Clinicopathologic and Molecular Analysis of Primary Central Nervous System Diffuse Large B Cell Lymphoma
Michael Lee, Christina Duckworth, Enrique Vigo, Wanhong Jiang, Li Shiyong. Emory University Hospital, Atlanta, GA
Background: Primary central nervous system (CNS) lymphomas account for approximately 5% of brain tumors and 2% of non-Hodgkin lymphomas with an increasing incidence in the past three decades. Etiologic factors include immunodeficiency and immunosuppression due to transplantation or aging. This study analyzed the clinicopathologic and molecular features of primary CNS diffuse large B cell lymphoma (DLBCL).
Design: A tissue microarray (TMA) was constructed from 47 primary CNS DLBCL (42 immunocompetent and 5 immunocompromised). Immunohistochemical stains (IHC) for CD10, BCL6, MUM1, LMP1 and MDM2, in situ hybridization for Epstein-Barr virus RNA (EBER), and fluorescence in situ hybridization (FISH) for C-MYC rearrangement and MDM2 amplification were performed and analyzed.
Results: The average age of primary CNS DLBCL at diagnosis was 37 years in immunocompromised (HIV+) patients, and 64 years in immunocompetent patients. The immunohistochemical and EBER findings are summarized in the following Table. Among the 32 cores available for evaluation, CMYC rearrangement is present in 1 (3%) core and loss of CMYC or monosomy 8 in 20 (63%) cores. MDM2 amplification is not observed in the 35 cores available for evaluation, but gain of 1-2 copies of MDM2 and monosomy 12 are present in 8 (23%) and 11 (31%) cores, respectively.
|Immunocompetent (HIV-)||Immunocompromised (HIV+)|
|All DLBCLs||57% (27/47)||32% (15/47)||9% (4/47)||2% (1/47)|
|MDM2**||6% (3/47)||6% (3/47)||0% (0/47)||2% (1/47)|
|EBV***||9% (4/47)||2% (1/47)||6% (3/47)||0% (0/47)|