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Dutta AR, Wenger DE, Thorpe MP, Frick MA, Folpe AL, Broski SM. MR Imaging Features of Malignant Tenosynovial Giant Cell Tumors. Acad Radiol 2025:S1076-6332(25)00313-7. [PMID: 40287291 DOI: 10.1016/j.acra.2025.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2025] [Revised: 04/03/2025] [Accepted: 04/06/2025] [Indexed: 04/29/2025]
Abstract
RATIONALE AND OBJECTIVES To examine MRI characteristics of malignant tenosynovial giant cell tumors (TSGCTs) and elucidate features to differentiate benign and malignant TSGCTs. MATERIALS AND METHODS With IRB approval, the medical record was retrospectively reviewed from 2004-2024 for cases of pathologically-proven benign and malignant TSGCTs evaluated by MRI. RESULTS 12 malignant TSGCTs (5F/7M, mean age 48.7 +/- 17.6 years) and 23 benign TSGCTs (13F/10M, mean age 43.7 +/- 18.7 years) were identified. There was no significant difference in age (p=0.45), gender (p=0.63), MRI signal characteristics (T1 signal p=0.57, T2 signal p=0.46, T2 signal heterogeneity p>0.99, presence of low T2 signal p>0.99), type of enhancement (presence of enhancement p=0.21, degree of enhancement p=0.12, heterogenous vs. homogenous enhancement p=0.21, presence of non-enhancing areas p=0.11), blooming artifact (p=0.065), or presence of perilesional edema (p=0.16) between benign and malignant TSGCTs. Four MRI features were more commonly associated with malignant TSGCTs: extra-articular location (p=0.009), irregular margins (p=0.0014), perilesional vessels (p=0.0014), and larger average maximal dimension (8.6 +/- 8.4 cm malignant vs. 2.8 +/- 2.2 cm benign, p=0.036). CONCLUSION Although there are overlapping MRI characteristics between benign and malignant TSGCTs, malignant TSGCTs are more likely to exhibit larger size, extra-articular location, irregular margins and prominent perilesional vessels compared to their benign counterparts. Some malignant TSGCTs may not be associated with a synovial-lined structure on imaging.
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Affiliation(s)
- Anika R Dutta
- Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (A.R.D., D.E.W., M.P.T., M.A.F., S.M.B.)
| | - Doris E Wenger
- Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (A.R.D., D.E.W., M.P.T., M.A.F., S.M.B.); Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota 55905 (D.E.W.)
| | - Matthew P Thorpe
- Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (A.R.D., D.E.W., M.P.T., M.A.F., S.M.B.)
| | - Matthew A Frick
- Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (A.R.D., D.E.W., M.P.T., M.A.F., S.M.B.)
| | - Andrew L Folpe
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905 (A.L.F.)
| | - Stephen M Broski
- Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (A.R.D., D.E.W., M.P.T., M.A.F., S.M.B.).
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Yu Y, Wei C, Yue M, Zhang C, Wang Y, Wang Z. From benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST): a gaming among multiple factors. Cell Oncol (Dordr) 2025:10.1007/s13402-025-01054-9. [PMID: 40172801 DOI: 10.1007/s13402-025-01054-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 03/04/2025] [Indexed: 04/04/2025] Open
Abstract
Almost all patients of Neurofibromatosis Type I (NF1) develop benign peripheral nerve tumors called neurofibromas, which are derived from neural crest Schwann cell lineage progenitors with biallelic NF1 gene mutations. More than 90% of NF1 patients develop dermal neurofibromas (DN), and 25-50% develop plexiform neurofibromas (PN). In 8-13% of individuals with NF1, PN can transform into malignant peripheral nerve sheath tumors (MPNSTs), a type of nerve soft tissue sarcoma that is the main cause of mortality of NF1 patients. In addition to arising from benign neurofibromas (50%), MPNSTs can also occur spontaneously (~40%) or following radiation therapy (~10%). Treatment for MPNST is limited to complete resection with negative margins. Still, the high recurrence of MPNST is a major concern. However, full resection of the pre-malignant lesions can largely reduce the recurrence and mortality of patients. So, early diagnosis and distinguishing malignancy from benign and premalignant lesions are particularly important. During the progression from benign neurofibromas to malignancy, a variety of changes including tumor morphology, genetic mutations, expression of multiple signaling pathways-related proteins and genome instability gradually occur. In this review, we detail these changes with the goals of identifying the histological and/or molecular signs of malignancy initiation, and an optimal therapeutic intervention window, to inhibit tumor progression and reduce the rate of mortality.
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Affiliation(s)
- Yanan Yu
- Department of Genetics, School of Life Science, Xuzhou Medical University, Xuzhou, 221004, China.
- Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
| | - Chengjiang Wei
- Neurofibromatosis Type 1 Center and Laboratory for Neurofibromatosis Type 1 Research, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Minghui Yue
- Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, 221002, China
- School of Stomatology, Xuzhou Medical University, Xuzhou, 221004, China
| | - Cheng Zhang
- Department of Genetics, School of Life Science, Xuzhou Medical University, Xuzhou, 221004, China
| | - Yixiao Wang
- Department of Genetics, School of Life Science, Xuzhou Medical University, Xuzhou, 221004, China
| | - Zhichao Wang
- Neurofibromatosis Type 1 Center and Laboratory for Neurofibromatosis Type 1 Research, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
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Thakur U, Ramachandran S, Mazal AT, Cheng J, Le L, Chhabra A. Multiparametric whole-body MRI of patients with neurofibromatosis type I: spectrum of imaging findings. Skeletal Radiol 2025; 54:407-422. [PMID: 39105762 DOI: 10.1007/s00256-024-04765-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 07/20/2024] [Accepted: 07/22/2024] [Indexed: 08/07/2024]
Abstract
Neurofibromatosis (NF) type I is a neuroectodermal and mesodermal dysplasia caused by a mutation of the neurofibromin tumor suppressor gene. Phenotypic features of NF1 vary, and patients develop benign peripheral nerve sheath tumors and malignant neoplasms, such as malignant peripheral nerve sheath tumor, malignant melanoma, and astrocytoma. Multiparametric whole-body MR imaging (WBMRI) plays a critical role in disease surveillance. Multiparametric MRI, typically used in prostate imaging, is a general term for a technique that includes multiple sequences, i.e. anatomic, diffusion, and Dixon-based pre- and post-contrast imaging. This article discusses the value of multiparametric WBMRI and illustrates the spectrum of whole-body lesions of NF1 in a single imaging setting. Examples of lesions include those in the skin (tumors and axillary freckling), soft tissues (benign and malignant peripheral nerve sheath tumors, visceral plexiform, and diffuse lesions), bone and joints (nutrient nerve lesions, non-ossifying fibromas, intra-articular neurofibroma, etc.), spine (acute-angled scoliosis, dural ectasia, intraspinal tumors, etc.), and brain/skull (optic nerve glioma, choroid plexus xanthogranuloma, sphenoid wing dysplasia, cerebral hamartomas, etc.). After reading this article, the reader will gain knowledge of the variety of lesions encountered with NF1 and their WBMRI appearances. Timely identification of such lesions can aid in accurate diagnosis and appropriate patient management.
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Affiliation(s)
- Uma Thakur
- Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75235, USA
| | - Shyam Ramachandran
- Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75235, USA
| | - Alexander T Mazal
- Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Jonathan Cheng
- Department of Plastic Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Lu Le
- Department of Dermatology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
| | - Avneesh Chhabra
- Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75235, USA.
- Department of Orthopedic Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
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Azab MA, Mostafa HA, Atallah O. FDG-PET/CT Avid Uptake of a Biopsy-Proven Aggressive Melanotic Schwannoma of the S2 Spinal Nerve Root. World J Nucl Med 2025; 24:71-74. [PMID: 39959154 PMCID: PMC11828635 DOI: 10.1055/s-0044-1791694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2025] Open
Abstract
Malignant melanotic nerve sheath tumors (MMNSTs), also known as a melanocytic schwannoma (MS), are a rare type of peripheral nerve sheath tumors including Schwann cells with melanocytic differentiation. Only a few cases of spinal MMNST have been reported in literature. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) could be used to detect these lesions. A 70-year-old man with a 6-month history of backache was admitted to our hospital. PET/CT showed a paravertebral soft tissue mass along the spinal nerve at the S2 level with strong FDG uptake, and a nodule with increased FDG uptake in the right lobe of the left liver. A CT-guided biopsy of the S2 lesion was performed. The final diagnosis was spinal MS with hepatic metastasis. The patient received stereotactic body radiation therapy. Herein, we report the PET/CT findings of a case of MS with hepatic metastasis. FDG-PET/CT is helpful in the differential diagnosis of benign and malignant lesions although nonspecific.
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Affiliation(s)
| | | | - Oday Atallah
- Department of Neurosurgery, Hannover School of Medicine, Hannover, Germany
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Shirodkar K, Hussein M, Reddy PS, Shah AB, Raniga S, Pal D, Iyengar KP, Botchu R. Imaging of Peripheral Intraneural Tumors: A Comprehensive Review for Radiologists. Cancers (Basel) 2025; 17:246. [PMID: 39858028 PMCID: PMC11763772 DOI: 10.3390/cancers17020246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Intraneural tumors (INTs) pose a diagnostic challenge, owing to their varied origins within nerve fascicles and their wide spectrum, which includes both benign and malignant forms. Accurate diagnosis and management of these tumors depends upon the skills of the radiologist in identifying key imaging features and correlating them with the patient's clinical symptoms and examination findings. METHODS This comprehensive review systematically analyzes the various imaging features in the diagnosis of intraneural tumors, ranging from basic MR to advanced MR imaging techniques such as MR neurography (MRN), diffusion tensor imaging (DTI), and dynamic contrast-enhanced (DCE) MRI. RESULTS The article emphasizes the differentiation of benign from malignant lesions using characteristic MRI features, such as the "target sign" and "split-fat sign" for tumor characterization. The role of advanced multiparametric MRI in improving biopsy planning, guiding surgical mapping, and enhancing post-treatment monitoring is also highlighted. The review also underlines the importance of common diagnostic pitfalls and highlights the need for a multi-disciplinary approach to achieve an accurate diagnosis, appropriate treatment strategy, and post-therapy surveillance planning. CONCLUSIONS In this review, we illustrate the main imaging findings of intraneural tumors, focusing on specific MR imaging features that are crucial for an accurate diagnosis and the differentiation between benign and malignant lesions.
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Affiliation(s)
| | | | | | | | - Sameer Raniga
- Sultan Qaboos University Hospital, Seeb H5QC+4HX, Oman
| | - Devpriyo Pal
- Stoke Mandeville Hospital, Aylesbury HP21 8AL, UK
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Noebauer-Huhmann IM, Vanhoenacker FM, Vilanova JC, Tagliafico AS, Weber MA, Lalam RK, Grieser T, Nikodinovska VV, de Rooy JWJ, Papakonstantinou O, Mccarthy C, Sconfienza LM, Verstraete K, Martel-Villagrán J, Szomolanyi P, Lecouvet FE, Afonso D, Albtoush OM, Aringhieri G, Arkun R, Aström G, Bazzocchi A, Botchu R, Breitenseher M, Chaudhary S, Dalili D, Davies M, de Jonge MC, Mete BD, Fritz J, Gielen JLMA, Hide G, Isaac A, Ivanoski S, Mansour RM, Muntaner-Gimbernat L, Navas A, O Donnell P, Örgüç Ş, Rennie WJ, Resano S, Robinson P, Sanal HT, Ter Horst SAJ, van Langevelde K, Wörtler K, Koelz M, Panotopoulos J, Windhager R, Bloem JL. Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR). Eur Radiol 2025; 35:351-359. [PMID: 39030374 PMCID: PMC11631817 DOI: 10.1007/s00330-024-10897-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/30/2024] [Accepted: 04/30/2024] [Indexed: 07/21/2024]
Abstract
OBJECTIVES The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. MATERIALS AND METHODS A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. RESULTS The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. CONCLUSION Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. CLINICAL RELEVANCE STATEMENT These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. KEY POINTS An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.
