Primary Cutaneous Large B Cell Lymphoma Shows Activation of Nuclear Factor Kappa B with Low Incidence of Epstein Barr Virus
S Bhagavathi, MC Patel, AM Blenc, S Warren, M Amin, RK Malhotra. Indiana University, Indianapolis, IN; William Beaumont Hospital, Royal Oak, MI
Background: Nuclear factor-kappa B (NF-kB) is a major transcription factors which has been identified as an important factor in the pathogenesis of lymphoma. Constitutive expression of the NF-kB pathway plays a critical role in the lymphomagenesis. In addition, Epstein Barr Virus (EBV) is also known to play an important role in lymphomagenesis and known to carry NF-kB activating oncoproteins. However, the role of NF-kappa B activation and EBV in primary cutaneous diffuse large B-cell lymphoma (PCDLBL), an extranodal non-hodgkin lymphoma confined to the skin at presentation, is largely unknown. The aim of this study is to determine the incidence of NF-kappa B activation and EBV infection in PCDLBL.
Design: We evaluated ten cases of PCDLBL in immunocompetent patients from our institutions between the years 2000 and 2008. A panel of immuoperoxidase stains; CD3, CD10, CD20, BCL2, BCL6, and MUM1 were performed on all cases. In addition, NF-kappa B pathway activation was evaluated using an immunostain for P65. Nuclear staining for P65 is determined as an indicator of activation of NF-kB, irrespective of cytoplasmic staining. The presence or absence of EBV was assessed using EBER in-situ hybridization (ISH) probe. Known prognostic markers in lymphoma such as P53, P16, and MIB1 by immunohistochemical stains were also performed.
Results: All ten cases were CD20 positive and CD3 negative. CD10, BCL6, BCL2, and MUM1 were positive in 4/10 (40%), 6/10 (60%), 7/10 (70%), and 6/10 (60%) cases respectively. NF-kappa B activation as determined by nuclear staining was detected in 7/10 (70%) cases. The remaining cases showed cytoplasmic staining only and hence were determined not to be NF-kB activated. One (10%) case was positive for EBV by ISH. Interestingly, the EBV positive case was also positive for MUM1 and negative for CD10, indicating an activated immunophenotype.
Conclusions: Our study demonstrated activation of the NF-kappa B pathway in a majority (70%) of PCDLBL. Thus, NF-kappa B may be a potential therapeutic target in patients with PCDLBL. Besides NF-kB pathway, the role of other pathways needs further exploration in cases of PCDLBL. Even though the inidence of EBV is low, the exact role of EBV in the pathogenesis of PCDLBL needs further clarification in a study with large patient samples.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 57, Tuesday Afternoon