Multimodal characterisation of spontaneous Merkel cell carcinoma in the endangered Caucasian squirrel (Sciurus anomalus pallescens): integrating spatial transcriptomics, imaging mass cytometry and metagenomic sequencing

Peyman Mohammadzadeh; Amin Pilvaieh; Arshia Dousti; Mohammad Reza Salim Bahrami; Farshad Ziaee

doi:10.2478/jvetres-2026-0034

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Multimodal characterisation of spontaneous Merkel cell carcinoma in the endangered Caucasian squirrel (Sciurus anomalus pallescens): integrating spatial transcriptomics, imaging mass cytometry and metagenomic sequencing

Journal of Veterinary Research

Volume 70 (2026): Issue 2 (June 2026)

By: Peyman Mohammadzadeh , Amin Pilvaieh , Arshia Dousti , Mohammad Reza Salim Bahrami and Farshad Ziaee

Open Access

|Jun 2026

Abstract

Introduction

Merkel cell carcinoma is an aggressive neuroendocrine skin malignancy rarely reported in non-domestic species.

Material and Methods

A cutaneous nodule from an endangered Caucasian squirrel (Sciurus anomalus pallescens) was examined using histopathology, immunohistochemistry, imaging mass cytometry, spatial transcriptomics (10× Visium) and metagenomic sequencing.

Results

Histology revealed a high-grade neuroendocrine carcinoma with frequent mitoses (52 per 2.37 mm²) and necrosis. Tumour cells were positive for cytokeratin 20 (paranuclear dot pattern), synaptophysin and chromogranin A, with a high Ki-67 index (68%). Spatial analyses delineated a distinct tumour core and combined invasive front and stromal compartments, revealing upregulation of neuroendocrine (atonal basic helix–loop–helix transcription factor 1 and neurogenic differentiation factor 1) and proliferative (marker of proliferation Ki-67) programmes, and activation of phosphoinositide 3-kinase–AKT serine/threonine kinase 1–mechanistic target of rapamycin and mitogen-activated protein kinase pathways. No evidence of Merkel cell polyomavirus was found. The tumour microenvironment was immune-excluded, with programmed-death ligand 1 expression on ~22% of tumour cells and CD8⁺ T cells restricted to the stroma.

Conclusion

This study provides a comprehensive methodological framework for high-resolution tumour profiling in conservation pathology and highlights the emergence of neoplasia in threatened wildlife.

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Articles in this issue

DOI: https://doi.org/10.2478/jvetres-2026-0034 | Journal eISSN: 2450-8608

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Language: English

Page range: 321 - 334

Submitted on: Nov 29, 2025

Accepted on: Jun 24, 2026

Published on: Jun 30, 2026

Published by: National Veterinary Research Institute in Pulawy

In partnership with: Paradigm Publishing Services

Keywords:

comparative oncology,

imaging mass cytometry,

Merkel cell carcinoma,

spatial transcriptomics,

Related subjects:

Microbiology and virology,

Life sciences,

Life sciences, other

© 2026 Peyman Mohammadzadeh, Amin Pilvaieh, Arshia Dousti, Mohammad Reza Salim Bahrami, Farshad Ziaee, published by National Veterinary Research Institute in Pulawy
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 70 (2026): Issue 2 (June 2026)