Gangliocytic Paraganglioma Research Articles

Multimodality imaging of multiple duodenal gangliocytic paragangliomas with post-surgical recurrence

A 68-year-old man consulted for abdominal pain. CT exam showed 3 clustered complex cystic lesions arising from or abutting the duodenum measuring 1.5, 2.5 and 8 cm (Fig. 1). An esophagogastroduodenoscopy was performed with the biopsy showing evidence of gangliocytic paraganglioma (GP). A subsequent F-18 FDG PET/CT scan showed hypermetabolic septations and mural nodules of the CT-depicted lesions (Fig. 1). The patient underwent excision of all the masses with the surgical pathology confirming GP.

Transient hypotension during endoscopic resection of gangliocytic paraganglioma with ampullary involvement.

Transient hypotension during endoscopic resection of gangliocytic paraganglioma with ampullary involvement.

1979 GI Bleed Secondary to Gangliocytic Paraganglioma Treated With Radiation Monotherapy

INTRODUCTION: Gangliocytic Paraganglioma (GP) is a rare, usually benign tumor typically found in the 2nd part of the duodenum. The rarity of the tumor hasn’t allowed development of treatment guidelines. Mainstay of treatment involves endoscopic or surgical resection. Adjuvant chemotherapy or radiation has been utilized in a few cases. The case described is of a patient with GP presenting with hematochezia. The patient’s gastrointestinal (GI) bleed was treated with radiotherapy alone, which is the first case to our knowledge in the literature. CASE DESCRIPTION/METHODS: A 78 year old male with past medical history of multiple comorbid cardiovascular conditions and Multiple Myeloma presented with a six month history of hematochezia. Complete Blood Count showed a hemoglobin (hgb) of 8.6 g/dL with a baseline hgb of 11 g/dL four months prior. Esophagogastroduodenoscopy (EGD) showed a 3 cm ulcerated, friable periampullary mass. Biopsies demonstrated epithelioid, spindle and “large” cells associated with GP. Computed Tomography (CT) scan of the abdomen showed a 5.1 cm soft tissue density appearing to originate from the pancreatic head and abutting the duodenum with no regional lymphadenopathy or distant metastasis (mets). Due to the patient’s comorbidities and high perioperative mortality risk, radiation monotherapy was pursued for treatment. After fourteen radiotherapy sessions, the patient’s GI bleed resolved. Repeat EGD showed decreased vascular markings in the duodenal mass. DISCUSSION: GP is a rare tumor composed of epithelioid, spindle and ganglion cells. Tumor behavior is usually benign with rare invasion of nearby structures and lymph node mets. CT scan and endoscopic ultrasound (EUS) are generally recommended for staging. Our patient underwent CT Scan, but EUS was deferred due to little utility with an increased perioperative mortality. Local surgical resection is the most common treatment, but endoscopic resection has shown lower morbidity and mortality in selected cases. The size of the tumor and invasion depth dictates treatment modality. Our patient’s tumor size (>5 cm) and pancreatic head origin would have necessitated pancreaticoduodenectomy in a healthy patient. Due to his comorbid conditions and positive literature data on adjuvant radiotherapy for benign paragangliomas of the pancreatic head and neck, our patient underwent successful monotherapy with radiation for control of bleeding. This case shows benefit of radiotherapy alone for control of bleeding due to GP in high risk surgical patients.

