Diagnostik und Therapie bei neuroendokrinen Neoplasien mit unklarem Primarius - ein Plädoyer für die offene Exploration

Background: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented. Patients/Methods: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n=10), K2 - unknown primary after operative exploration (n=10) and K3 - no operative exploration for various reasons (n=13). Results: Initially 13.4% (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7% (33/261) and after operative exploration 8.8% (23/261) remained with unknown primary tumour. The sex ratio was 1:1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9y, p=0.004), the 5-year-survival is lower (58 vs. 72%, n.s.). compared to NEN with known primary. Operative exploration was performed in 60.6% (20/33), 30% (6/20) of them were found to have inoperable situations, in 20% (4/20) single site metastases were removed completely and in 50% (10/20) a primary tumour was detected (8×midgut, 2×pancreas) intraoperatively. In these cases 70% (7/10) got complete tumour resection (R0) and in 30% (3/10) primary tumour resection with debulking of liver metastasis was done. In K3 (39.4%, 13/33) most patients [69.2% (9/13)] were treated with chemotherapy. The median age in K1 was significantly lower than in K3 (54.9y vs. 68.3y, p=0.028), male dominance was seen in K3 (3,3:1, n.s.). The average Ki-67 index was 4.3, 23.8 and 53% in K1, K2 and K3 (p<0.0001 for K1 and K3 and p=0.035 for K2 and K3), respectively. The death rate was 20, 30 and 76.9% in K1, K2 and K3, respectively. Conclusion: Primary tumours of the midgut and pancreas are often found in the subset of well differentiated neuroendocrine CUP syndrome after open surgical exploration. A high rate of complete tumour resection and cure can be achieved in these cases. After common diagnostic tools (CT, MRI and somatostatin receptor scintigraphy), immunhistochemistry can give important hints (CDX-2 for midgut, TTF-1 for lung and thyroid) for a primary lesion. Also in single site metastasis without primary tumour detection a good clinical outcome is seen after complete resection.