Mesenteric changes in an ultrasound examination can facilitate the diagnosis of neuroendocrine tumors of the small intestine.

UNLABELLED: Neuroendocrine tumors make up an interesting pathology of a variable clinical picture, prognosis, localization, endocrine activity and degree of malignancy. AIM: The aim of this paper is to assess whether ultrasonography can be helpful in diagnosing neuroendocrine tumors in the small intestine by analyzing changes in the mesentery.
MATERIAL AND METHODS: From 1996 to 2013, we encountered 17 patients (9 women and 8 men at the mean age of 57) with a neuroendocrine tumor in the small intestine. The diagnosis was confirmed in all patients by pathomorphological examinations. All retrospectively analyzed patients (n =17) had an abdominal US examination conducted in accordance with the previously mentioned protocol.
RESULTS: Primary neuroendocrine tumors were visualized ultrasonography in 13 of 17 patients (76.5%). In the remaining 4 patients, tumors in the small bowel were diagnosed in CT enteroclysis (n = 3) and conventional enteroclysis (n = 1). Somatostatin receptor scintigraphy and CT enteroclysis supplemented the ultrasound result by providing information about the stage of the disease in 7 cases. In most of the 17 patients with a neuroendocrine tumor diagnosed by ultrasound (n = 11, 64.7%), changes in the mesentery were prevailing pathological signs that raised suspicion and, consequently, helped localize the primary lesion. The hypoechoic mesenteric lymph nodes were the greatest (9-18 mm), well-circumscribed, and the largest of them showed signs of vascularization. The size of hypoechoic lesions in the mesentery ranged from 25 to 53 mm. These lesions showed moderate blood flow. All of them were single, usually poorly circumscribed; two lesions showed slight calcifications.
CONCLUSIONS: In an abdominal US examination, 2/3 of patients with neuroendocrine tumors in the small bowel manifest secondary lesions in the mesentery which are easier to visualize than the primary focus. 30% of them are manifested as hypoechoic masses. The detection of such lesions should prompt the search for the primary focus in the small intestine.

Neuroendocrine tumors (NETs) make up an interesting pathology of a variable clinical picture, prognosis, localization, endocrine activity and degree of malignancy(. In the past decades, the detection of this neoplasm has increased considerably (from 300 to 500%)(. Another sign of this trend was an increase of the NET incidence rate from 1.09/100,000 in 1973 to 5.25/100,000 in 2004(. Moreover, another noteworthy phenomenon is the significant changes in the most common localization of these tumors in the alimentary tract. In 1950–1969, it was usually localized in the appendix whereas in 1973–1977, the most common localization was the small intestine(. The greatest analysis from 1973–2004, which included 35,825 patients with NETs, demonstrated that tumors in the gastrointestinal tract developed in: the rectum (34%), the small intestine (26%), the stomach (12%), the large bowel (8%), the duodenum (8%), the cecum (6%) and the appendix (6%)(. Their well-known morphological feature is a small size. These tumors are rarely larger than 2 cm, which makes them difficult to detect in imaging examinations. The clinical manifestation of NETs in the intestine is usually late. The typical signs are obstruction or intussusception, gastrointestinal bleeding, metastases in the liver or carcinoid syndrome(.

The aim of this paper is to assess whether ultrasonography can be helpful in diagnosing neuroendocrine tumors in the small intestine by analyzing secondary changes in the mesentery.

Material and methods

From 1996 to 2013, 17 patients (9 women and 8 men, aged 23–62, mean age 57) with a neuroendocrine tumor in the small intestine were subject to a retrospective analysis. Most of them reported non-specific gastrointestinal symptoms (13 of 17). In each case, NETs were confirmed in pathomorphological examinations. All patients (n =17) had an abdominal US examination conducted in accordance with the previously mentioned protocol(. Ultrasound examinations were conducted with the use of various systems using convex probes with the frequency of 2.5–5 MHz and linear probes with the frequency of 5–12 MHz. All abdominal regions were scanned thoroughly, including the available loops of the small intestine, the mesentery and the colon. All scans were performed by one person, a physician with 25-year experience in ultrasound imaging. This study was mainly focused on secondary lesions in the mesentery. Moreover, the examined group was diagnosed with the use of multiphasic computed tomography or CT enteroclysis (n = 16), somatostatin receptor scintigraphy (n = 11) and conventional enteroclysis (n = 2). Also, biochemical tests, including non-specific and specific markers helpful in NET diagnosis, were performed in each patient.

