Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma.

STUDY DESIGN: Retrospective study. OBJECTIVE: In this study, the authors explore the potential relationship between hypoxia inducible factor-1α (HIF-1α) and the prognosis of patients with spinal chordoma. SUMMARY OF BACKGROUND DATA: Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between HIF-1α and tumor angiogenesis, metastasis, and recurrence have been widely reported, it has not been investigated in the context of spinal chordoma. MATERIALS AND METHODS: In this study, 32 samples of chordoma patients were compared with 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry. Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathologic characteristics of patients with chordoma was analyzed using the Pearson χ 2 test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. RESULTS: HIF-1α was mainly expressed in the cytoplasm or nucleus in all of the chordoma samples, which showed significantly higher than that in the normal nucleus pulposus tissue ( P =0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (hazard ratio (HR)=3.374; P =0.021) and OS (HR=4.511; P =0.012). In addition, we further found that high HIF-1α expression both in the cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P =0.011) and OS (HR=4.014; P =0.011) in spinal chordoma patients. CONCLUSION: High HIF-1α expression may become a potential new biological indicator to predict a poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.

A rare case of chordoma cutis.

Chordoma is a rare locally aggressive bone malignancy that originates from the notochord. It typically involves the sacrococcygeal area, spheno-occipital region of the skull, and spine. Cutaneous involvement of chordoma, termed as chordoma cutis, is uncommon and usually occurs via direct invasion or local recurrence. Distant metastasis to the skin is very rare. We report a case of chordoma cutis on the scalp, which lacked characteristic physaliferous cells but tested positive for brachyury, thus supporting the diagnosis of chordoma cutis. The patient, who presented with a solitary translucent nodule on the scalp, was previously diagnosed with chordoma on the vertebral column and skull 8 months prior. Microscopic examination showed a cord-like arrangement of plasmacytoid cells within a myxoid stroma. Physaliferous cells were not observed, and cytokeratin AE1/AE3 staining was negative; however, brachyury and epithelial membrane antigen staining was positive, leading to the diagnosis of chordoma cutis. Therefore, clinicians must include chordoma cutis in the differential diagnosis of translucent nodular lesions on the skin of patients formerly diagnosed with chordoma.

Predicting overall survival in chordoma patients using machine learning models: a web-app application.

OBJECTIVE: The goal of this study was to evaluate the efficacy of machine learning (ML) techniques in predicting survival for chordoma patients in comparison with the standard Cox proportional hazards (CoxPH) model. METHODS: Using a Surveillance, Epidemiology, and End Results database of consecutive newly diagnosed chordoma cases between January 2000 and December 2018, we created and validated three ML survival models as well as a traditional CoxPH model in this population-based cohort study. Randomly, the dataset was divided into training and validation datasets. Tuning hyperparameters on the training dataset involved a 1000-iteration random search with fivefold cross-validation. Concordance index (C-index), Brier score, and integrated Brier score were used to evaluate the performance of the model. The receiver operating characteristic (ROC) curves, calibration curves, and area under the ROC curves (AUC) were used to assess the reliability of the models by predicting 5- and 10-year survival probabilities. RESULTS: A total of 724 chordoma patients were divided into training (n = 508) and validation (n = 216) cohorts. Cox regression identified nine significant prognostic factors (p < 0.05). ML models showed superior performance over CoxPH model, with DeepSurv having the highest C-index (0.795) and the best discrimination for 5- and 10-year survival (AUC 0.84 and 0.88). Calibration curves revealed strong correlation between DeepSurv predictions and actual survival. Risk stratification by DeepSurv model effectively discriminated high- and low-risk groups (p < 0.01). The optimized DeepSurv model was implemented into a web application for clinical use that can be found at https://hust-chengp-ml-chordoma-app-19rjyr.streamlitapp.com/ . CONCLUSION: ML algorithms based on time-to-event results are effective in chordoma prediction, with DeepSurv having the best discrimination performance and calibration.

Chordoma concurrent with benign notochordal cell tumor of the mobile spine. Should the chordoma part be biopsied? - A stepwise approach for management.

Some evidence suggests that benign notochordal tumors (BNCTs) could be a potential precursor of chordoma. We present an educational rare case of lumbar vertebral BNCTs concomitant with a destructive lesion not reachable on biopsy but thought to be chordoma. We present a stepwise approach for management of these difficult entities based on radiological features.

Cytomorphology of a unique case of dedifferentiated chordoma involving a pleural effusion specimen.

Cytomorphology along with positive AE1/AE3 staining and Brachyury staining support the dignosis of metastatic dedifferentiated chordoma.

Competing risk nomogram for predicting prognosis of patients with spinal and pelvic chordoma: A SEER-based retrospective study.

