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1
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Morozov N, Fell R, Mahmood M. Pituitary Complications of Enchondromas Due to Maffucci Syndrome. JCEM CASE REPORTS 2025; 3:luaf072. [PMID: 40255442 PMCID: PMC12006738 DOI: 10.1210/jcemcr/luaf072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Indexed: 04/22/2025]
Abstract
Maffucci syndrome (MS) is a congenital disorder caused by a gain-of-function variant in isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) genes on chromosomes 2 and 15, respectively. Common manifestations include the development of multiple enchondromas, chondrosarcomas, and intracranial tumors such as pituitary adenomas. Endocrinological conditions are less frequently associated with MS. We present a patient with MS with complete anterior pituitary insufficiency with central hypothyroidism, adrenal insufficiency, and hypogonadotropic hypogonadism, which may be related to the mass effect of her intracranial enchondromas. With hormonal treatments including thyroid hormone replacement, hydrocortisone, and cabergoline, the patient's symptoms of fatigue and cold intolerance improved. We highlight the importance of endocrinological evaluation in patients with neurological tumors related to MS.
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Affiliation(s)
- Nicole Morozov
- Department of Internal Medicine, The Jewish Hospital (Bon Secours Mercy Health), Cincinnati, OH 45236, USA
| | - Rafael Fell
- Department of Internal Medicine, The Jewish Hospital (Bon Secours Mercy Health), Cincinnati, OH 45236, USA
| | - Muhammad Mahmood
- Department of Internal Medicine, The Jewish Hospital (Bon Secours Mercy Health), Cincinnati, OH 45236, USA
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2
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Connolly EA, Boye K, Bonvalot S, Kratz CP, Leithner A, Malkin D, Messiou C, Miah AB, Pantziarka P, Timmermann B, van der Graaf WT, Thomas DM, Stacchiotti S. Genetic predisposition in sarcomas: clinical implications and management. EClinicalMedicine 2025; 83:103203. [PMID: 40291347 PMCID: PMC12032185 DOI: 10.1016/j.eclinm.2025.103203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 03/14/2025] [Accepted: 03/28/2025] [Indexed: 04/30/2025] Open
Abstract
Recent studies indicate up to 20% of sarcomas may be associated with predisposition genes, and this number will probably increase as genetic testing becomes more available. Evidence on the management of patients with sarcoma and genetic predisposition remains, however, scarce. This review compiles available research on genetic predisposition syndromes associated with sarcoma and sarcoma treatment within such syndromes, addressing key gaps in knowledge. We explore the current evidence on how genetic predisposition may influence treatment decisions and clinical management, focusing on surgery, radiotherapy, systemic treatment, and surveillance. Evidence-based recommendations are currently not available for most syndromes, and we have therefore included pragmatic advice for clinicians. Unanswered questions and unmet needs are also identified, underscoring the importance of multidisciplinary input from specialists such as geneticists, radiologists, surgeons and oncologists. The review stresses the need for future research to improve clinical outcomes for patients with sarcoma and genetic predisposition. Funding No funding has been provided for this work.
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Affiliation(s)
- Elizabeth A. Connolly
- Department of Medical Oncology, Chris O’Brien Lifehouse, Sydney, Australia
- ProCan, Children’s Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia
| | - Kjetil Boye
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Sylvie Bonvalot
- Department of Surgery, Institut Curie, Comprehensive Cancer Center, Paris, France
| | - Christian P. Kratz
- Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
| | - Andreas Leithner
- Department of Orthopedics and Trauma, Medical University of Graz, Graz, Austria
| | - David Malkin
- Division of Haematology-Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
- Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada
| | - Christina Messiou
- Sarcoma Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London, United Kingdom
- The Institute of Cancer Research, London, United Kingdom
| | - Aisha B. Miah
- Sarcoma Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London, United Kingdom
- The Institute of Cancer Research, London, United Kingdom
| | - Pan Pantziarka
- Anticancer Fund, Meise, Belgium
- George Pantziarka TP53 Trust, London, United Kingdom
| | - Beate Timmermann
- Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), Essen, Germany
| | - Winette T.A. van der Graaf
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, the Netherlands
| | - David M. Thomas
- Garvan Institute of Medical Research, Sydney, Australia
- Centre for Molecular Oncology, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Silvia Stacchiotti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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3
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Zhao T, Hung YP, Devins KM, Young RH, Oliva E. The Spectrum of Vascular Lesions of the Upper Female Genital Tract: A Report of 55 Cases. Int J Gynecol Pathol 2025:00004347-990000000-00236. [PMID: 40372932 DOI: 10.1097/pgp.0000000000001109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2025]
Abstract
Upper female genital tract vascular proliferations are rare and generally not well characterized. We evaluated types, differences in distribution, and associations of such lesions. Fifty-five vascular lesions were identified: 42 benign (ovary 24; uterine corpus 11; para-adnexal 4; fallopian tube 1; ovaries, fallopian tubes, and corpus 1; ovary and fallopian tube 1) and 13 angiosarcomas. Patients with benign vascular lesions had a mean age of 55 (range: 13-82) yr. Twenty-six lesions were incidental findings, and 11 were associated with clinical manifestations. They had a mean size of 2.0 (range: <1-13) cm, and often were grossly cystic and hemorrhagic. Uterine benign vascular lesions included 6 arteriovenous malformations, 3 venous hemangiomas/malformations, 2 cavernous hemangiomas, and 1 mixed venous-cavernous hemangioma. In the ovary, there were 10 anastomosing hemangiomas, 8 arteriovenous malformations, 6 venous (2 in mature cystic teratomas, 1 bilateral in a patient with Klippel-Trenaunay syndrome), and 2 cavernous hemangiomas. Anastomosing hemangiomas were frequently associated with peripheral stromal luteinization/hilar cell hyperplasia; intravascular growth, extramedullary hematopoiesis, and one with adipocytic metaplasia. Venous hemangiomas/malformations were noted at a younger age in the ovary when compared to the uterine corpus. Patients with angiosarcomas had a mean age of 32 (range: 12-58) yr and a mean tumor size of 9.7 (range: 1.5-23) cm. Eight presented with a pelvic mass. Most angiosarcomas were grossly hemorrhagic and/or necrotic. Eleven arose in the ovary, 4 of them were associated with mature cystic teratoma, 1 with adenosarcoma with sarcomatous overgrowth, and 1 was part of a malignant mesenchymoma. Five were predominantly spindled, 3 epithelioid, 2 spindled and epithelioid, and one pleomorphic. Both uterine angiosarcomas were epithelioid. Follow-up was available for 8 patients: 7 died of disease between 6 and 43 mo, and 1 was alive and well at 106 mo. Vascular lesions in the upper female genital tract are uncommon, morphologically heterogeneous, and more frequent and clinically evident in the adnexa. Anastomosing hemangioma is the most common benign vascular lesion in the ovary and may be misdiagnosed as a steroid cell tumor due to associated stromal luteinization/hilar cell hyperplasia. Arteriovenous malformation is the most common benign vascular lesion in the uterine corpus. Angiosarcomas may be associated with another neoplasm, more commonly mature cystic teratoma, and have a poor prognosis.
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Affiliation(s)
- Ting Zhao
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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4
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Boudou-Rouquette P, Corradini N, Sunyach MP, Larousserie F, Cordero C, Cardine AM, Piperno-Neumann S, Bompas E, de Pinieux G, Gouin F, Nicolas N, Crombé A, Helfre S, Feydy A, Faruch M, Biau D. Chondrosarcomas: Multidisciplinary review and practical recommendations, on behalf of GroupOs. Bull Cancer 2025:S0007-4551(25)00078-5. [PMID: 40140320 DOI: 10.1016/j.bulcan.2024.07.013] [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: 05/12/2024] [Revised: 07/28/2024] [Accepted: 07/31/2024] [Indexed: 03/28/2025]
Abstract
Chondrosarcomas are rare tumors occurring in middle age and older adults, defined by malignant cartilaginous matrix-producing neoplasms. Chondrosarcomas represent a heterogeneous group of tumors with diverse characteristics, management strategies and prognosis. The aim is to establish recommendations to support optimal practice for the diagnosis and treatment of chondrosarcomas within the framework of an expert group at the request of GroupOs and the French Sarcoma Group. The recommendations were developed by a multidisciplinary working and underwent thorough proofreading. The level of evidence in scientific literature and the grading of recommendations by the French Haute Autorité de santé (HAS) were taken into account. Key recommendations cover: (i) diagnosis, management and follow-up enchondromatosis; (ii) initial assessment, diagnosis and staging of cartilaginous tumor; (iii) management of low-grade, clear cell and high-grade, localized resectable chondrosarcomas; (iv) indications for radiotherapy in chondrosarcomas; (v) management of locally advanced and metastatic disease; (vi) management of mesenchymal chondrosarcomas. Surgical resection at a specialized center remains the mainstay for localized chondrosarcomas management, tailored to grade and anatomical location. Limited evidence supports the use of neoadjuvant or adjuvant treatment in chondrosarcomas, except in mesenchymal chondrosarcomas. For patients with dedifferentiated chondrosarcomas, neo or adjuvant treatment with osteosarcoma-like regimens may be proposed. In cases of recurrence or metastasis, local treatment should be prioritized or participation in clinical trials including new targeted or immune therapies should be considered. This article presents consensus recommandations from adult and pediatric sarcoma experts of various disciplines on the practical management of chondrosarcomas patients.
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Affiliation(s)
- Pascaline Boudou-Rouquette
- Department of Medical Oncology, Cochin Hospital, Paris Cancer Institute CARPEM, AP-HP, 75014 Paris, France.
| | - Nadège Corradini
- Department of Pediatric Oncology, Pediatric Haematology and Oncology Institute, Léon-Bérard Centre, Lyon, France
| | | | - Frédérique Larousserie
- Department of Pathology, Cochin Hospital, Paris Cancer Institute CARPEM, AP-HP, Université Paris Cité, Paris, France
| | | | - Aude Marie Cardine
- Department of Pediatric Hematology and Oncology, Rouen University Hospital, Rouen, France
| | | | - Emmanuelle Bompas
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Site René Gauducheau, Saint-Herblain, France
| | | | - François Gouin
- Department of Surgical Oncology, Léon-Bérard Centre, Lyon, France
| | | | - Amandine Crombé
- Department of Musculoskeletal Radiology, Pellegrin University Hospital, Bordeaux University, 33000 Bordeaux, France
| | - Sylvie Helfre
- Institut Curie, Department of Radiation Oncology, Paris, France
| | - Antoine Feydy
- Department of Musculoskeletal Radiology, Cochin Hospital, AP-HP, Université Paris Cité, Paris, France
| | - Marie Faruch
- Department of Musculoskeletal Radiology, hôpital Pierre-Paul-Riquet, Toulouse, France
| | - David Biau
- Université Paris Cité, INSERM U1153, AP-HP, Hôpital Cochin, Service de chirurgie orthopédique, Paris, France
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5
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Paudel A, Chattopadhyay P, Rose B, Watson A, D’Amato G, Trent J, Bialick S, Jonczak E. Systemic Treatment in Soft Tissue Sarcomas: Are We Making a Difference? Cancers (Basel) 2025; 17:889. [PMID: 40075735 PMCID: PMC11898467 DOI: 10.3390/cancers17050889] [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: 02/05/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
Soft tissue sarcomas [STSs] are rare tumors of mesodermal origin that arise in diverse tissues such as muscles, fat, and nerves. There are over 100 subtypes of STS, each with distinct clinical behaviors and responses to treatment. Recent advances in treatment have moved towards histology-specific approaches, emphasizing the integration of pathological, immunohistochemical, and molecular features to guide treatment. Localized STS is primarily treated with surgery, often supplemented by neoadjuvant or adjuvant radiation and/or chemotherapy. However, about half of patients with localized disease will progress to an advanced stage, which is typically managed with systemic therapies including anthracycline-based chemotherapy such as doxorubicin or epirubicin. Despite these treatments, the survival rates for most subtypes of advanced metastatic STS remain relatively low. While anthracycline-based chemotherapy remains the mainstay of treatment, ongoing research into the biology of STSs is enhancing our understanding and approach to these complex tumors with an expansion beyond chemotherapy to include targeted therapy and immunotherapy to improve response rates and survival outcomes. This review focuses on STS other than gastrointestinal stromal tumors [GISTs], examines the current systemic treatment strategies, highlights recent advances, and explores future directions in the systemic therapy of sarcoma patients.
