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Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10 cases) were classified as activated B cell like type, with a higher PD-L1 score (21.9%) compared with that of the germinal center B cell like type (7.7%). The surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+) macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+) MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a polarization to M2 macrophages, which may contribute to the poor prognosis of DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD-L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this aggressive form of cutaneous B-cell lymphoma. © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Background: Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). Methods: Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. Results: We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(−) samples were mostly PD-L1 negative. Conclusions: Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Aims: Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas. Methods and results: Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed and recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and histologically have striking pagetoid epidermotrophism. A CD8+/CD45RA+/CD45RO-/CD2-/CD5-/CD56- phenotype, with one or more cytotoxic markers, was found in seven of 18 patients, with a very similar phenotype in the remainder. The tumours seldom involve lymph nodes, but mucosal and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp disease presented the typical features well documented in the CD4+ forms of those diseases. Conclusions: Aggressive epidermotropic cutaneous CD8+ lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications.

Background: In nodal anaplastic large cell lymphoma, strong expression of galectin-3 (Gal-3) has been found, but only very few cases of primary cutaneous lymphoma have so far been examined. Objectives: To investigate 11 primary cutaneous anaplastic large cell lymphomas (PCALCL), 47 lymphomatoid papuloses (LYP) and 14 cases of transformed mycosis fungoides with CD30 expression (MF-T) for Gal-3 expression. Methods: A Gal-3 score was applied using a photo-based morphometric evaluation program. Double staining for CD30 and Gal-3 was performed. Furthermore, we recorded the cellular and extracellular sublocalization of the signal. Results: The Gal-3 expression in CD30+ tumor cells was significantly lower in MF-T in contrast to CD30+ lymphoproliferative disorders (CD30 LPD; p < 0.001), but we found no differences between PCALCL and LYP (p = 0.42). In PCALCL Gal-3 was more often localized in the cytoplasm in contrast to LYP, in which an equal distribution in the cytoplasm and the nucleus was more common (p = 0.9). Conclusions: The lower Gal-3 expression in MF-T in comparison to CD30 LPD might be an additional criterion to differentiate both entities. The different sublocalization of the Gal-3 signal might reflect a different biological function and behavior. © 2015 S. Karger AG, Basel.

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