PURPOSE: Recently, competing risk nomograms were widely applied to predict prognosis in numerous tumors other than chordoma. Here, we aimed to construct and validate a competing-risk-based prognostic nomogram to predict 3- and 5-year cancer-specific death (CSD) in patients with spinal and pelvic chordoma. METHODS: All chordoma patient data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) resource, and a total of 485 chordoma patients were eventually included in this study. Multivariate competing risk model and multivariate Cox model were used to determine independent prognostic factors, respectively, and the results of the two models were compared. Nomogram was employed to visualize the competing risk model. The discrimination, calibration, and clinical utility of this model were evaluated by Harrell concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Ten-fold cross-validation was further utilized to validate the prognostic nomogram. RESULTS: Significant prognostic factors affecting CSD were age (P = 0.016), localized involvement (P < 0.0001), and radical resection (P < 0.001) in the multivariate competing risk model. C-indexes were 0.799 and 0.76, and AUC were 0.812 and 0.778 for 3- and 5-year CSD. Calibration plots demonstrated the nomogram was well-fitted, and DCA indicated good clinical utility. The nomogram showed good performance in the 10-fold cross-validation. CONCLUSION: We successfully built the first competing-risk-based nomogram to predict clinical outcomes in patients with spinal and pelvic chordoma. This well-established nomogram hopes to help clinicians with precise prognostic assessment and thus improve clinical outcomes.

Squash smear and fine needle aspiration features of conventional 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.

Intrasellar hemorrhagic chordoma masquerading as pituitary apoplexy: case report and review of the literature.

BACKGROUND AND IMPORTANCE: Chordomas are centrally located, expansile soft tissue neoplasms that arise from the remnants of the embryological notochord. Hemorrhagic presentation is exceedingly rare and can resemble pituitary apoplexy. Moreover, a purely intrasellar location of a chordoma is extremely uncommon. We report a case of a hemorrhagic intrasellar chordoma in an adult male, which presented similarly to pituitary apoplexy and was resolved with surgical resection. CLINICAL PRESENTATION: A 69-year-old male presented with a 4 week history of acute onset headache and concurrent diplopia, with significantly reduced testosterone and slightly reduced cortisol. His left eye demonstrated a sixth cranial nerve palsy. Magnetic resonance imaging of the brain showed a large hemorrhagic mass in the pituitary region with significant compression of the left cavernous sinus and superior displacement of the pituitary gland. The patient underwent an endoscopic endonasal transsphenoidal approach for the resection of the lesion. Near total resection was achieved. Final pathology revealed chordoma with evidence of intratumoral hemorrhage, further confirmed by immunopositive stain for brachyury. Post-operatively, the patient had improved diplopia and was discharged home on low dose hydrocortisone. At 3-month follow-up, his diplopia was resolved and new MRI showed stable small residual disease. CONCLUSIONS: Apoplectic chordomas are uncommon given chordoma's characteristic lack of intralesional vascularity and represent a diagnostic challenge in the sellar region. Our unique case demonstrates that despite our initial impression of pituitary apoplexy, this was ultimately a case of apoplectic chordoma that responded well to endoscopic endonasal surgery.

Chordoma: analysis of 47 fine-needle aspiration biopsy, cytologic imprint, and small biopsy specimens.

INTRODUCTION: Fine-needle aspiration (FNA) and small tissue biopsy of chordoma have been reported in several small series, but no large series exists. We undertook an examination of 47 cases (with concurrent core needle biopsy in a subset) to analyze diagnostic accuracy, cytomorphology, and immunohistochemistry. MATERIALS AND METHODS: Our cytopathology files were searched for examples of chordoma with histopathologic verification. FNA biopsy smears and core needle were performed using standard techniques. RESULTS: Forty-seven cases of chordoma were retrieved from 44 patients [M:F; 1.8:1; age range 5-81 years; mean age 55 years]. Twenty-seven presented with primary, 10 with locally recurrent, and 7 with metastatic tumors. Two aspirates were from the appendicular skeleton, 2 from the trunk, 1 from neck lymph node, and 42 aspirates (89%) from axial and peri-axial skeleton and surrounding soft tissues. Four were cytologic touch imprints while the remainder were FNA biopsy specimens. Specific cytologic diagnoses were chordoma/consistent with chordoma (44 cases, 94%), suspicious for chordoma (2), and malignant neoplasm (1). Along with a single case of benign notochordal tumor misdiagnosed as chordoma, our diagnostic accuracy was 91%. Concurrent tissue biopsy was performed in 51% of cases. Immunohistochemical staining of tumor in 29 (62%) cases showed expression of brachyury in 23 of 24 (96%) instances. Cytopathology consisted of cellular smears populated by large cells possessing enormous amounts of vacuolated and non-vacuolated cytoplasm with an abundant background myxoid/chondromyxoid stroma. CONCLUSIONS: FNA and small tissue biopsy specimens show a very high degree of diagnostic accuracy in recognition of chordoma.

