{"entity":{"id":"poorly-differentiated-chordoma","kind":"cancer","name":"Poorly differentiated chordoma (SMARCB1-deficient)","aka":["SMARCB1-deficient chordoma","INI1-negative chordoma","Paediatric poorly differentiated chordoma"],"tldr":"Poorly differentiated chordoma is a rare, aggressive form of chordoma of children and young adults, mostly at the base of the skull or in the neck, defined by loss of the SMARCB1 (INI1) protein. It grows faster and spreads more than ordinary chordoma, and the SMARCB1 loss makes it a candidate for drugs that block EZH2, though surgery and radiotherapy remain the treatment.","summary":"The WHO bone classification recognises poorly differentiated chordoma as a subtype defined by brachyury expression with loss of SMARCB1 (INI1), first characterised as a distinct molecular entity with dismal prognosis (Acta Neuropathologica 2016). In the 19-patient series, tumours arose in the skull base and clivus (53 percent), cervical spine (32 percent) and sacrum or coccyx (16 percent), were composed of sheets of epithelioid cells rather than the physaliphorous cells of conventional chordoma, and had worse survival than the other subtypes (Modern Pathology 2018).\n\nHow it differs from its parent: age (children rather than adults in their fifties and sixties), the SMARCB1 deletion that groups it biologically with atypical teratoid/rhabdoid tumour and epithelioid sarcoma, and a much shorter survival.\n\nHow common: no incidence figure; 19 cases at one referral centre in 27 years (Modern Pathology 2018).\n\nTreatment: maximal safe resection and proton or photon radiotherapy as on the chordoma page; systemic therapy has no standard, and EZH2 inhibition (tazemetostat, approved for SMARCB1-deficient epithelioid sarcoma) is the rational agent under study for SMARCB1-deficient tumours.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Chordoma","links":[{"label":"NCI PDQ: rare cancers of childhood","url":"https://www.cancer.gov/types/childhood-cancers/patient/rare-childhood-cancers-pdq"},{"label":"Acta Neuropathologica 2016: poorly differentiated chordoma with SMARCB1/INI1 loss, a distinct entity with dismal prognosis","url":"https://doi.org/10.1007/s00401-016-1574-9"},{"label":"Modern Pathology 2018: clinicopathologic characteristics of poorly differentiated chordoma, 19 patients","url":"https://doi.org/10.1038/s41379-018-0002-1"}],"tags":["subtype-page","wave4","rare"],"related":["chordoma","dedifferentiated-chordoma","atrt","childhood-cancers"],"cancers":[],"sections":[],"technologies":["proton-therapy"],"targets":["smarcb1","tbxt"],"drugs":["tazemetostat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"sarcoma","burden":"Very rare and mostly paediatric: the largest series holds 19 patients diagnosed at a median age of 11 (range 1 to 29) over 1990 to 2017 (Modern Pathology 2018).","subtypes":["Poorly differentiated chordoma of the skull base and clivus (about half)","Poorly differentiated chordoma of the cervical spine","Poorly differentiated chordoma of the sacrum or coccyx","Conventional and chondroid chordoma (the parent page; SMARCB1 retained)"],"biomarkers":["Brachyury (TBXT) positive with SMARCB1 (INI1) loss","SMARCB1 deletion on copy-number analysis","Cytokeratin positive; epithelioid morphology","Age under 30"],"standardOfCare":[{"setting":"All cases","approach":"Maximal safe resection and proton radiotherapy as on the chordoma page; EZH2 inhibition under study for SMARCB1-deficient tumours.","refs":["chordoma","proton-therapy","tazemetostat"]}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"chordoma"},"route":"/cancers/poorly-differentiated-chordoma/","neighbours":{"cancer":[{"id":"atrt","kind":"cancer","name":"Atypical teratoid/rhabdoid tumour (ATRT)","route":"/cancers/atrt/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"chordoma","kind":"cancer","name":"Chordoma","route":"/cancers/chordoma/"},{"id":"dedifferentiated-chordoma","kind":"cancer","name":"Dedifferentiated chordoma","route":"/cancers/dedifferentiated-chordoma/"}],"technology":[{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"}],"target":[{"id":"smarcb1","kind":"target","name":"SMARCB1","route":"/targets/smarcb1/"},{"id":"tbxt","kind":"target","name":"TBXT","route":"/targets/tbxt/"}],"drug":[{"id":"tazemetostat","kind":"drug","name":"Tazemetostat","route":"/drugs/tazemetostat/"}]}}