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Affiliation(s)
- Iris-Melanie Noebauer-Huhmann
- Department of Biomedical Imaging and Image Guided Therapy, Division of Neuroradiology and Musculoskeletal Radiology, Medical University of Vienna, Vienna, Austria.
| | - Filip M Vanhoenacker
- Department of Radiology, AZ Sint Maarten Mechelen University (Hospital) Antwerp, Antwerp, Belgium
- Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium
| | - Joan C Vilanova
- Department of Radiology, Clínica Girona, Institute of Diagnostic Imaging (IDI) Girona, University of Girona, Girona, Spain
| | - Alberto S Tagliafico
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
- Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Marc-André Weber
- Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, University Medical Center Rostock, Rostock, Germany
| | - Radhesh K Lalam
- Department of Radiology, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK
| | - Thomas Grieser
- Department for Diagnostic and Interventional Radiology, University Hospital Augsburg, Augsburg, Germany
| | - Violeta Vasilevska Nikodinovska
- Medical Faculty, Ss. Cyril and Methodius University, Skopje, Macedonia
- Department of Radiology, University Surgical Clinic "St. Naum Ohridski", Skopje, Macedonia
| | - Jacky W J de Rooy
- Department of Imaging, Radiology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Olympia Papakonstantinou
- 2nd Department of Radiology, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Catherine Mccarthy
- Oxford Musculoskeletal Radiology and Oxford University Hospitals, Oxford, UK
| | - Luca Maria Sconfienza
- IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Dipartimento Di Scienze Biomediche Per La Salute, Università Degli Studi Di Milano, Milan, Italy
| | | | | | - Pavol Szomolanyi
- High Field MR Center, Department of Biomedical Imaging and Image‑Guided Therapy, Medical University Vienna, Vienna, Austria
- Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Frédéric E Lecouvet
- Department of Radiology and Medical Imaging, Cliniques Universitaires Saint Luc, Institut de Recherche Expérimentale et Clinique (IREC), Institut du Cancer Roi Albert II (IRA2), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Diana Afonso
- Hospital Particular da Madeira and Hospital da Luz Lisboa, Lisbon, Portugal
| | - Omar M Albtoush
- Department of Radiology, University of Jordan, Ammam, Jordan
| | - Giacomo Aringhieri
- Academic Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Remide Arkun
- Ege University Medical School (Emeritus), Izmir, Türkiye
- Star Imaging Center, Izmir, Türkiye
| | - Gunnar Aström
- Department of Immunology, Genetics and Pathology (Oncology) and Department of Surgical Sciences (Radiology), Uppsala University, Uppsala, Sweden
| | - Alberto Bazzocchi
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Rajesh Botchu
- Department of Musculoskeletal Radiology, Royal Orthopedic Hospital, Birmingham, UK
| | | | | | - Danoob Dalili
- Academic Surgical Unit, South West London Elective Orthopaedic Centre (SWLEOC), London, UK
| | - Mark Davies
- Department of Musculoskeletal Radiology, Royal Orthopedic Hospital, Birmingham, UK
| | - Milko C de Jonge
- Department of Radiology, St. Antonius Hospital, Utrecht, The Netherlands
| | - Berna D Mete
- Department of Radiology School of Medicine, Izmir Demokrasi University, Izmir, Türkiye
| | - Jan Fritz
- Department of Radiology, NYU Grossman School of Medicine, New York, NY, USA
- Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, University Hospital Tuebingen, Tübingen, Germany
| | - Jan L M A Gielen
- Department of Radiology, Jessa Ziekenhuis, Campus Virga Jesse, Hasselt, Belgium
| | - Geoff Hide
- Department of Radiology, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Amanda Isaac
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Slavcho Ivanoski
- St. Erasmo Hospital for Orthopaedic Surgery and Traumatology Ohrid, Ohrid, Macedonia
| | | | | | - Ana Navas
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | - Winston J Rennie
- Clinical MSK Radiology, Loughborough University, Leicester Royal Infirmary, Leicester, UK
| | | | - Philip Robinson
- Musculoskeletal Radiology Department Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- NIHR Leeds Biomedical Research Centre, Leeds, UK
| | - Hatice T Sanal
- Radiology Department, University of Health Sciences, Gülhane Training and Research Hospital, Ankara, Türkiye
| | - Simone A J Ter Horst
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Radiology and Nuclear Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
| | | | - Klaus Wörtler
- Musculoskeletal Radiology Section, Klinikum Rechts der Isar, Technical University of Munich ‑ TUM School of Medicine, Munich, Germany
| | - Marita Koelz
- Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Joannis Panotopoulos
- Departement of Orthopaedics and Traumatology, Division of Orthopaedics, Medical University of Vienna, Vienna, Austria
| | - Reinhard Windhager
- Departement of Orthopaedics and Traumatology, Medical University of Vienna, Vienna, Austria
| | - Johan L Bloem
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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Ristow I, Apostolova I, Kaul MG, Stark M, Zapf A, Schmalhofer ML, Mautner VF, Farschtschi S, Adam G, Bannas P, Salamon J, Well L. Discrimination of benign, atypical, and malignant peripheral nerve sheath tumours in neurofibromatosis type 1 - intraindividual comparison of positron emission computed tomography and diffusion-weighted magnetic resonance imaging. EJNMMI Res 2024; 14:127. [PMID: 39729173 DOI: 10.1186/s13550-024-01189-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND To intraindividually compare the diagnostic performance of positron emission computed tomography (F-18-FDG-PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in a non-inferiority design for the discrimination of peripheral nerve sheath tumours as benign (BPNST), atypical (ANF), or malignant (MPNST) in patients with neurofibromatosis type 1 (NF1). RESULTS In this prospective single-centre study, thirty-four NF1 patients (18 male; 30 ± 11 years) underwent F-18-FDG-PET/CT and multi-b-value DW-MRI (11 b-values 0 - 800 s/mm²) at 3T. Sixty-six lesions corresponding to 39 BPNST, 11 ANF, and 16 MPNST were evaluated. Two radiologists independently assessed the maximum standardized uptake value (SUVmax) and mean and minimum apparent diffusion coefficient (ADCmean/min) as well as the ADC in areas of lowest signal intensity in each lesion (ADCdark). The AUCs of DW-MRI and F-18-FDG-PET/CT were compared to determine whether the ADC is non-inferior to SUVmax (non-inferiority margin equal to -10%). Follow-up of ≥ 24 months (BPNST) or histopathological evaluation (MPNST + ANF) served as diagnostic reference standard. Both SUVmax and ADC parameters demonstrated good diagnostic accuracy (AUCSUVmax 94.0%; AUCADCmean/min/dark 91.6% / 90.1% / 92.5%). However, non-inferiority could not be demonstrated for any of the three ADC parameters (lower limits of the confidence intervals of the difference between the AUC of ADCmean/min/dark and SUVmax -12.9% / -14.5% / -11.6%). Inter-rater reliability was excellent for both imaging techniques (Krippendorff's alpha all > 0.94). CONCLUSIONS Both PET/CT-derived SUVmax and MRI-derived ADC allow sensitive and non-invasive differentiation of benign and (pre)-malignant peripheral nerve sheath tumours. Nevertheless, DW-MRI cannot be considered as non-inferior to F-18-FDG-PET/CT in this prospective single-centre study.
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Affiliation(s)
- Inka Ristow
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
| | - Ivayla Apostolova
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Michael G Kaul
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Maria Stark
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Antonia Zapf
- Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marie-Lena Schmalhofer
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Victor F Mautner
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Said Farschtschi
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gerhard Adam
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Peter Bannas
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Johannes Salamon
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
- Department of Diagnostic and Interventional Radiology, Medical Care Center Beste Trave, Bad Oldesloe, Germany
| | - Lennart Well
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
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8
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Gervais MK, Basile G, Dulude JP, Mottard S, Gronchi A. Histology-Tailored Approach to Soft Tissue Sarcoma. Ann Surg Oncol 2024; 31:7915-7929. [PMID: 39174839 DOI: 10.1245/s10434-024-15981-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 07/23/2024] [Indexed: 08/24/2024]
Abstract
Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.
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Affiliation(s)
- Mai-Kim Gervais
- Division of Surgical Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Georges Basile
- Division of Orthopedic Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Jean-Philippe Dulude
- Division of Surgical Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Sophie Mottard
- Division of Orthopedic Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Alessandro Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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Guedes F, Llorian E, Henriques VM, Torrão-Junior FJL. Brachial plexus peripheral nerve sheath tumors (PNSTs): clinical and surgical management in the pediatric population. Childs Nerv Syst 2024; 40:3789-3800. [PMID: 38940956 DOI: 10.1007/s00381-024-06509-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 06/17/2024] [Indexed: 06/29/2024]
Abstract
PURPOSE Peripheral nerve sheath tumors (PNSTs) are rare in pediatric patients, especially in the brachial plexus. Research on PNSTs is lacking. This article presents a retrospective cohort study of pediatric patients diagnosed and treated with PNSTs, specifically brachial plexus tumors. METHODS All pediatric patients intervened in a single center between 2007 and 2023 with brachial plexus tumors were systemically analyzed. RESULTS Eleven pediatric patients with 14 brachial plexus PNSTs were studied. The gender distribution was 64% female and 36% male, with an average age of 10.7 years. Ninety-one percent had a previous NF-1 diagnosis. Right brachial plexus presented a higher prevalence (64%). Pain, Tinel's sign, and stiffness masses were common during diagnosis. Motor deficits were noted in 43% of the patients. Surgery was indicated for symptoms, particularly pain and rapid growth, increasing malignancy risk. Due to suspected malignancy, an en bloc resection with safety margins was performed. Among the patients, 57% received a histopathological diagnosis of MPNST (malignant peripheral nerve sheath tumor). Treatment included radiotherapy and chemotherapy. Clinical follow-up was conducted for all cases, involving clinical and oncological evaluations for all MPNSTs. CONCLUSIONS This article present a series of pediatric brachial plexus tumors, especially in NF-1, and emphasizes the importance of thorough evaluation for this group. Swift diagnosis is crucial in pediatrics, enabling successful surgery for small lesions with limited neurological symptoms, improving long-term outcomes. Prompt referral to specialized services is urged for suspected masses, irrespective of neurological symptoms. Benign tumor postsurgical progression shows better outcomes than MPNSTs, with complete resection as the primary goal. Needle-guided biopsy is not recommended.
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Affiliation(s)
- Fernando Guedes
- Department of Surgery, School of Medicine, Division of Neurosurgery, Gaffrée and Guinle University Hospital, Federal University of Rio de Janeiro State (UNIRIO), 775 Mariz E Barros Street, Rio de Janeiro, RJ, Brazil.
| | - Evelina Llorian
- Department of Surgery, School of Medicine, Division of Neurosurgery, Gaffrée and Guinle University Hospital, Federal University of Rio de Janeiro State (UNIRIO), 775 Mariz E Barros Street, Rio de Janeiro, RJ, Brazil
| | - Vinícius M Henriques
- Department of Surgery, School of Medicine, Division of Neurosurgery, Gaffrée and Guinle University Hospital, Federal University of Rio de Janeiro State (UNIRIO), 775 Mariz E Barros Street, Rio de Janeiro, RJ, Brazil
| | - Francisco José Lourenço Torrão-Junior
- Department of Surgery, School of Medicine, Division of Neurosurgery, Gaffrée and Guinle University Hospital, Federal University of Rio de Janeiro State (UNIRIO), 775 Mariz E Barros Street, Rio de Janeiro, RJ, Brazil
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10
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Sundby RT, Szymanski JJ, Pan AC, Jones PA, Mahmood SZ, Reid OH, Srihari D, Armstrong AE, Chamberlain S, Burgic S, Weekley K, Murray B, Patel S, Qaium F, Lucas AN, Fagan M, Dufek A, Meyer CF, Collins NB, Pratilas CA, Dombi E, Gross AM, Kim A, Chrisinger JS, Dehner CA, Widemann BC, Hirbe AC, Chaudhuri AA, Shern JF. Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics. Clin Cancer Res 2024; 30:4363-4376. [PMID: 39093127 PMCID: PMC11443212 DOI: 10.1158/1078-0432.ccr-24-0797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/16/2024] [Accepted: 07/31/2024] [Indexed: 08/04/2024]
Abstract
PURPOSE Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1. EXPERIMENTAL DESIGN cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures. RESULTS The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration-based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. CONCLUSIONS Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.
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Affiliation(s)
- R. Taylor Sundby
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Jeffrey J. Szymanski
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
- Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota.
| | - Alexander C. Pan
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Paul A. Jones
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri.
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
| | - Sana Z. Mahmood
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Olivia H. Reid
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Divya Srihari
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri.
| | - Amy E. Armstrong
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
| | - Stacey Chamberlain
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
| | - Sanita Burgic
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
| | - Kara Weekley
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
| | - Béga Murray
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Sneh Patel
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Faridi Qaium
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
| | - Andrea N. Lucas
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Margaret Fagan
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Anne Dufek
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Christian F. Meyer
- Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
| | - Natalie B. Collins
- Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
| | - Christine A. Pratilas
- Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
| | - Eva Dombi
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Andrea M. Gross
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - AeRang Kim
- Center for Cancer and Blood Disorders, Children’s National Hospital, Washington, District of Columbia.
| | - John S.A. Chrisinger
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri.
| | - Carina A. Dehner
- Department of Anatomic Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana.
| | - Brigitte C. Widemann
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
| | - Angela C. Hirbe
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri.
