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Covers the chronic gastritides and precursor lesions of the stomach for boards, unified by what each disease does to gastrin. Teaches autoimmune atrophic gastritis, the H. pylori Correa cascade toward intestinal-type cancer, Menetrier disease, and Zollinger-Ellison syndrome. Emphasizes the two high-yield differentials: high gastrin sorted by gastric pH, and giant gastric folds sorted by acid output and biopsy.
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Study the full chapter on Board Pearls, with practice questions, tables and primary-guideline references: Gastritis, Gastric Cancers, and Submucosal Tumors
Read this episode: boardpearls.com/gi/episodes/gastritis-gastric-cancers-smts-ep1
Questions or feedback: hello@boardpearls.com.
The most complete gastroenterology board-review podcast on the web, and it is entirely free. This is the GI series from Board Pearls: board review built around clinical reasoning, not recall. Every episode takes one high-yield topic and works it the way you would on rounds: a case to anchor it, the framework that sorts the differential, and the specific decisions the exam rewards. No trivia, no textbook dictation, just the thinking that earns the point.
Over 100 episodes span the full blueprint across nine modules (esophagus, stomach and duodenum, small bowel, colon, pelvic floor, liver, pancreas and biliary, endoscopy, and the cross-cutting topics), grouped by chapter and built from the guidelines and pivotal trials the boards are written from: ACG, AGA, AASLD, and ASGE.
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Welcome to Board Pearls. This is episode one of two of the Gastritis, Gastric Cancers, and Submucosal Tumors chapter, in the Stomach and Small Bowel Disorders module. This episode is the chronic gastritides and the precursor lesions: autoimmune atrophic gastritis, the H. pylori cascade toward cancer, Menetrier disease, and Zollinger-Ellison syndrome. Gastrin runs through most of it, so watch how each disease moves gastrin, because that's what ties the episode together.
Start with autoimmune atrophic gastritis, where every exam finding falls out of one fact about anatomy: the immune system destroys the parietal cells, and those cells live in the body and fundus, not the antrum. Parietal cells make acid and intrinsic factor, so losing them makes the stomach acid-free, B12 absorption fails because it needs intrinsic factor, and iron absorption fails because the duodenum needs acid to take up iron. Meanwhile the antrum is spared, so its gastrin-making cells keep going, and since acid normally restrains gastrin, losing the acid removes the brake and gastrin climbs. That sustained high gastrin is a growth signal to the enterochromaffin-like cells in the body, driving them to hyperplasia over years and producing type one gastric neuroendocrine tumors. So the anemia, the low acid, and the tumors are all one anatomic lesion showing up in three different systems.
The mechanism is antibody-driven. Anti-parietal-cell antibodies target the acid pump and are the most sensitive marker; anti-intrinsic-factor antibodies are less sensitive but more specific, so a positive one essentially clinches it when the picture fits. And the disease travels with other organ-specific autoimmunity, most often Hashimoto thyroiditis, along with type one diabetes, vitiligo, and Addison disease, so a middle-aged woman with a thyroid history and a macrocytic anemia is a deliberate hint.
The blood picture comes two ways. The classic one is megaloblastic anemia from B12 deficiency, with large red cells, hypersegmented neutrophils, elevated methylmalonic acid and homocysteine, and in advanced cases the neurologic syndrome of dorsal column and corticospinal loss, so ataxia, lost vibration and position sense, hyperreflexia, and an upgoing toe. The trap is treating with folate alone, which fixes the anemia while the neurologic disease keeps progressing, which is exactly why you never give folate for an unexplained macrocytic anemia without checking B12. But iron deficiency is just as common and often comes years earlier, because the low acid impairs iron absorption before intrinsic factor reserves run out, so the unexplained iron-deficiency anemia in an older patient who's H. pylori-negative and celiac-negative is the textbook stem.
On endoscopy it's an incidental finding: pale, smooth body mucosa with lost folds, sometimes with small nodules that turn out to be those type one neuroendocrine tumors. Biopsy technique matters, and the reason is the anatomy: the diagnosis is body atrophy with antral sparing, so the antrum and body have to be sampled and labeled separately, since a single mixed jar can't tell the pathologist which fragment came from where. The standard sampling is the Sydney protocol, two from the antrum, two from the body, and one from the incisura. Serology supports it: the parietal-cell and intrinsic-factor antibodies, a high fasting gastrin because the acid brake is gone, and a fall in pepsinogen one, made by the body's chief cells, so the pepsinogen one-to-two ratio drops as a marker of body atrophy. And you test for and exclude H. pylori, because a coexisting infection changes the cancer risk.
