Familial chordoma: A case report and review of the literature

Wang, K E; Wu, Zhen; Tian, Kaibing; Wang, Liang; Hao, Shuyu; Zhang, Liwei; Zhang, Junting

doi:10.3892/ol.2015.3687

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…9,14,15,50,55 Molecular Pathology Most chordomas are sporadic, but several familial cases have been identified. [56][57][58] Somatic duplication of TBXT was identified in 27% of sporadic cases. 16 Germline tandem duplication of TBXT was identified in 3 families with chordoma (in 16 family members) with an autosomal dominant pattern of inheritance.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Chordoma

Ulici

Hart

2021

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Chordomas are uncommon malignant neoplasms with notochordal differentiation encountered by neuropathologists, bone/soft tissue pathologists, and general surgical pathologists. These lesions most commonly arise in the axial skeleton. Optimal therapy typically involves complete surgical resection, which is often technically difficult owing to the anatomic location, leading to a high rate of recurrence. Lesions have been generally resistant to radiation and chemotherapy; however, experimental studies involving targeted therapy and immunotherapy are currently underway. Objective.— To summarize the clinical and pathologic findings of the various types of chordoma (conventional chordoma, dedifferentiated chordoma, and poorly differentiated chordoma), the differential diagnosis, and recent advances in molecular pathogenesis and therapeutic modalities that are reliant on accurate diagnosis. Data Sources.— Literature review based on PubMed searches containing the term “chordoma” that address novel targeted and immunomodulatory therapeutic modalities; ongoing clinical trials involved in treating chordoma with novel therapeutic modalities identified through the Chordoma Foundation and ClinicalTrials.gov; and the authors' practice experience combined with various authoritative texts concerning the subject. Conclusions.— Chordoma is a clinically and histologically unique malignant neoplasm, and numerous diagnostic considerations must be excluded to establish the correct diagnosis. Treatment options have largely been centered on surgical excision with marginal results; however, novel therapeutic options including targeted therapy and immunotherapy are promising means to improve prognosis.

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Section: Immunohistochemistrymentioning

confidence: 99%

Chordoma

Ulici

Hart

2021

Archives of Pathology &Amp; Laboratory Medicine

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“…Ten families with at least 2 blood relatives with histopathologically confirmed chordoma have been described worldwide. [3][4][5][6][7][8][11][12][13][14][15][16][17][18] The 6 families described in this report (listed by number in Table 5) include 3 of the 4 published T-dup+ chordoma families. The fourth T-dup+ chordoma family (family 3) has branches in both South Africa and England; we present the 2 branches separately but treat them as a single family.…”

Section: Clinical Findings Treatment and Outcome In T-dup-familiesmentioning

confidence: 99%

“…Although most chordomas are sporadic, 10 multiple-case families with at least 2 blood relatives with histopathologically confirmed chordoma have been reported. [3][4][5][6][7][8] We previously identified autosomal dominant inheritance of a duplication of the T gene (brachyury) by using a wholegenome human array-comparative genomic hybridization (array-CGH) chip followed by a quantitative polymerase chain reaction assay for confirmation in 4 of 7 families investigated. 8 To gain insight into the role of germline genetics in the development of chordoma and to evaluate whether any clinical features might impact surveillance or screening, we evaluated clinical data from 2 sets of patients with familial chordoma: those with a germline duplication of the T gene (T-dup+) and those without a T gene duplication (T-dup−).…”

