Diagnosis and Treatment of Abdominal ExtraGastrointestinal Stromal Tumors

Background: To investigate the clinicopathological features and treatment outcome of abdominal extra-gastrointestinal stromal tumors (EGISTs). Methods: The clinicopathological and follow-up results of 22 patients with abdominal EGISTs proved by pathology were reviewed retrospectively. Results: The main symptoms were abdominal mass in 14 cases, abdominal distention and pain in 6, detected by healthy screening in one, spontaneous rupture of tumor and intra-abdominal hemorrhage in one. The tumor locations were retroperitonum in 11 cases, mesentery in 6, and greater momentum in 3, liver in one and pancreas in one, and the tumor size<5cm in one case, 5-10cm in 9 and >10cm in 12. The immunochemistry stain revealed that the positive rate of CD117 was 95.5%, CD34 36.4%, DOG-1 13.6%, SMA 4.5%, and S-100 protein 4.5%. The resection rate was 81.8% (18/22 cases), including tumor resection in 16, an irregular hepatectomy in one, a distal pancreactomy in one, and simple laparotomy with biopsy in 4. The radicality of operation was R0 resection in 14 cases, R1 resection in 2 and R2 resection in 2. Eleven cases (50.0%) in this group received imatinib adjuvant treatment, including administration greater than 1 year in 6 cases, and greater than 3 years in 5. The 1, 3, 5-year overall survival rates in the study were 88.9% (16/18 cases), 72.2% (13/18), and 55.6% (10/21), respectively. Among them, 72.7% (8/11), 45.5% (5/11) and 45.5% (5/11) were for retroperitoneal tumors, respectively; and 100.0% (6/6), 100.0% (6/6) and 66.7% (4/6) for mesentery EGIST, respectively. Conclusions: Abdominal EGISTs have a high potential of malignancy, the surgery is the choice of the treatment, and the postoperative adjuvant treatment with imatinib may improve the survival rate of high-risk cases. in showed diffusely strong positivity for both cytoplasmic and membranous components, and the positive rate of CD117 was 95.5% (21/22), positivity36.4% (8/22), DOG-1 positivity 13.6%(3/22), SMA positivity 4.5%(1/22)S-100 positivity 4.5% (1/22). These suggest EGIST has a similar immunochemistry with GIST.


Postoperative follow-up
Patients were scheduled for follow-up with abdominal CT scanning and/or endoscopy according to risk classification, every 3 months during the first two years and every 12 months thereafter. Follow-up was completed by either chart review or telephone interview in December 2016.

Statistical analysis
Statistical analyses were performed using SPSS 20.0 (SPSS Inc., Chicago, IL, USA). The different characteristics were compared between the groups using a Chi-square test or Fisher's exact test for categorical variables and using a Student's t-test for continuous variables. P< 0.05 was considered as statistically significant.

The clinicopatholgical features of EGISTs
The All patients underwent endoscopy to rule out the tumor arising from gastrointestinal tract.

Histopathological findings and risk classification
The primary tumors were retroperitonum in 11 cases, mesentery in 6, and greater momentum in 3, liver and pancreas in one each. The median tumor size was 8.6cm in diameter (ranging from 4.0 to 22.0cm), including tumor size <5cm in two cases, among 5 to 10cm in 6 and >10cm in 14. The smallest tumor located at lesser omentum, and largest tumor located at retroperitoneum.

Surgical outcomes
All EGISTs underwent laparotomy, including elective surgery in 21 cases, and emergent surgery in 1 because of tumor rupture associated with intra-abdominal hemorrhage. The resection rate was 81.8% (18/22 cases), and the surgical procedure was removal of tumor in 16 (once case with removal of primary tumor and liver metastasis), an irregular hepatectomy in one, a distal pancreactomy in one, and simple laparotomy with biopsy in 4 due to tumor invasion of major vessels, and lymph node metastasis. The radicality of operation was R0 resection in 14 cases, R1 resection in 2, and R2 resection in 2.

Adjuvant treatment with imatinib after surgery
Information of adjuvant imatinib therapy were recorded in 11 patients (50.0%), and they underwent adjuvant therapy with imatinib 400mg qd by mouth, six of the 11 patients had taken imatinib more 7 than 1 year, and five had taken imatinib more than 3 year.
The main side-effects were hand-foot syndrome in 5 cases, liver dysfunction in 3, most of them were grade 1 or 2, and only one with pelvic EGIST complicated with grade IV side-effect and had to discontinue using the agent.