Management handles the downstream consequences in order. Replace B12, either by injection or high-dose oral, and the oral route works because at high doses a small fraction is absorbed by simple diffusion that bypasses the intrinsic-factor pathway. Replace iron, orally or intravenously. Screen for autoimmune thyroid disease, and here's a reward fact: thyroid cancer risk is not raised in this disease, it's actually slightly lower. And surveillance endoscopy every three to five years catches the type one neuroendocrine tumors and the rare dysplasia, with lesions over a centimeter resected endoscopically and smaller ones watched. Gastrectomy is essentially never the answer for those type one tumors alone, because removing the lesion doesn't remove the gastrin drive that produced it.
That brings us to the H. pylori cascade, the other major chronic gastritis and the one most tested as a cancer precursor. Chronic H. pylori gastritis doesn't become cancer overnight, it walks down a stepwise sequence: chronic active gastritis, to atrophy, to intestinal metaplasia, to dysplasia, to intestinal-type adenocarcinoma. The driver is sustained injury from the bacterium, with the more virulent strains and certain host inflammatory genotypes speeding it up. Eradicating H. pylori interrupts the sequence but doesn't erase the risk once metaplasia has appeared, which is why metaplasia is the threshold that brings surveillance into play. Worth flagging: the diffuse type of gastric cancer sits off this sequence entirely, arising from non-atrophic mucosa through loss of the E-cadherin protein, which is the type tied to the inherited CDH1 syndrome, and that's an episode-two thread; for now, the cascade is the intestinal-type story.
There are two staging systems that turn the distribution of disease into a surveillance plan, one grading atrophy and one grading intestinal metaplasia, both on a zero-to-four scale combining antrum and body, with the metaplasia version generally favored because it's more reproducible between pathologists. The low stages are low risk and need no surveillance; the high stages, with extensive atrophy or metaplasia, carry meaningfully higher cancer risk and get surveillance endoscopy about every three years with careful imaging and targeted biopsies. And modifiers can pull an intermediate patient into surveillance on their own: ancestry from a high-incidence country, a first-degree relative with gastric cancer, the incomplete colonic-type metaplasia rather than the complete small-bowel type, and involvement of both antrum and body rather than antrum alone. So a patient with both-region incomplete-type metaplasia and a sibling who died of gastric cancer goes on surveillance even with moderate-looking disease, because those modifiers stack on top of stage. On treatment, you eradicate H. pylori at every stage because it lowers ongoing injury and progression, but eradication lowers risk without erasing it, which is exactly why surveillance is added on top for the high-stage patient.
Menetrier disease is the last hypertrophic gastropathy here, grouped in because it shares the giant-fold look. Its mechanism has nothing to do with H. pylori or the cancer cascade; it's overproduction of a growth factor that signals through the EGF receptor on the surface foveolar cells, driving massive foveolar hyperplasia while causing the acid- and enzyme-making glands to atrophy. So you get giant folds in the body combined with low acid, and the overgrown surface cells pour out mucus, and that protein-rich mucus is lost across the stomach wall, producing the classic triad of low albumin, edema, and weight loss, along with diarrhea and occasional bleeding, again in a body-and-fundus distribution with antral sparing.
The differential of giant gastric folds is what actually gets tested, and you sort it by acid output and protein. Menetrier is low acid with protein loss. Zollinger-Ellison is high acid without protein loss, because gastrin is a growth signal to the mucosa. Lymphoma and adenocarcinoma with the linitis-plastica look need biopsy, and a few infiltrative diseases round it out. So histology plus gastric pH do most of the work. Diagnosing Menetrier needs a deep biopsy because the lesion lives in the surface layer that routine forceps often don't reach, with ultrasound showing the thickened, cystic mucosa and helping exclude cancer, and you always test H. pylori because it can produce a Menetrier-like picture that eradication resolves, and in children CMV can cause a self-limited version. Treatment targets the receptor driving it with an anti-EGFR antibody, which is the favored medical answer, while acid suppression only helps symptoms, and albumin and high-protein nutrition manage the protein loss, with gastrectomy reserved for refractory disease or dysplasia, since Menetrier carries an elevated cancer risk and gets surveillance. The mimic to discount is reactive gastropathy from bile or NSAIDs, which shows foveolar hyperplasia in the antrum and is managed by removing the exposure, not with the antibody.
The third part is Zollinger-Ellison syndrome, the gastrin-driven ulcer disease that masquerades as refractory peptic ulcer. Suspect it in any of five situations: multiple ulcers, ulcers beyond the duodenal bulb like jejunal ulcers, ulcers refractory to standard therapy, ulcers with secretory or fatty diarrhea, or ulcers in a patient with a family history of MEN1. The mechanism is a gastrin-secreting neuroendocrine tumor in the duodenum or pancreas that's escaped feedback, so gastrin stays high, the acid-making cell mass expands, and acid output overwhelms the defenses of the upper small bowel, producing severe esophagitis on top of duodenal and jejunal ulcers. The diarrhea has two parts: the sheer volume of acid hitting the small bowel, and fat malabsorption, because the acid load inactivates pancreatic lipase and precipitates bile salts.
