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

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 o...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Journal of Molecular Pathology
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Online Access:https://www.mdpi.com/2673-5261/6/2/10
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author 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
author_facet 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
author_sort Alessandro Bonis
collection DOAJ
description 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.
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spelling doaj-art-118cea3224ea433cbff33d040b855ebd2025-08-20T03:27:14ZengMDPI AGJournal of Molecular Pathology2673-52612025-05-01621010.3390/jmp6020010Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three PatientsAlessandro Bonis0Alberto Busetto1Federica Pezzuto2Giulia Pagliarini3Vincenzo Verzeletti4Mario Pezzella5Giorgio Cannone6Eleonora Faccioli7Marco Mammana8Giovanni Maria Comacchio9Alessandro Rebusso10Marco Schiavon11Chiara Giraudo12Fiorella Calabrese13Andrea Dell’Amore14Samuele Nicotra15Angelo Paolo Dei Tos16Federico Rea17Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyPathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyRadiology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyPathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalySurgical Pathology and Cytopathology Unit, Department of Medicine—DIMED, University of Padova, 35128 Padova, ItalyThoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health—DSCTV, University of Padova, 35128 Padova, ItalyMalignant 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.https://www.mdpi.com/2673-5261/6/2/10MPNSTintrathoracic triton tumorsoft tissue sarcomaNF1peripheral nerve sheath tumors
spellingShingle 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
Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients
Journal of Molecular Pathology
MPNST
intrathoracic triton tumor
soft tissue sarcoma
NF1
peripheral nerve sheath tumors
title Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients
title_full Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients
title_fullStr Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients
title_full_unstemmed Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients
title_short Surgical Management of Intrathoracic Triton Tumors: Insights into Emerging Molecular and Epigenetic Mechanisms with a Case Series of Three Patients
title_sort surgical management of intrathoracic triton tumors insights into emerging molecular and epigenetic mechanisms with a case series of three patients
topic MPNST
intrathoracic triton tumor
soft tissue sarcoma
NF1
peripheral nerve sheath tumors
url https://www.mdpi.com/2673-5261/6/2/10
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