Histopathological behavior
The diagnosis of EGIST is established based on the morphology and immunophenotyping [1][2]. In this study, the specimen showed a well circumscribed lobulated mass with surrounding fibrous capsule appearance, and the tumor cells were spindle, oral or round in shape, sometimes signet-ring like cells could be observed with a clear cytoplasm on microscopic observation. Moreover, the histopathological types included spindle cell morphology in 7 cases (31.6%), epithelioid morphology in 14 (63.6%) and mixed morphology in 1(4.5%).Those changes in this study revealed that the histopatholigic changes and types in EGISTs were similar to those in GISTs, they were in accordance with the description by Reith et al [9].

Surgical treatment of EGIST
Surgical removal is the gold standard treatment and the only known curative therapy for nonmetastatic GISTs and it is important to achieve a complete removal of the mass when "en block" with the contiguous tissues is possible [2,[5][6][7][8][18][19]. Following this principle, complete surgical resection with negative margins (R0 resection) is the choice of therapy, and lymph node dissection is not a routine standard practice, because diffuse intraabdominal spread and liver metastasis are the common spread pattern of tumor ways, whereas lymph node metastases are extremely rare [4][5][6][7][8][9].
Moreover, laparoscopic resection is not being suggested routinely owing to its easy rupture of tumor before or during surgery, which can cause abdominal dissemination and affect the prognosis of EGIST patients. In our study, the resection rate was 81.8% (18/22 cases), and the surgical procedure was removal of tumor in 16 (once case with removal of primary tumor and liver metastasis), an irregular hepatectomy in one, a distal pancreactomy in one, and simple laparotomy with biopsy in 2 due to tumor invasion of major vessels, and lymph node metastasis. The radicality of operation was R0 resection in 14 cases, R1 resection in 2, and R2 resection in 2.

Imanitib mesylate treatment
Imanitib mesylate, which is an inhibitor of the tyrosine kinase activity of C-Kit, has been effective in treatment of GISTs, and neoadjuvant and adjuvant therapy with imatinib has been shown to reduce the risk of recurrence and improve the survival [18][19][20][21][22][23][24][25]. Dimofte et al [20] reported that a case of a primary epithelioid EGIST of the greater omentum treating with surgery following Imatinib mesylate, was disease free at two-year follow-up. Yi et al [17] reported that 31 of 51patients with an EGIST had undergone surgery, and 10 had unresectable disease and accepted palliative imatinib treatment, which resulted in 22.7 mo of progression-free survival. In this study, 11 cases (35.5%) underwent adjuvant therapy with imanitib 400mg qd by mouth, 10 of them had taken imatinib more than 1 year, 4 had taken imatinib more than 3 years. 10

Survival and recurrence
Compared with GISTs, EGISTs are considered to exhibit a worse prognosis, because EGISTs are commonly accompanied by certain adverse prognostic factors, such as larger tumors, late detection and distant or lymph node metastases [1][2][4][5][6][7][8][9]11,[13][14][15][16]21]. The estimated 5-and 15-year recurrence-free survival rates for GISTs treated with surgery alone are 70.5 and 59.9%, respectively [2,[4][5][6][7][8][9]. Feng et al [12] In conclusion, EGISTs are very rare aggressive tumors with high metastatic potential and a high recurrence rate, though they have similar histological and immunohistochemical features. Complete tumor resection with a microscopic negative margin and the postoperative adjuvant treatment with imatinib are considered the optimal treatment option, and may improve the survival rate of high-risk cases. Though extra-gastrointestinal stromal tumor (EGIST) shares the same histological features and immunophenotype, the clinicopathological behavior and treatment has not been elicited. In this study, the data of 22 patients with abdominal EGIST was reviewed retrospectively. The results suggested that abdominal EGIST had a high malignant potential, surgery and postoperative adjuvant treatment with imatinib might improve the survival rate of high-risk cases.

Figures
16 Figure 1 The survival of patients with abdominal extra-gastrointestinal stromal tumor: Though the survival of mesentery EGIST seems better than retroperitoneal or total abdominal EGIST, the difference is not significant (P>0.05)