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. 2024 Feb 7;55(2):572–583. doi: 10.1007/s12029-024-01024-8

Primary Pancreatic GIST — A-Single Centre Case Series and Systematic Review of Literature

Vipul Gupta 1, Amit Chopde 1, Vikram Chaudhari 1, Munita Bal 2, Shailesh V Shrikhande 1, Manish S Bhandare 1,✉
PMCID: PMC13423967  PMID: 38324136

Abstract

Purpose

GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs. We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature.

Methods

A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. After literature search for all studies published before February 2023, 51 articles including 57 patients were identified. Their clinicopathological data and survival analysis were assessed.

Results

The median age of patients treated at our centre was 53 years with a female predominance. The most common epicentre was pancreatic head with abdominal pain as the most common presenting symptom. All 57 patients documented in literature belonged to a similar age group with similar gender predilection. The factors impacting DFS were histologic type, mitotic index, NIH risk category and adjuvant therapy. The median DFS was 74 months with a 5-year DFS being 71.9%, while the 5-year OS was 90.4%.

Conclusion

Pancreatic GIST is a rare entity. Due to limited evidence and evolving literature, results cannot be generalised to a larger population. Larger case series with longer follow-up data are required to further understand the disease biology and long-term outcomes of pancreatic GIST.

Keywords: Gatrointestinal Stromal tumors, GIST, Extragastrointestinal GIST, Pancreatic GIST

Introduction

Gastrointestinal stromal tumors (GIST) are the most common non-epithelial mesenchymal tumors of the gastrointestinal tract (GI) with median age being 60–65 years and predominance in male gender [1]. They are believed to be kit mutation–driven mesenchymal neoplasm specific to GI tract. They can occur at any site where there are interstitial cells of Cajal of circular muscle. Recently, alternative mechanisms of pathogenesis have also been suggested related to mutation in succinate dehydrogenase complex, NF1 and BRAF oncogene. The most common site of GIST has been described as stomach. GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). Though the origin cells of EGIST are not interstitial cells of Cajal but their histology, immunohistochemistry and molecular profiles are similar to GISTs. A vast majority of tumors have a localised extent while a small fraction having a metastatic disease. There is a difference in treatment between GIST and gastrointestinal cancers in that they rarely warrant lymph nodal dissection due to very low rates of nodal metastasis. The most important prognostic factors for GIST are tumor size and mitotic rate; however, a prognostic difference with respect to primary location site has also been suggested [1]. Zhou et al. have suggested that patients with EGIST have a younger age of onset, larger tumor size and poorer prognosis as compared to patients with GIST [2]. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs.

We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature.

Materials and Methods

A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. All cases were reviewed by a dedicated GI pathologist. Only those tumors where the epicentre was clearly described to be pancreatic in final histopathology report were included while others were excluded based on the premise that they might be gastrointestinal in origin. Immunohistochemistry was performed using a panel of CD 117, CD 34 and DOG 1. Neoadjuvant imatinib was given to patients where it could lead to less morbid surgery or in localised but inoperable tumors for an average duration of 6 months with more extended treatment to those where further clinical benefit was expected after rediscussion in multidisciplinary meeting. We followed up all patients in postoperative period at 3–6-month intervals (high risk and low risk respectively) with cross-sectional imaging for 5 years followed by annually. Clinical information and follow-up data were retrieved from electronic medical records. Literature search was done for previously published articles from Pubmed, MEDLINE, Google scholar and google database using key words “pancreas and GIST”, “pancreas and gastrointestinal stromal tumor”, “pancreas and extragastrointestinal stromal tumor”. Finally, 51 articles including 57 patients were identified. Studies published before February 2023 were included. Clinicopathological data including age, sex, symptoms, location, tumor size, imaging features, surgical intervention, histologic type, mitotic index, immunohistochemical features, mutational status, National Institute of Health (NIH) risk classification, adjuvant imatinib therapy and survival data were recorded.

Data were processed using SPSS 25.0 for windows. Risk factors for survival were identified by univariate analysis. Survival analysis including disease-free survival was obtained by Kaplan Meier method for a total of 49 patients for whom complete data of all the variables was available. The p values were considered to be significant at 5% level. Multivariate analysis was not performed because of limited number of events.

Figure 1 shows the flow chart representation of study selection process.

Fig. 1.

Fig. 1

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Study selection process

Results

A total of 9 patients of primary pancreatic GIST were treated at our centre from 2016 to 2023. The clinicopathological features are summarised in Table 1. The most common presenting symptom was abdominal pain (n = 4). All patients belonged to a median age group of 53 years (28 to 74 years). There were 55% females (n = 5) and 45% males (n = 4). The most common epicentre was pancreatic head (n = 7) with only two patients having tumor epicentre in tail of pancreas. The median tumor size was 6 cm (2–18 cm). Mitotic index of 5 patients were < 5/50 hpf (high power field) whereas data was not available for 4 patients and 4/8 patients were categorised as high risk (2/4 patients had tumor size > 10 cm) as per NIH (National institute of health) risk category. Six patients displayed solid mass on cross-sectional imaging. All patients had spindle morphology on histopathology. Three patients had exon 11 kit mutation on further analysis. Two patients had recurrence with site being liver in both of them.

Table 1.

