Barretts Esophagus Mary P. Bronner, M.D. Division Chief of Anatomic - - PowerPoint PPT Presentation

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Barretts Esophagus Mary P. Bronner, M.D. Division Chief of Anatomic - - PowerPoint PPT Presentation

Jun 23, 2023 267 likes •1.2k views

Barretts Esophagus Mary P. Bronner, M.D. Division Chief of Anatomic Pathology and Oncology University of Utah & ARUP Laboratories Salt Lake City, UT Two Main Problems in Barretts Pathology Over diagnosis of Barretts esophagus

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Barrett’s Esophagus

Mary P. Bronner, M.D. Division Chief of Anatomic Pathology and Oncology University of Utah & ARUP Laboratories Salt Lake City, UT

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Two Main Problems in Barrett’s Pathology

  • Over diagnosis of Barrett’s

esophagus

  • Over diagnosis of high-grade

dysplasia

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Barrett’s Esophagus

Definition: 2-Fold

  • Endoscopically visible columnar

epithelium in esophagus that on biopsy has:

  • Metaplastic columnar epithelium,

defined by goblet cells

ACG Practice guidelines. Am J Gastroenterol 2008;103:788

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Barrett’s Esophagus

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Questions in the Histologic Dx of Barrett’s Esophagus

  • Is it Barrett’s or normal columnar

epithelium in the esophagus?

  • Are all goblet-like cells metaplastic?
  • Does Alcian blue positivity = metaplasia?
  • How much metaplastic epithelium is

needed to diagnose Barrett’s?

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Columnar Epithelium in the Esophagus May Be Normal

  • The S-C junction (Z-line) may be

irregular with “tongues” of columnar epithelium in the esophagus, or

  • The entire S-C junction may lie within

the esophagus

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Normal Esophagus

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Any Columnar vs. Goblet Barrett’s??

300,000,000 Americans 100,000,000 GERD with columnar mucosa 4,000,000 Barrett’s with goblets 16,000 annual Barrett’s CA

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Esophageal Adenocarcinoma

Should we screen 100,000,000 “any columnar/gastric” Barrett’s? OR 4,000,000 with goblet-cell Barrett’s? Noto bene: Even using the goblet Barrett’s definition, screening is ineffective!

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Questions in the Histologic DX

  • f Barrett’s Esophagus
  • Is it Barrett’s or normal columnar

epithelium in the esophagus?

  • How much metaplastic epithelium is

needed to diagnose Barrett’s?

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Significance of Few Metaplastic Glands Unknown

  • Prevalence as high as 30%
  • No good evidence of cancer

predisposition

  • Avoid Barrett’s diagnosis, instead use:

“Focal Intestinal Metaplasia” (personal opinion)

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How Much Metaplastic Epithelium is Needed to Diagnose Barrett’s?

  • No one knows! But,
  • If only rare glands – I diagnose

intestinal metaplasia

  • Intestinal glands replacing biopsy
  • - consider diagnosing Barrett’s
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Case

  • History: 72-yr-old man with long-

standing reflux & Barrett’s esophagus

  • Endosc:8 cm Barrett’s segment;

no mass lesions

  • Bxs:

4 quadrant every 2 cm to rule out dysplasia

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Barrett’s Esophagus with Dysplasia

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Neoplastic Progression in Barrett’s Esophagus

Chronic Reflux GERD Metaplasia Dysplasia Adenocarcinoma

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Dysplasia

Definition Neoplastic epithelium confined within the basement membrane of the gland within which it arose

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Grading System for Dysplasia

  • Negative
  • Indefinite
  • Positive
  • Low-grade
  • High-grade

IBD/DMSG Hum Pathol 1983 Pathol 1983;14:831

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Barrett’s Dysplasia

  • Two types
  • Intestinal (85%)
  • Gastric Foveolar (15%)
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Barrett’s Intestinal-type Dysplasia

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Intramucosal Adenocarcinoma

  • Single cell lamina propria invasion
  • Sheets of malignant cells
  • Abortive angulated glands
  • Never ending gland pattern
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Invasive Adenocarcinoma