Cordoma sacral metastático / Metastatic sacral chordoma

Os cordomas sacrais (CS) são tumores ósseos malignos primários da coluna vertebral de ocorrência rara, com incidência entre 0,000005-0,000027%. O objetivo deste estudo é relatar um caso de CS metastático. Homem de 41 anos, sem comorbidades, chega ao serviço de referência apresentando lesão sacral. Ressonância magnética mostrou tratar-se de tumor com 9,3 cm sugestivo de mieloma ou cordoma. Realizou-se biópsia e histopatológico, confirmando o diagnóstico de CS. O paciente submeteu-se à excisão cirúrgica do tumor. Seis meses após a cirurgia, evoluiu com recidiva e implantes metastáticos em coluna vertebral, partes moles da parede torácica, fígado e espa-ço pleural, evoluindo com paraplegia. Não havia indicação de radioterapia e/ou quimioterapia adjuvante. Não havia também possibilidade de liberação de imatinibe pelo Sistema Único de Saúde. Em cerca de 28 meses de seguimento clínico mensal, o paciente foi a óbito. O caso apresentado mostrou um CS sem sucesso cirúrgico, o que é associa-do a pior prognóstico. O paciente apresentou disseminação sistêmica do tumor e paraplegia poucos meses após a cirurgia, indo a óbito em 28 meses de seguimento. (AU)

Sacral chordomas (SC) are rare primary malignant bone tumors of the vertebral column, with an incidence between 0.000005-0.000027%. This study aims to describe a case of metastatic SC. A 42-year-old man without comorbid conditions, arrived at the referral center, presenting with a sacral lesion. MRI showed a tumor measuring 9.3 cm that was suggestive of myeloma or chordoma. A biopsy with histopathology study was performed, confirming the diagnosis of SC. The patient underwent surgical tumor excision. Six months after surgery, the tumor recurred with metastatic vertebral column implants, soft tissues of the chest wall, liver, and pleural space, and the patient developed paraplegia. There was no indication of adjuvant radiotherapy and/or chemotherapy. There was also no possibility that the Unified Health System would approve imatinib. At about 28 months of monthly clinical follow-up, the patient died. The case presented showed unsuccessful SC surgery, which is associated with a worse prognosis. The patient had systemic tumor dissemination and paraplegia a few months after surgery, dying at 28 months of follow-up. (AU)

[Chordoma-An update]. / Chordome ­ Ein Update.

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.

Chordoma: To know means to recognize.

Chordoma is a rare type of bone cancer characterized by its locally aggressive and destructive behavior. Chordoma is located in one of the three primary regions: skull base/clivus, sacrum or mobile spine. Chordoma grows slowly, therefore its insidious onset leads to delayed diagnosis, accounting for the low survival rates. Treatment centers around successful en bloc resection with negative margins, though, considering the anatomically constrained site of growth, it frequently requires adjuvant radiotherapy. This article analyzes the existing literature with the aim to provide a better insight in the current state of research in chordoma classification, characteristics, and management.

Immune Checkpoint Inhibitors Have Clinical Activity in Patients With Recurrent Chordoma.

The aim of this study is to evaluate the outcomes and tolerance of immune checkpoint inhibitors (ICIs) for patients with recurrent chordoma. We reviewed the records of 17 patients with recurrent chordomas who received ICIs for progressing disease as part of their treatment between 2016 and 2020. Response was assessed using response evaluation criteria in solid tumors 1.1 criteria. The Kaplan-Meier method was used to estimate the duration of response, progression-free survival (PFS), and overall survival (OS). Clinical benefit was defined as having stable disease (SD), a partial response, or a complete response. The median follow-up from the start of ICIs was 29 months [interquartile range (IQR): 13-35 m]. The majority received pembrolizumab (n=9, 53%), and the median number of cycles delivered was 8 (IQR: 7-12). The 1-year OS was 87%, and the 1-year PFS was 56% with a median PFS of 14 months (95% CI, 5-17 mo). After ICI initiation, most patients (n=15, 88%) had clinical benefit consisting of a complete response (n=1, 6%), partial response (n=3, 18%), and stable disease (n=11, 65%). Among all responders (n=15), the median duration of response was 12 months. Toxicities were limited: 2 (12%) patients having grade 3/4 immune-related toxicities (colitis, grade 3; myocarditis, grade 4). We observed a high rate of clinical benefit and favorable durability from ICI use for patients with recurrent chordoma. These data provide support for the integration of ICIs as a standard first-line systemic therapy option for patients with recurrent chordoma. Prospective studies are warranted to further evaluate efficacy and enhance response rates.