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
| | - Aadel A. Chaudhuri
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
- Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota.
| | - Jack F. Shern
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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11
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Fertitta L, Jannic A, Zehou O, Bergqvist C, Ferkal S, Moryousef S, Lerman L, Mulé S, Luciani A, Bapst B, Ezzedine K, Ortonne N, Itti E, Wolkenstein P. Whole-Body Positron Emission Tomography with 18F-Fluorodeoxyglucose/Magnetic Resonance Imaging as a Screening Tool for the Detection of Malignant Transformation in Individuals with Neurofibromatosis Type 1. J Invest Dermatol 2024; 144:1754-1761.e1. [PMID: 38368929 DOI: 10.1016/j.jid.2024.01.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 01/23/2024] [Accepted: 01/30/2024] [Indexed: 02/20/2024]
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in patients with neurofibromatosis type 1. They can result from premalignant neurofibromas, including neurofibromas with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential. Some phenotypic characteristics have been described as associated with their development. The aim of this study was to outline our use of whole-body positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging in adults with neurofibromatosis type 1, especially in the screening of asymptomatic individuals with a higher risk of developing an MPNST, and to study its impact on neurofibroma classification (malignant vs premalignant) and MPNST staging over time. Individuals with neurofibromatosis type 1 who underwent a positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging between 2017 and 2021 were included, analyzing separately the screened population. Maximum standard uptake value and diffusion-weighted imaging were assessed. Biopsy/surgery confirmed the diagnosis. In all, 345 positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging were performed in 241 patients, including 149 asymptomatic (62%) but at-risk patients. Eight MPNSTs in 8 screened individuals (5%), 6 neurofibromas with atypia in 4 individuals (3%), and 29 atypical neurofibromatous neoplasms of uncertain biologic potential in 23 individuals (15%) were diagnosed. Over time, the proportion of grade 3 MPNST and the malignant/premalignant ratio in screened individuals significantly decreased (P = .03 and P < .001, respectively). This study emphasizes the diagnostic and screening performances of whole-body positron emission tomography with 18F-fluorodeoxyglucose/magnetic resonance imaging in adults with neurofibromatosis type 1.
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Affiliation(s)
- Laura Fertitta
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; INSERM U955, Créteil, France; INSERM, Centre d'Investigation Clinique 1430, Henri-Mondor Hospital, Assistance Publique-Hôpitaux Paris (AP-HP), Créteil, France
| | - Arnaud Jannic
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; INSERM, Centre d'Investigation Clinique 1430, Henri-Mondor Hospital, Assistance Publique-Hôpitaux Paris (AP-HP), Créteil, France
| | - Ouidad Zehou
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France
| | - Christina Bergqvist
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France
| | - Salah Ferkal
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; INSERM, Centre d'Investigation Clinique 1430, Henri-Mondor Hospital, Assistance Publique-Hôpitaux Paris (AP-HP), Créteil, France
| | - Sabine Moryousef
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France
| | - Lionel Lerman
- Department of Nuclear Medicine, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France
| | - Sébastien Mulé
- Department of Radiology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France
| | - Alain Luciani
- Department of Radiology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France
| | - Blanche Bapst
- Department of Neuro-radiology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France
| | - Khaled Ezzedine
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; INSERM, Centre d'Investigation Clinique 1430, Henri-Mondor Hospital, Assistance Publique-Hôpitaux Paris (AP-HP), Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France
| | - Nicolas Ortonne
- INSERM U955, Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France; Department of Pathology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France
| | - Emmanuel Itti
- Department of Nuclear Medicine, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France
| | - Pierre Wolkenstein
- Department of Dermatology, National Referral Center for Neurofibromatoses (CERENEF), Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP), Créteil, France; INSERM U955, Créteil, France; INSERM, Centre d'Investigation Clinique 1430, Henri-Mondor Hospital, Assistance Publique-Hôpitaux Paris (AP-HP), Créteil, France; Université Paris-Est Créteil (UPEC), Créteil, France.
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12
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Haddad G, Moussalem C, Saade MC, El Hayek M, Massaad E, Gibbs WN, Shin J. Imaging of Adult Malignant Soft Tissue Tumors of the Spinal Canal: A Guide for Spine Surgeons. World Neurosurg 2024; 187:133-140. [PMID: 38428809 DOI: 10.1016/j.wneu.2024.02.125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/03/2024]
Abstract
BACKGROUND Malignant soft tissue spinal canal tumors compromise 20% of all spinal neoplasms. They may be primary or metastatic lesions, originating from a diverse range of tissues within and surrounding the spinal canal. These masses can present as diverse emergencies such as secondary cauda equina syndrome, vascular compromise, or syringomyelia. Interpretation of malignant soft tissue spinal canal tumors imaging is an essential for non-radiologists in the setting of emergencies. This task is intricate due to a great radiologic pattern overlap among entities. METHODS We present a step-by-step strategy that can guide nonradiologists identify a likely malignant soft tissue lesion in the spinal canal based on imaging features, as well as a review of the radiologic features of malignant soft tissue spinal canal tumors. RESULTS Diagnosis of soft tissue spinal canal malignancies starts with the identification of the lesion's spinal level and its relationship to the dura and medulla. The second step consists of characterizing it as likely-malignant based on radiological signs like a larger size, ill-defined margins, central necrosis, and/or increased vascularity. The third step is to identify additional imaging features such as intratumoral hemorrhage or cyst formation that can suggest specific malignancies. The physician can then formulate a differential diagnosis. The most encountered malignant soft tissue tumors of the spinal canal are anaplastic ependymomas, anaplastic astrocytomas, metastatic tumors, lymphoma, peripheral nerve sheath tumors, and central nervous system melanomas. A review of the imaging features of every type/subtype of lesion is presented in this work. Although magnetic resonance imaging remains the modality of choice for spinal tumor assessment, other techniques such as dynamic contrast agent-enhanced perfusion magnetic resonance imaging or diffusion-weighted imaging could guide diagnosis in specific situations. CONCLUSIONS In this review, diagnostic strategies for several spinal cord tumors were presented, including anaplastic ependymoma, metastatic spinal cord tumors, anaplastic and malignant astrocytoma, lymphoma, malignant peripheral nerve sheath tumors , and primary central nervous system melanoma. Although the characterization of spinal cord tumors can be challenging, comprehensive knowledge of imaging features can help overcome these challenges and ensure optimal management of spinal canal lesions.
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Affiliation(s)
- Gaelle Haddad
- Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Marie Christelle Saade
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Mario El Hayek
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Elie Massaad
- Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Wende N Gibbs
- Department of Radiology, Barrow Neurological Institute, Phoenix, Arizona, USA
| | - John Shin
- Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA
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13
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Hirbe AC, Dehner CA, Dombi E, Eulo V, Gross AM, Sundby T, Lazar AJ, Widemann BC. Contemporary Approach to Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors. Am Soc Clin Oncol Educ Book 2024; 44:e432242. [PMID: 38710002 PMCID: PMC11656191 DOI: 10.1200/edbk_432242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2024]
Abstract
Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy. Treatment for metastatic disease is limited to cytotoxic chemotherapy and investigational clinical trials. In this article, we review the pathophysiology of this aggressive cancer and current approaches to surveillance and treatment.
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Affiliation(s)
- Angela C Hirbe
- Division of Oncology, Department of Medicine, Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St Louis, MO
| | - Carina A Dehner
- Department of Anatomic Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN
| | - Eva Dombi
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Vanessa Eulo
- Division of Oncology, Department of Medicine, University of Alabama, Birmingham, AL
| | - Andrea M Gross
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Taylor Sundby
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Alexander J Lazar
- Departments of Pathology & Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brigitte C Widemann
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
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14
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Jansma CYMN, Wan X, Acem I, Spaanderman DJ, Visser JJ, Hanff D, Taal W, Verhoef C, Klein S, Martin E, Starmans MPA. Preoperative Classification of Peripheral Nerve Sheath Tumors on MRI Using Radiomics. Cancers (Basel) 2024; 16:2039. [PMID: 38893158 PMCID: PMC11170987 DOI: 10.3390/cancers16112039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 05/21/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors prevalent in neurofibromatosis type 1 (NF1) patients, posing a significant risk of metastasis and recurrence. Current magnetic resonance imaging (MRI) imaging lacks decisiveness in distinguishing benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs, necessitating invasive biopsies. This study aims to develop a radiomics model using quantitative imaging features and machine learning to distinguish MPNSTs from BPNSTs. Clinical data and MRIs from MPNST and BPNST patients (2000-2019) were collected at a tertiary sarcoma referral center. Lesions were manually and semi-automatically segmented on MRI scans, and radiomics features were extracted using the Workflow for Optimal Radiomics Classification (WORC) algorithm, employing automated machine learning. The evaluation was conducted using a 100× random-split cross-validation. A total of 35 MPNSTs and 74 BPNSTs were included. The T1-weighted (T1w) MRI radiomics model outperformed others with an area under the curve (AUC) of 0.71. The incorporation of additional MRI scans did not enhance performance. Combining T1w MRI with clinical features achieved an AUC of 0.74. Experienced radiologists achieved AUCs of 0.75 and 0.66, respectively. Radiomics based on T1w MRI scans and clinical features show some ability to distinguish MPNSTs from BPNSTs, potentially aiding in the management of these tumors.
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Affiliation(s)
- Christianne Y. M. N. Jansma
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (I.A.); (C.V.)
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;
| | - Xinyi Wan
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands; (X.W.); (D.J.S.); (J.J.V.); (D.H.); (S.K.); (M.P.A.S.)
| | - Ibtissam Acem
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (I.A.); (C.V.)
| | - Douwe J. Spaanderman
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands; (X.W.); (D.J.S.); (J.J.V.); (D.H.); (S.K.); (M.P.A.S.)
| | - Jacob J. Visser
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands; (X.W.); (D.J.S.); (J.J.V.); (D.H.); (S.K.); (M.P.A.S.)
| | - David Hanff
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands; (X.W.); (D.J.S.); (J.J.V.); (D.H.); (S.K.); (M.P.A.S.)
| | - Walter Taal
- Department of Neurology, Erasmus MC Cancer Institute University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands;
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (I.A.); (C.V.)
| | - Stefan Klein
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands; (X.W.); (D.J.S.); (J.J.V.); (D.H.); (S.K.); (M.P.A.S.)
| | - Enrico Martin
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;
| | - Martijn P. A. Starmans
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands; (X.W.); (D.J.S.); (J.J.V.); (D.H.); (S.K.); (M.P.A.S.)
- Department of Pathology, Erasmus MC Cancer Institute University Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands
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15
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Taylor Sundby R, Szymanski JJ, Pan A, Jones PA, Mahmood SZ, Reid OH, Srihari D, Armstrong AE, Chamberlain S, Burgic S, Weekley K, Murray B, Patel S, Qaium F, Lucas AN, Fagan M, Dufek A, Meyer CF, Collins NB, Pratilas CA, Dombi E, Gross AM, Kim A, Chrisinger JSA, Dehner CA, Widemann BC, Hirbe AC, Chaudhuri AA, Shern JF. Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.01.18.24301053. [PMID: 38293154 PMCID: PMC10827240 DOI: 10.1101/2024.01.18.24301053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2024]
Abstract
Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 101 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.
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Affiliation(s)
- R Taylor Sundby
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Jeffrey J Szymanski
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
- Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA
| | - Alexander Pan
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Paul A Jones
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sana Z Mahmood
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Olivia H Reid
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Divya Srihari
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Amy E Armstrong
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Stacey Chamberlain
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sanita Burgic
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Kara Weekley
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Béga Murray
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Sneh Patel
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Faridi Qaium
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Andrea N Lucas
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Margaret Fagan
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Anne Dufek
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Christian F Meyer
- Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Natalie B Collins
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Christine A Pratilas
- Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD USA
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Eva Dombi
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Andrea M Gross
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - AeRang Kim
- Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC, USA
| | - John S A Chrisinger
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
| | - Carina A Dehner
- Department of Anatomic Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA
| | - Brigitte C Widemann
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Angela C Hirbe
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Aadel A Chaudhuri
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
- Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA
| | - Jack F Shern
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
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16
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Ko WS, Kim SJ. Direct comparison of the diagnostic accuracy of 2-[ 18F]-fluoro-2-deoxy-d-glucose PET/CT and MRI for the differentiation of malignant peripheral nerve sheath tumour in neurofibromatosis type I: a meta-analysis. Clin Radiol 2024; 79:142-149. [PMID: 37968227 DOI: 10.1016/j.crad.2023.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 09/06/2023] [Accepted: 10/18/2023] [Indexed: 11/17/2023]
Abstract
AIM To compare the diagnostic test of integrated 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG PET/CT) with that of magnetic resonance imaging (MRI) for the differentiation of malignant peripheral nerve sheath tumours (MPNSTs) in neurofibromatosis type 1 (NF1) patients. MATERIALS AND METHODS A systematic search was performed in PubMed and EMBASE (last updated in 30 November 2022). Studies investigating the performance of FDG PET/CT and MRI for differentiation of MPNSTs were eligible for inclusion. Only studies reporting a direct comparison between these imaging methods were considered to establish precise summary estimates in the same setting of patients. RESULTS The pooled estimate of sensitivity of FDG PET/CT was 0.99 and a pooled specificity of 0.53. The pooled estimate of sensitivity of MRI was 0.85 and a pooled specificity of 0.85. CONCLUSION Analysis of the available studies indicated that FDG PET/CT and MRI had similar diagnostic performances for differentiation of MPNSTs in patients with NF1; however, either technique can be a complement to the other rather than being used singly.
