Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms

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, Veronique Winnepenninckx*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)607-626
Number of pages20
JournalHistopathology
Volume78
Issue number4
Early online date19 Nov 2020
DOIs
Publication statusPublished - Mar 2021

Keywords

  • spitzoid melanocytic neoplasm
  • Spitz tumour
  • Spitz naevus (SN)
  • atypical Spitz tumour (AST)
  • malignant Spitz tumour (MST)
  • T lymphocyte
  • inflammation
  • TUMOR-INFILTRATING LYMPHOCYTES
  • PROGNOSTIC-SIGNIFICANCE
  • CUTANEOUS MELANOMA
  • ATYPICAL VARIANTS
  • CELLS
  • NEVI
  • EXPRESSION
  • INHIBITOR
  • APOPTOSIS
  • IDENTIFICATION

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