Groove pancreatitis due to periampullary gangliocytic paraganglioma with lymph node metastasis

Groove (paraduodenal) pancreatitis is a rare form of segmental pancreatitis affecting the ‘groove’ space located between the pancreatic head, duodenum, and common bile duct.^, The classic computed tomography (CT) scan or magnetic resonance imaging (MRI) feature consists of an ill-defined enhanced soft tissue mass extending between the pancreatic head and the duodenum.^, Thickening of the duodenal wall, dilatation of the pancreatic duct as well as common bile duct stricture can be seen. Therefore, clinically and radiologically, groove pancreatitis may be indistinguishable from malignancies (particularly pancreatic ductal adenocarcinoma and duodenal/periampullary adenocarcinoma), and many radiologists are unfamiliar with this entity.^, Given the inability to completely exclude malignancy, as well as symptoms (e.g., severe pain and pancreatic insufficiency) in long-standing groove pancreatitis, the vast majority of these patients ultimately undergo a Whipple procedure.

Gangliocytic paraganglioma is a rare, usually benign neoplasm composed of triphasic morphological elements including predominantly spindled to epithelioid neuroendocrine cells, spindled Schwannian cells, along with interspersed large ganglion-like cells. The majority of the tumour arises in the duodenum (in proximity to the major duodenal papilla of Vater), with rare cases reported in the jejunum or pylorus. The mean age of patients with gangliocytic paraganglioma is 53.5 years.^, Immunohistochemically, neuroendocrine cells are positive for synaptophysin, chromogranin, and cytokeratin; Schwannian cells are positive for S100 and SOX10; and ganglion-like cells are positive for neurofilament protein. Gangliocytic paraganglioma is considered a benign tumour in the majority of cases, although rarely it can metastasise to lymph node (11%) or liver (1%). Complete resection of the tumour by surgical or endoscopic means is the only definitive treatment with favourable long-term outcomes. Adjuvant chemotherapy and radiotherapy are unnecessary after complete excision.

A 55-year-old male with a past medical history significant for gastroesophageal reflux disease, hypertension, hyperlipidaemia, 20 pack-year smoking and at least 5 beers per day alcohol use, was noted to have a cystic lesion in the head of his pancreas approximately 2 years previously. He was given a radiographic diagnosis of side branch intraductal papillary mucinous neoplasm and 12 months follow-up with imaging was recommended. The patient did not follow-up with providers. He then developed several months of slowly progressive dysphagia, odynophagia, dyspepsia, high-volume emesis, abdominal pain, and 20 pounds unintentional weight loss. He denied jaundice, biliuria or acholic stools. He was evaluated by the gastroenterology team at our institution.

A CT scan revealed a heterogeneous low-attenuation mass at the level of the pancreatic head/uncinate process measuring approximately 4.1×3.6 cm (Fig. 1). This caused mass effect with probable invasion of the adjacent duodenum. The main pancreatic duct was dilated. There was no clear fat plane between the mass and the inferior vena cava posteriorly. An adjacent 1.4 cm lymph node was also noted anteriorly on imaging.

Laboratory examination showed elevated CEA (7.1 ng/mL; reference range 0–4.7 ng/mL), normal CA 19–9 (24 U/mL; 0–34 U/mL), elevated lipase (241 U/L; 13–60 U/L) and amylase (143 U/L; 28–100 U/L). An ultrasound-guided fine needle aspiration of the mass lesion was performed but was non-diagnostic. Overall, based on the clinical presentation as well as imaging findings, the clinical impression was pancreatic ductal adenocarcinoma which may have arisen from intraductal papillary mucinous neoplasm. The patient underwent pancreatoduodenectomy (Whipple procedure).

Macroscopically, the pancreatoduodenectomy specimen demonstrated a tan-white, ill-defined, firm, fibrous lesion at the head of the pancreas measuring 4.2×4.0×3.5 cm. The lesion partially obstructed the pancreatic duct causing distal pancreatic duct dilatation. A 1.1×1.1×0.7 cm tan, firm, well-circumscribed nodular mass was noted adjacent to and compressing the ampulla of Vater (Fig. 1). Histologically, the large pancreatic head lesion demonstrated marked fibrosis, frequent pancreatic duct cystic dilatation with inspissated secretions, acute inflammation, abscess formation and granulation tissue (Fig. 2). The findings were consistent with groove pancreatitis. There was no evidence of branch-duct intraductal papillary mucinous neoplasm or malignancy in the pancreas parenchyma.

The 1.1 cm periampullary mass demonstrated a low-grade well demarcated neoplasm. The tumour consisted of triphasic morphological elements including predominantly spindled to epithelioid neuroendocrine cells, spindled Schwannian cells, along with interspersed ganglion-like large cells. Immunohistochemically, the neuroendocrine cells were positive for cytokeratin AE1/AE3, synaptophysin, and chromogranin. The ganglion-like cells and spindle cells were positive for S100 and neurofilament protein. Ki-67 proliferation index was approximately 2%. The histomorphology and immunoprofile were classical for a ganglicocytic paraganglioma (Fig. 2, Fig. 3). Metastatic ganglicocytic paraganglioma was identified in one of 26 lymph nodes (Fig. 2). The pathological Stage [American Joint Committee on Cancer (AJCC) 8th Edition] was pT2 N1. The tumour sat right at the ampulla, with associated Brunner gland hyperplasia, duodenal wall fibrosis, dense fibrosis and inflammatory cysts of the pancreatic head. The above findings suggested that the clinically noted cystic lesion in the head of the pancreas as well as groove pancreatitis were due to ganglicocytic paraganglioma-induced pancreatic duct obstruction. The patient recovered well from the surgery with no evidence of recurrence or metastasis 1.5 years later.

In conclusion, we report a case of groove pancreatitis as a primary manifestation of periampullary gangliocytic paraganglioma with lymph node metastasis mimicking pancreatic ductal adenocarcinoma. The suspicion for malignancy was further enhanced by a previous clinical diagnosis of intraductal papillary mucinous neoplasm that could have served as the precursor lesion for pancreatic ductal adenocarcinoma. While a definitive diagnosis of groove pancreatitis by imaging can be extraordinarily difficult, features such as fibrotic change, mass lesion limited to the ‘groove’ space, and presence of duodenal wall cysts, may provide diagnostic clues. In those cases where the imaging features are highly characteristic, the radiologist may be able to strongly suggest the diagnosis of groove pancreatitis, and major surgery such as Whipple procedure can potentially be avoided. It is also important to keep in mind that gangliocytic paraganglioma, as well as other periampullary tumours, can be a rare cause of groove pancreatitis that mimics malignancies. Around 11% of gangliocytic paragangliomas were found to have lymph node metastasis. Okubo et al. reported that tumour infiltrating into the submucosa and the presence of lymphovascular invasion are risk factors of disease progression/lymph node metastasis. Regardless, gangliocytic paraganglioma generally has an excellent prognosis after complete surgical or endoscopic removal. Cathcart et al. reviewed 31 cases of duodenal/periampullary gangliocytic paraganglioma with lymph node/distal metastasis, among which only one patient died of liver and pelvic metastases. Histologically and immunohistochemically, gangliocytic paraganglioma can be misdiagnosed as well-differentiated neuroendocrine tumour, which is associated with a poorer prognosis than gangliocytic paraganglioma. To avoid such misdiagnoses, it is important to understand the histological and immunohistochemical features of gangliocytic paraganglioma.