Clinicopathological characteristics of patients treated in our institute

S. No. Characteristics n (%)
1. Age
    </= 53 5 (55)
    > 53 4 (45)
2. Sex
    Male 4 (45%)
    Female 5 (55%)
3. Epicentre
    Head 7 (77)
    Tail 2 (22)
4. Tumor size
    </= 6 5 (55)
    > 6 4 (45)
5. Histology
    Spindle 9 (100)
6. Mitotic index
    </= 5 5 (55)
    > 5 0
7. NIH risk category
    High 4 (45)0
    Low 4 (45)
8. Neoadjuvant therapy
    Yes 7 (77)
    No 2 (23)
9. Adjuvant therapy
    Yes 7 (77)
    No 1 (11)
10. Immunohistochemistry
    CD 117 8 (89)
    CD 34 5 (55)
    DOG 1 9 (100)
11. Mutational status
    Wild 2 (22)
    Exon 11 3 (33)
12. Imaging features
    Solid 6 (66)
    Mixed 3 (33)
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Review of Literature

A total of 57 patients were identified from 51 published articles. Clinicopathological characteristics of all patients have been summarised in Table 2. All patients belonged to a median age group of 55 years (30–84 years). There were 47% females (n = 27) and 45% males (n = 26). The most common location was pancreatic head/uncinated process (n = 35) followed by body/tail (n = 18) with one patient having involvement of entire pancreatic tissue. The majority of patients underwent Whipple procedure or distal pancreaticosplenectomy (DPS) as per tumor location. The median tumor size was 7 cm (0.8 to 35 cm). Eighteen patients had mitotic count > 5/50 hpf and 23 patients < / = 5/50 hpf. While 28 patients were categorised as high risk as per NIH risk stratification, 11 patients belonged to intermediate and 6 patients to low risk category. Fifty biopsy samples were positive for CD 117 while 1 was negative and data was not available for 6 patients. CD 34 was positive for 35 patients and negative for 9 patients while data was missing for 13 patients. Twenty-six patients received adjuvant imatinib while 10 patients did not receive any adjuvant therapy and adjuvant therapy details were not available for 21 patients. Eight patients had recurrence postoperatively and most common site of recurrence was the liver (n = 5). Spindle histology was found in 39 patients while 6 had mixed and only 1 patient had epitheloid histology and data was missing for 11 patients. Median follow-up time was 24 months.

Table 2.

