Gastrointestinal Stromal Tumor of the Ampulla of Vater: A Narrative Review

Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal tract accounting for 1% of all gastrointestinal neoplasms. GISTs are mainly located in the stomach, and duodenal location is rare, accounting only for <4% of all cases. Occurrence of GIST in the ampulla and periampullary region is even more uncommon [1].

To the best of our knowledge, 25 cases of ampullary GIST have been reported in the English literature so far. In this manuscript, we will review the clinicopathologic findings of all the reported ampullary GISTs [1-22].

Published case reports and case series in the English literature have been collected by searching in PubMed, Google, and Google Scholar in the last 20 years. The keywords for searching were “Ampulla of Vater,” “Periampullary,” “Ampullary,” “Duodenum,” “Small intestine,” and “Gastrointestinal stromal tumor.”

It is worthy to note that the included studies have specifically mentioned the presence of tumor in the ampullary or periampullary region. Twenty-five cases were found in the English literature.

Tables 1 and 2 show the clinicopathologic characteristics of these 25 reported and published cases with ampullary GIST in the English literature [1-22].

Fourteen patients were female, and 11 were male (male/female = 11/14). The age range was 28–67 years with a mean of 50.5 [1-22].

The majority of the patients presented with lower GI bleeding either as fresh rectal bleeding or melena. One of these patients presented with unconsciousness secondary to low blood pressure and GI bleeding [22]. Other symptoms were abdominal pain in 6 and jaundice in 5 patients. Other rare gastrointestinal symptoms were also reported such as bloating [3] and weight loss [1] as the primary clinical presentation [3]. One of the patients was incidentally found during investigation and follow-up of gastric adenocarcinoma [4].

In the majority of the patients, laboratory tests were normal, except for anemia which was the most common abnormal laboratory finding. Rare isolated reports of abnormal liver function tests and elevated bilirubin, especially high alkaline phosphatase, were also reported [5-8].

History of neurofibromatosis type 1 was reported in 3 patients [8-10]. One of the patients with neurofibromatosis and ampullary GIST had also celiac disease and pituitary adenoma [8]. Gastric cancer has been reported in 2 patients; in one, it was found 2 years prior to ampullary GIST diagnosis [4] and in the other, both GIST and gastric cancer were simultaneously diagnosed [7]. In another case, adenocarcinoma of the ampulla of Vater was reported [1]. Also, one of the patients was diagnosed to have pancreatic ductal adenocarcinoma at the time of diagnosis of GIST in the ampulla of Vater [10]. In 2 of the reported cases, simultaneous duodenal neuroendocrine tumor was also diagnosed within the duodenum [1, 8]. Another patient had a past medical history of diverticulitis [2]. Family history in the case report by Leung et al. [12] was positive for breast cancer, colon cancer, coronary artery disease, and stroke. The patient had a history of hypertension, tachycardia, and anxiety disorder.

In >20 reported cases of ampullary GIST, imaging studies were reported, consisting of ultrasonography, CT scan, and MRI. The most important imaging finding was common bile duct and/or pancreatic duct dilatation. In ultrasonography, GISTs in the ampulla are hypoechoic masses. CT scan of the mass reported hypervascular uniformly or peripherally enhanced masses with or without central necrosis. Ampullary GIST is reported as a well-defined mass with pushing border and indentation of adjacent organs without significant invasion. MRI of ampullary GIST has been reported to show low signal intensity on T1-weighted images and high signal intensity on the T2-weighted image [7-15].

Main differential diagnosis by imaging modalities is adenocarcinoma of the ampulla of Vater or pancreatic ductal adenocarcinoma in the pancreatic head. The only way for the best diagnosis is histology and biopsy before surgery [10-15].

In 16 cases, endoscopic findings have been reported as round to oval submucosal or subserosal mass or masses with overlying mucosal ulceration arose from the duodenal wall, without intraluminal projection. Some tumors showed minimal invasion to the adjacent pancreatic head as well [11, 16].

In 8 cases, presurgical biopsies have been taken which was correctly diagnosed in 5 patients [1, 2, 7, 12, 17], and other 3 cases were either nondiagnostic (normal mucosa) or incorrectly diagnosed as carcinoma [2, 16, 17]. In most of the patients without perioperative histology, the clinical impression has been carcinoma of the ampulla of Vater/head of pancreas, neuroendocrine tumor, and GIST.

Twenty-one out of 25 reported cases of GISTs in the English literature showed pure spindle-cell morphology with fascicular and storiform patterns. Only 4 cases showed focal epithelioid morphology [1, 7, 18, 20]. Skenoid fibers were reported in 2 cases [15, 18]. In the case reported by Candanedo-Gonzalez et al. [18], focal collections of skenoid fibers with osteoid-like material and focal aneurysmal bone cyst-like areas were seen. Six ampullary GISTs reported to have bizarre and atypical spindle-shaped cells [1, 7, 11, 14, 20].

Most of the reported cases of ampullary GIST are categorized as low risk, that is, the number of mitosis was low (<5/50 HPF), and the tumors were mostly small (<5 cm). Only 5 cases have been reported with large size, that is, >5 cm [1-22].

The main differential diagnosis in these cases is spindle-cell tumors of the gastrointestinal tract, mostly schwannoma, leiomyoma, leiomyosarcoma, malignant peripheral nerve sheath tumors, and desmoid tumors. Immunohistochemistry can be helpful for the definite diagnosis [10-21].

All the reported GISTs in the ampullary lesion were reactive with CD34. CD117 was negative in 2 cases [2, 15]. Also, all of the reported DOG-1 were positive. Smooth muscle actin has been stained in 9 cases, and 7 of them (77.8%) were negative and 2 were positive [13, 20]. Desmin has been stained in 6 cases; only one has been positive, and all the other 5 cases were negative [13].

In 8 out of 9 cases with reported S100, the antibody was nonreactive, and in only 1 case, S100 was positive [15]. In Liao et al.’s [13] case, they have done genetic studies, and the tumor showed KIT N822K gene mutation in exon 17.

In 13 patients, Whipple’s operation was performed. In 4 patients, duodenectomy and resection were done [7, 9, 12, 14]. In 5 patients, sleeve duodenectomy was the procedure [2, 21]. Two patients developed liver metastasis, and liver transplantation and Whipple were the procedures to resect the tumor and the metastasis [11, 13].

In only 1 case endoscopic mucosal dissection was done to resect the tumor [3]. In 1 case, duodenal sparing robotic resection has been performed [6]. All of the above surgical procedures have been performed in association with imatinib (tyrosine kinase inhibitor) administration [1-22].

Liver metastasis has been reported in 2 ampullary GISTs [11, 13]. Also, lymph node metastasis has been reported in 1 case [11]. In 1 patient, local recurrence was developed [10]. All of the other 21 patients were free of any recurrence or metastasis.

Ampullary GIST is a rare tumor, mostly present with lower GI bleeding and small size. The imaging in this tumor is not specific, and perioperative biopsies are not so accurate (because of the submucosal location). The majority show low mitoses and are reactive with C-KIT and DOG-1. Ampullary GISTs can be treated effectively with imatinib and surgical resection. Findings of GIST in the ampulla of Vater are very similar to our previous experiences in regard to the demographic findings, pathologic characteristics, and outcome [23-25].

The authors have no conflicts of interest to declare.

The authors did not receive any funding.

Bita Geramizadeh: idea of the project, searching the literature, and writing the manuscript. Alireza Shojazadeh: searching the literature and writing the manuscript.