Neuroendocrine Carcinomas of the Gallbladder: A Clinicopathologic Analysis of 23 Cases
G Sica, N Dursun, JC Roa, O Tapia, A Cakir, I Coban, J Sarmiento, O Basturk, N Ohike, J Cheng, NV Adsay. Emory U, GA; U de La Frontera, Temuco, Chile; NYU, NY
Background: It is increasingly recognized that high grade neuroendocrine (NE) carcinomas, even when comprising a small proportion of a neoplasm, disproportionately affect the biological behavior. In the gallbladder (GB), data regarding the incidence, significance and types of NEC has been very limited.
Design: Among 606 cholecystectomy specimens with carcinoma, 30 showing signs of NE differentiation as defined in the lung (both by pattern and cytomorphologic features) were identified. Dubious cases were analyzed with the 3 NE markers (CD56, synaptophysin and chromogranin) and 7 were excluded due to lack of positivity. Remaining 23 were included for analysis as NEC.
Results: M/F=6/1 (vs 3.8 in conventional GB carcinomas). Mean age=62 (range, 26-93). The majority of the cases (20/23) were mixed with an adenocarcinoma component: NE component was <25% of the tumor in 1, 25-75% in 7, and >75% in 15. All 3 pure NECs were pure small cell carcinoma; the remainder were mixed small cell/adenocarcinoma (n=6), and non-small cell NEC (n=14). 3 cases were associated with an intravesicular papillary-tubular neoplasm. Using WHO/ENETs scheme, 22/23 were high-grade (mitosis >20/10HPF) and 1 was intermediate-grade (mitosis >2-20/10 HPF) with focal necrosis. None was low-grade (carcinoid). Interestingly, 1 patient with pure small cell carcinoma had a recurrence (after therapy), which showed a mixed small cell/adenocarcinoma. Patients with NE morphology died faster (median survival 7.7 mos) compared to patients without NE morphology (median survival 14.6 mos; p=0.004). One patient had metastases that remained stable under therapy with adenocarcinoma protocol but had a striking (albeit short lasting) response to small cell carcinoma protocol. The one patient with intermediate-grade tumor was alive at last follow up of 5.5 mos.
Conclusions: NE component is present in 3.7% of GB carcinomas, seen predominantly in females. 95% are high-grade. About 40% is of the small-cell, 60%, non-small cell type. Half of the small cell types are pure, while non-small cell ones are uniformly associated with an adenocarcinoma component. The presence of NE morphology is associated with significantly lower median survival (p=0.004) and faster time to death when compared to conventional GB carcinomas, supporting the hypothesis that the high grade NE component drives the biology of the tumor.
Monday, March 22, 2010 1:00 PM
Poster Session II # 91, Monday Afternoon