Table 1.
Summary of clinicopathological and molecular findings in 14 patients undergoing debulking procedures for progressing GIST during TKI treatment
| Patient no. | Treatment | Age/sex | Location | Size (cm) | Morphology | Mitoses/ 50HPF |
Histological treatment response |
KIT/IHC | Primary KIT mutation | Secondary KIT mutation
|
|
|---|---|---|---|---|---|---|---|---|---|---|---|
| DHPLC | |||||||||||
| 1 | IM | 57M | Serosal nodule (1) | 1.8 | Spindle | 20 | 1 | + | Exon 9 (insertion AY502–503) |
NMF | NMF |
| Serosal nodule (2) | 2.7 | Spindle (perivascular growth) | 7 | 1 | + | NMF | |||||
| Serosal nodule (3) | 4.0 | Spindle (perivascular growth) | 18 | 1 | + | NMF | |||||
| 2 | IM,SU | 66M | Serosal nodule right lower quadrant | 1.7 | Mixed (clear CP) | 4 | 3 | + | Exon 9 (insertion AY502–503) |
NMF | NMF |
| Omental nodule | 0.7 | Spindle | 10 | 1 | + | NMF | |||||
| Sigmoid mass (1) | 5.0 | Epithelioid | 3 | 3 | + | NMF | |||||
| Sigmoid mass (2) | 5.0 | Epithelioid | 6 | 3 | − | NMF | |||||
| Periumbilical tumour | 12.0 | Mixed | 9 | 2 | + | Exon 17 | N822Y | ||||
| Serosal nodule right upper quadrant (1) | 2.0 | Epithelioid | 34 | 1 | + | N822K | |||||
| Serosal nodule right upper quadrant (2) | 4.0 | Epithelioid | 33 | 2 | + | N822K | |||||
| 3 | IM,SU | 62M | Stomach (1) | 24.0 | Spindle (palisading) | 100 | 2 | + | Exon 11 (deletion EVQWKV554–559) |
Exon 17 | D8I6H |
| Stomach (2) | 24.0 | Spindle (palisading) | 40 | 2 | NMF | NMF | |||||
| 4 | IM | 50M | Liver metastasis | 9.5 | Mixed | 19 | 1 | + | Exon 11 (deletion KPMYEVQWK550–558) |
Exon 18 | A829P |
| Stomach (1) | 12.3 | Mixed | 54 | 2 | Exon 13 | V654A | |||||
| Stomach (2) | 12.3 | Epithelioid (giant cells) | 26 | 1 | V654A | ||||||
| 5 | IM,SU | 59F | Liver metastasis | 6.5 | Spindle | 7 | 1 | + | Exon 1 1 (deletion PYD577–579) |
Exon 13 | V654A |
| Mesenteric nodule (1) | 0.9 | Spindle | 22 | 1 | Exon 17 | N822Y | |||||
| Mesenteric nodule (2) | 2.9 | Spindle | 34 | 1 | N822Y | ||||||
| Nodule attached to gallbladder | 3.0 | Spindle (giant cells) | 20 | 1 | D820G | ||||||
| 6 | IM | 75 M | Intra-abdominal 1 | 6.0 | Spindle | 36 | 1 | + | Exon 11 (deletion VEEINGNNYVYIDPTQL560–576) |
Exon 13 | V654A |
| Intra-abdominal 2 | 5.0 | Spindle | 88 | 1 | V654A | ||||||
| Intra-abdominal 2 | 5.0 | Spindle | 88 | 1 | V654A | ||||||
| 7 | IM,SU | 67F | Stomach | 35.0 | Epithelioid (intracytoplasmic inclusions) |
2 | 1 | − | Exon 11 (deletion WKV557-559(F)) |
NMF | NMF |
| Liver metastasis | 2.7 | Epithelioid (intracytoplasmic inclusions and atypia) |
13 | 2 | NMF | ||||||
| Serosal nodule | 3.0 | Epithelioid (intracytoplasmic inclusions and atypia) |
14 | 2 | NMF | ||||||
| 8 | IM | 54M | Abdominal tumour (1) | 3.0 | Spindle | 1 | 3 | + | Exon 11 (deletion WKV557-559C) |
NMF | NMF |
