This study represented the largest cases of pancreatic GIST so far. The clinicopathologic features and prognosis of pancreatic GISTs were analyzed and further compared with gastric GISTs from our center. We found pancreatic GISTs were larger in size and more malignant than gastric GISTs.
The most common location of the pancreatic GISTs was the head of pancreas, followed by the tail of pancreas. The location spectrum was similar to the largest series reported by Akbulut et al.42 It is well known that GISTs are considered to arise from ICC, the pacemaker cells of the alimentary tract. Yamaura et al39 have shown the presence of c-KIT positive interstitial cells surrounding the intercalated ducts and acinus in the pancreas. Popescu et al46 reported the existence of ICCs in the human exocrine pancreas which have a phenotype similar to the enteric ICCs. Wang et al47 have demonstrated that the c-Kit positive ICCs were mainly around the main duct as a function of pacemaker cells for the spontaneous rhythmic pancreatic duct contractions, and ICCs around the large blood vessels most likely affected vessel wall rhythmicity. Although the exact function of these cells is not clear, the discovery of pancreatic ICC supports the diagnosis of an EGIST arising solely from the pancreas. Although the above studies have demonstrated the existence of ICCs in the pancreas, they did not reveal the different distribution of ICCs among the different locations of pancreas. Thus, the different distribution of pancreatic GISTs in respect to locations remains further investigations.
In our present study, 14 tumors displayed cystic mass (35.9%) and 8 tumors showed mixed mass (20.5%). It is well known that cystic lesions of the pancreas are usually pseudocysts, related to chronic pancreatitis. Cystic tumors of the pancreas most commonly corresponds to serous microcystic adenoma, mucinous cystic tumor, intraductal mucinous tumor, and solid pseudopapillary tumor, while less commonly to cystic endocrine tumors, cystic teratomas, cystic metastasis, and lymphagiomas.48 Although very rare in the pancreas, GISTs should be considered in the differential diagnosis of cystic pancreatic masses. Correct diagnosis of cystic pancreatic GISTs is very difficult before operation. Computed tomography (CT) and endoscopic ultrasound guided fine needle aspiration (EUS-FNA) are usually used to confirm the diagnosis of pancreatic lesions. The accuracy of CT to predict malignant versus benign cystic lesion of the pancreas ranges between 76% and 82%, and the accuracy of CT determination of the histopathologic diagnosis of a pancreatic cystic lesion is <50%.49 EUS-FNA may be helpful for the diagnosis of pancreatic lesions.50 However, the accuracy of EUS-FNA of a cystic lesion is much lower than that of solid mass, because successful diagnosis of GIST using FNA depends on the adequacy of the specimen.
It is important to differentiate between pancreatic and duodenal GISTs adjacent to the pancreas immediately. The proximity of the C-loop of the duodenum to the pancreatic head may make it difficult to distinguish the origin of the GISTs by imaging examination alone. Given its ability to distinguish the different layers of the gastrointestinal tract with high accuracy, EUS is the most successful method at differentiating GISTs origin between the duodenum and head of pancreas.32,35
In our present study, nearly 60% of the pancreatic GISTs displayed cystic or mixed imaging features. Thus, we investigated the correlation between imaging features and clinicopathologic features. We found that the imaging features were correlated with tumor size and histologic type. All the pancreatic GISTs with cystic or mixed imaging features were classified as high risk category in our present study. This may due to the positive correlation between the cystic changes and tumor size. Interestingly, most of the solid pancreatic GISTs displayed spindle cell morphology. However, only half of the tumors with cystic or mixed features displayed spindle cell morphology. Whether there is a direct correlation between epithelioid cell morphology and cystic change needs further investigations.
It is reported that tumor size and mitotic index are the best prognostic indicators for determining the malignant potential of GISTs.51 In our present study, mitotic index was the only risk factor for the prognosis of pancreatic GISTs by univariate analysis. As a result, the multivariate analysis of independent risk factor for prognosis was not necessary in our present study. This may attribute to the limited sample size of pancreatic GISTs.
