[Diagnostics and therapy for neuroendocrine neoplasia of an unknown primary - a plea for open exploration]

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.

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).

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. 55.9 y, 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 (54.9 y vs. 68.3 y, 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.

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.