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Abstract
Introduction. Wild-type GISTs are a heterogeneous tumors with different clinical and molecular characteristics which account for about 15% of all GISTs. They include cases with MAPK and PI3K signaling pathways activation, as well as GISTs with a deficiency of succinate dehydrogenase (SDH). SDH deficiency causes uncontrolled cell proliferation and neoangiogenesis.
Purpose. To study the clinical and morphological features of GIST with SDH deficiency.
Materials and methods. In the study of 244 GISTs, 45 wild-type GISTs were identified, 20 of which tumors did not have BRAF or NF1 genes mutations, and tissue samples were available for IHC study. The expression of succinate dehydrogenase subunit B (SDHB) was analyzed using monoclonal antibodies (clone EP288, Epitomics, 1:2000).
Results. Disorder of SDHB expression is a marker of inactivation of the SDH complex function. A study of 20 wild-type GISTs revealed 13 tumors with SDHB deficiency. The median age was 32 years. Women prevailed, four patients having an incomplete Carney triad. The tumor was localized in the stomach in all patients. Multicentric lesions were found in four cases. The average size of the primary tumor was 8.1 cm. Most of the patients were treated for symptoms of gastrointestinal bleeding and pain syndrome. In five cases, the spindle-cell structure of cells was observed, in two cases ― epithelioid-cell structure, and in six cases- mixed structure. In half of the GIST cases, more than 5 mitoses were observed in 50 visual fields (×400). More than half of the patients were found to have distant metastases. The 10-year survival rate of this group of patients is 82%.
Conclusions. SDH-deficient GISTs are a rare variety of wild type GIST characterized by a predominant incidence occurring among young women, selective localization in the stomach, and a high incidence of regional lymph node metastases. In half of the cases, patients suffered from distant metastases in the peritoneum and liver it the time of diagnosis.
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