Gastrointestinal stromal tumors

Abstract

Introduction: The gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the intestinal tract, known to be refractory to conventional chemotherapy or radiation. Its pathogenesis is defined by mutations within the KIT and PDGFRA gene, which constitutively activate KIT and PDGFRA oncoproteins, and serve as crucial diagnostic and therapeutic targets.

Discussion: Besides surgery, therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. Still, the only curative option for GIST is given after complete surgical removal even in a metastatic setting, but recurrence is common, and the risk can be defined by surgical factors like incomplete resection, intraperitoneal rupture, or bleeding and tumor associated factors like tumor size, mitotic index, or localization.

Conclusion: Consequently, adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors is recommended for high-risk patients after complete resection. For unresectable and advanced GIST, a partial response or stable disease can be achieved in about 80% of patients with imatinib mesylate.

Fig. 1

Grossly, gastrointestinal stromal tumors (GIST) usually present as round and sharply demarcated submucosal mass lesions throughout the gastrointestinal tract, as in this case, in the wall of the stomach (a). They exhibit a solid, sometimes cystic, fleshy, tan white cut surface with occasional areas of hemorrhage (b) and sometimes ulcerations of the overlying mucosa

Fig. 2

On microscopic view, GIST either show spindle cell [a hematoxylin–stain (HE)] or epithelioid differentiation (b), HE, the latter of which being most frequent in gastric GIST. Immunostaining with CD117 (KIT) is characteristically positive in GIST of either differentiation (c spindle cell, d epithelioid). Immunostaining with PDGFRA is typically weaker in spindle cell GIST (e) than in epithelioid GIST (f) (×100)

Fig. 3

Mutational analysis of the KIT and PDGFRA genes has become an important prognostic tool with therapeutic impact as the exemplary point mutation at codon 557 at KIT exon 11, causing the replacement of the amino acid tryptophan by glycine (c.1669T >G;p.W557G) (arrow)

Fig. 4

Abdominal CT scan displaying a gastric GIST

Fig. 5

Endosonography for a gastric GIST (a) with the corresponding gastroscopic view of the tumor (b)