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Background The tumor microenvironment is essential for tumor survival, growth and progression. There are only a few studies on the tumor microenvironment in cutaneous CD30-positive lymphoproliferative disorders. Methods We assessed the composition of the tumor microenvironment using immunohistochemistry studies in skin biopsies from cases diagnosed with lymphomatoid papulosis ( LyP: 18 specimens), primary cutaneous anaplastic large-cell lymphoma ( PC-ALCL: 8 specimens), and reactive diseases harboring CD30-positive cells (18 specimens). Results The predominant cells present in LyP and PC-ALCL were CD163+ M2 macrophages (44.7%, 35%), followed by CD8+ tumor infiltrating lymphocytes (11%, 15%), FOXP3+ T-regulatory cells (9%, 4.5%) and programmed cell death 1( PD-1) + lymphocytes (2.2%, 6.8%). In contrast, CD30-positive reactive inflammatory and infectious disorders were characterized by higher numbers of CD123+ plasmacytoid dendritic cells (6.3%) when compared to LyP (1%), and PC-ALCL (1.1%). Conclusions Key differences exist between the microenvironment of CD30-positive lymphoproliferative disorders and reactive conditions harboring CD30-positive lymphocytes. The high number of tumor associated macrophages, and the close vicinity of these immune cells to the CD30-positive tumor cells might suggest that tumor associated macrophages have direct influence on tumorigenesis in LyP and ALCL. Therefore, modulation of M2 macrophages may represent a new therapeutic strategy in cutaneous CD30-positive lymphoproliferative disorders. [ABSTRACT FROM AUTHOR]

Patients with a lymphoma have an increased risk of developing a second lymphoproliferative disorder. The association of nodal Hodgkin lymphoma and primary cutaneous marginal zone lymphoma ( MALT type) is exceptional, and only very few cases have been documented. Anetoderma represents a circumscribed loss or rarefication of elastic fibers. Different underlying processes may result in anetoderma, including cutaneous marginal zone lymphoma. We report a 50-year-old male patient with Epstein-Barr virus ( EBV)-associated nodal Hodgkin lymphoma who presented with disseminated anetodermic skin lesions. Biopsies of the skin lesions revealed a B-cell infiltrate containing monoclonal plasma cells but without detection of EBV. The skin lesions represent an anetodermic form of primary cutaneous marginal zone lymphoma. It is the first case report of an association of anetodermic cutaneous marginal zone lymphoma and a synchronous EBV-associated nodal Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) is an oncogenic human Herpes virus involved in the pathogenesis of nasal NK/T-cell lymphoma. EBV encodes microRNAs (miRNAs) and induces changes in the host cellular miRNA profile. MiRNAs are short non- coding RNAs of about 19-25 nt length that regulate gene expression by post- transcriptional mechanisms and are frequently deregulated in human malignancies including cancer. The microRNA profiles of EBV-positive NK/T-cell lymphoma, non- infected T-cell lymphoma and normal thymus were established by deep sequencing of small RNA libraries. The comparison of the EBV-positive NK/T-cell vs. EBV- negative T-cell lymphoma revealed 15 up- und 16 down-regulated miRNAs. In contrast, the majority of miRNAs was repressed in the lymphomas compared to normal tissue. We also identified 10 novel miRNAs from known precursors and two so far unknown miRNAs. The sequencing results were confirmed for selected miRNAs by quantitative Real-Time PCR (qRT-PCR). We show that the proinflammatory cytokine interleukin 1 alpha (IL1A) is a target for miR-142-3p and the oncogenic BCL6 for miR-205. MiR-142-3p is down-regulated in the EBV-positive vs. EBV- negative lymphomas. MiR-205 was undetectable in EBV-negative lymphoma and strongly down-regulated in EBV-positive NK/T-cell lymphoma as compared to thymus. The targets were confirmed by reporter assays and by down-regulation of the proteins by ectopic expression of the cognate miRNAs. Taken together, our findings demonstrate the relevance of deregulated miRNAs for the post- transcriptional gene regulation in nasal NK/T-cell lymphomas. [ABSTRACT FROM AUTHOR]