Abstract
Simple SummaryEsophageal and esophago-gastric junction adenocarcinomas (EA/EGJAs) are a heterogeneous group of cancers. Stage is the most important prognostic factor, while morphology, determined by histologic analysis, has up until now played a minor role. Even new molecular classifications (which should be based on accurate histologic assessment) are a long way off from being used in day to day practice. The reassessment of nearly 300 EA/EGJAs enabled us to re-evaluate morphology and identify a two-tiered grading approach in glandular adenocarcinomas (80%) based on a cut off of 6% of poorly differentiated components (well differentiated versus poorly differentiated). Furthermore, rare, but prognostically significant, variants were recognized with an in-depth morphologic description. On this basis, two morphologic risk groups (lower risk and higher risk) were identified, adding significant prognostic value to the stage. The accurate morphologic description of EA/EGJAs must be a prerequisite for a better understanding of prognosis, molecular events, and response to treatment.Stage significantly affects survival of esophageal and esophago-gastric junction adenocarcinomas (EA/EGJAs), however, limited evidence for the prognostic role of histologic subtypes is available. The aim of the study was to describe a morphologic approach to EA/EGJAs and assess its discriminating prognostic power. Histologic slides from 299 neoadjuvant treatment-naïve EA/EGJAs, resected in five European Centers, were retrospectively reviewed. Morphologic features were re-assessed and correlated with survival. In glandular adenocarcinomas (240/299 cases—80%), WHO grade and tumors with a poorly differentiated component ≥6% were the most discriminant factors for survival (both p < 0.0001), distinguishing glandular well-differentiated from poorly differentiated adenocarcinomas. Two prognostically different histologic groups were identified: the lower risk group, comprising glandular well-differentiated (34.4%) and rare variants, such as mucinous muconodular carcinoma (2.7%) and diffuse desmoplastic carcinoma (1.7%), versus the higher risk group, comprising the glandular poorly differentiated subtype (45.8%), including invasive mucinous carcinoma (5.7%), diffuse anaplastic carcinoma (3%), mixed carcinoma (6.7%) (CSS p < 0.0001, DFS p = 0.001). Stage (p < 0.0001), histologic groups (p = 0.001), age >72 years (p = 0.008), and vascular invasion (p = 0.015) were prognostically significant in the multivariate analysis. The combined evaluation of stage/histologic group identified 5-year cancer-specific survival ranging from 87.6% (stage II, lower risk) to 14% (stage IVA, higher risk). Detailed characterization of histologic subtypes contributes to EA/EGJA prognostic prediction.
Highlights
Esophageal cancer is the sixth highest cause of cancer related death and the eighth most common cancer worldwide [1,2,3]
Patients with esophageal adenocarcinoma (EA)/esophagogastric junction adenocarcinoma (EGJA), submitted to radical surgical resection, were retrospectively recruited from the databases of five institutions belonging to the Esophageal Adenocarcinoma Study Group Europe (EACSGE)
Our study has shown that different rare histotypes impact survival, with some variants, namely mucinous muconodular carcinoma (MMC) and diffuse desmoplastic carcinomas (DDC), showing significantly better survival than others (IMC, diffuse anaplastic carcinomas (DAC), and mixed)
Summary
Esophageal cancer is the sixth highest cause of cancer related death and the eighth most common cancer worldwide [1,2,3]. The most powerful prognostic parameters driving therapy are, to date, clinical and pathological TNM staging—the former is far from reliable, while the latter is derived from the surgical specimen, detailed after resection, when the core of therapy (i.e., surgery or neoadjuvant therapy + surgery) is already over [13,14,15,16,17,18]. To overcome these limits, other prognostic features have been explored, including clinic–pathologic associations with
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