FL usually involves enlarged lymph nodes populated by abnormal follicles (see adjacent picture) that when examined histologically contain a mixture of centrocytes or centroblast surrounded by non-malignant cells, mostly T-cells. The centrocytes, which typically outnumber centroblasts, are small to medium-sized B-cell lymphocytes that characteristically exhibit cleaved nuclei; the centropblasts are larger B-cell lymphocytes without cleaved nuclei. Rare cases of FL may show lesions that contain tissue infiltrations dominated by B-cells with features of precursor (i.e. "blast") cells, monocytes, or malignant mantle cells such as those found in mantle cell lymphoma. Immunochemical analyses reveal that these cells generally express B-cell surface markers including the CD10 (60% of cases), CD20, CD19, CD22, and CD79 but not CD5, CD11c, or CD23 cell surface proteins; genomic analyses reveal that these cells contain t(14:18)(q32:q21.3) translocation (85-90% of cases), 1p36 deletions (60-70% of cases), and with far less frequency the other genomic abnormalities listed in the above sections on Pathophysiology and Presentation and course. None of these protein markers or genomic abnormalities are diagnostic for FL, e.g. the t(14:18)(q32:q21.3) translocation is found in 30% of diffuse large B-cell lymphoma and in a small number of reactive benign lymph nodes. Rather, the diagnosis is made by a combination of histological, immunological, and genomic abnormalities. According to World Health Organization (WHO) criteria, differences in the microscopically determined morphology of these tissues can be used to diagnose and categorized FL into the following 3 Grades with grade 3 having A and B subtypes:

Grade 1: follicles have <5 centroblasts per high-power field (hpf).
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.