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Affiliation(s)
- W S Ko
- Department of Internal Medicine, Pusan National University Hospital, Ami-dong, Seo-gu, Busan, 49241, Republic of Korea
| | - S-J Kim
- Department of Nuclear Medicine, Pusan National University School of Medicine, Busandaehak-ro 49, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea; BioMedical Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 50612, Republic of Korea.
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17
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Telleman JA, Sneag DB, Visser LH. The role of imaging in focal neuropathies. HANDBOOK OF CLINICAL NEUROLOGY 2024; 201:19-42. [PMID: 38697740 DOI: 10.1016/b978-0-323-90108-6.00001-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Electrodiagnostic testing (EDX) has been the diagnostic tool of choice in peripheral nerve disease for many years, but in recent years, peripheral nerve imaging has been used ever more frequently in daily clinical practice. Nerve ultrasound and magnetic resonance (MR) neurography are able to visualize nerve structures reliably. These techniques can aid in localizing nerve pathology and can reveal significant anatomical abnormalities underlying nerve pathology that may have been otherwise undetected by EDX. As such, nerve ultrasound and MR neurography can significantly improve diagnostic accuracy and can have a significant effect on treatment strategy. In this chapter, the basic principles and recent developments of these techniques will be discussed, as well as their potential application in several types of peripheral nerve disease, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), radial neuropathy, brachial and lumbosacral plexopathy, neuralgic amyotrophy (NA), fibular, tibial, sciatic, femoral neuropathy, meralgia paresthetica, peripheral nerve trauma, tumors, and inflammatory neuropathies.
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Affiliation(s)
- Johan A Telleman
- Department of Neurology and Clinical Neurophysiology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
| | - Darryl B Sneag
- Department of Radiology and Imaging, Hospital for Special Surgery, New York, NY, United States
| | - Leo H Visser
- Department of Neurology and Clinical Neurophysiology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands.
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18
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Jin Z, Wang C, Wang D, Li X, Guo W, Chen T. Malignant and Benign Peripheral Nerve Sheath Tumors in a Single Center: Value of Clinical and Ultrasound Features for the Diagnosis of Malignant Peripheral Nerve Sheath Tumor Compared With Magnetic Resonance Imaging. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2024; 43:21-31. [PMID: 37772628 DOI: 10.1002/jum.16330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/16/2023] [Accepted: 08/27/2023] [Indexed: 09/30/2023]
Abstract
OBJECTIVES This study aimed to investigate the combined use of ultrasonography and clinical features for the differentiation of malignant peripheral nerve sheath tumors (MPNST) from benign peripheral nerve sheath tumors (BPNST) and to compare the efficacy of ultrasonography with that of magnetic resonance imaging (MRI). METHODS This retrospective study included 28 MPNSTs and a control group of 57 BPNSTs. All patients underwent an ultrasound scan using the Logiq E9 (GE Health Care, Milwaukee, WI) or EPIQ7 equipment (Philips Medical System, Bothell, WA). A 3.0-T MRI machine (Ingenia; Philips Healthcare, Best, the Netherlands) was used for scanning, and conventional MRI was performed on different regions based on the patient's clinical situation. The following variables were evaluated: palpable mass, pain, nerve symptoms, maximum diameter, location, shape, boundary, encapsulation, echogenicity, echo homogeneity, presence of a cystic component, calcification, target sign, posterior echo, and intertumoral vascularity of the tumors. The diagnostic efficacy of ultrasonography and clinical factors was compared with that of MRI. Independent factors for predicting MPNST versus BPNST were also assessed. RESULTS The parameters of location, shape, boundary, encapsulation, and vascularity were significantly different between MPNSTs and BPNSTs. Multiple logistic regression analysis showed that shape, boundary, and vascularity were independent predictors of MPNSTs. The sensitivity, specificity, and Youden index of the three clinical and ultrasound factors (shape, boundary, and vascularity) were 0.89, 0.81, and 0.69, respectively, whereas those of MRI were 0.71, 0.89, and 0.61, respectively. No significant differences in the area under the curve (AUC) of the three combined clinical and ultrasound factors and those of MRI were found (P > .05). CONCLUSIONS MRI was useful in the differential diagnosis between MPNSTs and BPNSTs. However, the combination of clinical and ultrasound diagnoses can achieve the same effect as MRI, including shape, boundary, and vasculature.
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Affiliation(s)
- Zhenzhen Jin
- Department of Ultrasound, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Chao Wang
- National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Dandan Wang
- Department of Ultrasound, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Xintong Li
- Department of Radiology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Wen Guo
- Department of Ultrasound, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Tao Chen
- Department of Ultrasound, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
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19
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Lefebvre G, Le Corroller T. Ultrasound and MR imaging of peripheral nerve tumors: the state of the art. Skeletal Radiol 2023; 52:405-419. [PMID: 35713690 DOI: 10.1007/s00256-022-04087-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/09/2022] [Accepted: 05/30/2022] [Indexed: 02/02/2023]
Abstract
Peripheral nerve sheath tumors are a heterogeneous subgroup of soft tissue tumors that either arise from a peripheral nerve or show nerve sheath differentiation. On imaging, direct continuity with a neural structure or location along a typical nerve distribution represents the most important signs to suggest the diagnosis. Ultrasound and magnetic resonance imaging are the best modalities to evaluate these lesions. First, it is necessary to differentiate between a true tumor and a non-neoplastic nerve condition such as a neuroma, peripheral nerve ganglion, intraneural venous malformation, lipomatosis of nerve, or nerve focal hypertrophy. Then, with a combination of clinical features, conventional and advanced imaging appearances, it is usually possible to characterize neurogenic tumors confidently. This article reviews the features of benign and malignant peripheral nerve sheath tumors, including the rare and recently described tumor types. Furthermore, other malignant neoplasms of peripheral nerves as well as non-neoplastic conditions than can mimick neurogenic tumor are herein discussed.
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Affiliation(s)
- Guillaume Lefebvre
- Service de Radiologie Et d'Imagerie Musculosquelettique, Centre de Consultation Et d'Imagerie de L'Appareil Locomoteur, CHRU de Lille, Rue Emile Laine, 59037, Lille, France
| | - Thomas Le Corroller
- Radiology Department, APHM, Hôpital Sainte-Marguerite, 270 Bd de Sainte-Marguerite, 13009, Marseille, France. .,ISM UMR 7287, Aix Marseille University, CNRS, Marseille, France.
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20
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Vicentini JRT, Bredella MA. Whole body imaging in musculoskeletal oncology: when, why, and how. Skeletal Radiol 2023; 52:281-295. [PMID: 35809098 DOI: 10.1007/s00256-022-04112-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 06/03/2022] [Accepted: 06/29/2022] [Indexed: 02/02/2023]
Abstract
The use of whole-body imaging has become increasingly popular in oncology due to the possibility of evaluating total tumor burden with a single imaging study. This is particularly helpful in cases of widespread disease where dedicated regional imaging would make the evaluation more expensive, time consuming, and prone to more risks. Different techniques can be used, including whole-body MRI, whole-body CT, and PET-CT. Common indications include surveillance of cancer predisposing syndromes, evaluation of osseous metastases and clonal plasma cell disorders such as multiple myeloma, and evaluation of soft tissue lesions, including peripheral nerve sheath tumors. This review focuses on advanced whole-body imaging techniques and their main uses in musculoskeletal oncology.
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Affiliation(s)
- Joao R T Vicentini
- Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, YAW 6, Boston, MA, 02114, USA.
| | - Miriam A Bredella
- Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, YAW 6, Boston, MA, 02114, USA
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21
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Lee D, Yun H, Yun T, Koo Y, Chae Y, Nam H, Kang S, Lee H, Chang D, Yang MP, Kang BT, Kim H. 18F-fluorodeoxyglucose positron emission tomography findings of peripheral nerve sheath tumour of the nasal cavity in a dog. Vet Med Sci 2023; 9:584-590. [PMID: 36626300 PMCID: PMC10029900 DOI: 10.1002/vms3.1069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
An 8-year-old Miniature Poodle presented with chronic sneezing and unilateral epistaxis. A left-sided intranasal mass was identified on computed tomography. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed to evaluate the metabolic activity of the mass. The intranasal mass showed mildly increased 18F-FDG uptake. The maximal and mean standardized uptake values (SUVs) of the mass were 3.4 and 2.6, respectively. The maximal SUV of the mass/mean SUV of the normal liver was 2.5. The 7-cm soft, pink mass was easily removed through rhinoscopy, with subsequent dramatic improvement in clinical signs. Histopathological and immunohistochemical analyses determined that the mass was an intermediate-grade malignant peripheral nerve sheath tumour (PNST). This is the first report of 18F-FDG PET findings in a PNST in dogs.
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Affiliation(s)
- Dohee Lee
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Hyejin Yun
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Taesik Yun
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Yoonhoi Koo
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Yeon Chae
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Hyeyeon Nam
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Seonggweon Kang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Hayoon Lee
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Dongwoo Chang
- Department of Veterinary Imaging, Veterinary Teaching Hospital, College of Veterinary Medicine, Cheongju, Chungbuk, Republic of Korea
| | - Mhan-Pyo Yang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Byeong-Teck Kang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
| | - Hakhyun Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
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22
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Warren D, Koch C, Parsons MS, Pérez-Carrillo GJG, Eldaya RW. Head and Neck Sarcoma Tumor Board Survival Guide for Neuroradiologists: Imaging Findings, History, and Pathology. Curr Probl Diagn Radiol 2023; 52:275-288. [PMID: 36792427 DOI: 10.1067/j.cpradiol.2023.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 01/12/2023] [Accepted: 01/18/2023] [Indexed: 01/28/2023]
Abstract
Sarcomas of the head and neck carry a poor prognosis as diagnosis is often delayed until a late stage of the disease. Accordingly, it is essential to be familiar with the clinical and imaging features of sarcomas to suggest an appropriate differential diagnosis for collaborating surgeons and pathologists. However, as there are only 1000-1500 cases in the United States annually, many radiologists lack experience with pertinent imaging findings of sarcoma and lack knowledge of both treatment and necessary follow-up. In this review, a brief discussion of WHO definitions and histopathology is included to decode information provided by pathologists. Finally, staging and treatments are illuminated to aid the radiologist with initial imaging staging and follow-up care. This review aims to increase the comprehensive knowledge of a neuroradiologist and further their value to the multidisciplinary tumor board.
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Affiliation(s)
- Daniel Warren
- Neuroradiology Section, Mallinckrodt Institute of Radiology, St. Louis, MO.
| | - Cameron Koch
- Neuroradiology Section, Mallinckrodt Institute of Radiology, St. Louis, MO
| | - Matthew S Parsons
- Neuroradiology Section, Mallinckrodt Institute of Radiology, St. Louis, MO
| | | | - Rami W Eldaya
- Neuroradiology Section, Mallinckrodt Institute of Radiology, St. Louis, MO
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23
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Lee JS, Kelly CM, Bartlett EK. Management of pelvic sarcoma. Eur J Surg Oncol 2022; 48:2299-2307. [PMID: 36195471 DOI: 10.1016/j.ejso.2022.09.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 09/07/2022] [Accepted: 09/14/2022] [Indexed: 10/14/2022] Open
Abstract
Pelvic sarcomas are a rare and heterogenous group of tumors divided into two groups: soft tissue sarcomas and bone sarcomas. Soft tissue sarcomas of the pelvis include most commonly liposarcoma, leiomyosarcoma, gastrointestinal stromal tumors, malignant peripheral nerve sheath tumors, and solitary fibrous tumors. Bone sarcomas of the pelvis most commonly include osteosarcoma and chondrosarcoma. Multidisciplinary treatment at a center experienced in the treatment of sarcoma is essential. Management is dictated by histologic type and grade. Surgical resection with wide margins is the cornerstone of treatment for pelvic sarcomas, although this is often challenging due to anatomic constraints of the pelvis. Multimodal treatment is critical due to the high risk of local recurrence in the pelvis.
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Affiliation(s)
- Jay S Lee
- Department of Surgery, Duke University, Durham, NC, USA
| | - Ciara M Kelly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Edmund K Bartlett
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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24
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Liu J, Huang JN, Wang MH, Ni ZY, Jiang WH, Chung M, Wei CJ, Wang ZC. Image-Based Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1. Front Oncol 2022; 12:898971. [PMID: 35677169 PMCID: PMC9168278 DOI: 10.3389/fonc.2022.898971] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/18/2022] [Indexed: 11/16/2022] Open
Abstract
Neurofibromatosis type 1 (NF1) is a dominant hereditary disease characterized by the mutation of the NF1 gene, affecting 1/3000 individuals worldwide. Most NF1 patients are predisposed to benign peripheral nerve sheath tumors (PNSTs), including cutaneous neurofibromas (CNFs) and plexiform neurofibromas (PNFs). However, 5%-10% of PNFs will ultimately develop into malignant peripheral nerve sheath tumors (MPNSTs), which have a poor prognosis. Early and reliable differentiation of benign and malignant tumors in NF1 patients is of great necessity. Pathological evaluation is the “gold standard” for a definite diagnosis, but the invasive nature of the biopsy procedure restricts it from applying as a screening tool during the decades-long follow-up of these patients. Non-invasive image-based diagnostic methods such as CT and MRI are often considered essential screening tools for multiple types of tumors. For NF1 patients’ lifelong regular follow-ups, these radiological methods are currently used for tumor evaluation. However, no consensus was established on screening the malignant transformation of benign PNSTs. Moreover, novel technologies like radiogenomics and PET-MRI have not been well evaluated and fully adopted for NF1 patients. This review summarizes current studies of different imaging methods for differentiating benign and malignant tumors in NF1. Meanwhile, we discussed the prospects of the usage of new tools such as radiogenomics and PET-MRI to distinguish MPNST from benign PNSTs more precisely. Summarizing these findings will help clarify the directions of future studies in this area and ultimately contribute to the radiology images-based clinical screening of MPNST in NF1 patients and finally improve the overall survival rates of these patients.