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Affiliation(s)
- Amrit Paudel
- Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; (A.W.); (G.D.); (J.T.); (S.B.)
| | - Priya Chattopadhyay
- Department of Internal Medicine, Jackson Health System, University of Miami, Miami, FL 33136, USA; (P.C.); (B.R.)
| | - Brandon Rose
- Department of Internal Medicine, Jackson Health System, University of Miami, Miami, FL 33136, USA; (P.C.); (B.R.)
| | - Aleksandra Watson
- Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; (A.W.); (G.D.); (J.T.); (S.B.)
| | - Gina D’Amato
- Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; (A.W.); (G.D.); (J.T.); (S.B.)
| | - Jonathan Trent
- Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; (A.W.); (G.D.); (J.T.); (S.B.)
| | - Steven Bialick
- Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; (A.W.); (G.D.); (J.T.); (S.B.)
| | - Emily Jonczak
- Department of Medicine, Division of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; (A.W.); (G.D.); (J.T.); (S.B.)
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6
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Celayir A, Elibollar C, Demirdas AB, Sahin E, Onenerk AM, Botanlioglu H. A Rare Case of Low-Grade Bilateral Proximal Humerus Chondrosarcomas Managed With Staged Curettage and Cementation. Cureus 2025; 17:e80854. [PMID: 40255759 PMCID: PMC12007974 DOI: 10.7759/cureus.80854] [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] [Accepted: 03/18/2025] [Indexed: 04/22/2025] Open
Abstract
Low-grade chondrosarcomas are rare malignant cartilaginous tumors with slow growth and low metastatic potential. Bilateral involvement, especially in the proximal humerus, is an exceedingly rare presentation. This report discusses a 45-year-old female patient who presented with intermittent left shoulder pain and was subsequently found to have bilateral proximal humeral masses on imaging. Bilateral contrast-enhanced MRI suggested a diagnosis of enchondroma or low-grade chondrosarcoma. The patient underwent curettage and cementation, first on the left side, followed by the right side four months later. Pathological analysis of the left lesion confirmed low-grade chondrosarcoma. During the second surgery, a frozen section revealed atypical chondromatous cells, with final pathology also supporting the diagnosis of low-grade chondrosarcoma. This case underscores the importance of careful diagnostic evaluation, including imaging and histopathological assessment, to differentiate low-grade chondrosarcoma from enchondroma. The multidisciplinary approach facilitated timely treatment, emphasizing the efficacy of curettage and cementation in managing these rare bilateral lesions while preserving function.
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Affiliation(s)
- Arın Celayir
- Department of Orthopaedics and Traumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, TUR
| | - Cansu Elibollar
- Department of Orthopaedics and Traumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, TUR
| | - Ahmet Burak Demirdas
- Department of Orthopaedics and Traumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, TUR
| | - Erdem Sahin
- Department of Orthopaedics and Traumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, TUR
| | - Ayse Mine Onenerk
- Department of Pathology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, TUR
| | - Huseyin Botanlioglu
- Department of Orthopaedics and Traumatology, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, TUR
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7
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Michaeli O, Kim SY, Mitchell SG, Jongmans MCJ, Wasserman JD, Perrino MR, Das A, MacFarland SP, Scollon SR, Greer MLC, Sobreira N, Gallinger B, Lupo PJ, Malkin D, Schneider KW, Schultz KAP, Foulkes WD, Woodward ER, Stewart DR. Update on Cancer Screening in Children with Syndromes of Bone Lesions, Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome, and Other Rare Syndromes. Clin Cancer Res 2025; 31:457-465. [PMID: 39601780 PMCID: PMC11790369 DOI: 10.1158/1078-0432.ccr-24-2171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 10/27/2024] [Accepted: 11/26/2024] [Indexed: 11/29/2024]
Abstract
The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for health care professionals. The 2023 American Association for Cancer Research Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection and intervention and reduce morbidity associated with such neoplasms. In this article, we review several of the rare conditions discussed in this workshop. Ollier disease and Maffucci syndrome are enchondromatoses (disorders featuring benign bone lesions) with up to 50% risk of malignancy, including chondrosarcoma. These patients require surveillance with baseline whole-body MRI and routine monitoring of potential malignant transformation of bony lesions. Hereditary multiple osteochondromas carry a lower risk of chondrosarcoma (<6%) but still require lifelong surveillance and baseline imaging. Related syndromes of benign bone lesions are also described. Hereditary leiomyomatosis and renal cell carcinoma syndrome, associated with fumarate hydratase pathogenic variants, is discussed in detail. Surveillance for renal cell carcinoma in pediatric age is recommended, as well as prompt intervention when a lesion is detected. Schinzel-Giedion syndrome and Rubinstein-Taybi syndrome are described for their associated malignancies and other complications, as well as expert consensus on the need for childhood cancer surveillance. Clinical recommendations, including imaging modalities and frequency of screenings, are proposed and are tailored to each syndrome's age-specific tumor risk profile. In all syndromes, patients and their families should be educated about the potential malignancy risk and advised to seek medical care for rapid growth of a mass, persistent pain, or other unexplained symptoms.
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Affiliation(s)
- Orli Michaeli
- Division of Hematology/Oncology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel
| | - Sun Young Kim
- Division of Human Genetics, Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH, United States
| | - Sarah G. Mitchell
- Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Atlanta, Georgia, United States
| | - Marjolijn C. J. Jongmans
- Princess Máxima Center for Pediatric Oncology, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jonathan D. Wasserman
- Division of Endocrinology, The Hospital for Sick Children / Department of Paediatrics, University of Toronto, Toronto, Canada
| | - Melissa R. Perrino
- Department of Oncology, St Jude Children’s Research Hospital, Memphis, Tennessee, United States
| | - Anirban Das
- Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Canada
| | - Suzanne P MacFarland
- Division of Oncology, The Children’s Hospital of Philadelphia, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Sarah R Scollon
- Department of Pediatrics, Division of Hematology/Oncology, Texas Children’s Cancer and Hematology Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas, United States
| | - Mary-Louise C. Greer
- Department of Diagnostic and Interventional Radiology, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Nara Sobreira
- McKusick-Nathans Department of Genetic Medicine Johns Hopkins University, Baltimore, MD, United States
| | - Bailey Gallinger
- Clinical and Metabolic Genetics, The Hospital for Sick Children. Toronto, ON. Canada. Department of Molecular Genetics, The University of Toronto. Toronto, ON. Canada
| | - Philip J. Lupo
- Division of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States
| | - David Malkin
- Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Canada
| | - Kami Wolfe Schneider
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Children’s Hospital Colorado, Aurora, CO
| | - Kris Ann P. Schultz
- International Pleuropulmonary Blastoma/DICER1 Registry, Cancer and Blood Disorders, Children’s Minnesota, Minneapolis, MN
| | | | - Emma R Woodward
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester Centre for Genomic Medicine, Manchester, United Kingdom
| | - Douglas R. Stewart
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD; United States
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8
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Yadav AK, Panchal S, Gawhale S, Wadia F. Deformity Correction and Limb Lengthening in Maffucci Syndrome - A Case Report. J Orthop Case Rep 2025; 15:55-59. [PMID: 39957938 PMCID: PMC11823836 DOI: 10.13107/jocr.2025.v15.i02.5226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/30/2024] [Indexed: 02/18/2025] Open
Abstract
Introduction ?Maffucci syndrome (MS) is a rare disorder with enchondromatosis associated with multiple hemangiomas in soft tissue and internal organs. Enchondromas in the long bone lead to limb length discrepancy, deformity, and pathological fractures that usually need corrective osteotomies and limb lengthening. Case Report A female in her late adolescence with MS presented with significant varus deformity of the distal femur and left lower limb shortening of 11.5 cm. She underwent an acute correction of the varus with a distal femur osteotomy and gradual femoral lengthening using a monolateral fixator. She sustained a pathological fracture through the regenerate, needing an intramedullary nail stabilisation during follow-up. At a 2-year follow-up, the patient was left with a residual shortening of 5 cm, corrected with a shoe raise. She could walk full weight bearing and independently with her day-to-day activities and function. Conclusion MS can present with significant limb length discrepancy and angular deformities. This case aims to inform clinicians of the diagnosis and management of this rare condition and highlight the importance of regular follow-up after complex surgery, and the impact coronavirus disease-19 lockdowns had on the inability of patients to do so.
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Affiliation(s)
| | | | - Sangeet Gawhale
- Grant Government Medical College and Sir JJ Group of Hospitals Mumbai, India
| | - Farokh Wadia
- Department of Paediatric Orthopaedics, Southampton Children’s Hospital, UK
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9
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Tlemsani C, Bougeard G, Gauthier-Villars M, Denizeau P, Winter S, Michot C, Baujat G, Bressac B, Adam de Beaumais T, Rouchaud A, Mihoubi-Bouvier F, Bourdeaut F, Brugières L, Leblanc T, Kasper E, Corradini N. Bone sarcomas and cancer predisposition syndromes. Bull Cancer 2025:S0007-4551(25)00017-7. [PMID: 39848894 DOI: 10.1016/j.bulcan.2024.10.014] [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: 06/30/2024] [Revised: 10/03/2024] [Accepted: 10/05/2024] [Indexed: 01/25/2025]
Abstract
Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GROUPOS and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists. For various bone sarcomas including osteosarcomas, chondrosarcomas and Ewing sarcomas, we delineate tumour presentation, management strategies, and follow-up within the context of cancer predisposition syndromes. The inherited predisposition syndrome, associated with germline TP53 variants, known as the Li-Fraumeni syndrome, is the most frequent implicated in osteosarcoma cases. Other cancer predisposition syndromes, such as RB1, RECQ or CDKN2A disorders in osteosarcomas and Ollier and Maffucci diseases in chondrosarcomas, are also recognized. Additionally, we discuss rarer cancer predisposition syndromes associated with bone sarcomas and suggest tailored treatment approaches in some cancer predisposition syndromes to mitigate severe toxicities or secondary oncological events. Furthermore, we emphasize the role of identification somatic molecular variations in identifying constitutional germline variants and describe national and international screening programs, reference networks and molecular tumour boards available for collegial and collaborative management discussion. This comprehensive review provides insights into the intricate interplay between genetic predisposition, tumour biology, and therapeutic interventions in bone sarcoma patients with cancer predisposition syndrome.
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Affiliation(s)
- Camille Tlemsani
- Department of Medical Oncology, Cochin Hospital, Paris Cancer Institute CARPEM, AP-HP, Université Paris Cité, Paris, France; Institut Cochin, Inserm U1016, CNRS UMR8104, CARPEM, Université Paris Cité, Paris, France
| | - Gaëlle Bougeard
- Department of Genetics, Inserm U1245, CHU de Rouen, Normandie Université, Université Rouen Normandie, 76000 Rouen, France
| | | | - Philippe Denizeau
- Department of Medical Genetic, Centre Hospitalier Universitaire de Rennes, Rennes, France
| | - Sarah Winter
- SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer) Institut Curie, PSL University, Paris, France
| | - Caroline Michot
- Reference Center for Skeletal Dysplasia, Necker-Enfants-Malades Hospital, AP-HP, 75015 Paris, France
| | - Geneviève Baujat
- Reference Center for Skeletal Dysplasia, Necker-Enfants-Malades Hospital, AP-HP, 75015 Paris, France
| | - Brigitte Bressac
- Biopathology Department, Inserm U1279, Gustave-Roussy, Paris-Saclay University, 94805 Villejuif, France
| | | | - Aymeric Rouchaud
- Department of Radiology (IMVOC), Clinique du Val d'Ouest, Écully, France
| | - Fadila Mihoubi-Bouvier
- Department of Diagnostic and Interventional Musculoskeletal Radiology, Cochin Hospital, Paris Cancer Institute CARPEM, AP-HP. Centre, Université Paris Cité, Paris, France
| | - Franck Bourdeaut
- SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer) Institut Curie, PSL University, Paris, France
| | - Laurence Brugières
- Department of Children and Adolescents Oncology, Gustave-Roussy Cancer, Paris-Saclay University, Villejuif, France
| | - Thierry Leblanc
- Service d'Immunologie et d'Hématologie Pédiatrique, Hôpital Universitaire Robert-Debré, AP-HP, Université Paris Cité, Paris, France
| | - Edwige Kasper
- Department of Genetics, Inserm U1245, CHU de Rouen, Normandie Université, Université Rouen Normandie, 76000 Rouen, France
| | - Nadège Corradini
- Department of Paediatric Oncology, Institut d'Haematologie et d'Oncologie Pédiatrique, Centre Léon-Bérard, Lyon, France.
