Nathan H. Fowler, MD: When you see a patient for the first time in the clinic, one of the most important things is to differentiate their type of indolent lymphoma. Many times when patients come in, we review the pathology and we’ll look at all of their staging. Now there are 3 very common types of low-grade lymphomas: SLL (small lymphocytic lymphoma), marginal zone lymphoma, and follicular lymphoma. With follicular lymphomas, the way we often differentiate between the 2 is how they look under the microscope as well as through immunohistochemistry. Follicular lymphomas are usually CD10-positive, CD5-negative, and CD20- and CD19-positive by immunohistochemistry. This differs from marginal zone lymphoma as well as small lymphocytic lymphoma, or CLL.
Carla Casulo, MD: The diagnosis of follicular lymphoma should ideally be made with an excisional biopsy. The reason for this is that a fine-needle aspirate is really too small to give you the information that you need to take care of the patient. An excisional biopsy gives you the entire lymph node architecture, and it helps you to distinguish follicular lymphoma from other slow-growing low-grade lymphomas. It helps you to rule out whether there’s a presence of occult transformation, and it also helps you to grade the lymphomas, which sometimes impacts your selection of treatment. All of those reasons really make it important that you always choose an excisional biopsy when you’re diagnosing follicular lymphoma. But there are a few exceptions to that. If there is an inaccessible lymph node, or if the patient is too ill to undergo an excisional biopsy, you might consider a core biopsy. But a fine-needle aspirate is really not, in my opinion, sufficient to make the diagnosis.
Nathan H. Fowler, MD: Follicular lymphoma is staged like any other type of cancer, and we currently use a revised Ann Arbor staging system. The Ann Arbor staging system basically looks at the location of different nodes, as well as the involvement of organs that are not nodes, when determining staging. Stage 1 is 1 nodal site, stage 2 is 2 nodal sites on 1 side of the diaphragm, stage 3 is nodal disease above and below the diaphragm, and stage 4 is when there’s an organ that is not a node that is involved. Honestly, this mostly means the bone marrow, but it can sometimes mean the skin, somewhere in the GI tract, or other places. There’s also one slight variant, and that’s called stage 1E. That’s when patients have stage 1 disease in a site that is not a node. So, stage 1 is extra-nodal. For example, marginal cell lymphoma only in the stomach would be stage 1E.
In follicular lymphomas, we grade according to WHO staging/grading criteria. Basically, this looks at the number of large cells within a sample. When looking at follicular lymphoma under the microscope, if there are between 0 and 5 large cells, or centroblasts, in a sample, we call it grade 1. If there are up to 15, we call it grade 2. If there are 15 or more, we call that grade 3 follicular lymphoma. We then subdivide grade 3 into grades 3A and 3B, depending on the presence of centrocytes.
I personally think that the grading is somewhat of a spectrum. It isn’t that the patient has a different disease if they have 15 large cells in a sample versus 16 large cells in a sample. When I am thinking about how to treat a patient, I do look at the grade, but I also look at other factors such as how hot the PET scan is, the Ki-67, as well as the clinical history of a patient. I use staging and grade as part of that whole picture to determine what the best frontline therapy should be.
Transcript Edited for Clarity