1861 Duodenal Gangliocytic Paraganglioma in Patient With Rectal Adenocarcinoma

INTRODUCTION: Gangliocytic paragangliomas are a rare subclass of neuroendocrine tumors that usually appear in the periampullary region of duodenum. They are generally benign, although may have potential for metastases depending on size and extension. They most commonly present with bleeding or abdominal pain, but cases with obstructive jaundice and pancreatitis have also been reported. They are often misdiagnosed as GISTs or other neoplasms, but with histologic examination, an accurate diagnosis can be reached. However, intraoperative diagnosis with FNA and frozen section analysis are often inaccurate and could affect surgical decision. CASE DESCRIPTION/METHODS: 62-year-old male with past medical history of diverticulitis, internal hemorrhoids, and iron deficiency anemia presented with syncope and gastrointestinal bleeding. During evaluation with colonoscopy, a mass was found in the rectum, which was later confirmed to be an adenocarcinoma. An FDG-avid duodenal segment was incidentally found while undergoing workup with PET-scan. He had neoadjuvant chemoradiation, with resection of rectal cancer and temporal ileostomy. Biopsy of duodenum with endoscopic ultrasound revealed normal duodenal mucosa on 2 separate occasions. Ultimately, the duodenal tumor was excised via exploratory laparotomy. Intraoperative frozen biopsy of mass revealed a GIST and a Whipple procedure was performed due to proximity to ampulla. Final pathology report revealed a gangliocytic paraganglioma, after staining positive with synaptophysin (as well as S-100 and neuron specific enolase) and negative for antibody to CD117, which is a sensitive marker for GISTs. DISCUSSION: Duodenal gangliocytic paragangliomas remain to be rare entities. There is yet no clear consensus in regards to appropriate workup, treatment or follow-up, especially in patients with metastases or concurrent adenocarcinoma. It is uncertain if coexistence with a rectal adenocarcinoma (as seen in this case) was coincidental or due to similar pathogenesis. Diagnosis with FNA and frozen section biopsies can be useful, but are often inaccurate. The success largely relies on the operator and clinical suspicion, but it is especially hard when there are no symptoms or relevant history. The recommended management is margin-free resection endoscopically, with local surgical excision or Whipple procedure. Studies have shown that some molecular markers can predict malignant potential. Yet, whether they are useful for management or surveillance has not been determined.

A Incidentally Diagnosed Duodenal Subepithelial Mass: Gangliocytic Paraganglioma Treated by Endoscopic Mucosal Resection

A Incidentally Diagnosed Duodenal Subepithelial Mass: Gangliocytic Paraganglioma Treated by Endoscopic Mucosal Resection

Neuroendocrine Tumors (NETs) of the Minor Papilla/Ampulla: Analysis of 16 Cases Underlines Homology With Major Ampulla NETs and Differences From Extra-Ampullary Duodenal NETs.

Neuroendocrine tumors (NETs) of the minor papilla/ampulla (MIPA) are rare and poorly studied. Only individual case reports and no comprehensive analysis are available from the literature. We collected 16 MIPA NETs and investigated their clinicopathologic and immunohistochemical features, including markers such as somatostatin, pancreatic polypeptide, gastrin, serotonin, MUC1, cytokeratin 7, and somatostatin receptors type 2A and 5. The median age at diagnosis was 57.5 years, and the female-to-male ratio was 2.2:1. The median NET size was 1.45 cm, and most (94%) were low-grade (G1) tumors. Similarly to what was observed in the major ampulla, 3 histotypes were found: (i) ampullary-type somatostatin-producing tumors (ASTs, 10 cases), characterized by somatostatin expression in most tumor cells, focal-to-extensive tubulo-acinar structures, often with psammoma bodies, MUC1 reactivity, and no or rare membranous reactivity for somatostatin receptor type 2A; (ii) gangliocytic paragangliomas (3 cases), characterized by the coexistence of 3 tumor cell types: epithelioid, often reactive for pancreatic polypeptide, ganglion-like cells, and S100 reactive sustentacular/stromal cells; and (iii) ordinary nonfunctioning NETs (3 cases), resembling those more commonly observed in the extra-ampullary duodenum. Comparable histotypes could also be recognized among the 30 MIPA NETs from the literature. No NET-related patient death among MIPA cases was observed during a median follow-up of 38 months; however, MIPA ASTs showed lymph node metastases and invasion of the duodenal muscularis propria or beyond in 44% and 40% of cases, respectively. In conclusion, MIPA NETs closely resemble tumors arising in the major ampulla, with predominance of ASTs.

Carcinoids of the ampulla: Long-term follow-up after endoscopic resection.

