Bcl-2bright Follicular Colonization Pattern Is Not Always Indicative of Incipient or Indolent Follicular Lymphoma
John C Lee, Vundavalli Murty, Schecter Jordan, Bachir Alobeid, Bhagat Govind. Columbia University Medical Center, New York, NY
Background: Follicular lymphoma (FL) in-situ (FLIS) is an entity characterized by germinal centers showing colonization by BCL2bright and CD10bright B-cells in lymph nodes with preserved architecture. Limited studies to date have proposed this pattern to reflect a precursor stage of FL or be associated with indolent FL.
Design: We searched our database for cases compatible with FLIS diagnosed over 9 yrs (2002-2011). Immunohistochemical stains, including CD20, CD3, CD10, BCL-2, BCL-6, and Ki-67 were performed. Karyotypes were determined by Giemsa-banding (n=5). FISH analysis using IGH/BCL2 break-apart probes was performed on fixed cells (n=4) and paraffin-embedded tissue (n=7).
Results: A total of 11 cases showing germinal center colonization were identified in 4 males and 7 females (age range 43-78 yrs, median 58 yrs). All except 1 case showed concomitant CD10bright expression. Biopsies were from nodal (n=6) and extranodal (n=5) sites including small bowel (n=3), pancreas (n=1), and skin (n=1). Of the 5 patients with no evidence of lymphoma at presentation, 2 patients subsequently developed lymphoma; one patient developed FL 9.6 and diffuse large B-cell lymphoma (DLBCL) 9.6 and 10.1 years later respectively and another patient developed a low-grade FL 5.9 years later. Synchronous lymphoma was detected in 6 patients (2 FL, 2 DLBCL, and 2 aggressive B-cell lymphomas). One CD10- DLBCL patient had germinal center colonization in both mesenteric lymph nodes and mucosal sites away from the DLBCL. Cytogenetic analysis in these synchronous lymphomas showed IGH/BCL-2 translocations in 5 cases. An additional t(3;8)(q27;q24) was detected in one aggressive B-cell lymphoma case representing a BCL-6/C-MYC rearrangement. This translocation was present in both a lymph node showing FLIS and a separate lymph node showing aggressive B-cell lymphoma.
Conclusions: In contrast to prior series, we observed a high incidence of synchronous lymphomas (55%), including DLBCL and aggressive B-cell lymphomas, in association with germinal center colonization by Bcl-2 bright B-cells or FLIS. The germinal center colonization pattern was also noted at extranodal sites. Our findings raise the possibility that upregulation of BCL2 (and CD10) may reflect a feature of neoplastic cell homing to reactive germinal centers, rather than indicating a preneoplastic stage or indolent variant of FL in some cases.
Monday, March 19, 2012 1:00 PM
Poster Session II # 210, Monday Afternoon