Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases.

Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p < 0.001 for G2 vs G1), as well as patient age at diagnosis > 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.

Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations.

The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn's disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn's disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.

Comparison of pathology sampling protocols for pancreatoduodenectomy specimens.

Pancreatoduodenectomy is one of the most challenging surgical specimens for pathologists. Recently, two different, standardized protocols have been proposed: the axial slicing Leeds protocol (LP) and the bi-valving Adsay protocol (AP). Comparison between standardized and non-standardized protocols (NSP) was performed with emphasis on margin involvement and lymph node yield. Pancreatoduodenectomy cases were retrospectively recruited: 46 sampled with LP, 52 cases with AP and 46 cases with NSP. Clinico-pathologic data and rates of margin/surface involvement were collected and their prognostic influence on survival was assessed. Statistical differences between NSP and AP and LP were seen for nodal yield (p = 0.0001), N+ (p = 0.0001) and lymph node ratio - LNR (p < 0.0008) but not between AP and LP. Differences in R1/R0 status were statistically significant between NSP group (R1-15%) and both the LP (R1-73.9%) and AP (R1-70%) groups (p = 0.0001) but not between LP and AP groups. At univariate survival analysis, grade (p = 0.0023) and number of involved margins (p = 0.0096) in AP and "N-category" (p = 0.0057) "resection margin status" (p = 0.0094), "stage" (p = 0.0143), and "number of involved margins" (p = 0.00398) in LP were statistically significant, while no variable was significant in the NSP group. At multivariate analysis "N category," "resection margin status," "stage," "number of involved margins," and "LNR" retained significance for the LP group. These results show that both LP and AP perform better than non-standardized sampling making standardization mandatory in pancreatoduodenectomy cut up. Both AP and LP show strengths and weaknesses, and these may impact on the choice of protocol in different institutions.

Grade 3 Neuroendocrine Tumor (G3 NET) in a Background of Multiple Serotonin Cell Neoplasms of the Ileum Associated with Carcinoid Syndrome and Aggressive Behavior.

Grade 3 well-differentiated neuroendocrine tumors (G3 NETs) have been characterized in the pancreas and stomach and distinguished from low-to-intermediate grade (G1-G2) NETs, as well as from highly malignant, poorly differentiated neuroendocrine carcinomas (NECs). Up to now, no G3 NET has been thoroughly described in the distal small intestine. We herein report a case of a 61-year-old man presenting with carcinoid syndrome. The surgical specimen showed, in a background of small G1 ileal NETs, a larger, grade 3 NET, which retained the nesting pattern and the expression of serotonin, chromogranin-A, and type 2A somatostatin receptors, typical of well-differentiated jejuno-ileal NETs. The patient had G3 NET metastasis to the liver and he died 14 months after surgery, due to deterioration in his clinical conditions.