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Gut. 2007 October; 56(10): 1479.
PMCID: PMC2000280

Chemotherapy for mantle cell lymphoma

I read with interest the letter by Watanabe et al on a case of mantle cell lymphoma (MCL), which showed a complete response to combination chemotherapy (Gut 2007;56:449–50). Their patient had multiple lymphomatous polyposis and subsequent biopsy confirmed the diagnosis of colonic MCL. In the Europe and North America it has been known that multiple lymphomatous polyposis is commonly considered to be a representation of MCL. The authors have rightly observed that in Japan cases of MCL with multiple lymphomatous polyposis are rare. Several theories have been put forward regarding this difference, including the differences in physiology, between patients in Japan and Western countries. One observation is that MCL is characterised by positive immunoreactivity for cyclin D1 in the biopsied samples reported from Western centres. The authors refer to a study published from Japan which showed that about 10% cases with a confirmed diagnosis of MCL showed no cyclin D1 overexpression. It has been argued that true MCL should show positive immunoreactivity for cyclin D1, and that MCL with no immunoreactivity to cyclin D1 should be considered to be a low grade MCL‐like B cell lymphoma. Cyclin D1 negative MCLs, however, can be positive for cyclin D2, as shown in a recent Chinese series.1

A male patient of ours presented with a history of frequent bowel motions with rectal bleeding and weight loss. The patient told us that he had been diagnosed with ulcerative colitis many years earlier. He was not taking any form of anti‐inflammatory drugs (for example sulphasalazine), and no reference was made to him taking immune modifier drugs such as azathioprine at any stage of his illness. Clinical examination was unremarkable. Inflammatory markers were raised and he had normal blood counts. Barium enema and sigmoidoscopy showed a picture of active ulcerative colitis with pseudopolyp formations in the sigmoid colon. Immunohistochemistry of the biopsied samples showed overexpression of cyclin D1 protein, which is the histological hallmark of MCL. Whole body computed tomography and other investigations failed to reveal the presence of lymphoma elsewhere. It was difficult to tell whether this patient had a primary multiple lymphomatous polyposis representing as MCL or whether he developed MCL on the background of his long standing ulcerative colitis.

The colon is a rare location for non‐Hodgkin's lymphoma (NHL). NHL may develop in ulcerative colitis, but the risk is considered to be small (0.01% per person‐year).2 Immune modifier treatment may be implicated in only 5% cases of lymphoma occurring in the setting of ulcerative colitis.3 Multiple lymphomatous polyposis can present like an exacerbation of ulcerative colitis. MCL arises from the mantle zone of a lymphoid follicle and is a distinct type of NHL which commonly affects extranodal sites. Immunohistochemistry is essential for the diagnosis of lymphoma.3 In MCL, cyclin D1 (a cell cycle control protein) is always overexpressed as a result of deregulation of PRAD1, activated by t(11:14) gene translocation.3

It has been estimated that MCL constitutes 2.6% of all the cases of NHL. It is a disease primarily of the elderly. The frequency of gastrointestinal tract involvement into MCL at diagnosis is reported to be below 30%. The MCL is a rare B cell NHL, but it can take an aggressive course, turning into a blastoid variant which then becomes resistant to the traditional combination chemotherapy. Modern developments in biological therapy (such as anti‐CD20 antibody which Watanabe et al used to treat their patient) added to the traditional chemotherapy regimen may bring about a difference in prognosis even in the most aggressive cases of MCL, as shown in Watanabe's case. The possibility of ulcerative colitis transforming into NHL should be borne in mind.

Footnotes

Conflict of interest: None declared.

References

1. Chuang S S, Huang W T, Hsieh P P. et al Mantle cell lymphoma in Taiwan: clinicopathologic and molecular study of 21 cases including one cyclin D1‐negative tumor expressing cyclin D2. Pathol Int 2006. 56440–448.448 [PubMed]
2. Loftus E V, Tremaine W J, Habermann T M. et al Risk of lymphoma in inflammatory bowel disease. Am J Gastroenterology 2000. 952308–2312.2312 [PubMed]
3. Korin H W, Scwartz M R, Chirala M. et al Optimized cyclin D1 immunoperoxidase staining in mantle cell lymphoma. Immunohistrochem Mol Morphol 2000. 857–60.60 [PubMed]

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