430 Background: Neuroendocrine tumors (NET) or carcinoids of the ampulla are exceedingly rare in comparison to duodenal NET. Surgical management is widely accepted as the treatment of choice, but for patients that refuse surgery or are poor operative candidates, endoscopic resection may be option. We present a consecutive case series at a tertiary care center describing our experience with endoscopic resection of ampullary NET. Methods: This is a restrospective review with a long-term follow-up of patients with ampullary NET that were endoscopically resected. Outcomes were analyzed based on the histopathologic classification system proposed by the World Health Organization in 2000. Results: Twelve patients (9 male, 3 female), ranging in age from 41 to 86 (mean 59) underwent endoscopic ampullectomy for ampullary NET, with a mean follow-up time of 5 years. Patients had refused surgery or were poor surgical candidates. All, but one incidentally found case, were symptomatic on presentation, with gastrointestinal bleeding being the main symptom. No patients had a hormonal syndrome. The mean size of the lesions was 21 mm (6 mm to 35 cm). Six (50%) patients had a well-differentiated, benign lesion, 6 (50%) patients had a well-differentiated NET with unknown malignant potential (gangliocytic paragangliomas). Eight (67%) were completely excised during the initial endoscopy with 4 requiring re-excision. Only 2 patients developed recurrence, after 2.5 and 10 years and this necessitated a pancreaticoduodenectomy. Five patients had complications (2 for bleeding and 3 for post-ERCP pancreatitis), with zero deaths. Conclusions: Unlike duodenal carcinoids, ampullary NET are rare. Pancreaticoduodenectomy can be offered to fit patients except for gangliocytic paragangliomas that do not require an aggressive operation. However, for those that refuse surgery or are poor candidates, endoscopic ampullectomy can be an option with acceptable short and long-term outcomes.

An Unusual Cause of Acute Pancreatitis in a Young Woman

Question: A 27-year-old woman presented to the emergency department with intermittent epigastric pain radiating to the back of one week’s duration. The pain was dull and associated with nausea. Her medical and family history was unremarkable. She denied any alcohol or drug intake. There was no history of fever, yellowish discoloration of the sclera or urine, or weight loss. Upon arrival, she had mild tachycardia (heart rate: 103 beats per minute). Physical examination revealed tenderness in the epigastric and right upper quadrant of the abdomen. The Murphy’s sign was negative, and there were no peritoneal signs. The remainder of the physical examination was unremarkable. Laboratory studies showed an elevated serum aspartate aminotransferase level of 176 IU/l, alanine aminotransferase of 240 IU/l, gamma-glutamyl transpeptidase of 757 IU/L, alkaline phosphatase of 308 IU/l, total bilirubin of 0.6 mg/dL, lipase of 6,641 U/L, amylase of 667 U/L, and high sensitivity C-reactive protein of 3.416 mg/L; white blood cell count, serum bilirubin, triglyceride, and calcium levels were all within normal limits. Contrast-enhanced computed tomography (CT) of the abdomen showed marked peripancreatic fat stranding, no dilatation of the biliary tract or pancreatic duct, and no evidence of regional lymphadenopathy (Figure A). An endoscopic retrograde cholangiopancreatography (ERCP) was carried out to rule out biliary pancreatitis. Duodenoscopy showed a 3-cm pedunculated tumor with a smooth surface and soft texture at the Vater’s papilla (Figure B and C). Endoscopic ultrasonography (EUS) revealed the tumor as smooth-margined, homogenous, hypoechoic lesion arising from the submucosal layer (Figure D). What is your diagnosis of the lesion of the Vater’s papilla?A.CholedochocoeleB.Neuroendocrine tumor (NET)C.Gastrointestinal stromal tumor (GIST)D.Gangliocytic paraganglioma Look on page 621 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image(s) to Practical Teaching Cases. The correct answer is D. Gangliocytic paraganglioma (GP) of the Vater’s papilla. The patient underwent surgical wedge resection of the tumor (Figure E). The histopathological examination showed the tumor located in the submucosa (Figure F, H&E, 40×). GP is typically composed of spindle cells, ganglion cells, and epithelioid cells with the appearance of neuroendocrine cells (Figure G, H&E, 200×; Figure H, H&E, 400×). There was no mitosis or necrosis in the tumor. Immunohistochemistry examination revealed that the neuroendocrine cells stained positive for CD56 and chromogranin A, and the spindle cells were immunoreactive for S100 protein. These findings confirmed the diagnosis of GP. Answer A is incorrect because choledochocele is an anechoic lesion on EUS. Gastrointestinal NETs are homogenously hypoechoic lesions arising from the second or third layer, sometimes with muscularis propria expansion (Answer B). The EUS imaging feature of a GIST is a hypoechoic mass arising from the muscularis propria, and larger GIST are sometimes composed of heterogeneous echo patterns and anechoic spaces (Answer C). However, the definitive diagnosis of the lesion requires histology. GP is a rare, generally benign neuroendocrine tumor. However, GP with regional lymph node involvement and distant metastasis have been reported.1Li B. Li Y. Tian X.Y. et al.Malignant gangliocytic paraganglioma of the duodenum with distant metastases and a lethal course.World J Gastroenterol. 2014; 20: 15454-15461Crossref PubMed Scopus (28) Google Scholar The most common site of the tumor is the second portion of the duodenum.2Okubo Y. Nemoto T. Wakayama M. et al.Gangliocytic paraganglioma: a multi-institutional retrospective study in Japan.BMC Cancer. 2015; 15: 269Crossref PubMed Scopus (28) Google Scholar, 3Okubo Y. Wakayama M. Nemoto T. et al.Literature survey on epidemiology and pathology of gangliocytic paraganglioma.BMC Cancer. 2011; 11: 187Crossref PubMed Scopus (74) Google Scholar Gastrointestinal bleeding—followed by abdominal pain and anemia—are the most common symptoms of the disease.3Okubo Y. Wakayama M. Nemoto T. et al.Literature survey on epidemiology and pathology of gangliocytic paraganglioma.BMC Cancer. 2011; 11: 187Crossref PubMed Scopus (74) Google Scholar GPs without distant metastasis are usually treated via endoscopic resection or pylorus-preserving pancreaticoduodenectomy.2Okubo Y. Nemoto T. Wakayama M. et al.Gangliocytic paraganglioma: a multi-institutional retrospective study in Japan.BMC Cancer. 2015; 15: 269Crossref PubMed Scopus (28) Google Scholar The patient recovered uneventfully and had no evidence of tumor recurrence after a surgical wedge resection of the duodenal GP at the one-year follow-up. In conclusion, GP may be an uncommon cause of acute pancreatitis. This rare and benign disease can be treated via endoscopic or surgical resection of the tumor. CME Exam 1: An Unusual Cause of Acute Pancreatitis in a Young WomanGastroenterologyVol. 157Issue 3Preview Full-Text PDF

