Q. I have a quick question regarding Richter’s transformation in CLL. In my notes, I have that an “aggressive” lymphoma can develop (without specifying which), and Wikipedia (which I realize is not always accurate) said that it is most commonly a diffuse large-cell lymphoma that comes from either hairy cell leukemia or CLL. Then, today a lecturer mentioned that a CLL –> prolymphocytic leukemia was the “true” Richter’s transformation. Can you clarify which, if any/all, are considered a Richter’s transformation that can be expected to occur in patients with milder leukemias? Thanks!

A. The topic of progression and transformation of CLL is a somewhat confusing one. As you’ve noticed, different people say different things!

The answer can be boiled down into two scenarios: 1) progression, and 2) transformation.

Progression
According to the latest World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Systems (which most experts in hematopathology would acknowledge as the most correct and authoritative source), CLL can show an increase in cell size and proliferative activity over time. In CLL, there are areas called proliferation centers which are composed mostly of prolymphocytes (some of which you can see in the above image) which are slightly larger than the small, mature CLL cells, and they have a prominent nucleolus. These prolfieration centers can coalesce, and you may see prolymphocytes in the blood. Progression to actual prolymphocytic leukemia, though, is extremely rare. (Prolymphocytic leukemia nearly always arises de novo, not from another disease like CLL.) This process is loosely termed “progression” and the words Richter’s transformation are not used in this setting.

Transformation
A minority of patients (between 2-8%) develop diffuse large B cell lymphoma (DLBCL). These patients are said to have Richter’s transformation or Richter’s syndrome. The median survival for these patients is less than one year. And this might seem strange, but a very small minority of patients (less than 1%) actually develop Hodgkin disease!

When you’re early on in your learning, this kind of stuff can be way too much information – but as long as you brought it up, it’s a good time to clarify things!