Mantle Cell Lymphoma

A lot of people have been worried by the confusion between these two diseases. Superficially they can seem the same. Both can have a small cell lymphocytosis in the blood and both can be indolent or aggressive. Most importantly, these are the only common B cell lymphomas that are CD5 positive. Moreover MCL has only been recognised for about 10 years - previously it was called diffuse centrocytic lymphoma or intermediate cell lymphoma. The clinical features of mantle cell lymphoma as described in the textbooks include widespread lymph node enlargement, usually both sides of the diaphragm, liver and spleen enlargement, bone marrow involvement in over 50% and blood involvement in 25%. The gastrointestinal tract is involved in more than a third. Often the colon is involved and here it iis called lymphomatous polyposis. Characteristically, it gets into unusual places. I have seen a couple of cases where it surrounded the heart, constricting it.

The immunophenotyping differs slightly from CLL:

Although an experienced hematopathologist can usually tell the difference, I prefer to interpret the flow profiles myself rather than look at somebody else's reports. One man's moderate is another man's strong. I also prefer to look at the blood film myself. The trouble is that CLL itself can be a bit variable Those with trisomy 12 tend to have rather brighter Ig, CD20 and FMC7. The same is true of the small minority with the t(14;19) translocation. Again some markers do not stay as positive if the sample is old or has been frozen and thawed. CD23 is notorious for this, whereas CD22 is present in the cytoplasm in CLL though not on the surface, but in an old sample it can leak out and give a false positive. Nevertheless, experience has shown that some MCLs are CD23 positive.

What the cells look like down the microscope should sort it out, but MCL masquerades as a wide variety of diseases. It has become clear that at least 20% of PLLs are really MCLs and some MCLs look just like CLLs.

The clincher is the t(11;14) translocation. This puts the cyclin D1 gene next to the promoter region of the immunoglobulin gene and causes increased expression of cyclin D1. In lymph nodes it is reasonably easy to stain for cyclin D1 to confirm that this is what the translocation is doing, but the antibody is designed to do this; it is not designed for flow tests. So flow tests for cyclin D1 in apparent CLLs with the t(11;14) translocation are often negative. It is also not designed to work on bone marrow, because the bone has to be decalcified with acid before it can be cut into sections, and the acid destroys many antigens. So here again the cyclin D1 test may be negative.

Therefore the way we diagnose MCL that looks like CLL is on the FISH test for t(11;14) together with the atypical immunophenotyping.

Does this matter?

Well it turns out the IgVH gene mutations and CD38 are also important in MCL. Though it is not as clearcut as with CLL, those MCLs that are confined to lymph nodes all have unmutated IgVH genes, whereas in those with involvement of the blood about half have mutated genes. Those MCLs involving the blood that look like CLL and have a very slow, indolent course tend to be mutated and CD38 negative, just as in CLL.

The greatest danger is in suddenly discovering that your slow-growing CLL that has been no worry to you is really MCL and then jumping into treatment - even aggressive treatment like hyperCVAD and transplant - just because MCL has such a nasty reputation. Some MCLs behave just like indolent CLLs.