Dataset Information

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

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.

SUBMITTER: Hillen LM

PROVIDER: S-EPMC7894529 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Hillen Lisa M LM Vandyck Hendrik L D HLD Leunissen Daphne J G DJG de Greef Bianca T A BTA Bosisio Francesca M FM Zur Hausen Axel A van den Oord Joost J Winnepenninckx Véronique V

Histopathology 20201119 4

<h4>Aims</h4>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 sp ...[more]

PMID: 32970867

Similar Datasets

Project description:Spitzoid neoplasms are a challenging group of cutaneous melanocytic proliferations that occur in children or adolescents but can also arise in the elderly. They are characterized by epithelioid and/ or spindle-shaped melanocytes with a stromal background of variable amounts of lymphocytes, blood vessels and sclerosis. According to the WHO 2018 classification, Spitzoid melanocytic lesions are classified as benign Spitz nevi (SN), atypical Spitz tumors (AST) or malignant Spitz tumors (MST). The intermediate AST category represents a diagnostically challenging group since on purely histopathological grounds, their benign or malignant character remains unpredictable. This results in uncertainties in patient management and prognosis. The molecular properties of Spitzoid lesions, especially their transcriptomic landscape, remain poorly understood and genomic alterations in melanoma-associated oncogenes are typically absent. The aim of this study was to characterize the transcriptome of Spitzoid melanocytic neoplasms with digital mRNA expression profiling. Formalin-fixed-paraffin-embedded samples (including 27 SN, 10 AST and 14 MST) were analyzed using the RNA NanoString nCounter PanCancer Pathways Gene Expression panel. The number of significantly differentially expressed genes in SN vs. MST, SN vs. AST and AST vs. MST was 68, 167 and 18, respectively. Gene set enrichment analysis revealed an upregulation of pathways related to epithelial mesenchymal transition, immunomodulatory-, angiogenesis- as well as myogenesis associated processes in AST and MST. In addition, a specific gene expression signature of SN vs. MST was discovered based on the top-ranked six most informative gene expression markers: NRAS, NF1, BMP2, EIF2B4, IFNA17 and FZD9. The AST samples showed intermediate levels of the identified signature. This implies that the identified gene expression signature can potentially be used to distinguish high-grade from low-grade AST. This combined histopathological and transcriptomic methodology is promising for diagnostics of Spitzoid neoplasms and patient management in dermatological oncology in the future.

Dataset Information

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

Aims

Methods and results

Conclusion

Publications

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

Similar Datasets

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