Synovial Chondrosarcoma: a Single Institution Experience
Conditions: Synovial Chondrosarcoma
Sponsor: Istituto Ortopedico Rizzoli

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“Synovial chondrosarcoma: a single Institution experience” 
 
Study code SynoChondroS 
Sponsor’s Name and 
Address: 
Istituto Ortopedico Rizzoli 
Via di Barbiano 1/10 
40136 Bologna 
Italy 
Study 
Number/Version/Date: 
Vers 1.0  
16 May 2018 
Coordinating Center: IRCCS Istituto Ortopedico Rizzoli 
Pathology Unit 
Via Pupilli 1 
40136 Bologna, Italy 
Coordinating 
Investigator and 
address: 
Marco Gambarotti MD 
Phone: 051-6366.652 
Email: marco.gambarotti@ior.it 
Methodology: Experimental study with biological material 
(Single insitution case series review of clinical and 
histological data) 
Type: Academic 
 
Founding: None 
 
Principal Investigator 
Signature 
I confirm that I’ve read this protocol and I accept to run the study 
in compliance with what is stated in the protocol and with the 
ICh-GCP and all applicable law 
 
Marco Gambarotti MD 
 
Firma 
 
_________________________ 
 
 

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TABLE of CONTENTS 
Background 
 
 
 
 
 
 
 
 
 
pg. 3 
Objective of the study 
 
 
 
 
 
 
 
pg.  3 
Study design   
 
 
 
 
 
 
 
 
pg  3 
Population     
 
 
 
 
 
 
 
 
pg.  3 
Material and Methods   
 
 
 
 
 
 
 
pg.  4 
Statistics 
 
   
 
 
 
 
 
 
 
pg.  4 
Enrolment procedure   
 
 
 
 
 
 
 
pg.  4 
Data Collection            
  
 
 
 
 
 
 
pg.  4 
Informed Consent   
 
  
 
 
 
 
 
 
pg.  5 
Ethic and quality assurance   
 
 
 
 
 
 
pg.  5 
General principles for human biological material (HBM) collection 
 
pg.  6 
Confidentiality                                                                                       
 
 
pg.  6 
Publication of results                                                        
 
 
             pg.  7 
References 
                                                                                       
 
 
pg.  7 
 
 

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BACKGROUND 
Chondrosarcoma of the synovium (also called synovial chondrosarcoma) is an exceeding rare 
entity. It can arise de novo or as a malignant transformation of synovial chondromatosis. In the 
latter situation, synovial chondrosarcoma can arise on a pre-existing synovial chondromatosis or 
co-exhist with a synovial chondromatosis. The rate of malignant transformation of synovial 
chondromatosis is very rare (about 5% of cases), generally after several recurrences, many years 
after the first diagnosis. 
Several case report and review of synovial chondrosarcoma are described in the literature1-5. 
Radiologically, synovial chondrosarcomas may show aggressive features; however the differential 
diagnosis between synovial chondromatosis and synovial chonndrosarcoma can be challenging. 
Histologically, features in favour of malignancy are hypercellulrity, loss of clustering of the 
cnhondrocytes, myxoid change of the matrix, necrosis, and infiltration of bone and soft tissues 
with permeative margins5. 
Although the majority of synovial chondrosarcomas behave as low-grade conventional 
chondrosarcomas, metastasis can develop in about 29% of cases4. For this reason, a wide surgical 
treatment is recommended and the differential diagnosis with synovial chondromatosis is very 
important, as the latter is generally treated with a more conservatory surgical approach. 
OBJECTIVE OF THE STUDY  
The aim of the present study is to review all the cases with a diagnosis of synovial chondrosarcoma 
treated at the Rizzoli Institute from 1982, retrospectively examining all the clinical, radiological, 
and histological features of these tumors, in order to better understand their characteristics and 
to identify the best therapeutic approach. 
 
STUDY DESIGN 
This is single institution cases series review of histological, radiological and clinical data 
 
POPULATION 
Inclusion criteria 
1) Male and female patients treated at Rizzoli Institute from 01 January 1982 to 31 
December 2017 
2) Diagnosis of synovial chondrosarcoma 

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3) Age ≥ 18 years 
4) Histological slides / formalin-fixed paraffin-embedded tissue tumor (FFPE) blocks from 
archive available to perform the histology analysis 
5) Written informed consent prior to any study-specific analysis and/or data collection  
Exclusion criteria 
1) Patients with histological diagnosis different from synovial chondrosarcoma  
 
MATERIAL AND METHODS 
We will retrieve from the archives of the Rizzoli institute all the cases with a histological diagnosis 
of synovial chondrosarcoma.  
We aspect to find approximately ten cases.  
We will review all the medical records, radiological imaging, and histological slides of these cases.  
In all cases with enough available material, immunohistochemistry for IDH-1 and IDH-2 will be 
performed on FFPE material. IDH-1 and IDH-2 are positive in conventional chondrosarcomas. 
 
STATISTICS 
To the case series will be applied a descriptive statistic. 
 
