Dirnhofer, S.

Tzankov, A.

Went, P.

Zimpfer, A.

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Annals of Oncology 20: 789–798, 2009letters to the editorCD5 expression in de novodiffuse large B-cell lymphomasEnnishi et al. [1] recently described de novo CD5-positivediffuse large B-cell lymphomas (CD5+ DLBCLs), which arenow recognized in the new 2008 World Health Organization(WHO) classification of hematopoietic and lymphoid tumorsas an immunohistochemical subgroup of DLBCL not otherwisespecified. We looked for immunohistochemical CD5expression in a previously well-characterized DLBCL tissuemicroarray [2] of patients treated with a combinationchemotherapy with cyclophosphamide, doxorubicin,vincristine and prednisone (CHOP) or CHOP-like regimenwithout rituximab and found CD5 expression in 10 of 260tumors (4%). Secondary transformed or preexisting DLBCLswere excluded.In our cohort, 82 tumors were classified as primaryextranodal, whereas 178 were nodal DLBCLs. All 10 de novoCD5+ DLBCLs showed BCL2 expression and eight showedMUM1/IRF4 expression (Table 1). MUM1/IRF4 indicates thepossibility of a post-germinal-center-cell phenotype. Thetranscription factor BCL6 was expressed in 50% of thesetumors; by FISH analysis trisomy 3 as origin of BCL6deregulation was excluded. Although patients with de novoCD5+ DLBCL showed a tendency toward higher stages, therewas no correlation of CD5 expression with Ann Arbor stage,sex, B symptoms, International Prognostic Index, lactatedehydrogenase or survival. We, therefore, agree with Ennishiet al. that large-scale prospective studies are required to furtherdefine the relevance of CD5 in DLBCL. In this context, futurestudies should address specifically the primary site, as theseparation of primary nodal and extranodal lymphomas isemphasized by the 2008 WHO classification, which defines newsite-specific large B-cell lymphomas, e.g. DLBCL of the centralnervous system (CNS). Although at times it can be difficult todiscriminate primary nodal from primary extranodallymphomas with major nodal involvement, extranodallymphomas may not equal to nodal counterparts. This mattersespecially in de novo CD5+ DLBCL, as the often CD5+intravascular large B-cell lymphomas are now recognized asown subgroup of DLBCL. The concept of site-specific impacton tumor biology is strikingly challenged in de novo CD5+DLBCLs: (i) several studies found a relation of prognosis andCD5 protein expression and (ii) they are often primaryextranodal, but the primary site can be found in various organs.Of our 10 CD5+ DLBCLs, one was of testicular origin, whiletwo of four nodal lymphomas showed extranodal involvement.In the study of Ennishi et al., 45% of the reported cases wereprimary extranodal lymphomas. CNS involvement in 13% ofde novo CD5+ DLBCLs has been reported in the large study ofYamaguchi et al. [3], which is substantially higher than inconventional DLBCL.The basis of this association of involvement of extranodaland immunoprivileged sites and biological behavior inde novo CD5+ DLBCLs still remains to be elucidated.Comprehension of physiological CD5+ B-cell homingproperties may help to understand why in theselymphomas expression of CD5 is of higher relevance thanprimary site.P. Went*, A. Zimpfer, A. Tzankov & S. DirnhoferInstitute of Pathology, University Hospital of Basel, Switzerland(*E-mail: philip.went@mac.com)Table 1. Features of de novo CD5+ diffuse large B-cell lymphoma. Percentages of immunohistochemically positive tumor cells are indicatedAge/sex CD10 (%) BCL2 (%) BCL6 (%) MUM1 (%) Stage FU DOD1 n.a. 0 100 0 100 n.a. n.a. n.a.2 79/M 80 90 80 50 n.a. 3 Yes3 76/F 80 10 80 50 n.a. 72 Yes4 83/F 0 90 50 30 III 6 No5 n.a. 0 80 0 40 III 17 Yes6 79/M 0 90 0 0 n.a. n.a. n.a.7 81/F 20 90 50 25 III 16 No8 80/M 0 70 n.a. 35 II 62 No9 82/F 0 90 10 30 II 11 Yes10 39/F 0 80 n.a. 0 IV 106 NoFU, follow-up in months; DOD, dead of disease; n.a., not available; M, male; F, female.letterstotheeditorª The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology.All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.orgreferences1. Ennishi D, Takeuchi K, Yokoyama M et al. CD5 expression is potentially predictiveof poor outcome among biomarkers in patients with diffuse large B-cell lymphomareceiving rituximab plus CHOP therapy. Ann Oncol 2008; 19: 1921–1926.2. Tzankov A, Went P, Dirnhofer S. Prognostic significance of in situ phenotypic markerexpression in diffuse large B-cell lymphomas. Biomark Insights 2007; 2: 403–417.3. Yamaguchi M, Nakamura N, Suzuki R et al. De novo CD5+ diffuse large B-celllymphoma: results of a detailed clinicopathological review in 120 patients.Haematologica 2008; 93: 1195–1202.doi:10.1093/annonc/mdn793Published online 23 January 2009letters to the editor Annals of Oncology790 | letters to the editor Volume 20 |No. 4 | April 2009

CD5 expression in de novo diffuse large B-cell lymphomas

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