Clinicopathological characteristics of 57 patients identified from literature

Reference Year Age (years) Sex Presentation Tumor
location		 Tumor size
(cm)		 Histology NIH risk Mitotic count
(per 50 hpf)		 CD 117 CD 34 Surgery Recurrence (site, duration) Outcome (follow-up) Medical treatment
Beji et al. [19] 2022 53 M Abdominal pain Body + Tail NA NA High NA +  - Enucleation No Alive (8 months) Imatinib
Zackria and Jayaraman [20] 2022 74 F Incidental finding Uncinate 2.9 × 2.5 Spindle Intermediate NA +  +  NA NA NA Imatinib
Uzunoglu and Tosun [21] 2021 39 M NA Head 0.8 Mixed Intermediate NA NA NA Whipple + right colectomy NA NA NA
Ene et al. [22] 2021 53 F Malena + weight loss Head 8 × 7 × 5 Spindle High > 5 +  - Whipple No Alive (6 months) Imatinib
Castellon et al. [23] 2020 50 M Abdominal pain + Weight loss Head 3.5 × 2.8 × 2 Spindle NA < 5 +  - Local resection + Roux en Y DJ No Alive (11 months) Imatinib
Yau [24] 2019 53 M Malena Head 2.3 × 1.5 Spindle NA NA +  NA NA NA NA Imatinib
Tounsi [25] 2018 49 F Abdominal pain Head 2.4 NA NA < 5 +  +  Enucleation No Alive (9 months) No
Rasool et al. [26] 2018 60 M Abdominal pain + weight loss Head 3.5 NA High < 5 NA NA PPPD No NA NA
Yol et al. [27] 2018 56 M Abdominal pain Head 15 Spindle NA < 5 +  +  Whipple NA NA Imatinib
Yeo et al. [28] 2018 45 F Abdominal pain Head + uncinate 6.5 Spindle Low < 5 +  +  PPPD No Alive (12 months) NA
Abderraheman et al. [29] 2017 53 F Abdominal pain Head 11.6 × 10.5 × 9 Mixed High > 5 +  +  Whipple + partial colectomy Yes Alive (2 years) Gleevec
Kwon [30] 2017 64 F Incidental finding Head 7 Spindle High 5 +  +  Whipple No Alive (83 months) No
Zhang et al. [31] 2016 60 F Abdominal pain Head 3.6 Spindle Low NA NA NA Whipple NA NA NA
Liu et al. [32] 2016 56 F Incidental Body 5.7 × 2.7 Spindle NA < 5 +  - NA Yes Alive (17 months) Gleevec
Elgeidi et al. [33] 2016 30 M Abdominal pain + weight loss Tail 1.2 × 1.1 × 0.3 Spindle NA > 5 +  +  DPS No Alive (3 months) Imatinib
Aziret et al. [34] 2015 56 M Abdominal pain Head 4 NA High NA +  +  Whipple No Alive (NA) Imatinib
Joseph et al. [35] 2015 60 M Abdominal pain Body + Tail 2.1 × 1.8 × 1.4 Epitheloid Intermediate < 5 +  +  No NA Dead (9 months) Imatinib
Stanek et al. [36] 2015 55 M Incidental finding Uncinate 2 × 1.7 × 1.6 Spindle High < 5 +  +  Tumor enucleation No Alive (6 months) NA
Hansen et al. [37] 2014 74 F Malena NA 12 × 8 × 5 Mixed High > 5 +  - Enucleation NA NA NA
Ambrosio et al. [38] 2014 72 M Abdominal pain Head 1.9 × 1.4 × 1.2 Mixed Low > 5 +  +  Whipple Yes (Liver) Dead (8 months) Imatinib
50 F Abdominal lump Head 7 × 4 × 3 Spindle Low < 5 +  +  Whipple No Alive (4 years) NA
NA NA NA Head 7 × 5.5 × 3.5 Mixed Intermediate > 5 +  +  Whipple No Alive (18 months) NA
Tian et al. [6] 2014 61 NA Incidental finding Tail 6 × 8 Spindle NA < 5 +  +  DPS No Alive (36 months) No
60 M Incidental finding Head 6 × 5 Spindle Intermediate > 5 +  NA Tumor resection Yes (liver, 12 mo) Alive (36 months) Gleevec + TACE
Akbulut et al. [16] 2014 61 F Weight loss Head 5 × 4 Spindle Low NA NA NA Whipple No Alive (48 months) Imatinib
Beltrame et al. [39] 2014 63 F NA Uncinate 2.4 NA High < 5 +  NA Enucleation No Alive (6 months) NA
Paklina et al. [40] 2013 38 F Abdominal discomfort Head 9 Spindle NA < 5 +  NA NA NA NA NA
Serin et al. [5] 2013 30 M Abdominal distension Tail 13 NA High NA +  NA DPS No Alive (21 months) No
Soufi et a.l [11] 2013 39 M Weight loss + abd pain + constipation Head 9 × 7 × 5 Spindle Intermediate < 5 +  +  Whipple + segmental colectomy No Alive (24 months) Gleevec
Wegge et al. [41] 2012 55 M Haematemesis + haematochezia Head 4.6 × 4.5 × 4.4 Spindle High > 5 +  +  Whipple No Alive (5 months) Gleevec
Babu et al. [10] 2012 55 F Upper abdominal pain Head 5 × 4 × 3 Spindle High > 5 +  +  Pancreatic head resection No Alive (11 months) No
Kim et al. [42] 2012 55 M Abdominal discomfort Tail 13 × 9 × 8.5 Spindle Intermediate > 5 +  +  DPS No Alive (4 months) Gleevec
Cecka et al. [7] 2012 74 F Abdominal mass Tail 11 × 8 × 4 Spindle Intermediate 5 +  +  DPS No Alive (66 months) No
Vij et al. [12] 2011 35 M Weight loss + abdominal discomfort Head 8 × 6 Spindle High > 5 +  - Whipple Yes (liver, 24 months) Alive (48 months) Gleevec
Meng et al. [43] 2011 42 M Abdominal lump Head 10 × 8 × 3 Spindle Intermediate < 5 +  +  NA NA NA NA
Rao et al. [44] 2011 40 M Weight loss + abdominal pain + anemia Head + Body 6.5 × 6 Spindle High > 5 +  +  Whipple Yes (liver, 24 months) Alive (30 months) Gleevec
Yang et al. [45] 2011 55 M Abdominal discomfort Body + Tail 17.8 × 19.6 Spindle High > 5 +  +  DPS Yes (intraperitoneal, 24 months) Alive (41 months) Gleevec
Barros et al. [8] 2011 63 F Abdominal pain + ponderal loss NA NA NA High < 5 +  +  No Surgery not performed Death (8 months) No
81 F Difficult gastric emptying + ponderal loss NA 10 NA High < 5 +  +  Laparotomy + biopsy Surgery not performed Alive (12 months) Gleevec
Joshi et al. [46] 2010 84 M Weight loss + abdominal distension Entire pancreatic tissue 34 × 24 × 27 Spindle High NA +  +  No Surgery not performed Death (5 days) No
Crisan et al. [47] 2010 61 M Weight loss + fever Tail + Body 14 Spindle High NA +  +  DPS + partial colectomy NA Alive (3 months) NA
Saif et al. [48] 2010 31 M Weight loss + abdominal pain + anemia Head 5.6 × 5.1 × 4.2 Spindle High > 5 +  - Whipple, pylorus preserving Yes (liver, 9 mo) Alive (NA) Gleevec
Padhi et al. [3] 2010 42 F Weight loss + abdominal pain Body + Tail 35 × 3 × 25 Spindle High > 5 +   +  DPS + left hemicolectomy No Alive (10 months) No
Harindhanavudhi et al. [49] 2009 63 F Fatigue + weakness + anemia Body 16 × 11 Spindle High < 5 +  +  Cystojejunostomy NA Alive (NA) Gleevec
Trabelsi et al. [50] 2009 52 F Epigastric pain Head 10.5 × 8 × 3 Spindle High > 5 +  +  Whipple + partial colectomy No Alive (10 months) No
Goh et al. [9] 2009 58 M Incidental finding Head 9 Spindle High > 5 +  NA Whipple No Alive (58 months) NA
Showalter et al. [51] 2008 72 F Incidental finding Tail 7 NA Intermediate < 5 +  - DPS No Alive (27 mo) NA
Yan et al. [52] 2008 47 M Nausea + vomiting Uncinate 2.4 × 2.1 Spindle NA < 5 +  NA NA NA NA NA
Ganesh et al. [53] 2008 76 F Weight loss + abdominal pain Tail + body NA Spindle Intermediate NA +  +  No (inoperable) Surgery not performed Alive (30 months) Gleevec
Daum et al. [54] 2005 70 F Incidental finding Head 10 × 8 × 6 Spindle High < 5 +  - Whipple No Alive (6 months) Gleevec
Krska et al. [55] 2005 38 F Abdominal pain Head + Body 17 × 12 Spindle NA < 5 - +  Partial pancreatectomy No Alive (30 months) NA
Pauser et al. [56] 2005 51 M Incidental finding Tail 3 Spindle NA NA +  +  Resection No Alive (24 months) NA
54 F Abdominal discomfort Body 2 Spindle High NA +  +  Resection No Alive (48 months) NA
Neto et al. [57] 2004 67 F Weight loss + abd pain Body + Tail 20 × 19 × 12 Mixed High > 5 +  +  Distal pancreatectomy Yes (peritoneum) Alive (NA) Gleevec
Yamaura et al. [58] 2004 54 F Incidental finding Tail 14 × 12 × 8 Spindle Low NA +  +  DPS + partial gastrectomy NA Alive (30 months) NA
Boyer et al. [59] 2001 52 NA NA Head NA NA High NA NA NA Surgical biopsy NA NA NA
61 NA NA Head NA NA NA NA NA NA Partial duodenopancreatectomy NA NA NA
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Prognostic factors for DFS according to univariate analysis are summarised in Table 3.

