Goblet cell carcinoid tumor, mixed goblet cell carcinoid-adenocarcinoma, and adenocarcinoma of the appendix: comparison of clinicopathologic features and prognosis.

CONTEXT: The prognosis of appendiceal goblet cell carcinoid tumors (GCTs) is believed to be intermediate between appendiceal adenocarcinomas and conventional carcinoid tumors. However, GCTs can have mixed morphologic patterns, with variable amount of adenocarcinoma. OBJECTIVE: To evaluate the behavior of GCTs and related entities with variable components of adenocarcinoma. DESIGN: We classified 74 cases of appendiceal tumors into 3 groups: group 1, GCTs or GCTs with less than 25% adenocarcinoma; group 2, GCTs with 25% to 50% adenocarcinoma; group 3, GCTs with more than 50% adenocarcinoma; and a comparison group of 68 adenocarcinomas without a GCT component (group 4). Well-differentiated mucinous adenocarcinomas were excluded. Clinicopathologic features and follow-up were obtained from computerized medical records and the US Social Security Death Index. RESULTS: Of the 142 tumors studied, 23 tumors (16%) were classified as group 1; 27 (19%) as group 2; 24 (17%) as group 3; and 68 (48%) as group 4. Staging and survival differed significantly among these groups. Among 140 patients (99%) with available staging data, stages II, III, and IV were present in 87%, 4%, and 4% of patients in group 1 patients; 67%, 7%, and 22% of patients in group 2; 29%, 4%, and 67% of patients in group 3; and 19%, 6%, and 75% of patients in group 4, respectively (P = .01). Mean (SD) overall survival was 83.8 (34.6), 60.6 (30.3), 45.6 (39.7), and 33.6 (27.6) months for groups 1, 2, 3, and 4, respectively (P = .01). By multivariate analysis, only stage and tumor category were independent predictors of overall survival. CONCLUSION: Our data highlight the importance of subclassifying the proportion of adenocarcinoma in appendiceal tumors with GCT morphology because that finding reflects disease stage and affects survival.

Paget cells in the esophagus: assessment of their histopathologic features and near-universal association with underlying esophageal adenocarcinoma.

Pagetoid spread of primary esophageal melanomas and several cases of pagetoid esophageal squamous cell carcinoma are known. However, true esophageal Paget disease (intraepithelial growth of neoplastic cells with glandular differentiation) has only rarely been reported. We encountered 3 endoscopic biopsy specimens containing Paget cells in squamous epithelium associated with adenocarcinomas in Barrett esophagus (BE) and in the esophagogastric junction. To determine the prevalence of Paget cells in the esophagus, we studied 81 endoscopic mucosal resections and 27 esophagectomies from patients with invasive or intramucosal adenocarcinoma, and compared the findings to a control group of 47 endoscopic mucosal resections and 25 esophagectomies from patients with high-grade dysplasia in BE. Paget cells were present in squamous epithelium overlying 5 (4.9%) of 108 adenocarcinomas but in none (0%) of 72 BE with high-grade dysplasia (P=0.16). A computerized search for primary Paget disease using the terms "Paget's and esophagus" or "pagetoid and esophagus" from 1994 to 2007 did not yield any additional cases. Among the 8 patients with Paget cells (including the 2 index biopsies) there were no differences in either sex distribution (7M:1F) or age (mean 62.4 y) as compared with 103 adenocarcinomas without Paget cells (93M:10F, P=0.58; mean age 69.2 y, P=0.78). Morphologically, all adenocarcinomas with Paget cells contained at least a component of diffuse, poorly differentiated adenocarcinoma, and 1 was a signet ring cell carcinoma. Paget cells involved only squamous epithelium directly above the poorly differentiated tumor foci. Histochemistry for periodic acid-Schiff with diastase (PAS-D) and mucicarmine, and immunohistochemistry for CK7, CK20, p53, and E-cadherin, were performed on 7 Paget cases with the following results: PAS-D+ (7 of 7, 100%), mucicarmine+ (6 of 7, 86%), CK7+ (7 of 7, 100%), CK20+ (5 of 7, 71%), p53 overexpression (3 of 7, 43%), and E-cadherin loss (complete loss in 1 and faint expression in 3, 57%). Overall, PAS-D was the most efficacious stain for highlighting Paget cells. A control group of 19 adenocarcinomas without Paget cells were also stained for E-cadherin; only 1 showed faint expression (5%) and none showed complete loss (P=0.01). These results demonstrate a low but significant prevalence (4.9%) of Paget cells in esophageal and esophagogastric junction adenocarcinomas. Unlike previously described cases of mammary, vulvar, and perianal Paget disease, esophageal Paget cells are almost universally associated with underlying adenocarcinoma and not with high grade dysplasia ("in situ" disease) or primary Paget disease. A commonality among cases with Paget cells is the presence of focal or diffuse, poorly differentiated adenocarcinoma with discohesive cells. E-cadherin alterations seem to play a less significant role.

An assessment of chromosomal alterations detected by fluorescence in situ hybridization and p16 expression in sporadic and primary sclerosing cholangitis-associated cholangiocarcinomas.

The objective of this study was to assess and compare the chromosome abnormalities present in sporadic and primary sclerosing cholangitis (PSC)-associated cholangiocarcinomas (CCAs) and biliary dysplasias. Histologic sections from 22 patients with CCA (16 sporadic and 6 PSC associated), 5 of whom had associated dysplasia, and 2 PSC patients with biliary dysplasia alone were assessed for chromosomal alterations with fluorescence in situ hybridization (FISH). FISH involved the use of a multiprobe set consisting of centromere-specific probes for chromosomes 3, 7, and 17 and a locus-specific probe for 9p21. The number of signals for each of these probes was enumerated in 50 nonoverlapping interphase nuclei, and the percentage of nuclei containing 0, 1, 2, and 3 or more signals was recorded for each probe. p16 expression was assessed using immunohistochemistry. Gain of at least 1 chromosome was identified in 19 of 22 (86%) invasive tumors and in 4 of 7 (57%) biliary dysplasias. Gain of 2 or more chromosomes (polysomy) was observed in 17 of 22 (77%) invasive tumors and in 3 of 7 (43%) biliary dysplasias. Homozygous loss of 9p21 was identified in 11 of 22 (50%) invasive tumors and in 3 of 7 (43%) biliary dysplasias. The patterns of chromosomal abnormalities detected by FISH in PSC-associated and sporadic CCAs were similar. Nine of 13 (69%) invasive tumors and 2 of 5 (40%) biliary dysplasias with complete loss of p16 expression by immunohistochemistry showed allelic loss of 9p21 by FISH. Polysomy and homozygous 9p21 deletion are common in both sporadic and PSC-associated CCAs and are frequently detectable in PSC-associated biliary dysplasia.