ring cells = (usually) gastric carcinoma.
    • Can be very easy to miss in some biopsies.
  • Inflammation + small bacteria = suspect H. pylori gastritis.

Non-specific disease

Gastric ulcer

General

Complications:

  • Hemorrhage.
  • Obstruction.
  • Perforation.

Gross

  • Epithelial defect:
    • Heaped edges - suggestive of cancer.
    • Punched-out edges - suggestive of a benign process.

Microscopic

Features:

  • Depends on the etiology.

Non-neoplastic disease

Gastritis

Etiology

A specific cause is uncommonly identified histologically.

Gastritis causes:[9]

Endoscopic appearance

  • Erythematous.

Microscopic

  • Inflammatory cells - see below.

Acute gastritis

  • AKA active gastritis.

Features:

  • Neutrophils - especially when intraepithelial.
Focal active gastritis

DDx:

  1. Drugs,[10] esp. NSAIDs.
  2. Infectious.
  3. Inflammatory bowel disease.

Chronic gastritis

Features:

  • Plasma cells (in lamina propria).
    • Various criteria:
      1. Two plasma cells kissing, i.e. two plasma cells touching/overlapping.
      2. Three is a crowd, i.e. three plasma cells in close proximity.
Lymphocytic gastritis

The DDx is limited:

  1. Helicobacter gastritis.
  2. Celiac disease.
  3. NSAIDs.
  4. Idiopathic.

Sydney criteria for gastritis

A bunch of pathologists in Sydney came-up with criteria... and these were revised in Houston.[11]

Classification

Updated Sydney classification:[11]

Non-atrophic Helicobacter Atrophic Helicobacter Autoimmune
Inflammation pattern antral or diffuse antrum & corpus, mild inflammation corpus only
Atrophy & metaplasia nil atrophy present, metaplasia at incisura corpus only

Notes:

  • Corpus = gastric body.
  • Incisura = angular incisure, incisura angularis (Latin) - notched transition point on lesser curvature of the stomach between pylorus and body.[12]

Severity

The Sydney group suggests grading severity with the following language:[11]

  • Mild.
  • Moderate.
  • Marked.

These terms are applied to the parameters described in a biopsy. The Sydney criteria lists H. pylori, neutrophils, mononuclear cells, antrum (atrophy), corpus (atrophy) and intestinal metaplasia. The paper that discusses this also give a visual analogue scale.

Parameters & Severity (adapted from Dixon et al.[11]):

Mild Moderate Marked
H. pylori few touching many touching piles
Neutrophils few bunches crowded
Mononuclear cells not touching kissing partying

Helicobacter gastritis

General

  • Several Helicobacter species can cause gastritis:
    • Helicobacter pylori - most common.
    • Helicobacter heilmannii.

Epidemiologic associations - Helicobacter infections are associated with:[13]

Microscopic

Features:

  • Small - smaller than the nucleus of the gastric foveolar cell.
    • On 400x they are still possible to miss.
  • Look close to the opening of the gastric glands.
  • Are often are found in groups.
  • Location - can be antrum and/or body.[14]
  • Helicobacter don't like the intestinal mucosa or mucosa that has undergone intestinal metaplasia -- you're unlikely to find 'em there.
  • Helicobacter pylori:
    • Typically have a "v" shape or a comma-like shape.
  • Helicobacter heilmannii:
    • Corkscrew appearance.

Images:

Stains

IHC

  • Helicobacter pylori IHC stain +ve.

Intestinal metaplasia

General

  • Often part of surgical pathology report, e.g. "negative for intestinal metaplasia" or "intestinal metaplasia present".
  • May be associated with Helicobacter spp. infection -- though Helicobacter don't like intestinal type mucosa, i.e. H. pylori are not typically found in regions with intestinal metaplasia.

Significance

  • Moderate risk increase for carcinoma; risk less than for Barrett's esophagus.[16]

Microscopic

Features:

  • Goblet cells are present in the stomach.[17]
    • With cresyl violet vacuole stains blue.
    • With H&E vacuole may stain greyish.