Table 3.

Univariate analysis for DFS

Characteristic 2 year DFS probability N Event N p-value1
Age 0.4
    < = 55 72% (54%, 97%) 31 6
    > 55 68% (49%, 96%) 18 6
Sex 0.14
    Male 58% (38%, 89%) 24 8
    Female 83% (67%, 100%) 25 4
Epicentre 0.8
    Body/Tail 71% (51%, 100%) 17 4
    Head/uncinate 72% (54%, 94%) 30 8
Tumor size (cm) 0.5
    < = 7 (Median) 70% (52%, 94%) 25 8
    > 7 (Median) 71% (51%, 100%) 22 4
Histologic type < 0.001
    Spindle 77% (62%, 95%) 36 8
    Mixed/ Epitheloid 0% (37%, 100%) 8 4
Mitotic Index 0.002
    < = 5 88% (73%, 100%) 21 2
    > 5 14% (2.3%, 83%) 17 8
NIH Risk 0.013
    Low / Intermediate 100% (100%, 100%) 18 1
    High 52% (33%, 82%) 26 10
Mutational status 0.3
    Wild 100% (100%, 100%) 2 0
    Exon 9 kit — (—, —) 2 1
    Exon 11 kit 86% (63%, 100%) 7 2
    Exon 18 kit — (—, —) 1 1
Adjuvant 0.013
    No 100% (100%, 100%) 13 0
    Yes 53% (35%, 80%) 28 12
Neoadjuvant > 0.9
    No 66% (50%, 88%) 39 9
    Yes 88% (67%, 100%) 8 3
Overall 72% (58%, 89%)
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The p-values highlighted in bold indicate statistical significance

The calculated median DFS was 74 months (28.6–119.3, 95% CI) with 5-year DFS being 71.9% (Fig. 2).

Fig. 2.

Fig. 2

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Disease free survival of pancreatic GIST patients

Discussion

The most frequent sites in GI tract are the stomach (40–70%) followed by small intestine (20–40%), colon and rectum (5%) and esophagus (< 1%) [1, 3]. The term extragastrointestinal stromal tumors (EGIST) was first used by Reith et al. to describe histologically similar stromal tumors arising from soft tissues of the abdomen outside the GI tract [4]. EGISTs comprise 5–10% of all GISTs [3, 5–8]. The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it [9–11]. EGISTs are usually diagnosed in adult age group with predominance in female gender [12]. The pathogenesis is explained by a gain of function mutation in c-KIT gene (90%) or platelet-derived growth factor receptor alpha, PDGFRA gene (5–7%) resulting in overexpression of their respective receptors and thus leading to cell proliferation [3, 5]. Multiple studies have suggested that they may arise either by extensive extramural growth resulting in loss of contact with muscularis propria of small intestine or as metastasis from a primary tumor [13].

Computed tomography (CT) is usually the first modality to evaluate like other GI tumors. In case of tumors arising from the pancreas, it may be confused with other solid or cystic tumors of the pancreas like adenocarcinoma, pseudocyst, serous or mucinous cystadenoma/cystadenocarcinoma, lymphangioma or neuroendocrine tumors but endoscopic ultrasound-guided FNA can provide an adjunct in diagnosis [14]. Positron emission tomography (PET CT) can be used in both diagnosis and response assessment to neoadjuvant therapy and is of special help where both CT and magnetic resonance imaging (MRI) are inconclusive [15].

The clinical presentation and symptom severity are determined by the tumor size and its location in the pancreatic tissue. The most common symptoms reported are abdominal pain, weight loss, fatigue, abdominal mass and distension, GI bleeding, anemia and jaundice [6, 16]. In our review, most common symptoms were abdominal pain and weight loss (48.4%) and 18.2% cases were diagnosed incidentally.