Periampullary Gangliocytic Paraganglioma

Introduction: Gangliocytic paraganglioma (GP) is rare and difficult to be differentiated from other periampullary neoplasms. The clinical characteristics and optimal treatment of periampullary GPs have not been clarified. Method: The data pool for the analysis comprised of cases of periampullary GP encountered in our institution and sporadic cases reported in the English literature. Result: A total of 117 cases with periampullary GP were studied, including 2 from our institute, and among them, duodenal GP was the most common (53.0%). GP size ranged from 0.7 cm to 19.0 cm, with a median of 2.2 cm. The most common presenting symptom for overall periampullary GPs was epigastric pain in 49.5% cases, followed by gastrointestinal bleeding in 35.4% cases. Most (84.1%) of the periampullary GPs were benign, whereas 15.9% were malignant. Metastasis was noted in 26.3% of periampullary GPs, with 14.5% showing lymph node metastasis and 1.8% showing liver metastasis. Of the periampullary GP cases included, 30.1% were treated with pancreaticoduodenectomy, 40.6% with local excision, and 17.7% with endoscopic resection. Conclusion: Periampullary GP should be considered as a tumor with malignant potential. Endoscopic resection is the treatment of choice for most of the duodenal GPs, whereas pancreaticoduodenectomy is recommended for GPs with possible malignancy, such as large size, with submucosal invasion, or pancreatic GP.

Duodenal neuroendocrine tumors

Significant augmentation of the incidence of duodenal neuroendocrine tumors duodenum has been observed in recent decades. There are 5 histological types of these tumors: gastrinoma (50-60%), somatostatin-producing tumor (15%), inactive serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinoma (<3%) and gangliocytic paraganglioma (<2%). The majority of tumors are localized within the bulb and postbulbar part of duodenum, 20% are found in periampular area. Treatment strategy depends on dimensions, localization, histological class, stage and type of tumor. It is believed that endoscopic resection is permissible for small inactive tumors (G1) located above major duodenal papilla. The majority of other neoplasms requires surgical resection. Personal experience of various surgeons is limited by small group of patients. Therefore, it is necessary to summarize results for selection of optimal treatment.

