Introduction

Ganglioneuroma is a benign tumor derived from neural crest cells, typically found along the sympathetic nervous system, with common locations including the mediastinum, adrenal gland, and the retroperitoneum. Retroperitoneal and mediastinal ganglioneuromas are typically seen in the pediatric population, while adrenal ganglioneuromas tend to occur in slightly older individuals, around 35-40 years of age.[1] Pancreatic localization of ganglioneuromas is rare, with only a few case reports documented in the literature.[2] They pose a significant diagnostic challenge due to the complexity of the procedure, lack of specific radiological features, and typically poor cellular yield on fine needle aspiration cytology (FNAC), owing to the fibrous nature of the lesion. We present a case of pancreatic ganglioneuroma, initially detected on radiological imaging as a solid-cystic lesion with differentials of lymphangioma or mucinous cystadenoma. However, following surgical resection and histopathological examination, the final diagnosis was confirmed as ganglioneuroma.

Case history

A 65-year-old woman presented with a one-year history of abdominal discomfort. On physical examination, her vital signs were normal, and the abdomen was soft and non-distended, with no tenderness. Laboratory tests revealed Carcinoembryonic antigen (CEA), CA 19-9, liver function tests were within normal limits. Raised CA 19-9 levels in the cyst fluid was observed.

Abdominal and pelvic CT with intravenous and oral contrast revealed a large well-defined hypodense lesion, showing no significant post contrast enhancement, noted in the retroperitoneal region on the right, measuring 2.6 x 6.3 x 5.4 cm, corresponding to L1/L2 vertebral level with the head of the pancreas was noted to be wrapping around the lesion. (Figure 1 A and B). Endosonography showed a large hypoechoic lesion in retroperitoneum predominantly solid with few cystic components. The preoperative diagnosis in our case was cystic neoplasm of the pancreas. FNAC was performed, revealing strips of epithelial cells with mucin and goblet cells. Based on these findings and the cystic appearance noted on endosonography, the lesion was diagnosed as a possible mucinous cystic neoplasm and histopathology was requested for accurate diagnosis. The surgical plan was enucleation vs Whipple’s procedure. Intraoperatively, there was well defined tumor adherent to posterior part of head of pancreas and free from ampulla, pancreatic duct and all vasculatures. As there was maintained plane between the tumor and pancreas, it was decided to go ahead with enucleation and avoiding morbid Whipple’s procedure (Figure 1C and 1D).

Figure 1: A large well-defined hypodense lesion (avg. ~37 HU) located posterior aspect of Head of Pancreas, showing no significant post contrast enhancement measuring 2.6x6.3x5.4 cm A. arterial view. B. portal view. C. Intraoperatively tumour was adherent to posterior aspect of head of the pancreas D- specimen with intact capsule

Postoperatively, patient developed pancreatic fistula, which was managed conservatively by keeping drain for 3 weeks. Gross examination of the specimen revealed a predominantly solid mass with a few cystic areas, measuring 6x5x2.5 cm and covered by serosa. Adjacent normal pancreatic tissue was identified. The lesion was well-circumscribed, firm, glistening and white to yellow in colour (Figure 2A). Necrosis was not observed. Histopathological examination revealed a final diagnosis of ganglioneuroma (Figure 2B, C and D). Immunohistochemical staining demonstrated S100 positivity highlighting the Schwannian stroma, while synaptophysin marked ganglion cells (Figure 2E and F). The patient was discharged and is currently under follow-up, four months after discharge, with no complaints.

Figure 2: Gross specimen of ganglioneuroma showing predominantly solid lesion, yellowish with fibrous to myxoid areas (A), with pancreatic tissue (B). The lesion shows Schwann cells arranged as sheets admixed with ganglion cells (C). Image D shows ganglion cells. S100 highlights the Schwannian stroma with Schwann cells (E) with synaptophysin positivity in the ganglion cells

Discussion

Ganglioneuromas are composed of a mixture of Schwann cells and ganglion cells and are associated with the best prognosis among peripheral neuroblastic tumors. They are most commonly found in the thorax, followed by the adrenal gland.[1] Including our case, ten reported cases of pancreatic ganglioneuromas have been exclusively observed in females across all age groups. Ganglioneuromas are rare, benign tumors that can occur across a wide age range, from 3 to 86 years, with the majority of cases reported in individuals under 30 years of age. [2] Shaheen et al. documented a case in an 86-year-old patient, marking the upper limit of this age spectrum. In our case, we report a 65-year-old woman, emphasizing that these lesions, although rare, can also occur in older individuals. Notably, this is only the second case reported in the literature in a patient over the age of 60.[3]