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Affiliation(s)
- Jun Liu
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing-Ning Huang
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ming-Han Wang
- School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhen-Yang Ni
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Wei-Hao Jiang
- School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Manhon Chung
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Cheng-Jiang Wei
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhi-Chao Wang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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25
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Ristow I, Madesta F, Well L, Shenas F, Wright F, Molwitz I, Farschtschi S, Bannas P, Adam G, Mautner VF, Werner R, Salamon J. Evaluation of magnetic resonance imaging-based radiomics characteristics for differentiation of benign and malignant peripheral nerve sheath tumors in neurofibromatosis type 1. Neuro Oncol 2022; 24:1790-1798. [PMID: 35426432 PMCID: PMC9527508 DOI: 10.1093/neuonc/noac100] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Patients with neurofibromatosis type 1 (NF1) develop benign (BPNST), premalignant atypical (ANF), and malignant (MPNST) peripheral nerve sheath tumors. Radiological differentiation of these entities is challenging. Therefore, we aimed to evaluate the value of a magnetic resonance imaging (MRI)-based radiomics machine-learning (ML) classifier for differentiation of these three entities of internal peripheral nerve sheath tumors in NF1 patients. METHODS MRI was performed at 3T in 36 NF1 patients (20 male; age: 31 ± 11 years). Segmentation of 117 BPNSTs, 17 MPNSTs, and 8 ANFs was manually performed using T2w spectral attenuated inversion recovery sequences. One hundred seven features per lesion were extracted using PyRadiomics and applied for BPNST versus MPNST differentiation. A 5-feature radiomics signature was defined based on the most important features and tested for signature-based BPNST versus MPNST classification (random forest [RF] classification, leave-one-patient-out evaluation). In a second step, signature feature expressions for BPNSTs, ANFs, and MPNSTs were evaluated for radiomics-based classification for these three entities. RESULTS The mean area under the receiver operator characteristic curve (AUC) for the radiomics-based BPNST versus MPNST differentiation was 0.94, corresponding to correct classification of on average 16/17 MPNSTs and 114/117 BPNSTs (sensitivity: 94%, specificity: 97%). Exploratory analysis with the eight ANFs revealed intermediate radiomic feature characteristics in-between BPNST and MPNST tumor feature expression. CONCLUSION In this proof-of-principle study, ML using MRI-based radiomics characteristics allows sensitive and specific differentiation of BPNSTs and MPNSTs in NF1 patients. Feature expression of premalignant atypical tumors was distributed in-between benign and malignant tumor feature expressions, which illustrates biological plausibility of the considered radiomics characteristics.
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Affiliation(s)
- Inka Ristow
- Corresponding Author: Inka Ristow, MD, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany ()
| | - Frederic Madesta
- Institute of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lennart Well
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Farzad Shenas
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Felicia Wright
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Isabel Molwitz
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Said Farschtschi
- Department of Neurology, University Medical Center Hamburg-Eppendorf
, Hamburg, Germany
| | - Peter Bannas
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gerhard Adam
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Victor F Mautner
- Department of Neurology, University Medical Center Hamburg-Eppendorf
, Hamburg, Germany
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26
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Mattox AK, Douville C, Silliman N, Ptak J, Dobbyn L, Schaefer J, Popoli M, Blair C, Judge K, Pollard K, Pratilas C, Blakeley J, Rodriguez F, Papadopoulos N, Belzberg A, Bettegowda C. Detection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis using aneuploidy and mutation identification in plasma. eLife 2022; 11:e74238. [PMID: 35244537 PMCID: PMC9094745 DOI: 10.7554/elife.74238] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 02/01/2022] [Indexed: 11/28/2022] Open
Abstract
Malignant peripheral nerve sheath tumors (MPNST) are the deadliest cancer that arises in individuals diagnosed with neurofibromatosis and account for nearly 5% of the 15,000 soft tissue sarcomas diagnosed in the United States each year. Comprised of neoplastic Schwann cells, primary risk factors for developing MPNST include existing plexiform neurofibromas (PN), prior radiotherapy treatment, and expansive germline mutations involving the entire NF1 gene and surrounding genes. PN develop in nearly 30-50% of patients with neurofibromatosis type 1 (NF1) and most often grow rapidly in the first decade of life. One of the most important aspects of clinical care for NF1 patients is monitoring PN for signs of malignant transformation to MPNST that occurs in 10-15% of patients. We perform aneuploidy analysis on ctDNA from 883 ostensibly healthy individuals and 28 patients with neurofibromas, including 7 patients with benign neurofibroma, 9 patients with PN and 12 patients with MPNST. Overall sensitivity for detecting MPNST using genome wide aneuploidy scoring was 33%, and analysis of sub-chromosomal copy number alterations (CNAs) improved sensitivity to 50% while retaining a high specificity of 97%. In addition, we performed mutation analysis on plasma cfDNA for a subset of patients and identified mutations in NF1, NF2, RB1, TP53BP2, and GOLGA2. Given the high throughput and relatively low sequencing coverage required by our assay, liquid biopsy represents a promising technology to identify incipient MPNST.
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Affiliation(s)
- Austin K Mattox
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Christopher Douville
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Natalie Silliman
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Janine Ptak
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Lisa Dobbyn
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Joy Schaefer
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Maria Popoli
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Cherie Blair
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Kathy Judge
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Kai Pollard
- Department of Pediatrics, Johns Hopkins University School of MedicineBaltimoreUnited States
- Department of Oncology, Sidney Kimmel Comprehensive Cancer, Johns Hopkins UniversityBaltimoreUnited States
| | - Christine Pratilas
- Department of Pediatrics, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Jaishri Blakeley
- Department of Neurology, Johns Hopkins University School of Medicine, MD School of MedicineBaltimoreUnited States
| | - Fausto Rodriguez
- Department of Pathology, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Nickolas Papadopoulos
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
- Department of Oncology, Sidney Kimmel Comprehensive Cancer, Johns Hopkins UniversityBaltimoreUnited States
- Department of Pathology, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Allan Belzberg
- Department of Neurosurgery, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Chetan Bettegowda
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineBaltimoreUnited States
- Department of Oncology, Sidney Kimmel Comprehensive Cancer, Johns Hopkins UniversityBaltimoreUnited States
- Department of Neurosurgery, Johns Hopkins University School of MedicineBaltimoreUnited States
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Geitenbeek RTJ, Martin E, Graven LH, Broen MPG, Anten MHME, van der Pol JAJ, Verhoef C, Taal W. Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients. J Neurooncol 2022; 156:559-567. [PMID: 35025020 PMCID: PMC8860956 DOI: 10.1007/s11060-021-03936-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 12/24/2021] [Indexed: 11/26/2022]
Abstract
Purpose Detecting malignant peripheral nerve sheath tumors (MPNSTs) remains difficult. 18F-FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used 18F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated. Methods A retrospective cohort study was performed including patients from two hospitals with a clinical or radiological suspicion of MPNST between 2013 and 2019. Several markers were studied for ideal threshold values and differences among adults and children. A diagnostic algorithm was subsequently developed. Results Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved. Conclusion 18F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity. Supplementary Information The online version contains supplementary material available at 10.1007/s11060-021-03936-y.
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Affiliation(s)
- Ritch T J Geitenbeek
- Department of Plastic and Reconstructive Surgery G04.126, University Medical Center Utrecht, PO Box 85060, 3508 AB, Utrecht, The Netherlands.,Department of Surgical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands
| | - Enrico Martin
- Department of Plastic and Reconstructive Surgery G04.126, University Medical Center Utrecht, PO Box 85060, 3508 AB, Utrecht, The Netherlands. .,Department of Surgical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
| | - Laura H Graven
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands
| | - Martijn P G Broen
- Department of Neurology, Maastricht University Medical Center, Maastricht, Netherlands
| | - Monique H M E Anten
- Department of Neurology, Maastricht University Medical Center, Maastricht, Netherlands
| | - Jochem A J van der Pol
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands
| | - Walter Taal
- Department of Neurology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands
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28
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Pedersen C, Link HD, Aboian M. Pediatric Spine. HYBRID PET/MR NEUROIMAGING 2022:765-777. [DOI: 10.1007/978-3-030-82367-2_65] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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29
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Zhang M, Tong E, Hamrick F, Lee EH, Tam LT, Pendleton C, Smith BW, Hug NF, Biswal S, Seekins J, Mattonen SA, Napel S, Campen CJ, Spinner RJ, Yeom KW, Wilson TJ, Mahan MA. Machine-Learning Approach to Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors: A Multicenter Study. Neurosurgery 2021; 89:509-517. [PMID: 34131749 PMCID: PMC8364819 DOI: 10.1093/neuros/nyab212] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 04/27/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Clinicoradiologic differentiation between benign and malignant peripheral nerve sheath tumors (PNSTs) has important management implications. OBJECTIVE To develop and evaluate machine-learning approaches to differentiate benign from malignant PNSTs. METHODS We identified PNSTs treated at 3 institutions and extracted high-dimensional radiomics features from gadolinium-enhanced, T1-weighted magnetic resonance imaging (MRI) sequences. Training and test sets were selected randomly in a 70:30 ratio. A total of 900 image features were automatically extracted using the PyRadiomics package from Quantitative Imaging Feature Pipeline. Clinical data including age, sex, neurogenetic syndrome presence, spontaneous pain, and motor deficit were also incorporated. Features were selected using sparse regression analysis and retained features were further refined by gradient boost modeling to optimize the area under the curve (AUC) for diagnosis. We evaluated the performance of radiomics-based classifiers with and without clinical features and compared performance against human readers. RESULTS A total of 95 malignant and 171 benign PNSTs were included. The final classifier model included 21 imaging and clinical features. Sensitivity, specificity, and AUC of 0.676, 0.882, and 0.845, respectively, were achieved on the test set. Using imaging and clinical features, human experts collectively achieved sensitivity, specificity, and AUC of 0.786, 0.431, and 0.624, respectively. The AUC of the classifier was statistically better than expert humans (P = .002). Expert humans were not statistically better than the no-information rate, whereas the classifier was (P = .001). CONCLUSION Radiomics-based machine learning using routine MRI sequences and clinical features can aid in evaluation of PNSTs. Further improvement may be achieved by incorporating additional imaging sequences and clinical variables into future models.
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Affiliation(s)
- Michael Zhang
- Department of Neurosurgery, Stanford University, Stanford, California, USA
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Elizabeth Tong
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Forrest Hamrick
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, USA
| | - Edward H Lee
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Lydia T Tam
- Stanford School of Medicine, Stanford University, Stanford, California, USA
| | | | - Brandon W Smith
- Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Nicholas F Hug
- Stanford School of Medicine, Stanford University, Stanford, California, USA
| | - Sandip Biswal
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Jayne Seekins
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Sarah A Mattonen
- Department of Medical Biophysics, Western University, London, Canada
| | - Sandy Napel
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Cynthia J Campen
- Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA
| | - Robert J Spinner
- Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Kristen W Yeom
- Department of Radiology, Stanford University, Stanford, California, USA
| | - Thomas J Wilson
- Department of Neurosurgery, Stanford University, Stanford, California, USA
| | - Mark A Mahan
- Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, USA
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30
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Szymanski JJ, Sundby RT, Jones PA, Srihari D, Earland N, Harris PK, Feng W, Qaium F, Lei H, Roberts D, Landeau M, Bell J, Huang Y, Hoffman L, Spencer M, Spraker MB, Ding L, Widemann BC, Shern JF, Hirbe AC, Chaudhuri AA. Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study. PLoS Med 2021; 18:e1003734. [PMID: 34464388 PMCID: PMC8407545 DOI: 10.1371/journal.pmed.1003734] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 07/14/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors. METHODS AND FINDINGS This multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass whole genome sequencing (ULP-WGS) of plasma cell-free DNA (cfDNA) to distinguish between MPNST and PN in patients with NF1. Following in silico enrichment for short cfDNA fragments and copy number analysis to estimate the fraction of plasma cfDNA originating from tumor (tumor fraction), we developed a noninvasive classifier that differentiates MPNST from PN with 86% pretreatment accuracy (91% specificity, 75% sensitivity) and 89% accuracy on serial analysis (91% specificity, 83% sensitivity). Healthy controls without NF1 (participants = 16, plasma samples = 16), PN (participants = 23, plasma samples = 23), and MPNST (participants = 14, plasma samples = 46) cohorts showed significant differences in tumor fraction in plasma (P = 0.001) as well as cfDNA fragment length (P < 0.001) with MPNST samples harboring shorter fragments and being enriched for tumor-derived cfDNA relative to PN and healthy controls. No other covariates were significant on multivariate logistic regression. Mutational analysis demonstrated focal NF1 copy number loss in PN and MPNST patient plasma but not in healthy controls. Greater genomic instability including alterations associated with malignant transformation (focal copy number gains in chromosome arms 1q, 7p, 8q, 9q, and 17q; focal copy number losses in SUZ12, SMARCA2, CDKN2A/B, and chromosome arms 6p and 9p) was more prominently observed in MPNST plasma. Furthermore, the sum of longest tumor diameters (SLD) visualized by cross-sectional imaging correlated significantly with paired tumor fractions in plasma from MPNST patients (r = 0.39, P = 0.024). On serial analysis, tumor fraction levels in plasma dynamically correlated with treatment response to therapy and minimal residual disease (MRD) detection before relapse. Study limitations include a modest MPNST sample size despite accrual from 2 major referral centers for this rare malignancy, and lack of uniform treatment and imaging protocols representing a real-world cohort. CONCLUSIONS Tumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations.