Gangliocytic paragangliomas: a clinicopathologic study

Objective: To investigate the clinicopathological features of gangliocytic paraganglioma(GP). Methods: Clinical data and pathological diagnosis of the 4 cases of GP were obtained through the medical record inquiry from January 2011 to December 2017 at the First Affiliated Hospital of Zhengzhou University. Routine HE staining and immunohistochemistry of CKpan, Syn, CgA, CD56, NSE and NF were performed. Clinical follow-up of the patients was obtained through telephone communication. Results: All 4 patients, including 2 male and 2 female patients, presented with intermittent abdominal pain and distention. The median age was 56 years. Preoperative CT showed local thickening of the duodenum wall with slight enhancement in all four cases. Endoscopic ultrasonography showed low level echo in the mucous layer and submucosa involved by the tumor in 3 of 4 cases. The maximal diameter of the tumor ranged from 0.6 to 1.8 cm with an average of 1.2 cm. Microscopically, the tumors consisted of epithelioid, spindle and ganglion-like cells, and the proportion of the three cell types was different among cases. Epithelioid cells expressed CKpan, Syn, CgA and CD56. Spindle cells expressed S-100 protein and SOX-10 and ganglion-like cells expressed NF, Syn, CgA and CD56.All tumour cells expressed NSE. All 4 patients had no recurrence a post-surgery follow-up period of 3 to 30 months. Conclusions: GP of the duodenum is a benign tumor with excellent prognosis after endoscopic excision. Although its incidence is very low, its diagnosis should be considered for any mass lesion of the duodenum, especially involving mucosa and submucosa of the second dudenal segment.

Rare Case of Gangliocytic Paraganglioma

Gangliocytic paragangliomas (GP) are very rare tumors, almost exclusively found in duodenum. These are considered benign tumors but rarely may recur or metastasize. The common clinical presentation includes gastrointestinal bleeding, abdominal pain, and in rare cases as obstruction. Definitive treatment is complete resection of tumor, endoscopically or surgically. We present a case of 44-year-old female, who presented with persistent nausea, vomiting, abdominal pain along with on and off melena. She had benign physical exam. Extensive workup done was negative, except CT Enterography showed filling defect. Endoscopy biopsy done showed possible ganglionueroma. She underwent surgery and final pathology results came back as Gangliocytic paraganglioma. Discussion GP is a rare tumor that is located in the duodenum in 90% of cases with a particular predilection to the region of the ampulla of Vater although can be rarely seen in 3rdand 4thportion. Outside duodenum, its occurrence is extremely rare. Due to submucosal nature, exact origin of GP is unknown. The age of presentation is very vast ranging from 15-84 years, with slight male predominance. Clinical presentation is variable, with almost 50% of cases presenting with bleed, followed by anemia and abdominal pain. Rare presentation with duodenal obstruction and biliary obstruction is also seen in some case reports Differentials are related to any mass lesion in duodenum with typical examples of duodenal cancer (benign and malignant) or polyps<./p> Diagnosis is usually made by recognizing the mass according to diagnostic guidelines of presenting case, as in our case of melena and abdominal pain and is confirmed by histopathology. Its main histologic features are epithelioid cells, spindle-shaped cells and ganglion-like cells. Treatment of GPs is resection, endoscopically or surgery, usually depending on size, local invasion and LNs involvement. As most of the GPs are benign, the treatment of choice for gangliocytic paragangliomas is endoscopic resection4. An aggressive behavior may also be suggested by the presence of nuclear pleomorphism, mitotic activity and infiltrative margin. In the case of ampullary paragangliomas, these findings favor radical surgical resection. Reoccurrence rate is very rare but can be seen.2501_A Figure 1. CT abdomen/pelvis with PO/IV Enterography Contrast protocol showing filling defect in periampullary region2501_B Figure 2. high power showing focal aggregates of ganglion cells amidst numerous nerve sheath Schwann cells2501_C Figure 3. low power showing spindle cell tumor underlying the duodenal mucosa

A case of duodenal gangliocytic paraganglioma with regional lymph node metastasis

Introduction: Gangliocytic paraganglioma derived from neural crest is an unusual neuroendocrine tumor having a characteristic triphasic microscopic appearance with epitheloid cells, spindle cells, and ganglion cells. It is generally considered to be a benign. Here, we report a case of gangliocytic paraganglioma with regional lymph node metastasis. Case: A 41-year-old man was admitted due to hematemesis. Upon arrival, he was evaluated and underwent an esophagogastroduodenoscopy that revealed a large submucosal tumor at second portion of duodenum near ampulla of Vater. Surgical resection was planned. On exploration, there was an 1.5 cm-sized lymph node in the paraduodenal area. The lymph node was proven to be a metastatic malignant lesion in the frozen biopsy. Therefore we decided to perform pancreaticoduodenectomy. Grossly, the mass was soft, 2.5 × 1.7 × 0.9 cm in size, well demarcated, located near the ampulla of Vater. Pathologically, the duodenal mass was a gangliocytic paragangliomoa. The tumor was positive cellular reaction for chromogranin, synaptophysin, neurofilament by immunohistochemistry. There was one metastatic lymph node among 11 retrieved lymph nodes. He was recovered without complication and discharged at postoperative day 9. After 7 year after operation, he was alive without recurrence. Conclusion: Radical surgery was necessary in a patient with lymph node metastasis. Close follow-up was advocated because gangliocytic paraganglioma with lymph node metastasis was considered as tumors with uncertain malignant potential.

