GISTs are mesenchymal tumors originating primarily from interstitial cells of Cajal or related stem cell-like precursors [
3] of the gastrointestinal tract wall. Typically, they are characterized by the expression of the receptor tyrosine kinase Kit (CD117)[
4], although some GISTs do not or only weakly express this marker [
5]. Primary omental GISTs, Sakurai et al. implicated their possible pathogenesis from ICC-like Kit-positive cells existing in the normal omentum [
6]. It is commonly accepted that mutually exclusive mutations in Kit or PDGFRA receptor tyrosine kinase proteins play a central role in GIST pathogenesis [
7‐
10]. This is clearly illustrated by the collected data from primary omental GISTs (Table
2). Mutually exclusive gain-of-function Kit or PDGFRA mutations represent in-frame deletions, point mutations, duplications or insertions. Mutations in the Kit juxtamembrane domain (exon 11) are the most common in GISTs of all sites, whereas a rare Kit extracellular domain (exon 9) Ala502-Tyr503 duplication is specific for intestinal GISTs. Mutations in PDGFRA have been identified in the juxtamembrane (exon 12), as observed in our case, and tyrosine kinase domains (exons 14 and 18), nearly exclusively in gastric GISTs, mostly epithelioid variants. Some Kit and PDGFRA mutations carry prognostic value. The Kit/PDGFRA tyrosine kinase inhibitor Imatinib has been successfully used in the treatment of metastatic GISTs for more than 5 years [
10,
11]. Microscopic features are site-dependent and the majority (more than 85%) appears as spindle cell tumors [
11,
12]. However, only half of our collected omental GISTs appeared to be spindle cell tumors, the remaining being epithelioid and myxoid (Table
1). No correlation between prognosis and histologic type has been reported. On the other hand, it is well known that tumor size and mitotic activity are the best prognostic features [
10]. In our case, the tumor size and the mitotic activity expressed per 50 HPFs were 20 cm and 2, respectively. It is hardly predict accurately the risk for disease progression and malignant potential of our case, because of scarcity of the primary omental GIST. Based on the criteria advocated by Miettinen and Lasota, these two tumor parameters place the tumor in group 3b, at the intermediate risk [
10], although according to the risk assessment proposed by Fletcher, et al., our patient displayed high-risk feature (tumor size above 10 cm, irrespective of low number of mitoses) [
13].
Table 1
Case review of the primary omental GISTs
1 | Takahashi [17] (1998) | 71/M | 17 | Sp | 1–3 | ANED, 2-Mo |
2 | Miettinen [18] (1999) | 58/F | 2.5 | Ep | 1 | Dead of colon cancer, 2.3-Yrs |
3 | | 89/M | 2.5 | Mixed | 7 | DUC, 3-Yrs |
4 | | 31/F | 7.5 | Sp | 19 | ANED, 3.5-Yrs |
5 | | 80/F | 10 | Ep | 7 | ANED, 2.0-Yrs |
6 | | 44/M | 12 | Ep | <1 | ANED, 1.6-Yrs |
7 | | 72/M | 15 | Mixed | 26 | ANED, 1.5-Yrs |
8 | | 67/F | 16.5 | Sp | 5 | LTF |
9 | | 56/F | 20 | Ep | 0 | LTF |
10 | | 64/M | 20 | Sp | 4 | ANED, 2.0-Yrs |
11 | | 34/M | 23 | Sp | 1 | LTF |
12 | | 60/M | 24 | Ep | 1 | ANED, 3.4-Yrs |
13 | | 68/F | 26 | Sp | 2 | ANED, 8.5-Yrs |
14 | | 70/F | 36 | Ep | <1 | LTF |
15 | Sakurai [6] (2001) | 39/F | 6 | Sp | 7.7** | NA |
16 | | 52/F | 11.5 | Sp | 4.3** | NA |
17 | | 74/F | 8 | Sp | <1** | NA |
18 | | 65/F | 16 | Sp | 0.9** | NA |
19 | | 61/F | 23 | Sp | 22** | NA |
20 | Fukuda [19] (2001) | 45/M | 4.5 | Sp | <1* | ANED, 0.9-Yrs |
21 | Suzuki [15] (2003) | 65/M | 13 | Sp | 5–8 13.8* | DOD 1.3-Yrs (Liver mets.) |
22 | Sakurai [8] (2004) | 73/F | 4 | Myxoid | 3* | ANED, 4-Mo |
23 | | 52/M | >20 | Ep | 4* | ANED, 13-Mo |
24 | Yamamoto [9](2004) | 62/F | 11 | Ep | 3 | ANED, 0.5-Yrs |
25 | | 54//M | 15 | Ep | 3 | ANED, 5.2-Yrs |
26 | | 49/F | 17 | Ep | 1 | ANED, 4.0-Yrs |
27 | Caricato [20] (2005) | 84/F | ≤5 | Sp | NA | ANED, 0.3-Yrs |
28 | Present case (2006) | 65/M | 20 | Myxoid | 2 | ANED, 0.5-Yrs |
Table 2
Immunohistochemistry and Mutations in the primary omental GISTs
| | KIT | CD34 | S100 | SMA | Desmin | Gene | Site |
15 | Spindle | Positive | + | - | - | - | C-kit | Exon11, MS |
16 | Spindle | Positive | + | - | - | - | C-kit | Exon11, IFD |
17 | Spindle | Positive | + | - | - | - | C-kit | Exon11, MS |
18 | Spindle | Positive | + | - | - | - | C-kit | Exon11, MS |
19 | Spindle | Positive | + | - | Weak | - | C-kit | Exon11, IFD |
22 | Myxoid epithelioid | Weak | + | - | + | - | PDGFRA | Exon18 del D842V |
23 | Epithelioid | Weak | - | - | - | - | PDGFRA | Exon18 DIMH842-845 |
26 | Epithelioid | Weak | + | NA | NA | NA | PDGFRA | Exon18 |
28 | Myxoid epithelioid | Weak | + | - | - | - | PDGFRA | Exon12, V561D |
Because of possible relapse even after complete resection of omental GISTs [
14‐
16] and the objective response rate of 67 % of Imatinib to the mutation in PDGFRA exon 12 [
11], our patient received daily oral administration of 300 mg Glevec
®, (we applied 15% reduced dose, referring to a report by Cormier, et al. after took account of a smaller average of Japanese build than American) [
14,
16]. At the present time, there are no signs of toxicity and no evidence of relapse. However, because of the short follow-up period and rarity of the primary omental GISTs, it is difficult to assess appropriately their malignant potential, efficacy of different treatment procedures and their overall prognosis. In order to improve overall understanding of the primary omental GISTs, it is useful to analyze the collected detailed data from reported cases.