Skip to main content
SpringerLink
Log in

Chordome – Ein Update

Chordoma—An update

  • Hauptreferate: Hauptprogramm der DGP
  • Published:
Die Pathologie Aims and scope Submit manuscript

Zusammenfassung

Chordome sind seltene, maligne Tumoren des Achsenskeletts mit notochordaler Differenzierung. Morphologisch können sie eine erhebliche Bandbreite von der klassischen, konventionellen Form über hepatoide und nierenzellkarzinomähnliche Varianten oder auch niedrig differenzierte und dedifferenzierte Formen aufweisen. Der Nachweis von Brachyury als immunhistologischer Marker ist ein wesentliches, wenn auch nicht exklusives diagnostisches Merkmal. Die Differenzialdiagnose zum benignen notochordalen Tumor (BNCT) erfordert neben der Morphologie zwingend die Einbeziehung der Bildgebung, da der BNCT auf den Wirbelkörper beschränkt bleibt und nicht osteolytisch imponiert. Zielgerichtet Ansätze für die Therapie sind im Fokus der Forschung und Zelllinienmodelle eine der Voraussetzung dieser zunächst in-vitro-basierten Ansätze.

Abstract

Chordomas are rare malignant tumors of the axial skeleton with notochordal differentiation. From a morphological point of view, chordomas display a broad spectrum ranging from the classical, conventional form not otherwise specified (NOS) to forms with hepatoid or renal carcinoma-like differentiation or even poorly or dedifferentiated variants. The detection of brachyury is highly characteristic, though not exclusive. The morphological differential diagnosis from a benign notochordal tumor (BNCT) requires integration of imaging since BNCT is limited to the vertebral bodies and is not osteolytic. Targeted therapy is a current research focus and cell lines as in vitro models are a precondition for the establishment and validation of this approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM (2001) Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control 12(1):1–11

    Article  CAS  Google Scholar 

  2. Stacchiotti S, Gronchi A, Fossati P, Akiyama T, Alapetite C, Baumann M, Blay JY, Bolle S, Boriani S, Bruzzi P et al (2017) Best practices for the management of local-regional recurrent chordoma: a position paper by the chordoma global consensus group. Ann Oncol 28(6):1230–1242

    Article  CAS  Google Scholar 

  3. Ailon T, Torabi R, Fisher CG, Rhines LD, Clarke MJ, Bettegowda C, Boriani S, Yamada YJ, Kawahara N, Varga PP et al (2016) Management of locally recurrent chordoma of the mobile spine and sacrum: a systematic review. Spine 41(20):S193–S198

    Article  Google Scholar 

  4. Radaelli S, Stacchiotti S, Ruggieri P, Donati D, Casali PG, Palmerini E, Collini P, Gambarotti M, Porcu L, Boriani S et al (2016) Sacral chordoma: long-term outcome of a large series of patients surgically treated at two reference centers. Spine 41(12):1049–1057

    Article  Google Scholar 

  5. Stacchiotti S, Sommer J, Chordoma Global Consensus Group (2015) Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol 16(2):e71–83

    Article  Google Scholar 

  6. von Witzleben A, Goerttler LT, Lennerz J, Weissinger S, Kornmann M, Mayer-Steinacker R, von Baer A, Schultheiss M, Moller P, Barth TF (2016) In chordoma, metastasis, recurrences, Ki-67 index, and a matrix-poor phenotype are associated with patients’ shorter overall survival. Eur Spine J 25(12):4016–4024

    Article  Google Scholar 

  7. Hung YP, Diaz-Perez JA, Cote GM, Wejde J, Schwab JH, Nardi V, Chebib IA, Deshpande V, Selig MK, Bredella MA et al (2020) Dedifferentiated chordoma: clinicopathologic and molecular characteristics with integrative analysis. Am J Surg Pathol 44(9):1213–1223

    Article  Google Scholar 

  8. Hasselblatt M, Thomas C, Hovestadt V, Schrimpf D, Johann P, Bens S, Oyen F, Peetz-Dienhart S, Crede Y, Wefers A et al (2016) Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis. Acta Neuropathol 132(1):149–151

    Article  Google Scholar 

  9. Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM (2006) Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 209(2):157–165

    Article  CAS  Google Scholar 

  10. Akhavan-Sigari R, Gaab MR, Rohde V, Abili M, Ostertag H (2014) Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma. Eur Spine J 23(11):2416–2422

    Article  Google Scholar 

  11. Saad AG, Collins MH (2005) Prognostic value of MIB‑1, E‑cadherin, and CD44 in pediatric chordomas. Pediatr Dev Pathol 8(3):362–368

