Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid tissues such as lymph nodes. The cancerous cells in FL typically form follicular or follicle-like structures (see adjacent Figure) in the tissues they invade. These structures are usually the dominant histological feature of this cancer.There are several synonymous and obsolete terms for FL such as CB/CC lymphoma (centroblastic and centrocytic lymphoma), nodular lymphoma, Brill-Symmers Disease, and the subtype designation, follicular large-cell lymphoma. In the US and Europe, this disease is the second most common form of non-Hodgkins lymphomas, exceeded only by diffuse large B-cell lymphoma. FL accounts for 10-20% of non-Hodgkins lymphomas with ~15,000 new cases of it being newly diagnosed each year in the US and Europe. Recent studies indicate that FL is similarly prevalent in Japan.FL is a broad and extremely complex clinical entity with a wide range of manifestations which have not yet been fully systematized. It is commonly preceded by a benign precancerous disorder in which abnormal centrocytes and/or centroblasts accumulate in lymphoid tissue. They may then circulate in the blood to cause an asymptomatic condition termed in situ lymphoid neoplasia of the follicular lymphoma type (i.e. ISFL). A small percentage of these cases progress to FL.
While studies are inconclusive, autologous stem cell bone marrow transplantation appears to prolong survival in early treatment failure patients who are healthy enough to withstand this therapy. Unfit patients may benefit from initial treatment with obinutuzumab plus bendamustine followed by maintenance treatment with obinutuzumab (if they have not been treated previously with obinutuzumab).Other mostly experimental treatments currently under study in patients with multiple treatment failures include: 1) Phosphoinositide 3-kinase inhibitors such as copanlisib, duvelisib, and idelalisib which block the phosphoinositide 3-kinase signaling pathway that promotes the survival, proliferation, and other potentially malignant behaviors of cells; 2) infusion of tisagenlecleucel chimeric antigen receptor T cells (i.e. CAR T cells) (i.e. T cells that have been isolated from patients, engineered to express a receptor for the CD19 protein on, and thereby kill, T cells, and then infused back into the donor patient); 3) Bruons tyrosine kinase inhibitor, ibrutinib, to block the B-cell maturating actions of this kianase; 4) BCL inhibitor  venetoclax to block Bcl2s action in promoting B-cell survival and proliferation; 5) histone deacetylase inhibitors abexinostat and tazemetostat to modify the expression of various genes; and 6) Checkpoint inhibitors nivolumab, pidilizumab, and pembrolizumab to promote the immune systems ability to suppress cancer cell growth. In preliminary studies on FL patients who were known or thought to be refractor to more conventional therapies these drugs, when combined with more conventional drugs, particularly rituximab, produced promising results.