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Year : 2018  |  Volume : 61  |  Issue : 4  |  Page : 580-582
Duodenal gangliocytic paraganglioma: A rare cause for gastrointestinal polyp

1 Department of Histopathology, Sir Ganga Ram Hospital, New Delhi, India
2 Institute of Liver Gastroenterology and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India

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Date of Web Publication10-Oct-2018


Duodenal gangliocytic paragangliomas are rare neoplasms often arising in the duodenum in close proximity to the ampulla of Vater. These neoplasms are considered to have a benign behavior with lymph node metastases being a rare phenomenon and distant metastases even more so. Although a standardized treatment has not been determined, a margin-free tumor resection seems to be the best treatment modality. We report herein the case of a 36-year-old female who presented with abdominal pain and was found to have a polyp in the second part of duodenum which was excised endoscopically. Histopathology and immunohistochemistry revealed characteristic features of this rare tumor.

Keywords: Differential diagnosis, duodenal polyp, gangliocytic paraganglioma

How to cite this article:
Bakshi N, Rao S, Dhawan S, Singla V. Duodenal gangliocytic paraganglioma: A rare cause for gastrointestinal polyp. Indian J Pathol Microbiol 2018;61:580-2

How to cite this URL:
Bakshi N, Rao S, Dhawan S, Singla V. Duodenal gangliocytic paraganglioma: A rare cause for gastrointestinal polyp. Indian J Pathol Microbiol [serial online] 2018 [cited 2023 Mar 27];61:580-2. Available from:

   Introduction Top

Gangliocytic paraganglioma is a rare, poorly understood tumor that most commonly involves the second part of the duodenum.[1] Upper gastrointestinal (GI) bleeding and abdominal pain are common presenting manifestations.[1],[2] In some cases, this tumor presents asymptomatically and is detected incidentally through diagnostic studies or autopsy.[2] Generally, this tumor has a benign clinical course, although rarely, it may recur or metastasize to regional lymph nodes.[1],[3] Awareness of this rare entity is vital to avoid misdiagnosis and facilitate appropriate treatment.

   Case Report Top

A 36-year-old female patient presented to the gastroenterology outpatient department with complaints of recurrent abdominal pain for the past 3 months. The pain was localized to the right upper abdomen without radiating to the back. The patient was evaluated using upper GI endoscopy (Olympus GIF-H180 Gurgaon, India) which revealed a polypoidal mass in the second part of duodenum, near the ampulla of Vater [Figure 1]. No regional lymphadenopathy was identified preoperatively. A provisional diagnosis of carcinoid tumor was made; the mass was endoscopically excised and sent for histopathology.
Figure 1: Endoscopy image revealing a submucosal polypoidal lesion in the second part of duodenum

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On gross examination, the tumor was polypoidal and measured 1.5 cm × 1 cm. Overlying mucosa was stretched out and focally ulcerated. The cut surface was solid and homogeneously gray-white. Microscopic examination revealed a nonencapsulated, well-circumscribed tumor in the duodenal submucosa [Figure 2]a. The tumor had triphasic morphology with bland-looking spindle cells arranged in intersecting fascicles forming the predominant component [Figure 2]b. Interspersed nests and loose clusters of epithelioid cells having oval nuclei with stippled chromatin, inconspicuous nucleoli, and a moderate amount of eosinophilic to clear cytoplasm were noted [Figure 2]c. In addition, few singly scattered large cells having eccentrically placed vesicular nuclei, prominent nucleoli, and abundant amphophilic cytoplasm were noted [Figure 2]d. Mitotic activity was low in all three tumor components; no necrosis or cellular atypia was seen. The lesion was limited to the duodenal submucosa and the resected margin was free.
Figure 2: A panel of photomicrographs revealing: (a) Well-circumscribed tumor in the duodenal submucosa (H and E, ×4). (b) Bland spindle cells in intersecting fascicles forming the predominant component (H and E, ×10). (c) Interspersed nests of epithelioid cells having oval nuclei with stippled chromatin, and pale eosinophilic to clear cytoplasm (H and E, ×20). (d) Few singly scattered ganglion cells (arrow) having eccentrically placed nuclei, prominent nucleoli, and abundant amphophilic cytoplasm (H and E, ×40)

