Unfound gastric signet ring-cell adenocarcinoma after gastric biopsy

In the September issue of Endoscopy, Kim et al. [1] described a group of 20 patients (out of 633 endoscopic mucosal resections [EMR] or endoscopic submucosal dissections [ESD]; 3.2 %) with negative histologic findings, despite the fact that the previous forceps biopsy displayed a high-grade dysplasia or intramucosal carcinoma. The authors suggest that the tumor might have been so small that it was probably removed with the forceps biopsy before the EMR or ESD. As another option for this lack of tumor in the resection tissue is sampling error, the authors recommend good communication between endoscopist and pathologist. A recent study by Rabenstein et al. described 22 patients with invisible gastric cancer (IGC) in whom gastrectomy would normally be recommended. The authors suggest that gastrectomy may not be the only option for IGC, which might follow an uneventful natural course, provided careful follow-up is scheduled. They also used photodynamic therapy in the area where the biopsy was taken; however further studies are needed in relation to this type of treatment [2].

We report the case of a 55-year-old male who, in May 2006, underwent a gastroscopy due to Helicobacter pylori infection and failure of the eradication therapy. Biopsies were taken for pathologic examination and antibiogram. Most histologic samples displayed H. pylori-associated chronic gastritis with severe inflammatory infiltrates, but one sample obtained from the body of the stomach showed a small focus of signet ring-cell adenocarcinoma that infiltrated the lamina propria. The cells showed expanded, globoid, and optically clear cytoplasm with displacement of nuclei to the cell border ([Fig. 1]).

Fig. 1 Intramucosal signet ring-cell gastric adenocarcinoma. Hematoxylin and eosin stain.

Cytoplasms were positive for periodic acid-Schiff (PAS)-Alcian blue and PAS ([Fig. 2]).

Fig. 2 Intramucosal signet ring-cell gastric adenocarcinoma with periodic acid Schiff staining under high magnification.

Near this focus of cells, there was also an intense inflammatory infiltrate of lymphocytes, neutrophils, and plasmatic cells as well as ballooning of the epithelial cells related to the abundant H. pylori bacilli on the surface. According to these histologic findings, the diagnosis of intramucosal signet ring-cell adenocarcinoma was established and total gastrectomy was recommended.

However, to corroborate this diagnosis, as no macroscopic lesion was seen, additional gastroscopies were performed. Biopsies displayed H. pylori-related chronic gastritis, predominantly in the antrum, but no evidence of dysplasia or carcinoma was ever found in the multiple biopsies taken. Because the patient was reluctant to undergo surgery, he was sent to our hospital for a second opinion.

In our hospital he underwent many periodic gastroscopies, even with chromoendoscopy and magnification, and numerous biopsies were taken during each of the procedures. All of these biopsies were informed as chronic antral gastritis. In order to search for submucosal infiltration, upper endosonography was performed at this stage and also 2 years later, but on both occasions the results were normal. Computed tomography scan and abdominal ultrasonography to search for possible metastases were also normal. All tumor markers were within range.

Several pathologists from our hospital reviewed the biopsies from the previous hospital and confirmed the diagnosis of signet ring-cell adenocarcinoma. However, they could not find any signs of dysplasia or neoplasia on the numerous biopsies taken at subsequent endoscopies. In order to rule out an error in collecting and processing of samples and to ensure that they belonged to the patient, we performed a genetic test. We analyzed the microsatellites penta C and D in the paraffin block of the adenocarcinoma-containing sample, as well as in the subsequent biopsies and in peripheral blood samples obtained from the patient. This molecular study concluded with a probability of greater than 98 % that all samples belonged to the same patient.

In our opinion, these diagnostic problems are being found with an increased frequency in clinical practice and constitute a challenge to the decision-making skills of the clinician. In our case, and judging from the 4-year survival of the patient, who is asymptomatic and has no signs of disease, we have little doubt that the focus of tumor cells was eliminated with the forceps biopsy [1].

Of course, we cannot exclude that new foci will be formed in the future; therefore, 6 – 12-month endoscopic follow-up with numerous random biopsies seems appropriate in this case, as the patient has strong feelings against radical surgery. After the initial histologic findings, and considering the ominous prognosis of this tumor, it is likely that most experts would have recommended total gastrectomy. In general terms, that is what is now recommended. However, if the area of biopsy is known, the new ESD procedure [3] [4] offers the chance of performing a less-radical resection of the affected area as well as giving additional histologic information on whether surgery is needed or, if the tumor is intramucosal and has been completely removed, a close endoscopic follow-up can be recommended in most cases. However, as Nakamoto et al. prove in their recently published paper, if the lesion is less than 1 cm it can be managed with EMR with the same results as ESD [5]; therefore, in those cases EMR may suffice [6]. Although ESD increased en bloc and histologically complete resection rates and may reduce the local recurrence rate, it also increased the time and complications of the procedure compared with EMR. New measures are needed to avoid ESD ulcerations and to reduce the rates of perforation and incomplete resection [3] [7].

Competing interests: None

References

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