Complete surgical resection with negative microscopic margins is the standard treatment used to address GISTs.52 It is well known that extended resection, including lymphadenectomy is unnecessary, because lymph node metastases are rare (prevalence is about 1%)53 and skip metastases have never been reported. Although variety of surgical procedures have been reported in the literature, surgical resections depends upon the location of pancreatic GISTs. GISTs of the pancreaticoduodenal complex present many technical challenges because of the anatomy of the region. In this situation, pancreaticoduodenectomy (Whipple procedure) is demonstrated to be feasible.15 Duodenum preserving pancreatic head resection or simple tumor excision can also be applied, if the tumor is small with clear boundary or the patient cannot tolerate pancreaticoduodenectomy.13 Pancreatic body and tail resection with splenectomy or partial resection of the pancreas could be performed if the tumor is located in the body or tail of pancreas. Gastrectomy, segmental bowel resection and hemicolectomy could also be performed depending on the location of pancreatic GISTs.42
Besides tumor size and mitotic index, tumor location is also one of the recurrent risk factors for GISTs after radical resection.54 However, the modified NIH risk classification system distinguishes only gastric from nongastric tumors,45 and the prognostic characteristics of pancreatic GISTs are not discussed. Thus, the prognosis of pancreatic and gastric GISTs were compared in our study. We found that the DFS of pancreatic GISTs was significantly worse than that of gastric GISTs, while the DSS was comparable between the 2 groups. Multivariate analysis showed that location was an independent prognostic factor for DFS between pancreatic and gastric GISTs, but not for DSS.
There are some limitations in our present study. First, it is a retrospective analysis. Therefore, completeness of the data is limited. Second, the sample size of pancreatic GISTs was not large enough, which will result in sampling error. Third, due to the limited sample size of duodenal, small intestinal and rectal GISTs in our center, we could not compare the clinicopathologic features and prognosis of pancreatic with nongastric GISTs.
The most common location was head of pancreas. The majority of pancreatic GISTs exceeded 5 cm in diameter, displayed cystic or mixed imaging features, and were high risk. The imaging features were correlated with tumor size and histologic type. Mitotic index was the only risk factor for DFS of pancreatic GISTs. Pancreatic GISTs differed significantly from gastric GISTs in respect to clinicopathologic features. The DFS of pancreatic GISTs was worse than that of gastric GISTs.
1. Grignol VP, Termuhlen PM. Gastrointestinal stromal tumor surgery and adjuvant therapy. Surg Clin North Am. 2011;91:1079–1087.
2. Yang J, Feng F, Li M, et al. Surgical resection should be taken into consideration for the treatment of small gastric gastrointestinal stromal tumors. World J Surg Oncol. 2013;11:273.
3. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science (New York, NY). 1998;279:577–580.
4. Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130:1466–1478.
5. Agaimy A, Wang LM, Eck M, et al. Loss of DOG-1 expression associated with shift from spindled to epithelioid morphology in gastric gastrointestinal stromal tumors with KIT and platelet-derived growth factor receptor alpha mutations. Ann Diagn Pathol. 2013;17:187–191.
6. Joensuu H, Vehtari A, Riihimaki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13:265–274.
7. Stanek M, Pedziwiatr M, Matlok M, et al. Laparoscopic removal of gastrointestinal stromal tumors of uncinate process of pancreas. Wideochir Inne Tech Maloinwazyjne. 2015;10:311–315.
8. Aziret M, Cetinkunar S, Aktas E, et al. Pancreatic gastrointestinal stromal tumor after upper gastrointestinal hemorrhage and performance of whipple procedure: a case report and literature review. Am J Case Rep. 2015;16:509–513.
9. Joseph P, Goyal R, Bansal P, et al. Pancreatic extra-gastrointestinal stromal tumour with documentation of C-kit mutation: a case report. Journal of clinical and diagnostic research. JCDR. 2015;9:Ed17–Ed18.
10. Hansen Cde A, Jose FF, Caluz NP. Gastrointestinal stromal tumor (GIST) mistaken for pancreatic pseudocyst—case report and literature review. Clin Case Rep. 2014;2:197–200.
