Review

The case report by Reyes¹ exposes an unusual case of esophageal mantle-cell lymphoma (MCL) in a patient with underlying Barrett esophagus who presented with abdominal discomfort and gastrointestinal (GI) bleeding and then underwent diagnostic upper endoscopy. The case also provides a review of this rare disease and its GI involvement.

The GI tract is the predominant site where extranodal non-Hodgkin lymphomas appear. Most non-Hodgkin lymphomas are of B-cell origin and include mucosaassociated lymphoid tissue (MALT) and MCL, as well as Burkitt and Burkitt-like lymphomas.^2,3 In Europe, MCL comprises 5–7% of non-Hodgkin lymphomas.² Most patients with MCL present with advanced-stage disease, and up to 80% have involvement of extranodal sites including bone marrow, spleen, liver, and GI tract. On the other hand, MCL can also present as a primary GI lymphoma.^4,5 MCL tumor cells express pan-B-cell markers such as CD20 and the T-cell marker CD5, an antigen that is normally expressed by a minor subpopulation of B-cells in the adult follicular mantle zone of lymph nodes.

MCL can be diagnosed by different methods, including histologic evaluation, immunohistochemistry using specific antibodies for CD5, CD20, CD79a, and cyclin D1, and molecular analyses such as polymerase chain reaction analysis and fluorescence in situ hybridization. Although histologic evaluation has a low sensitivity, it is a mandatory step in the diagnosis. Nevertheless, in the majority of cases, one of the other methods is needed in order to secure the diagnosis. Immunohistochemistry is perhaps the best technique, being that abnormal cyclin D1 expression is one of the most specific markers. MCL and MALT lymphoma can be similar histologically, especially when diffuse cell proliferation is present; therefore, immunohistochemistry analyses are always necessary.

In clinical practice, the reported frequency of GI involvement in MCL is estimated to be approximately 15–30%.^6,7 Nonetheless, it is likely that this prevalence is underestimated due to the fact that only those patients with GI symptoms and MCL undergo endoscopy.^6,7 Moreover, the most common endoscopic finding is completely normal mucosa. Nodules, inflammation, ulcers, thick folds, masses, and polyps are also found in upper endoscopy, whereas nodules and polyps (usually in the form of multiple lymphomatous polyposis [MLP]) are most frequent in colonoscopy.^8,9 MLP is a term used to describe a distinctive pattern of primary GI involvement by lymphoma, in which any area of the GI tract from the esophagus to the rectum can be infiltrated by white nodular or polypoid tumors.^10,11 The MLP histologic pattern was previously thought to be specific of MCL, but several cases of MALT and follicular lymphoma with an MLP pattern have been reported.¹² Two studies prospectively investigated the frequency of GI involvement in MCL. In both studies, patients with untreated MCL underwent upper and lower endoscopy.^10,11 Only a small proportion of patients (20–30%) presented with GI symptoms, mostly in the form of abdominal pain and diarrhea. Only 38% and 51% of all the patients presented with abnormal upper and lower endoscopy, respectively. However, MCL was present in 71–84% of biopsy samples of patients with normal colonoscopy and in 45–63% of biopsy samples of patients with normal upper endoscopy. As a result, positive predictive value of endoscopy for the diagnosis of MCP involvement in upper and lower GI was approximately 80%, whereas negative predictive value was approximately 20% in both cases. These data likely explain the fact that the reported frequency of GI tract involvement in MCL was underestimated because of significant microscopic involvement with macroscopic normal mucosa. Despite these results, the authors concluded that it is not necessary to perform endoscopy with biopsy in these patients because most of them (90–95%) have bone marrow involvement when the GI tract is infiltrated, and as a consequence, clinical management is not affected. On the other hand, whether or not the GI tract should be evaluated at the end of therapy and as part of surveillance studies is still unknown.

Reyes' case is the first report in the literature that relates MCL and Barrett esophagus. It is known that MCL can involve any part of the GI tract, but the esophagus is a rare location. GI bleeding in MCL has been described previously,⁵ but as low-degree bleeding or microcytic anemia. In this case, MCL was diagnosed casually because endoscopy was not indicative of lymphoma infiltration. However, it would have been interesting to obtain biopsies from the duodenal ulcer to investigate if there was also infiltration by MCL in this site, even if the therapeutic approach would not have changed.

In conclusion, we agree with Reyes that the presence of MCL in Barrett esophagus is merely coincidental because the pathogenesis of both entities is completely different.