The pancreatic origin of ganglioneuroma may arise from peripancreatic nerves, with subsequent infiltration into the pancreas, rather than originating from within the pancreas itself. [2,4] These tumors are typically asymptomatic, often detected incidentally, or present with mild, non-specific symptoms such as abdominal pain, back pain, or vomiting due to compression of surrounding structures.[1]

The radiological findings of pancreatic ganglioneuroma are non-specific, with CT typically showing a low-attenuation mass and poor enhancement on contrast-enhanced CT. [2,5] It is important to note that the lesion may mimic as a cyst radiologically, which could result in misdiagnosis as a cystic neoplasm of the pancreas, as in our case. [6] A core needle biopsy can be helpful for preoperative diagnosis, as it allows usage of immunohistochemistry (IHC) to aid in confirming the diagnosis. Ultrasound-guided FNAC is often less effective because of the fibrous nature of the lesion and its low cellularity, which can lead to a non-diagnostic aspirate or potential misdiagnosis. However, accurate diagnosis can only be made after resection. [7]

On gross examination, lesions typically appear as solid, well-circumscribed masses. Histopathological examination shows a predominance of Schwann cells admixed with ganglion cells which are dispersed singly or clustered. Lymphoid aggregates can be seen, which must be differentiated by neuroblasts, using either IHC CD45 or synaptophysin.[1]

Surgical excision of the lesion with adequate margins remains the cornerstone of treatment.[2] Despite the proximity to vital structures, the lesion generally has an excellent prognosis, even if complete removal is not achieved. Hence, authors recommend enucleation unless the tumor infiltrating pancreatic parenchyma. The Table 1 below summarises the pancreatic ganglioneuroma cases reported in the literature. [2-10]

In conclusion, pancreatic ganglioneuromas are extremely rare and pose significant diagnostic challenges owing to their non-specific clinical presentation, radiological findings, and low cellular yield on FNAC. Although, cytology can be helpful, accurate diagnosis typically requires surgical excision and thorough histopathological examination. Awareness of this rare entity is crucial to avoid misdiagnosis, particularly with cystic neoplasms, and to ensure appropriate management and patient care.

References

1. Alaggio R, Hill DA, Jacques TS et al. WHO Classification of Tumors: Pediatric Tumors. Lyon, France: IARC; 2021
2. Mazzola M, Bertoglio C, Achilli P et al. Pancreatic ganglioneuroma: a rare entity with a difficult
   approach: a case report and systematic review. Dig Med Res 2019;2:35
3. Shaheen AA, Gill I, Edhi AI, Amin M, Cappell MS. Pancreatic Ganglioneuroma Presenting in an Octogenarian. ACG Case Rep J. 2021 Mar 19;8(3):e00546. doi: 10.14309/crj.0000000000000546.
4. Poves I, Burdío F, Iglesias M, Martínez-Serrano Mde L, Aguilar G, Grande L. Resection of the uncinate process of the pancreas due to a ganglioneuroma. World J Gastroenterol. 2009 Sep 14;15(34):4334-8. doi: 10.3748/wjg.15.4334.
5. Ikoma N, Santamaria-Barria JA, Wray C, Tsao K. Ganglioneuroma of the pancreas in a 4-year-old girl. BMJ Case Rep. 2016 Nov 14;2016:bcr2016217425. doi: 10.1136/bcr-2016-217425.
6. Christein JD, Kim AW, Golshan MA, Maxhimer J, Deziel DJ, Prinz RA. Central pancreatectomy for the resection of benign or low malignant potential neoplasms. World J Surg. 2003 May;27(5):595-8. doi: 10.1007/s00268-003-6848-4.
7. Yildirim O, Ozgen KH, Alkhatalin M, Elwakil M, Camurdan VB. Pancreatic ganglioneuroma in a young female. Rep Pract Oncol Radiother. 2022 Oct 31;27(5):929-930. doi: 10.5603/RPOR.a2022.0095.
8. Domanski HA. Fine-needle aspiration of ganglioneuroma. Diagn Cytopathol. 2005 Jun;32(6):363-6. doi: 10.1002/dc.20269.
9. Scandavini C, Valente R, Rangelova E et al. Pancreatectomies for pancreatic neoplasms in pediatric and adolescent age: A single institution experience. Pancreatology. 2018 Mar;18(2):204-207. doi: 10.1016/j.pan.2017.12.009.
10. Avila-Sanchez P, Barron-Cervantes NM, Martinez-Esteban A, Chan-Nuñez LC. Retroperitoneal Peripancreatic Ganglioneuroma Encasing the Celiac Trunk and Superior Mesenteric Artery. Cureus. 2024 Jan 16;16(1):e52405. doi: 10.7759/cureus.52405.