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.
OBJECTIVE
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.


CONCLUSIONS
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.
Coupland
S E
SE
Department of Pathology, Charité-Medical Faculty Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12203 Berlin, Germany. sarah.coupland@charite.de
Hellmich
M
M
Auw-Haedrich
C
C
Lee
W R
WR
Anagnostopoulos
I
I
Stein
H
H
D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D001324:Autoantigens / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D050882:CREB-Binding Protein; D016022:Case-Control Studies; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000032:analysis; D005134:Eye Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D050835:Interferon Regulatory Factors; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000032:analysis; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis; D012189:Retrospective Studies; D053668:Syndecan-1; D053667:Syndecans; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D000099218:Interferon Regulatory Factor-4
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001324:Autoantigens; D014408:Biomarkers, Tumor; D050882:CREB-Binding Protein; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; D015534:Trans-Activators; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C508241:SDC1 protein, human; C100347:VS38 monoclonal antibody; C494363:CREBBP protein, human; C498154:CD38 protein, human
Am J Surg Pathol. 2000 Jun;24(6):846-52
10843287
Blood. 1999 Jul 15;94(2):701-12
10397737
Br J Ophthalmol. 2001 Jan;85(1):63-9
11133714
Mod Pathol. 2001 Jul;14(7):641-9
11454995
Mod Pathol. 2001 Jul;14(7):686-94
11455001
J Pathol. 2002 Jul;197(3):333-40
12115879
Surv Ophthalmol. 2002 Sep-Oct;47(5):470-90
12431695
Blood. 2002 Dec 15;100(13):4671-5
12393648
Graefes Arch Clin Exp Ophthalmol. 2004 Feb;242(2):130-45
14685876
Ophthalmology. 1978 Aug;85(8):818-43
101924
J Histochem Cytochem. 1981 Apr;29(4):577-80
6166661
J Histochem Cytochem. 1984 Feb;32(2):219-29
6198355
Hematol Oncol. 1989 Jan-Feb;7(1):19-35
2909457
Trans Am Ophthalmol Soc. 1989;87:420-42; discussion 442-4
2562543
Genes Dev. 1990 May;4(5):849-59
2116362
Hum Pathol. 1990 Sep;21(9):959-73
2394438
Cell Regul. 1989 Nov;1(1):27-35
2519615
Am J Clin Pathol. 1993 Apr;99(4):472-85
8475914
Annu Rev Immunol. 1994;12:117-39
8011279
Blood. 1994 Sep 1;84(5):1361-92
8068936
Arch Ophthalmol. 1994 Sep;112(9):1207-12
8085964
J Pathol. 1994 Aug;173(4):371-9
7965396
FASEB J. 1996 Oct;10(12):1408-17
8903511
Ophthalmology. 1995 Dec;102(12):1994-2006
9098307
Semin Immunol. 1997 Aug;9(4):229-34
9237928
Eur J Cancer. 1997 Nov;33(13):2273-7
9470818
Ophthalmology. 1998 Aug;105(8):1430-41
9709754
Ann Oncol. 1998 Jul;9(7):779-81
9739446
J Clin Oncol. 1999 Sep;17(9):2847-53
10561361
Leuk Res. 2000 Feb;24(2):153-9
10654451
Blood. 2000 Mar 15;95(6):2084-92
10706878
Leukemia. 2000 Mar;14(3):449-56
10720141
J Biol Regul Homeost Agents. 1998 Jul-Sep;12(3):81-91
9795836
Am J Clin Pathol. 1999 Jan;111(1 Suppl 1):S126-32
9894477
Br J Haematol. 1999 Jan;104(1):138-43
10027726
Leuk Lymphoma. 1999 Feb;32(5-6):533-43
10048426
Pathol Biol (Paris). 1999 Feb;47(2):119-27
10192879
Semin Hematol. 1999 Apr;36(2):139-47
10319382
Ophthal Plast Reconstr Surg. 1999 May;15(3):171-9
10355835
Br J Ophthalmol. 2000 Aug;84(8):907-13
10906102