The results of this study must be interpreted with caution, as there are certain limitations. First, due to the retrospective study design this study might be subject to selection bias. In particular, about 30% of patients were lost to follow-up, i.e., phone contact or follow-up MRI was not possible. Further selection bias might be present, as included ECs were relatively small in size with a mean largest diameter at initial diagnosis of 23 mm. Larger EC were more likely to undergo primary resection since at the time of EC diagnosis, indication for surgical treatment was often made when EC was > 5 cm. Although the results might not be generalizable to larger ECs, the mean initial size of EC in this study is representative of the majority of all EC (1, 77, 83).
Another limitation arises from the small number of study participants, making it difficult to detailed statistical analyses about EC growth and the risk of malignant transformation. However, this sample has analyzed the longest average follow-up for EC reported so far and a very accurate measurement of change in EC size.
A further limitation of the study is that in some patients, the initial diagnostic imaging was performed on a 1.5T device, whereas the follow-up was performed on a 3T MRI device which influences the image quality and consequently an image analysis.
Finally, concerning secondary surgeries the pressure that the patient exerts on the orthopedic surgeon and vice versa concerning their subjective feeling (e.g., fear of malignant transformation, pain association with the tumor) might influence treatment decisions.
5 Conclusion
This study has shown that long-term imaging follow-up is justified for all EC, irrespective of initial lesion size, as suggested in the past. EC have shown unpredictable growth patterns, and if they increase in size, they progress slowly.
Thus, it seems reasonable to extend follow-up intervals to several years instead of annual or biannual follow-up. The absolute threshold values of size should also be critically assessed and redefined when deciding whether a lesion should be subjected to a follow-up check or not.
Secondary operations in EC are rare and, in our study, patients did not benefit from the operation. All lesions undergoing secondary surgeries were histologically confirmed as EC and if pain was indicated for surgery, the pain persisted after the operation. Therefore, a decision about secondary surgery should always be questioned critically and a conservative approach should be preferred.
MRI is the preferred imaging modality as it reliably detects features of progression of EC. The presence of solitary features of biological aggressiveness, such as endosteal scalloping, without clinical symptoms, does not require surgery but follow–up. This difficult distinction between EC and ACT/ CS1 results in a possible field of research. In this work, it was not always possible to conclusively clarify whether it is an EC or an ACT/ CS1. A further examination of this entity and the elaboration of additional reliable differentiation criteria would be worthwhile in clinical work.
When assessing EC, it is important to consider individual criteria such as anatomical localization, growth direction, and growth rate, which underlines the importance of multidisciplinary work.
6 References
1. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours of Soft Tissue and Bone. 5th ed. Lyon, France: IARC Press; 2020.
2. Mulligan ME. How to Diagnose Enchondroma, Bone Infarct, and Chondrosarcoma.
Curr Probl Diagn Radiol 2019; 48(3):262–73.
3. Pernick N. Enchondroma of long bones [PathologyOutlines.com website] [cited 2021 Apr 25]. Available from: URL:
https://www.pathologyoutlines.com/topic/bonechondromaenchondromaslongbones.ht ml.
4. Bovée JV, van Roggen JF, Cleton-Jansen AM, Taminiau AH, van der Woude HJ, Hogendoorn PC. Malignant progression in multiple enchondromatosis (Ollier's disease): an autopsy-based molecular genetic study. Hum Pathol 2000; 31(10):1299–
303.
5. Verdegaal SHM, Bovée JVMG, Pansuriya TC, Grimer RJ, Ozger H, Jutte PC et al.
Incidence, predictive factors, and prognosis of chondrosarcoma in patients with Ollier disease and Maffucci syndrome: an international multicenter study of 161 patients.
Oncologist 2011; 16(12):1771–9.
6. Suster D, Hung YP, Nielsen GP. Differential Diagnosis of Cartilaginous Lesions of Bone. Arch Pathol Lab Med 2020; 144(1):71–82.
7. Mirra JM, Gold R, Downs J, Eckardt JJ. A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases. Clin Orthop Relat Res 1985; (201):214–37.