Image:

Inflammatory bowel disease & the stomach

See inflammatory bowel disease.
  • Histopathologic findings are usually non-specific.
  • Conventional thinking was upper GI involvement = Crohn's disease; this is changing.[18]

Microscopic

Features:[19]

  • Focal inflammation.
    • Common finding - non-specific.
  • +/-Granulomas.

Miscellaneous

This is a grab bag of stuff seen in the stomach. Some of it is quite rare.

Gastric antral vascular ectasia

General

  • Abbreviated GAVE.
  • Antrum lesion - due dilated capillaries.
  • AKA watermelon stomach - due to characteristic endoscopic appearance.[20]

Gross/endoscopic appearance

  • Linear red streaks in antrum - oriented toward the pyloric valve... vaguely resembles a watermelon.

Endoscopic images:

Microscopic

Features:[21]

  • Fibrin thrombi - characteristic feature.
  • Dilated capillaries in lamina propria.

Images:

Reactive gastropathy

General

  • AKA chemical gastropathy,[22] incorrectly referred to as chemical gastritis (see below).
  • May be seen in the context of a previous resection/surgical reconstruction, e.g. Billroth II.

Epidemiology

Associated with:[23]

  • Excess acid.
  • EtOH.
  • Bile.
  • H. pylori.
  • Drugs:[22]
    • Iron (brown pigment on histology).
    • NSAIDs - synergistic effect with corticosteroids.

Drugs that cause erosions and/or ulcers -- adapted from Genta:[22]

Drug Comment Indication for Rx
NSAIDs common cause pain, reduce cardiovascular risk
Corticosteroids synergistic effect with NSAIDs rheumatologic diseases + others
Potassium (KCl) common cause renal failure
Bisphophonates uncommon cause osteoporosis
Ferrous sulfate very common if symptomatic iron deficiency anemia
Chloroquine uncommon only in the context of malaria
Sodium polystyrene sulfonate (Kayexalate) rare renal failure patients

Relation to gastritis

  • May mimic a (true) gastritis symptomatically and visually in an endoscopic examination.
  • "Chemical gastritis" is misnomer. Etymologically, the -itis in gastritis, implies an inflammatory process. Chemical gastropathy is not (predominantly) an inflammatory process.
    • This type of confusion is not uncommon. Steatohepatitis is another example of this; it is not a process with significant inflammation yet, confusingly, carries the -itis ending.

Microscopic

Features - triad:[24][22]

  1. Foveolar hyperplasia.
    • Tortuosity of glands in the "neck" region of the gastric glands.
    • Associated with "mucin depletion" - cytoplasm not clear -- as is usual.
  2. Smooth muscle fibre hyperplasia.
    • Abundant eosinophilic lamina propria.
  3. Scant acute & chronic inflammatory cells.

Additional features.

  • +/-Edema.
  • +/-Erosions.

Notes:

  • Triad rarely present; mild inflammation common.

DDx:

Images:

Gastric atrophy

General

  • Has a wide differential diagnosis.

Microscopic

Can take three general forms:

  1. Intestinal metaplasia - see intestinal metaplasia section.
  2. Pseudopyloric metaplasia; gastric body looks like gastric antrum.
    • Characterized by foveolar hyperplasia.
  3. Cell loss without replacement.
    • Clue is deep inflammation in the body.

Lymphocytic gastritis

General

DDx:

  • Celiac disease.
  • H. pylori.
  • HIV/AIDS.

Microscopic

Features:[25]

  • 25 lymphocytes / 100 epithelial cells.

Pernicious anemia

General

  • Gastric atrophy.
  • Loss of parietal cells.
  • Intrinsic factor antibodies present in serum.
    • Intrinsic factor -- absorbs vitamin B12.
  • Macrocytic anemia.

Microscopic

Features:

  • Corpus predominant inflammation.
  • Increased G cells in the antrum.
      • Increased gastrin level to try and stimulate (missing) parietal cells.
  • See gastric atrophy section.

Collagenous gastritis

General

Microscopic

Features:

  • Eosinophilic material (collagen) expands lamina propria.
    • Band of collagen must be ~thick as RBC diameter.

Granulomatous gastritis

  • Usual DDx of granulomatous disease (see Basics article):
    • DNF AAII:
      • Drugs, Neoplasms, Foreign body, Autoimmune, Allergic, Infectious, Idiopathic.

