Gangliocytic paraganglioma (GP) is a benign tumor, occurring in the majority of cases in the duodenum. It is considered a rare tumor, very often misdiagnosed as neuroendocrine tumor [1].

Many controversies surround this tumor, from its origin to its prevalence, diagnosis, treatment, and follow-up. A surgical resection is enough in the vast majority of cases. But awareness of this disease is important to avoid misdiagnosis and facilitate treatment.

We are reporting a case of duodenal gangliocytic paraganglioma (DGP) with clinical follow-up after a period of seven years.

This is a case of a 42-year-old man, with no significant past medical history, no food or drug allergy, who presented to our clinic for a history of general state alteration, anemia, weight loss of 10 kg over two years, on–off jaundice over two years. He was refusing all kinds of investigations until he became very ill. He had no nausea, no vomiting, no diarrhea, or constipation. On physical exam he was jaundiced, pale, afebrile, had a pulse of 60, blood pressure 125/70, respiratory rate 20. He had good bilateral air entry, and had right upper quadrant pain. Blood tests were immediately done: bilirubin slightly elevated, Hb 9 g/dL.

Then a computed tomography scan of the abdomen was done showing an intraluminal defect in D2–D3 without obstruction (Figure 1).

An endoscopic retrograde cholangiopancreatography (ERCP) was done thereafter showing a mass and we couldn’t localize the papilla.

Then an endoscopic ultrasound (EUS) was done and showed a submucosal mass of 5 cm, well circumscribed abutting the ampulla, suspended by a stalk, with iso-echogenic borders, in favor of a benign tumor (Figure 2) no lymph nodes were seen.

Biopsy by EUS was taken and came back as normal epithelium, so it was inconclusive.

A laparoscopic transduodenal tumorectomy or laparoscopic duedonotomy was then scheduled. We put an endo GIA stapler on the stalk of the mass and resected the mass and its stalk entirely. We did a cholecystectomy for the gallstones due to the history of repetitive obstructive jaundice.

The post-operatory course was uneventful.

Blood tests at d1 postoperatively were as follow: Bilirubin T 1 (N range 0.2–1 mg/dL), Direct 0.33 (N range 0–0.2 mg/dL), amylase 32 (N range 22–80 U/L), lipase 30 (N range 13/60 U/L).

An upper gastrografin imaging was performed at d5 post-operatory to see if there is any leak or stenosis after the laparoscopy. It was normal, no leakage of contrast material, no strictures. At d8 post-op, the patient was discharged home.

The final pathology came back. No malignant cells in gallbladder. There were few gallstones. The 5 cm tumor and its stalk were analyzed. Margins were negative. The 5 cm mass suspended by the stalk was consistent with a gangliocytic paraganglioma. Figure 3 shows 40* hematoxylin and eosin (HE) stain: well differentiated triphasic neoplasm consists mainly of low grade neuroendocrine cells with regular nuclei (ascending arrow), schwan cells (descending arrow), and several ganglion cells (oblique arrow). No anaplasia. No mitosis seen (Ki67 less than 1%).

20* immunohistochemical (IHC) stain showing the same tumor with diffuse intense positivity for synaptophysin (descending arrow) in submucosa of unremarkable duodenal mucosa (ascending arrow) Figure 4.

40* IHC stain showing obvious diffusely positivity for synaptophysin in all neoplastic cells (oblique arrow) Figure 5.

The patient was followed regularly and he remains in good health for the past seven years since he had his surgery. Physical exam remains within normal limits.

Gangliocytic paraganglioma is a benign tumor, occurring in the majority of cases in the duodenum (89% of cases). It can also occur in the respiratory tract, spinal cord, pancreas, jejunum, esophagus, and appendix [1],[2].

The first description of this tumor was in 1957 by Dahl et al. and the term gangliocytic paraganglioma was adopted in 1971 by Kepas Zacharias based on common features with paraganglioma and ganglioneuroma. Buchler et al. reported the first case of GP with positive lymph nodes [2].

The mean age at diagnosis is 54 years and males are more affected than females with a ratio of 1.5:1. The mean tumor size is 2.5 cm [3]. Although GP is a benign tumor as we saw in our case, it has a capacity to spread to lymph nodes and distant organs [2]. Some experts even name this disease “tumor with uncertain malignant potential” [4] as it led to death in 3 reported cases [1]. We note that GP from other sites of duodenum have a greater potential for metastasis [5].

Even though considered a rare tumor, we believe that DGP is an under-diagnosed tumor [6], and the incidence of positive lymph nodes is under evaluated [2],[7]. It is often misdiagnosed as neuro-endocrine tumor [8].

Its occurrence is almost always sporadic as in our case but there are some reported cases of gangliocytic paraganglioma in the context of a Von Recklinghausen disease [9].

Many theories concerning its origin exist: first some experts think that it has a hamartomatous origin [1]. Other experts say that it has and ectodermal origin. In the other hand there are experts who say that it has an endodermal origin for epithelial cells and neuroectodermal origin for ganglion and spindle cells [6],[10].

