—  SPECIALTY CONFERENCE  —

Gastrointestinal Pathology

Case 5 - No Significant Abnormality?

Henry D. Appelman
University of Michigan Medical School
Ann Arbor, MI


Click on each slide thumbnail image for an enlarged view
Clinical History
This is a middle aged adult of either sex, who has suffered from chronic dyspepsia for several years, and the symptoms have gradually worsened. So, he/she went to his/her family doctor who prescribed a protein pump inhibitor. When this failed to control the symptoms, he/she was referred to a gastroenterologist who performed an upper endoscopy, during which an erythematous GE junction was noticed, an enticement for biopsies. What about these biopsies must be mentioned in the diagnosis that has unequivocal clinical significance?


Case 5 - Figure 1 - The biopsy at 10x: columnar mucosa with pits, expanded lamina propria and different gland types
Case 5 - Figure 2 - Higher power of the cellular lamina propria


Case 5 - Figure 3 - Higher power of 2 of the gland types
Case 5 - Figure 4 - Two tubules in another fragment looked like this

Microscopic Description:
The biopsies include the squamocolumnar junction. The columnar mucosa has a mixture of mucus glands and structures resembling pancreatic acini, sometimes mixed with the mucus glands. Occasional glands contain parietal cells. This mucosa is chronically inflamed with intense superficial plasmacytosis, and there is no neutrophilic activity and no H pylori. In one of the pieces, there are two tubules that contain goblet cells mixed with gastric type surface epithelial cells.

Discussion
The columnar mucosa from the endoscopic gastroesophageal junction is from the anatomic cardia, the most proximal part of the stomach. It is inflamed, that is, there is a carditis; it has pancreatic acinar cells mixed with the mucus gland cells; and it contains two tubules with goblet cells, that is, intestinal metaplasia. Do any of these changes explain symptoms, or if not, do they have any clinical significance? If not, are they worthy of mention in the diagnosis?

Symptoms:
There is no evidence that any gastritis, including carditis, produces symptoms. The most common severe gastritis, H pylori gastritis, has not been proven to cause symptoms. In fact, in this country, most dyspeptic symptoms occur in patients with histologically normal stomachs or those with reactive or chemical gastropathy.

Inflammation:
Chronic inflammation in the cardia occurs in almost every cardia that is biopsied. The causes of chronic carditis are not known in every case, although in several studies, H pylori, gastroesophageal reflux and reflux of duodenal contents have been implicated. In the most detailed recent study comparing reflux-type and H pylori-type carditis, there was considerable overlap in histologic findings, and, besides, diagnoses of reflux and H pylori infection are not made by looking at cardiac biopsies but by other means such as pH monitoring and/or esophageal motility studies for reflux, and urease, antibody or breath tests for the bugs. If H pylori is present in the cardia then it should be mentioned in case treatment is indicated. So, if carditis is almost ubiquitous and if we don't know the cause in most cases, is there anything that makes a diagnosis of carditis without H pylori important? I cannot think of a single reason.

Pancreatic acinar cells:
These cells have been found in cardiac biopsies 1/6 of children in one study and in ¼ of adults in another, and in neither study were circumferential cardiac biopsies taken in order to conduct a systematic search, so the prevalence is likely to be higher. We do not know if they are congenital misplacements or metaplasias, although, usually they are referred to as pancreatic acinar metaplasia or PAM. Regardless of how they arrived at the cardia, there is no study that has attached any clinical significance to them Therefore, if they are so common, and if they have no significance, is there any reason to highlight them in a diagnosis? I cannot think of a single reason.

Goblet cells:
We know that goblet cells are the histologic hallmark of Barrett's mucosa, and we know that the diagnosis of Barrett's mucosa requires both endoscopic evidence of abnormal columnar mucosa in the distal tubular esophagus and goblet cells in biopsies from that abnormal mucosa. In this case, the endoscopist did not mention anything abnormal in the esophagus. Only erythema at the junction was described. Therefore, these goblet cells do not indicate that the patient has Barrett's mucosa. Instead, they are goblet cells in cardiac mucosa. The pathology and gastroenterology literature is littered with studies of cardiac goblet cells. The sites of biopsies said by the authors of these studies to have come from cardiac mucosa vary from within the distal esophagus, 3 cm above the GE junction to as far as 3 cm into the proximal stomach, so clearly the data from these studies is based on different types of mucosae. That is probably why the prevalence of goblet cells said to reside in the cardia varies from 3% to 36%. There is one exquisitely performed study of 195 adult patients without endoscopic Barrett's mucosa, whose junctions were sprayed with acetic acid to accentuate the cardiac mucosae followed by magnification endoscopy and targeted biopsies of that mucosa. Based only on at least 2 biopsies form each cardia, 44% of these patients had cardiac goblet cells. It is possible or even probable that had more biopsies been taken, cardiac goblet cells would have been even more common. The concern over cardiac goblet cells is that they may indicate substantial risk for cardiac carcinoma. However, if the above data is correct, then tens of millions of adults in this country have goblet cells, and as best as can be determined from cancer statistics, there are probably no more than 10-12000 new cases of cardiac cancer a year in this country. 10,000 out of tens of millions does not translate into significant risk. Therefore, is there any reason to mentions goblet cells in the cardia in the diagnosis? I cannot think of a single reason.

Conclusion:
Based on this data, how should you sign out this biopsy and others like it? Any way that makes you feel comfortable, that does no harm to the patient and that does not confuse the recipient, the endoscopist. Examples include:

Chronic carditis with goblet cells and pancreatic acinar metaplasia of known cause, if you know the cause, or
Chronic carditis with goblet cells and pancreatic acinar metaplasia of unknown cause, if you don't know the cause, or
Any of the individual features that you feel compelled to report, with or without a cause statement or
No significant abnormality if you want to save words.

References: General

  1. Sampliner RE and the Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol 97:1888-1895, 2002
  2. Sarbia M, Donner A, Baggert HE: Histotpathology of the gastroesophageal junction. A study on 36 operation specimens. Am J Surg Pathol . 26:1207-1212, 2002 (a careful anatomic study detailing how small the cardia is and where it is.)

Carditis

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Intestinal Metaplasia

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  8. Guelrud M, Herrera I, Essenfeld H, et al: Intestinal metaplasia of the gastric cardia: a prospective study with enhanced magnification endoscopy. Am J Gastroenterol. 97:584-589, 2002 (They found cardiac goblet cells in 44% of 195 patients undergoing upper endoscopy who did not have endoscopic Barrett's.)
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  16. Richter JE: Editorial: Intestinal metaplasia and the squamocolumnar junction: what does it all mean? Gut. 42:604-605, 1998
  17. Spechler SJ. Intestinal metaplasia at the gastroesophageal junction. Gastroenterol. 126:567-575, 2004. A superb review of all the issues as of February, 2004
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Pancreatic Acinar Metaplasia

  1. Polkowski W, van Lanschot JJB, ten Kate FJW, et al. Intestinal and pancreatic metaplasia at the esophagogastric junction in patients without Barrett's esophagus. Am J Gastroenterol. 95:617-625, 2000
  2. Popiolek D, Kahn E, Markowitz J, Daum F. Prevalence and pathogenesis of pancreatic acinar tissue at the gastroesophageal junction in children and young adults. Arch Pathol Lab Med. 124:1165-1167, 2000
  3. Wang HH, Zeroogian JM, Spechler SJ, Goyal RK, Antonioli DA. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction. Am J Surg Pathol. 20:1507, 1996