Important ones:

  • Autoimmune - Crohn's disease.
  • Infectious - Tuberculosis.
  • Idiopathic - Sarcoidosis.

Plasma cells in the stomach

DDx of plasmacytosis:

Gastritis cystitis profunda

General

  • AKA Gastritic cystica profunda. (???)
  • May be assoc. with glandular proliferation as well.[26] (???)
  • Super rare.
  • Similar to cystitis cystica.

Microscopic

Features:

  • Cystic spaces lined by foveolar epithelium.

Ménétrier's disease

  • AKA diffuse foveolar cell hyperplasia.[27]

General

  • Super rare.
  • Increased risk of gastric adenocarcinoma.[27]

Clinical:[28]

  • Classic: nausea, emesis, abdominal pain and peripheral edema.

Other:

  • Gastric mass (may mimic cancer).
  • Hypochlorhydria.
  • Protein loss - leads to peripheral edema.

Microscopic

Features:[27]

  • Foveolar cell hyperplasia - key feature.

DDx:

Images:

Gastric xanthoma

  • Abbreviated GX.
  • AKA xanthelasma.
  • AKA stomach lipidosis.

General

  • Uncommon.
  • Benign.

Gross/endoscopic

  • Yellowish nodule or plaque.[30]
    • Classically lesser curvature and antrum.[31]

Microscopic

Features:[30]

  • Collections of gastric lamina propria with lipid-laden macrophages.

DDx:

Images:

IHC

  • CD68 +ve.
  • Panker (AE1/AE3) -ve.

Gastric polyps

Similar to colonic polyps - see intestinal polyps.

DDx polyp (similar to colon & rectum):

Inflammatory fibroid polyp

General

  • Benign.
  • Through-out GI tract.
  • Can be thought of as granulation tissue-like.[32]

Microscopic

Features:[33]

  • Proliferating spindle cells (fibroid) - key feature.
    • Loosely arranged, concentrically, around blood vessels.[34]
    • Perivascular hypocellular zones.[32]
  • Inflammation:
    • Eosinophils - often prominent.
  • +/-Leiomyoma/schwannoma-like areas - with nuclear palisading.[32]
  • +/-Vascular for fibrous tissue.

DDx:

Notes:

  • Concentric = share the same centre.[35]

Images:

IHC

Features:[33]

  • CD34 +ve.
    • There is a CD34 -ve variant.
  • Vimentin +ve -- diffuse.[36]

Others:

  • CD117 -ve.[37]
  • S100 -ve.

Molecular

  • A subset have mutations in PDGFRA.[33]

Hyperplastic polyp of the stomach

  • AKA gastric hyperplastic polyp.

General

  • Benign.
  • Most common gastric polyp.[38]

Microscopic

Features:[39]

  • Abundant foveolar cells and elongated glands - key feature.

Negatives:

  • No atypical nuclei.
  • No hyperchromasia.
  • No loss of pseudostratification.

Notes:

  • No serrations - as in the colon.

DDx:

Images:

Adenomatous polyps

General

  • Divided into "gastric" and "intestinal type". (???)
  • Can be grouped various ways.[40] (???)

Microscopic

  • Type.
    • Intestinal: goblet cells or Paneth cells.
    • Gastric: foveolar epithelium. (???)
  • Architectural crowding of glands.
  • Hyperchromasia of cytoplasm.
  • Nuclear changes:
    • Loss of nuclear polarity.
    • Increased NC ratio.
    • Elongation of nucleus.

Fundic gland polyp

General

  • Most common stomach polyp.[41]
  • Fundic location - duh!
    • May be in the body.[41]

Clinical significance

Notes:

Microscopic

Features:[45]

  • Polypoid shape (may not be appreciated on microscopy).
  • Dilated gastric glands.
    • Flatted epithelial lining (consisting of normal foveolar epithelium) - key feature.

Image:

Notes:

  • The presence of dysplastic changes should prompt consideration of FAP.

Neoplastic

The spectrum from benign to malignant is divided into five:[46]

  1. Benign.
  2. Indefinite for gastric epithelial dysplasia.
  3. Low-grade gastric epithelial dysplasia.
  4. High-grade gastric epithelial dysplasia.
  5. Gastric carcinoma.

