Lisa M Hillen1, Hendrik L D Vandyck1, Daphne J G Leunissen1, Bianca T A de Greef2, Francesca M Bosisio3, Axel Zur Hausen1, Joost van den Oord3,4, Véronique Winnepenninckx1. 1. Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands. 2. Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, the Netherlands. 3. Laboratory for Translational Cell and Tissue Research (TCTR), University of Leuven, KUL, Leuven, Belgium. 4. Department of Pathology, University Hospitals, Leuven, Belgium.
Abstract
AIMS: The role of inflammation in conventional cutaneous melanoma has been extensively studied, whereas only little is known about the inflammatory microenvironment and immunogenic properties of spitzoid melanocytic neoplasms. The composition of infiltrating immune cells and the architectural distribution of the inflammation, in particular, are still obscure. This is the first study, to our knowledge, to systematically characterise the inflammatory patterns and the leucocyte subsets in spitzoid melanocytic lesions. METHODS AND RESULTS: We examined 79 spitzoid neoplasms including banal Spitz naevi (SN, n = 50), atypical Spitz tumours (AST, n = 17) and malignant Spitz tumours (MST, n = 12) using histopathological analysis and immunohistochemistry. Spitzoid melanocytic lesions showed a high frequency (67.1%, n = 53 of 79) of inflammation. Four inflammatory patterns were identified according to architectural composition, distribution and intensity of inflammation. The majority of the inflammatory infiltrate corresponded to CD3+ /CD8+ T lymphocytes (56.1%), followed by CD3+ /CD4+ T cells (35.7%) and CD68+ histiocytes (20.3%). CD3+ /TIA-1+ cytotoxic T lymphocytes constituted 3.7% of inflammatory cells. Rarely, CD3+ / granzyme B+ cytotoxic T lymphocytes (2.7%) and CD138+ plasma cells (0.5%) were detected in the infiltrating immune cells. There was no significant difference in the inflammatory cellular composition among the spitzoid melanocytic subgroups (SN versus AST versus MST). CONCLUSION: Our findings demonstrate that Spitz tumours are highly immunogenic lesions. Inflammation with the presence of lymphocytic aggregates predominated in SN, but was not distinctive for this melanocytic category. A strong and intense inflammation was suggestive of an underlying malignancy. The infiltrating cytotoxic T lymphocyte subsets in Spitz tumours deserve further investigation in larger study cohorts to elucidate prognostic and immuno-oncological therapeutic relevance.
AIMS: The role of inflammation in conventional cutaneous melanoma has been extensively studied, whereas only little is known about the inflammatory microenvironment and immunogenic properties of spitzoid melanocytic neoplasms. The composition of infiltrating immune cells and the architectural distribution of the inflammation, in particular, are still obscure. This is the first study, to our knowledge, to systematically characterise the inflammatory patterns and the leucocyte subsets in spitzoid melanocytic lesions. METHODS AND RESULTS: We examined 79 spitzoid neoplasms including banal Spitz naevi (SN, n = 50), atypical Spitz tumours (AST, n = 17) and malignant Spitz tumours (MST, n = 12) using histopathological analysis and immunohistochemistry. Spitzoid melanocytic lesions showed a high frequency (67.1%, n = 53 of 79) of inflammation. Four inflammatory patterns were identified according to architectural composition, distribution and intensity of inflammation. The majority of the inflammatory infiltrate corresponded to CD3+ /CD8+ T lymphocytes (56.1%), followed by CD3+ /CD4+ T cells (35.7%) and CD68+ histiocytes (20.3%). CD3+ /TIA-1+ cytotoxic T lymphocytes constituted 3.7% of inflammatory cells. Rarely, CD3+ / granzyme B+ cytotoxic T lymphocytes (2.7%) and CD138+ plasma cells (0.5%) were detected in the infiltrating immune cells. There was no significant difference in the inflammatory cellular composition among the spitzoid melanocytic subgroups (SN versus AST versus MST). CONCLUSION: Our findings demonstrate that Spitz tumours are highly immunogenic lesions. Inflammation with the presence of lymphocytic aggregates predominated in SN, but was not distinctive for this melanocytic category. A strong and intense inflammation was suggestive of an underlying malignancy. The infiltrating cytotoxic T lymphocyte subsets in Spitz tumours deserve further investigation in larger study cohorts to elucidate prognostic and immuno-oncological therapeutic relevance.
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Authors: Lisa M Hillen; Joost Van den Oord; Milan S Geybels; Jürgen C Becker; Axel Zur Hausen; Véronique Winnepenninckx Journal: Front Med (Lausanne) Date: 2018-12-13
Authors: H Halse; A J Colebatch; P Petrone; M A Henderson; J K Mills; H Snow; J A Westwood; S Sandhu; J M Raleigh; A Behren; J Cebon; P K Darcy; M H Kershaw; G A McArthur; D E Gyorki; P J Neeson Journal: Sci Rep Date: 2018-07-24 Impact factor: 4.379
Authors: Lisa M Hillen; Hendrik L D Vandyck; Daphne J G Leunissen; Bianca T A de Greef; Francesca M Bosisio; Axel Zur Hausen; Joost van den Oord; Véronique Winnepenninckx Journal: Histopathology Date: 2020-11-19 Impact factor: 5.087