The tumor usually sits in the gastrinoma triangle, bounded by the cystic-and-common-bile-duct junction above, the second and third parts of the duodenum on the side, and the neck and body of the pancreas medially. Most gastrinomas are in the duodenum, where they tend to be small and multiple, with the rest in the pancreas, tending to be solitary and larger. About a quarter occur in MEN1, the inherited syndrome with the three P's: parathyroid causing hyperparathyroidism, pituitary causing an adenoma most often a prolactinoma, and pancreas or duodenum causing neuroendocrine tumors, of which gastrinoma is the most common. MEN1 gastrinomas are essentially always multiple, almost always duodenal, and almost never cured by surgery, which shapes management.
Diagnosis starts with a fasting gastrin and a gastric pH, and the interpretation splits cleanly. A fasting gastrin over a thousand with a gastric pH under two confirms the syndrome outright, because nothing else produces both high gastrin and high acid at once. A gastrin over a thousand with a pH above two is high gastrin from an acid-free stomach instead, which fits autoimmune or other atrophic gastritis, where the low acid is driving a secondary gastrin rise. So the acid is the discriminator: high gastrin with low pH is a gastrinoma, high gastrin with high pH is atrophy. The patient has to be off the acid blocker for at least a week before measuring, since it raises gastrin and confounds the test, unless stopping is unsafe because of severe ulcer or bleeding history, in which case you lean on imaging and acid output instead. An intermediate gastrin, between a hundred and a thousand, needs the secretin stimulation test, and the physiology is the teaching point: secretin normally suppresses gastrin from the antral cells, so a non-gastrinoma cause shows a flat or falling response, while gastrinoma cells, having escaped feedback, do the opposite and release gastrin. The number to know is a paradoxical rise of more than a hundred and twenty above baseline within about ten to fifteen minutes of intravenous secretin, and some references use a higher cutoff, so be comfortable with both; the word they want is paradoxical, because secretin inhibits normal cells but stimulates the tumor.
Imaging localizes the tumor for surgery, and the modern answer is somatostatin-receptor PET imaging with DOTATATE, now preferred over the older octreotide scan for its better resolution and sensitivity, alongside CT or MRI for larger pancreatic tumors and liver metastases. Endoscopic ultrasound is most sensitive for tumors inside the pancreas, while the DOTATATE PET is better for the small duodenal ones, so the two complement each other. Treatment has two parallel goals: control the acid and address the tumor. Acid control uses high-dose acid suppression, often several times the usual reflux dose, titrated to an acid-output target rather than a fixed dose, aiming under about ten milliequivalents an hour in an intact stomach, lower after gastric surgery or with severe reflux. For the tumor, a sporadic localized gastrinoma is explored surgically for cure, with the surgeon opening and palpating the duodenum to find the small tumors imaging misses, whereas MEN1 gastrinomas generally aren't pursued for cure because they're multiple, so acid suppression is the mainstay with surgery reserved for larger tumors that carry more metastatic risk. And one MEN1 move worth knowing: you treat the hyperparathyroidism first with parathyroidectomy, because lowering calcium reduces gastrin and acid, often substantially. Metastatic disease is managed with somatostatin analogs, receptor-targeted radionuclide therapy, and targeted agents.
So hold the episode together by what each disease does to gastrin. Autoimmune gastritis raises it from the wrong direction, because the parietal cells are gone and the antrum has lost its acid brake. H. pylori drives injury unrelated to gastrin but produces the cancer cascade and the precursor lesions that justify surveillance. Menetrier makes giant folds through growth-factor signaling with low acid and protein loss. And Zollinger-Ellison raises gastrin from the right direction, an autonomous tumor pouring gastrin into a stomach that still has parietal cells, so it makes acid in excess. Two differentials fall out: high gastrin sorts on gastric pH, low pH being a gastrinoma and high pH being atrophy, with an intermediate value needing secretin to find the paradoxical rise; and giant folds sort on acid output and biopsy.
Episode two picks up the gastric tumors themselves: adenocarcinoma by Lauren type with the molecular profile that drives HER2 and PD-L1 testing, H. pylori-driven MALT lymphoma versus the more aggressive diffuse large B-cell lymphoma, the three types of gastric neuroendocrine tumor split by gastrin, and the KIT-driven GIST as the model targeted-therapy cancer.