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Affiliation(s)
- Jeffrey J. Szymanski
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - R. Taylor Sundby
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Paul A. Jones
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Divya Srihari
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Noah Earland
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Peter K. Harris
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Wenjia Feng
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Faridi Qaium
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Haiyan Lei
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - David Roberts
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Michele Landeau
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Jamie Bell
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Yi Huang
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Leah Hoffman
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Melissa Spencer
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Matthew B. Spraker
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Li Ding
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri, United States of America
- McDonnel Genome Institute, Washington University in Saint Louis, Missouri, United States of America
- Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Brigitte C. Widemann
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Jack F. Shern
- Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
- * E-mail: (JFS); (ACH); (AAC)
| | - Angela C. Hirbe
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America
- * E-mail: (JFS); (ACH); (AAC)
| | - Aadel A. Chaudhuri
- Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Siteman Cancer Center, Barnes Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America
- * E-mail: (JFS); (ACH); (AAC)
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31
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Friedrich RE, Tuzcu CT. Surgery for Peripheral Nerve Sheath Tumours of the Buttocks, Legs and Feet in 90 Patients With Neurofibromatosis Type 1. In Vivo 2021; 35:889-905. [PMID: 33622881 DOI: 10.21873/invivo.12329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 11/19/2020] [Accepted: 12/10/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Neurofibromatosis type 1 (NF1) is an autosomal dominant tumour predisposition syndrome that can cause plexiform neurofibromas (PNFs). This study examines the surgical procedures that have been performed on large PNFs of the lower extremities. PATIENTS AND METHODS Surgical procedures on the lower extremity performed on 90 patients with NF1 with PNFs were evaluated. The topography of the tumours was classified according to dermatomes and functional units. RESULTS A total of 243 surgical interventions on the regions of interest were performed. Neurological complications were rarely noted and usually occurred temporarily. There was no preference for dermatomes affected by PNF. The proportion of patients with malignant peripheral nerve sheath tumours (MPNSTs) in this group was 4/90 (4.4%). CONCLUSION PNFs often require repeated local interventions to achieve the treatment goal. Local tumour recurrences are to be expected even after extensive tumour reduction. Rapid tumour growth combined with new pain sensations can be signs of a MPNST.
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Affiliation(s)
- Reinhard E Friedrich
- Department of Oral and Craniomaxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany
| | - Caglayan T Tuzcu
- Department of Oral and Craniomaxillofacial Surgery, Eppendorf University Hospital, University of Hamburg, Hamburg, Germany
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32
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Martin E, Geitenbeek RTJ, Coert JH, Hanff DF, Graven LH, Grünhagen DJ, Verhoef C, Taal W. A Bayesian approach for diagnostic accuracy of malignant peripheral nerve sheath tumors: a systematic review and meta-analysis. Neuro Oncol 2021; 23:557-571. [PMID: 33326583 PMCID: PMC8041346 DOI: 10.1093/neuonc/noaa280] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Malignant peripheral nerve sheath tumors (MPNST) carry a dismal prognosis and require early detection and complete resection. However, MPNSTs are prone to sampling errors and biopsies or resections are cumbersome and possibly damaging in benign peripheral nerve sheath tumor (BPNST). This study aimed to systematically review and quantify the diagnostic accuracy of noninvasive tests for distinguishing MPNST from BPNST. Methods Studies on accuracy of MRI, FDG-PET (fluorodeoxyglucose positron emission tomography), and liquid biopsies were identified in PubMed and Embase from 2000 to 2019. Pooled accuracies were calculated using Bayesian bivariate meta-analyses. Individual level-patient data were analyzed for ideal maximum standardized uptake value (SUVmax) threshold on FDG-PET. Results Forty-three studies were selected for qualitative synthesis including data on 1875 patients and 2939 lesions. Thirty-five studies were included for meta-analyses. For MRI, the absence of target sign showed highest sensitivity (0.99, 95% CI: 0.94-1.00); ill-defined margins (0.94, 95% CI: 0.88-0.98); and perilesional edema (0.95, 95% CI: 0.83-1.00) showed highest specificity. For FDG-PET, SUVmax and tumor-to-liver ratio show similar accuracy; sensitivity 0.94, 95% CI: 0.91-0.97 and 0.93, 95% CI: 0.87-0.97, respectively, specificity 0.81, 95% CI: 0.76-0.87 and 0.79, 95% CI: 0.70-0.86, respectively. SUVmax ≥3.5 yielded the best accuracy with a sensitivity of 0.99 (95% CI: 0.93-1.00) and specificity of 0.75 (95% CI: 0.56-0.90). Conclusions Biopsies may be omitted in the presence of a target sign and the absence of ill-defined margins or perilesional edema. Because of diverse radiological characteristics of MPNST, biopsies may still commonly be required. In neurofibromatosis type 1, FDG-PET scans may further reduce biopsies. Ideal SUVmax threshold is ≥3.5.
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Affiliation(s)
- Enrico Martin
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Surgical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Ritchie T J Geitenbeek
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.,Department of Surgical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - J Henk Coert
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
| | - David F Hanff
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Laura H Graven
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Dirk J Grünhagen
- Department of Surgical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Walter Taal
- Department of Neuro-Oncology/Neurology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands
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Diagnostic Accuracy of MRI for the Detection of Malignant Peripheral Nerve Sheath Tumors: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol 2021; 217:31-39. [PMID: 33909462 DOI: 10.2214/ajr.20.23403] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE. This systematic review and meta-analysis evaluates the diagnostic accuracy of MRI for differentiating malignant (MPNSTs) from benign peripheral nerve sheath tumors (BPNSTs). MATERIALS AND METHODS. A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature from inception to December 2019 was performed. Original articles that involved at least 10 patients and that evaluated the accuracy of MRI for detecting MPNSTs were included. Two reviewers independently extracted clinical and radiologic data from included articles to calculate sensitivity, specificity, PPV, NPV, and accuracy. A meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using QUADAS-2. RESULTS. Fifteen studies involving 798 lesions (252 MPNSTs and 546 BPNSTs) were included in the analysis. Pooled and weighted sensitivity, specificity, and AUC values for MRI in detecting MPNSTs were 68% (95% CI, 52-80%), 93% (95% CI, 85-97%), and 0.89 (95% CI, 0.86-0.92) when using feature combination and 88% (95% CI, 74-95%), 94% (95% CI, 89-96%), and 0.97 (95% CI, 0.95-0.98) using diffusion restriction with or without feature combination. Subgroup analysis, such as patients with neurofibromatosis type 1 (NF1) versus those without NF1, could not be performed because of insufficient data. Risk of bias was predominantly high or unclear for patient selection, mixed for index test, low for reference standard, and unclear for flow and timing. CONCLUSION. Combining features such as diffusion restriction optimizes the diagnostic accuracy of MRI for detecting MPNSTs. However, limitations in the literature, including variability and risk of bias, necessitate additional methodologically rigorous studies to allow subgroup analysis and further evaluate the combination of clinical and MRI features for MPNST diagnosis.
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Basaldella F, Rasera A, Zanette G, Moscolo F, Sala F, Bonetti B, Squintani G. Utility of Preoperative Electrodiagnosis Together with Peripheral Nerve High-Resolution Ultrasound: A Complex Case Report of Neurofibromatosis Type I. J Neurol Surg A Cent Eur Neurosurg 2021; 82:392-396. [PMID: 33845502 DOI: 10.1055/s-0041-1724110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Our case report underscores the importance of electroneuromyography (ENMG) combined with peripheral nerve high-resolution ultrasound (HRUS) in the evaluation of neurofibromatosis type 1 (NF1). A 49-year-old woman affected by NF1 came to our attention because of new-onset left arm weakness and atrophy. Debulking of a cervicothoracic C7-T1 neurofibroma had been performed 8 years earlier. On current admission, magnetic resonance imaging disclosed increased lesion volume that was thought to cause the neurologic deficits by compressing the C8 root. Findings from intraoperative neurophysiologic monitoring during repeat debulking suggested that C8 root integrity had been compromised during the first operation and that the new-onset symptoms probably stemmed from peripheral nervous system damage distal to the cervical roots. Postoperative ENMG showed chronic denervation signs in the muscles innervated by C7-C8-T1 roots, moderate carpal tunnel syndrome (CTS), and ulnar nerve conduction block at the elbow. HRUS confirmed the CTS and revealed multiple neurofibromas involving the distal tract of the radial, ulnar, and median nerves. Surgical debulking was considered unnecessary in this case. ENMG combined with nerve and plexus HRUS evaluation may help identify the cause of neurologic deficits and choose the best surgical option in such complex clinical conditions as NF1.
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Affiliation(s)
- Federica Basaldella
- Department of Neurology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Veneto, Italy
| | - Andrea Rasera
- Department of Neuroscience, University of Verona, Verona, Italy
| | - Giampietro Zanette
- Department of Neurology, Ospedale P. Pederzoli Casa di Cura Privata SpA, Veneto, Italy
| | - Fabio Moscolo
- Department of Neurosurgery, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Veneto, Italy
| | - Francesco Sala
- Department of Neurosurgery, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Veneto, Italy
| | - Bruno Bonetti
- Department of Neurology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Veneto, Italy
| | - Giovanna Squintani
- Department of Neurology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Veneto, Italy
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Dewey BJ, Howe BM, Spinner RJ, Johnson GB, Nathan MA, Wenger DE, Broski SM. FDG PET/CT and MRI Features of Pathologically Proven Schwannomas. Clin Nucl Med 2021; 46:289-296. [PMID: 33443952 DOI: 10.1097/rlu.0000000000003485] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE The aim of this study was to examine the MRI and FDG PET/CT imaging features of pathologically proven schwannomas. PATIENTS AND METHODS This institutional review board-approved retrospective study examined biopsy-proven schwannomas that underwent FDG PET/CT and/or MRI at our institution between January 1, 2002, and April 1, 2018. PET/CT features analyzed included SUVmax, metabolic ratios, volumetric metabolic measures, presence of calcification, and pattern of FDG activity. MRI features included T1/T2 signal, enhancement pattern, margins, perilesional edema, presence of muscular denervation, and size. RESULTS Ninety-five biopsy-proven schwannomas were identified (40 with both PET and MRI, 35 with PET only, and 20 with MRI only), 46 females and 49 males, average age of 57.7 ± 15.3 years. The average largest dimension was 4.6 ± 2.7 cm, the average SUVmax was 5.4 ± 2.7, and lesion SUVmax/liver SUVmean was 2.2 ± 1.2. Eleven (15%) of 75 lesions had SUVmax greater than 8.1, 26/75 (35%) had SUVmax greater than 6.1, and 14/75 (19%) had lesion SUVmax/liver SUVmean greater than 3.0. On MRI, 29/53 (55%) demonstrated internal nonenhancing areas. Twenty-eight (70%) of 40 lesions with both MRI and PET demonstrated at least 1 imaging feature concerning for malignant peripheral nerve sheath tumor (irregular margins, internal nonenhancement, perilesional edema, heterogeneous FDG uptake, or SUVmax >8.1). Lesions with heterogeneous FDG activity had higher SUVmax (6.5 ± 0.5 vs 4.7 ± 0.4, P = 0.0031) and more frequent internal nonenhancement on MRI (P = 0.0218). CONCLUSIONS Schwannomas may be large, be intensely FDG avid, and demonstrate significant heterogeneity, features typically associated with malignant peripheral nerve sheath tumors. A significant proportion exhibit FDG activity above cutoff levels previously thought useful in differentiating malignant from benign peripheral nerve sheath tumors.
