Clinical significance and management of Barrett’s esophagus with epithelial changes indefinite for dysplasia

Table 1 Histopathologic criteria for Barrett’s esophagus with epithelial change indefinite for dysplasia

Ref.	Criteria
Reid et al[2], 1988; Montgomery et al[7], 2001	The architecture may be moderately distorted. Nuclear abnormalities are less marked than those seen in dysplasia. Other features that may lead to a diagnosis of IND include more numerous dystrophic goblet cells, more extensive nuclear stratification, diminished or absent mucus production, increased cytoplasmic basophilia, and increased mitoses
Sonwalkar et al[9], 2010	Preserved gland architecture, mild crypt distortion, minimal nuclear stratification and slight nuclear atypia or enlargement
Kestens et al[15], 2015	When a diagnosis of genuine dysplasia cannot be made. This is often due to the co-occurrence of inflammatory changes or when evaluation of surface maturation is not possible
Sinh et al[16], 2015	Cytologic changes similar to those seen in LGD but with surface maturation or presence of inflammation
Duits et al[13], 2015	Downgraded from BE LGD to BE IND by an expert pathology panel
Horvath et al[12], 2015	The presence of architectural and cytologic atypia in small and mal-oriented biopsy specimen or those with inflammation or ulceration exceeding those expected for reactive changes. In some cases, it is due to basal dysplasia with surface maturation

BE: Barrett’s esophagus; BE IND: Barrett’s esophagus with epithelial change indefinite for dysplasia; LGD: Low-grade dysplasia.

Table 2 Risk of Prevalent neoplasia in patients with Barrett’s esophagus with epithelial change indefinite for dysplasia

Ref.	Number of cases	Prevalent LGD, n (%)	Prevalent HGD, n (%)	Prevalent adenocarcinoma n (%)	Prevalent advanced neoplasia
Montgomery et al[11], 2001	7	0 (0)	0 (0)	1 (15)	At least 1 (15)
Sonwalkar et al[9], 2010	41	At least 1 (2.4)	0 (0)	At least 1 (2.4)	At least 1 (2.4)
Choi et al[14], 2015	96	At least 14 (14.5)	Not known	Not known	At least 10 (10)
Horvath et al[12], 2015	107	7 (8.2)	2 (2.35)	2 (2.35)	4 (4.7)
Kestens et al[15], 2015	842	101 (12.1)	Not known	Not known	16 (1.9)
Sinh et al[16], 2015	83	Not known	0 (0)	0 (0)	0 (0)

LGD: Low-grade dysplasia; HGD: High-grade dysplasia.

Table 3 Risk of Incident neoplasia in patients with Barrett’s esophagus with epithelial change indefinite for dysplasia

Ref.	No. of cases	Follow up in months (range)	Incident LGD n (%)	Incident HGD n (%)	Incident adeno carcinoma n (%)	Incident advanced neoplasia (per 100 person-years	Risk factors for progression to advanced neoplasia
Duits et al[13], 2015	40	Median 31 (16-59)	0	1 (2.5)	0 (0)	0.9	Not done
Horvath et al[12], 2015	82	Mean 59 (13-182)	14 (8.3)	3 (2.3)	2 (2.3)	1.2	p53 expression in >5% nuclei
Kestens et al[15], 2015	631	Not known	No data	10 (1.6)	6 (1.0)	0.43	Older age
Sinh et al[16], 2015	83	Mean 68.4 (SD: 37.2)	No data	3 (3.6)	1 (1.2)	0.86	Not done for BE IND group
Sonwalkar et al[9], 2010	37	Median 38.7 (6-122)	3 (8.1)	0 (0)	3 (8.1)	Not done	Expression of AMACR in more than 1% of cells

BE IND: Barrett’s esophagus with epithelial change indefinite for dysplasia; LGD: Low-grade dysplasia; HGD: High-grade dysplasia; SD: Standard deviation; AMACR: Alpha-methylacyl-CoA racemase.

Table 4 Guideline recommendations for the management of Barrett’s esophagus with epithelial change indefinite for dysplasia

Guidelines	Diagnosis	Treatment and surveillance
ACG guidelines[1]		Acid suppressive medications for 3-6 mo A repeat endoscopy after optimization of should be performed If BE IND, surveillance in 12 mo
BSG guidelines[18]	Review by a second GI pathologist, and the reasons for use of the ‘indefinite for dysplasia’ category should be given in the histology report in order to aid patient management	Optimisation of antireflux medication Repeat endoscopy in 6 mo If no dysplasia is found, then the surveillance per non-dysplastic Barrett’s oesophagus
ASGE[19]	Clarify presence and grade of dysplasia with expert GI pathologist	Increase antisecretory therapy to eliminate esophageal inflammation. Repeat EGD and biopsy to clarify dysplasia status
Australian Guidelines[20]	Confirm by a second pathologist, ideally an expert gastrointestinal pathologist.	Repeat endoscopy in 6 mo with Seattle protocol biopsies for suspected dysplasia (biopsy of any mucosal irregularity and quadrantic biopsies every 1 cm) on maximal acid suppression If repeat shows no dysplasia, then follow as per non-dysplastic protocol If repeat shows low-grade or high-grade dysplasia or adenocarcinoma, then follow protocols for these respective conditions If repeat again shows confirmed indefinite for dysplasia, then repeat endoscopy in 6 mo with Seattle protocol biopsies for suspected dysplasia

BE IND: Barrett’s esophagus with epithelial change indefinite for dysplasia.