Histopathologically, GISTs are classified into spindle cell (70%), epitheloid (20%) or mixed types (10%) of which spindle cell is the most common type [6]. EGISTs have typical immunohistochemical features most common of which is CD 117 (95%) followed by CD 34 (60–70%). In cases with negative staining for CD 117, further testing for PDGFRA is suggested [4]. Additional staining markers of GISTs are heavy caldesmon (80%), SMA (30–40%), S100 (5%), and desmin (< 5%) [3, 6, 7, 16]. In the present review, out of the histopathological data available for 44 patients, 82% cases had spindle cell morphology while mixed and epitheloid comprising only 18% with spindle cell morphology associated with 2-year DFS of 77% (p < 0.001). CD 117 was positive for 98.3% (59 out of 60 patients) and CD 34 in 83% (40 out of 48 patients) which is in accordance with the literature. The characteristic histopathological features are depicted in Fig. 3.

Fig. 3.

Fig. 3

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Histopathologic features of pancreatic gastrointestinal stromal tumors (GIST). A–D Haematoxylin and eosin-stained sections. A Low magnification reveals a tumor with pushing borders invading pancreatic parenchyma (star). B Higher magnification shows spindled tumor cells arranged in short fascicles and exhibiting moderate nuclear atypia and low mitosis. C Tumor is composed of uniform appearing spindle cells in a collagenous stroma; pancreatic tissue is visible at one aspect (star). D Pancreatic biopsy cores showing a spindle cell GIST with scant myxoid stroma. E, F Immunohistochemistry stains. E Immunohistochemistry for CD117 (c-kit) reveals strong and diffuse cytoplasmic positivity in the tumor cells. F Tumor cells are strongly positive for DOG1 immunohistochemistry

Understanding risk stratification of disease is important for management. Fletcher et al. [17] defined a criteria for defining risk of aggressive behaviour in GISTs based on tumor size and mitotic count. As per criteria, GISTs are classified into very low risk (< 2 cm, < 5/50 hpf), low risk (2–5 cm, < 5/50 hpf), intermediate risk (< 5 cm, 6–10/50 hpf; 5–10 cm, < 5/50 hpf), high risk (> 5 cm, > 5/50 hpf; > 10 cm, any mitotic rate; any size, > 10/50 hpf). This classification aids in neoadjuvant and/or adjuvant treatment selection and planning. In the present review, risk stratification was available for 44 patients out of which, 59% of the patients belonged to high risk category while 41% to intermediate and low risk.

Surgery with microscopically negative margins is the treatment of choice for pancreatic GISTs [3, 6]. Extent of surgery depends on the tumor location. Regional lymph nodal involvement is rare in pancreatic EGISTs and hence routine systematic regional lymph node dissection can be avoided [6, 10].

With the advent of imatinib, c-kit tyrosine kinase inhibitor for GIST management, median overall survival now gets extended upto 5 years with a positive response rate to therapy upto 60–70% [6, 16]. It can be used either as neoadjuvant therapy for downstaging or as adjuvant therapy in case of positive margin, aggressive risk category and poor prognostic features [3, 6]. It can also be used for metastatic or advanced unresectable tumors for downstaging, thus making surgical resection feasible and providing better prognosis [6]. In the absence of randomised phase III data, the impact of neoadjuvant imatinib as compared to upfront surgery remains unknown. However, various phase II trials and retrospective studies have reported clinical benefit with the use of neoadjuvant therapy. The largest retrospective study by EORTC Soft tissue and bone sarcoma group assessed the long-term results of preoperative imatinib therapy in primary kit positive GISTs. With median time of neoadjuvant therapy of 10 months, they reported 80% response rates with 5-year DFS and OS of 65% and 87% respectively [18]. In the present review, only 18.2% of the patients received neoadjuvant therapy with Imatinib while details were not known for 12%. At our institute, we give neoadjuvant therapy to all patients with locally advanced GIST who might require extensive resection which in our series was given to 7 out of 9 patients.

Conclusion

There is evolving literature on similarities and differences between GIST and EGIST. Despite their behavioural similarities, results cannot be generalised to larger population due to lack of evidence. Pancreatic GIST is a rare entity. There are many documented case reports; however, long-term data is unavailable. Our case series is by far the largest single-centre series with long follow-up data but with limited number of cases. Survival values cannot be generalised due to limited data. Larger case series are required to further understand the disease biology and long-term outcomes of pancreatic GIST.

Author Contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by V.G., A.C.. The first draft of the manuscript was written by V.G. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

Open access funding provided by Department of Atomic Energy. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics Approval

The study is compliant with ethical standards.

Consent to Participate

Written informed consent was obtained from the patient for the surgery.

