Goblet Cell Carcinoids and Related Tumors of the Vermiform Appendix

Abstract

Appendiceal carcinoids with glandular differentiation pose difficulties in classification and prediction of clinical behavior. Sixty-four such cases were divided into three histologic groups on the basis of routine and immunohistochemical stains: (1) Tubular carcinoids were small and confined to the appendix, had small amounts of intraluminal mucin with few or no goblet cells, were nonargentaffin, lacked serotonin, and were diffusely positive for glucagon. All ten with follow-up (mean, 17 months) were without metastasis. (2) Goblet cell carcinoids were confined to the appendix and mesoappendix, circumferentially surrounded the appendiceal lumen, and were often not suspected grossly. Histologically, they were often mixed with small crypt-like glands and were serotonin positive. All 22 with follow-up (mean, 19 months) were without metastasis whether or not right hemicolectomy was performed. (3) Mixed carcinoid-adenocarcinomas showed spread into the cecum or adjacent viscera at the time of diagnosis and had a large carcinomatous pattern with areas of mucinous, signet-ring, or single-file structure, in addition to goblet cell or insular carcinoid. All patients had right hemicolectomies, and all but two with follow-up died of the disease (mean, 16 months). Although a histologic spectrum exists among carcinoid tumors and certain adenocarcinomas of the appendix, it is possible to delineate three biologically distinct groups. Surgical margins should be taken of all appendices because these tumors often do not form discrete masses.

Goblet Cell Carcinoid Tumor, Mixed Goblet Cell Carcinoid-Adenocarcinoma, and Adenocarcinoma of the Appendix: Comparison of Clinicopathologic Features and Prognosis

“…For comparison purposes, we divided tumors containing any element of GCT into 3 groups based on the amount of adenocarcinoma component (adapted from Burke et al 8 ): group 1, GCTs or GCTs with less than 25% adenocarcinoma (GCTs with an adenocarcinoma component comprising ,25% of the tumor; Figure 1, A through C); group 2, GCTs with 25% to 50% adenocarcinoma (GCTs with an adenocarcinoma component between 25% and 50% of the tumor; Figure 2, A and B); and group 3, more than 50% adenocarcinoma (GCTs with an adenocarcinoma component .50% of the tumor; Figure 3, A and B). For comparison, we included group 4, poorly differentiated appendiceal adenocarcinoma (signet-ring cell, mucinous, solid, or glandular patterns) without a recognizable GCT component.…”

“…The classic histologic features of GCTs are those of a tumor composed of multiple cell types (predominately goblet cells, a few neuroendocrine cells, and occasional Paneth cells), arranged as discrete nests arising in the deep lamina propria and involving the wall of the appendix in a concentric fashion. 3,5,[8][9][10] The GCTs' organoid growth pattern, presence of scattered neuroendocrine cells, ultrastructural evidence of neurosecretory granules, lack of cytologic atypia, lack of p53 mutations, and lack of an in situ mucosal precursor lesion have compelled many authors to consider GCTs as a type of carcinoid tumor. 2,5,[11][12][13][14][15] In addition, rare tumors with both GCT and classic carcinoid tumor components have been described.…”

“…29,33 A complicating issue with GCTs is that they can display areas that are indistinguishable from moderately to poorly differentiated adenocarcinoma, including pools of mucin, signet-ring cells, solid sheets of cells, fused or cribriform glands, and single-file structures. 8,34,35 The World Health Organization classification of appendiceal tumors in 2010 recognized a category of adenocarcinoma arising from GCT (mixed adenoneuroendocrine carcinoma). 36 In other references, the term mixed carcinoid/adenocarcinoma is not specifically used; however, the poor prognostic significance of a large (.50%) adenocarcinomatous component in GCTs is recognized.…”

“…19 In population-based tumor registries, however, no category is available for mixed tumors, and it is unclear whether those cases are classified as carcinoid tumors, GCTs, or adenocarcinomas. 29,30 Despite the recognition of mixed patterns in GCTs, only 2 previous studies, to our knowledge, have specifically examined the prognosis of GCTs relative to the amount 8 or type 35 of admixed carcinoma and proposed quantitative criteria for classification and treatment. In 1990, Burke et al 8 established quantitative criteria to distinguish mixed carcinoid-adenocarcinoma from GCT based on the percentage of carcinomatous growth.…”

“…29,30 Despite the recognition of mixed patterns in GCTs, only 2 previous studies, to our knowledge, have specifically examined the prognosis of GCTs relative to the amount 8 or type 35 of admixed carcinoma and proposed quantitative criteria for classification and treatment. In 1990, Burke et al 8 established quantitative criteria to distinguish mixed carcinoid-adenocarcinoma from GCT based on the percentage of carcinomatous growth. They concluded that patients who had GCT with more that 50% of the tumor consisting of a carcinomatous component had a poor prognosis and recommended that those tumors be treated as an adenocarcinoma, whereas patients who had GCT with less than 25% carcinomatous component did well, with no patients in that group having metastases or residual disease.…”