The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the gene. Partial loss of SMARCB1/INI1 was correlated with cervical-thoracic-lumbar tumor location ( = 0.033) and inadequate surgical margins ( = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.

Chordomas are rare, locally aggressive neoplasms recognized as derivatives of the notochord vestiges. These tumors typically involve the midline axial skeleton, and intracranial chordomas exhibit proclivity for the spheno-occipital region. However, purely intrasellar occurrences are extremely rare. We report a case of intrasellar chordoma, which masqueraded as a pituitary neuroendocrine tumor.

Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS).

Chordomas are rare malignant bone tumors arising in the axial skeleton, with an incidence of 0.3-0.88 per million inhabitants. We studied the annual incidence rate and centralization of treatment for chordoma in the Netherlands.

Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.

Chordoma is a slow-growing local invasive tumor with high mortality and recurrence rates after surgical resection. It can affect the clivus and sacrum and rarely involve the lumbar vertebra. There is limited literature research describing lumbar embolization before surgical resection in lumbar chordoma. Thus, this case report describes an atypical patient with chronic lower back pain who presented to the hospital for worsening pain. Radiological images show an aggressive focal lesion at the second lumbar spine extending into the posterior element. The patient underwent lumbar artery embolization before surgical resection. The final pathology diagnosis confirmed a conventional chordoma. Therefore, patients with radiological imaging features of conventional chordoma may benefit from embolization prior to surgical resection to decrease intraoperative bleeding.

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

Chordoma is a rare primary central nervous system tumour of notochordal origin. Proper intraoperative or preoperative diagnosis of this entity is crucial for appropriate surgical management. The most common histopathological subtype is conventional chordoma. Cytological characteristics of this subtype are quite distinctive and the diagnosis can be easily made by cytology. There are two particularly important features that are observed in both squash smear and fine needle aspiration specimens: an abundant myxochondroid stroma and cells with large vacuoles, including physaliferous cells. The main differential diagnosis is conventional chondrosarcoma, but in problematic cases immunohistochemical studies are useful to establish the correct diagnosis.

Chordoma is a rare and locally invasive neoplasm, and the prognostic factors are limited. Deregulation of Histone 3 lysine 27 (H3K27) trimethylation (H3K27me3) is considered to be related with poor prognosis in some tumors. The purpose of this study was to detect the expression of H3K27me3 in chordomas and analyze the correlation with clinicopathological features and explore the roles as potential prognostic markers and therapeutic targets.

De-differentiated chordoma is defined as a high-grade sarcoma lacking notochordal differentiation, which arises in association with conventional chordoma. The mechanism underlying de-differentiation remains unclear. We immunohistochemically investigated trimethylation at lysine 27 of histone 3 (H3K27me3) in nine de-differentiated chordomas. The tumours occurred at the skull base (n = 5) or the sacrum (n = 4) in four men and five women with a median age of 50 years. De-differentiation occurred de novo in four cases and at recurrence/metastasis in five cases. Five tumours retained H3K27me3, whereas four showed complete loss of H3K27me3 only in the de-differentiated component, while the conventional chordoma component retained H3K27me3. All the H3K27me3-negative tumours showed co-loss of dimethylation at H3K27 (H3K27me2), consistent with inactivation of polycomb repressive complex 2. Two genetically analysed H3K27me3-negative tumours harboured EED homozygous deletions. All four H3K27me3-negative de-differentiated chordomas affected the skull base of young or middle-aged women. Unlike dense proliferation of highly pleomorphic spindle or epithelioid cells in the H3K27me3-positive de-differentiated chordomas, all H3K27me3-negative tumours displayed swirling fascicles of relatively uniform spindle cells with alternating cellularity and perivascular accentuation, resembling malignant peripheral nerve sheath tumour (MPNST). Rhabdomyoblastic differentiation was present in one H3K27me3-negative tumour. We identified a novel group of de-differentiated chordomas in the skull base that lost H3K27me3/me2 only in the de-differentiated component, which was associated with EED homozygous deletion and MPNST-like histology. Our data suggest a distinct 'polycomb-type' de-differentiation pathway in chordoma, similar to a recently described de-differentiated chondrosarcoma with H3K27me3 loss.