Question: Hi Dr Klapper, does seeing necrosis adjacent to low grade follicular lymphoma make you suspicious for DLBCL? Can you see necrosis in just low grade follicular lymphoma?

Answer: We breifly touthed this issue in the live discussion. Necrosis is a feature that can be accompanied with low grade FL (Grade 1, 2 or 3a). The reason is, that a small subgroup of FL (I am not sure how many) are vasculotropic, invade vessel walls and lead to vascular obstruction. As a conseqience the lymph node frequently becomes completely necrotic. Necrosis is a feature that is not seen in other low grade lymphomas. It may be seen in high grade lymphomas such as DLBCL. However, in the latter it is usually not so extended as in FL. Thus, if there is extended (subtotal) necorsis of a sufficiently large lymph node biopsy (ideally a surgical excision biopsy), you should suspect FL rather than a transformed lymphoma.

Question: Prof. Klapper: How do you consider the presence of a DLBCL component on an FL biopsy? Could we consider this as HT? Prof. Luminari: How do you treat those patients, as FL or DLBCL?

Answer: In cases with an area resembling DLBCL, I consider this a transformation. However, at first diagnosis of a FL, transformation is rare. In fact indirect evidence suggest that pathologists overestimate the rate of transformation at first diagnosis. THe indirect evidence I am referring to are clinical data that show an outcome of FL trasnformed at first diagnosis comparted to untrsformed (normal) FL. In my opinion, many of the FL that are signed out nby pathologist as transformed at the time of first presentation/diagnosis may just “mimic” transformation. As I mentioned in the live discussion the conditions that mimic transformation are (i) diffuse growth (ii) necrosis (iii) presence of MYC translocations or double hit despite low grade morphology and (iv) high ki67 (more than 50%) in otherwise low grade lymphoma. Thus, check clinical presentation ehen you get a pathology report with a combined FL/DLBCL at first diagnosis to see if clinically transformation is comprehensible and discuss with your pathologist, when you feel that there is a discepancy between clinical presentation and path report.

Question: What does Mr. Molina think, in how many years will the genetic subgroups (e.g. C0-C5) be tested in everyday day routine?

Answer: Today in routine practice more and more genetic tests are implemented in DLBCL such as FISH , targeted gene expression tools or targeted NGS
The new genetic subgroups in DLBCL NOS will be implemented once reproducibility issues between labs proved , feasibility on ffpe demonstrated and utility being demonstrated when evaluated prospectively in clinical protocols for DLBCL
My guess is that within the next three years we will be able to better define subgroups also with the help of AI
Thierry Molina.

Question: If there’s no interference between pola and CAR-T, then does it mean that bystander activation of non CAR-T cells of the microenvironment is a key mechanism ?

Answer: We believe that there is a significant bystander reaction during CAR-T therapy that involves non-CAR-T cells. This has been observed in biopsies obtained during therapy. Polatuzumab (with rituximab) is a good third line therapy because it does not deplete T cells and allows successful apheresis and T cell collection.