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10
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Deshmukh S, Kelly C, Tinoco G. IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma. Target Oncol 2025; 20:13-25. [PMID: 39546097 DOI: 10.1007/s11523-024-01115-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/30/2024] [Indexed: 11/17/2024]
Abstract
Chondrosarcomas, a rare form of bone sarcomas with multiple subtypes, pose a pressing clinical challenge for patients with advanced or metastatic disease. The lack of US Food and Drug Administration (FDA)-approved medications underscores the urgent need for further research and development in this area. Patients and their families face challenges as there are no systemic therapeutic options available with substantial effectiveness. A significant number (50-80%) of chondrosarcomas have a mutation in the isocitrate dehydrogenase (IDH) genes. This review focuses on IDH-mediated pathogenesis and recent pharmacological advances with novel IDH inhibitors, explores their potential therapeutic value, and proposes potential future avenues for clinical trials combining IDH inhibitors with other systemic agents for chondrosarcomas.
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Affiliation(s)
- Shriya Deshmukh
- Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
| | - Ciara Kelly
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Gabriel Tinoco
- Division of Medical Oncology, The Ohio State University, Columbus, OH, USA.
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11
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Rabban JT, McCluggage WG. Ovarian Sex Cord-Stromal Neoplasms: An Overview of Molecular Events and How to Correlate Morphology With Molecular Findings. Adv Anat Pathol 2025; 32:70-84. [PMID: 39492459 DOI: 10.1097/pap.0000000000000474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
Since the discovery in 2009 that missence pathogenic variants/mutations in FOXL2 are extremely common in ovarian adult granulosa cell tumours, the last 2 decades have witnessed significant developments in our understanding of the molecular events underlying the pathogenesis of other ovarian sex cord-stromal tumours (SCSTs). In this review, we cover the molecular events in ovarian SCSTs and provide practical guidance to the reporting pathologist as to how and when molecular testing may be useful in diagnosis. We stress the need to correlate the morphology and molecular since most of the molecular events are not entirely specific for a particular tumour type and our knowledge is continually evolving with the elucidation of "new" molecular events. We also discuss that in some tumours, molecular testing is helpful in triaging the patient for genetic referral and germline testing since some of the molecular events may be germline in nature.
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Affiliation(s)
- Joseph T Rabban
- Department of Pathology, University of California San Francisco Medical Center, San Francisco, CA
| | - W Glenn McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom
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12
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Devins KM, Goldstein AM, French AV. A Rare Ovarian Mixed Sex Cord Stromal Tumor in a Patient with Ollier Disease: A Case Report. J Pediatr Adolesc Gynecol 2024; 37:629-631. [PMID: 39098546 DOI: 10.1016/j.jpag.2024.07.009] [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: 02/06/2024] [Revised: 07/04/2024] [Accepted: 07/26/2024] [Indexed: 08/06/2024]
Abstract
This is a case report of a 10-year-old with Ollier disease and an ovarian mass. Ollier disease, a rare disorder characterized by multiple enchondromas resulting in bone deformities, has been occasionally associated with ovarian juvenile granulosa cell tumor. This patient developed signs of precocious puberty and was found to have an ovarian tumor; however, pathology revealed a mixed sex-cord stromal tumor with components of juvenile granulosa and Sertoli-Leydig cell tumor. Tumor genomic testing revealed an IDH1 mutation. Mixed sex-cord stromal tumors of this type, also called "gynandroblastomas," have been associated with DICER1 mutations and DICER1 tumor predisposition syndrome but never with Ollier disease. Our findings expand the known spectrum of syndromic associations with this tumor type, with implications for tumor screening.
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Affiliation(s)
- Kyle M Devins
- Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
| | - Allan M Goldstein
- Department of Pediatric Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts
| | - Amanda V French
- Department of Obstetrics & Gynecology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts.
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13
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Wang WJ, Chen PL, Shao HZ. Blue rubber blister nevus syndrome: A case report. World J Gastrointest Surg 2024; 16:3584-3589. [PMID: 39649196 PMCID: PMC11622090 DOI: 10.4240/wjgs.v16.i11.3584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 09/05/2024] [Accepted: 09/25/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Blue rubber blister nevus syndrome (BRBNS) is a congenital, rare disease characterized by venous malformations of the skin and internal organs, affecting all systems throughout the body. The pathogenesis is unknown. There is no consensus on the treatment of BRBNS. Most of the previously reported cases were mild to moderate with a good prognosis, and this case was a critically ill patient with severe gastrointestinal hemorrhage, disseminated intravascular coagulation (DIC), and severe joint fusion that was different from previously reported cases. CASE SUMMARY An 18-year-old man with early onset of BRBNS in early childhood is reported. He presented with recurrent melena and underwent malformed phlebectomy and partial jejunectomy and ileal resection. The patient had melena before and after surgery. After active treatment, the patient's gastrointestinal bleeding improved. This was a case of atypical BRBNS with severe gastrointestinal bleeding and severe joint fusion, which should be differentiated from other serious joint lesions and provide clinicians with better understanding of this rare disease. CONCLUSION This case of critical BRBNS with gastrointestinal hemorrhage, DIC and severe joint fusion provides further understanding of this rare disease.
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Affiliation(s)
- Wen-Jing Wang
- Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
- Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Henan University, Zhengzhou 450003, Henan Province, China
| | - Pei-Li Chen
- Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
- Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Henan University, Zhengzhou 450003, Henan Province, China
| | - Huan-Zhang Shao
- Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
- Department of Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Henan University, Zhengzhou 450003, Henan Province, China
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14
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Mandonnet E, Funck-Brentano T, Hugnot JP, Touat M. Spectrum of IDH-mutant tumors in Ollier-Maffucci disease: the triple interaction theory. Orphanet J Rare Dis 2024; 19:434. [PMID: 39587599 PMCID: PMC11587773 DOI: 10.1186/s13023-024-03457-7] [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: 10/17/2023] [Accepted: 11/11/2024] [Indexed: 11/27/2024] Open
Abstract
We propose to refine our understanding of the pathophysiology underlying the tumor spectrum observed in patients with Ollier disease (OD) and Maffucci syndrome (MS). On one hand, assuming that all IDH-mutated tumors (as well as enchondromas) observed in OD-MS patients derive from one IDH-mutant cell giving rise to different lineages, the observation of different tumors arising in organs deriving from the neuroectoderm, mesoderm and endoderm points towards a very early post-zygotic event for the IDH mutation. To explain then that the spectrum of IDH-mutated tumors is restricted to some types of tumors, we propose the following hypothesis: - First, we posit that not every mutated cell of the lineage will "express" the IDH mutant phenotype. This can be due i/ to the disappearance in some tissue of the IDH-mutated clone due to negative selection pressure later in embryo development ii/ to the lack of expression of the IDH1 protein in specific cell types iii/ to a functional cell state not leading to the accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) in that tissue/organ. - Second, generalizing the recent understanding of the gliomagenesis in the general population bearing the rs55705857 G-allele variant at 8q24.21, we postulate that OD-MS patients with an inheritable predisposing single nucleotide polymorphism (SNP) are more likely to develop a malignancy, with a specific SNP for each kind of tumor/organ. In summary, our theory provides a new understanding of IDH-mutated tumors in OD-MS patients, as arising from the triple interaction within the same cell of a developmental defect (the somatic mutation that occurs early during the embryogenesis), an organ-specific functional state "expressing" the IDH mutation and leading to an accumulation of D-2HG, and an inheritable predisposing factor (a risky SNP, also specific to each organ). We discuss how this theory could guide future research in OD-MS patients and, more generally, in patients harboring sporadic IDH-mutated tumors.
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Affiliation(s)
- Emmanuel Mandonnet
- Department of Neurosurgery, Lariboisière Hospital, AP-HP, 2 rue Ambroise Paré, Paris, 75010, France.
- Frontlab, CNRS UMR 7225, INSERM U1127, Paris Brain Institute (ICM), Paris, France.
- Université Paris Cité, Paris, France.
| | - Thomas Funck-Brentano
- Department of Rheumatology, Lariboisière Hospital, APHP.Nord, Université Paris Cité, Paris, France
- Université Paris Cité, Inserm U1132, BIOSCAR, Paris, F-75010, France
| | - Jean-Philippe Hugnot
- Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, 34091, France
| | - Mehdi Touat
- Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neuro-oncologie, Paris, France
- Department of Neurology, Brigham and Women's Hospital, Boston, USA
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15
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Biz C, Angelini A, Fantoni I, Cerchiaro M, Longhi V, Ruggieri P. Benign bone and soft tissue tumors of the foot. EFORT Open Rev 2024; 9:1060-1076. [PMID: 39513737 PMCID: PMC11619725 DOI: 10.1530/eor-22-0116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2024] Open
Abstract
Tumors of the foot are a heterogeneous group of neoplasms that either affect soft tissues or bone, with a predominance being benign. Mistakes in the diagnosis of neoplastic conditions are common. A correct diagnostic approach supported by radiological and histological examination is mandatory. In this review, we highlight current standards in diagnosis, clinicopathological presentation, and imaging features.
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Affiliation(s)
- Carlo Biz
- Department of Orthopedics and Orthopedic Oncology, University of Padova, Padova, Italy
| | - Andrea Angelini
- Department of Orthopedics and Orthopedic Oncology, University of Padova, Padova, Italy
| | - Ilaria Fantoni
- Department of Orthopedics and Orthopedic Oncology, University of Padova, Padova, Italy
| | - Mariachiara Cerchiaro
- Department of Orthopedics and Orthopedic Oncology, University of Padova, Padova, Italy
| | - Valentina Longhi
- Department of Orthopedics and Orthopedic Oncology, University of Padova, Padova, Italy
| | - Pietro Ruggieri
- Department of Orthopedics and Orthopedic Oncology, University of Padova, Padova, Italy
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16
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Funck-Brentano T, Cohen-Solal M, Ducray F, Mandonnet E. Clinical and radiological response of Maffucci related enchondromas to mutant IDH1 inhibitor Ivosidenib. Bone 2024; 188:117221. [PMID: 39097182 DOI: 10.1016/j.bone.2024.117221] [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: 03/08/2024] [Revised: 07/17/2024] [Accepted: 07/31/2024] [Indexed: 08/05/2024]
Abstract
Ollier Disease (OD) and Maffucci syndrome (MS) is a rare bone disorder that affects the growth and development of the bones, with an estimated prevalence of 1 in 100,000 people. It is associated with somatic mosaicism of isocitrate dehydrogenase-1 (IDH1) or 2 (IDH2) pathogenic variants. Ivosidenib is indicated for the treatment of acute myeloid leukemia and locally advanced or metastatic cholangiocarcinoma and is currently investigated in low-grade glioma with a susceptible isocitrate dehydrogenase-1 (IDH1) pathogenic variant, but its effects in patients with OD or MS are unknown. We here report the first case of a patient with MS who was treated with Ivosidenib for recurrent IDH-1 mutated glioma. Besides the stabilization of the tumor size, the patient observed significant improvement in his enchondromas that became stiffer, with reduced pain, and significant modification of the mineralization of the enchondromas observed on X-rays. This first case report provides hope for the medical management of patients suffering because of OD or MS. Future clinical research is urgently needed to evaluate long-term benefit risk profile of IDH inhibitors in these rare diseases.
