Gastrointestinal Stromal Tumour

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 SMALL INTESTINE

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    Dr Sampurna Roy MD

 

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Gastric carcinoids are rare tumours.

Clinical setting:

Type I  - Associated with chronic atrophic gastritis with or without pernicious anemia.
In
autoimmune gastritis progressive destruction of the specialised parietal and chief cell zone leads to atrophy , intestinal metaplasia , hypochlorhydria and hypergastrinemia.

- Type II - In Zollinger Ellison syndrome, particularly in patients associated with multiple endocrine neoplasia type 1.        
   
Type III - Sporadic tumours
   - Not related to hypergastrinemia
   - In the antrum or corpus
   - Larger lesion, may be ulcerated.
   - May have an aggressive course.
Endocrine cell hyperplasia : Characterized by increased numbers of cells/unit area of the mucosa.


Types:
  
I  G-cell hyperplasia: Associated with increased number of G -cells in the antrum,hypergastrinemia and ulcerogenic syndrome resembling Zollinger Ellison syndrome.
  
II ECL cell hyperplasia:


Types of gastric carcinoids:
   
I  Tumour composed of G-cells (gastrinoma)
  
II  Tumour cells are composed of enterochromaffin-like (ECL) cells in the oxyntic  mucosa. 

Hypergastrinemia plays an important role in the pathogenesis of gastric carcinoids.

MEN type 1 gene locus may also be involved in the pathogenesis.

G-CELL HYPERPLASIA AND G-CELL CARCINOIDS:

- G-cell hyperplasia (increased number of G-cells in the middle and lower third of antral glands)
- Progress to form micronodular G-cell clusters.
- Finally form  G-cell carcinoids (Gastrinoma) .
- These are usually solitary lesions.
- Located in the gastric antrum.
- G-cell hyperplasia should be distinguished from G-cell carcinoids.
- Gastrinomas are commonly present in the pancreas and duodenum.

HYPERPLASIA OF ENTEROCHROMAFFIN - LIKE (ECL) CELLS AND CARCINOIDS COMPOSED OF ECL CELLS.

- There is corpus ECL cell hyperplasia following antral G- cell hyperplasia. Gastrin has a stimulatory action on ECL cells.
-  ECL cell are scattered singly or in clusters.(upto 3 cells / glands).
-  Linear hyperplasia along glandular basement
membrane.
-  Followed by formation of solid micronodular endocrine cell nests ( microcarcinoids ). These are
100 - 150 mm in diameter.
-  Micronodules enlarge show cytological atypia  and break basement membrane.
-  Finally these nodules form overt carcinoid tumour. These have a lobular or trabecular pattern and are more than 0.5 mm in diameter. 

FEATURES OF  ECL CELL CARCINOIDS:

- Most common type of gastric carcinoid.
- These are usually multiple lesions.
- Distributed  throughout  the fundus.
- Non- argentaffin but strongly argyrophilic.
- ECL cell carcinoid  in chronic corpus gastritis (autoimmune) are usually small (less than 1cm in diameter)  and rarely metastasize.
- Virtually never lethal.
- Never produce clinical hypersecretion syndrome.
- May regress spontaneously or following antrectomy.
- Treated by local excision or endoscopic polypectomy
- Gastrectomy is indicated in rare cases where tumours are larger (more than 2cm) and numerous or small tumours with angioinvasion.

FEATURES OF ECL CELL CARCINOIDS:

- Most common type of gastric carcinoid.
- These are usually multiple lesions.
- Distributed  throughout  the fundus.
- Non- argentaffin but strongly argyrophilic.
- ECL cell carcinoid  in chronic corpus gastritis (autoimmune) are usually small (less than 1cm in diameter)  and rarely metastasize.
- Virtually never lethal.
- Never produce clinical hypersecretion syndrome.
- May regress spontaneously or following antrectomy.
- Treated by local excision or endoscopic polypectomy
- Gastrectomy is indicated in rare cases where tumours are larger (more than 2cm) and numerous  or small tumours with angioinvasion.

Gross features of gastric carcinoids:

- Small polypoid, well circumscribed raised lesion covered by mucosa.
- Larger lesions infiltrate through the full  thickness of the stomach wall.
- Cut surface has a yellow-gray appearance.
 
Microscopic features:

-Microglandular or trabecular growth pattern.
-Composed of small regular cells with finely granular cytoplasm.
-Clear cell  variant has been reported.
-Round or oval nuclei.
-Minimal pleomorphism.
-Mitoses are scanty. Necrosis is usually absent.
-Retraction artifact noted around nests of cells.

         
Capella C et al. 1995. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch. 425 (6): 547-60  

BENIGN: Limited to mucosa and submucosa.  No angioinvasion : Less than 1cm.

BORDERLINE:     Limited to mucosa & submucosa.
                            Angioinvasion (+) : Less than 1cm
                            Angioinvasion (- ) : 1  to  2 cm

LOW GRADE MALIGNANT:  Any functioning tumour.
                             Invade beyond submucosa.
                             Angioinvasion  (+)   :   1  to 2 cm
                             Angioinvasion: (-) :  More than 2 cm

HIGH GRADE MALIGNANT: Atypical carcinoid / small cell carcinoma.
                                                   

     Atypical carcinoids are characterized by :
    - infiltrative growth pattern
    - presence of vascular invasion
    - necrosis
    - nuclear pleomorphism
    - hyperchromasia
    - mitotic activity  more  than 2 per 10 HPF.

                                        

 

 
Immunohistochemistry :
The tumour shows immunopositivity for:
  Neuron specific enolase
  Chromogranin A
  Synaptophysin
  Leu 7
  PGP 9.5
  Carcinoembryonic antigen in some cases

Abstracts:

Morphological, molecular, and prognostic aspects of gastric endocrine tumors.Microsc Res Tech. 2000 Mar 15;48(6):339-48.

Endocrine cell growths in atrophic body gastritis. Critical evaluation of a histological classification. J Pathol. 1997 Jul;182(3):339-46.

Carcinoid tumors of the stomach in atrophic autoimmune gastritis: classification, differential diagnosis and prognosisVerh Dtsch Ges Pathol. 1996;80:199-207.

Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and histogenesis.Am J Surg Pathol. 1995;19 Suppl 1:S1-7.

Enterochromaffin-like (ECL) cells and their growths: relationships to gastrin, reduced acid secretion and gastritis.Baillieres Clin Gastroenterol. 1993 Mar;7(1):149-65.

Gastric endocrine cell hyperplasia and carcinoid tumors in atrophic gastritis type A. Am J Surg Pathol. 1987 Dec;11(12):909-17.

Gastric carcinoids. An immunohistochemical and clinicopathologic study of 104 patients. Cancer. 1994 Apr 15;73(8):2053-8.

Pattern of gastric endocrine cells in microcarcinoidosis--an immunohistochemical study of 14 gastric biopsies. Virchows Arch. 1996 Jul;428 (4-5):237-41.

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An outline of the anatomy and normal histology of the  stomach for pathologists.

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