Variable Cytology and Ki67 Proliferative Rate and a BCL2 Positive Germinal Center Phenotype Typify "Double Hit" Lymphomas in the Bone Marrow
Justin L Seningen, Ahmet Dogan, Rhett P Ketterling, Paul J Kurtin, Brooke E McCann, William R Macon. Mayo Clinic, Rochester, MN
Background: "Double Hit" B-cell lymphoma (DHBCL) is characterized by chromosomal rearrangements involving MYC/8q24 plus another locus, typically BCL2/18q21 or BCL6/3q27. Bone marrow (BM) involvement is common (59%) and may be the presenting site (Am J Surg Pathol 2010; 34:327). Because the morphologic and phenotypic spectrum of DHBCL involving the BM is incompletely described,we retrospectively evaluated morphologic, immunophenotypic, and cytogenetic features of this tumor in BM samples.
Design: Fifteen DHBCLs with BM involvement were identified in a cytogenetic database on which fluorescence in situ hybridization (FISH) and/or karyotypic studies had been previously performed and for which paraffin-embedded tissue was available. Morphology was reviewed from aspirate smears and biopsy cores, and immunohistochemistry was performed using antibodies to CD3, CD10, CD20, BCL2, BCL6, GCET1, FOXP1, Ki67, MUM1, and MYC.
Results: The 15 patients included 11 males and 4 females aged 36 to 87 years (mean, 60.4). Tumor was identified in all biopsy cores and 14 (93%) aspirate smears. Tumor growth was interstitial in 12 (80%) cases and nodular and paratrabecular in 3 (20%). Range of BM involvement was 30-95% (mean, 60%). Cytology was small centroblastic (small non-cleaved) in 8 (53%) cases, immunoblastic in 3 (20%), large centroblastic in 3 (20%), and lymphoblastic (LB) in 1 (7%). All cases were CD20 positive with nuclear MYC staining; 12 (75%) were CD10+, 13 (87%) were BCL2+, 7 (47%) were BCL6+, 5 (33%) were MUM1+, 0 were GCET1+, and 14 (93%) were FOXP1+. Ki67 staining ranged from 5-100% (mean, 52%), and only 2 cases exceeded 90% positivity. By the WHO classification, 9 cases were B-cell lymphoma, unclassifiable (BCLU) with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, 6 cases were DLBCL, and 1 remained unclassifiable (LB). When classified phenotypically, 12 (80%) cases were germinal center-like (GCB). The translocation partners of MYC/8q24 were IGH@/14q32 in 8 (53%) cases, IGK@/2p12 in 2 (13%), and IGL@/22q11.2 in 1 (7%). T(14;18)(q32;q21.3) was present in 10 (67%) cases; 4 (33%) showed rearrangement of BCL6/3q27.
Conclusions: DHBCLs in BM have variable cytologic features including BCLU, DLBCL and LB-like. Most cases have a GCB phenotype and express BCL2 and nuclear MYC. The proliferation rate based on Ki67 staining is an unreliable indicator of the presence of double hit genetic abnormalities.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 180, Tuesday Afternoon