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Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Immune suppression is a risk factor for malignant lymphoma development. Progress in medical science has increased the numbers of immunosuppressed patients due to organ transplantations or successful treatment of autoimmune diseases. Different forms of immune suppression and the respective lymphoma entities are discussed in this article. Another issue treated are gray zone lymphomas between Hodgkin's lymphoma and diffuse large B cell lymphoma. This category not only represents a diagnostic challenge but also represents more a true biological continuum.

Malignant lymphomas are classified into different entities according to their morphology, immunohistochemical parameters and clinical behavior. Several important pathogenetic events can be assigned to certain lymphoma entity types. Nevertheless, some cases present overlapping morphologic and immunohistochemical characteristics and a clear-cut diagnosis cannot be made. This is particularly the case with aggressive lymphomas for which a clear distinction cannot be made between the entities of diffuse large cell lymphoma/Burkitt lymphoma or primary mediastinal B cell lymphoma/classic Hodgkin's lymphoma. In order to redress this situation, two new gray zone entities were introduced in the WHO 2008 classification. Until further knowledge regarding the therapy, behavior and prognosis of these gray zone lymphomas has been gained, they should continue to be considered as distinct entities.

Primary mediastinal B-cell lymphoma (PMBL) is a well-defined subtype of diffuse large B-cell lymphoma. Molecular cytogenetics revealed frequent gains of 9 p24. JAK2, mapping in this region, is presently regarded as a candidate oncogene since expression profiling showed high JAK2 transcript levels and JAK2 was found to be constitutively phosphorylated in mediastinal B-cell lymphomas. We confirm that in the MedB-1 mediastinal B-cell line, harbouring a trisomy 9, JAK2 transcription is elevated and the product is highly phosphorylated. However, JAK2 is not over-expressed at the protein level. On top, JAK2 protein turnover is even delayed. This unexpected finding coincides with a biallelic mutation of the SOCS-1 gene in this cell, which abrogates SOCS box function of the protein. Ectopic expression of wt-SOCS-1 in MedB-1 leads to growth arrest, dramatic reduction of phospho-JAK2 and its downstream partner phospho-STAT5. We conclude that, in MedB-1, action of phospho-JAK2 is sustained due to defective SOCS-1. Hence, SOCS-1 qualifies as a novel tumor suppressor. Of note, the SOCS-1 mutations are also present in the parental tumor of MedB-1 and were detected in 9 of 20 PMBL.