Abstract
Duodenal neuroendocrine tumors are rare neoplasms arising from endocrine cells. Here we present a case of 32-year-old woman with Duodenal neuroendocrine tumors, report the imaging and contrast-enhanced Ultrasound (CEUS) features and review previous literatures of neuroendocrine tumors, which may be valuable for the differential diagnosis of duodenal neoplasms.
Background
Neuroendocrine neoplasms (NENs) are rare neoplasms that arise from the peripheral neuroendocrine system dispersed in various organs with neuroendocrine markers and capable of secreting bioactive amines and/or peptide hormones [1]. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) can produce metabolites of 5-hydroxytryptamine (5-HT) or polypeptide hormones, such as glucagon, insulin or gastrin, etc. According to whether the tumor secretes hormone which cause clinical symptoms, GEP-NENs are clinically categorized as either non-functional or functional [2]. According to the WHO classification published in 2000, compared with their degree of cell differentiation, mitotic count and Ki-67 index, NENs can be categorised into well-differentiated neuroendocrine tumors (NET, G1 : 50–75% and G2 : 25–50%) and poorly differentiated neuroendocrine carcinoma (NEC, G3:≤3%) [3–5]. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) account for 65–75% of NETs and 1.2–1.5% of digestive system tumors [6].
Duodenal neuroendocrine neoplasms (D-NENs) are relatively rare, only accounts for 2–3% of the NETs and 3.4–11.9% of duodenal tumors [7]. D-NETs are slightly more common in males than in females [8, 9].
Case presentation
A 32-year-old female was admitted to our hospital with a complaint of nausea more than 10 years. Laboratory analysis displayed negative results of tumor markers, including AFP, CEA, CA19-9, CA125 and NSE. The liver and kidney function test value were in normal range.
The patient fasted for more than 8 h and underwent conventional abdominal ultrasound for routine examination. An experienced examiner performed the ultrasound scanning with Aplio 500 ultrasound system (Canon Healthcare, Japan; PVT-375BT, 1–6 MHz). A heterogeneous lesion with size of 4.0×3.2×3.5 cm3 was detected posterior the pancreatic head on gray-scale ultrasound. Color Doppler ultrasound showed abundant linear blood flow signals in and around the lesion (Fig. 1).
In the CEUS, low-acoustic power modes were used at a mechanical index (MI) ranging from 0.05 to 0.10 to avoid early microbubble destruction [10]. The patient received an intravenous 2.4 mL bolus injection of SonoVue (SF6, Bracco, Milan, Italy), followed by a flush of 5 mL saline and asked to hold breath as long as possible. A timer was activated after injection. Perfusion of the lesion and adjacent pancreas parenchyma were continuously recorded on the hard disk for 5 minutes. The lesion was enhanced at the beginning of arterial phase from periphery to the center, with hyper and homogeneous enhancement compared with peripheral parenchyma (Fig. 2). The lesion was considered as a pancreatic neuroendocrine tumor or other retroperitoneal tumor.
Gray-scale ultrasound revealed heterogeneous hypo-echoic mass with definite border (a). The color Doppler ultrasound showed abundant linear blood flow signals in and around the lesion (b).
CEUS showed peripheral with quick centripetal hyper-enhancement in the arterial phase, intense homogeneous enhancement at peak; hyper-enhancement compared with peripheral parenchyma (no wash-out) in the venous phase. T: tumor; PAN: pancreas.
The Aquilion 64-slice helical Computed tomography (CT) machine (Tokyo, Japan) was used for CT examination. The imaging settings for CT examination were 0.5 mm×64 mm collimation, 120 kV, 150–200 mAs. The standard dual-phase scanning procedure was used. 50–100 ml (1.5 ml/kg) of nonionic iodinated contrast material (Ultravist, Schering, Berlin, Germany) was administered via antecubital vein by power injection at a rate of 4 ml/s. The arterial phase sequence was obtained at 25–32 s after contrast material administration, followed by a portal venous phase sequence beginning at 60 s after contrast infusion. Pancreatic enhanced CT revealed a soft tissue lesion in retroperitoneal area, with heterogeneous intense and the lesion was uneven hyper-enhanced in the arterial phase, then wash-out during venous phase (Fig. 3), which was considered as paraganglioma or duodenal stromal tumor in retroperitoneal area.
Then the patient diagnosed as a pancreatic neuroendocrine tumor was transferred for surgery. Intraoperative examination revealed that the tumor was located between the external wall of the descending duodenum and the pancreas, with no signs of invasion to other organs or metastatic lymph nodes. Therefore, the mass was completely excised. Histological examination revealed that the neoplastic cell atypia was not obvious and small nucleoli are present. The histological examination also revealed that the tumor invaded the duodenal wall. The resection peripheral vessels and lymph nodes were not infiltrated. Immunohistochemical analysis showed that neoplastic cells were positive for ki67 (2%), chromogranin A (CgA), synaptophysin (syn) and SSTR2 (Fig. 4). The final pathological diagnosis was a duodenal neuroendocrine tumor (NET, G2).