mentioning

confidence: 99%

Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program

Parry¹,

McMaster

Liebsch

et al. 2021

Journal of Neurosurgery

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OBJECTIVETo gain insight into the role of germline genetics in the development of chordoma, the authors evaluated data from 2 sets of patients with familial chordoma, those with and without a germline duplication of the T gene (T-dup+ vs T-dup−), which was previously identified as a susceptibility mechanism in some families. The authors then compared the patients with familial tumors to patients with sporadic chordoma in the US general population reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program through 2015.METHODSEvaluation of family members included review of personal and family medical history, physical and neurological examination, and pre- and postcontrast MRI of the skull base and spine. Sixteen patients from 6 white families with chordoma had a chordoma diagnosis at family referral. Screening MR images of 35 relatives revealed clival lesions in 6, 4 of which were excised and confirmed to be chordoma. Thus, data were available for 20 patients with histologically confirmed familial chordoma. There were 1759 patients with histologically confirmed chordoma in SEER whose race was known.RESULTSThe median age at chordoma diagnosis differed across the groups: it was lowest in T-dup+ familial patients (26.8 years, range 5.3–68.4 years); intermediate in T-dup− patients (46.2 years, range 11.8–60.1 years); and highest in SEER patients (57 years, range 0–98 years). There was a marked preponderance of skull base tumors in patients with familial chordoma (93% in T-dup+ and 83% in T-dup−) versus 38% in the SEER program (37% in white, 53% in black, and 48.5% in Asian/Pacific Islander/American Indian/Alaska Native patients). Furthermore, 29% of white and 16%–17% of nonwhite SEER patients had mobile-spine chordoma, versus no patients in the familial group. Several T-dup+ familial chordoma patients had putative second/multiple primary chordomas.CONCLUSIONSThe occurrence of young age at diagnosis, skull base presentation, or multiple primary chordomas should encourage careful review of family history for patients diagnosed with chordoma as well as screening of at-risk family members by MRI for early detection of chordoma. Furthermore, given genetic predisposition in some patients with familial chordoma, identification of a specific mutation in a family will permit surveillance to be limited to mutation carriers—and consideration should be given for imaging the entire neuraxis in any chordoma patient presenting at an early age or with a blood relative with chordoma. Finally, future studies should explore racial differences in age at diagnosis and presenting site in chordoma.

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“…Common genetic lesions in chordomas, but not pathognomonic, are loss of heterozygosity (LOH) of chromosomes 1p36, 9p, 10q, and 17p [ 56 ]. Although chordomas are usually sporadic, a few familiar cases have been described [ 8 , 56 , 57 ].…”

Section: Pathologic Mechanisms and Biological Markers In Chordomas: Cmentioning

confidence: 99%

“…Chromosome loss of 1p36 was found to be the most frequent genetic abnormality, occurring in 75–85% of both sporadic and familiar chordomas [ 8 , 57 , 58 ]. Several groups have postulated that the notochord development transcription factor brachyury (uncertainly expressed in almost all chordomas and suggested as an oncogenic driver) could be a novel discriminating biomarker for chordoma subtypes.…”

Section: Pathologic Mechanisms and Biological Markers In Chordomas: Cmentioning

confidence: 99%

Immunophenotypic features of dedifferentiated skull base chordoma: An insight into the intratumoural heterogeneity

Batista

Reyes

Lopez³

et al. 2017

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Chordomas are rare and low-grade malignant solid tumours, despite their histologically benign appearance, that arise in the bone from embryonic notochordal vestiges of the axial skeleton, a mesoderm-derived structure that is involved in the process of neurulation and embryonic development. Chordomas occurring in the skull base tend to arise in the basiocciput along the clivus. Three major morphological variants have been described (classical, chondroid, and atypical/dedifferentiated). The pathogenesis and molecular mechanisms involved in chordoma development remain uncertain. From a pathological standpoint, the microenvironment of a chordoma is heterogeneous, showing a dual epithelial-mesenchymal differentiation. These tumours are characterised by slow modality of biologic growth, local recurrence, low incidence of metastasis rates, and cancer stem cell (CSC) phenotype. The main molecular findings are connected with brachyury immunoexpression and activation of the downstream Akt and mTOR signalling pathways. The differentiation between typical and atypical chordomas is relevant because the tumoural microenvironment and prognosis are partially different. This review provides an insight into the recent and relevant concepts and histochemical markers expressed in chordomas, with special emphasis on dedifferentiated chordomas and their prognostic implications.

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Familial chordoma: A case report and review of the literature

Cited by 6 publications

References 29 publications

Chordoma

Chordoma

Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program

Immunophenotypic features of dedifferentiated skull base chordoma: An insight into the intratumoural heterogeneity

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