11. Ambrosio MR, Rocca BJ, Mastrogiulio MG, et al. Cystic gastrointestinal stromal tumors of the pancreas simulating cystoadenocarcinoma. Report of three cases and short review of the literature. Histol Histopathol. 2014;29:1583–1591.
12. Beltrame V, Gruppo M, Pastorelli D, et al. Extra-gastrointestinal stromal tumor of the pancreas: case report and review of the literature. World J Surg Oncol. 2014;12:105.
13. Tian YT, Liu H, Shi SS, et al. Malignant extra-gastrointestinal stromal tumor of the pancreas: report of two cases and review of the literature. World J Gastroenterol. 2014;20:863–868.
14. Serin KR, Keskin M, Gulluoglu M, et al. An atypically localized gastrointestinal stromal tumor: a case report of pancreas gastrointestinal stromal tumor. Ulusal Cerrahi Derg. 2013;29:42–44.
15. Soufi M, Bouziane M, Massrouri R, et al. Pancreatic GIST with pancreas divisum: A new entity. Int J Surg Case Rep. 2013;4:68–71.
16. Wegge J, Bartholomew DM, Burke LH, et al. Pancreatic extra-gastrointestinal stromal tumour masquerading as a bleeding duodenal mass. BMJ Case Rep. 2012;2012. doi: 10.1136/bcr-2012-007040.
17. Kim HH, Koh YS, Park EK, et al. Primary extragastrointestinal stromal tumor arising in the pancreas: report of a case. Surg Today. 2012;42:386–390.
18. Babu S, Sushila K, Zhang Y, et al. Extra-gastrointestinal stromal tumor arising in the pancreas: a case report and litreature review. J Gastroenterol Hepatol Res. 2012;1:80–83.
19. Cecka F, Jon B, Ferko A, et al. Long-term survival of a patient after resection of a gastrointestinal stromal tumor arising from the pancreas. Hepatobiliary Pancreat Dis Int. 2011;10:330–332.
20. Rao RN, Vij M, Singla N, et al. Malignant pancreatic extra-gastrointestinal stromal tumor diagnosed by ultrasound guided fine needle aspiration cytology. A case report with a review of the literature. JOP. 2011;12:283–286.
21. Vij M, Agrawal V, Pandey R. Malignant extra-gastrointestinal stromal tumor of the pancreas. A case report and review of literature. JOP. 2011;12:200–204.
22. Meng L, Fang SH, Jin M. An unusual case of pancreatic and gastric neoplasms (2010: 12b). Malignant GISTs originating from the pancreas and stomach. Eur Radiol. 2011;21:663–665.
23. Yang F, Jin C, Fu D, et al. Extra-gastrointestinal stromal tumor of the pancreas: clinical characteristics, diagnosis, treatment, and outcome. J Surg Oncol. 2011;103:739–740.
24. Barros A, Linhares E, Valadao M, et al. Extragastrointestinal stromal tumors (EGIST): a series of case reports. Hepatogastroenterology. 2011;58:865–868.
25. Saif MW, Hotchkiss S, Kaley K. Gastrointestinal stromal tumors of the pancreas. JOP. 2010;11:405–406. Author reply 12.
26. Padhi S, Kongara R, Uppin SG, et al. Extragastrointestinal stromal tumor arising in the pancreas: a case report with a review of the literature. JOP. 2010;11:244–248.
27. Joshi J, Rustagi T. Pancreatic extra-gastrointestinal stromal tumor: an unusual presentation of a rare diagnosis. Gastrointest Cancer Res. 2010;(suppl 1):S29–S30.
28. Crisan A, Nicoara E, Cucui V, et al. Prolonged fever associated with gastrointestinal stromal tumor-case report. J Exp Med Surg Res. 2010;17:219–224.
29. Goh BK, Kesavan SM, Wong WK. An unusual cause of a pancreatic head tumor. Gastroenterology. 2009;137:e5–e6.
30. Trabelsi A, Yacoub-Abid LB, Mtimet A, et al. Gastrointestinal stromal tumor of the pancreas: a case report and review of the literature. North Am J Med Sci. 2009;1:324–326.