Diagnosis, Pathological Findings, and Clinical Management of Gangliocytic Paraganglioma: A Systematic Review.

Background: Although gangliocytic paraganglioma (GP) is considered a rare benign neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is misdiagnosed as neuroendocrine tumor G1, which is associated with a poorer prognosis than GP. To avoid such misdiagnoses, it is important to understand the clinicopathological characteristics of GP. Thus, herein, we discuss the current literature on the clinicopathological characteristics of GP.Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed and Japana Centra Revuo Medicina searches were used to identify papers describing GP. Inclusion criteria included confirmation of epithelioid, spindle-shaped, and ganglion-like cells in the main article and/or figures and whether the paper was cited in other studies of GP. Data were collected on age, sex, site of the primary lesion, tumor size, treatment, prognosis, lymph node metastasis (LNM), depth of tumor invasion, rate of preoperative diagnosis, and clinical symptoms.Results: In total, 162 papers containing 263 cases of GP met the criteria. The mean age at diagnosis was 53.5 years. The male-to-female ratio was 157:104. The mean tumor size was 25.7 mm. The predominant site of the primary tumor was the duodenum (89.7%). The most common clinical sign of GP was gastrointestinal bleeding (47.9%). Other signs and symptoms of GP included abdominal pain (44.7%), anemia (20.3%), incidental findings (12.9%), nausea (6.9%), weight loss (5.5%), general fatigue (5.1%), jaundice (4.6%), and incidental autopsy findings (5.1%). LNM was observed in 11.4% of patients. Liver metastasis was observed in 1.1% of patients. Depth of tumor invasion (penetrating beyond the submucosal layer or sphincter of Oddi) was by far the most significant risk factor for LNM in patients with GP. This suggests, along with histological heterogeneity, that GP may have hamartomatous characteristics. Furthermore, immunohistochemical expression of progesterone receptor and pancreatic polypeptide were useful in distinguishing between GP and neuroendocrine tumor G1, even in small biopsy specimens.Conclusions: We reveal the clinicopathological characteristics of GP, including risk factors for LNM, differential diagnostic approaches, and improvements in the clinical management of this tumor.In addition, GP may have hamartomatous characteristics.

Cytological Diagnosis of Duodenal Gangliocytic Paraganglioma on Ultrasound-Guided Fine Needle Aspirate: A Case Report with Review of the Literature

Cytological Diagnosis of Duodenal Gangliocytic Paraganglioma on Ultrasound-Guided Fine Needle Aspirate: A Case Report with Review of the Literature

“Ampullary Gangliocytic Paraganglioma:” A Rare Neuroendocrine Tumor Can Be Safely Treated with Ampullectomy

ABSTRACT Ampullary Gangliocytic paraganglioma is a rare gastro-entero-pancreatic neuroendocrine tumor with a characteristic histologic appearance involving epitheliod, spindle and ganglion cells. Endoscopic ultrasound is useful to determine depth of invasion and regional metastasis. Endoscopic resection, Ampullectomy and pancreato-duodenenectomy have been described as management options in literature but no consensus has been established. The index case describes an asymptomatic 42 y/o lady with a background of plexiform neurofibromatosis referred for cholestatic derangement of liver function. She was found to have a dilated biliary system with a periampullary mass which proved to be a Gangliocytic Paraganglioma without local lymph node metastasis. She underwent successful endoscopic ampullectomy with complete normalization of LFT and decompression of the biliary system with no clinical or endoscopic recurrence at 2 years follow up. We advocate that Partial Ampullectomy could be done safely as a treatment of localized Ampullary GP allowing long term resolution of symptoms.