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Affiliation(s)
- Thomas Funck-Brentano
- Department of Rheumatology, National Reference Center for Rare Bone Disease in Adults, Lariboisière Hospital, APHP.Nord, France; Inserm U1132, BIOSCAR, F-75010 Paris, Université Paris Cité, Paris, France.
| | - Martine Cohen-Solal
- Department of Rheumatology, National Reference Center for Rare Bone Disease in Adults, Lariboisière Hospital, APHP.Nord, France; Inserm U1132, BIOSCAR, F-75010 Paris, Université Paris Cité, Paris, France
| | - François Ducray
- Department of Neuro-oncology, Hospices Civils de Lyon, Lyon, France; LabEx Dev2CAN, Institut Convergence Plascan, Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR5286, Université de Lyon, Université Claude Bernard, France
| | - Emmanuel Mandonnet
- Department of Neurosurgery, Lariboisière Hospital, APHP.Nord, France; Frontlab, CNRS UMR 7225, INSERM U1127, Paris Brain Institute (ICM), Paris, France; Université Paris Cité, Paris, France
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17
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Boarini M, Romeo A, Banchelli F, Grippa E, Forni S, la Forgia MC, Scognamiglio D, Ferraris PC, Sangiorgi L. Nature-based interventions for individuals with rare skeletal disorders: evaluation of a 5-day sailing program on health-related quality of life. Sci Rep 2024; 14:26339. [PMID: 39487306 PMCID: PMC11530639 DOI: 10.1038/s41598-024-77934-1] [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: 04/30/2024] [Accepted: 10/28/2024] [Indexed: 11/04/2024] Open
Abstract
Individuals with rare skeletal disorders like Multiple Osteochondromas and Ollier Disease often experience physical and psychological burdens. Adventure therapy, with activities like sailing in outdoor settings, promotes personal growth and psychological well-being, potentially improving health-related quality of life (HRQoL). This study aimed to evaluate the impact of a sailing program on health-related quality of life and participant satisfaction in individuals with Multiple Osteochondromas and Ollier Disease. A quasi-experimental one-group pre-post design was employed, with HRQoL assessed using the EQ-5D® instrument and participant satisfaction measured via a feedback survey. Data were collected before and after the five-day sailing program conducted in the Mediterranean Sea in 2022 and 2023, involving participants diagnosed with Multiple Osteochondromas and Ollier Disease. Statistical analyses were performed using the Wilcoxon signed-rank test and McNemar's test for paired data. A significance level of p < 0.05 and p < 0.10 was considered. A total of 25 participants, predominantly male (52%), with a median age of 16 years (ranking from 11 to 31), were included in the study. The sailing program had mixed impact on HRQoL. Specifically, individuals who were female (p = 0.03), aged 16 and older (p = 0.04), with higher educational attainment (p = 0.10) or stronger self-management (p = 0.09), resilience (p = 0.01) and self-engagement (p = 0.09) skills experienced enhanced HRQoL. Conversely, other participants exhibited an increase in self-care difficulties (p = 0.02) and a trend towards worsening pain/discomfort (p = 0.38). Overall satisfaction with the program was high, with 90% of participants expressing satisfaction.This is the first study which examined HRQoL in Multiple Osteochondromas and Ollier Disease patients within an outdoor adventure therapy setting. Findings suggest that adventure therapy, integrated into healthcare strategies, may offer a valuable complement to conventional treatments for rare skeletal disorders. Future research, including randomized controlled trials, are necessary to confirm these results and develop robust interventions for improving the well-being in this population.
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Affiliation(s)
- Manila Boarini
- Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
| | - Andrea Romeo
- Associazione Conto Alla Rovescia-ACAR Aps, Roma, Italy
| | - Federico Banchelli
- Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | | | - Silvia Forni
- Associazione Conto Alla Rovescia-ACAR Aps, Roma, Italy
| | | | - Davide Scognamiglio
- Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | | | - Luca Sangiorgi
- Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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18
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Tzoumpa S, Nuñez J, Postigo-Mac Dowall M, Lopez-Ilasaca M, Bejar C. Multiple enchondromas and hobnail hemangiomas revealing a rare type of Maffucci syndrome. Int J Dermatol 2024; 63:1447-1449. [PMID: 38647156 DOI: 10.1111/ijd.17203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 04/25/2024]
Affiliation(s)
- Sofia Tzoumpa
- Department of Dermatology, Avicenne University Hospital, AP-HP, Sorbonne-Paris-Nord University, Bobigny, France
| | - Jeanette Nuñez
- Department of Dermatology, Goyeneche Hospital, Arequipa, Peru
| | | | - Marco Lopez-Ilasaca
- Center for Molecular Diagnostics, Lima, Peru
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Claudia Bejar
- Department of Dermatology, Avicenne University Hospital, AP-HP, Sorbonne-Paris-Nord University, Bobigny, France
- Department of Dermatology, Goyeneche Hospital, Arequipa, Peru
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19
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Corvino S, Somma T, Certo F, Bonomo G, Grasso E, Esposito F, Berardinelli J, Barbagallo G. Ollier Disease, Acute Myeloid Leukemia, and Brain Glioma: IDH as the Common Denominator. Cancers (Basel) 2024; 16:3125. [PMID: 39335096 PMCID: PMC11430233 DOI: 10.3390/cancers16183125] [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: 08/19/2024] [Revised: 09/08/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Ollier disease (OD), acute myeloid leukemia (AML), and brain glioma (BG) are three apparently completely different neoplasms in terms of histopathology, clinic, natural history, and management, but they can affect the same patient. This study aimed to identify the common molecular pathways involved in the pathogenesis of all three diseases and discuss their current and potential role as therapeutic targets. A detailed and comprehensive systematic literature review according to PRISMA guidelines on OD patients harboring BG and/or AML was made. In addition, the unique case of a patient affected by all three considered diseases has been added to our case series. Demographic, pathological, treatment, and outcome data were analyzed and discussed, mainly focusing on the molecular findings. Twenty-eight studies reported thirty-three patients affected by OD and BG, and only one study reported one patient with OD and AML, while only our patient harbored all three pathologies. The IDH R132H mutation was the only genetic alteration shared by all three pathologies and was simultaneously detected in enchondromas and brain glioma in 100% (3/3) of OD patients with BG and also in the neoplastic blood cells of the single patient hosting all three diseases. The IDH1-R132H gene mutation is the etiopathogenetic common denominator among three apparently different tumors coexisting in the same patient. The adoption of mutant-specific IDH1 inhibitor molecules could represent a potential panacea for these conditions in the era of targeted therapies. Further studies with larger clinical series are needed to confirm our results and hypothesis.
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Affiliation(s)
- Sergio Corvino
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, Università di Napoli "Federico II", 80131 Naples, Italy
| | - Teresa Somma
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, Università di Napoli "Federico II", 80131 Naples, Italy
| | - Francesco Certo
- Department of Neurosciences, Division of Neurosurgery, Policlinico "G. Rodolico-S. Marco", University Hospital, 95123 Catania, Italy
| | - Giulio Bonomo
- Department of Neurosciences, Division of Neurosurgery, Policlinico "G. Rodolico-S. Marco", University Hospital, 95123 Catania, Italy
| | - Erica Grasso
- Department of Neurosciences, Division of Neurosurgery, Policlinico "G. Rodolico-S. Marco", University Hospital, 95123 Catania, Italy
| | - Felice Esposito
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, Università di Napoli "Federico II", 80131 Naples, Italy
| | - Jacopo Berardinelli
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, Università di Napoli "Federico II", 80131 Naples, Italy
| | - Giuseppe Barbagallo
- Department of Neurosciences, Division of Neurosurgery, Policlinico "G. Rodolico-S. Marco", University Hospital, 95123 Catania, Italy
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20
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Watanabe G, Fujii Y, Hanaoka Y, Tanaka M, Iwaya M, Horiuchi T. [Malignant transformation of Ollier disease-related multiple glioma with IDH1 p.R132C mutation]. Rinsho Shinkeigaku 2024; 64:474-479. [PMID: 38897973 DOI: 10.5692/clinicalneurol.cn-001955] [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] [Indexed: 06/21/2024]
Abstract
A 21-year-old man who was diagnosed with Ollier disease at the age of 1 year developed incidental multiple gliomas at the age of 15 years. Subsequently, the multiple gliomas enlarged and the patient underwent three surgical removals. Genetic analysis revealed the IDH1 p.R132C mutation in the gliomas, and histopathology showed malignant transformation. Despite multimodality treatment, the gliomas could not be controlled, and the patient died at the age of 23 years. Ollier disease is a rare disease with IDH1/2 mutations and is often associated with gliomas. However, there are very few reports on genetic analysis of IDH1/2 mutations and long-term follow-up in Ollier disease-related gliomas. Genetic analysis of IDH mutations may contribute to the elucidation of its pathogenesis. The cross-departmental collaboration is required for long-term follow-up of Ollier disease-related gliomas.
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Affiliation(s)
- Gen Watanabe
- Department of Neurosurgery, Shinshu University School of Medicine
| | - Yu Fujii
- Department of Neurosurgery, Shinshu University School of Medicine
| | - Yoshiki Hanaoka
- Department of Neurosurgery, Shinshu University School of Medicine
| | - Miyuki Tanaka
- Department of Pediatrics, Shinshu University School of Medicine
| | - Mai Iwaya
- Department of Laboratory Medicine, Shinshu University Hospital
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21
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Salduz A, Bayram S, Bulakci M. Rare radiological manifestation of enchondromatosis in children: Columnar pattern: A retrospective cohort study. Medicine (Baltimore) 2024; 103:e39106. [PMID: 39058880 PMCID: PMC11272238 DOI: 10.1097/md.0000000000039106] [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: 02/29/2024] [Accepted: 04/25/2024] [Indexed: 07/28/2024] Open
Abstract
The columnar cartilage pattern is characterized by parallel aligned cartilage tissue columns related to the physis without matrix calcification separated by the surrounding osseous tissue. Usually, it is seen in patients with multiple enchondromas. The objective of this study was to elucidate the clinical and radiological features of this rare radiological pattern in the physis, which remains unfamiliar to most physician. We retrospectively evaluated the clinical features and imaging findings of 15 patients (9 men and 6 women) who have a columnar pattern with varied spectrum of enchondromatosis. On X-ray and computed tomography (CT) examination, all these lesions were seen as vertical or oblique oriented tubular zones, which have relatively low radiologic density compared with normal bone. The lesions have similar signal characteristics relative to epiphyseal cartilage plates, on T1W and T2W magnetic resonance images. Columnar pattern was observed in different appearances from one single column in one physis to multiple columns in multiple physis. The mean follow-up was 62 months (range: 36-96 months). The mean age was 9.7 (range: 4-14) years at the initial admission. Eight patients had 3 or less affected physis. Five patients had only one affected physis. We defined these patients' group who had up to 3 affected physis as "limited enchondromatosis with columnar pattern (LE-CP)." We observed that most of the columnar cartilage was turning into the normal bone via endochondral ossification. Based on our observations, the columnar pattern is a rare manifestation of the enchondromas. Columnar pattern, along with the related physis, acts as a normal endochondral ossification process, and surgery is not necessary unless there is a risk of fracture or severe deformity. Further awareness of this unique subset of patients may improve our understanding of the disease and lead to better patient outcomes. We have modified non-hereditarily enchondromatosis into 2 categories: limited enchondromatosis with the columnar pattern and multiple enchondromatosis. We believe that LE-CM reflects a developmental anomaly of the physis rather than a true neoplasia, and it acts as a normal endochondral ossification process. Level IV (case series).
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Affiliation(s)
- Ahmet Salduz
- Department of Orthopaedics and Traumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Serkan Bayram
- Department of Orthopaedics and Traumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Mesut Bulakci
- Department of Radiology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
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22
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Giżewska-Kacprzak K, Śliwiński M, Nicieja K, Babiak-Choroszczak L, Walaszek I. Macrodactyly. CHILDREN (BASEL, SWITZERLAND) 2024; 11:753. [PMID: 39062202 PMCID: PMC11274991 DOI: 10.3390/children11070753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/29/2024] [Accepted: 06/17/2024] [Indexed: 07/28/2024]
Abstract
Macrodactyly is a rare congenital limb difference manifesting as an overgrowth of one or more fingers or toes. The pathological process affects all tissues of the ray in the hand or foot. The enlargement can significantly alter the limb's appearance and impair its function. The role of a pediatrician is to distinguish isolated macrodactyly from syndromic conditions (including PIK3CA-Related Overgrowth Spectrum) or mimicking conditions to enable early interdisciplinary consultation and treatment planning. The psychological stigma associated with this often disfiguring condition necessitates support for patients and their family. We present a practical guide for physicians who might be the first to raise suspicion of macrodactyly and initiate further diagnostics to achieve adequate treatment and support for children and caregivers.
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Affiliation(s)
- Kaja Giżewska-Kacprzak
- Department of Pediatric and Oncological Surgery, Urology and Hand Surgery, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland; (M.Ś.)
| | - Maximilian Śliwiński
- Department of Pediatric and Oncological Surgery, Urology and Hand Surgery, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland; (M.Ś.)
| | - Karol Nicieja
- Department of Pediatric and Oncological Surgery, Urology and Hand Surgery, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland; (M.Ś.)
| | - Lidia Babiak-Choroszczak
- Department of Pediatric and Oncological Surgery, Urology and Hand Surgery, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland; (M.Ś.)
| | - Ireneusz Walaszek
- Department of Pediatric and Oncological Surgery, Urology and Hand Surgery, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej Street, 71-252 Szczecin, Poland; (M.Ś.)
