November 2023 – Gastroenterology Pathology Case 2

A 17-year-old girl presents to her primary care physician with episodic watery diarrhea, nausea, and crampy abdominal pains. She is up to date on her vaccinations and denies any recent travels or changes in her diet. Family history and past medical history are both unremarkable; moreover, physical exam is only significant for mild, diffuse abdominal tenderness. Upper GI endoscopy demonstrates diffuse nodular mucosa in the fundus. A fundic biopsy is taken and shown below.

Figure 1: Upper GI Endoscopy
Figure 2: Stomach biopsy

Which of the following is most characteristic of her condition?

  • Anemia and upper gastrointestinal bleeding symptoms are more common in younger patients.
  • Definitive therapy is a combination of PPI and antibiotics.
  • Biopsy of nodules on endoscopy will demonstrate diagnostic pathology.
  • The subepithelial space will stain with Congo red.

The correct answer is ...

Anemia and upper gastrointestinal bleeding symptoms are more common in younger patients.

Collagenous gastritis is described in the literature has having a bimodal distribution: a pediatric subtype and an adult subtype. The pediatric variant of the condition is more likely to present with anemia and upper GI bleeds. The bleeding episodes are thought to be due to entrapment of blood vessels within the subepithelial collagen plate (please review the biopsy image and note the many vessels within said collagen). The adult form of the condition, while less likely to be associated with anemia/UGIBs, often presents within the setting of other comorbidities, such as lymphocytic gastritis, celiac sprue, autoimmune disorders (e.g., Hashimoto thyroiditis, polymyositis), as well as collagenous colitis.1 There has also been a case report of collagenous gastritis in a patient with systemic lupus erythematosus, but more research needs to be done to conclusively determine whether or not there is an association between the two clinical entities.2 It is also worth noting that this dichotomy is merely a trend and not definitive; for instance, anemia and bleeding symptoms have been reported in some adult patients as well, though it appears to be a more common presentation in the younger population.

The subepithelial space will stain with Congo red.

While the subepithelial material may resemble amyloid deposits, it is important to allow the patient presentation and history to guide the diagnosis. While amyloidosis is certainly worth placing in the differential given the biopsy specimen, amyloidosis is much more common in the setting of other comorbidities. For instance, primary amyloidosis (AL amyloidosis) is typically secondary to the overproduction of immunoglobulin light chains in the setting of a plasma cell dyscrasia — such as multiple myeloma or Waldenström macroglobulinemia. Moreover, secondary amyloidosis (AA amyloidosis) is due to deposition of serum amyloid A protein. This is seen in chronic inflammatory conditions such as rheumatoid arthritis, as well as juvenile rheumatoid arthritis. Another class of amyloidosis worth mentioning involves the deposition of transthyretin within liver and cardiac tissue. These patients tend to present with symptoms of heart failure.3

Definitive therapy is a combination of PPI and antibiotics.

To date, no definitive therapy has been agreed upon. An important concept to keep in mind for this entire case (and any case for that matter) is that, while we learn textbook cases, we generally do not live textbook lives. Still, we hope that our medical tomes might at least guide us towards piecing together some clinicopathologic gestalt. But what should we do when the textbook is still being written? Collagenous gastritis, as a clinical entity, was first described in 1989 by Colletti and Trainer.As such, this condition is relatively new in its description in the literature; consequently, there is currently no definitive cure or treatment for this condition. Varying therapies — such as PPIs, H2 blockers, sucralfate, misoprostol, 5-aminosalicylates, and corticosteroids — have been tried with variable success. Topical, targeted budesonide administration has shown promising results for managing symptoms; that said, a standard of care has yet to be definitively defined for collagenous gastritis.5 Antibiotics are only used when there is an underlying infectious etiology, which is not the case in majority of reported cases.

Biopsy of nodules on endoscopy will demonstrate diagnostic pathology.

This may seem counterintuitive, but the raised, polyp-like areas of nodularity actually demonstrate normal stomach histology. It is actually the areas of depression around these nodules which are best for biopsy, as these depressed areas evince subepithelial collagenous thickening. Think of it another way: the nodular areas are normal histologically but appear more salient grossly because they are surrounded by areas of collagen deposition.6

Other information regarding collagenous gastritis:

This is a very rare condition. There may be around 300 cases described worldwide, though this is a somewhat liberal estimate, with some experts claiming even fewer cases globally. So far, there does not appear to be a geographic preference. Additionally, some studies suggest there may be a slight female preponderance, though other studies have reported no gender preference. Presenting symptoms may include nausea, vomiting, recurrent crampy abdominal pain, and watery diarrhea. To date, there have been no reported cases of dysplasia or carcinoma arising from or as a consequence of collagenous gastritis. The pathogenesis is unclear, but it is thought that an inciting inflammatory process occurs, which results in subsequent collagen deposition.7


  1. Leung ST, Chandan VS, Murray JA, Wu TT. Collagenous Gastritis: Histopathologic Features and Associations with Other Gastrointestinal Diseases. Am J Surg Pathol. 2009; 33: 788-798.
  2. Al-Kandari A, Al-Alardati H, Sayadi H, Al-Jubaibi B, Mawardi M. An unusual case of collagenous gastritis in a middle- aged woman with system lupus erythematosus: a case report. J Med Case Reports. 2014; 8:278.
  3. Muchtar E, Dispenzieri A, Magen H, Grogan M, Mauermann M, McPhail ED, Kurtin PJ, Leung N, Buadi FK, Dingli D, Kumar SK, Gertz MA. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med. 2021 Mar;289(3):268-292.
  4. Colletti RB & Trainer TD. Collagenous gastritis. Gastroenterology. 1989; 97(6): 1552-1555.
  5. Choung RS, Sharma A, Chedid VG, Absah I, Chen ZE, Murray JA. Collagenous gastritis: Characteristics and Response to Topical Budesonide. Clin Gastroenterology and Hepatology. 2022;
  6. Jin X, Koike T, Chiba T, Kondo Y, Ara N, Uno K, et al. Collagenous gastritis. Digestive Endoscopy. 2013; 25: 547-549.
  7. Jain R & Chetty R. Collagenous gastritis. Int J Surg Path. 2010; 18(6): 534-536.

Dustin Parsons, M.D. 

Resident, Anatomic & Clinical Pathology
Mayo Clinic

Eric Chen, M.D., Ph.D.

Consultant, Anatomic Pathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.