Results

The ultrasound examinations visualized foci of neuroendocrine tumors in 13 of 17 patients (76.5%). In the remaining 4 patients, tumors in the small bowel were localized in CT enteroclysis (n = 3) and conventional enteroclysis (n = 1). The localization was also confirmed by somatostatin receptor scintigraphy in 3 of 4 such patients. Somatostatin receptor scintigraphy and CT enteroclysis supplemented the ultrasound result by providing information about the stage of the disease in 7 cases. This concerned the number of involved mesenteric lymph nodes (n = 4), metastases to the lungs (n = 2) and to the ovary in one woman.

The examinations revealed single intramural nodules with the size of 15–35 mm in the small intestine of 17 patients. Secondary mesenteric changes, which were striking ultrasound signs of an existing pathology in 11 patients (64.7%), were analyzed in greater detail (Tab. 1). It should also be mentioned that the hypoechoic mesenteric lymph nodes were the largest (9–18 mm) and well-circumscribed (Fig. 1 and 2). In most cases, only single nodes were visible (n = 9), but two patients presented 2–3 pairs of lymph nodes – they were all localized in the vicinity of the primary lesion. A hypoechoic mass in the mesentery was detected in five patients (29.4%). Its size ranged from 25–53 mm and showed slight blood flow. All lesions were single, poorly circumscribed, and slight calcifications were detected in two cases (Fig. 3, 4, 5, 6 A and 6 B). Figures 7a and 7b illustrate a similar case: a NET focus (20 mm) in the terminal ileum and a hypoechoic mass (35 mm) in the mesentery. CT enteroclysis confirmed the presence of these lesions and additionally revealed slight enlargement of four mesenteric lymph nodes (Fig. 7 C and 7 D) and two slight metastatic foci in the lower field of the right lung (not shown in figures).

Tab. 1

Secondary mesenteric changes in 17 patients with small bowel NETs detected by ultrasonography

No.	Ultrasound sign	Number of patient (percentage)	No. of the figure
1	Hypoechoic mesenteric lymph nodes	11 (64.7)	1, 2
2	Hypoechoic mass in the mesentery	5 (29.4)	3, 4, 5, 6 A, B, 7 A, B, C, D
3	Wrinkled and thickened mesentery	2 (11.8)	8 A, B
4	Irregular thickening of the mesentery	1 (5.9)	9

Fig. 1

Metastatic lymph nodes (N) in the mesentery reflect the presence of a small intestinal carcinoid tumor (not shown in the figure)

Fig. 2

One view shows irregular infiltration of a carcinoid tumor of the terminal ileum (C) and a sentinel lymph node (N)

Fig. 3

Carcinoid tumor (12 mm) of the small bowel (not shown in the figure). In this case, an irregular hypoechoic and vascularized infiltration is visible in the mesentery

Fig. 4

An irregular hypoechoic mass in the mesentery is the only manifestation of a carcinoid tumor in the ileum (not shown in the figure)

Fig. 5

Two views of a hypoechoic mass (4 cm) in the mesentery of a 32-year-old patient with the body mass of 122 kg as the only ultrasound sign of a carcinoid tumor in the ileum

Fig. 6 A

A sizeable, partially calcified hypoechoic mass (M) in the mesentery is a prominent manifestation of a carcinoid tumor in the ileum (not shown in the figure)

Fig. 6 B

The same case. The vascularization of the lesion shown in a different view

Fig. 7 A

One view captures a carcinoid tumor in the ileum (C) and a hypoechoic mass in the mesentery, which is greater than the primary lesion

Fig. 7 B

The same patient. This view shows only the bean-shaped carcinoid tumor in the intestine, visualized with the use of a linear probe

Fig. 7 C

The same patient, but the lesions are visualized in CT enteroclysis. The tumor of the terminal ileum (C) is of an identical shape to that visualized by ultrasonography. Moreover, two affected mesenteric lymph nodes are visible

Fig. 7 D

The same patient. A different CT layer. It presents the mass (M) in the small intestine and two different affected mesenteric lymph nodes (n). Moreover, two metastatic foci were detected in the right lung (not shown here)

The wrinkled and thickened mesentery was hyperechoic (Fig. 8 A), and in one patient mesenteric retraction had caused small bowel obstruction (Fig. 8 B). In one patient, a NET was manifested by the heterogeneously thickened mesentery, in which a focal lesion was not visualized with certainty (Fig. 9). In five cases, the affected lymph nodes accompanied a hypoechoic mesenteric mass. Liver metastases were detected in 5 of 17 patients.