- Department of Nursing, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, 48 Żołnierska St., 71-210 Szczecin, Poland
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23
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Vagher J, Mehrhoff CJ, Florou V, Maese LD. Genetic Predisposition to Sarcoma: What Should Clinicians Know? Curr Treat Options Oncol 2024; 25:769-783. [PMID: 38713268 DOI: 10.1007/s11864-024-01192-6] [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] [Accepted: 02/15/2024] [Indexed: 05/08/2024]
Abstract
OPINION STATEMENT Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.
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Affiliation(s)
- Jennie Vagher
- Department of Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA
| | - Casey J Mehrhoff
- Department of Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA
- Division of Hematology/Oncology, Primary Children's Hospital, University of Utah, 100 Mario Capecchi Dr, Salt Lake City, UT, 84113, USA
| | - Vaia Florou
- Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
| | - Luke D Maese
- Department of Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
- Division of Hematology/Oncology, Primary Children's Hospital, University of Utah, 100 Mario Capecchi Dr, Salt Lake City, UT, 84113, USA.
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24
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Velders BJ, Braun J, Oudeman MA, Regeer MV, van der Wal RJ, Hayashi J, Klautz RJ, Palmen M. Robotic mitral valve repair and resection of a pericardial cyst in Maffucci syndrome with sternal manifestations: A case report. JTCVS Tech 2024; 24:86-88. [PMID: 38835564 PMCID: PMC11145389 DOI: 10.1016/j.xjtc.2024.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/21/2023] [Accepted: 01/08/2024] [Indexed: 06/06/2024] Open
Affiliation(s)
- Bart J.J. Velders
- Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Jerry Braun
- Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
- Department of Cardiothoracic Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Maurice A.P. Oudeman
- Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
- Department of Cardiothoracic Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Madelien V. Regeer
- Center for Congenital Heart Disease Amsterdam Leiden (CAHAL), Leiden University Medical Center, Leiden, The Netherlands
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Jun Hayashi
- Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Robert J.M. Klautz
- Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
- Department of Cardiothoracic Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Meindert Palmen
- Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
- Department of Cardiothoracic Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands
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25
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Scognamiglio D, Boarini M, la Forgia MC, Grippa E, Forni S, Sergi A, Romeo A, Massa G, Sangiorgi L. Defining priorities in the transition from paediatric to adult healthcare for rare bone disease patients: a dialogic approach. Eur J Med Genet 2024; 67:104891. [PMID: 38040052 DOI: 10.1016/j.ejmg.2023.104891] [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: 06/30/2023] [Revised: 10/18/2023] [Accepted: 11/25/2023] [Indexed: 12/03/2023]
Abstract
The Italian patient association for Multiple Osteochondromas, Ollier Disease, and Maffucci Syndrome, Associazione Conto Alla Rovescia-ACAR Aps, conducted a mixed-methods study at its 2023 annual conference. The study included the Open Dialogue Approach and a feedback survey to identify the main priorities in the transitioning process from paediatric to adult healthcare for patients with Multiple Osteochondromas, Ollier Disease, and Maffucci Syndrome. The common needs identified by patients, families, caregivers, and healthcare professionals were coordination and continuity of care, patient empowerment and communication, social and practical support, and transition planning and support. This experience fostered a sense of collaboration and cooperation among stakeholders, helping to build trust and create a shared vision for improving the quality of care for these patients. Furthermore, it could be considered a starting point for other patient associations interested in using different approaches to identify the needs of their members and actively involve all stakeholders.
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Affiliation(s)
- D Scognamiglio
- A.C.A.R. Aps - Associazione Conto Alla Rovescia, Rome, Italy
| | - M Boarini
- Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
| | - M C la Forgia
- A.C.A.R. Aps - Associazione Conto Alla Rovescia, Rome, Italy
| | - E Grippa
- A.C.A.R. Aps - Associazione Conto Alla Rovescia, Rome, Italy
| | - S Forni
- A.C.A.R. Aps - Associazione Conto Alla Rovescia, Rome, Italy
| | - A Sergi
- SOC Monitoraggio e Programmazione Performance Clinico-assistenziale, Azienda USL Toscana Centro, Italy
| | - A Romeo
- A.C.A.R. Aps - Associazione Conto Alla Rovescia, Rome, Italy
| | - G Massa
- A.C.A.R. Aps - Associazione Conto Alla Rovescia, Rome, Italy
| | - L Sangiorgi
- Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
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26
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El Mandour J, Khouchoua S, Adjou N, El Haddad S, Allali N, Chat L. Ollier disease: A case report and literature review. Radiol Case Rep 2023; 18:3652-3656. [PMID: 37593331 PMCID: PMC10432136 DOI: 10.1016/j.radcr.2023.07.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/05/2023] [Accepted: 07/18/2023] [Indexed: 08/19/2023] Open
Abstract
Ollier disease is an uncommon disease characterized by several enchondromas and an asymmetric distribution of cartilage lesions, which can vary significantly in size, location, age, and gender. The primary symptom of this condition is a nonossifying chondrocyte mass or hamartomatous chondrocyte growth in the metaphysis of a short or long bone. Specific cases can progress to chondrosarcoma or osteosarcoma. X-ray is the most fundamental diagnostic technique for skeletal illnesses. In this article, we present a case of Ollier disease from Mother and Child Hospital IBN SINA, Rabat, Morocco.
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Affiliation(s)
- Jihane El Mandour
- Department of Radiology, Mother and Child Hospital, CHU IBN SINA, Rabat, Morocco
| | - Selma Khouchoua
- Department of Radiology, Mother and Child Hospital, CHU IBN SINA, Rabat, Morocco
| | - Nada Adjou
- Department of Radiology, Mother and Child Hospital, CHU IBN SINA, Rabat, Morocco
| | - Siham El Haddad
- Department of Radiology, Mother and Child Hospital, CHU IBN SINA, Rabat, Morocco
| | - Nazik Allali
- Department of Radiology, Mother and Child Hospital, CHU IBN SINA, Rabat, Morocco
| | - Latifa Chat
- Department of Radiology, Mother and Child Hospital, CHU IBN SINA, Rabat, Morocco
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27
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Ikeda H, Yamaguchi S, Ishi Y, Wakabayashi K, Shimizu A, Kanno-Okada H, Endo T, Ota M, Okamoto M, Motegi H, Iwasaki N, Fujimura M. Supratentorial multifocal gliomas associated with Ollier disease harboring IDH1 R132H mutation: A case report. Neuropathology 2023; 43:413-420. [PMID: 36942363 DOI: 10.1111/neup.12902] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 02/24/2023] [Accepted: 02/26/2023] [Indexed: 03/23/2023]
Abstract
Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.
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Affiliation(s)
- Hiroshi Ikeda
- Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Shigeru Yamaguchi
- Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Yukitomo Ishi
- Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan
| | | | - Ai Shimizu
- Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | | | - Takeshi Endo
- Department of Orthopedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Mitsutoshi Ota
- Department of Orthopedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Michinari Okamoto
- Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Hiroaki Motegi
- Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Norimasa Iwasaki
- Department of Orthopedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan
| | - Miki Fujimura
- Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan
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28
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Wang YP, Di WJ, Qin SL, Yang S, Wang Z, Xu YF, Han PF. A rare presentation of Maffucci syndrome: A case report and literature review. Exp Ther Med 2023; 26:435. [PMID: 37602309 PMCID: PMC10433447 DOI: 10.3892/etm.2023.12134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 04/28/2023] [Indexed: 08/22/2023] Open
Abstract
Maffucci syndrome is an extremely rare disease which can manifest symptoms as early as childhood. It is estimated that there have been <300 cases reported globally; however, this number is likely to be an underestimate. Maffucci syndrome is characterized by multiple enchondromas and soft tissue hemangiomas, which can cause growth and developmental malformations. In addition to bone deformities, pathological fractures and a loss of mobility, patients with Maffucci syndrome may develop secondary central chondrosarcoma and have a higher risk of developing non-skeletal malignant tumors, such as gliomas and mesenchymal ovarian tumors. The present study provides information for clinicians about this disease through the use of imaging, physical examinations, clinical manifestations and the treatment strategy used. There is need to summarize the existing cases of this disease around the world and produce an effective framework for the diagnosis, treatment and prevention of Maffucci syndrome, in order to better understand this disease. The present study reports on a 15-year-old male diagnosed with Maffucci syndrome. . Due to the risk of malignant tumor development in the absence of effective treatment, regular and careful observation through monitoring of tumor markers and imaging studies is important for patients with Maffucci syndrome. As cases of this disease are rare and case data is limited, it is difficult to create a clear treatment plan. There is an urgent need to establish a case database of Maffucci syndrome patients and explore its pathogenesis for early diagnosis, treatment and prevention of disease.
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Affiliation(s)
- Yue-Peng Wang
- Graduate School, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
| | - Wen-Jia Di
- Graduate School, Baotou Medical College of Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014040, P.R. China
| | - Shi-Lei Qin
- Department of Orthopaedics, Changzhi Yunfeng Hospital, Changzhi, Shanxi 046000, P.R. China
| | - Su Yang
- Graduate School, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
| | - Zhen Wang
- Department of Orthopaedics, Changzhi Yunfeng Hospital, Changzhi, Shanxi 046000, P.R. China
| | - Yun-Feng Xu
- Department of Orthopaedics, Changzhi Yunfeng Hospital, Changzhi, Shanxi 046000, P.R. China
| | - Peng-Fei Han
- Department of Orthopaedics, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
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29
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Zając W, Dróżdż J, Kisielewska W, Karwowska W, Dudzisz-Śledź M, Zając AE, Borkowska A, Szumera-Ciećkiewicz A, Szostakowski B, Rutkowski P, Czarnecka AM. Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials. Cancers (Basel) 2023; 15:3924. [PMID: 37568740 PMCID: PMC10417069 DOI: 10.3390/cancers15153924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/13/2023] Open
Abstract
Dedifferentiated chondrosarcoma (DDCS) is a rare subtype of chondrosarcoma, a primary cartilaginous malignant neoplasm. It accounts for up to 1-2% of all chondrosarcomas and is generally associated with one of the poorest prognoses among all chondrosarcomas with the highest risk of metastasis. The 5-year survival rates range from 7% to 24%. DDCS may develop at any age, but the average presentation age is over 50. The most common locations are the femur, pelvis humerus, scapula, rib, and tibia. The standard treatment for localised disease is surgical resection. Most patients are diagnosed in unresectable and advanced stages, and chemotherapy for localised and metastatic dedifferentiated DDCS follows protocols used for osteosarcoma.
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Affiliation(s)
- Weronika Zając
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
- Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Julia Dróżdż
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
- Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Weronika Kisielewska
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
- Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Weronika Karwowska
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
- Faculty of Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Monika Dudzisz-Śledź
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
| | - Agnieszka E. Zając
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
| | - Aneta Borkowska
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
| | - Anna Szumera-Ciećkiewicz
- Department of Pathology, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland;
| | - Bartłomiej Szostakowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
| | - Anna M. Czarnecka
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 Warsaw, Poland (M.D.-Ś.); (A.E.Z.); (A.B.); (B.S.); (P.R.)
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30
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Li Y, Ji T, Wang Q, Guo W. 99mTc-MDP bone scintigraphy-based growth evaluation and prediction of epiphysis around the knee: a study of paediatric limb salvage for malignant bone tumours. Clin Radiol 2023; 78:608-615. [PMID: 37308349 DOI: 10.1016/j.crad.2023.05.002] [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: 04/21/2022] [Revised: 02/13/2023] [Accepted: 05/02/2023] [Indexed: 06/14/2023]
Abstract
AIM To investigate the feasibility of bone scintigraphy in the assessment and prediction of bone growth potential after limb-salvage surgery in children with bone tumours. MATERIALS AND METHODS Fifty-five skeletally immature patients with primary bone malignancies in distal femur was enrolled. Thirty-two patients received epiphysis minimally invasive endoprosthesis (EMIE) reconstruction, seven received hemiarthroplasty, and 16 received adult-type rotation-hinged endoprosthesis (ATRHE) reconstruction. All enrolled patients underwent radiographic examination at regular intervals and followed-up for >12 months. The actual limb length discrepancy (LLDa) of the tibia was measured on the radiography image. The expected LLD of tibia (LLDp) was calculated according to multiplier method. The uptake ratio of the ipsilateral epiphysis to the contralateral epiphysis (Ri/c) was calculated at bone scintigraphy. The Ri/c value was accommodated in the formula of multiplier method for a modification. The difference and correlation between the modified expected LLD (LLDm), LLDp and LLDa were analysed. RESULTS The growth potential of ipsilateral epiphysis was reserved in all patients who underwent hemiarthroplasty and one fourth of EMIE reconstruction. The Ri/c values in the hemiarthroplasty endoprosthesis group were significantly higher than the EMIE and ATRHE groups. There was no significant difference in Ri/c values between the EMIE and ATRHE group. Data from the 26 patients who reached bone maturation showed that there was a significant difference between LLDp and LLDa. LLDm showed a higher correlation with LLDa than LLDp. CONCLUSION Bone scintigraphy is helpful to evaluate the growth potential of epiphysis after surgery. The multiplier method modified by Ri/c value improves prediction accuracy of bone growth.