| Tumour Stomach wall | 15.4 | Mixed | 26 | 2 | Exon 17 | Y823D | |||||
| Abdominal tumour (2) | 2.5 | Epithelioid | 8 | 3 | D820Y | ||||||
| Abdominal tumour (3) | 2.5 | Epithelioid | 8 | 3 | D820Y | ||||||
| 9 | IM,SU | 75M | Mesenteric nodule 1 | 1.9 | Spindle | 16 | 2 | + | Exon 11 (point mutation L576P) |
Exon 13 | V654A |
| Skin metastasis | 3.5 | Spindle | 57 | 1 | V654A | ||||||
| Mesenteric nodule 2 | 3.3 | Spindle | 72 | 2 | V654A | ||||||
| Mesenteric nodule 4 | 1.8 | Spindle | 24 | 1 | V654A | ||||||
| Mesenteric nodule 3 | 2.9 | Spindle | 44 | 1 | Exon 13 and 17 | V654A, D820G | |||||
| 10 | IM | 74M | Stomach wall (1) | 13.0 | Epithelioid (intracytoplasmic inclusions) |
15 | 1 | + | Exon 13 (point mutation K642E) |
NMF | NMF |
| Stomach wall (2) | Epithelioid | 52 | 1 | + | NMF | ||||||
| Stomach wall (3) | Epithelioid | 61 | 2 | + | NMF | ||||||
| 11 | IM,SU | 63M | Tumour mid-abdomen | 3.8 | Mixed | 1 | 2 | − | Exon 13 (point mutation K642E) |
NMF | NMF |
| Serosal nodule left upper quadrant (1) | 3.6 | Spindle | 1 | 4 | + | Exon 14 | T670I | ||||
| Serosal nodule ileum (1) | 0.5 | Spindle | 7 | 1 | + | Exon 17 | D8I6H | ||||
| Serosal nodule ileum (2) | 1.0 | Epithelioid | 34 | 1 | + | D8I6H | |||||
| Serosal nodule terminal ileum | 0.7 | Spindle | 1 | 1 | + | D8I6H | |||||
| Serosal nodule left upper quadrant (2) | 2.8 | Mixed | 3 | 2 | + | D8I6H | |||||
| 12 | IM,SU | 60M | Omental nodule | 4.5 | Epithelioid | 36 | 1 | + | NMF | NMF | |
| Liver metastasis (1) | 2.8 | Epithelioid (huge eosinophilic CP) |
18 | 1 | + | ||||||
| Tumour sigmoid wall | 14.0 | Epithelioid | 15 | 1 | + | ||||||
| Liver metastasis (2) | 2.1 | Epithelioid (huge eosinophilic CP) |
16 | 1 | + | ||||||
| 13, NF Type 1 | IM,SU | 44M | Serosal nodule adjacent to bowel | 3.5 | Spindle (storiform) | 1 | 2 | + | NMF | NMF | |
| Nodule lig. of Tritz | 3.0 | Spindle | 1 | 3 | + | ||||||
| Nodule duodenum | 2.5 | Spindle (storiform) | 2 | 2 | + | ||||||
| Mesenteric nodule | 15.0 | Spindle (storiform) | 6 | 2 | + | ||||||
| 14 | IM,SU | 65M | Perigastric mass (1) | 1.5 | Spindle with atypia | 48 | 1 | − | NMF | NMF | |
| Perigastric mass (2) | 2.5 | Epithelioid | 4 | 1 | + | ||||||
| Perigastric mass (3) | 2.4 | Epithelioid | 14 | 2 | + | ||||||
| Liver metastasis | 19.8 | Epithelioid | 58 | 1 | + | ||||||
| Large nodule lesser curvature (1) | 3.5 | Epithelioid with mild atypia | 19 | 1 | + | ||||||
| Large nodule lesser curvature (2) | 3.5 | Spindle with atypia | 60 | 1 | − | ||||||
pt, patient; IM, imatinib; SU, sunitinib; CP, cytoplasm; +, positive; −, negative; NMF, no mutation found.
All listed samples were examinated for KIT mutations in exons 9, 11, 12, 13, 14, 15, 16, 17, 18 and PDGFRA mutations in exons 12, 14, 18. Exons not specifically listed are wild-type.