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Zhou HY, Jiang S, Ma FX, Lu H. Peripheral nerve tumors of the hand: Clinical features, diagnosis, and treatment. World J Clin Cases 2020; 8:5086-5098. [PMID: 33269245 PMCID: PMC7674743 DOI: 10.12998/wjcc.v8.i21.5086] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 09/15/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
The majority of the tumors arising from the peripheral nerves of the hand are relatively benign. However, a tumor diagnosed as malignant peripheral nerve sheath tumor (MPNST) has destructive consequences. Clinical signs and symptoms are usually caused by direct and indirect effects of the tumor, such as nerve invasion or compression and infiltration of surrounding tissues. Definitive diagnosis is made by tumor biopsy. Complete surgical removal with maximum reservation of residual neurologic function is the most appropriate intervention for most symptomatic benign peripheral nerve tumors (PNTs) of the hand; however, MPNSTs require surgical resection with a sufficiently wide margin or even amputation to improve prognosis. In this article, we review the clinical presentation and radiographic features, summarize the evidence for an accurate diagnosis, and discuss the available treatment options for PNTs of the hand.
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Affiliation(s)
- Hai-Ying Zhou
- Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Shuai Jiang
- Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Fei-Xia Ma
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Hui Lu
- Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Nelson CN, Dombi E, Rosenblum JS, Miettinen MM, Lehky TJ, Whitcomb PO, Hayes C, Scott G, Benzo S, Widemann BC, Chittiboina P. Safe marginal resection of atypical neurofibromas in neurofibromatosis type 1. J Neurosurg 2020; 133:1516-1526. [PMID: 31653805 PMCID: PMC8320705 DOI: 10.3171/2019.7.jns191353] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 07/12/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Patients with neurofibromatosis type 1 (NF1) are predisposed to visceral neurofibromas, some of which can progress to premalignant atypical neurofibromas (ANFs) and malignant peripheral nerve sheath tumors (MPNSTs). Though subtotal resection of ANF may prevent malignant transformation and thus deaths with no neural complications, local recurrences require reoperation. The aim of this study was to assess the surgical morbidity associated with marginal resection of targeted ANF nodules identified via preoperative serial volumetric MRI and 18F-FDG-PET imaging. METHODS The authors analyzed clinical outcomes of 16 NF resections of 21 tumors in 11 NF1 patients treated at the NIH Clinical Center between 2008 and 2018. Preoperative volumetric growth rates and 18F-FDG-PET SUVMax (maximum standardized uptake value within the tumor) of the target lesions and any electromyographic or nerve conduction velocity abnormalities of the parent nerves were measured and assessed in tandem with postoperative complications, histopathological classification of the resected tumors, and surgical margins through Dunnett's multiple comparisons test and t-test. The surgical approach for safe marginal resection of ANF was also described. RESULTS Eleven consecutive NF1 patients (4 male, 7 female; median age 18.5 years) underwent 16 surgical procedures for marginal resections of 21 tumors. Preoperatively, 13 of the 14 (93%) sets of serial MRI studies and 10 of the 11 (91%) 18F-FDG-PET scans showed rapid growth (≥ 20% increase in volume per year) and avidity (SUVMax ≥ 3.5) of the identified tumor, respectively (median tumor size 48.7 cm3; median growth rate 92% per year; median SUVMax 6.45). Most surgeries (n = 14, 88%) resulted in no persistent postoperative parent nerve-related complications, and to date, none of the resected tumors have recurred. The median length of postoperative follow-up has been 2.45 years (range 0.00-10.39 years). Histopathological analysis confirmed significantly greater SUVMax among the ANFs (6.51 ± 0.83, p = 0.0042) and low-grade MPNSTs (13.8, p = 0.0001) than in benign neurofibromas (1.9). CONCLUSIONS This report evaluates the utility of serial imaging (MRI and 18F-FDG-PET SUVMax) to successfully detect ANF and demonstrates that safe, fascicle-sparing gross-total, extracapsular resection of ANF is possible with the use of intraoperative nerve stimulation and microdissection of nerve fascicles.
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Affiliation(s)
- Charlie N. Nelson
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
- College of Medicine, Northeast Ohio Medical University, Rootstown, Ohio
| | - Eva Dombi
- Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Jared S. Rosenblum
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
- Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Markku M. Miettinen
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Tanya J. Lehky
- Electromyography Section, National Institute of Neurological Disorders and Stroke
| | - Patricia O. Whitcomb
- Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Christina Hayes
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
| | - Gretchen Scott
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
| | - Sarah Benzo
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
| | - Brigitte C. Widemann
- Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Prashant Chittiboina
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
- Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke
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Prudner BC, Ball T, Rathore R, Hirbe AC. Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives. Neurooncol Adv 2020; 2:i40-i49. [PMID: 32642731 PMCID: PMC7317062 DOI: 10.1093/noajnl/vdz047] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
One of the most common malignancies affecting adults with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the malignant peripheral nerve sheath tumor (MPNST), a highly aggressive sarcoma that typically develops from benign plexiform neurofibromas. Approximately 8-13% of individuals with NF1 will develop MPNST during young adulthood. There are few therapeutic options, and the vast majority of people with these cancers will die within 5 years of diagnosis. Despite efforts to understand the pathogenesis of these aggressive tumors, the overall prognosis remains dismal. This manuscript will review the current understanding of the cellular and molecular progression of MPNST, diagnostic workup of patients with these tumors, current treatment paradigms, and investigational treatment options. Additionally, we highlight novel areas of preclinical research, which may lead to future clinical trials. In summary, MPNST remains a diagnostic and therapeutic challenge, and future work is needed to develop novel and rational combinational therapy for these tumors.
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Affiliation(s)
- Bethany C Prudner
- Division of Medical Oncology, Department of Medicine, Washington University, St. Louis
| | - Tyler Ball
- Division of Medical Oncology, Department of Medicine, Washington University, St. Louis
| | - Richa Rathore
- Division of Medical Oncology, Department of Medicine, Washington University, St. Louis
| | - Angela C Hirbe
- Division of Medical Oncology, Department of Medicine, Washington University, St. Louis
- Neurofibromatosis Center, Washington University, St. Louis MO
- Siteman Cancer Center, Washington University, St. Louis
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Well L, Salamon J, Kaul MG, Farschtschi S, Herrmann J, Geier KI, Hagel C, Bockhorn M, Bannas P, Adam G, Mautner VF, Derlin T. Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging. Neuro Oncol 2020; 21:508-516. [PMID: 30496452 DOI: 10.1093/neuonc/noy199] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND We sought to determine the value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for characterization of benign and malignant peripheral nerve sheath tumors (PNSTs) in patients with neurofibromatosis type 1 (NF1). METHODS Twenty-six patients with NF1 and suspicion of malignant transformation of PNSTs were prospectively enrolled and underwent DW MRI at 3T. For a set of benign (n = 55) and malignant (n = 12) PNSTs, functional MRI parameters were derived from both biexponential intravoxel incoherent motion (diffusion coefficient D and perfusion fraction f) and monoexponential data analysis (apparent diffusion coefficients [ADCs]). A panel of morphological MRI features was evaluated using T1- and T2-weighted imaging. Mann-Whitney U-test, Fisher's exact test, and receiver operating characteristic (ROC) analyses were applied to assess the diagnostic accuracy of quantitative and qualitative MRI. Cohen's kappa was used to determine interrater reliability. RESULTS Malignant PNSTs demonstrated significantly lower diffusivity (P < 0.0001) compared with benign PNSTs. The perfusion fraction f was significantly higher in malignant PNSTs (P < 0.001). In ROC analysis, functional MRI parameters showed high diagnostic accuracy for differentiation of PNSTs (eg, ADCmean, 92% sensitivity with 98% specificity, AUC 0.98; Dmean, 92% sensitivity with 98% specificity, AUC 0.98). By contrast, morphological imaging features had only limited sensitivity (18-94%) and specificity (18-82%) for identification of malignancy. Interrater reliability was higher for monoexponential data analysis. CONCLUSION DW imaging shows better diagnostic performance than morphological features and allows accurate differentiation of benign and malignant peripheral nerve sheath tumors in NF1.
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Affiliation(s)
- Lennart Well
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Johannes Salamon
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Michael G Kaul
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Said Farschtschi
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jochen Herrmann
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Karin I Geier
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Hagel
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Bockhorn
- Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Peter Bannas
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gerhard Adam
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Victor F Mautner
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Thorsten Derlin
- Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany
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Koeller KK, Shih RY. Intradural Extramedullary Spinal Neoplasms: Radiologic-Pathologic Correlation. Radiographics 2020; 39:468-490. [PMID: 30844353 DOI: 10.1148/rg.2019180200] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
While intradural extramedullary spinal disease varies widely, identification of tumors in this location and their radiologic manifestations greatly facilitates narrowing of the diagnostic considerations. Meningioma and schwannoma are the two most common intradural extramedullary tumors, and both are associated with neurofibromatosis. Meningiomas are most common in the thoracic spine and show a strong female predilection and a clinical manifestation related to compression of the spinal cord or nerve roots. Schwannomas typically are associated with radicular pain and other sensory symptoms. Melanotic schwannoma frequently shows T1 hyperintensity at MRI related to the presence of paramagnetic free radicals in melanin. Neurofibroma, known for its T2 hyperintensity, frequently involves the cervical spine, where it may make surgical resection challenging. Less commonly, malignant peripheral nerve sheath tumor commonly mimics the imaging appearance of a schwannoma but has decidedly more aggressive biologic behavior. In the cauda equina, myxopapillary ependymoma and paraganglioma are believed to arise from the filum terminale and have characteristic imaging manifestations based on their underlying pathologic features. Recent identification of a common genetic marker has led to reclassification of what had previously been regarded as separate tumors and are now known as solitary fibrous tumor/hemangiopericytoma. In the proper clinical setting, the presence of nodular intradural enhancement strongly suggests the presence of leptomeningeal metastatic disease, even when results of cerebrospinal fluid analysis are negative. This article highlights the characteristic neuroimaging manifestations of these neoplasms, with emphasis on radiologic-pathologic correlation. See Illumination by Frazier .
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Affiliation(s)
- Kelly K Koeller
- From the Department of Neuroradiology, American Institute for Radiologic Pathology, 1011 Wayne Ave, Suite 320, Silver Spring, MD 20910 (K.K.K., R.Y.S.); Department of Radiology, Mayo Clinic, Rochester, Minn (K.K.K.); Uniformed Services University of the Health Sciences, Bethesda, Md (R.Y.S.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (R.Y.S.)
| | - Robert Y Shih
- From the Department of Neuroradiology, American Institute for Radiologic Pathology, 1011 Wayne Ave, Suite 320, Silver Spring, MD 20910 (K.K.K., R.Y.S.); Department of Radiology, Mayo Clinic, Rochester, Minn (K.K.K.); Uniformed Services University of the Health Sciences, Bethesda, Md (R.Y.S.); and Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Md (R.Y.S.)
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Bergqvist C, Servy A, Valeyrie-Allanore L, Ferkal S, Combemale P, Wolkenstein P. Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966. Orphanet J Rare Dis 2020; 15:37. [PMID: 32014052 PMCID: PMC6998847 DOI: 10.1186/s13023-020-1310-3] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 01/17/2020] [Indexed: 12/13/2022] Open
Abstract
Neurofibromatosis type 1 is a relatively common genetic disease, with a prevalence ranging between 1/3000 and 1/6000 people worldwide. The disease affects multiple systems with cutaneous, neurologic, and orthopedic as major manifestations which lead to significant morbidity or mortality. Indeed, NF1 patients are at an increased risk of malignancy and have a life expectancy about 10-15 years shorter than the general population. The mainstay of management of NF1 is a patient-centered longitudinal care with age-specific monitoring of clinical manifestations, aiming at the early recognition and symptomatic treatment of complications as they occur. Protocole national de diagnostic et de soins (PNDS) are mandatory French clinical practice guidelines for rare diseases required by the French national plan for rare diseases. Their purpose is to provide health care professionals with guidance regarding the optimal diagnostic and therapeutic management of patients affected with a rare disease; and thus, harmonizing their management nationwide. PNDS are usually developed through a critical literature review and a multidisciplinary expert consensus. The purpose of this article is to present the French guidelines on NF1, making them even more available to the international medical community. We further dwelled on the emerging new evidence that might have therapeutic potential or a strong impact on NF1 management in the coming feature. Given the complexity of the disease, the management of children and adults with NF1 entails the full complement healthcare providers and communication among the various specialties.
