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From brain to testis: immune escape and clonal selection in a B cell lymphoma with selective out-growth in two immune sanctuariesy

¹ Dept. of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen
² Dept. of Internal Medicine, Medisch Spectrum Twente, Enschede
³ Laboratorium Pathologie Oost-Nederland, Enschede, The Netherlands

Correspondence: Marije Booman, University Medical Center Groningen Dept. of Pathology, Hanzeplein 1 9713 GZ Groningen, The Netherlands, Phone +31 50 3611284; Fax +31 50 3632510, E-mail: m.booman{at}path.umcg.nl

We describe a patient with a primary diffuse large B-cell lymphoma of the central nervous system who developed a localized testicular relapse after 8 years. Both tumours lacked HLA-DR expression, the relapse additionally lost HLA class I expression. Immunoglobulin heavy chain gene rearrangements were identical in both lymphomas with extensive and ongoing somatic hypermutations resulting in extensive idiotype modulation. We hypothesize that these immune sanctuaries initially provided a safe haven for the tumour cells. When the environment becomes more permissive for an anti-tumour response, the continuous idiotype modulation and progressive loss of HLA expression on the tumour cells facilitates further immune escape.