Diagnostic clues of BCL2-negative, faint, or controversial follicular lymphomas: a study of 103 cases

BCL2 positivity by immunohistochemistry is helpful for the diagnosis of follicular lymphoma (FL); however, a minority of FL cases are BCL2-negative, and the diagnosis is thus challenging. We retrospectively analyzed the incidence, morphology, immunophenotype, and genetic status of BCL21+ (weakly/focally positive by clone 124), BCL20 (negative), and BCL2controversial FLs compared with BCL22+ (strongly positive) FLs to clarify diagnostic clues. In 1068 FL cases, 103 (10%) with BCL21+ (37 cases, 4%), BCL20 (61 cases, 6%), or BCL2controversial (5 cases, 0.5%) were included in the final analysis. BCL21+ and BCL20 FLs tended to have limited stage disease, nodal disease, and grades 3A/3B histology and showed a higher complete response rate than BCL22+ FLs. Among 103 BCL20, BCL21+, or BCL2controversial FL cases, 34 (33%) had a diffuse area composed of CD20-positive small-to medium-sized lymphoid cells, a feature of low-grade B-cell lymphoma. Interfollicular dense CD20-positive cells and interfollicular clusters of CD10-positive cells were observed in 59% and 37% of cases, respectively. In remaining 13/40 cases (33%), BCL2 was converted to BCL22+ by other clones E17/SP66. CD23 and MUM1 were positive in 10/40 (25%) and 1/40 (3%) cases, respectively. IGH/BCL2 fusion and clonality were detected in 6/37 (16%) and 31/34 (91%) cases, respectively. In conclusion, morphological examination of the distribution of CD20-and/or CD10-positive cells and the presence of diffuse area could be used to diagnose FL in most cases. The majority of the remaining FL cases could be diagnosed using other BCL2 clones and clonality analyses.