NCCN Guidelines for Patients® | Follicular Lymphoma Grade 1-2

12 NCCN Guidelines for Patients ® : Follicular Lymphoma, Grade 1–2, 2017 1 Follicular lymphoma basics Diagnosis Follicular features The name, follicular lymphoma, is based on where this cancer grows and how it looks. Germinal centers form in the follicles of lymphatic organs. The hematopathologist will look for related cells— centroblasts and centrocytes. More importantly, he or she will look for a follicular growth pattern. This pattern has the shape of a circle. Cancer grade The hematopathologist will also assign a cancer grade. Grading of follicular lymphoma is based on the number of centroblasts seen when the microscope is at its highest power. Grade 1-2 is defined by 15 or fewer centroblasts per high-power field. Grade 3 is defined by more than 15 centroblasts per high-power field. Grade 3 is further divided into 3A and 3B. Grade 3A is defined by a mix of centrocytes and centroblasts. Grade 3B is defined by sheets of large centroblasts and no centrocytes. Protein tests For diagnosis, the hematopathologist needs to study the proteins in the cells’ surface (membrane). This is called immunophenotyping. Follicular cancer has a common pattern or “signature” of proteins. See Figure 4 . An IHC ( i mmuno h isto c hemistry) panel is a test for such proteins. It involves applying a chemical marker to cells and then looking at them with a microscope. IHC panel The IHC panel should test for CD3, CD5, CD10, CD20, BCL2, BCL6, and CD21 or CD23. Follicular lymphoma cells typically express CD10, CD20, BCL2, and BCL6 but not CD5 or CD43. Rare cases may be missing CD10 or BCL2. CD23 is found on some but not all follicular lymphoma cells. Sometimes it is helpful to include Ki-67, IRF4/MUM1, and cyclin D1 in the IHC panel. Some research has linked high numbers of Ki-67 with faster-growing cancers. IRF4/MUM1 is often expressed in grade 3 follicular lymphomas. Follicular lymphoma cells don’t express cyclin D1. Flow cytometry Flow cytometry is a newer method that can also be used to assess the surface proteins on lymphoma cells. This method involves first adding a marker—a light-sensitive dye—to cells. Then, your blood will be passed through a flow cytometry machine. The machine measures surface proteins on thousands of cells. Flow cytometry may be done in addition to an IHC panel. If done, it should test for CD5, CD10, CD19, CD20, CD23, and kappa and lambda light chain proteins. Light chain proteins are part of antibodies. Genetic tests Follicular lymphoma has common abnormal changes in chromosomes and genes. A translocation is a switching of parts between two chromosomes. A gene rearrangement is the fusion of one gene with another gene to create a new gene. Genetic testing may be useful. BCL rearrangements A translocation of chromosomes 14 and 18 that results in a BCL2 gene rearrangement is very common to follicular lymphoma. However, these abnormal changes are not found in pediatric-type follicular lymphoma. A BCL6 gene rearrangement is also absent in the pediatric type. Testing may be useful to diagnosis pediatric type. Deleted 1p36 Some follicular lymphomas have a deleted 1p36 chromosome part. These lymphomas grow throughout tissue rather than in clusters. This is called a diffuse pattern. They also express CD23. These lymphomas are usually confined to lymph nodes within the groin (inquinal nodes). They grow

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