8. Andreou D, Gilg MM, Gosheger G, Werner M, Hardes J, Pink D et al. Metastatic Potential of Grade I Chondrosarcoma of Bone: Results of a Multi-institutional Study.
Ann Surg Oncol 2016; 23(1):120–5.
9. Chung BM, Hong SH, Yoo HJ, Choi J-Y, Chae H-D, Kim DH. Magnetic resonance imaging follow-up of chondroid tumors: regression vs. progression. Skeletal Radiol 2018; 47(6):755–61.
10. Altay M, Bayrakci K, Yildiz Y, Erekul S, Saglik Y. Secondary chondrosarcoma in cartilage bone tumors: report of 32 patients. J Orthop Sci 2007; 12(5):415–23.
11. Deckers C, Schreuder BHW, Hannink G, Rooy JWJ de, van der Geest ICM. Radiologic follow-up of untreated enchondroma and atypical cartilaginous tumors in the long bones. J Surg Oncol 2016; 114(8):987–91.
12. Schwab JH, Wenger D, Unni K, Sim FH. Does local recurrence impact survival in low-grade chondrosarcoma of the long bones? Clin Orthop Relat Res 2007; 462:175–80.
13. Douis H, Saifuddin A. The imaging of cartilaginous bone tumours. I. Benign lesions.
Skeletal Radiol 2012; 41(10):1195–212.
14. Errani C, Tsukamoto S, Ciani G, Akahane M, Cevolani L, Tanzi P et al. Risk factors for local recurrence from atypical cartilaginous tumour and enchondroma of the long
16. Angelini A, Guerra G, Mavrogenis AF, Pala E, Picci P, Ruggieri P. Clinical outcome of central conventional chondrosarcoma. J Surg Oncol 2012; 106(8):929–37.
17. Brien EW, Mirra JM, Kerr R. Benign and malignant cartilage tumors of bone and joint:
their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. I. The intramedullary cartilage tumors. Skeletal Radiol 1997;
26(6):325–53.
18. Kristensen IB, Sunde LM, Jensen OM. Chondrosarcoma. Increasing grade of malignancy in local recurrence. Acta Pathol Microbiol Immunol Scand A 1986;
94(2):73–7.
19. Evans HL, Ayala AG, Romsdahl MM. Prognostic factors in chondrosarcoma of bone.A clinicopathologic analysis with emphasis on histologic grading. Cancer 1977;
40(2):818–31.
20. Duchman KR, Lynch CF, Buckwalter JA, Miller BJ. Estimated cause-specific survival continues to improve over time in patients with chondrosarcoma. Clin Orthop Relat Res 2014; 472(8):2516–25.
21. Giuffrida AY, Burgueno JE, Koniaris LG, Gutierrez JC, Duncan R, Scully SP.
Chondrosarcoma in the United States (1973 to 2003): an analysis of 2890 cases from the SEER database. J Bone Joint Surg Am 2009; 91(5):1063–72.
22. Fromm J, Klein A, Baur-Melnyk A, Knösel T, Lindner L, Birkenmaier C et al. Survival and prognostic factors in conventional central chondrosarcoma. BMC Cancer 2018;
18(1):849.
23. van Praag Veroniek VM, Rueten-Budde AJ, Ho V, Dijkstra PDS, Fiocco M, van de Sande MAJ. Incidence, outcomes and prognostic factors during 25 years of treatment of chondrosarcomas. Surg Oncol 2018; 27(3):402–8.
24. Gelderblom H, Hogendoorn PCW, Dijkstra SD, van Rijswijk CS, Krol AD, Taminiau AHM et al. The clinical approach towards chondrosarcoma. Oncologist 2008;
13(3):320–9.
25. Bindiganavile S, Han I, Yun JY, Kim H-S. Long-term Outcome of Chondrosarcoma: A Single Institutional Experience. Cancer Res Treat 2015; 47(4):897–903.
