Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases

Abstract

High-grade versions of appendiceal goblet cell carcinoids (‘adenocarcinoma ex-goblet cell carcinoids’) are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29–84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n =3) and lung (n =1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed ‘other’ carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular (‘carcinoid pattern’) was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (<55) were independently associated with worse outcome while lymph-vascular invasion, stage, and nodal status trended toward, but failed to reach, statistical significance. Worse behavior in younger patients combined with female predilection and ovarian-affinity raise the possibility of hormone-assisted tumor progression. In conclusion, ‘adenocarcinoma ex-goblet cell carcinoid’ is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy, and spreads along peritoneal surfaces with only rare hematogenous metastasis. It appears to be significantly more aggressive than appendiceal mucinous neoplasms.

A study of appendiceal crypt cell adenocarcinoma (so-called goblet cell carcinoid and its related adenocarcinoma)

“…Tang LH et al attempted to classify this group of tumor into type A, B and C, and they demonstrated the subtyping correlated with survival, with type A and C being at low and high grade end, respectively [1]. Their results were reproduced by one study [31] but were not confirmed by two other studies [2,8]. Our group also published analysis regarding the prognostic value of this system in a cohort similar to the current study [6].…”

“…In the majority of tumors (81%), more than one growth pattern was seen and various patterns were often intermixed. Notably high grade histology comprised a wide range of histologic features as recently described [8]. As a definition of our system, there was loss of organoid morphology, including irregular, angulated, was seen in 58 tumors, ranging from 0 to 95% (median 30%).…”

Appendiceal adenocarcinoma—Two unique cases of adenocarcinoma ex‐goblet cell carcinoid

“…Tumors occurred predominantly in females (74%), mean age 55 years (29‐84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma …”

Adenocarcinoma Ex-Goblet Cell: a Retrospective Experience

“…Our analysis, to the best of our knowledge, is the first one to document the chemotherapy experience of this group. Prior to delving into this, we will be comparing the clinicopathologic characteristics and outcomes of our AGCC patients with those from four retrospective AGCC patient analyses (Tang et al, Taggart et al, Reid et al, and Hristov et al) to place our findings in context [2, 3, 7, 8]. …”