Editor,Aggregates of non-neoplastic signet ring cells have been previously described in the small intestine mucosa in ischaemia 1 and in association with Peutz-Jeghers polyps,2 and in the colonic mucosa in ulcerated adenomas 3 and pseudomembranous colitis.4 They are an uncommon finding that may be mistaken for signet ring cell carcinoma.A similar phenomenon has also been identified outside the gastrointestinal tract.5, 6, 7 We report a case in which non-neoplastic signet ring cells in the subserosa of the small intestine could potentially have been mistaken for signet ring cell carcinoma. As far as we are aware, benign signet ring cells mimicking signet ring cell carcinoma have never before been described in the subserosa of the intestine.
CASE REPORT
A 76-year-old man presented with subacute bowel obstruction. Three years previously he had an extended right hemicolectomy for colonic adenocarcinoma. His past medical history included ischaemic heart disease and an abdominal aortic aneurysm. A barium enema showed a tight stricture, proximal to the point of previous anastamosis, suggestive of an obstructing tumour. He subsequently underwent laparotomy, resection of the strictured intestine and ileocolic anastamosis.The surgical specimen consisted of 28cm of small intestine anastamosed to 3cm of large intestine. The distal small intestine was concentrically strictured adjacent to the point of anastamosis. Fibrinous exudate was present on the serosal surface and the small intestine wall was thickened. There was shallow mucosal ulceration in the strictured area.Multiple sections were examined histologically. These showed features of an ischaemic stricture. There was mucosal ulceration and the submucosa was lined by inflamed granulation tissue. There was also fibrosis of the submucosa and subserosa. Where the mucosa was intact there was hyalinisation of the lamina propria. However, in several sections there was an abundance of cells with signet ring morphology localised to the subserosa (Figure 1). We were immediately concerned that these cells represented locally recurrent or metastatic signet ring cell carcinoma.
Fig 1A
Subserosal signet ring cells in groups and singly dispersed.
Subserosal signet ring cells in groups and singly dispersed.High power view showing signet ring morphology.We reviewed the histology from the initial case. This was found to be an adenocarcinoma with an intestinal pattern and there was no signet ring differentiation. In addition we performed immunohistochemistry. The signet ring cells were negative for the epithelial markers CAM5.2 and AE1/AE3. We concluded that these cells were in fact not malignant and are a non-neoplastic mimicker of signet ring cell carcinoma.
DISCUSSION
Stricture of the small intestine can arise from a number of causes including ischaemia, carcinoma, lymphoma, Crohn's disease and tuberculosis.8 This patient had a past history of vascular disease including myocardial infarction and an abdominal aortic aneurysm, and while histology of the small intestine showed features of an ischaemic stricture, the abundance of signet ring cells in the subserosa was alarming.He had a previous colectomy for adenocarcinoma and we considered the possibility that these signet ring cells represented local recurrence. We reviewed the histology from this tumour and found it to have an intestinal pattern with no signet ring differentiation. In addition we thought that these cells could represent metastatic signet ring cell carcinoma from a distant primary site such as the stomach. However in view of the overall context of ischaemia the possibility of a non-neoplastic process was entertained. Negative staining with epithelial markers and awareness of previously described accounts of benign signet ring cells in the intestine and at other sites helped us make the diagnosis of a non-neoplastic mimicker of signet ring cell carcinoma.Aggregates of benign signet ring cells in the intestinal mucosa have previously been documented and are characterised by cells that are cytologically similar to signet ring cell carcinoma.9 Distinguishing signet ring cell carcinoma from these non-neoplastic signet ring cells is difficult using morphology alone as features of malignancy, such as cytological atypia, are often not marked in signet ring cell carcinoma.9 The subserosal benign signet ring cells in this case are a similar diagnostic dilemma and in our opinion, could have been mistaken for signet ring cell carcinoma.A wide panel of immunohistochemical markers was performed. We considered a mesothelial origin for these cells given the subserosal location but staining with calretinin, thrombomodulin and WT1 proved negative. The histiocytic marker CD68 was also negative. The cells were positive with S100. While S100 positivity is seen in wide variety of cell types, in view of the morphology of these cells and given their location in the subserosa, we feel that they are most likely adipocytes distorted by subserosal fibrosis that has occurred secondary to intestinal ischaemia.In contrast, mucosal aggregates of benign signet ring cells are thought to be dispersed Goblet cells derived from multipotent stem cells in the crypt base following ischaemic injury.1 These cells stain positive for neutral mucins 1 and they are also positive immunohistochemically with pancytokeratin. 1 The subserosal aggregates of signet ring cells in this case are negative for both neutral mucins and epithelial immunohistochemical markers.In summary, the distinction of non-neoplastic signet ring cells from signet ring cell carcinoma is vital as the incorrect diagnosis of signet ring cell carcinoma has obvious prognostic and therapeutic implications. We have described a case in which aggregates of benign signet ring cells in the subserosa of the small intestine could have been mistaken for signet ring cell carcinoma. An erroneous diagnosis was avoided by consideration of this finding in the context of all the changes present, through awareness of the existence of benign mimickers of signet ring cell carcinoma, and by the use of immunohistochemistry.
Fig 1A