Conflict of Interest

The authors declare no competing interests.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Miettinen M, Lasota J. Gastrointestinal stromal tumors. Gastroenterol Clin North Am. 2013;42(2):399–415. 10.1016/j.gtc.2013.01.001. Epub 2013 Mar 13. PMID: 23639648; PMCID: PMC3644178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Zhou J, Yan T, Huang Z, Zhao J, Bi X, Zhao H, Zhang YF, Cai J. Clinical features and prognosis of extragastrointestinal stromal tumors. Int J Clin Exp Med. 2016;9(8):16367–72. [Google Scholar]
  • 3.Padhi S, Sarangi R, Mallick S. Pancreatic extragastrointestinal stromal tumors, interstitial Cajal like cells, and telocytes. JOP. 2013;14:1–14. [PubMed] [Google Scholar]. [DOI] [PubMed] [Google Scholar]
  • 4.Reith J, Goldblum J, Lyles R, et al. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol. 2000;13:577–85. 10.1038/modpathol.3880099. [DOI] [PubMed] [Google Scholar]
  • 5.Serin KR, Keskin M, Gulluoglu M, Emre A. Atypical localisation of a gastrointestinal stromal tumor: a case report of pancreas gastrointestinal stromal tumor. Ulusal Cer Derg. 2013;29:42–4. 10.5152/UCD.2013.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Tian YT, Liu H, Shi SS, Xie YB, Xu Q, Zhang JW, Zhao DB, Wang CF, Chen YT. Malignant extra-gastrointestinal stromal tumor of the pancreas: report of two cases and review of the literature. World J Gastroenterol. 2014;20:863–8. 10.3748/wjg.v20.i3.863. PMID:24574760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Cecka F, Jon B, Ferko A, Šubrt Z, Nikolov DH, Tyčová V. Long-term survival of a patient after resection of a gastrointestinal stromal tumor arising from the pancreas. Hepatobiliary Pancreat Dis Int. 2011;10:330–2. 10.1016/S1499-3872(11)60056-8. PMID: 21669581. [DOI] [PubMed] [Google Scholar]
  • 8.Barros A, Linhares E, Valadão M, Gonçalves R, Vilhena B, Gil C, Ramos C. Extragastrointestinal stromal tumors (EGIST): a series of case reports. Hepatogastroenterology. 2011;58:865–8. PMID: 21830406. [PubMed] [Google Scholar]
  • 9.Goh BK, Chow PK, Kesavan SM, Yap WM, Chung YF, Wong WK. A single-institution experience with eight CD117- positive primary extragastrointestinal stromal tumors: critical appraisal and a comparison with their gastrointestinal counterparts. J Gastrointest Surg. 2009;13:1094–8. 10.1007/s11605-009-0828-4. PMID: 19238492. [DOI] [PubMed] [Google Scholar]
  • 10.Babu SR, Kumari S, Zhang Y, Su A, Wang W, Tian B. Extra gastrointestinal stromal tumor arising in the pancreas: a case report and literature review. J Gastroenterol Hepatol Res. 2012;1:80–3. [Google Scholar]
  • 11.Soufi M, Bouziane M, Massrouri R, Chad B. Pancreatic GIST with pancreas divisum: a new entity. Int J Surg Case Rep. 2013;4:68–71. 10.1016/j.ijscr.2012.09.007. PMID: 23123418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Vij M, Agrawal V, Pandey R. Malignant extra-gastrointestinal stromal tumor of the pancreas. A case report and review of literature. JOP. 2011;12:200–4 PMID: 21386653. [PubMed] [Google Scholar]
  • 13.Agaimy A, Wünsch PH. Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation. A review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumours. Langenbecks Arch Surg. 2006;391(4):322–9. 10.1007/s00423-005-0005-5. Epub 2006 Jan 10. PMID: 16402273. [DOI] [PubMed] [Google Scholar]
  • 14.Akahoshi K, Sumida Y, Matsui N, Oya M, Akinaga R, Kubokawa M, Motomura Y, Honda K, Watanabe M, Nagaie T. Preoperative diagnosis of gastrointestinal stromal tumour by endoscopic ultrasound-guided fine needle aspiration. World J Gastroenterol. 2007;13:2077–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Williams A, Gutzeit A, Germer M, Pless M. PET-negative gastrointestinal stromal tumors. Case Rep Oncol. 2013;6:508–13. 10.1159/000355432. PMID: 24403895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Akbulut S, Yavuz R, Otan E, Hatipoglu S. Pancreatic extragastrointestinal stromal tumor: a case report and comprehensive literature review. World J Gastrointest Surg. 2014;6(9):175–82. 10.4240/wjgs.v6.i9.175.PMID:25276287;PMCID:PMC4176778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O’Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33(5):459–65. 10.1053/hupa.2002.123545. PMID: 12094370. [DOI] [PubMed] [Google Scholar]
  • 18.Rutkowski P, Gronchi A, Hohenberger P, et al. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors (GIST): the EORTC STBSG experience. Ann Surg Oncol. 2013;20(9):2937–43. [DOI] [PubMed] [Google Scholar]