Patients present with abdominal pain or gastrointestinal (GI) bleeding and consequent anemia as in our case. The lesion can be found incidentally. It can present also with nausea, weight loss, fatigue, or jaundice [11].

Computed tomography (CT) scan of the abdomen and pelvis and endoscopic ultrasound (EUS) are done for staging and serve to R/o invasion of lymph nodes, as 47% and 64% of lymph nodes positivity are detected respectively by CT and EUS [11]. Our patient didn’t have positive lymph node (LN) on scan that’s why a LN dissection wasn’t performed. Other types of imaging have been used to detect a DGP such as gastrografin swallow, magnetic resonance imaging (MRI), intraoperative US, positron emission tomography (PET), Octreotide scan, but they are less specific than CT and EUS for detecting LN [11].

This tumor has a submucosal location as we saw in our patient. It is a well demarcated not encapsulated solid mass [2] with an overlying mucosal ulcer. Bleeding is common even without mucosal ulceration [2]. It is most frequently polypoid pedunculated or sessile [10]. Thus, the pre-op diagnosis by EUS is difficult [3] as it can contain 1 or 2 types of cells [2] and only 19% of cases are diagnosed preoperatively [1] by fine needle aspiration (FNA) or core biopsy. We couldn’t had a diagnosis preoperatively with our patient that’s why we’ve done a laparoscopy to be able to have an en-bloc resection of the totality of the mass for accurate diagnosis.

Our patient didn’t have the risk factors for lymph node positivity: young age [3], tumor invasion beyond the submucosa [10].

The size of the tumor and the depth of its invasion will indicate the treatment modality [10].

If the tumor is [11]. If the tumor is peri-ampullary, >5cm, no stalk or suspicion of positive lymph nodes by imaging then a surgical resection with lymph node dissection must be conducted. In our case, the tumor was 5 cm diameter and peri-ampullary, we decided to do laparoscopic duodenotomy for a complete en bloc resection. In case of positive lymph nodes experts agree on the importance of doing a curative pancreatico-duodenectomy even though this operation carry its own risk of morbidity and mortality. Doing it otherwise will require further studies and long periods of surveillance [12].

The final diagnosis is done only after the tumor is completely resected. This tumor consists of three different cellular types: spindle cells, epithelial cells, and ganglion cells, that can exist in different proportion and we need the presence of all three types of cells to be able to make the final diagnosis of GP [3],[12].

Immunohistochemistry (IHC) is indispensable in the case spindle and ganglion cells are scarce. Immunohistochemical stain differs for each cell type. Epithelial cells are often positive for synaptophysin, cytokeratin, CD56, chromogranin, neuron-specific enolase, pancreatic polypeptide, progesterone receptor. Ganglion-like cells are positive for synaptophysin, CD56, neuron-specific enolase, somatostatin, and pancreatic polypeptide. Spindle cells are positive for S100, bcl2, CD56, neuron-specific enolase, and synaptophysin [2],[6],[8]

As for the differential diagnosis, low grade neuroendocrine tumor will not contain spindle and ganglion cells, neither progesterone receptor. But it will be positive for synaptophysin, specific-enolase protein, and S100. As for ganglioneuroma, we’ll see only ganglion cells without spindle or epithelial cells. On the other hand, there is no ganglion cells in paraganglioma. Finally, in schwannoma we’ll see only spindle cells [1],[3],[6].

It’s imperative to get an accurate diagnosis because the clinical course, prognosis, follow-up and treatment will differ depending on the type of tumor.

There is no role for adjuvant chemotherapy (cyclophosphamide vincristine dacarbazine) [12] and radiotherapy (RT) for DGP even in the metastatic cases [4]. But RT can be used if the patient is unfit for pancreatico-duodenectomy [13]. In fact, a study done by Van et al. showed that 14 sessions of RT can control bleeding in a patient having a peri-ampullary GP with multiple comorbidities who is unfit for surgery.

The majority of tumors are endocrinologically inactive. Some secrete somatostatin and pancreatic polypeptide [2]. These levels, if elevated, can be used to monitor recurrence or metastasis after a surgical resection [3]. Katayama et al. reported a case of DGP with catecholamine secretion during the surgery, revealing that pheochromocytoma could be in the differential diagnosis [14].

Studies showed that there could be a role for somatostatin analogs in the treatment of DGP [12] specially in patients who are unfit for surgery or those who still have positive margins after surgery.

Concerning the follow-up of this disease there are no consensus on how and when to do imaging studies, but the experts agree on the necessity of a more frequent follow-up including clinical and imaging studies, in the cases where there are lymph nodes involvement [12].

Duodenal gangliocytic paraganglioma is a rare tumor most frequently benign located in the duodenum, arise in mid-age man. Surgery is needed in the case the tumor is more than 5 cm, peri-ampullary, and also in the rare cases of lymph node positivity. A good physical exam, complete resection, IHC, and surveillance are key in this disease.