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Affiliation(s)
- Y Li
- Department of Nuclear Medicine, Peking University People's Hospital, China
| | - T Ji
- Musculoskeletal Tumor Center, Peking University People's Hospital, China.
| | - Q Wang
- Department of Nuclear Medicine, Peking University People's Hospital, China.
| | - W Guo
- Musculoskeletal Tumor Center, Peking University People's Hospital, China
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31
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Băilescu I, Popescu M, Dumitrescu D, Mîndrilă I, Vișan O, Moraru MC, Bălan RM, Albulescu DM. Imaging Aspects of Enchondromas in Pediatric Patients. CURRENT HEALTH SCIENCES JOURNAL 2023; 49:457-466. [PMID: 38314207 PMCID: PMC10832875 DOI: 10.12865/chsj.49.03.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 08/25/2023] [Indexed: 02/06/2024]
Abstract
Enchondromas are benign tumors located primarily in long bones, some of which can be accidentally discovered during imaging exams conducted for other pathologies. These benign cartilaginous tumors are hard to differentiate from low grade chondrosarcomas, which require periodic follow ups. The purpose of this study was to identify the incidence of enchondromas in pediatric patients, to determine medical imaging criteria (Computed Tomography-CT and Magnetic Resonance Imaging-MRI) in order to differentiate enchondromas from other atypical cartilaginous tumors, and to identify a potential correlation between imaging aspects and clinical signs. The aim of this study was to review imaging findings of enchondromas in children.
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Affiliation(s)
- Iulia Băilescu
- Doctoral School, University of Medicine and Pharmacy of Craiova, Romania
| | - Mihai Popescu
- Department of Radiology and Medical Imaging, University Emergency County Hospital, Craiova, Romania
- Department of Radiology and Medical Imaging University of Medicine and Pharmacy of Craiova, Romania
| | - Daniela Dumitrescu
- Department of Radiology and Medical Imaging, University Emergency County Hospital, Craiova, Romania
- Department of Radiology and Medical Imaging University of Medicine and Pharmacy of Craiova, Romania
| | - Ion Mîndrilă
- Department of Anatomy, University of Medicine and Pharmacy of Craiova, Romania
| | - Oana Vișan
- Department of Radiology and Medical Imaging, University Emergency County Hospital, Craiova, Romania
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32
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Dabbas WF, Hiasat MY, Ibrahim B, Allababede R, Alkhaldi TA, Al Warawrah A, Nadi M. A Report of Two Simultaneous Different Skull Vault Boney Pathologies: An Extremely Rare Clinical Scenario. Cureus 2023; 15:e40248. [PMID: 37440816 PMCID: PMC10334685 DOI: 10.7759/cureus.40248] [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] [Accepted: 06/10/2023] [Indexed: 07/15/2023] Open
Abstract
Primary calvarial boney tumors are generally rare in clinical practice. Multiple primary skull neoplasms are less frequent, typically associated with genetic disorders or familial syndromes. Sporadic cases of multiple skull tumors are exceptionally rare. We present a unique scenario of a 32-year-old female patient who had two right-sided skull vault lesions, one located over the right parietal area and the other in the right retro-auricular region. The lesions exhibited different behaviors over several years. The workup revealed that the two skull lesions were of two pathologies. The standard academic approach for clinical analysis attributes the symptoms often to one pathological process until proven otherwise. This case highlights the significance of expanding the differential diagnoses and incites clinicians to consider multiple pathologies in specific clinical settings.
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Affiliation(s)
- Waleed F Dabbas
- Division of Neurosurgery, Department of Special Surgery, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, JOR
| | | | - Bilal Ibrahim
- Division of Neurosurgery, Department of Special Surgery, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, JOR
| | - Razan Allababede
- Division of Neurosurgery, Department of Special Surgery, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, JOR
| | - Tareq A Alkhaldi
- Division of Neurosurgery, Department of Special Surgery, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, JOR
| | - Ayah Al Warawrah
- Division of Neurosurgery, Department of Special Surgery, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, JOR
| | - Mustafa Nadi
- Division of Neurosurgery, Department of Special Surgery, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, JOR
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Ashirov N, Mammadinova I, Moldabekov A, Zhetpisbaev B, Teltayev D, Ryskeldiyev N, Akshulakov S. A Rare Co-Occurrence of Maffucci Syndrome and Astrocytoma with IDH1 R132H Mutation: A Case Report. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1056. [PMID: 37374260 DOI: 10.3390/medicina59061056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/14/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023]
Abstract
Background: Maffucci syndrome is a rare genetic disorder associated with the development of multiple enchondromas and soft tissue cavernous hemangiomas, as well as an increased risk of malignant tumors. Case Description: Here we report a case of Maffucci syndrome in a patient who presented with a giant left frontal lobe tumor. Molecular genetic analysis of the tumor revealed an isocitrate dehydrogenase (IDH) mutation p.R132H (c.395C>A) mutation in the IDH1 gene and a heterozygous duplication of the CDKN2A genes. Conclusions: The presence of an IDH1 mutation is notable because this mutation is frequently seen in glial tumors and other neoplasms, and its co-occurrence with Maffucci syndrome may represent a novel risk factor for the development of gliomas. This case underscores the importance of genetic testing in patients with Maffucci syndrome who present with central nervous system tumors, as well as the need for further research to understand the relationship between IDH1 mutations and the development of gliomas in this population.
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Affiliation(s)
- Nurali Ashirov
- Minimal Invasive Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
| | - Iroda Mammadinova
- Minimal Invasive Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
| | - Aidos Moldabekov
- Brain Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
| | - Berik Zhetpisbaev
- Department of Pathology, National Centre for Neurosurgery, Astana 010000, Kazakhstan
| | - Daniyar Teltayev
- Minimal Invasive Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
| | - Nurzhan Ryskeldiyev
- Brain Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
| | - Serik Akshulakov
- Minimal Invasive Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
- Brain Neurosurgery Department, National Centre for Neurosurgery, Astana 010000, Kazakhstan
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Zhang J, Hua R, Ma L, Liu C, Zhang Y, Lü X, Wang T, Wan N. Ovarian juvenile granulosa cell tumors with Ollier's disease in children with IDH1 gene somatic mutation. Front Endocrinol (Lausanne) 2023; 14:1093273. [PMID: 37324278 PMCID: PMC10265673 DOI: 10.3389/fendo.2023.1093273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 04/21/2023] [Indexed: 06/17/2023] Open
Abstract
Objective The aim of this study was to explore the symptoms, treatment, and pathogenesis of ovarian juvenile granulosa cell tumors with Ollier's disease in children. Methods From October 2019 to October 2020, clinical data were retrospectively analyzed for one case of ovarian juvenile granulosa cell tumors with Ollier's disease. Whole-exome sequencing and Sanger sequencing were used to detect gene mutation in ovarian tumor and chondroma tissue. NADP-dependent isocitrate dehydrogenase-1 (IDH1) and S6 ribosomal protein expression levels in cells transfected with wild-type or mutant plasmid were analyzed by Western blot. Results The 4-year-old female showed multiple skeletal deformities, bilateral breast development with chromatosis, and vulvar discharge. Sex hormone assay suggested that estradiol and prolactin were elevated, and the x-ray of limbs suggested enchondroma. Pelvic ultrasound and abdominal CT revealed a right ovarian solid mass. Pathologic examination of the right ovarian solid mass showed a juvenile granulosa cell type. A c.394C>T (p. Arg132Cys) mutation of the IDH1 gene was detected in both the ovarian juvenile granulosa cell tumors and enchondroma. Transfection of HeLa cells with either WT or Mut plasmid caused 4.46- or 3.77-fold overexpression of IDH1 gene compared to non-transfected control cells, respectively. R132C mutation inhibited the phosphorylation of S6 ribosomal protein, which is central to the mTOR pathway. Postoperatively, estradiol and prolactin levels fell to values normal for her age and bilateral breast gradual retraction. Conclusion The incidence of ovarian juvenile granulosa cell tumors with Ollier's disease in children may be caused by generalized mesodermal dysplasia; IDH1 gene mutation may play a facilitated role in this process. Surgical operation is the main treatment. We suggest that patients with ovarian juvenile granulosa cell tumors and Ollier's disease should undergo regular investigation.
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Affiliation(s)
- Jin Zhang
- Department of Pediatrics, Beijing Jishuitan Hospital, Beijing, China
| | - Renwu Hua
- Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine Center, The University of Hong Kong-Shenzhen, Shenzhen, China
| | - Lishuang Ma
- Department of General Surgery, Capital Institute of Pediatrics, Beijing, China
| | - Chao Liu
- Department of General Surgery, Capital Institute of Pediatrics, Beijing, China
| | - Yanxia Zhang
- Department of General Surgery, Capital Institute of Pediatrics, Beijing, China
| | - Xuemin Lü
- Department of Pediatric Orthopedics, Beijing Jishuitan Hospital, Beijing, China
| | - Tianren Wang
- Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine Center, The University of Hong Kong-Shenzhen, Shenzhen, China
| | - Naijun Wan
- Department of Pediatrics, Beijing Jishuitan Hospital, Beijing, China
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Mackel CE, Rosenberg H, Varma H, Uhlmann EJ, Vega RA, Alterman RL. Intracranial Metastasis of Extracranial Chondrosarcoma: Systematic Review With Illustrative Case. Brain Tumor Res Treat 2023; 11:103-113. [PMID: 37151152 PMCID: PMC10172009 DOI: 10.14791/btrt.2023.0003] [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: 01/16/2023] [Revised: 02/22/2023] [Accepted: 02/23/2023] [Indexed: 05/09/2023] Open
Abstract
BACKGROUND Cerebral chondrosarcoma metastases are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. We further present the first case with Maffucci syndrome. METHODS Three databases, PubMed, Embase, and Google Scholar, and crossed references were queried for cerebral chondrosarcoma metastases. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analyses were performed. RESULTS Fifty-six patients were included from 1,489 literature results. The average age at brain metastasis was 46.6±17.6 years and occurred at a median of 24±2.8 months from primary diagnosis. Primary tumor histology (dedifferentiated 5.0±1.5 months, mesenchymal 24±3.0 months, conventional 41±7.4 months, p<0.05) and grade (low grade 54±16.7 months vs. high-grade 10±6.4 months, p<0.001) correlated with time interval until brain metastasis. A multiple enchondromatosis syndrome occurred in 13.2% of cases. At time of brain metastases diagnosis, extracranial metastases were identified in 76.2% of cases. Median survival after the development of brain metastasis was 2.0±0.78 months with a 1-year survival of 10.0%. On regression analysis, surgery reduced brain metastasis mortality risk and radiation trended towards reduced mortality risk (surgery: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.064-0.763, p=0.017; radiation: HR 0.31, 95% CI 0.091-1.072, p=0.064). CONCLUSION We present a systematic review of cerebral chondrosarcoma metastases. Primary tumor histology and grade correlate with time until cerebral metastasis. Following cerebral metastasis, these tumors have poor prognosis and modestly benefit from surgery.