  • Unequivocal desmoplasia
  • Indicates at least submucosal

invasion

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Barrett’s Gastric Foveolar-type Dysplasia

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Gastric-Type Barrett’s Dysplasia

  • Very different criteria from

intestinal-type dysplasia

  • Non-stratified, basal nuclei precludes

loss of nuclear polarity criterion

Mahajan D, et al. Mod Pathol 23:1-11, 2010

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Gastric-Type Barrett’s Dysplasia

  • Gastric-type LGD & HGD distinguished by
  • nuclear size cut off of 3-4X small lymph
  • increased but mild pleomorphism
  • prominent nucleoli
  • eosinophilic to oncocytic cytoplasm
  • crowded, irregular gland architecture

Mahajan D, et al. Mod Pathol 23:1-11, 2010

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Gastric-Type Barrett’s Dysplasia

Natural history poorly defined

  • 49 patients in present composite literature
  • F:M = 2.7:1
  • Decade older than intestinal-type dysplasia

(73 vs 63 yrs mean age)

  • More often high-grade (70%)
  • Neoplastic progression in 64% over 8 years
  • f follow-up

Mahajan D, et al. Mod Pathol 23:1-11, 2010

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DDX GERD vs. Foveolar Dysplasia

  • 3,698 EGD

bxs from 461 Barrett’s patients

  • 80 bxs

foveolar gastric-type dysplasia (13 LGD, 30 HGD)

  • 60 severe

GERD

Patil DT, et al. Hum Pathol 44:1146-53, 2013.

GERD FOV DYSP P- Value Nuclear stratif 80% <.00001 Top-heavy atypia 80% <.00001 Full thick atypia 80% <.00001 Villiform 6% 53% 0.0006 Crowded glands 78% <.00001 Nucleoli 79% 33% 0.0003 Pleomorph–mild 35% 10% 0.09

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Reactive Cardia/GERD Villiform Architecture & ‘Top-Heavy” Atypia

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Reactive Cardia/GERD: Stratified Surface Nuclei

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Gastric-type Dysplasia: Full-thickness Atypia

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Gastric-type Dysplasia: Non-stratified Nuclei

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Dysplasia: Problems

  • Sampling
  • Distinction from reactive

change

  • Observer variation
  • Squamous overgrowth
  • Natural history incompletely

understood

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Distribution of Dysplasia

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Biopsy Protocol

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Dysplasia: Problems

  • Sampling
  • Distinction from reactive

change

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Dysplasia: Problems

  • Sampling
  • Distinction from reactive

change

  • Observer variation
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Spectrum of Dysplasia

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Interobserver Agreement: Dysplasia in Barrett’s Esophagus

Diagnosis Kappa Statistic Agreement HGD/CA 0.65 Substantial LGD 0.32 Fair Indefinite 0.15 Poor Negative 0.58 Moderate

From: Montgomery E, et al. Hum Pathol 32:368-78; 2001

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Two Main Problems In Barrett’s Pathology

  • Over diagnosis of Barrett’s

esophagus

  • Over diagnosis of high-grade

dysplasia

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Inaccuracy in the Diagnosis of Barrett’s with HGD

  • PDT multi-center trial for Barrett’s HGD
  • 485 patients with “HGD” screened
  • Review original slides
  • Repeat protocol study endoscopy 4 quad q2cm
  • 248 with confirmed HGD (51%)
  • 193 patients downgraded (40%)

Sangle N, Bronner MP: Mod Pathol, In press 2015

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193 Downgraded Patients

Reinterpretations No. Percent Gastric only 18 9% Barrett’s negative 35 18% Barrett’s indefinite 61 32% Barrett’s LGD 79 41%

Sangle N and Bronner MP: Mod Pathol, In press 2015

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Diagnostic Pitfalls: HGD in Barrett’s Esophagus

  • NOT atypia limited to basal glands
  • NOT reactive gastric cardiac-type

mucosa

  • NOT inflammatory reactive change
  • Sampling error
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NOT Baseline Glandular Atypia

