Case Report

A 53-year-old man with recurrent nephrolithiasis underwent abdominal CT, which revealed a small hypodense and hypoenhancing lesion in the pancreatic body. Magnetic resonance imaging demonstrated a new 18-mm lesion in the mid-pancreas, with a partially cystic appearance and subtle enhancement of the wall and posterior component. There was no pancreatic duct dilatation or suspicious diffusion restriction.

Endoscopic ultrasound (EUS) showed a 16.1 × 13.4 mm lobulated lesion in the pancreatic isthmus/body, well-defined margins. The lesion had a complex cystic appearance, with a prominent hyperechoic intracystic component occupying more than half of its lumen and a thickened, echogenic wall (Figure 1). No communication with the main pancreatic duct was identified, and the pancreatic duct had normal calibre and morphology. The remaining examination was unremarkable.

Figure 1. Endoscopic ultrasound showing a well-defined lobulated lesion in the pancreatic isthmus/body, measuring 16.1 × 13.4 mm, with a complex cystic appearance, a prominent hyperechoic intraluminal component and a thickened, echogenic wall.

 

EUS-guided fine-needle biopsy (EUS-FNB) was performed using a 22-gauge needle. Tissue was obtained for histology and cyst fluid was aspirated for biochemical analysis (Figure 2). Cyst fluid glucose was 113 mg/dL, CEA 3.6 ng/mL and amylase 1619 U/L.

Figure 2. Endoscopic ultrasound-guided fine-needle biopsy of the pancreatic lesion using a 22G needle.

What is the most likely diagnosis?

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Histological examination showed a well-differentiated neuroendocrine neoplasm, with diffuse expression of CK8/18, synaptophysin and chromogranin. β-catenin showed membranous and cytoplasmic expression without nuclear staining, supporting the diagnosis of pancreatic neuroendocrine tumor (PanNET) and excluding a solid pseudopapillary neoplasm. The Ki-67 index was 4.8%, consistent with a (PanNET), G2 in this sample (Figure 3). ⁶⁸Ga-DOTA-TOC PET/CT showed intense somatostatin receptor expression in the pancreatic lesion, without nodal or distant disease. The patient underwent laparoscopic distal pancreatectomy. Final pathology confirmed a well-differentiated PanNET, G1, measuring 1.5 cm, pT1N0R0, with a Ki-67 index of 1.7%.

Figure 3. Histological examination showed fragments of a solid neoplasm composed of cells with round to oval nuclei and finely granular “salt-and-pepper” chromatin. No necrosis or mitotic figures were observed [A] (H&E, 400×). Immunohistochemistry showed expression of CK8/18 in neoplastic cells [B] (400×), as well as neuroendocrine markers: synaptophysin [C] (400×) and chromogranin [D] (400×). Cytoplasmic and membranous expression of β-catenin was identified [E] (400×). The Ki-67 proliferative index was estimated at 4.8% in the hotspot area [F] (400×).

 

Discussion

Approximately 13–17% of pancreatic neuroendocrine tumours exhibit cystic change, although reported prevalence varies between series. These lesions may closely mimic true pancreatic cystic neoplasms. Cyst formation is thought to result from central ischaemia, necrosis or intratumoural haemorrhage in slowly growing lesions. In the present case, the apparent cystic morphology likely reflected cystic degeneration within an otherwise solid neuroendocrine tumour. ^1,2

The differential diagnosis includes branch-duct IPMN, mucinous cystic neoplasm, solid pseudopapillary neoplasm, pseudocyst, and cystic PanNET. In this patient, the absence of ductal communication, the low cyst fluid CEA concentration and the preserved intracystic glucose level made a mucinous cystic lesion less likely.^3,4 Although elevated, intracystic amylase is non-specific and may also occur in non-mucinous lesions; it should not be interpreted in isolation as evidence of ductal communication. This illustrates that cyst fluid analysis should be interpreted alongside morphology and histology rather than in isolation.

EUS identified a large echogenic intracystic component within a complex cystic lesion, an atypical feature of a simple mucinous cyst. EUS-guided biopsy provided core tissue for histology and immunohistochemistry, including β-catenin immunostaining, which supported the diagnosis and helped distinguish the lesion from a solid pseudopapillary neoplasm. In contrast to cyst fluid aspiration alone, EUS-FNB enabled architectural assessment and immunohistochemistry, allowing a definitive preoperative diagnosis.^3,5

The discrepancy between the biopsy Ki-67 (G2) and the surgical specimen (G1) reflects sampling variability in small biopsy fragments and reinforces the need to interpret proliferative indices within the overall clinical, imaging, and pathological context.⁶

In the present case, surgical resection was considered appropriate following multidisciplinary discussion, taking into account the preoperative diagnosis of PanNET, the initial suspicion of a pancreatic cystic neoplasm, and an individualized risk–benefit assessment.

This case illustrates that not every pancreatic cyst represents a true cystic neoplasm. Reliance on cross-sectional imaging alone could have misclassified the lesion as a pancreatic cystic neoplasm. EUS-guided tissue acquisition proved pivotal in establishing the correct preoperative diagnosis.

References

1. Caglià P, Cannizzaro MT, Tracia A, et al. Cystic pancreatic neuroendocrine tumors: To date a diagnostic challenge. Int J Surg. 2015;21 Suppl 1:S44–S49.
2. Kawamoto S, Johnson PT, Shi C, et al. Pancreatic neuroendocrine tumor with cystlike changes: evaluation with MDCT. AJR Am J Roentgenol. 2013;200(3):W283–W290.
3. European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. 2018;67(5):789–804.
4. Lopes CV, Machado RS, Vilaça AF, et al. Cyst fluid glucose: an alternative to carcinoembryonic antigen for pancreatic mucinous cysts. World J Gastroenterol. 2019;25(17):2271–2278.
5. Facciorusso A, Arvanitakis M, Crinò SF, et al. Endoscopic ultrasound-guided tissue sampling: European Society of Gastrointestinal Endoscopy (ESGE) Technical and Technology Review. 2025;57(4):390–418.
6. Tacelli M, Bina N, Crinò SF, Facciorusso A, Celsa C, Vanni AS, et al. Reliability of grading preoperative pancreatic neuroendocrine tumors on EUS specimens: a systematic review with meta-analysis of aggregate and individual data. Gastrointest Endosc. 2022;96(6):898–908.e23.

Authors

Rui Vieira^1,2, Joana Magalhães^1,2, Pedro Campelo^1,2, João Pacheco ³, José Cotter^1,2

¹ Gastroenterology Department, Unidade Local de Saúde do Alto Ave, Guimarães, Portugal

² Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

³ Department of Pathology, Unidade Local de Saúde do Alto Ave, Guimarães, Portugal;