5/24/2014 Controversial stuff that occurs slightly above, within or slightly below the gastroesophageal junction, including Barrett’s mucosa: Henry Moon was one of the What role do we giants in academic pathology pathologists play? during my early years. We fuss a lot over Pretty small This is it! goblet cells & cancer considering in and around the the size of GE junction, everything but do they deserve around it! all the fuss? 1
5/24/2014 Sometimes the lower Let’s start esophagus and the GEJ are connected by the same with 2 cases changes, almost as if they are a single entity Biopsies of erythema are #1: Dyspeptic adult woman not among the least informative responding to medication But we won’t discourage (PPIs) has upper endoscopy. of all biopsies. the GI people from The endoscopist saw erythema biopsying erythema at the gastroesophageal We need the business!! junction. Nothing else. The erythema was biopsied Biopsies of erythema account for about 7% of my income 2
5/24/2014 #1 3 columnar 1 columnar squamous squamous columnar #1 squamous #2 columnar 2 columnar squamous Chronic inflammation! 1 Plasma cells 3
5/24/2014 Pancreatic acinar metaplasia (PAM) 2 Pancreatic acinar cells mixed with Huge pit cells: pseudogoblet cells cardiac gland 3 mucus cells #2 Don’t confuse these Squamo-columnar junction with real goblet cells No goblet cells! 4
5/24/2014 Summary Finally, way off at the edge of the biopsy Endoscopic erythema at the GE Junction. No endoscopic Barrett’s mucosa Squamous and columnar mucosae The evil, The columnar mucosa has SO? Inflammation: plasma cells dreaded Goblet cells….and mimics goblet Pancreatic acinar cells in the cells!! cardiac glands This is a common biopsy. #2: Obese adult white male (the Barrett model) It is annoying, because it Heartburn for 20 years, recently worse Not responding to PPIs endoscopy does not have a standard name GEJ tongues: “cannot tell if this is an exaggerated Z-line or has a lot of features, but what do short segment Barrett’s” they all mean? I will deal with this. Bx taken of the tongues does not answer the clinical Pathologist told (not asked) question: what caused dyspepsia? to R/O Barrett’s (The true request was to R/I Barrett’s) 5
5/24/2014 Inflammation Summary like the first bx Endoscopic: changes that may be either an exaggerated Z-line (squamocolumnar junction) or short segment Barrett’s mucosa Goblet Pseudogoblet cells Histologic: cells Columnar mucosa Inflammation Goblet cells…..and mimics These 2 sets of biopsies around the gastroesophageal junction have Columnar mucosa SO? Impressive chronic inflammation Goblet cells 6
5/24/2014 First: Because it includes There are 2 Barrett’s mucosa and the gastric cardia, both of which have cancer compelling associations reasons Everything interesting and Adenocarcinomas at and around the Gastroesophageal Junction contentious about the cardia and Barrett’s is driven by cancer risk Sometimes (often?) we cannot tell where because cancers in and around Distal the cancer is arising! the GEJ are said to have been Esophagus (Barrett’s) increasing at a great rate in western societies. Junctional NOS Fundus Cardia Otherwise, we wouldn’t care! Upper Body 7
5/24/2014 Second: This is it! Disclaimer: The GE junction affects About 10% of my standard of living my income is derived from much more than its size specimens taken from suggests it should! the GEJ and nearby. Junction #1 The Squamocolumnar Our clients, the Junction (Z-line) an endoscopic (gross) visible line gastroenterologists actually have to deal with 2 junctions. Spechler SJ. Gastroenterol 117:218, 1999 8
5/24/2014 Junction #2 Top of the The Gastroesophageal proximal fold Junction: Also, the squamo- Thus, the an endoscopic less obvious columnar GE Junction line….. junction Defined somewhat arbitrarily, as the level of (Z-line) the most proximal extent of the gastric folds Spechler SJ. Gastroenterol 117:218, 1999 Columnar epithelium lined lower esophagus Top of the SCJ proximal fold Also, the (Z-line) GEJ squamo- Thus, the (top of columnar GE Junction folds & junction (Z-line) point of flare) Another definition of the GEJ is the point where the lumen flares 9
5/24/2014 Normal Cardiac Mucosa The Cardia There are 2 cardias Pits and 1. The gross anatomic glands equal structure thickness 2. The microscopic mucosa Of these, the important one is the microscopic mucosa Clustered mucus glands The Gross Cardia Where in the hell is it? If we want to study the cardia, where should we find it? 10