Gastric columnar dysplasia

  • AKA gastric dysplasia.

General

  • Criteria similar to columnar dysplasia in the esophagus.

Divided into:

  • Low grade.
  • High grade.

Microscopic

Low-grade gastric columnar dysplasia

Features:

  • Nuclear changes:
    • Nuclear crowding/pseudostratification with hyperchromasia.
    • Elongation of nuclei (cigar-shaped nuclei).
    • Nuclear stratification intact; nuclei close to the basement membrane.
  • Architecture:
    • Focal irregularities in the glandular contours.

Negatives:

  • No desmoplasia.
  • No necrosis.
  • No surface maturation.

Images:

High-grade gastric columnar dysplasia

Features:

  • Nuclear changes:
    • Round hyperchromatic nuclei.
    • Loss of normal nuclear stratification.
  • Architecture:
    • Irregularities in the glandular contours.
    • Back-to-back glands.
    • Cribriforming of the glands.
    • +/-Necrosis.

Negatives:

  • No desmoplasia.

Images:

Neoplastic rare

Gastric calcifying fibrous tumour

Gastric cancer

Gastric lymphoma

General

  • Associated with helicobacter infection.[47]
  • Usually MALT lymphoma (mucosa-associated lymphoid tissue lymphoma).

Microscopic

Features:

  • Sheets of lymphoid cells.
  • "Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes.[48]
    • Features:
      1. Cluster of lymphocytes - three cells or more - key feature.
        • Single lymphocytes don't count.
      2. Clearing around the lymphocyte cluster.
    • Associated with MALT lymphoma;[49] however, not specific.

DDx:

IHC

  • Panker -- most useful.

Others:

  • CD3 (T cells) - scatter positivity.
  • CD20 (B cells) +ve.
  • CD138 (plasma cells).
  • kappa, lambda -- often one is predominant, suggesting clonality.
  • BCL2 +ve.

Treatment

  • Triple therapy (two antibiotics, proton pump inhibitor (PPI)).[52]
  • Surgery - if triple therapy fails.

Review paper: PMID 16950858.

Familial gastric carcinoma

  • Signet ring carcinoma - associated with E-cadherin (CDH1[53]) mutation.[54]

Gastric adenocarcinoma

General

Epidemiology:

  • Associated with helicobacter infections, i.e. helicobacter gastritis.
  • Prognosis is often poor as it is discovered at a late stage.
  • Higher prevalence in countries in the far east (e.g. Japan) - thought to be environmental, e.g. diet.

Treatment:

  • Surgical excision.
    • Proximal tumours may require a complete gastrectomy as the stomach is innervated from its proximal part.

Classification

  • Two different classification schemes.
    • Lauren[55] - two types:
      • Intestinal type (mass forming).
      • Diffuse type (infiltrative).
    • WHO classification - 6 subtypes for adenocarcinoma:[56]
      1. Papillary carcinoma.
      2. Tubular carcinoma.
      3. Mucinous carcinoma.
      4. Signet-ring carcinoma.
      5. Undifferentiated carcinoma.
      6. Adenosquamous carcinoma.

Lame memory device STOMACH:

  • Signet ring, Tubular, Oh papillary, Mucinous, Adenosquamouas, Crappy High grade (Undifferentiated).

Microscopic

Features - variable, either of the two following:

  1. "Typical adenocarcinoma":
    • Gland-forming lesion that infiltrates into the lamina propria or beyond.
    • Nuclear pleomorphism - common.
  2. +/-Signet ring carcinoma.
    • Scattered single cells in the lamina propria or beyond with:
      • Abundant cytoplasm containing one large (mucin-filled) vacuole.
      • A peripheral nucleus (displaced by the vacuole).

DDx:

Images:

IHC

CK7 +ve. CK20 -ve, occasionally +ve.

See also

References

  1. ALS. 4 Feb 2009.
  2. Osborn M, Mazzoleni G, Santini D, Marrano D, Martinelli G, Weber K (1988). "Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas". Virchows Arch A Pathol Anat Histopathol 413 (4): 303–12. PMID 2459839.
  3. Sternberg H4P 2nd Ed., P.484
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