[Chordoma as a neurosurgical pathology]. / Khordoma kak neirokhirurgicheskaya patologiya.

OBJECTIVE: Assess the significance of chordoma as a neurosurgical pathology, taking into account the latest edition of the WHO classification of soft tissues and bone tumors (2020). MATERIAL AND METHODS: An analysis of 28 chordomas was carried out. All chordomas were histologically verified, including using immunohistochemical markers of notochordal differentiation (S100, EMA, keratin, brachiuria protein). RESULTS: Patients with chordomas accounted for 0.25% of the total number of neurosurgical patients. The vast majority (27) of chordomas had a cranio-vertebral localization. Sacral localization (S3-S5) of the tumor was detected in 1 patient. In 4 (15%) cases, operations were performed for the recurrence of chordoma. The tumors tended to grow into the structures of the skull, overgrown the vessels and nerves, and compress the adjacent brain structures. This was manifested by pain syndrome, neurological symptoms, impaired liquorodynamics. According to histopathological criteria, 27 (96%) cases of tumors were classified as conventional (usual) chordoma type, among them 7 corresponded to the chondroid subtype of the chordoma. In 1 case (4%), a dedifferentiated chordoma was detected. CONCLUSION: Chordoma, due to its axial localization, naturally involves adjacent structures of the nervous system, has clinically significant neuropathological manifestations, and often provides direct indications for a special neurosurgical approach. This requires its consideration not only as a bone, but also as a neurosurgical oncological pathology, along with other non-meningothelial (mesenchymal) tumors of the CNS.

Possible notochordal chordoma in a fossil fish from the Late Cretaceous of Lebanon.

OBJECTIVE: To describe a case of an expansive endocavitary lesion at the level of the caudal tract of the vertebral column of a juvenile fish (Pycnodont) from the Late Cretaceous (Cenomanian) of Lebanon (Hjoula). MATERIALS: The specimen is part of the Paleontological Collection of the University Museum of Chieti, Italy, Inventory Number P #23752. METHODS: The specimen was observed macroscopically, as well as under the stereo-microscope (Leica Wild M 8); aspersion with ethanol and razing light were used to improve the observations and to take micro-photos. RESULTS: The fossil juvenile fish has a visibly altered macroscopic anatomical morphology at the level of the caudal part of the vertebral column, which is pathological in comparison with the normal anatomy of the Pycnodonts. CONCLUSIONS: Although diagnosis cannot be certain, comparative analysis notes morphological and topographic affinity between the paleopathological case described here and notochordal chordoma, which affects some living fish. SIGNIFICANCE: This lesion represents the first case of a nonosseous tumor in a fossil fish, and suggests that this type of neoplasm was among the first of the neoplastic diseases to appear on Earth. LIMITATIONS: Diagnosis rendered from fossil remains is complex and is further limited by the rarity of the condition in the past. SUGGESTIONS FOR FURTHER RESEARCH: Continued comparative analysis of bony changes noted in this specimen with other fossil and living fish will contribute to our understanding of disease in the Earth's earliest inhabitants.

[Pediatric SMARCB1/INI1-deficient poorly differentiated chordoma of the skull base: report of five cases and review of literature].

Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.

[Notochordal tumors: From notochord to chordoma]. / Les tumeurs notochordales : de la notochorde au chordome.

The group of notochordal tumors consists of the benign notochordal cell tumor and the conventional, dedifferentiated and poorly differentiated chordomas in the fifth edition of the WHO classification of bone and soft tissue tumors. This update covers recent advances in the knowledge of the histogenesis and biology of these tumors and their implications in terms of diagnosis, prognosis assessment and therapeutic management.

Poorly Differentiated Chordoma of the Clivus With Loss of SMARCB1 Expression in a Pediatric Patient: A Case Report.

Poorly differentiated chordoma (PDC) is a rare, aggressive subtype of chordoma. A two-year-old girl presented with cervical pain, limb paralysis and respiratory failure. Magnetic resonance imaging and positron emission tomography-computed tomography revealed a tumor compressing the pons at the clivus and osteoblastic metastatic lesions of the left upper arm and right iliac bone. Her tumors shrank substantially after treatment with chemotherapy and proton beam therapy. Our initial diagnosis was an atypical teratoma/rhabdoid tumor, but final diagnosis of PDC was made on the basis of the immunohistochemical expression of brachyury. In addition, the detection of SMARCB1/INI1 mutation confirmed the diagnosis of PDC.

Less common extracerebral tumors.

This chapter examines the results of GKNS on a variety of extraparenchymal skull base tumors some benign and some malignant. For the benign tumors there is good evidence on the effectiveness of the method for pretty much all diagnoses. For malignant extraparenchymal tumors the results are more limited and GKNS only has a supportive role in these lesions.