Whyoung Lee ,Xiodong Li ,Soni Lee ,Vishl S Chndn ,*

a Department of Pathology and Laboratory Medicine, University of California, Irvine, CA 92868, USA

b Department of Radiological Sciences, University of California, Irvine, CA 92868, USA

Gastrointestinal stromal tumor (GIST) arises from the interstitial cells of Cajal (ICC) and is the most common mesenchymal tumor of the gastrointestinal tract,accounting for approximately 1%-2% of all malignant gastrointestinal tract tumors [1] .The most common sites of origin are stomach and small bowel.Rarely extra-gastrointestinal GISTs are reported originating from omentum,mesentery and retroperitoneum [2,3] .Primary pancreatic GIST is exceedingly rare with only approximately 50 reported cases [4-7] .The reported age for patients with primary pancreatic GIST ranges from 30 to 84 years,without sex predilection.The common clinical manifestations include dull abdominal pain,abdominal mass,bleeding/anemia and weight loss;however,some cases are diagnosed incidentally [4,8] .Here,we report a very rare case of primary pancreatic GIST presenting as a 6 cm solid mass with cystic component in the pancreatic head region.

A 57-year-old female with no prior history of malignancy,presented with abdominal pain.CT scan of the abdomen with intravenous and oral contrast axial plane images showed a 6 cm predominantly solid mass with cystic component in the pancreatic head region (Fig.1 A).Subsequent endoscopic ultrasound (EUS)guided fine-needle aspiration showed a spindle cell neoplasm.This tumor was diffusely positive for CD117 and DOG1,consistent with a diagnosis of GIST.No other focus of tumor was seen in the gastrointestinal tract on radiology or endoscopy.The patient started treatment with imatinib.CT scan of the abdomen three months after starting therapy with imatinib showed a similar size mass with significant decrease in solid component likely representing tumor necrosis (Fig.1 B).A pancreaticoduodenectomy (Whipple procedure) was performed.The resected pathology specimen revealed a tan-pink,encapsulated and friable mass in the head of the pancreas,measuring 6 × 6 × 4.5 cm.Microscopically,the tumor was composed of cytologically bland,haphazardly arranged spindle cells with focal areas showing perinuclear vacuoles (Fig.2 A and B).Foci of necrosis consistent with treatment effect were also identified within the tumor (Fig.2 C).Immunostains for CD117 (Fig.2 D)and DOG1 were diffusely positive within the tumor,supporting the final diagnosis of primary pancreatic GIST.Mitotic activity was low(2 mitoses/5 mm2) and all the resection margins were negative for tumor.No metastasis was identified within 13 lymph nodes.The patient had no recurrence in the subsequent 20 months of followup.

Spindle cell neoplasms of the pancreas are uncommon.The ICC is the cell of origin for GIST.Studies [9-11] have shown ICC to be normally present around the main pancreatic duct as well as around the large blood vessels and exocrine pancreas.The most common location is in the head of the pancreas.The size of the lesion ranges from 1.8 to 35 cm and imaging displays a circumscribed solid mass with frequent cystic change and associated hemorrhage [4,12,13] .EUS guided fine needle biopsy is often helpful in establishing the diagnosis of a pancreatic GIST [12,13] .Immunostains for CD117 (c-kit) and DOG1 can be performed on this material for confirming the diagnosis.Expression of CD117 and DOG1 in the tumor cells is highly sensitive,with more than 95%positivity in pancreatic GIST.However,a subset of them can also show variable expression for CD34,caldesmon,and smooth muscle actin [8,14] .Of note,some GISTs can lose CD117 expression following preoperative treatment with imatinib,a tyrosine kinase inhibitor [7] .The differential diagnosis for spindle cell neoplasms in the pancreas,all of which should be negative for CD117 and DOG1 stains,includes fibromatosis,leiomyosarcoma,liposarcoma,hemangiopericytoma,schwannoma,solitary fibrous tumor,and undifferentiated pleomorphic sarcoma [5,6,13] .

Similar to GISTs elsewhere in the gastrointestinal tract,pancreatic GISTs can demonstrate spindle cell,epithelioid,or mixed histology.Solid pancreatic GISTs on imaging tend to exhibit spindle cell morphology,whereas tumors with cystic or mixed features display epithelioid morphology in about half of the cases.In a recent study,all the tumors showing cystic or mixed features on imaging were categorized in the high risk category [4] .Limited data are available regarding specific gene mutations in pancreatic GIST,however,most tumors harbor KIT mutations while an occasional case of PDGFR mutated tumor has also been reported [4] .

Due to its rarity,the guidelines for risk assessment (i.e.size and mitotic rate) have not been established to predict the prognosis of primary pancreatic GIST.It has been reported that pancreatic GISTs tend to be larger in size and show an aggressive behavior with significantly worse disease free survival when compared to those of gastric GISTs [4] .Most metastases of GIST originating outside the luminal gastrointestinal tract occur in the peritoneum and liver,usually within 24 months of initial diagnosis [8] .

Fig.1.A:CT scan of the abdomen showing a 6-cm mass in the pancreatic head region that is predominantly solid with some cystic component (arrows).B:Follow-up CT scan imaging three months after starting therapy with imatinib,showing similar size mass with significant decrease in solid component likely representing tumor necrosis(white asterisk).

Fig.2.A:The tumor is composed of monotonous and bland appearing spindle cells (HE staining,original magnification × 200).B:High power view showing perinuclear vacuoles within some of the tumor cells (arrows) (HE staining,original magnification × 600).C:The tumor also shows foci of hemorrhage and necrosis (arrow),consistent with prior treatment effect (HE staining,original magnification × 40).D:CD117 immunostain is diffusely positive within the tumor (original magnification × 200).

Complete surgical resection with negative margin appears to be the treatment of choice,even in cases with recurrent disease.The type of surgical resection depends on the location of the tumor.A pancreaticoduodenectomy (Whipple procedure) is typically performed for a tumor located with the pancreatic head while partial resection of the pancreas may be performed for tumors located within the body or tail of the pancreas.Conventional chemotherapy and radiation therapy do not appear to add significant benefit.However,neoadjuvant imatinib therapy can be helpful to reduce the tumor volume or eradicate residual tumor cells [8,14] .Frequent clinical surveillance after the surgical treatment is usually recommended considering the high risk for recurrence and/or metastasis.

Acknowledgments

None.

CRediTauthorshipcontributionstatement

WhayoungLee:Data curation,Investigation,Methodology,Resources,Writing -original draft.XiaodongLi:Writing -review&editing.SoniaLee:Writing -review &editing.VishalSChandan:Conceptualization,Data curation,Formal analysis,Methodology,Writing -original draft,Writing -review &editing.

Funding

None.

Ethicalapproval

Not needed.As per the Ethics Committee of University of California (Irvine,USA),institutional review board approval or patient consent is not needed for case reports.

Competinginterest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.