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On immunohistochemistry (IHC), the spindle cells were diffusely positive for Vimentin and S-100 and were negative for cytokeratin (AE1/AE3) as well as Synaptophysin [Figure 3]a. The epithelioid cell component revealed dual positivity for cytokeratin and synaptophysin, confirming its neuroendocrine nature [Figure 3]b. The large cells with eccentric nuclei were immunoreactive only for synaptophysin and were identified as ganglion cells [Figure 3]c. CD117, DOG1, and SMA were negative ruling out other differentials. Based on the morphologic and IHC features, a final diagnosis of gangliocytic paraganglioma of the duodenum was rendered. The patient is under follow-up and is currently doing well.
Figure 3: A panel of immunohistochemistry photomicrographs revealing: (a) Diffuse immunolabeling of the spindle cell component with S100 (×10). (b and c) Dual positivity for cytokeratin (b)and synaptophysin (c) in the epithelioid cell component with selective immunolabeling of ganglion cells for synaptophysin (×20 and ×10)

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   Discussion Top

Gangliocytic paraganglioma was first described by Dahl et al. in 1957.[4] It is a rare neuroendocrine tumor (NET), with only about 200 cases reported since, most of which have been in the form of single case reports by various authors.[2],[3],[5] In 2010, Okubo et al. comprehensively analyzed 192 reported cases of gangliocytic paraganglioma retrieved from PubMed and Igaku Chuo Zasshi databases.[1] Based on available literature, this tumor has a slight male predominance and most commonly affects individuals in their fifth decade of life, though affected age can range from 15 to 84 years.[1],[3] The second part of duodenum is the most commonly affected site, with about 90% of tumors arising near the ampulla of Vater.[1],[3],[6] Although the exact origin of this tumor remains unclear, two theories have been proposed to explain its development. The first suggests an ectodermal origin from pluripotent cells, which are derived from the neural crest and are found in the glands of Lieberkühn or the celiac ganglia during fetal development. The second proposes that these tumors originate from endodermally derived epithelial cells in the ventral primordium of the pancreas and neuroectodermal ganglion or spindle cells.[7]

This tumor accounts for 6%–9% of duodenal GI NETs and is the third most frequent histopathologic type after gastrinomas and somatostatinomas.[8] Symptomatic patients may present with GI bleeding (45.1%) due to mucosal ulceration, abdominal pain (42.8%), anemia (14.5%), or rarely biliary obstruction.[1],[2] The tumor usually arises as a single mass, and it typically presents as a polypoid, pedunculated, or sessile lesion.[1] Due to the submucosal location of this tumor, preoperative pathologic diagnosis is difficult based on endoscopic biopsy alone with a diagnostic rate of only 11.4%.[1] Rarely, other sites throughout the upper to mid GIT as well as extraintestinal sites such as the lung, lower spinal cord, and respiratory tract may be involved.[1],[3],[5]

Histopathologically, the triphasic appearance with intimate admixture of spindle cells, epithelioid cells, and ganglion cells is characteristic of this tumor and essentially rules out other possibilities. However, diagnosis may be missed if all three elements are not carefully searched for since they may not be equally present in any given lesion. In our case also, though the spindle and epithelioid cell components were readily identified, only a few singly scattered ganglion cells were present making it difficult to rule out other possible differentials. Possible differential diagnoses to be considered in such a scenario are gastrointestinal stromal tumor (GIST), paraganglioma, ganglioneuroma, carcinoid tumor, and well-differentiated neuroendocrine carcinoma.[6],[8] Ganglioneuroma lacks the epithelioid component which is usually prominent in gangliocytic paraganglioma. Paraganglioma lacks ganglion cells and is exceedingly rare in the duodenum. NET does not show the ganglion cell and spindle cell components. IHC may be a valuable aid in such a setting. Although IHC analysis of these tumors may show reactivity for various makers such as neuron-specific enolase, synaptophysin, pancreatic polypeptide, somatostatin, chromogranin-A, cytokeratin, serotonin, myelin basic protein, neurofilament protein, and S-100 protein, diffuse immunolabeling of the spindle cell component with S100, labeling of both epithelioid cells and ganglion cells with synaptophysin, and selective staining of the epithelioid cells with Cytokeratin help to clinch the diagnosis.[1]

Tumor behavior is usually benign with regional lymph node metastasis occurring in only about 5%–7% of cases.[1],[3] However, few authors have reported bone and liver metastasis.[9],[10] Li et al. reported a single case with multifocal distant (liver and pelvic cavity) metastasis who succumbed to the disease despite receiving both chemotherapy and radiotherapy after surgical resection.[10] These experiences suggest that it would be unwise to consider this tumor as a purely benign entity and its biologic behavior may be redefined in the future.[9],[10] Li et al. recommended use of the term “Tumor with uncertain malignant potential,” especially for tumors with nodal and/or distant metastasis.[10]

Younger age group, female gender, and tumor spread beyond the submucosa have been described as risk factors for lymph node metastasis.[1] Our case was a middle-aged female patient, the tumor was limited to the submucosa, and no regional lymphadenopathy was identified preoperatively. The patient is subsequently under follow-up and is doing well.