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Affiliation(s)
- Charles E Mackel
- Department of Neurosurgery, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, USA.
| | - Harry Rosenberg
- Department of Pathology, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, USA
| | - Hemant Varma
- Department of Pathology, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, USA
| | - Erik J Uhlmann
- Department of Neurology, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, USA
| | - Rafael A Vega
- Department of Neurosurgery, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, USA
| | - Ron L Alterman
- Department of Neurosurgery, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, USA
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Poll SR, Martin R, Wohler E, Partan ES, Walek E, Salman S, Groepper D, Kratz L, Cernach M, Jesus-Garcia R, Haldeman-Englert C, Choi YJ, Morris CD, Cohen B, Hoover-Fong J, Valle D, Semenza GL, Sobreira NLM. Disruption of the HIF-1 pathway in individuals with Ollier disease and Maffucci syndrome. PLoS Genet 2022; 18:e1010504. [PMID: 36480544 PMCID: PMC9767349 DOI: 10.1371/journal.pgen.1010504] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 12/20/2022] [Accepted: 11/01/2022] [Indexed: 12/13/2022] Open
Abstract
Ollier disease (OD) and Maffucci Syndrome (MS) are rare disorders characterized by multiple enchondromas, commonly causing bone deformities, limb length discrepancies, and pathological fractures. MS is distinguished from OD by the development of vascular anomalies. Both disorders are cancer predisposition syndromes with malignancies developing in ~50% of the individuals with OD or MS. Somatic gain-of-function variants in IDH1 and IDH2 have been described in the enchondromas, vascular anomalies and chondrosarcomas of approximately 80% of the individuals with OD and MS. To date, however, no investigation of germline causative variants for these diseases has been comprehensively performed. To search for germline causative variants, we performed whole exome sequencing or whole genome sequencing of blood or saliva DNA in 94 unrelated probands (68 trios). We found that 7 had rare germline missense variants in HIF1A, 6 had rare germline missense variants in VHL, and 3 had IDH1 variants including 2 with mosaic IDH1-p.Arg132His variant. A burden analysis using 94 probands assigned as cases and 2,054 unrelated individuals presenting no OD- or MS-related features as controls, found that variants in HIF1A, VHL, and IDH1 were all significantly enriched in cases compared to controls. To further investigate the role of HIF-1 pathway in the pathogenesis of OD and MS, we performed RNA sequencing of fibroblasts from 4 probands with OD or MS at normoxia and at hypoxia. When cultured in hypoxic conditions, both proband and control cells showed altered expression of a subset of HIF-1 regulated genes. However, the set of differentially expressed genes in proband fibroblasts included a significantly reduced number of HIF-1 regulated genes compared to controls. Our findings suggest that germline or early post-zygotic variants identified in HIF1A, VHL, and IDH1 in probands with OD and MS underlie the development of the phenotypic abnormalities in a subset of individuals with OD and MS, but extensive functional studies are needed to further confirm it.
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Affiliation(s)
- Sarah R. Poll
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Renan Martin
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Elizabeth Wohler
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Elizabeth S. Partan
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Elizabeth Walek
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Shaima Salman
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Daniel Groepper
- Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America
| | - Lisa Kratz
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Mirlene Cernach
- Universidade Metropolitana de Santos, Santos, São Paulo, Brazil
| | - Reynaldo Jesus-Garcia
- Department of Orthopedics-Oncology, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Chad Haldeman-Englert
- Mission Fullerton Genetics Center, Asheville, North Carolina, United States of America
| | - Yoon Jae Choi
- Department of Neurology, University of California, Irvine, California, United States of America
| | - Carol D. Morris
- Department of Orthopedic Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
- Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
| | - Bernard Cohen
- Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, Untied States of America
| | - Julie Hoover-Fong
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - David Valle
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Gregg L. Semenza
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Nara L. M. Sobreira
- McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
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Premalignant Conditions of Bone. JAAOS: GLOBAL RESEARCH AND REVIEWS 2022; 6:01979360-202210000-00004. [PMID: 36227850 PMCID: PMC9575816 DOI: 10.5435/jaaosglobal-d-22-00097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 07/29/2022] [Indexed: 01/10/2023]
Abstract
Development of malignancy is a multifactorial process, and there are multitude of conditions of bone that may predispose patients to malignancy. Etiologies of malignancy include benign osseous conditions, genetic predisposition, and extrinsic conditions. New-onset pain or growth in a previously stable lesion is that should concern for malignant change and should prompt a diagnostic workup for malignancy.
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Teodoreanu RN, Grosu-Bularda A, Liţă FF, Hodea FV, Enache V, Frunză A, Lăzărescu AL, Muraru D, Lascăr I, Hariga CS. Benign cartilaginous tumors of the hand, a five-year retrospective study. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2022; 63:625-632. [PMID: 36808197 PMCID: PMC10026922 DOI: 10.47162/rjme.63.4.04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
Abstract
Benign and malignant cartilaginous bone tumors of the hand are rare findings, however representing a particular pathology due to the capacity to induce significant functional impairment. Even though a large proportion of tumors of the hand and wrist are benign, these may present destructive characteristics, deforming adjacent structures until compromising function. The most appropriate surgical approach for most benign tumors is intralesional lesion resection. Malignant tumors often require wide excision, up to segment amputation to obtain tumor control. A five-year retrospective study was performed on patients admitted in our Clinic with benign cartilaginous tumors of the hand, in which 15 patients were admitted within this period, 10 presenting with enchondroma, four presenting with osteochondroma, and lastly one with chondromatosis. After clinical and imaging evaluation, all the aforementioned tumors were surgically removed. Definitive diagnosis for all bone tumors, either benign or malignant, was established by tissue biopsy and histopathological examination, dictating therapeutic strategy.
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Affiliation(s)
- Răzvan Nicolae Teodoreanu
- Clinic of Plastic Surgery and Reconstructive Microsurgery, Emergency Clinical Hospital Bucharest, Romania;
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Khan MT, Arooj S, Mukhtar MU, Raman R. Maffucci syndrome: Case report and review of diagnostic signs of the rare disease. Radiol Case Rep 2022; 17:3674-3677. [PMID: 35936883 PMCID: PMC9352800 DOI: 10.1016/j.radcr.2022.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/28/2022] [Accepted: 07/01/2022] [Indexed: 12/03/2022] Open
Abstract
Maffucci syndrome is a non-hereditary congenital condition that affects the skin and skeleton. Enchondromas (benign cartilage enlargements), bone abnormalities, and venous anomalies (hemangiomas) are all symptoms. Enchondromas occur as a result of mesodermal dysplasia and have the potential to become cancerous. They are most commonly found on the phalanges and long bones. Venous abnormalities commonly manifest themselves as soft lumps or tumors on the distal extremities. A 19-year-old boy presented with swellings on his fingers and left foot since the age of 5, along with a few bluish soft tissue swellings on his left heel. Multiple expansile lytic lesions and soft tissue swellings with phleboliths were seen on X-ray. Histology confirmed the diagnosis of hemangiomas and enchondromas. Soft tissue swellings were found to have hyper echoic areas, as well as modest marginal blood flow on Doppler, which could indicate hemangiomas. Maffucci syndrome was identified, and treatment with a multidisciplinary approach was initiated. Maffucci syndrome is a rare genetic illness reported in the literature less than 200 times. The enchondromas and hemangiomas have a strong link to malignant changes, with chondrosarcomas accounting for 30% of the associated malignancies. On X-ray, enchondromas are easily identified as osteolytic lesions with cortex thinning and endosteal scalloping while color Doppler ultrasound detects the presence of hemangiomas. Phleboliths are easily identified as small calcifications on X-rays. Radiographic examinations should be considered in patients presenting with bone or soft tissue swellings for an early diagnosis of Maffucci syndrome.
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Affiliation(s)
- Muhammad Tahir Khan
- Department of Radiology, Punjab Institute of Neurosciences, Lahore, Pakistan
- Corresponding author at: Room No: 3, Doctor's Hostel, Lahore General Hospital, Ferozpur road, Lahore, 54000 Pakistan.
| | - Sadaf Arooj
- Department of Radiology, Punjab Institute of Neurosciences, Lahore, Pakistan
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Murphey K, George PE, Pencheva B, Porter CC, Wechsler SB, Gambello MJ, Li H. Acute myeloid leukemia and dilated cardiomyopathy in a pediatric patient with D-2-hydroxyglutaric aciduria type I. Am J Med Genet A 2022; 188:2707-2711. [PMID: 35785415 DOI: 10.1002/ajmg.a.62891] [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: 03/07/2022] [Revised: 04/18/2022] [Accepted: 04/25/2022] [Indexed: 01/25/2023]
Abstract
D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare neurometabolic disease with two main subtypes, caused by either inactivating variants in D2HGDH (type I) or germline gain of function variants in IDH2 (type II), that result in accumulation of the same toxic metabolite, D-2-hydroxyglutarate. The main clinical features of both are neurologic, including developmental delay, hypotonia, and seizures. Dilated cardiomyopathy is a unique feature thus far only reported in type II. As somatic variants in IDH2 are frequently identified in several different types of cancer, including acute myeloid leukemia (AML), a link between cancer and this metabolic disease has been proposed; however, there is no reported cancer in patients with either type of D-2-HGA. Murine models have demonstrated how D-2-hydroxyglutarate alters metabolism and epigenetics, a potential mechanism by which this metabolite may cause cancer and cardiomyopathy. Here, we report the first case of both AML and dilated cardiomyopathy in a pediatric patient with D-2-HGA type I, who was treated with an anthracycline-free regimen. This report may expand the clinical spectrum of this rare metabolic disease and provide insight on long-term surveillance and care. However, this case is complicated by the presence of a complex chromosomal rearrangement resulting in a 25.5 Mb duplication of 1q41 and a 2.38 Mb deletion of 2q37.3. Thus, the direct causal relationship between D-2-HGA and leukemogenesis or cardiomyopathy warrants further scrutiny.
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Affiliation(s)
- Kristen Murphey
- Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Paul E George
- Aflac Cancer and Blood Disorders Center, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA.,Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Bojana Pencheva
- Aflac Cancer and Blood Disorders Center, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA.,Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Christopher C Porter
- Aflac Cancer and Blood Disorders Center, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA.,Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Stephanie Burns Wechsler
- Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.,Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA.,Sibley Heart Center Cardiology, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Michael J Gambello
- Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.,Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Hong Li
- Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.,Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, Atlanta, Georgia, USA
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Shen Y, Su L, Fan X, Wang D. Images in Vascular Medicine: Clinical and radiological features of Maffucci syndrome. Vasc Med 2022; 27:515-517. [PMID: 35903973 DOI: 10.1177/1358863x221101654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Yuchen Shen
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lixin Su
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xindong Fan
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Deming Wang
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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42
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Hamoudi C, Bouillet B, Martins A. Malignant transformation of a phalangeal enchondroma into a recurrent grade II chondrosarcoma requiring successive transcarpal amputations: a case report. Case Reports Plast Surg Hand Surg 2022; 9:179-184. [PMID: 35873925 PMCID: PMC9302012 DOI: 10.1080/23320885.2022.2099864] [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] [Received: 05/16/2022] [Accepted: 07/05/2022] [Indexed: 06/15/2023]
Abstract
We report a case of malignant transformation of a phalangeal enchondroma into a grade II chondrosarcoma requiring two successive transcarpal amputations owing to recurrence. Soft tissue defects were repaired using single-stage reconstruction with a posterior interosseous artery flap. The 2-year follow-up assessment was satisfactory and no recurrence was observed.
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Affiliation(s)
- Ceyran Hamoudi
- Department of Hand Surgery, SOS main, University hospital of Strasbourg, Strasbourg, France
| | - Benjamin Bouillet
- Hand, Peripheral Nerves, and Microsurgery Unit, SOS Main Auvergne, La Chataigneraie Hospital, Beaumont, France
| | - Antoine Martins
- Department of Hand Surgery, SOS main, University hospital of Strasbourg, Strasbourg, France
- Hand, Peripheral Nerves, and Microsurgery Unit, SOS Main Auvergne, La Chataigneraie Hospital, Beaumont, France
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Corvino S, Mariniello G, Corazzelli G, Franca RA, Del Basso De Caro M, Della Monica R, Chiariotti L, Maiuri F. Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors? Cancers (Basel) 2022; 14:cancers14143464. [PMID: 35884525 PMCID: PMC9324397 DOI: 10.3390/cancers14143464] [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: 06/08/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 01/27/2023] Open
Abstract
Background: Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of malignant transformation of enchondromas and of occurrence of other neoplasms. Methods: A wide literature review disclosed thirty cases of glioma associated with OD, most of them belonging to the pre-molecular era. Our own case was also included. Demographic, clinical, pathologic, molecular, management, and outcome data were analyzed and compared to those of sporadic gliomas. Results: Gliomas associated with OD more frequently occur at younger age, present higher rates of multicentric lesions (49%), brainstem localizations (29%), and significantly lower rates of glioblastomas (7%) histotype. The IDH1 R132H mutation was detected in 80% of gliomas of OD patients and simultaneously in enchondromas and gliomas in 100% of cases. Conclusions: The molecular data suggest a higher risk of occurrence of glioma in patients with enchondromas harboring the IDH1 R132H mutation than those with the IDH1 R132C mutation. Thus, we suggest considering the IDH1 R132H mutation in enchondromas of patients with OD as a predictive risk factor of occurrence of glioma.
