Clinicopathologic correlations of superficial esophageal adenocarcinoma in endoscopic submucosal dissection specimens

Abstract

Background: Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists' experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett's esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions.

Methods: We retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking.

Results: Two patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 μm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up.

Conclusions: Our results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

Keywords: Barrett’s esophagus; Endoscopic submucosal dissection; Mucosal adenocarcinoma; Submucosal adenocarcinoma; Tumor budding.

Fig. 1

A. Endoscopic image of post esophageal endoscopic submucosal dissection. B. Gross image of the endoscopic submucosal dissection specimen

Fig. 2

A. Invasive adenocarcinoma with tubuloinfiltrative pattern. Hematoxylin and Eosin stain. × 100. B. Invasive adenocarcinoma with tubulocystic pattern. Hematoxylin and Eosin stain. × 40

Fig. 3

A. Invasive intramucosal adenocarcinoma infiltrating into the superficial layer of muscularis mucosae, Vieth and Stolte DOI: m2. B. Invasive intramucosal adenocarcinoma infiltrating into layer between superficial and deep muscularis mucosae, Vieth and Stolte DOI: m3. C. Invasive intramucosal adenocarcinoma infiltrating into the deep layer of muscularis mucosae, Vieth and Stolte DOI: m4. D. Invasive intramucosal adenocarcinoma infiltrating into the superficial submucosa ≤ 500 μm, Vieth and Stolte DOI: sm1. E. Invasive intramucosal adenocarcinoma infiltrating into submucosa to a depth between 500 to 1000 μm, Vieth and Stolte DOI: sm2. F. Invasive intramucosal adenocarcinoma infiltrating into deep submucosa > 1000 μm, Vieth and Stolte DOI: sm3. Hematoxylin and Eosin stain. × 40

Fig. 4

A. Low tumor budding. B. Intermediate tumor budding. Hematoxylin and Eosin stain × 400. C. High tumor budding. Hematoxylin and Eosin stain × 200. D. Pankeratin immunostain with intermediate tumor budding, × 400. E. Pankeratin immunostain with high tumor budding, × 400

Fig. 5

A. Tissue folding artefact due to improper processing and embedding. Hematoxylin and Eosin stain × 20. B. Pinhole artefact causing curling of tissue at edges leading to difficulty in peripheral margin interpretation. Hematoxylin and Eosin stain. × 40. C. Large pinhole artefact causing disruption of tissue at the edge. × 20

Fig. 6

Deep margin, positive for tumor due to superficial plane of resection. Hematoxylin and Eosin stain. × 40

Fig. 7

A. Recommended thin paper pins for pinning the tissue on the board for proper fixation. B. Small pin hole and excellent orientation of the tissue edges for optimal assessment of peripheral margins. Hematoxylin and Eosin stain × 20