Clinicopathologic study of neuroendocrine tumors of gastroenteropancreatic tract: a single institutional experience

Abstract

Background: The gastroenteropancreatic neuroendocrine tumors (GEPNET) have a characteristic histologic appearance unrelated of the exact site of origin. However the behavior of these tumors are different in each of these sites. In this article we study the clinicopathological features of GEPNET. These tumors were classified and graded according to WHO 2010 criteria. The immunohistochemical (IHC) features were evaluated and the grade of the tumor was correlated with Ki67.

Methods: A total of 40 cases of GEPNET diagnosed on biopsies as well as resected specimens were analyzed from January 2012 to June 2015.

Results: There were 28 resected specimens and 12 biopsies. Majority of the gastric neuroendocrine tumors (NET) showed classic morphology of cells arranged in islands. There were 3 cases each of grade 1 and grade 2 and one was diagnosed as mixed adenoneuroendocrine carcinoma (MANEC). All the duodenal NET were well differentiated (grade 1). There were 8 cases in colon and rectum, of which 4 cases were grade 3 and 3 cases were grade 2. Majority of the pancreatic tumors were grade 1. The mean mitotic count along with ki67 had good correlation in NET of stomach, duodenum colon and rectum.

Conclusions: The most common site was small intestine followed by pancreas. Majority of the tumors were NET G1. Tumors from colorectal region were mostly NEC G3. There was a strong correlation by spearman correlation analysis between Ki67 and mitotic count and moderate correlation between ki67 and tumor grade as well as mitotic rate and tumor grade. Ki67 was helpful in grading these tumors.

Keywords: Ki67; Neuroendocrine tumors (NET); grade.

Figure 1

Gross photograph of (A) well circumscribed nodule in pyloric antrum; (B) a case of ulcerative colitis with growth in the descending colon showing features of adenocarcinoma. The adjacent colon had multiple mucosal elevations with features of well differentiated neuroendocrine tumors, multiple micro carcinoids; (C) Whipples resection specimen presenting as multiple polyps [44] in small intestine in a case of well differentiated neuroendocrine tumor; (D) gross photograph of a well circumscribed mass in a case of pancreatic well differentiated NET; (E,F) mass in the uncinated process of pancreas.

Figure 2

Duodenal grade 2 neuroendocrine tumor. (A) Lesion in the submucosa of the duodenum [hematoxylin and eosin (H & E) ×40]; (B) cells are arranged in island and lobules (H & E ×100); (C) cells have stippled nuclear chromatin (H & E ×400); (D,E) immunohistochemical (IHC) positivity for chromogranin and synaptophysin (IHC chromogranin and synaptophysin ×400); (F) Ki67 labeling index −1% (IHC Ki67 ×40).

Figure 3

Neuroendocrine tumor grade 3. (A) Cells arranged in sheets [hematoxylin and eosin (H & E) ×100]; (B) Ki67 labelling index −30% (IHC Ki67 ×100).

Figure 4

Histopathology and immunohistochemical (IHC) of mixed adenoneuroendocrine carcinoma. (A-C) Mixed adenoneuroendocrine carcinoma (MANEC) of stomach [hematoxylin and eosin (H & E) ×40 (A) and ×100 (B,C)]; (D) adenocarcinoma component show signet ring cell morphology (H & E ×100). Intracytoplasmic mucin is highlighted in the inset (Alcian PAS stain ×400); (E) cytokeratin positivity in adenocarcinoma component (IHC cytokeratin ×400); (F,G) neuroendocrine component showing positivity for chromogranin and synaptophysin (IHC chromogranin ×100 and synaptophysin ×400); (H) high Ki67 labeling index in both the components (IHC Ki67 ×40).

Figure 5

Correlation between Ki67 and mitotic count.

Figure 6

Spearman correlation analysis between Ki67 and tumor grade.

Figure 7

Correlation between mitotic count and tumor grade.