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Affiliation(s)
- Sergio Corvino
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (G.M.); (G.C.); (F.M.)
- Correspondence: ; Tel.: +39-3927524046
| | - Giuseppe Mariniello
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (G.M.); (G.C.); (F.M.)
| | - Giuseppe Corazzelli
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (G.M.); (G.C.); (F.M.)
| | - Raduan Ahmed Franca
- Department of Advanced Biomedical Sciences, Section of Pathology, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (R.A.F.); (M.D.B.D.C.)
| | - Marialaura Del Basso De Caro
- Department of Advanced Biomedical Sciences, Section of Pathology, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (R.A.F.); (M.D.B.D.C.)
| | - Rosa Della Monica
- Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (R.D.M.); (L.C.)
| | - Lorenzo Chiariotti
- Department of Molecular Medicine and Medical Biotechnology, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (R.D.M.); (L.C.)
| | - Francesco Maiuri
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Neurosurgical Clinic, School of Medicine, University of Naples “Federico II”, 80131 Naples, Italy; (G.M.); (G.C.); (F.M.)
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Lv H, Jiang H, Zhang M, Luo H, Hong Z, Yang H, Xu W, Shen B, Zhang W, Qiu H, Zhu R. Maffucci syndrome complicated by giant chondrosarcoma in the left ankle with an IDH1 R132C mutation: a case report. World J Surg Oncol 2022; 20:218. [PMID: 35765075 PMCID: PMC9241289 DOI: 10.1186/s12957-022-02686-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 06/14/2022] [Indexed: 12/01/2022] Open
Abstract
Background Maffucci syndrome (MS) is a rare, nonhereditary congenital mesodermal dysplasia characterized by multiple enchondromas and hemangiomas, associated with an increased risk of developing malignant tumors. Given their rarity, the pathogenesis of these tumors has not been clarified, and there is no standard treatment. Case presentation We present a case of a 45-year-old man with MS to supplement the clinical manifestations and explore the molecular mechanism of MS. The patient underwent amputation surgery to inhibit tumor development and was diagnosed with MS with 1–2 grade giant chondrosarcoma in the left ankle. In addition, the whole exon analysis results revealed isocitrate dehydrogenase 1 (IDH1) R132C mutation in chondrosarcoma lesions but not in blood DNA. Conclusions This case report showed MS complicated by giant chondrosarcoma in the left ankle with an IDH1 R132C mutation, which is appropriate to monitor the development of MS pathology and other concomitant lesions. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02686-z.
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Affiliation(s)
- Haiyan Lv
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Hantao Jiang
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Minge Zhang
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Huarong Luo
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Zhenghua Hong
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Hai Yang
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Weiming Xu
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Bo Shen
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China
| | - Wei Zhang
- DIAN Diagnostics, Hangzhou, 310058, Zhejiang, China
| | - Hao Qiu
- DIAN Diagnostics, Hangzhou, 310058, Zhejiang, China
| | - Rangteng Zhu
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Road, Linhai, 317000, Zhejiang, China.
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Sharif B, Lindsay D, Saifuddin A. Update on the imaging features of the enchondromatosis syndromes. Skeletal Radiol 2022; 51:747-762. [PMID: 34302201 DOI: 10.1007/s00256-021-03870-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 07/12/2021] [Accepted: 07/14/2021] [Indexed: 02/02/2023]
Abstract
Ollier disease and Maffucci syndrome are the commonest enchondromatosis subtypes, arising from non-hereditary mutations in the IDH1 and IDH2 genes, presenting in childhood and being characterised by multiple enchondromas. Maffucci syndrome also includes multiple soft tissue haemangiomas. Aside from developing bony masses, osseous deformity and pathological fracture, ~ 40% of these patients develop secondary central chondrosarcoma, and there is increased risk of non-skeletal malignancies such as gliomas and mesenchymal ovarian tumours. In this review, we outline the molecular genetics, pathology and multimodality imaging features of solitary enchondroma, Ollier disease and Maffucci syndrome, along with their associated skeletal complications, in particular secondary chondrosarcoma. Given the lifelong risk of malignancy, imaging follow-up will also be explored. Metachondromatosis, a rare enchondromatosis subtype characterised by enchondromas and exostoses, will also be briefly outlined.
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Affiliation(s)
- Ban Sharif
- Imaging Department, Northwick Park Hospital, Harrow, UK.
| | - Daniel Lindsay
- Pathology Department, Royal National Orthopaedic Hospital, Stanmore, UK
| | - Asif Saifuddin
- Imaging Department, Royal National Orthopaedic Hospital, Stanmore, UK
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Sun Y, Fan X, Rao Y, Wang Z, Wang D, Yang X, Zheng L, Wen M, Cai R, Su L. Cell-free DNA from plasma as a promising alternative for detection of gene mutations in patients with Maffucci syndrome. Hereditas 2022; 159:4. [PMID: 35042566 PMCID: PMC8764769 DOI: 10.1186/s41065-022-00223-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/29/2021] [Indexed: 11/10/2022] Open
Abstract
Maffucci syndrome (MS, OMIM 166000) is an extremely unusual, nonhereditary, multisystemic disorder that is characterized with multiple enchondromas and vascular lesions, most of which are spindle cell hemangiomas. Complications of MS, such as bone deformities and dysfunction caused by enchondromas, usually increase during childhood and adolescence. Malignant transformation of enchondromas and other malignancies are the most severe complications. MS is caused by somatic mosaic IDH1/2 mutations, 65% of which are the IDH1 p.Arg132Cys variant. Due to its rarity, there is no international consensus for the most appropriate treatment option of MS. Here, we report a case of a female patient presenting with multiple enchondromas and spindle cell hemangiomas (SCHs) on bilateral hand and feet diagnosed as MS. A detailed clinical, pathological and genetic diagnosis of MS was rendered. Integrative Genomics Viewer (IGV) visualization of next-generation sequencing (NGS) data revealed the consistent detection of the low-frequency somatic IDH1 p.Arg132Cys mutation between SCH tissue and cystic blood-derived cfDNA. This is the first successful molecular diagnosis of MS complicated with SCH utilizing minimally invasive cfDNA techniques. We suggest that cfDNA sequencing could potentially be used as an alternative, reliable and sensitive method to identify molecular information for genetic diagnosis and for future targeted therapies of MS.
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Affiliation(s)
- Yi Sun
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Xindong Fan
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Yamin Rao
- Department of pathology, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Zhenfeng Wang
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Deming Wang
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Xitao Yang
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Lianzhou Zheng
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Mingzhe Wen
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Ren Cai
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
| | - Lixin Su
- Department of Interventional Therapy, Multidisciplinary Team of Vascular Anomalies, Shanghai Ninth People's hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
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Wangaryattawanich P, Agarwal M, Rath T. Imaging features of cartilaginous tumors of the head and neck. J Clin Imaging Sci 2022; 11:66. [PMID: 34992942 PMCID: PMC8720426 DOI: 10.25259/jcis_186_2021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/18/2021] [Indexed: 11/29/2022] Open
Abstract
There is a wide spectrum of head and neck cartilaginous lesions which include both neoplastic and nonneoplastic processes. Cartilaginous tumors of the head and neck are uncommon, posing a diagnostic challenge. Benign cartilaginous tumors that may occur in the head and neck include chondroma, chondroblastoma, chondromyxoid fibroma, osteochondroma, and synovial chondromatosis. Chondromesenchymal hamartoma is a rare non-neoplastic cartilaginous lesion that is included for the 1first time in the new WHO classification and radiologically can mimic a tumor. Malignant cartilaginous tumors include chondrosarcoma and chondroid variant of chordoma. Characteristic tumor locations, internal chondroid matrix calcification, and typical T2 hyperintense signal secondary to high-water content within the extracellular matrix of the hyaline cartilage are useful imaging features that narrow the differential diagnosis and help in diagnosing these diseases. This article presents a narrative review of the anatomy of the head and neck cartilaginous structures, discusses the current knowledge and imaging spectrum of benign and malignant cartilaginous tumors and tumor-like lesions of the head and neck.
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Affiliation(s)
- Pattana Wangaryattawanich
- Department of Radiology, Division of Neuroradiology, University of Washington School of Medicine, Seattle, Washington, United States
| | - Mohit Agarwal
- Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
| | - Tanya Rath
- Department of Radiology, Mayo Clinic Arizona, Phoenix, Arizona, United States
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Pennington Z, Ehresman J, Pittman PD, Ahmed AK, Lubelski D, McCarthy EF, Goodwin CR, Sciubba DM. Chondrosarcoma of the spine: a narrative review. Spine J 2021; 21:2078-2096. [PMID: 33971325 DOI: 10.1016/j.spinee.2021.04.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 01/19/2021] [Accepted: 04/28/2021] [Indexed: 02/03/2023]
Abstract
Chondrosarcoma is an uncommon primary bone tumor with an estimated incidence of 0.5 per 100,000 patient-years. Primary chondrosarcoma of the mobile spine and sacrum cumulatively account for less than 20% of all cases, most .commonly causing patients to present with focal pain with or without radiculopathy, or myelopathy secondary to neural element compression. Because of the rarity, patients benefit from multidisciplinary care at academic tertiary-care centers. Current standard-of-care consists of en bloc surgical resection with negative margins; for high grade lesions adjuvant focused radiation with ≥60 gray equivalents is taking an increased role in improving local control. Prognosis is dictated by lesion grade at the time of resection. Several groups have put forth survival calculators and epidemiological evidence suggests prognosis is quite good for lesions receiving R0 resection. Future efforts will be focused on identifying potential chemotherapeutic adjuvants and refining radiation treatments as a means of improving local control.
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Affiliation(s)
- Zach Pennington
- Department of Neurosurgery, Mayo Clinic, Rochester, MN USA 55905; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287.
| | - Jeff Ehresman
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287; Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ USA 85013.
| | - Patricia D Pittman
- Department of Neuropathology, Duke University School of Medicine, Durham, NC USA 27710
| | - A Karim Ahmed
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287
| | - Daniel Lubelski
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287
| | - Edward F McCarthy
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287
| | - C Rory Goodwin
- Department of Neurosurgery, Duke University School of Medicine, Durham, NC USA 27710
| | - Daniel M Sciubba
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD USA 21287; Department of Neurosurgery, Zucker School of Medicine at Hofstra, Long Island Jewish Medical Center and North Shore University Hospital, Northwell Health, Manhasset, NY USA 11030.
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Govalan R, Guindi M, Yang JD. Liver Mass in a Young Male With Ollier Disease. Gastroenterology 2021; 161:e4-e5. [PMID: 33812890 DOI: 10.1053/j.gastro.2021.03.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/18/2021] [Accepted: 03/23/2021] [Indexed: 12/02/2022]
Affiliation(s)
| | - Maha Guindi
- Department of Pathology and Laboratory Medicine
| | - Ju Dong Yang
- Department of Medicine; Comprehensive Transplant Center; Samuel Oschin Comprehensive Cancer Institute; Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California.
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Pediatric brain tumors as a developmental disease. Curr Opin Oncol 2021; 33:608-614. [PMID: 34431811 DOI: 10.1097/cco.0000000000000782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Brain tumors are the most frequent solid cancer in the pediatric population. Owing to the rarity of environmental clues about their origin, it is tempting to consider these neoplasms as developmental processes gone awry. Our review will explore the heuristic power of this hypothesis and the influence of these findings on the clinical management. RECENT FINDING A more accurate description of cancer predisposition syndrome has shown their frequent association with developmental abnormalities. Several genes involved in pediatric brain tumor oncogenesis are involved in developmental processes. Modeling of several pediatric brain tumor in cerebral organoids, mimicking embryonal stage of brain development, indicates that early events during brain development create the conditions necessary for their oncogenesis. SUMMARY The onset of multiple brain tumor types early in life suggests a functional relationship between brain development and oncogenesis. A growing body of evidence seems to support the hypothesis that some of the main developmental steps in the brain can be highjacked by the tumors during their initiation. Collaborations between neuroscientists and oncologists should provide room for improvement in the knowledge for these neoplasms.
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