  • 19.Beji H, Bouassida M, Mroua B, Belfkih H, M’farrej MK, Touinsi H. Extra-gastrointestinal stromal tumor of the pancreas: a case report. Int J Surg Case Rep. 2022;98:107581. 10.1016/j.ijscr.2022.107581. Epub 2022 Aug 31. PMID: 36057252; PMCID: PMC9482973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Zackria R, Jayaraman V. The gastrointestinal stromal tumor (GIST) of a pancreatic cyst. Cureus. 2022;14(6):e26197. 10.7759/cureus.26197. PMID:35891821; PMCID:PMC9306679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Uzunoglu H, Tosun Y. Primary extra gastrointestinal stromal tumors of the abdomen. North Clin Istanb. 2021;8(5):464–71. 10.14744/nci.2021.46794. PMID: 34909584; PMCID: PMC8630720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Ene D, Florescu LM, Ene R, Popescu B, Gheonea IA. An extremely uncommon case of pancreatic extragastrointestinal stromal tumor in a 53-year-old female patient. Rom J Morphol Embryol. 2021;62(2):569–73. 10.47162/RJME.62.2.24. PMID: 35024746; PMCID: PMC8848218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Castellón CJ, Díaz GA, López P, Paz BA, Morales S, Durán M. Local resection of a pancreatic GIST in the area of the pancreatoduodenal groove. Is the surgical technique a prognostic factor? J Case Rep Images Surg. 2020;6:100080Z12CC2020. [Google Scholar]
  • 24.Yau I. Pancreatic extragastrointestinal stromal tumor in a patient with neurofibromas presenting with iron deficiency anemia. Case reports. Open Access. 2019;4:1–3. [Google Scholar]
  • 25.Tounsi N. Primary extragastrointestinal stromal tumor arising In the pancreas: report of a case. IOSR-JDMS. 2018;17(2):20–3. [DOI] [PubMed] [Google Scholar]
  • 26.Rasool Z, Mushtaq S, Samoon N, Malik S, Gul S, Khan M, Shah O, Bangri SA, Shah M. Pancreatic extra gastrointestinal stromal tumor: a case report and review of the literature. J Med Sci Clin Res. 2018;6. 10.18535/jmscr/v6i5.133. [Google Scholar]
  • 27.Yol S, Polat E, Duman M, Uzun O, Yaşar NF, Peker KD, Akyüz C, Kayahan S. Pancreatic extragastrointestinal stromal tumor invading the duodenum. Turk J Surg. 2018;34(3):231–3. 10.5152/turkjsurg.2017.2715.PMID:30302427;PMCID:PMC6173591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Yeo SJ, Cho CM, Kwon HJ, Cho SH, Kim GC, Seo AN, Bae HI. An extragastrointestinal stromal tumor originating from the pancreas. Case Rep Gastroenterol. 2018;12(3):671–8. 10.1159/000494553.PMID:30519153;PMCID:PMC6276739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Abderrahmen D, Waad F, Mohamed B, Fathia H, Mohamed A, Ali B. Pancreatic gastrointestinal stromal tumour: a case report and review of the literature. J Cancer Ther. 2017;8:954–61. 10.4236/jct.2017.811085. [Google Scholar]
  • 30.Kwon HJ. Extra-gastrointestinal stromal tumor of the pancreas: report of a case. Ann Hepatobiliary Pancreat Surg. 2017;21(4):237–42. 10.14701/ahbps.2017.21.4.237. Epub 2017 Nov 30. PMID: 29264589; PMCID: PMC5736746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Zhang H, Yu S, Wang W, Cheng Y, Xiao Y, Lu Z, Chen J. Primary mesenchymal tumors of the pancreas in a single center over 15 years. Oncol Lett. 2016;12(5):4027–34. 10.3892/ol.2016.5155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Liu L, Zhu Y, Wang D, Yang C, Zhang QI, Li X, Bai Y. Coexisting and possible primary extra-gastrointestinal stromal tumors of the pancreas and liver: a single case report. Oncol Lett. 2016;11(5):3303–7. 10.3892/ol.2016.4420. Epub 2016 Apr 7. PMID: 27123107; PMCID: PMC4841060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Elgeidie A, El-Magd EA, El-Maaty SRA, El-Hawary AK. Pancreatic gastrointestinal stromal tumor: a case report. Int J Surg Case Rep. 2016;29:67–70. 10.1016/j.ijscr.2016.08.019. Epub 2016 Aug 17. PMID: 27816691; PMCID: PMC5099278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Aziret M, Çetinkünar S, Aktaş E, İrkörücü O, Bali İ, Erdem H. Pancreatic gastrointestinal stromal tumor after upper gastrointestinal hemorrhage and performance of whipple procedure: a case report and literature review. Am J Case Rep. 2015;16:509–13. 10.12659/AJCR.893803. PMID: 26237079; PMCID: PMC4527206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Joseph P, Goyal R, Bansal P, Parmar R, Dutt S. Pancreatic extra-gastrointestinal stromal tumour with documentation of C-kit mutation: a case report. J Clin Diagn Res. 2015;9(4):ED17–8. 10.7860/JCDR/2015/13018.5821. Epub 2015 Apr 1. PMID: 26023562; PMCID: PMC4437076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Stanek M, Pędziwiatr M, Matłok M, Budzyński A. Laparoscopic removal of gastrointestinal stromal tumors of uncinate process of pancreas. Wideochir Inne Tech Maloinwazyjne. 2015;10(2):311–5. 10.5114/wiitm.2015.52141. Epub 2015 Jun 10. PMID: 26240634; PMCID: PMC4520844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Hansen Cde A, José FF, Caluz NP. Gastrointestinal stromal tumor (GIST) mistaken for pancreatic pseudocyst - case report and literature review. Clin Case Rep. 2014;2(5):197–200. 10.1002/ccr3.92. Epub 2014 Jul 17. PMID: 25614811; PMCID: PMC4302625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Ambrosio MR, Rocca BJ, Mastrogiulio MG, Pesci A, De Martino A, Mazzei MA, Volterrani L, Arcuri F, Cintorino M, Tripodi SA. Cystic gastrointestinal stromal tumors of the pancreas simulating cystoadenocarcinoma. Report of three cases and short review of the literature. Histol Histopathol. 2014;29(12):1583–91. 10.14670/HH-29.1583. Epub 2014 Jun 11. PMID: 24918465. [DOI] [PubMed] [Google Scholar]