There is no true consensus on a standard management protocol, in part due to the rarity of the lesion. However, many authors agree that endoscopic resection is a safe and effective treatment option with tumors as large as 5 cm resected successfully using this method.[3],[5],[10] In the case of a periampullary or a large lesion, however, endoscopic resection may be difficult, and surgical resection of the lesion remains the only therapeutic option. For tumors with local lymph node metastasis, a more radical approach in the form of pancreaticoduodenectomy and lymph node dissection may be carried out. However, considering the rarity of nodal metastasis, such a radical approach may be avoided in most cases by utilizing preoperative imaging studies to rule out regional lymphadenopathy.[3],[6] Only limited experience with chemotherapy and radiation is available in metastatic disease, and these reports suggest that this tumor is unresponsive to conventional chemo and radiotherapy.[10] Therefore, in cases in which the tumor is resected with negative margins, it appears to be safe to embark on a course of surveillance and forego adjuvant therapy.[1],[9]

   Conclusion Top

Gangliocytic paraganglioma remains a poorly understood tumor due to its rarity despite being first described more than 60 years ago. Awareness among clinicians and pathologists alike, careful and complete evaluation with multidepartmental cooperation, and the use of IHC is vital in the accurate diagnosis of this rare neoplasm.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Okubo Y, Wakayama M, Nemoto T, Kitahara K, Nakayama H, Shibuya K, et al. Literature survey on epidemiology and pathology of gangliocytic paraganglioma. BMC Cancer 2011;11:187.  Back to cited text no. 1
Sharma S, Gaspar BL, Kumar P, Yadav TD, Vasishta RK. Gangliocytic paraganglioma with atypical immunohistochemical features presenting as extrahepatic biliary obstruction. Int J Surg Pathol 2015;23:561-6.  Back to cited text no. 2
Okubo Y, Yokose T, Tuchiya M, Mituda A, Wakayama M, Hasegawa C, et al. Duodenal gangliocytic paraganglioma showing lymph node metastasis: A rare case report. Diagn Pathol 2010;5:27.  Back to cited text no. 3
Dahl EV, Waugh JM, Dahlin DC. Gastrointestinal ganglioneuromas; brief review with report of a duodenal ganglioneuroma. Am J Pathol 1957;33:953-65.  Back to cited text no. 4
Scheithauer BW, Nora FE, LeChago J, Wick MR, Crawford BG, Weiland LH, et al. Duodenal gangliocytic paraganglioma. Clinicopathologic and immunocytochemical study of 11 cases. Am J Clin Pathol 1986;86:559-65.  Back to cited text no. 5
Hechtman JF, Harpaz N. Neurogenic polyps of the gastrointestinal tract: A clinicopathologic review with emphasis on differential diagnosis and syndromic associations. Arch Pathol Lab Med 2015;139:133-9.  Back to cited text no. 6
Perrone T, Sibley RK, Rosai J. Duodenal gangliocytic paraganglioma. An immunohistochemical and ultrastructural study and a hypothesis concerning its origin. Am J Surg Pathol 1985;9:31-41.  Back to cited text no. 7
Hoffmann KM, Furukawa M, Jensen RT. Duodenal neuroendocrine tumors: Classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 2005;19:675-97.  Back to cited text no. 8
Park HK, Han HS. Duodenal gangliocytic paraganglioma with lymph node metastasis. Arch Pathol Lab Med 2016;140:94-8.  Back to cited text no. 9
Li B, Li Y, Tian XY, Luo BN, Li Z. Malignant gangliocytic paraganglioma of the duodenum with distant metastases and a lethal course. World J Gastroenterol 2014;20:15454-61.  Back to cited text no. 10

Correspondence Address:
Seema Rao
Department of Histopathology, Sir Ganga Ram Hospital, Rajender Nagar, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_479_17

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