26. Uhle M-J, Herget GW, Rottenburger C. Radiologische Diagnostik von Knochentumoren. 1st ed. Stuttgart: Thieme; 2008.
27. Flemming, D., J., Murphey, M., D. Enchondroma and Chondrosarcoma. Semin Musculoskelet Radiol 2000; 4(1):59–71.
28. Czerniak B, Dorfman HD. Dorfman and Czerniak's bone tumors. Second edition.
Philadelphia PA: Elsevier; 2016.
29. Qasem SA, DeYoung BR. Cartilage-forming tumors. Semin Diagn Pathol 2014;
31(1):10–20.
30. Limaiem F, Davis DD, Sticco KL. Chondrosarcoma: StatPearls; 2021 [cited 2021 Apr 27]. Available from: URL: https://www.ncbi.nlm.nih.gov/books/NBK538132/.
31. P. Robinson, L. M. White, M. Sundaram, R. Kandel, J. Wunder, D. J. McDonald et al.
Periosteal Chondroid Tumors.
33. Höfler G, Kreipe HH, Moch H, Böcker W, Denk H, editors. Pathologie. 6., vollständig überarbeitete Auflage. München: Elsevier; 2019.
34. Murphey MD, Walker EA, Wilson AJ, Kransdorf MJ, Temple HT, Gannon FH. From the archives of the AFIP: imaging of primary chondrosarcoma: radiologic-pathologic correlation. Radiographics 2003; 23(5):1245–78.
35. Schrage YM, Lam S, Jochemsen AG, Cleton-Jansen A-M, Taminiau AHM,
Hogendoorn PCW et al. Central chondrosarcoma progression is associated with pRb pathway alterations: CDK4 down-regulation and p16 overexpression inhibit cell growth in vitro. J Cell Mol Med 2009; 13(9A):2843–52.
36. Bridge JA, Bhatia PS, Anderson JR, Neff JR. Biologic and clinical significance of cytogenetic and molecular cytogenetic abnormalities in benign and malignant cartilaginous lesions. Cancer Genetics and Cytogenetics 1993; 69(2):79–90.
37. Mandahl N, Gustafson P, Mertens F, Akerman M, Baldetorp B, Gisselsson D et al.
Cytogenetic aberrations and their prognostic impact in chondrosarcoma. Genes Chromosomes Cancer 2002; 33(2):188–200.
38. Tallini G, Dorfman H, Brys P, Dal Cin P, Wever I de, Fletcher CDM et al. Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. J Pathol 2002; 196(2):194–203.
39. van Beerendonk HM, Rozeman LB, Taminiau AHM, Sciot R, Bovée JVMG, Cleton-Jansen A-M et al. Molecular analysis of the INK4A/INK4A-ARF gene locus in conventional (central) chondrosarcomas and enchondromas: indication of an important gene for tumour progression. J Pathol 2004; 202(3):359–66.
40. Cho H-Y, Lee M, Takei H, Dancer J, Ro JY, Zhai QJ. Immunohistochemical comparison of chordoma with chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma. Appl Immunohistochem Mol Morphol 2009; 17(2):131–8.
41. Jong Y de, Monderer D, Brandinelli E, Monchanin M, van den Akker BE, van Oosterwijk JG et al. Bcl-xl as the most promising Bcl-2 family member in targeted treatment of chondrosarcoma. Oncogenesis 2018; 7(9):74.
42. van Oosterwijk JG, Herpers B, Meijer D, Briaire-de Bruijn IH, Cleton-Jansen AM, Gelderblom H et al. Restoration of chemosensitivity for doxorubicin and cisplatin in chondrosarcoma in vitro: BCL-2 family members cause chemoresistance. Ann Oncol 2012; 23(6):1617–26.
43. Björnsson J, McLeod RA, Unni KK, Ilstrup DM, Pritchard DJ. Primary
chondrosarcoma of long bones and limb girdles. Cancer 1998; 83(10):2105–19.
44. Nota SPFT, Braun Y, Schwab JH, van Dijk CN, Bramer JAM. The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma.
Sarcoma 2015; 2015:623746.
45. Akoh, C.,C., Craig E, Troester, A.,E., Miller, B.,J. Radiographic Enchondroma Surveillance: Assessing Clinical Outcomes and Costs Effectiveness. The Iowa
tumors, and high-grade chondrosarcomas-Improving tumor-specific treatment: A paradigm in transit? Cancer 2019; 125(19):3288–91.