A Rare Case of Periampullary Tumor

Gangliocytic paraganglioma is a rare tumor that can affect anywhere in the gastrointestinal tract, though it is most frequently found in the second portion of the duodenum. They commonly present with abdominal pain, gastrointestinal bleeding, or rarely with obstructive jaundice. This is a case of an asymptomatic periampullary gangliocytic paraganglioma. A 45 year old male with a history gastroesophageal reflux well controlled on a PPI was referred for iron deficiency anemia with no overt bleeding. He underwent an upper endoscopy that revealed a submucosal nodule involving the ampulla. The endoscopic ultrasound subsequently revealed a 2.3x1.5cm hypoechoic heterogeneous mass of the periampullary region. Fine needle aspiration showed a neoplasm with neuroendocrine differentiation. The immunohistochemical stain was strongly positive for synaptophysin and negative chromogranin, S-100, CD-117, and DOG-1. The periampullary mass was resected using endoscopic mucosal resection, with the final pathology consistent with gangliocytic paraganglioma. The patient had further testing with negative urine metanephrines and catecholamines. There was no radiographic evidence of distal metastatic disease. Gangliocytic paraganglioma (GP) is a rare neuroendocrine tumor, with only around 200 cases reported. It consists of three distinct cellular elements: spindle cells, epithelial cells, and ganglion cells. In spindle-cell predominant tumors, the differential diagnosis includes schwannomas and GIST. When visualized endoscopically, GPs are difficult to distinguish from other submucosal tumors and may appear as a pedunculated or sessile polypoid mass that may be smooth or ulcerated. Endoscopic biopsies are frequently negative since the tumor is submucosal. An EUS is frequently necessary to obtain a fine-needle aspiration as well as evaluate for local spread of the tumor and detect metastatic lymph nodes. The majority of GPs are benign without local or distant spread. However, lymph nodes metastases and distant metastases to other organs have been reported. Treatment is dependent on the size of the tumor and the presence of any metastatic lymph nodes or other metastatic sites. Case reports have shown that overall the prognosis is good but there have been reported deaths from metastatic tumors. In conclusion, we present the case of an incidental periampullary gangliocytic paraganglioma.Figure: Ganglion cells have abundant cytoplasm, round nuclei, and prominent nucleoli (small arrows). Spindle cells are arranged in fascicles (large arrows).Epithelioid endocrine cells are arranged in trabeculae (arrowheads).Figure: Endoscopic image of the periampullary mass.Figure: Endoscopic ultrasound image of the periampullary mass.

Duodenal Gangliocytic Paraganglioma: A Rare Neuroendocrine Tumor

Gangliocytic paragangliomas, predominantly found in the second part of duodenum, are rare, usually benign tumors with occasional lymph node metastasis. Clinical presentation varies from incidental finding upon endoscopy, or abdominal pain and upper gastrointestinal bleeding. A 73-year old woman with past medical history of non-Hodgkin's lymphoma, presented with intermittent post-prandial epigastric pain, radiating to right upper quadrant, without any weight loss or melena. Physical examination was unremarkable. Laboratory analysis was normal. Cross-sectional imaging of abdomen revealed a possible duodenal diverticulum. Esophagogastroduodenoscopy revealed 17mm, sessile polyp in second part of duodenum. Endoscopic ultrasound (EUS) showed a hypoechoic mass, measuring 17mm x 13mm, extending from mucosa to submucosa and having well-defined margins. EUS-guided fine needle aspiration (FNA) cytology was consistent with a neuroendocrine tumor with immunohistochemical stains positive for synaptophysin, chromogranin and CD56 antibodies. A decision was made to proceed with endoscopic mucosal resection (EMR) which revealed a hypoechoic intramural lesion, appearing to originate from submucosa, overlaid by focal ulcerating flattened duodenal mucosa. The pathology was remarkable for variable admixture of bundles of spindle cells, clusters of ganglion cells and epithelial cells. Immunohistochemical stains showed positive S100 protein in the spindle cells; the epithelioid cells were positive for synaptophysin and CD56 consistent with neuroendocrine differentiation; and the ganglion cells positive for calretinin. Gangliocytic paragangliomas, first reported by Dahl et al. in 1957, is a peculiar neuroendocrine tumor thought to be derived from neural crest with 88% reported lesions located in the second part of duodenum. These tumors are benign and consist of variable admixture of spindle cells, epithelioid cells, and ganglion cells. Rare malignant cases have been reported with regional lymph node metastasis. The epithelioid component was found to be present in the patients with lymph node metastasis; the causal relationship of which is unclear. Due to the submucosal location of the tumor, diagnosis is difficult on endoscopic biopsy which emphasizes the role of EMR in the diagnosis. As most of these tumors are benign and non-functional, EMR is therefore the treatment of choice especially in cases in which the tumor may be removed in its entirety with negative margins.Figure: A 17mm x 13mm, hypoechoic intramural lesion, appearing to originate from submucosa.Figure: Duodenal mass showing variable admixture of ganglion cells, spindle cells, and epithelioid cells (arrow shows ganglion cell). H&E X 100.Figure: Well-controlled immunostain with antibody to synaptophysin shows strong positivity for epithelioid cells. Synaptophysin X 100.