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NOT Reactive Gastric Mucosa

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NOT Inflammatory Atypia

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Over Diagnosis of HGD in BE

  • Under utilization of loss of nuclear polarity

as most objective criterion

  • Morphologic spectrum without precise

definable boundaries

  • Accuracy is experience and volume

dependent

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Loss of Nuclear Polarity to Distinguish Low and High-Grade Dysplasia

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ACG GUIDELINES

High-grade dysplasia in Barrett’s esophagus should be confirmed by an expert GI pathologist

Wang KK, Sampliner RE. Am J Gastroenterol 2008;103:788.

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High Grade Dysplasia

Ablation (e.g.PDT) Surveillance Surgery

Management Options

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HGD IMC SMC Can we tell BAD from WORSE?

Shaheen NJ. Gastroenterology 2003; 125:260.

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Interobserver Variability: At Least High-grade Dysplasia

Diagnosis Kappa P-value 95% CI Interp

ALL 0.30 <0.001 0.28-0.32 Poor HGD 0.47 <0.001 0.44-0.51 Mod HGD-MAD 0.21 <0.001 0.18-0.25 Poor IMC 0.30 <0.001 0.26-0.33 Poor SMC 0.17 <0.001 0.14-0.21 Poor

Erinn Downs-Kelly, et al. Am J Gastroenterol 103:2333-2340, 2008

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  • NO! Not on Biopsies!
  • Management based on distinction

between HGD, IMC & SMC in biopsies is questionable

  • What about EMR?

Can we tell BAD from WORSE?

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Bx vs. EMR Histology

Study #

  • f

Pt Up- stage by EMR Down- stage by EMR Total EMR Altered Larghi, 2005 48 13% 2% 15% Hull, 2006 41 34% 5% 39% Chennat, 2009 49 14% 31% 45% Moss, 2010 75 20% 28% 48% Note: EMR results altered the bx diagnosis 15-48% of the time

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T1a T1b e

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T1a Esophageal CA

  • Intramucosal carcinoma
  • Invades into
  • lamina propria
  • muscularis mucosae
  • Low metastatic rate 1-2%
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T1b Esophageal CA

  • Submucosal carcinoma
  • Subdivided into thirds (no

reliable significance)

  • High metastatic rate

~30%

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EMR for T1a (HGD/IMC)

Study # Pt’s Avg F/U Compl Resp Recur/ Metachr Ell, 2000 35 12 mo 97% 14% May, 2002 70 34 mo 98% 30% Pech, 2008 279 64 mo 97% 22% Chennat, 2009 CBE-EMR 32 23 mo 97%

3%

Moss, 2010 75 31 mo 94% 11%

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Estrella, et.al. Am J Surg Pathol 2011; 35:1045

Duplicated Muscularis Mucosae in Barrett’s

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Duplicated Muscularis Mucosae

  • Easy to overcall split MM space

as submucosal invasion (T1b)

  • EMR & EUS also overstage
  • >60% of IMC cases overstaged

Mandal, et.al. AJSP 2009;33:620

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Estrella JS, et.al. Am J Surg Pathol 2011; 35:1045

Invasion Depth Nodal Mets Mucosa & Dupl MM 1/69 (1.4%) Submucosa 10/30 (33.3%)

Split MM CA’s are T1a

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BE Dysplasia Summary-1

  • Grading of dysplasia: intestinal & gastric

foveolar types

  • Problems with dysplasia
  • Sampling
  • Observer variation
  • Natural history: prevalent vs. incident
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BE Dysplasia Summary-2

  • Over diagnosis of HGD
  • Baseline atypia of metaplasia
  • Reactive cardia
  • Inflammatory change
  • Loss of nuclear polarity
  • HGD management options broadening
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BE Dysplasia Summary-3

  • HGD management options broadening
  • Continued surveillance: incident HGD
  • Ablation
  • CBE-EMR
  • Duplicated muscularis mucosae:

beware of overstaging T1a to T1b

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