  • 39.Beltrame V, Gruppo M, Pastorelli D, Pizzi S, Merigliano S, Sperti C. Extra-gastrointestinal stromal tumor of the pancreas: case report and review of the literature. World J Surg Oncol. 2014;12:105. 10.1186/1477-7819-12-105.PMID:24755359;PMCID:PMC4000617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Paklina OV, Setdikova GR, Voskanyan SE. Gastrointestinal stromal tumor of a pancreas: case report and literature review. Meдицинcкaя визyaлизaция. 2013;2:122. [Google Scholar]
  • 41.Wegge J, Bartholomew DM, Burke LH, Miller LA. Pancreatic extra-gastrointestinal stromal tumour masquerading as a bleeding duodenal mass. BMJ Case Rep. 2012;2012:bcr2012007040. 10.1136/bcr-2012-007040. PMID: 23087281; PMCID: PMC4544221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Kim HH, Koh YS, Park EK, Seoung JS, Hur YH, Kim JC, Cho CK, Kim HJ. Primary extragastrointestinal stromal tumor arising in the pancreas: report of a case. Surg Today. 2012;42:386–90. 10.1007/s00595-011-0080-x. PMID: 22258729. [DOI] [PubMed] [Google Scholar]
  • 43.Meng L, Fang SH, Jin M. An unusual case of pancreatic and gastric neoplasms (2010b): malignant GISTs originating from the pancreas and stomach. Eur Radiol. 2011;21(3):663–5. [DOI] [PubMed] [Google Scholar]
  • 44.Rao RN, Vij M, Singla N, Kumar A. 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;12:283–6 PMID: 21546710. [PubMed] [Google Scholar]
  • 45.Yang F, Jin C, Fu D, Ni Q. Extra-gastrointestinal stromal tumor of the pancreas: clinical characteristics, diagnosis, treatment, and outcome. J Surg Oncol. 2011;103:739–40. 10.1002/jso.21833. PMID: 21240986. [DOI] [PubMed] [Google Scholar]
  • 46.Joshi J, Rustagi T. Pancreatic extra-gastrointestinal stromal tumor: an unusual presentation of a rare diagnosis. Gastrointest Cancer Res. 2010;(Suppl 1):S29–30 PMCID: PMC3047023. [Google Scholar]
  • 47.Crisan A, Nicoara E, Cucui V, Cornea G, Laza R. Prolonged fever associated with gastrointestinal stromal tumor-case report. J Exp Med Surg Res. 2010;17:219–24. [Google Scholar]
  • 48.Saif MW, Hotchkiss S, Kaley K. Gastrointestinal stromal tumors of the pancreas. JOP. 2010;11:405–6; author reply 412. PMID: 20601822. [PubMed] [Google Scholar]
  • 49.Harindhanavudhi T, Tanawuttiwat T, Pyle J, Silva R. Extragastrointestinal stromal tumor presenting as hemorrhagic pancreatic cyst diagnosed by EUS-FNA. JOP. 2009;10:189–91. PMID: 19287116. [PubMed] [Google Scholar]
  • 50.Trabelsi A, Yacoub-Abid LB, Mtimet A, Abdelkrim SB, Hammedi F, Ali AB, Mokni M. Gastrointestinal stromal tumor of the pancreas: a case report and review of the literature. N Am J Med Sci. 2009;1:324–6. PMID: 22666718. [PMC free article] [PubMed] [Google Scholar]
  • 51.Showalter SL, Lloyd JM, Glassman DT, Berger AC. Extragastrointestinal stromal tumor of the pancreas: case report and a review of the literature. Arch Surg. 2008;143:305–8. 10.1001/archsurg.2007.68. PMID: 18347279. [DOI] [PubMed] [Google Scholar]
  • 52.Yan BM, Pai RK, Van Dam J. Diagnosis of pancreatic gastrointestinal stromal tumor by EUS guided FNA. JOP. 2008;9:192–6. PMID: 18326928. [PubMed] [Google Scholar]
  • 53.Ganesh M, Kumar S, Krishnamoorthy R, Ang Y. Rare cause of pancreatic mass responding to imatinib treatment. Gastroenterology Today. 2008;18:50–1. [Google Scholar]
  • 54.Daum O, Klecka J, Ferda J, Treska V, Vanecek T, Sima R, Mukensnabl P, Michal M. Gastrointestinal stromal tumor of the pancreas: case report with documentation of KIT gene mutation. Virchows Arch. 2005;446:470–2. 10.1007/s00428-004-1200-4. PMID: 15756592. [DOI] [PubMed] [Google Scholar]
  • 55.Krska Z, Pesková M, Povýsil C, Horejs J, Sedlácková E, Kudrnová Z. GIST of pancreas. Prague Med Rep. 2005;106:201–8. PMID: 16315768. [PubMed] [Google Scholar]
  • 56.Pauser U, da Silva MT, Placke J, Klimstra DS, Klöppel G. Cellular hamartoma resembling gastrointestinal stromal tumor: a solid tumor of the pancreas expressing c-kit (CD117). Mod Pathol. 2005;18:1211–6. 10.1038/modpathol.3800406. PMID: 15803185. [DOI] [PubMed] [Google Scholar]
  • 57.Neto MR, Machuca TN, Pinho RV, Yuasa LD, Bleggi-Torres LF. Gastrointestinal stromal tumor: report of two unusual cases. Virchows Arch. 2004;444(594):596. 10.1007/s00428-004-1009-1. PMID: 15118853. [DOI] [PubMed] [Google Scholar]
  • 58.Yamaura K, Kato K, Miyazawa M, Haba Y, Muramatsu A, Miyata K, Koide N. Stromal tumor of the pancreas with expression of c-kit protein: report of a case. J Gastroenterol Hepatol. 2004;19:467–70. 10.1111/j.1440-1746.2003.02891.x. PMID: 15012791. [DOI] [PubMed] [Google Scholar]
  • 59.Boyer C, Duvet S, Wacrenier A, Toursel H, et al. Leiomyosarcoma and stromal tumor of the pancreas. J Radiol. 2001;82:1723–5. [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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