Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients

Alessandro Bonis; Alberto Busetto; Federica Pezzuto; Giulia Pagliarini; Vincenzo Verzeletti; Mario Pezzella; Giorgio Cannone; Eleonora Faccioli; Marco Mammana; Giovanni Maria Comacchio; Alessandro Rebusso; Marco Schiavon; Chiara Giraudo; Fiorella Calabrese; Andrea Dell’Amore; Samuele Nicotra; Angelo Paolo Dei Tos; Federico Rea

doi:10.3390/jmp6020010

Journal of Molecular Pathology (May 2025)

Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients

Alessandro Bonis,
Alberto Busetto,
Federica Pezzuto,
Giulia Pagliarini,
Vincenzo Verzeletti,
Mario Pezzella,
Giorgio Cannone,
Eleonora Faccioli,
Marco Mammana,
Giovanni Maria Comacchio,
Alessandro Rebusso,
Marco Schiavon,
Chiara Giraudo,
Fiorella Calabrese,
Andrea Dell’Amore,
Samuele Nicotra,
Angelo Paolo Dei Tos,
Federico Rea

Affiliations

Alessandro Bonis: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Alberto Busetto: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Federica Pezzuto: Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Giulia Pagliarini: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Vincenzo Verzeletti: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Mario Pezzella: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Giorgio Cannone: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Eleonora Faccioli: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Marco Mammana: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Giovanni Maria Comacchio: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Alessandro Rebusso: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Marco Schiavon: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Chiara Giraudo: Radiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Fiorella Calabrese: Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Andrea Dell’Amore: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Samuele Nicotra: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy
Angelo Paolo Dei Tos: Surgical Pathology and Cytopathology Unit, Department of Medicine—DIMED, University of Padova, 35128 Padova, Italy
Federico Rea: Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, Italy

DOI: https://doi.org/10.3390/jmp6020010
Journal volume & issue: Vol. 6, no. 2
p. 10

Abstract

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Malignant Triton Tumors (MTTs) are rare, high-grade malignant peripheral nerve sheath tumors (MPNSTs) frequently associated with Type 1 Neurofibromatosis (NF1). NF1, an autosomal dominant disorder, predisposes approximately 10% of affected individuals to developing MPNSTs, with 50% of these tumors occurring in NF1 patients, while others arise sporadically or in association with radiation exposure. MTTs predominantly affect anatomical regions rich in large nerves, such as the limbs, spinal root, and cranial nerves. Mediastinal presentations are exceedingly rare, posing significant diagnostic and therapeutic challenges. Current treatment strategies include surgical resection, chemotherapy, radiotherapy, and lung-sparing procedures for metastatic disease. Molecular studies of MPNSTs have revealed that NF1 mutations lead to dysregulation of the RAS signalling pathway, while epigenetic alterations (e.g., SUZ12/EED mutations) further contribute to tumor progression. Dysregulated phylogenetically conserved pathways, including Wnt/beta-catenin and non-canonical SHH signalling, play a role in sarcoma progression and Schwann cell transformation. Recent advances in miRNA research highlight their involvement in tumor invasion and progression, with dysregulated miRNA expression and chromatin remodeling contributing to the pathogenesis of these neoplasms. However, the distinct molecular profiles for MTTs remain incompletely understood. Further investigation of the genetic and epigenetic landscape is essential for improving our understanding and identifying potential therapies. Herein, we present a single-center retrospective case series of three patients with an intrathoracic triton tumor treated at our University Hospital between 2000 and 2024, serving as a starting point for future insights into MPNST pathobiology.

Published in Journal of Molecular Pathology

ISSN: 2673-5261 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pathology
Website: https://www.mdpi.com/journal/jmp

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