ENROLLMENT PROCEDURE 
Patients considered eligible will be included in the study, after providing a written informed 
consent.  
Due to the high incidence of mortality of the disease under investigation, it would be possible that 
some eligible subjects will be deceased. 
 
DATA COLLECTION 
Clinical data will be retrieved by patient charts. 
A protocol-specific CRF reporting the results of the review will be provided. 
A CRF is required and should be completed for each included subject. 
 
 
 
 

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ETHICS AND QUALITY ASSURANCE 
The clinical trial protocol and its documents will be sent before initiating the study to the 
competent Authorities and Ethics Committees of each participating country for its approval. 
The responsible investigator will ensure that this study is conducted in agreement with either the 
most updated Declaration of Helsinki and all the international and local  laws that apply to clinical 
trials and to patient protection.  
The protocol has been written, and the study will be conducted according to the principles of the 
ICH Harmonized Tripartite Guideline for Good Clinical Practice  
(ref: http://www.emea.eu.int/pdfs/human/ich/013595en.pdf).  
 
INFORMED CONSENT 
All patients will be informed, by the investigator, of the aims of the study, the possible risks and 
benefits that will derive from the study participation.  
The Investigator must clearly inform that the patient is free to refuse participation in the study and 
that can withdraw consent at any time and for any reason.  
They will be informed as to the strict confidentiality of their patient data, but that their medical 
records may be reviewed for trial purposes by authorized individuals other than their treating 
physician.  
The informed consent procedure must conform to the ICH guidelines on Good Clinical Practice. 
This implies that "the written informed consent form should be signed and personally dated by the 
patient or by the patient's legally acceptable representative".   
The Investigator must also sign the Informed Consent form, and will keep the original at the site 
and a copy of the original must be handed to the patient.  
The competent ethics committee for each Institution participating to the study must validate local 
informed consent documents before the study can be opened. It will be emphasized that the 
participation is voluntary and that the patient is allowed to refuse further participation in the 
study whenever he/she wants. This will not prejudice the patient's subsequent care.  
Due to the high incidence of mortality of the disease under investigation, it would be possible that 
some potential eligible subjects will be deceased.  
 
 
 

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GENERAL PRINCIPLES FOR HUMAN BIOLOGICAL MATERIAL (HBM) COLLECTION 
Human biological material (HBM) collection involves the collection and storage of biological 
material, residual biological material or derivatives in compliance with ethical and technical 
requirements.  
Biological material (FFPE blocks of tumor sample) are already stored in the Bone Biobanks at 
Istituto Ortopedico Rizzoli Pathology Department. 
The biological material will be used and stored according with the sample characteristic and 
applicable regulation. 
 The  Istituto Ortopedico Rizzoli will have a designated person responsible for collection and 
will act as a communication point  
 The collected HBM should be documented, i.e. the amount remaining and its location. act 
as a communication point  
 IDH1 and IDH2 analysis will be performed the Pathological Anatomy dept. of the Treviso’s 
Hospital under Prof. Angelo Paolo Dei Tos responsability 
 
CONFIDENTIALITY 
In order to ensure confidentiality of clinical trial data as disposed the national and European 
applicable regulation, data will be only accessible for the trial Sponsor and its designees, for 
monitoring/auditing procedures, the Investigator and collaborators, the Ethics Committee of each 
corresponding site and the Health Authority. 
Investigator and the Institution will allow access to data and source documentation for 
monitoring, auditing, Ethic Committee revision and inspections of Health Authority, but 
maintaining at all times subject personal data confidentiality as specified in the “Directive 
95/46/EC of the European Parliament and of the Council of 24 October 1995”.  
 The Investigator must guarantee that patient anonymity is kept at all times and their identity 
must be protected from unauthorized persons and institutions.  
All patients included in the study will be identified with a numeric code, so that no identifiable 
personal data will be collected  (pseudo anonymization) 
The Investigator must have and conserve a patients’ inclusion registry where it figures the 
personal data of the patient: name, surname, address and corresponding identification code into 
the study, this register will be kept on the Investigator File. 
 

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PUBBLICATION OF RESULTS  
The results from this study will be published or shown at scientific conferences. The final 
publication of the study results will be written by the Principal Investigator. 
 
REFERENCES 
[1] Ng VY, Louie P, Punt S, Conrad EU. Malignant Transformation of Synovial Chondromatosis: A 
Systematic Review. Open Orthop J. 2017 May 31;11:517-524. 
[2] Biazzo A, Confalonieri N. Synovial chondrosarcoma. Ann Transl Med. 2016 Aug;4(15):280. 
[3] Zamora EE, Mansor A, Vanel D, Errani C, Mercuri M, Picci P, Alberghini M. Synovial 
chondrosarcoma: report of two cases and literature review. Eur J Radiol. 2009 Oct;72(1):38-43. 
[4] Campanacci DA, Matera D, Franchi A, Capanna R. Synovial chondrosarcoma of the hip: report 
of two cases and literature review. Chir Organi Mov. 2008 Dec;92(3):139-44. 
[5] Bertoni F, Unni KK, Beabout JW, Sim FH. Chondrosarcomas of the synovium.  Cancer. 1991 Jan 
1;67(1):155-62.