*5.1.1. Gastrointestinal stromal tumour (GIST)*

GISTs represent the great majority of mesenchymal tumour of the stomach and arise from the GI-pacemaker cells of Cajal; nearly all of gastric GISTs have a close contact to the gastric muscle wall (muscularis propria). Due to the wide morphological differences in the appearances of GIST: every mesenchymal tumour in the gastric wall is a GIST—until proven otherwise (compare differential diagnosis in Section 5.1.2.).

GISTs are usually tumours of adults with equal sex distribution but can affect children as well. Most of GISTs are solitary (rarely multiple) sporadic tumours but in some predisposing conditions like neurofibromatosis type 1, Carney-Stratakis syndrome (with paraganglioma and deficiency of succinate dehydrogenase) or associated with Carney triade (with extra-adrenal paraganglioma and pulmonary chondroma) tumours are more often multiple and show some other unusual features like epitheloid cell morphology or anatomical locations like oesophagus (compare **Table 7**) [22–28].

GISTs vary in size from very small only incidentally identified to very large bulky tumours. Particularly, the large tumours demonstrate with cysts, haemorrhage or necrosis. The histomorphology appearance is quite variable. Most GISTs show whorls, bundles or fascicle of monotonous spindle-cells with blunt-ended nuclei and eosinophilic cytoplasm (similar to tumours with muscle differentiation, compare **Figure 3**). Pleomorphism of tumour cells is not a typical feature (nevertheless some tumours can show striking pleomorphic nuclei). Sometimes paranuclear clear vacuoles or GISTs with small and intense eosinophilc homogenous filamentous material between tumour cells (skeinoid fibres; but usually seen in GIST of the small bowl) are seen. Some GISTs have an epitheloid cell appearance and these tumours are more often immunohistochemically CD117 negative. DOG1 ('discovered on GIST') is currently the protein with the highest sensitivity and specificity for GIST and is consistently positive in all epitheloid GISTs as well (compare **Tables 7** and **8**) [23, 29, 30].

The molecular basis for the CD117 protein-overexpression is an activating mutation of the c-kit gene (usually in the exons 9 or 11). A few tumours have mutations in platelet-derived growth factor receptor, alpha (PDGFRa), only.

Different mutations show different sensitivity to drug-related CD117 blockade (compare **Table 9**) [31]. Therefore, it is important to settle the exact underlying mutation.


**Table 7.** Clinico-pathological characteristics in GIST.

**Figure 3.** Spindle cell GIST (c-kit and DOG1 immunohistochemistry): (A) spindle cell GIST (HE), (B) DOG1 and (C) CD117.


**Table 8.** Immunohistochemical markers in GIST.


**Table 9.** Imatinib dosage.

It is important to realize that all GISTs have the potential to metastasize. But most gastric GISTs follow a benign biological behaviour. The most important tumour characteristics associated with risk of progression are size, mitotic rate and anatomical location (but here we discuss gastric GIST, only) (compare **Tables 9** and **10**).

Malignant Gastric Tumours: The Role of Pathologist in the Diagnosis and for Therapeutic Decisions http://dx.doi.org/10.5772/intechopen.69838 281


**Table 10.** Risk of progression of gastric GIST.

*5.1.2. Main differential diagnosis to GIST (including typical immunohistochemical/molecular findings)*


It is important to realize that all GISTs have the potential to metastasize. But most gastric GISTs follow a benign biological behaviour. The most important tumour characteristics associated with risk of progression are size, mitotic rate and anatomical location (but here we

discuss gastric GIST, only) (compare **Tables 9** and **10**).

3A 3B 3C

DOG-1 ≈100 Highest sensitivity and specificity

**Antibody % of cases Remarks**

CD34 80 Low specificity

S100 1–5 Focally

**Table 8.** Immunohistochemical markers in GIST.

*Source*: Modified from onkopedia; GIST.

**Table 9.** Imatinib dosage.

**Imatinib dosage in dependence of c-kit/PDGFRA-genotype**

c-kit Exon 11, 13, 17, wildtype 400 mg c-kit Exon 9 800 mg PDGFR-α-wild-type, Exon 12, 14 400 mg

SMA +h-Caldesmon 30

CD117.

280 Gastric Cancer

**Figure 3.** Spindle cell GIST (c-kit and DOG1 immunohistochemistry): (A) spindle cell GIST (HE), (B) DOG1 and (C)

CD117(=c-kit) 90 Membrane staining; sometimes paranuclear dot; can be negative mainly in

epitheloid GIST

Vimentin ≈100 Very poor specificity; leiomyoma are negative for 'Vimentin'

Desmin <5 Most GIST are completely negative, sometimes patchy

MelanA <1 Mainly in epitheloid GIST; DD: epitheloid PEComa

**Genotype Imatinib dosage per day**

PDGFR-α Exon 18 (D842V) mutation Imatinib resistant

