Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.

Keywords: PET; computed tomography; diagnosis; gastroenteropancreatic; magnetic resonance; neoplasms; neuroendocrine; radiology; somatostatin receptor imaging; ultrasound.

Figure 1

Sample size (A) of small bowel NEN with desmoplastic reaction (arrows in (A) and (B)), evaluated on CT (B) in portal phase of contrast study. In (C), arrow shows the intraluminal small tumor as an enhanced polypoid lesion.

Figure 2

The pancreatic NEN lesion at the tail is highlighted with an arrow. DWI at low and high b-values, respectively, in Subfigures (A,B), showing the restricted diffusion detecting the little lesion, typically characterized by 68Gallium uptaking in PET/CT (C) and high arterious enhancement at CT (D).

Figure 3

Arterious CT scan (A) demonstrating a hypodense lesion at pancreatic tail (arrow), which, at echoendoscopy, showed anechoic content (B) with hypervacularized thick walls at Doppler, and after a bolus of ultrasound contrast agent (C). The tumor was surgically removed and diagnosed as G1 NEN tumor with cystic appearance.

Figure 4

A pancreatic NEN tumor (arrow) was discovered as hypoechoic mass at ultrasound, showing high vascularization at CEUS (A) and CT (B). At MRI examination, the mass was not clearly defined with T2W fat-suppression sequence (C), while the restriction at diffusion imaging improved the definition of the mass (D).

Figure 5

MRI evaluation of liver NEN metastases. Contrast study ((A): arterial; (B): portal phase) show a single lesion (arrow), while, in DWI (C) and T2-W FS (D), more lesions were detected compared to (A,B).

Figure 6

Ileal NEN tumors shown with different endoluminal contrasts and in PET-CT exam. The hypervascularized tumors are clearly different from normal bowel walls due to being highlighted in relation to endoluminal hypodense and hyperosmolar contrast media. The same patients previously had a colon CT performed, showing a slight air distension of lumen with minimal wall thickening that did not improve the tumor evidence, as well as a later contrast-enhanced CT with oral hyperosmolar iodinated contrast, which improved the intestinal lumen visualization but strongly limited the enhancement of tumors. PET/CT-68Gallium showed the same highly uptaking lesions, with the highest sensitivity compared to others, but this last one is not routinely performed without neuroendocrine suspicion being specific for highly probable or known NEN tumors. (A) CT-enterography, (B) virtual colonoscopy, (C) CECT with oral contrast, and (D) PET-⁶⁸Ga.