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 Blood, 15 October 2008, Vol. 112, No. 8, pp. 3355-3361.
Prepublished online as a Blood First Edition Paper on August 7, 2008; DOI 10.1182/blood-2008-01-132415.

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NEOPLASIA

The majority of cutaneous marginal zone B-cell lymphomas expresses class-switched immunoglobulins and develops in a T-helper type 2 inflammatory environment

Febe van Maldegem1, Remco van Dijk1, Thera A. M. Wormhoudt1, Philip M. Kluin2, Rein Willemze3, Lorenzo Cerroni4, Carel J. M. van Noesel1, and Richard J. Bende1

1 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands; 2 Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands; 3 Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands; and 4 Department of Dermatology, Medical University of Graz, Graz, Austria

Extranodal marginal zone B-cell lymphomas (MZBCLs) arise on a background of chronic inflammation resulting from organ-specific autoimmunity, infection, or by unknown causes. Well-known examples are salivary gland MZBCL in Sjögren's sialadenitis and gastric MZBCL in Helicobacter pylori gastritis. MZBCLs express CXCR3, a receptor for interferon-{gamma}–induced chemokines highly expressed in the chronic inflammatory environment. The immunoglobulin (Ig) variable heavy/light chain (IgVH/IgVL) gene repertoire of salivary gland and gastric MZBCL appears restricted and frequently encodes B-cell receptors with rheumatoid factor reactivity. Primary cutaneous marginal zone B-cell lymphomas (PCMZLs) are regarded as the skin-involving counterparts of extranodal MZBCLs. Although PCMZLs have been associated with Borrelia burgdorferi dermatitis, PCMZLs generally arise because of unknown causes. We studied an extensive panel of PCMZLs and show that PCMZLs do not conform to the general profile of extranodal MZBCL. Whereas most noncutaneous MZBCLs express IgM, PCMZLs in majority express IgG, IgA, and IgE and do not show an obvious immunoglobulin repertoire bias. Furthermore, the isotype-switched PCMZLs lack CXCR3 and seem to arise in a different inflammatory environment, compared with other extranodal MZBCLs.


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