31. Pauser U, Hinz S, Merz H, et al. Gastrointestinal stromal tumors with pseudocystic change mimicking a pancreatic tumor: two case reports. J Med Case Reports. 2009;3:7592.
32. Harindhanavudhi T, Tanawuttiwat T, Pyle J, et al. Extra-gastrointestinal stromal tumor presenting as hemorrhagic pancreatic cyst diagnosed by EUS-FNA. JOP. 2009;10:189–191.
33. Yang F, Long J, Di Y, et al. A giant cystic lesion in the epigastric region. Pancreatic malignant gastrointestinal stromal tumour (GIST). Gut. 2008;57:1494. 636.
34. Showalter SL, Lloyd JM, Glassman DT, et al. Extra-gastrointestinal stromal tumor of the pancreas: case report and a review of the literature. Archiv Surg. 2008;143:305–308.
35. Yan BM, Pai RK, Van Dam J. Diagnosis of pancreatic gastrointestinal stromal tumor by EUS guided FNA. JOP. 2008;9:192–196.
36. Krska Z, Peskova M, Povysil C, et al. GIST of pancreas. Prague Med Rep. 2005;106:201–208.
37. Daum O, Klecka J, Ferda J, et al. Gastrointestinal stromal tumor of the pancreas: case report with documentation of KIT gene mutation. Virchows Archiv. 2005;446:470–472.
38. Pauser U, da Silva MT, Placke J, et al. Cellular hamartoma resembling gastrointestinal stromal tumor: a solid tumor of the pancreas expressing c-kit (CD117). Mod Pathol. 2005;18:1211–1216.
39. Yamaura K, Kato K, Miyazawa M, et al. Stromal tumor of the pancreas with expression of c-kit protein: report of a case. J Gastroenterol Hepatol. 2004;19:467–470.
40. Neto MR, Machuca TN, Pinho RV, et al. Gastrointestinal stromal tumor: report of two unusual cases. Virchows Archiv. 2004;444:594–596.
41. Boyer C, Duvet S, Wacrenier A, et al. [Leiomyosarcoma and stromal tumor of the pancreas]. J Radiol. 2001;82(pt 1):1723–1725.
42. Akbulut S, Yavuz R, Otan E, et al. Pancreatic extragastrointestinal stromal tumor: a case report and comprehensive literature review. World J Gastrointest Surg. 2014;6:175–182.
43. Ganesh M, Kumar S, Krishnamoorthy R, et al. Rare cause of pancreatic mass responding to imatinib treatment. Gastroenterol Today. 2008;18:50–51.
44. Paklina O, Setdikova G, Voskanyan S. Extragastrointestinal stromal tumor of the pancreas: a case report. 25th European Congress of Pathology, Lisbon. 2013; Poster No:14.
45. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–1419.
46. Popescu LM, Hinescu ME, Ionescu N, et al. Interstitial cells of Cajal in pancreas. J Cell Mol Med. 2005;9:169–190.
47. Wang XY, Diamant NE, Huizinga JD. Interstitial cells of Cajal: pacemaker cells of the pancreatic duct? Pancreas. 2011;40:137–143.
48. Gintowt A, Hac S, Dobrowolski S, et al. An unusual presentation of pancreatic pseudocyst mimicking cystic neoplasm of the pancreas: a case report. Cases J. 2009;2:9138.
49. Visser BC, Yeh BM, Qayyum A, et al. Characterization of cystic pancreatic masses: relative accuracy of CT and MRI. AJR Am J Roentgenol. 2007;189:648–656.
50. Akahoshi K, Sumida Y, Matsui N, et al. Preoperative diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration. World J Gastroenterol. 2007;13:2077–2082.
51. Dematteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008;112:608–615.
52. Valsangkar N, Sehdev A, Misra S, et al. Current management of gastrointestinal stromal tumors: surgery, current biomarkers, mutations, and therapy. Surgery. 2015;158:1149–1164.
53. Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumour. Lancet. 2013;382:973–983.
54. Rutkowski P, Nowecki ZI, Michej W, et al. Risk criteria and prognostic factors for predicting recurrences after resection of primary gastrointestinal stromal tumor. Ann Surg Oncol. 2007;14:2018–2027.