5/24/2014 The Gross Cardia Published Definitions of the Cardia: seem to mix gross and microscopic Where in the hell is it? The AJCC gave it a 1. No size. site code: C16.0 which 2. About 1 cm long includes 3. 1-2 cm long cardia and EG jct. Their definition of the 4. Several cm long cardia in 2010: 5. 0.5 to 4 cm long “The proximal 5 cm of stomach“ Published Definitions of the Cardia Where is the cardia? 6. Within 5 cm of EGJ 7. 1 cm proximal to 2 cm distal to the EGJ Somewhere 8. Narrow zone between around esophagus and stomac h 9. A small ill-defined area, here extending 1-3 cm from the GEJ (Owens, Hist for Pathol, 2012) 11
5/24/2014 Cardiac mucosa Cardiac mucosa If you want to study the cardia, may be minute. The only way to where do you take biopsies? study it is to biopsy the SCJ Squamous Across the normal mucosa squamo-columnar junction � Hiatal � hernia 5 cm AJCC cardia Body mucosa Is cardiac mucosa normal? It doesn’t matter Studies from U Southern California conclude that if cardiac mucosa is cardiac mucosa is abnormal and due to reflux, and that it is the precursor of Barrett’s mucosa (Chandrasoma, et al, AJSP, 2000 to present) normal or abnormal. Other studies indicate cardiac mucosa occurs in infants and children, suggesting that it is It exists, so we normal (Zhou, et al, Mod Pathol, 1999, Kilgore,et al, AJG, 2000) have to deal with it! Suggestions that it may be normal in some and abnormal in others 12
5/24/2014 Carditis Cardiac mucosa is Cardiac mucosa is Chronic: Plasma cells usually inflamed usually inflamed Activity: PMNs Carditis Definition: microscopic inflammation in cardiac mucosa Almost every cardiac mucosa has some Causes: Currently an enigma H pylori? The intense active/chronic forms Acid Reflux? Data inconsistent Bile Reflux? one study from Leeds Unknown? Many ?most mild cases Cardiac intense Oxyntic very mild Multifactorial? Possibly inflammation inflammation 13
5/24/2014 Carditis: 2 types in Boston Definitions PAM H pylori Type GERD active sx esophagitis gastritis Reflux yes yes no H pylori Looks like no no yes overlap to Results of analysis me! Type Overall PMNs Plasma multilayered M:F inflam cells epithelium Pancreatic Reflux less fewer fewer yes 7:3 H pylori more more more no 3:5+ Acinar Wieczorek, Wang, Antonioli, Glickman, Odze (BI-Deaconess Metaplasia & Brig-Woman's), Am J Surg Pathol, 27:960, 2003 Pancreatic Acinar Metaplasia � Is it a metaplasia, or is it congenital? 16% peds cardiac bx � Is it a disease, or is it normal? Goblet Goblet Common in the cardia cells cells 24% of 155 adult junction bxs � So far: no significance 14
5/24/2014 How common is cardiac IM Goblet Cells in Cardiac Mucosa 4 US centers, 940 adults 40 yrs and older who came Numerous studies This is utter for colonoscopy and agreed to have upper endoscopy. Sites of biopsies vary from 122 (12.9%) cardiac goblet cells nonsense! lower 2-3 cm of esophagus (as long as the SCJ is normal) to associated with advancing age 2-3 cm below the GEJ and +H pylori test Prevalence of goblet cells: 3% to 36% Rex, et al, Gastroenterol. 125:1670, 2003 The M:F = 0.4:1 to 9:1 Goblet Cells in Cardiac Mucosa 195 patients, elective upper endoscopy Goblet Cells in Cardiac Mucosa no endoscopic Barrett’s magnification endoscopy with acetic acid spraying Causes single targeted biopsy of specific mucosal types 86 (44%) had intestinal metaplasia (goblet cells) � acid reflux � bile reflux � H pylori � at least 2 of the above villiform pattern: 60% Cerebriform pattern: 96% � something else conclusion: with this technique, cardiac goblet cells are very common Guelrud, et, Am J Gastroenterol 97:584-9, 2002 15
5/24/2014 Cardiac IM called “histologic Goblet Cells in Cardiac Mucosa Barrett’s mucosa” in a German study 128 patients with 5 yr follow-up 33 (26%) developed endoscopic Barrett’s Significance: Known length in 26 of the 33 We worry that they are 12 pts: <1cm short markers of high cancer risk. 11 pts: 1 to <3cm segment There is no data that they are. 3 pts: ≥ 3cm (long segment) No idea what this means for neoplastic risk Leodolter, et al: Scand J Gastoenterol 2012;47:1429 So whenever cardiac mucosa is biopsied, you get various Goblet Inflammation cells combinations of… PAM 16
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