[1336] Double Hit Lymphomas: Immunohistochemical, In Situ Hybridization and Molecular Study

Sharathkumar Bhagavathi, Hana Aviv, Lauri Goodell, Kevin David, Roger Strair, Gratian Salaru, David Weissman, Denisa Slova, Nisha Ahuja, Pashna Munshi, Evita Sadimin, Nadine Johnson, Joseph Bertino. UMDNJ-RWJMS, New Brunswick, NJ; UMDNJ-RWJMS & CINJ, New Brunswick, NJ

Background: Double hit lymphomas (DHL) are an aggressive non-Hodgkin B cell lymphomas (NHL) and are characterized by concurrent or sequential translocations involving c-MYC with one or more of partner genes; BCL2, BCL6, and CCND1.
Design: The pathology database was searched for large B cell lymphoma with high grade morphology. We performed FISH probes involving c-MYC, BCL2, BCL6, and CCND1. Karyotypic information was collected. Immunohistochemistry and in-situ hybridization were performed and DHL were subclassified into germinal center (GCB) or activated B cell (ABC) type.
Results: The majority of DHL (78%) had C-MYC and BCL2 translocations. Three cases showed c-MYC and BCL6 trasnlocations only. CCND1 was translocated in 3 (16%) cases. Karyotypic analysis showed complex karyotype (7/7). GCB subtype was most common (89%) and an average proliferation rate was 89%. PAX8, Cyclin D1 and P53 was positive in all, 3 and 2 cases repectively.

Table 1
c-MYCBCL2BCL6CCND1Karyotype
+++-ND
+-++Complex
+++-ND
++--ND
+-++ND
++ +Complex
++--ND
+-+-Complex
++--Complex
+-+-Complex
++--ND
++--ND
++--Complex
++--Complex
++--ND
++--ND
++--ND
+++-ND
+Positive -Negative ND Not done



Table 2
CD20/PAX5CD3/BCL2CD10/BCL6MUM1/SubtypeKi-67/CyclinD1/P53CD15/CD30PAX8/EBERTdT/CD34/ALK-1
+/+-/++/+-/GCB100%/-/--/-+/--/-/-
+/+-/+-/+-/GCB50%/+/--/-+/--/-/-
+/+-/++/++/GCB90%/-/+-/++/--/-/-
+/+-/++/+-/GCB50%/-/--/-+/--/-/-
+/+-/++/--/GCB80%/-/--/-+/--/-/-
+/++/++/+-/GCB90%/-/--/-+/--/-/-
+/+-/-+/+-/GCB100%/-/--/-+/--/-/-
+/+-/+-/+-/GCB70%/-/--/-+/--/-/-
+/+-/++/+-/GCB90%/-/+-/-+/--/-/-
+/+-/+-/+-/GCB95%/-/--/-+/--/-/-
+/+-/+-/++/ABC90%/-/--/-+/--/-/-
+/+-/++/--/GCB80%/-/--/-+/--/-/-
+/+-/++/++/GCB95%/-/--/-+/--/-/-
+/+-/++/+-/GCB90%/-/--/-+/--/-/-
15/+/+-/++/--/GCB70%/-/--/-+/--/-/-
+/+-/+-/++/ABC95/+/--/-+/--/-/-
+/+-/-+/--/GCB80%/-/--/-+/-/--/-/-
+/+-/++/+-/GCB90%/-/--/-+/-/--/-/-
- Negative, + Positive, GCB-Germinal center B cell subtype, ABC- Activated B cell subtype


Conclusions: The majority of the DHL are associated with c-MYC and BCL2 translocation and in minority, c-MYC was rearranged in addition to rearrangement of BCL6 and /or CCND1. In majority of cases, the translocation partner of c-MYC was a non-immunoglobulin gene and showed a complex karyotype. The majority of DHL cases are of GCB subtype with a high proliferation rate.
Category: Hematopathology

Monday, March 4, 2013 1:00 PM

Poster Session II # 200, Monday Afternoon

 

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