48. Ferrer-Santacreu EM, Ortiz-Cruz EJ, Díaz-Almirón M, Pozo Kreilinger JJ.
Enchondroma versus Chondrosarcoma in Long Bones of Appendicular Skeleton:
Clinical and Radiological Criteria-A Follow-Up. J Oncol 2016; 2016:8262079.
49. Murphey MD, Flemming DJ, Boyea SR, Bojescul JA, Sweet DE, Temple HT.
Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features. Radiographics 1998; 18(5):1213-37;
50. Crim J, Schmidt R, Layfield L, Hanrahan C, Manaster BJ. Can imaging criteria distinguish enchondroma from grade 1 chondrosarcoma? Eur J Radiol 2015;
84(11):2222–30.
51. Uhl M, Herget G, Kurz P. Chondrogene Knochentumoren : Pathologie und Radiomorphologie. Radiologe 2016; 56(6):476–88.
52. Geirnaerdt MJ, Hermans J, Bloem JL, Kroon HM, Pope TL, Taminiau AH et al.
Usefulness of radiography in differentiating enchondroma from central grade 1 chondrosarcoma. AJR Am J Roentgenol 1997; 169(4):1097–104.
53. Hodel S, Laux C, Farei-Campagna J, Götschi T, Bode-Lesniewska B, Müller DA. The impact of biopsy sampling errors and the quality of surgical margins on local
recurrence and survival in chondrosarcoma. Cancer Manag Res 2018; 10:3765–71.
54. Douis H, Parry M, Vaiyapuri S, Davies AM. What are the differentiating clinical and MRI-features of enchondromas from low-grade chondrosarcomas? Eur Radiol 2018;
28(1):398–409.
55. Lin PP, Moussallem CD, Deavers MT. Secondary chondrosarcoma. J Am Acad Orthop Surg 2010; 18(10):608–15.
56. Douis H, Singh L, Saifuddin A. MRI differentiation of low-grade from high-grade appendicular chondrosarcoma. Eur Radiol 2014; 24(1):232–40.
57. Coninck T de, Jans L, Sys G, Huysse W, Verstraeten T, Forsyth R et al. Dynamic contrast-enhanced MR imaging for differentiation between enchondroma and chondrosarcoma. Eur Radiol 2013; 23(11):3140–52.
58. Geirnaerdt MJ, Hogendoorn PC, Bloem JL, Taminiau AH, van der Woude HJ.
Cartilaginous tumors: fast contrast-enhanced MR imaging. Radiology 2000;
214(2):539–46.
59. Douis H, Jeys L, Grimer R, Vaiyapuri S, Davies AM. Is there a role for diffusion-weighted MRI (DWI) in the diagnosis of central cartilage tumors? Skeletal Radiol 2015; 44(7):963–9.
60. Bhojwani N, Szpakowski P, Partovi S, Maurer MH, Grosse U, Tengg-Kobligk H von et al. Diffusion-weighted imaging in musculoskeletal radiology-clinical applications and future directions. Quant Imaging Med Surg 2015; 5(5):740–53.
61. Soldatos T, McCarthy EF, Attar S, Carrino JA, Fayad LM. Imaging features of chondrosarcoma. J Comput Assist Tomogr 2011; 35(4):504–11.
62. McCarthy EF, Tyler WK. Distinguishing Enchondroma From Low-Grade Central
63. Lee FY-I, Yu J, Chang S-S, Fawwaz R, Parisien MV. Diagnostic value and limitations of fluorine-18 fluorodeoxyglucose positron emission tomography for cartilaginous tumors of bone. J Bone Joint Surg Am 2004; 86(12):2677–85.
64. Subhawong TK, Winn A, Shemesh SS, Pretell-Mazzini J. F-18 FDG PET
differentiation of benign from malignant chondroid neoplasms: a systematic review of the literature. Skeletal Radiol 2017; 46(9):1233–9.