    Article  CAS  Google Scholar 

  12. Sakai K, Hongo K, Tanaka Y, Nakayama J (2007) Analysis of immunohistochemical expression of p53 and the proliferation marker Ki-67 antigen in skull base chordomas: relationships between their expression and prognosis. Brain Tumor Pathol 24(2):57–62

    Article  CAS  Google Scholar 

  13. Dobrovolskaia-Zavadskaia N (1927) Sur la mortification spontanee de la queue chez la souris nouveau-nee et sur l’existence d’un caractere (facteur) hereditaire “non-viable”. C R Seances Soc Biol Fil 97:114–116

    Google Scholar 

  14. Showell C, Binder O, Conlon FL (2004) T‑box genes in early embryogenesis. Dev Dyn 229(1):201–218

    Article  CAS  Google Scholar 

  15. Miettinen M, Wang Z, Lasota J, Heery C, Schlom J, Palena C (2015) Nuclear brachyury expression is consistent in chordoma, common in germ cell tumors and small cell carcinomas, and rare in other carcinomas and sarcomas: an Immunohistochemical study of 5229 cases. Am J Surg Pathol 39(10):1305–1312

    Article  Google Scholar 

  16. Yamaguchi T, Suzuki S, Ishiiwa H, Shimizu K, Ueda Y (2004) Benign notochordal cell tumors: a comparative histological study of benign notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal intervertebral discs. Am J Surg Pathol 28(6):756–761

    Article  Google Scholar 

  17. Yamaguchi T, Suzuki S, Ishiiwa H, Ueda Y (2004) Intraosseous benign notochordal cell tumours: overlooked precursors of classic chordomas? Histopathology 44(6):597–602

    Article  CAS  Google Scholar 

  18. Sheppard HE, Dall’Agnese A, Park WD, Shamim MH, Dubrulle J, Johnson HL, Stossi F, Cogswell P, Sommer J, Levy J et al (2021) Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity. Cell Rep Med 2(1):100188

    Article  CAS  Google Scholar 

  19. Hu Y, Singh R, Deng Z, Mintz A, Hsu W (2016) Liposome-protamine-DNA nanoparticle-mediated delivery of short hairpin RNA targeting brachyury inhibits chordoma cell growth. J Biomed Nanotechnol 12(10):1952–1961

    Article  CAS  Google Scholar 

  20. Sharifnia T, Wawer MJ, Chen T, Huang QY, Weir BA, Sizemore A, Lawlor MA, Goodale A, Cowley GS, Vazquez F et al (2019) Small-molecule targeting of brachyury transcription factor addiction in chordoma. Nat Med 25(2):292–300

    Article  CAS  Google Scholar 

  21. Jäger D (2017) HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral chordomas. Sci Rep 7(1):2032. https://doi.org/10.1038/s41598-017-02174-5

    Article  CAS  Google Scholar 

  22. Holley C, Breining T, Scheithauer M, Moller P, Barth TFE (2021) Primary extra-axial chondroid chordoma of the anterior nasal septum: case report of a rare chordoma with literature review. HNO 69(3):221–228

    Article  CAS  Google Scholar 

  23. Neumann J, Gersing AS, Barth TF, Boxberg M, Woertler K (2019) Intra-articular extra-axial chordoma of the wrist: a case report with review of the current literature. Skelet Radiol 48(12):2015–2020

    Article  Google Scholar 

  24. Scheil S, Bruderlein S, Liehr T, Starke H, Herms J, Schulte M, Moller P (2001) Genome-wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U‑CH1. Genes Chromosom Cancer 32(3):203–211

    Article  CAS  Google Scholar 

  25. Seeling C, Lechel A, Svinarenko M, Moller P, Barth TFE, Mellert K (2021) Molecular features and vulnerabilities of recurrent chordomas. J Exp Clin Cancer Res 40(1):244

    Article  CAS  Google Scholar 

  26. Jäger D, Lechel A, Tharehalli U, Seeling C, Möller P, Barth TFE, Mellert K (2018) U‑CH17P, -M and -S, a new cell culture system for tumor diversity and progression in chordoma. Int J Cancer 142(7):1369–1378. https://doi.org/10.1002/ijc.31161

    Article  CAS  Google Scholar 

  27. de Castro CV, Guimaraes G, Aguiar S Jr., Lopes A, Baiocchi G, da Cunha IW, Campos AH, Soares FA, Begnami MD (2013) Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome. Hum Pathol 44(9):1747–1755

