Severe Macrocytic Anemia Uncovering Pernicious Anemia and Early-Stage Gastric Adenocarcinoma: A Case Report

Pernicious anemia (PA) is an autoimmune cause of vitamin B12 deficiency, often secondary to chronic atrophic gastritis, which increases the risk of gastric malignancies. Early signs, like mild macrocytosis, are frequently overlooked, especially in patients with other risk factors such as long-term metformin use. We present a case illustrating the full clinical trajectory from long-standing, unexplored macrocytosis to severe anemia, ultimately leading to the diagnosis of PA and detection of early-stage gastric adenocarcinoma on surveillance esophagogastroduodenoscopy (EGD). Informed consent was obtained from the patient to publish the case. The patient was a 59-year-old man with type 2 diabetes, treated with metformin 2 g daily for over four years, who presented with severe symptomatic macrocytic anemia after approximately one year of unexplored macrocytosis on routine laboratory testing. Evaluation revealed profound vitamin B12 deficiency with evidence of hemolysis, and serologic testing confirmed PA. Surveillance EGD identified a gastric polyp, which was resected for histopathologic evaluation. Examination of the lesion revealed a moderately differentiated adenocarcinoma with associated high-grade dysplasia and submucosal invasion. Random gastric biopsies demonstrated chronic inflammation with focal atypia and were negative for Helicobacter pylori. Subsequent staging investigations confirmed stage I disease (cT1b, cN0, and cM0). The patient underwent partial gastrectomy and continued intramuscular vitamin B12 therapy, with excellent clinical recovery and no evidence of recurrent disease on follow-up. Our case highlights that persistent macrocytosis should not be overlooked, particularly in patients with risk factors for vitamin B12 deficiency such as long-term metformin use. Early evaluation may uncover important underlying diagnoses such as PA, prevent severe hematologic complications, and facilitate detection of associated gastric malignancies at a potentially curable stage.