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Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases

S E Coupland¹, M Hellmich², C Auw-Haedrich³, W R Lee⁴, I Anagnostopoulos¹ and H Stein¹

¹ Department of Pathology, Charité-Medical Faculty Berlin, Campus Benjamin Franklin, Berlin, Germany
² Department of Medical Statistics, Informatics and Epidemiology, University of Cologne, Germany
³ Department of Ophthalmology, University Hospital Freiburg, Germany
⁴ Department of Pathology, Western Infirmary, Glasgow, UK

Correspondence to:
Correspondence to:
Dr S E Coupland
Institute of Pathology, Charité-Medical Faculty Berlin, Campus Benjamin Franklin, Germany, Hindenburgdamm 30, D-12203 Berlin, Germany; sarah.coupland{at}charite.de

Aim: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours.

Methods: A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as "plasmacellular differentiated" on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death.

Results: 57 (42%) of the 136 ocular adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis.

Conclusion: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.

Abbreviations: APAAP, alkaline phosphatase anti-alkaline phosphatase; B-CLL, B cell chronic lymphocytic leukaemia; BSAP, B cell specific activator protein; CBP, CREB binding protein; CREB, cyclic AMP responsive element binding protein; EMZL, extranodal marginal zone B cell lymphomas; Ig, immunoglobulin; IgH, immunoglobulin heavy chain; IgL, immunoglobulin light chain; MUM1/IRF4, multiple myeloma oncogene-1-protein; NHL, non-Hodgkin’s lymphomas; OAL, ocular adnexal lymphomas; RLH, reactively hyperplastic lymphoid tissue

Keywords: ocular adnexal lymphoma; extranodal marginal zone B cell lymphoma; lymphoma classification; plasmacellular differentiation

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