    Article  Google Scholar 

  28. D’Agati G, Cabello EM, Frontzek K, Rushing EJ, Klemm R, Robinson MD, White RM, Mosimann C, Burger A (2019) Active receptor tyrosine kinases, but not Brachyury, are sufficient to trigger chordoma in zebrafish. Dis Model Mech 12(7):dmm39545. https://doi.org/10.1242/dmm.039545

    Article  CAS  Google Scholar 

  29. Hof H, Welzel T, Debus J (2006) Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma. Onkologie 29(12):572–574

    Google Scholar 

  30. Linden O, Stenberg L, Kjellen E (2009) Regression of cervical spinal cord compression in a patient with chordoma following treatment with cetuximab and gefitinib. Acta Oncol 48(1):158–159

    Article  Google Scholar 

  31. Stacchiotti S, Tamborini E, Lo Vullo S, Bozzi F, Messina A, Morosi C, Casale A, Crippa F, Conca E, Negri T et al (2013) Phase II study on lapatinib in advanced EGFR-positive chordoma. Ann Oncol 24(7):1931–1936

    Article  CAS  Google Scholar 

  32. Magnaghi P, Salom B, Cozzi L, Amboldi N, Ballinari D, Tamborini E, Gasparri F, Montagnoli A, Raddrizzani L, Somaschini A et al (2018) Afatinib is a new therapeutic approach in chordoma with a unique ability to target EGFR and brachyury. Mol Cancer Ther 17(3):603–613

    Article  CAS  Google Scholar 

  33. Stacchiotti S, Longhi A, Ferraresi V, Grignani G, Comandone A, Stupp R, Bertuzzi A, Tamborini E, Pilotti S, Messina A et al (2012) Phase II study of imatinib in advanced chordoma. J Clin Oncol 30(9):914–920

    Article  CAS  Google Scholar 

  34. Choy E, MacConaill LE, Cote GM, Le LP, Shen JK, Nielsen GP, Iafrate AJ, Garraway LA, Hornicek FJ, Duan Z (2014) Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1. PLoS One 9(7):e101283

    Article  Google Scholar 

  35. Hallor KH, Staaf J, Jonsson G, Heidenblad M, Vult von Steyern F, Bauer HC, Ijszenga M, Hogendoorn PC, Mandahl N, Szuhai K et al (2008) Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation. Br J Cancer 98(2):434–442

    Article  CAS  Google Scholar 

  36. Brüderlein S, Sommer JB, Meltzer PS, Li S, Osada T, Ng D, Möller P, Alcorta DA, Kelley MJ (2010) Molecular characterization of putative chordoma cell lines. Sarcoma 2010:630129

    Article  Google Scholar 

  37. Cottone L, Eden N, Usher I, Lombard P, Ye H, Ligammari L, Lindsay D, Brandner S, Pizem J, Pillay N et al (2020) Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma. J Pathol Clin Res 6(2):113–123

    Article  CAS  Google Scholar 

  38. von Witzleben A, Goerttler LT, Marienfeld R, Barth H, Lechel A, Mellert K, Bohm M, Kornmann M, Mayer-Steinacker R, von Baer A et al (2015) Preclinical characterization of novel chordoma cell systems and their targeting by pharmocological inhibitors of the CDK4/6 cell-cycle pathway. Cancer Res 75(18):3823–3831

    Article  Google Scholar 

  39. Morgan R, In der Rieden P, Hooiveld MH, Durston AJ (2000) Identifying HOX paralog groups by the PBX-binding region. Trends Genet 16(2):66–67

    Article  CAS  Google Scholar 

  40. Morgan R, El-Tanani M, Hunter KD, Harrington KJ, Pandha HS (2017) Targeting HOX/PBX dimers in cancer. Oncotarget 8(19):32322–32331

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Deutschland

    K. Mellert, C. Seeling, P. Möller &  T. F. E. Barth

  2. Klinik für Innere Medizin III, Universitätsklinikum Ulm, Ulm, Deutschland

    C. Seeling

Authors
  1. K. Mellert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Seeling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Möller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. F. E. Barth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. F. E. Barth.

Ethics declarations

Interessenkonflikt

K. Mellert, C. Seeling, P. Möller und T.F.E. Barth geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

The supplement containing this article is not sponsored by industry.

Additional information

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mellert, K., Seeling, C., Möller, P. et al. Chordome – Ein Update. Pathologie 43 (Suppl 1), 50–55 (2022). https://doi.org/10.1007/s00292-022-01118-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-022-01118-9

Schlüsselwörter

Keywords

Search

Navigation