Fig. 8 A

Carcinoid tumor (2 cm) of the ileum with features of hyperemia and with the markedly hyperechoic mesentery

Fig. 8 B

The same patient. Dilated loops of the small intestine surrounding the thickened mesentery (M) indicate ileus

Fig. 9

Thickened mesentery shows lesions that are difficult to visualize. They are an ultrasound representation of a carcinoid tumor in the small intestine (not shown in the figure)

Discussion

Out of all NETs in the gastrointestinal tract, those in the small bowel are characterized by the greatest ability to metastasize, both locally and distantly(. This localization decides about the prognosis. Hari et al.( list the following 5-year survival rates depending on the localization of the primary focus: 85–90 in the appendix, colon and rectum, 73 in the stomach, 68 in the cecum and 67 in the small bowel. The aforementioned authors have not demonstrated a strong relationship in their multivariate analysis. Despite small sizes, NETs in the small bowel rapidly metastasize to the lymph nodes: 1 cm lesions metastasize in 15–25% of cases, tumors between 1 and 2 cm – in 58–80% of cases, and larger masses (greater than 2 cm) – in over 70% of cases(. The role of abdominal ultrasound (apart from its endoscopic version) in diagnosing NETs is rather limited. The literature usually mentions that US can detect metastatic foci in the liver and lymph nodes, or the method is not included at all in the diagnostic algorithms of small bowel NETs(. There are only case reports that present single cases of NETs in the small intestine diagnosed by ultrasonography(. The attempts to introduce ultrasound contrast agents have not changed the attitude to abdominal ultrasonography either(. However, it seems that, in experienced hands, this modality can be useful in the initial diagnosis of patients with suspicions of NETs in the small intestine(. Secondary changes in the mesentery can indicate that such a pathology exists. These changes are sometimes more visible than the primary focus concealed in the intestinal wall. This issue was the main subject of the analysis conducted in our 17 patients with small bowel NETs. All hypoechoic changes are well visible against the mesentery of intermediate or slightly increased echogenicity. This concerns affected lymph nodes and hypoechoic masses. Mesenteric thickening and centrally folding structure( are usually manifested by a pattern of slightly increased reflection intensity compared with the normal mesentery, and that is why such a reaction can be more difficult to detect. To date, pathological masses is the mesentery, which can signal the presence of a NET in the small intestine, have been the subject of only few papers(. The only detailed retrospective analysis was conducted by Pantongrag-Brown et al.( based on CT and histologic findings. Of 29 patients with a tumorous carcinoid mass, 30 foci were detected in the mesentery. Their sizes ranged from 0.5 cm to 6.0 cm (mean 3.3 cm) and most of them (24/30, 70%) contained calcifications of various types. 21 specimens were tested histologically, but only 7 (33%) showed fragments of the lymph node architecture. However, the authors of this paper( do not specify the percentage of patients with NETs in whom mesenteric changes were found. In our patients, such changes were detected in 5 of 17 cases (29.4%). It must be therefore concluded that a hypoechoic mass in the mesentery is not a rare phenomenon in patients with NETs in the small bowel and can be an important manifestation of such a pathology in an abdominal US scan. This finding should prompt the ultrasonographer to assess the small intestine carefully, particularly when such a pathological process is suspected clinically. It is obvious that a change detected in the mesentery can also be a different neoplasm, either primary (e.g. lymphoma, liposarcoma, mesothelioma, etc.) or secondary (e.g. metastases of colorectal cancer or carcinoma of the small intestine or ovary, etc.) The differential diagnosis should also include inflammatory lesions (tuberculosis, sarcoidosis, etc.) and other processes (amyloidosis, fibromatosis, etc.). However, the detection of the affected mesenteric lymph nodes as the only finding requires even more pathologies to be ruled out, mainly numerous infectious lesions and Crohn's disease. Fragmentary thickening of the mesentery in NETs is difficult to differentiate from mesenteritis (particularly its fibrotic form) which can also lead to small bowel obstruction(. Sonography should be treated as an initial examination in the diagnostic algorithm of NETs because of its limited ability to assess the generalization of the pathological process, the possibility of multiple NETs in the small bowel (which is relatively frequent) and increased risk of the development of other neoplastic lesions, either synchronous or metachronous(.

Conclusions

In an abdominal US examination, 2/3 of patients with neuroendocrine tumors in the small bowel manifest secondary lesions in the mesentery which are easier to visualize than the primary focus. Thirty percent of them are manifested as hypoechoic masses.

The detection of such lesions should prompt the search for the primary focus in the small intestine.