In August 2020, a 67-year-old Chinese woman was admitted to our hospital for review 6 years after gastric adenoma resection. Her symptoms included fatigue, poor appetite and lost 4kg in a year, and she was accompanied by a six-year history of iron deficiency anemia, which has been taking orally with iron and folic acid. The results from blood tests performed showed an iron deficiency anemia and decreased hemoglobin. No abnormalities were found in the Female Tumor Markers or Gastrointestinal Tumor Markers (Table 1). Upper endoscopy revealed multiple lobulated polyps with a size of 0.3-2.0cm in the gastric body (Fig. 1A). Subsequently, electrotomy, electrocautery and endoscopic hemostasis were performed (Fig. 1B), and the diameter of the removed polyp specimen was 0.3-1.2cm, which was gray and soft. The biopsy specimen obtained from the polyp was histologically diagnosed as gastric adenomatous polyp as before.
Interestingly, we discovered that the patient had undergone multiple polypectomies in the same part of the corpus, and was accompanied with anemia all the time. Therefore, adenomatous polyp did not seem to be able to explain the disease completely. Then we did histological examination and revealed that partial epithelial hyperplasia and dysplasia, and the neoplastic areas were interlaced with normal mucosa, as indicated by positive Ki-67 staining in the whole layer of tumor area and a decrease in mucus-secreting goblet cells in the surface epithelium. (Fig. 1C-1F). These results supported the diagnosis of neoplastic transformation of gastric hyperplastic polyp, not gastric adenomatous polyp.
Through further clinical and pathological collaboration, we further found that the normal mucosa around polyps showed atrophy of inherent glands in gastric mucosa with intestinal metaplasia and pyloric gland metaplasia (Fig. 1G, 1H), and linear and nodular hyperplasia of ECL cells based on chromogranin A and synaptophysin staining (Fig. 1I, 1J). Meanwhile, the anti-parietal cell antibody was positive (Table 1). Collectively, these data demonstrated that the background diagnosis was AIG.
The patient had multiple surgeries with a long history of anemia, the onset of AIG, so what was the relationship between neoplastic polyps and AIG? Is there any possibility of misdiagnosis in this patient before? To address these questions, we reviewed the medical history.
Table 1
Laboratory data in August 2020
| Laboratory findings | Value | Unit |
| White blood cells | 4.07 | ⅹ109/µl |
| Red blood cells | 4.2 | ⅹ106/µl |
| Mean corpuscular volume | 83.3 | fl |
| Hemoglobin | 112 ↓ | g/dl |
| Hematocrit | 35 | % |
| Platelets | 135 | ⅹ104/µl |
| Serum iron | 7.23 ↓ | µmol/l |
| Total iron binding capacity | 68 | µmol/l |
| Ferritin | 13.3 | ng/ml |
| CA724 | < 1.500 | U/ml |
| CEA | 2.22 | ng/ml |
| AFP | 3.630 | ng/ml |
| Anti-parietal cell antibody | (+) | |
| ↓ The patient’s value was below normal. |
In November 2014, the first visit of this patient was due to a physical examination. The results from positron emission tomography-computed tomography revealed gastric space occupation, as demonstrated by the vegetable pattern mass of the gastric wall on the greater curvature of the gastric body protrudes into the gastric cavity, and metabolism increases. Therefore, neoplastic lesions were considered. Upper endoscopy showed that there were 1.5×2.0cm polyps in lobulated shape on the greater curvature of the gastric body, with scattered erosion on the surface (Fig. 2A, 2B). The pathological results showed that partial epithelial hyperplasia, and dysplasia, the tumor lesions were strongly positive for Ki-67 and PAS staining showed mucus secretion reduced, (gastric body) tubular adenomatous polyps were considered (Fig. 2C-2F). The results of blood tests listed in Table 2 showed no obvious abnormality. Collectively, these results seemed to point to the diagnosis of adenomatous polyp.
However, what is the truth? Retrospective analysis of the sections of the original fundus glandular gastric mucosa showed fewer inherent glands and pyloric gland metaplasia (Fig. 2G, 2H). Supplementary immunohistochemical staining confirmed the presence of specific linear and nodular hyperplasia of ECL cells in the gastric mucosa around adenomatous polyps, which was typical morphological evidence for AIG. (Fig. 2I, 2J). Unfortunately, serological tests were not performed at that moment. Therefore, no special treatment was done except that the follow-up was informed six months later.
Table 2
Laboratory data in November 2014
| Laboratory findings | Value | Unit |
| White blood cells | 3.11 | ⅹ109/µl |
| Red blood cells | 4.2 | ⅹ106/µl |
| Mean corpuscular volume | 89.3 | fl |
| Hemoglobin | 118 | g/dl |
| Hematocrit | 37.5 | % |
| Platelets | 169 | ⅹ104/µl |
| Serum iron | 8.50 | µmol/l |
| Total iron binding capacity | 48 | µmol/l |
| Ferritin | 17.1 | ng/ml |
| CA724 | 1.340 | U/ml |
| CEA | 4.01 | ng/ml |
| AFP | 3.860 | ng/ml |
In July 2015, upper endoscopy was repeated, and the results revealed that there were several titanium clips fixed on the mucosa in 2014, and an arty polypoid ridge with a size of about 0.4*0.4cm in the same place. The mucosa around the surface of the hyperplasia was rough and less smooth, and polyp electrotomy was performed (Fig. 3A, 3B). Retrospective analysis of the biopsy pathology showed gastric hyperplastic polyp with neoplastic change in part of epithelium and nodular hyperplasia of a few ECL cells in surrounding background mucosa (Fig. 3C-3E). It suggested that the patient may have autoimmune gastritis, despite the absence of serological tests and the recurrent polyp may have been misdiagnosed as an adenomatous polyp.
In April 2016, the patient underwent upper endoscopy again and discovered the original titanium clip of the gastric body remained with small polyps around it, as shown in Fig. 4. Later, removed together with the titanium clip. After that, the patient felt that his symptoms were well and did not undergo electronic gastroscopy review. which is a very regrettable for the health of patient.
Therefore, the patient developed recurrent hyperplastic polyps with neoplastic changes on the same gastric mucosa, but which was misdiagnosed as adenomatous polyp due to the neglect of the background of autoimmune gastritis. The whole clinical process and timeline of this patient is exhibited in Fig. 5. Fortunately, the correct diagnosis was eventually confirmed by comprehensive analysis of gastroscopy, pathology and serology. Of course, many important information has also been ignored. For example, the patient was elderly female, the onset site was gastric corpus and polyps recurred in a short period after repeated resection, which were consistent with the epidemiological characteristics of AIG. Therefore, when patients recurrent GHP in the body of gastric with a history of anemia, we should be alert to the possibility of AIG, especially repeated recurrence in the same position after polyp resection.