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Affiliation(s)
- Christina Bergqvist
- Faculty of medicine, Université Paris-Est Creteil (UPEC), F-94010 Créteil Cedex, France
- Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, Service de Dermatologie, F-94010 Créteil, France
| | - Amandine Servy
- Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, Service de Dermatologie, F-94010 Créteil, France
| | - Laurence Valeyrie-Allanore
- INSERM, Centre d’Investigation Clinique 006, Referral Center of Neurofibromatosis, Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, F-94010 Créteil, France
| | - Salah Ferkal
- INSERM, Centre d’Investigation Clinique 006, Referral Center of Neurofibromatosis, Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, F-94010 Créteil, France
| | - Patrick Combemale
- Rhône-Alpes Auvergne Competence Center for the treatment of Neurofibromatosis type 1, Léon Bérard Comprehensive Cancer Center, Hôpitaux Universitaires de Lyon, Université de Lyon, F-69008 Lyon, France
| | - Pierre Wolkenstein
- Faculty of medicine, Université Paris-Est Creteil (UPEC), F-94010 Créteil Cedex, France
- Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, Service de Dermatologie, F-94010 Créteil, France
- INSERM, Centre d’Investigation Clinique 006, Referral Center of Neurofibromatosis, Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, F-94010 Créteil, France
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Current status and recommendations for imaging in neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. Skeletal Radiol 2020; 49:199-219. [PMID: 31396668 DOI: 10.1007/s00256-019-03290-1] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 07/23/2019] [Accepted: 07/24/2019] [Indexed: 02/02/2023]
Abstract
Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are three clinically distinct tumor predisposition syndromes with a shared tendency to develop peripheral and central nervous system neoplasms. Disease expression and complications of NF1, NF2, and SWN are highly variable, necessitating a multidisciplinary approach to care in order to optimize outcomes. This review will discuss the imaging appearance of NF1, NF2, and SWN and highlight the important role that imaging plays in informing management decisions in people with tumors associated with these syndromes. Recent technological advances, including the role of both whole-body and localized imaging strategies, routine anatomic and advanced magnetic resonance (MR) imaging sequences such as diffusion-weighted imaging (DWI) with quantitative apparent diffusion coefficient (ADC) mapping, and metabolic imaging techniques (MR spectroscopy and positron emission testing) are discussed in the context of the diagnosis and management of people with NF1, NF2, and SWN based on the most up-to-date clinical imaging studies.
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Martin E, Flucke UE, Coert JH, van Noesel MM. Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease. Childs Nerv Syst 2020; 36:2453-2462. [PMID: 32494969 PMCID: PMC7575473 DOI: 10.1007/s00381-020-04687-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 05/14/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas. Children with neurofibromatosis type 1 (NF1) have a 10% lifetime risk for development of MPNST. Prognosis remains poor and survival seems worse for NF1 patients. METHODS This narrative review highlights current practices and pitfalls in the management of MPNST in pediatric NF1 patients. RESULTS Preoperative diagnostics can be challenging, but PET scans have shown to be useful tools. More recently, functional MRI holds promise as well. Surgery remains the mainstay treatment for these patients, but careful planning is needed to minimize postoperative morbidity. Functional reconstructions can play a role in improving functional status. Radiotherapy can be administered to enhance local control in selected cases, but care should be taken to minimize radiation effects as well as reduce the risk of secondary malignancies. The exact role of chemotherapy has yet to be determined. Reports on the efficacy of chemotherapy vary as some report lower effects in NF1 populations. Promisingly, survival seems to ameliorate in the last few decades and response rates of chemotherapy may increase in NF1 populations when administering it as part of standard of care. However, in metastasized disease, response rates remain poor. New systemic therapies are therefore desperately warranted and multiple trials are currently investigating the role of drugs. Targeted drugs are nevertheless not yet included in first line treatment. CONCLUSION Both research and clinical efforts benefit from multidisciplinary approaches with international collaborations in this rare malignancy.
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Affiliation(s)
- Enrico Martin
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, G04.126, PO Box 85060, 3508, AB, Utrecht, the Netherlands.
| | - Uta E. Flucke
- Department of Solid Tumors, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands ,Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - J. Henk Coert
- Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, G04.126, PO Box 85060, 3508 AB Utrecht, the Netherlands
| | - Max M. van Noesel
- Department of Solid Tumors, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Witt RG, Baldini EH, Raut CP. Screening populations at high risk for soft tissue sarcoma and surveillance following soft tissue sarcoma resection. J Surg Oncol 2019; 120:882-890. [PMID: 31432526 DOI: 10.1002/jso.25676] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 08/07/2019] [Indexed: 11/12/2022]
Abstract
Soft tissue sarcomas (STS) are a rare and diverse group of tumors that affect both adult and pediatric populations. This review discusses current screening recommendations for populations at increased risk for STS, including those with genetic predispositions. We also review surveillance guidelines for those at risk for recurrence following curative-intent surgery.
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Affiliation(s)
- Russell G Witt
- Department of Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Elizabeth H Baldini
- Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Chandrajit P Raut
- Department of Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
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Ahlawat S, Blakeley JO, Rodriguez FJ, Fayad LM. Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1. Neurology 2019; 93:e1076-e1084. [PMID: 31395668 DOI: 10.1212/wnl.0000000000008092] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 04/16/2019] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE To determine the utility of quantitative metrics obtained from fMRI using diffusion-weighted imaging (DWI)/apparent diffusion coefficient (ADC) mapping compared with metabolic (18F-fluorodeoxyglucose [FDG]-PET/CT) imaging in patients with neurofibromatosis type 1 (NF1) for the characterization of peripheral nerve sheath tumors (PNSTs) as benign or malignant. METHODS This Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant study retrospectively reviewed imaging of 55 PNSTs in 21 patients with NF1. Imaging included anatomic (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted), functional DWI (b = 50, 400, 800 s/mm2) and ADC mapping, magnetic resonance sequences, and FDG-PET/CT imaging. Anatomic (size), functional (minimum ADC values), and metabolic (maximum standardized uptake values [SUVmax]) imaging characteristics were recorded. ADC values were correlated with SUVmax. With histologic correlation for all malignant PNSTs (MPNSTs) or clinical or imaging stability (>12 months) for benign lesions used as reference standards, diagnostic accuracy was calculated. RESULTS Of 55 PNSTs, there were 19 (35%) malignant and 36 (65%) benign PNSTs. Benign PNSTs were overall smaller than MPNSTs (largest diameter 4.3 ± 1.3 vs 8.2 ± 3.3 cm, respectively, p = 0.014). Benign PNSTs had higher ADCmin (×10-3 mm2/s) than MPNSTs (1.6 ± 0.4 vs 0.6 ± 0.2, respectively, p < 0.0001) and lower SUVmax than MPNSTs (3.2 ± 1.8 vs 8 ± 3.9, p < 0.0001, respectively). ADCmin correlated inversely with SUVmax (correlation coefficient r = -0.0.58, p < 0.0001). Maintaining a sensitivity of 100% with threshold values of ADCmin ≤1 or SUVmax >3.2, DWI yielded a specificity of 94% while FDG-PET/CT offered a specificity of 83%. CONCLUSIONS Both quantitative metabolic imaging and functional imaging offer high sensitivity for the characterization of PNSTs in NF1; however, DWI/ADC mapping offers increased specificity and may be a more useful modality. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that for patients with NF1, MRI using DWI/ADC mapping accurately distinguishes malignant and benign PNSTs.
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Affiliation(s)
- Shivani Ahlawat
- From The Johns Hopkins University School of Medicine, Baltimore, MD.
| | | | | | - Laura M Fayad
- From The Johns Hopkins University School of Medicine, Baltimore, MD
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46
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MR Imaging of Pediatric Musculoskeletal Tumors:: Recent Advances and Clinical Applications. Magn Reson Imaging Clin N Am 2019; 27:341-371. [PMID: 30910102 DOI: 10.1016/j.mric.2019.01.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Pediatric musculoskeletal tumors comprise approximately 10% of childhood neoplasms, and MR imaging has been used as the imaging evaluation standard for these tumors. The role of MR imaging in these cases includes identification of tumor origin, tissue characterization, and definition of tumor extent and relationship to adjacent structures as well as therapeutic response in posttreatment surveillance. Technical advances have enabled quantitative evaluation of biochemical changes in tumors. This article reviews recent updates to MR imaging of pediatric musculoskeletal tumors, focusing on advanced MR imaging techniques and providing information on the relevant physics of these techniques, clinical applications, and pitfalls.
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47
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48
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Reinert CP, Schuhmann MU, Bender B, Gugel I, la Fougère C, Schäfer J, Gatidis S. Comprehensive anatomical and functional imaging in patients with type I neurofibromatosis using simultaneous FDG-PET/MRI. Eur J Nucl Med Mol Imaging 2018; 46:776-787. [DOI: 10.1007/s00259-018-4227-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 11/25/2018] [Indexed: 12/31/2022]
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Evaluation of the most commonly used (semi-)quantitative parameters of 18F-FDG PET/CT to detect malignant transformation of neurofibromas in neurofibromatosis type 1. Nucl Med Commun 2018; 39:961-968. [PMID: 30106798 DOI: 10.1097/mnm.0000000000000889] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
In patients with neurofibromatosis type 1, transformation of neurofibromas into a malignant peripheral nerve sheath tumor (MPNST) is a severe complication of the disease. Fluorine-18-fluorodeoxyglucose PET/computed tomography (PET/CT) is a viable option for detecting malignant tumors in neurofibromatosis type 1 patients. The aim of this review was to assess the diagnostic performance of the most frequently used parameters of PET/CT in detecting MPNST. An extensive computer search was performed using the Cochrane Library, Pubmed, and Medline/Embase databases. Two reviewers independently extracted data of relevant studies and assessed the methodological quality (QUADAS-2). The diagnostic performance of PET/CT parameters in individual studies was determined by calculating a diagnostic odds ratio (DOR) using the absolute numbers of true-positive, true-negative, false-positive, and false-negative test results. A total of eight studies were included, of which three evaluated the standardized uptake value as a diagnostic parameter, two assessed the tumor-to-liver (T/L) ratio, and three articles described both parameters. The cut-off values for maximum standardized uptake value (SUVmax) ranged from 3.2 to 4.5; for the T/L ratio, the cut-off values were between 1.0 and 4.3. The sensitivity and specificity ranged from 90 to 100% and from 80 to 100%, respectively (SUVmax). T/L ratios were associated with 92-100% sensitivity and 72-94% specificity. The corresponding DORs ranged from 57 to 145 (SUVmax) and 35 to 655 (T/L ratio). Both the SUV and the T/L ratio are associated with high sensitivity combined with acceptable specificity in detecting MPNST. There is a tendency toward higher DORs using the T/L ratio, but the number of studies is limited.
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50
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Uthoff J, De Stefano FA, Panzer K, Darbro BW, Sato TS, Khanna R, Quelle DE, Meyerholz DK, Weimer J, Sieren JC. Radiomic biomarkers informative of cancerous transformation in neurofibromatosis-1 plexiform tumors. J Neuroradiol 2018; 46:179-185. [PMID: 29958847 DOI: 10.1016/j.neurad.2018.05.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 05/11/2018] [Accepted: 05/28/2018] [Indexed: 01/30/2023]
Abstract
BACKGROUND This study explores whether objective, quantitative radiomic biomarkers derived from magnetic resonance (MR), positron emission tomography (PET), and computed tomography (CT) may be useful in reliably distinguishing malignant peripheral nerve sheath tumors (MPNST) from benign plexiform neurofibromas (PN). METHODS A registration and segmentation pipeline was established using a cohort of NF1 patients with histopathological diagnosis of PN or MPNST, and medical imaging of the PN including MR and PET-CT. The corrected MR datasets were registered to the corresponding PET-CT via landmark-based registration. PET standard-uptake value (SUV) thresholds were used to guide segmentation of volumes of interest: MPNST-associated PET-hot regions (SUV≥3.5) and PN-associated PET-elevated regions (2.0<SUV<3.5). Quantitative imaging features were extracted from the MR, PET, and CT data and compared for statistical differences. Intensity histogram features included (mean, media, maximum, variance, full width at half maximum, entropy, kurtosis, and skewness), while image texture was quantified using Law's texture energy measures, grey-level co-occurrence matrices, and neighborhood grey-tone difference matrices. RESULTS For each of the 20 NF1 subjects, a total of 320 features were extracted from the image data. Feature reduction and statistical testing identified 9 independent radiomic biomarkers from the MR data (4 intensity and 5 texture) and 4 PET (2 intensity and 2 texture) were different between the PET-hot versus PET-elevated volumes of interest. CONCLUSIONS Our data suggests imaging features can be used to distinguish malignancy in NF1-realted tumors, which could improve MPNST risk assessment and positively impact clinical management of NF1 patients.
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Affiliation(s)
- J Uthoff
- Department of Radiology, University of Iowa, Iowa City, Iowa, United States of America; Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States of America
| | - F A De Stefano
- Department of Radiology, University of Iowa, Iowa City, Iowa, United States of America
| | - K Panzer
- Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America
| | - B W Darbro
- Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America
| | - T S Sato
- Department of Radiology, University of Iowa, Iowa City, Iowa, United States of America
| | - R Khanna
- Department of Pharmacology, University of Arizona, Arizona, United States of America
| | - D E Quelle
- Department of Pharmacology, University of Iowa, Iowa City, Iowa, United States of America
| | - D K Meyerholz
- Department of Pathology, University of Iowa, Iowa City, Iowa, United States of America
| | - J Weimer
- Pediatric and Rare Disease Group, Sanford Research, Sioux Falls, South Dakota, United States of America
| | - J C Sieren
- Department of Radiology, University of Iowa, Iowa City, Iowa, United States of America; Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States of America.
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