Contrast-enhanced CT revealed a soft tissue lesion with definite border (a). intense heterogeneous hyper-enhancement in the arterial phase (b) and wash-out during venous phases (c, d).
Histological examination revealed that the neoplastic cell atypia was not obvious and small nucleoli are present (hematoxylin-eosin staining, a, 100× and b, 200×). Immunohistochemical analysis showed that neoplastic cells were positive for ki67 (2%; c, 100×), chromogranin A, synaptophysin and SSTR2 (d-f, 100×).
D-NETs are neoplasms of enterochromaffin cell origin. These cells display neurosecretory capacity that secrete 5-HT, histamine and bradykinin, etc, and may result in carcinoid syndrome, which may be manifested by skin flush, diarrhea, dyspnea and cardiovascular abnormalities. As the condition is insidious and advances gradually, patients were discovered by gastroscopy due to dyspepsia [11].
D-NETs are mainly located in the first or second part of the duodenum [8, 9], which consistent with the distribution characteristics of neuroendocrine cells. Most of masses were in intraluminal or intestinal wall, and a few of them were outside. Mass in this case revealed in the pancreatic uncinate process on ultrasound but in retroperitoneal on CT-enhanced. The tumor was located between the external wall of the descending duodenum and the pancreas during intraoperative examination.
The exophytic mass in the descending part of duodenum is easily misdiagnosed as pancreatic or retroperitoneal neoplasm because of the surrounding anatomical structures and not easy to be located. We can observe the synchronous motion of the mass and duodenum by drinking water, which is significantly useful to clinical auxiliary diagnosis. In this case, CEUS could not exactly distinguish the tumor location between posterior pancreas and duodenum. In comparison, enhanced CT scanning has broader vision and can display more clearly the adjacent anatomy relationship of mass. In a systematic review including 22 studies, 68Ga-DOTA-peptides PET/CT had an excellent diagnostic accuracy and can provides precise information of the location, with a sensitivity and specificity of 93 and 96% [12, 13]. PET/CT is the gold standard functional imaging method for studying well-differentiated NENs in Europe, which has been included in the European guidelines [14]. CEUS could be helpful in combination with PET/CT for better location of a NET.
Functional NENs have abundant blood supply. The lesions are homogeneous isodensity on CT and show obvious enhancement during the arterial phase, gradually weakened during the venous phase, but also remains significantly enhanced. The display of NENs on MRI are moderate or intense enhancement in the early arterial phase, which characterized by homogeneous, ring or diffuse hetergeneous [15]. The imaging feature of this lesion were consistent with neuroendocrine tumors. CEUS demonstrated the high perfusion in the tumor and appeared as a sustained high enhancement which was a typical sign of neuroendocrine tumor. Moreover, CEUS can detect hypervascular metastases from NENs to lymph nodes and liver (95%). Heterogeneous lymph node enhancement with focal filling defect is present in metastatic invasive lymph nodes, while most benign lymph nodes show homogeneous enhancement [16].
This case needs to be differentiated from duodenal stromal tumor, duodenal paraganglioma and mass located in pancreas and retroperitoneum in ultrasound. (1) Duodenal stromal tumors on ultrasound are often characterized by a round hypoechoic mass, which is rich in flow signal. Most of them have extravasive swelling and closely related to the duodenal wall. CEUS often shows slight or moderate peripheral enhancement. (2) Duodenal paragangliomas are intense enhancement during the middle of arterial phase and without wash-out during venous phases. Clinically, gastrointestinal bleeding and obstructive jaundice are often the main manifestations. (3) Pancreatic NENs also show intense enhancement in early arterial phase on ultrasound, and CEUS is characterized by obvious hyper-enhancement during the arterial and without wash-out during venous phase. The key to identify is that pancreatic tail and body could be predilection site of pancreatic NEN. (4) The position of the retroperitoneal mass is fixed and away from the abdominal wall. The mass has a slight movement with the change of body position and respiratory activity.
In summary, D-NETs are characterized by abundant blood supply. Imaging features provide useful information regarding D-NETs location, density, enhancement pattern and metastasis. Each imaging method has its own advantages and limitations. CEUS can improve the specificity of US in differential diagnosis by highlighting dynamic microvascular characteristics. However, It is difficult for transabdominal US to visualize all anatomical position, furthermore intestinal peristalsis and luminal air will impair image quality. CEUS is not a specific imaging method for NETs. Therefore, the optimal combination may increase the success of diagnosis [17]. These features are helpful to increase the diagnostic accuracy, but a definitive diagnosis is usually established by histopathological evaluation and immunohistochemistry. For the patients who have localized tumors or limited metastatic disease, surgical excision is the preferred method of treatment for achieving a potentially curative effect and prolonging 5-year survival up to 90% [18].
Funding
This study was supported by Shanghai Municipal Key Clinical Specialty (shslczdzk03501 to Wen-ping Wang), Fujian Province for Health and Science Research Project (2019-ZQNB-39 to Hai-xia Yuan) and a program from Xiamen Science and Technology Plan (3502Z20184002 to Hai-xia Yuan).