Friday, September 20, 2013

Grading Follicular Lymphoma

Another thick artcile from a medical journal: "Immunophenotypic Features and t(14;18) (q32;q21) Translocation of Chinese Follicular Lymphomas Helps to Distinguish Subgroups," by a Chinese research team, to be published very soon in the journal Diagnostic Pathology.

The researchers looked at the genetic make up of different grades of Follicular Lymphoma to determine whether or not grading is helpful. In some ways, what they have to say isn't really all that new. But the way they got there is, and may have some important implications.

First, some background: Follicular Lymphomas are graded as 1, 2, or 3. Grading is a measure of, basically, how aggressive the disease is. (This is different from staging, which tells where in the body the lymphoma is occurring.) This has traditionally been a microscope issue, counting the number of large (and more aggressive) cells there are in a sample. Grade 1 and 2 are typically considered indolent, or slow-growing, less aggressive lymphomas -- not as many large cells. Grade 3 gets a little trickier. A Follicular Lymphoma graded 3A is generally thought to be indolent as well, and is usually treated as such. Grade 3B, however, while appearing to be Follicular Lymphoma, is often more aggressive, and is treated as an aggressive lymphoma, such as DLBCL (which stands for Diffuse Large B Cell Lymphoma -- it's those Large Cells that get all aggressive).

The grading scheme was developed by the World Health Organization, and is still a little controversial -- particularly the stage 3 splitting into A and B. They're still working on that one....

The article linked above tries to address this issue. Rather than looking only at the numbers of large calls, they did some funky genetic analysis, to see if there were differences on a much more "morphologic" level, to use their word (that is, looking at the form, not necessarily the behavior of the cells).

The group looked at 115 specimens from Chinese FL patients, and did some genetic testing to look for some very specific markers: CD10, a surface protein common to FL cells; BCL6, a protein commonly found in DLBCL cells; BCL2, which is thought to cause resistance to lymphoma treatments; MUM1, another protein present in DLBCL; and the t(14; 18) and q(32;q31) gene translocations (they switch places, perhaps causing Follicular Lymphoma).

In short, they looked at a lot of stuff in the cells.

What they found was a lot of stuff that distingushes the different stages.

You can see the stats for yourself, but basically, Grade 1 is more "Follicular-y" than Grade 2, which is more so than 3A. Grade 3B is the least Follicular-y of them all. That is, it contains the most DLBCL cells of all the stages, and the most markers associated with DLBCL.

As I said, I don't know if this is really news. We knew that grades 1, 2, and 3A act more like indolent lymphomas, and 3B acts more like an aggressive lymphoma. What's new is that there is morphological confirmation -- that is, it's not just a matter of behavior, but of actual cell make-up. They conclude with this: "Thus we hypothesize that FL may in fact be a heterogeneous indolent lymphoma encompassing entities with distinct molecular pathogenesis and genetic characteristics."

In other words, we might actually be talking about 4 different lymphomas here. They found that FL with the CD10 protein, for example, was more likely to have MUM1 and t(14;18) translocation. This suggests that it started in a different way, genetically, than other types. There are important implications there for how we might treat it, especially since we seem to be moving toward genetic-based treatment options.

The upshot of all of this: for now, it doesn't change a thing. But it might help focus the debate about the WHO grading classification, and that could influence the way treatment decisions are made down the line. More likely, it will help researchers focus on diagnosing and treating by distinguishing between different sub-groups of Follicular Lymphomas. This might help us figure out which treatments will work best for which patients.

A thick article with a minor immediate payoff, but promising for the future.

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