65. Lisson CS, Lisson CG, Flosdorf K, Mayer-Steinacker R, Schultheiss M, Baer A von et al. Diagnostic value of MRI-based 3D texture analysis for tissue characterisation and discrimination of low-grade chondrosarcoma from enchondroma: a pilot study. Eur Radiol 2018; 28(2):468–77.
66. Douis H, Saifuddin A. The imaging of cartilaginous bone tumours. II.
Chondrosarcoma. Skeletal Radiol 2013; 42(5):611–26.
67. Lenze U, Knebel C, Rechl H, Eisenhart-Rothe R von. Diagnostik und Therapie primärer Knochentumoren. Orthopädie und Unfallchirurgie up2date 2018;
13(04):403–22.
68. Eefting D, Schrage YM, Geirnaerdt MJA, Le Cessie S, Taminiau AHM, Bovée JVMG et al. Assessment of interobserver variability and histologic parameters to improve reliability in classification and grading of central cartilaginous tumors. Am J Surg Pathol 2009; 33(1):50–7.
69. Deckers C, Leijer EM de, Flucke U, Rooy JWJ de, Schreuder HWB, Dierselhuis EF et al. Curettage and cryosurgery for enchondroma and atypical cartilaginous tumors of the long bones: Oncological results of a large series. J Surg Oncol 2021.
70. Patel A, Davies AM, Botchu R, James S. A pragmatic approach to the imaging and follow-up of solitary central cartilage tumours of the proximal humerus and knee.
Clin Radiol 2019; 74(7):517–26.
71. Parlier-Cuau C, Bousson V, Ogilvie CM, Lackman RD, Laredo J-D. When should we biopsy a solitary central cartilaginous tumor of long bones? Literature review and management proposal. Eur J Radiol 2011; 77(1):6–12.
72. van der Geest ICM, Valk MH de, Rooy JWJ de, Pruszczynski M, Veth RPH, Schreuder HWB. Oncological and functional results of cryosurgical therapy of enchondromas and chondrosarcomas grade 1. J Surg Oncol 2008; 98(6):421–6.
73. Roitman PD, Farfalli GL, Ayerza MA, Múscolo DL, Milano FE, Aponte-Tinao LA. Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones? Clin Orthop Relat Res 2017; 475(3):808–14.
74. Gelderblom AJ, Bovée JVMG. Chondrosarcoma; 2021 [cited 2021 Apr 23]. Available from: URL:
https://www-1uptodate-1com-1wwbz639l0725.han.medunigraz.at/contents/chondrosarcoma?search=Chondrosarco ma&source=search_result&selectedTitle=1~53&usage_type=default&display_rank=
1.
75. Stevenson JD, Laitinen MK, Parry MC, Sumathi V, Grimer RJ, Jeys LM. The role of
77. Sampath Kumar V, Tyrrell PNM, Singh J, Gregory J, Cribb GL, Cool P. Surveillance of intramedullary cartilage tumours in long bones. Bone Joint J 2016;
98-B(11):1542–7.
78. Campanacci DA, Scoccianti G, Franchi A, Roselli G, Beltrami G, Ippolito M et al.
Surgical treatment of central grade 1 chondrosarcoma of the appendicular skeleton. J Orthop Traumatol 2013; 14(2):101–7.
79. Davies AM, Patel A, James SL, Azzopardi C, Botchu R. An imaging protocol for the management of central cartilage tumours of the proximal fibula. Clin Radiol 2020;
75(9):714.e1-714.e6.
80. Wilson RJ, Zumsteg JW, Hartley KA, Long JH, Mesko NW, Halpern JL et al.
Overutilization and Cost of Advanced Imaging for Long-Bone Cartilaginous Lesions.
Ann Surg Oncol 2015; 22(11):3466–73.
81. Afonso PD, Isaac A, Villagrán JM. Chondroid Tumors as Incidental Findings and Differential Diagnosis between Enchondromas and Low-grade Chondrosarcomas.
Semin Musculoskelet Radiol 2019; 23(1):3–18.