Successful Endoscopic Resection of a Rare Minor Ampullary Duodenal Gangliocytic Paraganglioma: A Case Report

Duodenal gangliocytic paragangliomas (DGP) are extremely rare neuroendocrine tumors. We present a case of a successful endoscopic resection of an incidental DGP. A 61-year-old Caucasian male with a history of cholecystectomy, iron deficiency anemia and GERD was incidentally found to have a 1.3cm periampullary duodenal polyp without any lymphadenopathy on a routine CT scan. The findings were confirmed with an abdominal MRI. He denied abdominal pain, early satiety, nausea, diarrhea, constipation, flushing, wheezing, weight loss, melena or any family history of gastrointestinal malignancies. An EUS examination showed markedly enlarged minor papilla with a hypoechoic mass and intact muscularis propria. A prominent pancreatic duct (PD) was also visualized. The EUS was followed by an ERCP to resect the polyp and a 5Fx4cm stent was placed in the PD due to high suspicion of pancreatic divisum. The specimen was a tan-colored, well-circumscribed 1.3x0.8x1cm soft, polypoid mass. Histologically, it was mostly a submucosal mass with a focal mucosal component. It exhibited a triple cellular differentiation with the epithelioid tumor cells arranged in nests along with occasional ganglion-like cells and surrounding scant spindle cells without atypia. The margins were clean. The epithelioid cells stained strongly positive for synaptophysin and chromogranin, and weakly positive for keratin. They were negative for S100, gastrin and somatostatin. The spindle cells stained positive for S100, synaptophysin and were negative for keratin. The mitotic active was low with a Mib-1 proliferative index of 3%. A 6-month follow up EGD with minor ampullary biopsy showed no signs of dysplasia or malignancy. DGPs are extremely rare and non-functional neuroendocrine tumors. They are twice more prevalent in males and usually found in the 6th to 7th decades of life. They are mostly benign tumors with excellent prognosis post resection. However, there have been about 20 case reports with lymph node metastasis and 1 report of fatal metastatic DGP. Traditionally, pancreaticoduodenectomy has been the treatment of choice when lymph nodes are involved. However, endoscopic resection, as in this case, remains a safe alternative for a localized DGP. In the lack of official guidelines, more studies are required to understand the nature of the disease, optimal treatment and follow up duration.Figure: Duodenal Gangliocytic Paraganglioma, ultrasound view.Figure: Duodenal Gangliocytic Paraganlioma, endoscopic view.Figure: The ampulla post resection.

神経内分泌腫瘍との鑑別が困難であったgangliocytic paragangliomaの1例

An upper gastrointestinal endoscopy showed a submucosal tumor of the papilla of Vater for a 38 year-old woman. Endoscopic ultrasonography (EUS) showed a mixed echoic mass (12mm) in the submucosal layer of papilla of Vater and showed no remarkable findings in the common bile duct and the main pancreatic duct. Endoscopic biopsy was performed, but pathologic findings showed normal duodenal mucosa. Abdominal computed tomography showed a well-enhanced tumor in the papilla of Vater. These findings led us to suspect a neuroendocrine tumor or gangliocytic paraganglioma. EUS-FNA was not performed because of high level of catecholamine and a transduodenal extirpation of the tumor was performed. The yellowish tumor was located in the duodenal submucosal layer. We identified three components in the tumor : epithelioid cells, ganglion-like cells, and spindle cells. The tumor was finally diagnosed as a gangliocytic paraganglioma of the duodenum according to the histological findings. Gangliocytic paraganglioma is a rare disease in the duodenum. Therefore, we report a case of gangliocytic paraganglioma with a review of the literature.