ORIGINAL ARTICLES: Clinical researchLymphoid aggregates in desmoplastic melanoma have features of tertiary lymphoid structuresStowman, Anne M.a; Hickman, Alexandra W.b; Mauldin, Ileana S.c; Mahmutovic, Adelac; Gru, Alejandro A.d; Slingluff, Craig L. JrcAuthor Information aDepartment of Pathology, University of Vermont Medical Center, Burlington, Vermont bUniversity of Virginia School of Medicine Departments of cSurgery dPathology, University of Virginia Health System, Charlottesville, Virginia, USA Correspondence to Craig L. Slingluff Jr, MD, Department of Surgery, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22908, USA Tel: +1 434 924 2129; fax: +1 434 982 5959; e-mail: [email protected] Melanoma Research: June 2018 - Volume 28 - Issue 3 - p 237-245 doi: 10.1097/CMR.0000000000000439 Buy Metrics Abstract Desmoplastic melanomas (DM) have unique and challenging clinical presentations and histomorphology. A characteristic feature is the presence of scattered lymphoid aggregates. However, the nature of these aggregates is not defined. We hypothesized that they may be tertiary lymphoid structures (TLS), and may be associated with programmed death ligand 1 (PD-L1) expression. We searched our tissue database for ‘pure’ DMs and for scars as control tissues, collected clinical information, and reviewed H&E histology. We performed multispectral imaging after staining for CD8, CD20, PNAd, FoxP3, CD83, and Ki67, and assessed PD-L1 expression by immunohistochemistry. Pure DM samples were evaluable in 11 patients. All had desmoplastic stroma and lymphoid aggregates on H&E. The lymphoid aggregates of eight of the 11 (72%) DM samples and only three of the 11 scars contained features of TLS, defined as distinct clusters of B cells and CD8+ T cells, CD83+ dendritic cells in T-cell zones, and PNAd+ vasculature resembling high endothelial venules. PD-L1 was expressed by at least 1% of melanoma cells in six and by at least 5% of immune cells in 10 of the 11 DM samples. We found that most lymphoid aggregates in DM are organized, classical TLS. PD-L1 expression was detected in most cases and was highest in two cases of DM with TLS. However, low PD-L1 expression in some cases suggests that some DM cells may be unresponsive to interferon-γ. TLS support antigen presentation and T-cell responses in chronic inflammation and cancer. Their presence in DM likely reflects an adaptive immune response, which may be enhanced with immune therapies. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.