Search

Objective The aim of the study was to study the clinicopathological and immunohistochemical features of gastrointestinal stromal tumours and correlation with KIT/PDGFRA mutations. Material and method Eighty consecutive resected cases were genotyped for KIT exons 11, 9, 13, 17 and PDGFRA exons 18, 14, 12 and correlated with histomorphology by nonparametric tests. Results Forty-seven cases (58.8%) were in the high-risk group. Males had higher rates of KIT exon 11 and PDGFRA exon 18 mutations than females (p=0.03). KIT and PDGFRA mutation frequencies were lower (58.8%) than western data showing KIT exon 11 mutation in 63.8%, KIT exon 9 mutation in 19% and PDGFRA exon 18 mutation in 17% of the cases. Extragastrointestinal stromal tumours (n=6) showed 100% mutation. KIT exon 11 deletion was associated with gastric location (60%) (p=0.04), spindle cells (63.3%), and high-risk stratification (66.6%) (p=0.01) while KIT exon 9 mutation was common in small intestine (66.7%) (p=0.04), in higher risk groups (66.7%) (p=0.01) and 75% of codon 502-503 duplications (p=0.03). PDGFRA 18 mutation was common in males (p=0.03), in gastric location (62.5%) (p=0.04), in cases showing mild to moderate atypia (62.5%) (p=0.01) and lower risk stratification (62.5%) (p=0.01). KIT/PDGFRA mutations were significantly associated with gender (p=0.03), location (p=0.04), nuclear atypia (p=0.01) and risk stratification (p=0.01). Conclusion Morphological features and anatomic location may be useful in deciding molecular testing strategy, particularly in resource-limited settings, when a plethora of targetable mutations are present. An algorithm may be derived for genotyping with KIT exon 11 and PDGFRA exon 18 heading the list of targetable mutations. This approach may reduce financial burden on patients as well as workload on hospital staff.

Background Gastrointestinal stromal tumors are the most common mesenchymal tumors of the stomach and small bowel. Their myriad morphology sometimes renders the diagnosis very challenging. Case presentation The 57 years old man was admitted to hospital for a gastric mass found in a routine physical examination. Gastroscopy examination showed scattered mucosa congestion and edema, there were no ulcer or mass. Computed tomography scan uncovered a round shadow in the right upper abdominal cavity, closely related to the gastric antrum. The patient underwent tumor resection and partial gastrectomy. On gross examination of the specimen the tumor was 7 cm × 5 cm × 5 cm and the cut surface was greyish white with multifocal small cysts. Microscopically, there are two sharply separated morphologic pattern. One side was hypocellular with short spindle cell randomly distributed in sclerosing stroma in which are some branched staghorn-like vessels, mimicking solitary fibrous tumor. The other side was cellular with loose bundle-like growth of spindle cells in fibromyxoid stroma with lymphocytes infiltration, mimicking inflammatory myofibroblastic tumor. The number of mitosis was less than 5 per 5 mm2 field. There was no necrosis. Immunophenotypically, the spindle cells were focally CD117 weakly positive and Dog1 positive. They were negative for S100, MDM2, ALK, CK-pan, CD34, CDK4, STAT6, SMA, desmin. SDHB expression was intact. Gene sequencing revealed PDGFRA exon 18 mutation (D842V). The final diagnosis was gastrointestinal stromal tumor, low risk. The patient was followed up with 10 months after operation, no recurrence or metastasis was found. Conclusion We present an unusual case of gastrointestinal stromal tumor harboring PDGFRA p.D842 mutation with unusual morphology. Our case expanded the morphological spectrum of those tumors, recognizing this rare morphological variation of the tumor would avoid misdiagnosis and inappropriate treatment.

Purpose: Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients.Patients and methods: A retrospective cohort study was conducted in PDGFRA exon 18 mutation GIST patients treated in six expert centres in the Netherlands and the United States. Two independent radiologists assessed radiological response to imatinib according to Choi's criteria in all patients with measurable disease treated with imatinib in neo-adjuvant or palliative intent.Results: Seventy-one patients with PDGFRA exon 18 mutation were identified of whom 48 patients (69%) had a D842V mutation. Twenty-two (45.8%) D842V-mutated GIST patients received imatinib treatment, 16 had measurable disease. Fourteen out of the 23 (60.9%) patients with non-D842V mutations received imatinib treatment, eight had measurable disease. Two out of 16 (12.5%) D842V-mutated GIST patients had partial response, 3 patients (18.8%) had stable disease and 9 patients (56.3%) had progressive disease as best response. Two patients did not have follow-up computed tomography scans to assess response. Six out of 8 (75%) patients with non-D842V exon 18 mutations had partial response and two (25%) had stable disease as best response.Conclusion: Patients with D842V-mutated GISTs can occasionally respond to imatinib. In the absence of better therapeutic options, imatinib should therefore not be universally withheld in patients with this mutation. (C) 2017 Elsevier Ltd. All rights reserved.