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Gut. 2007 October; 56(10): 1479–1480.
PMCID: PMC2000284

Authors' reply

We appreciate Dr Sinharay's interest in our article. Our reported case of colonic mantle cell lymphoma (MCL) revealed negative immunoreactivity for cyclin D1 and did not assess the immunoreactivity for cyclin D2. Some of cyclin D1 negative MCL cases expressed higher levels of cyclin D2 or cyclin D3 gene than were detected in cyclin D1 positive MCL, suggesting that these tumours might have alternative ways of increasing cell cycle progression in the absence of cyclin D1.1 It has been reported by Fu et al2 that several cases of cyclin D1 negative MCL expressed either cyclin D2 or cyclin D3. These patients with cyclin D1 negative MCL were clinically similar to those with cyclin D1 positive MCL. The immuno‐reactivity for cyclin D2 in our reported case remains to be examined. Final confirmation for cyclin D2 or D3 in these patients with cyclin D1 negative MCL will be carried out in future studies.

A literature search using Japana Centra Revuo Medicina (in Japanese) (keywords: ulcerative colitis, mantle cell lymphoma; retrieval period: 1983–2007) found no cases, and a similar search in Medline (keywords: ulcerative colitis, mantle cell lymphoma) found only one case worldwide of colonic MCL with ulcerative colitis.3 Therefore we consider this to be the second reported case to date of colonic MCL with ulcerative colitis. In the case reported by Dr Sinharay, the biopsied samples from pseudopolyps with active ulcerative colitis indicated an overexpression of cyclin‐D1 protein, and a diagnosis of colonic MCL was made. The samples revealed multiple lymphomatous polyposis arising from a background of ulcerative colitis. However, it should be clarified whether the colonic MCL with multiple lymphomatous polyposis was primary or whether the patient developed MCL on a background of long standing ulcerative colitis, as described above.

Loftus et al (reference 2 in Dr Sinharay's letter) reported that the risk of developing NHL in ulcerative colitis does not exceed that of the general population. Dr Sinharay said that the possibility of ulcerative colitis transforming into NHL should be considered. We disagree, however, because the incidence is low. A definite correlation between ulcerative colitis and colonic lymphoma has not been reported, though it should be noted that colonic lymphoma can develop in cases of ulcerative colitis.

Immune modifier therapy involving an anti‐CD20 antibody (rituximab) could be implicated in a small percentage of lymphoma patients, occurring in the setting of inflammatory bowel disease as described by Loftus et al. However, a multicentre phase II pilot study indicated that rituximab following induction chemoimmunotherapy appeared to prolong progression‐free survival in various types of MCL without increasing toxicity, and is not limited to gastrointestinal lymphoma.4 Forstpointner et al have also reported that maintenance therapy with rituximab was effective after salvage therapy with rituximab along with traditional chemotherapy, and significantly prolonged the response duration in patients with follicular lymphoma and MCL.5 Furthermore, Ritchie et al have reported that combination therapy with hyper‐CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus rituximab increases event‐free survival in patients with previously untreated MCL.6 Very recently Herold et al reported that rituximab added to first line mitoxantrone, chlorambucil, and prednisolone chemotherapy, followed by interferon maintenance, prolongs survival in patients with advanced follicular lymphoma.7 We strongly suspect that immune modifier treatment involving rituximab added to traditional chemotherapy will produce more significant prolongation of progression‐free survival. We look forward to future prospective studies of these important subjects.

References

1. Rosenwald A, Wright G, Wiestner A. et al The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer cell 2003. 3185–197.197 [PubMed]
2. Fu K, Weisenburger D D, Greiner T C. et al Cyclin D1‐negative mantle cell lymphoma: a clinocopathologic study based on gene expression profiling. Blood 2005. 1064315–4321.4321 [PubMed]
3. Robert M E, Kuo F C, Longtine J A. et al Diffuse colonic mantle cell lymphoma in a patient with presumed ulcerative colitis: detection of a precursor monoclonal lymphoid population using polymerase chain reaction and immunohistochemistry. Am J Surg Pathol 1996. 201024–1031.1031 [PubMed]
4. Kahl B S, Longo W L, Eickhoff J C. et al Maintenance rituximab following induction chemotherapy may prolong progression‐free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network. Ann Oncol 2006. 171418–1423.1423 [PubMed]
5. Forstpointner R, Unterhalt M, Dreyling M. et al Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R‐FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 2006. 1084003–4008.4008 [PubMed]
6. Ritchie D S, Seymour J F, Grigg A P. et al The hyper‐CVAD‐rituximab chemotherapy programme followed by high‐dose busulfan, melphalan and autologous stem cell transplantation produces excellent event‐free survival in patients with previously untreated mantle cell lymphoma. Ann Hematol 2007. 86101–105.105 [PubMed]
7. Herold M, Haas A, Srock S. et al Rituximab added to first‐line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group hematology and oncology study. J Clin Oncol, published Online First 9 April 2007. doi: 10, 1120/JCO. 2006. 06. 4618

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