Follicular Large Cleaved Cell Lymphoma Is a Distinctive Morphological and Clinical Variant of Follicular Lymphoma
Radwa A El Behery, Javier A Laurini, Dennis D Weisenburger, Lynette M Smith, Bhavana J Dave, Wing C Chan, Kai Fu, Timothy C Greiner, Patricia Aoun. University of Nebraska Medical Center, Omaha, NE
Background: Follicular lymphoma (FL) is divided into 3 grades based on the number of centroblasts per high-power field (HPF). However, an under-recognized variant of follicular lymphoma is the large cleaved cell subtype (FLC) in which the follicles are composed predominantly of intermediate to large cleaved and multilobated cells, without enough centroblasts to meet the criteria for FL grade 3 (FL3). FLC was described in the Working Formulation but is not recognized in the WHO classification. The aim of this study is to evaluate the histopathologic and clinical characteristics of FLC and compare it to the other subtypes of FL.
Design: Seventy-two cases of FLC were identified. Using image analysis, the nuclear size of large cleaved cells was measured in 10 representative neoplastic follicles in each of 10 cases, and compared to the nuclear size of endothelial cells and small lymphocytes in the same biopsy. Immunoperoxidase stains for CD10, BCL2, and BCL6, as well as cytogenetic studies for BCL2 and BCL6 translocations were reviewed. Clinical features and overall survival (OS) were compared to a historical cohort of FL cases including FL1 (N= 141), FL2 (N=191), and FL3 (N=181).
Results: For FLC cases, the average number of centroblasts/HPF was 9.2 (range, 4.6-14.7). The average nuclear size of the large cleaved cells was 10.1 μm (range 8.1-14.9 μm), which was > 2 times the nuclear size of small lymphocytes (ratio 2.1) and the same as the nuclear size of endothelial cells (ratio 1.0). Immunostains for BCL6 were positive in 100%, BCL2 in 83.7% and CD10 in 88% of cases. Cytogenetic studies identified the t(14;18) in 86% and 3q27 rearrangements in 12% of analyzed cases. There were no significant differences in clinical features between FLC and FL1, FL2 or FL3. However, FLC had a significantly worse 5-year OS compared to FL1 (69% vs. 83%, respectively, p=0.002) or FL2 (77%, p=0.057), but was similar to FL3 (67%, p=0.74), especially for patients who did not receive rituximab-containing regimens.
Conclusions: FLC is a morphologically recognizable variant of FL and is clinically most like FL3. Therefore, cases of FLC should be considered a special variant of FL3, and should not be classified with FL1 or FL2 for treatment or prognosis.
Monday, March 4, 2013 9:00 AM
Proffered Papers: Section C, Monday Morning