Neuroendocrine tumors: characterization with contrast-enhanced ultrasonography

The aim of this study was to characterize the ultrasonographic features of neuroendocrine tumors (NET) and their metastases with contrast-enhanced ultrasonography (CEUS) and to compare this to clinical data.

During a period of 5 years, 82 patients with 83 histologically proven NET were prospectively examined using conventional US and pulse inversion US with a second generation contrast agent (SonoVue, Contrast Pulse Sequencing) focusing on the arterial (10-20 s p. i.), capillary (20-25 sec p.i.), portal venous (25-120 sec p.i.), and late phases (>120 sec p.i.). 69 patients had metastases in the abdominal tract, including eight patients with poorly differentiated neuroendocrine carcinomas with high-grade behavior. In 31 patients the proliferation index (MIB-1) of the NET was < or = 2%, in 46 patients > 2%, in 6 patients > or = 20%. Thirteen patients had one primary lesion without metastases.

In NET of the lung, stomach, and colon we found only hypoechoic or isoechoic liver metastases. NET of the small intestine and pancreas represented hypoechoic, isoechoic, and/or hyperechoic liver lesions, sometimes combined. Insulin producing tumors (6) had hypoechoic metastases. Necrotic areas (25/83) were detected after interferon therapy, embolization, systemic chemotherapy, and radiofrequency ablation of liver metastases, but did not develop after somatostatin receptor radionuclide therapy. In large NET (> 3 cm) with a proliferation index of > 2%, necrotic areas appeared spontaneously. In 93% (77/83) of the cases the NET and their metastases showed an early arterial influx of microbubbles. Rim-like contrast enhancement occurred during the capillary phase in 78% (65/83) of all lesions, and hypervascularization occurred during the arterial phase and at the beginning of the capillary phase in 95% (79/83). The hypervascularized tissue was found in the primary lesions, in liver, lymph node metastases and any kind of abdominal metastases. In liver metastases with a proliferation index >2%, tumor arteries showed a chaotic growth pattern. In 93% (77/83) the NET lesions appeared as dark "defects" at the beginning of the late phase.

CEUS with CPS demonstrates typical NET imaging characteristics. Differences in imaging features may depend on their primary lesion, size, proliferation marker, and extent of the degenerative changes. In most cases real-time CEUS may replace other imaging techniques.