82. Herget GW, Kontny U, Saueressig U, Baumhoer D, Hauschild O, Elger T et al.
Osteochondrom und multiple Osteochondrome : Empfehlungen zur Diagnostik und Vorsorge unter besonderer Berücksichtigung des Auftretens sekundärer
Chondrosarkome. Radiologe 2013; 53(12):1125–36.
83. Stomp W, Reijnierse M, Kloppenburg M, Mutsert R de, Bovée JVMG, Heijer M den et al. Prevalence of cartilaginous tumours as an incidental finding on MRI of the knee.
Eur Radiol 2015; 25(12):3480–7.
84. The Skeletal Lesions Interobserver Correlation among Expert Diagnosticians (SLICED) study Group. Reliability of histopathologic and radiologic grading of cartilaginous neoplasms in long bones. J Bone Joint Surg Am 2007; 89(10):2113–23.
85. Kendell SD, Collins MS, Adkins MC, Sundaram M, Unni KK. Radiographic differentiation of enchondroma from low-grade chondrosarcoma in the fibula.
Skeletal Radiol 2004; 33(8):458–66.
86. Ahmed S, Jubouri S, Mulligan M. Incidental long bone cartilage lesions: is any further imaging workup needed? Skeletal Radiol 2021; 50(6):1189–96.
87. Omlor GW, Lohnherr V, Lange J, Gantz S, Mechtersheimer G, Merle C et al. Outcome of conservative and surgical treatment of enchondromas and atypical cartilaginous tumors of the long bones: retrospective analysis of 228 patients. BMC Musculoskelet Disord 2019; 20(1):134.
7 Attachment
Case Report Form
Observational study on conservatively managed cartilage tumors of unknown malignant potential of the long bones
Patient ID:
Datum der Nachkontrolle:
UntersucherIn:
Einwilligung des/der PatientIn vorhanden:
Labor:
Serum-Kreatinin (mg/dl) GFR > 30 (ml/min) Datum der Untersuchung
Kontrastmittel Allergie?
Metallimplantate vorhanden?
Telekonsil:
ERSTDIAGNOSE
Datum der Erstdiagnose:
Therapie: operativ / konservativ Datum/ Ort erstes MRT:
Erstes MRT vorhanden:
Wie wurde die Erstdiagnose gestellt:
Wurden seit der Erstdiagnose weitere Kontrollen durchgeführt:
Ja Nein Hausarzt LKH
Ja Nein Ja Nein Ja Nein
wenn ja, welche (Prothesen (Knie/Hüfte), Schrittmacher, Z.n. Verletzung mit Metallsplittern, etc.):
Ja Nein
Konservativ operativ
Ja Nein
Zufallsbefund lokale Beschwerden
Ja Nein
Wenn ja, wo und in welchen Abständen:
Wenn ja, mit welchen Methoden:
klinisch
nativradiologisch
MRT (ohne KM) (mit KM) CT (ohne KM) (mit KM)
Wurde eine Knochenszintigraphie durchgeführt:
wenn ja, wo und Tracer Uptake
Ort: Tracer Uptake:
Ort: Tracer Uptake:
MRT Kontrolle MRT Gerät (Tesla):
MR Protokoll:
Verwendetes Kontrastmittel
Kontrastmittelreaktion:
Nachbesprechung an der Orthopädie stattgefunden:
Andere Komplikationen
Fragebogen (Brief Ilness Perception Questionnaire) ausgefüllt:
Nachuntersuchung Orthopädie
Klinische Symptomatik an der betroffenen Region:
Lokalstatus:
Wurden an der betroffenen Region Operationen durchgeführt (K-TEP, ASK, etc.) Ja Welche:
Ja Nein
LKH Tesla: Auswärts Tesla:
Ja Nein Ja Nein Wenn ja, Meldung erfolgt/notwendig?
Ja Nein Ja Nein Ja Nein
Fazit Nachkontrolle: Befundprogredienz Vereinbarung Nachsorgetermin mit Patienten:
Wenn ja -> Ort: Datum: Intervall:
Wenn nein -> Ursache: Ablehnung durch Patienten Anderer Ursache für Ablehnung:
_______________________
Unterschrift
Ja Nein Ja Nein