Clinicopathological, immunohistochemical, molecular-genetic and risk profiles of gastrointestinal stromal tumors in a cohort of Sudanese patients

Abstract

Background: Determining the risk of malignant behaviour and mutational status of gastrointestinal stromal tumours (GISTs) guide the management decision and allow optimal individualized patient treatment.

Objectives: To determine clinicopathological, immunohistochemical (IHC), risk and KIT mutational findings of GISTs in Sudanese patients.

Methods: Histological slides were reviewed, IHC for DOG-1 and CD117 performed and hotspot KIT mutations examined. The risk group was assigned using combined risk criteria.

Results: 21 of the 36 patients (58.3%) were males (mean age, 54.83 ±12.57; range, 26-71). Abdominal pain and mass were the most frequent symptoms. Mean tumor size (±SD) was 11.6(±5.82) cm. Either CD117, DOG1 or both were positive in all cases. Using risk criteria, 33.3% (n=12) were clinically malignant at presentation, 13.9% (n=5) high risk, 16.7% (n=6) intermediate, 27.8% (n=10) low risk and 2.8% (n=1) very low risk. Sixteen of 23 (70%) tested cases had KIT (14 exon 11 and two exon 9) mutations. Six tumors were wild type. Exon 11 deletions (p.I563-L576 del and p.V559-N566delinsD) significantly correlate with disease recurrence (p-value: 0.028).

Conclusions: Sudanese patients with GIST tend to present late. Nearly half of them correspond to the malignant/high-risk category. The frequency of KIT mutations (79.31%) is in line with the literature.

Keywords: DOG1; GIST; Gastrointestinal stromal tumour; Imatinib; KIT; genotyping; malignant behaviour; metastasis; risk assessment; risk stratification; tumour rupture.

Figure 1

A: Intestinal GIST with spindle cell histologic pattern (H&E, X400). B: Gastric epithelioid GIST exhibiting signet ring-like vacuolated cytoplasm (H&E, X400). C: Epithelioid GIST showing monotonous epithelioid morphology with fine reticular fibrosis resulting in organoid nesting pattern (H&E, X400). D: CD117 Immunohistochemical (IHC) expression in spindle cell GIST (CD117 IHC, X400). E: Epithelioid GIST showing strong membranous positivity for DOG1 (DOG1 IHC, X400). F: Gastric epithelioid GIST showing cytoplasmic and characteristic strong Golgi-pattern (arrow) positivity for PDGFRA (PDGFRA IHC, X400).