Consideration of the natural history of BCL2-positive follicular lymphoma: based on tumor site, histological grade, and histological transformation rate.

BCL2 follicular lymphomas (FLs) of grades 1-3A are defined as classic FL, and duodenal and skin FLs are known as special subtypes. To clarify the natural history of BCL2 FLs, we analyzed the tumor site, histological grade, and histological transformation rate. We analyzed 2260 FL grade 1-3B samples from 1389 patients. BCL2 expression was positive in 94 % (2115/2260) of the samples, with higher positivity in gastrointestinal (GI) (98 % [duodenum, 99 %]) and bone marrow (BM) (97 %) FLs than in lymph node (LN) (92 %) and extranodal (EN) (93 %) FLs (P = 3.4E-06). Histological grade increased in the order of BM and duodenum, GI (excluding duodenum) and EN, and LN. The histological transformation rate in the same biopsy sample diagnosed with FL was the highest in GI (excluding duodenum) (12 %), followed by LN (10 %), EN (5 %), BM (1 %), and duodenum (0.5 %). No significant differences were observed between duodenal and BM FLs regarding BCL2-positivity rate (P = 0.326), histological grade (P = 0.131), and histological transformation rate (P = 0.408). In EN sites, FLs most commonly involved skin, ocular adnexa, connective tissue, bone, and paravertebra. No specific organ showed a particularly low BCL2 percentage (range, 67 %-100 %). Because both primary (88 %) and secondary (95 %) skin FLs showed a high incidence of BCL2 expression, most skin FLs may represent one aspect of BCL2 FL. These findings suggest that BM and duodenum FLs may represent early-phase BCL2 FL, whereas EN, GI (excluding duodenum), and LN FLs may correspond to more advanced phases.