A rare case of skin metastasis from a chordoma.

Chordoma is an uncommon, indolent malignant tumor arising from notochordal remnants. The incidence of distant metastasis varies between 30 and 40% in different series. Even though local involvement of the skin by direct invasion of chordoma is common, distant skin metastasis are rare, with less than 30 cases reported in the literature. The present clinical case illustrates the slow-growing natural history of a sacral chordoma, which evolved with lung metastasis, followed three years later by skin metastasis, thus giving us the opportunity to review the diagnostic approach, as well as the clinical and histopathological characteristics of this rare tumor.

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.

Chordoma metastatic to skin: A report of two cases and a brief review of the literature.

Chordomas are rare, locally aggressive tumors of notochordal origin usually arising in the spine or base of the skull. Skin involvement is rare and typically occurs via direct extension of the primary tumor to the skin. Although there are increasing reports of the skin being involved as a distant metastatic site in patients with chordoma, this remains an exceedingly rare occurrence. We present two cases of patients diagnosed with metastasis of chordoma to the skin that represented distant metastasis. In the first case, a patient with a primary thoracic/lumbar chordoma presented with isolated metastasis to the skin of the left lower jaw 9 years after initial diagnosis of the chordoma. To our knowledge, this is the first reported case of a chordoma of this site to develop distant skin metastasis. In the second case, a patient with a primary sacral chordoma presented with metastasis to the skin of the right side of his chin 6 years after initial diagnosis of the chordoma, following previous metastatic spread to the liver and lung. Finally, we briefly review the literature on chordoma metastasis to the skin and highlight salient features to raise awareness of this uncommon occurrence.

Cardiac Metastasis of Sacral Chordoma.

Chordoma is a rare tumor, usually diagnosed when the disease is advanced. Despite its slow growth, it is locally aggressive and has a poor long-term prognosis. Surgery is the mainstay treatment. Although cardiac metastases are very rare, the heart is frequently involved in systemic neoplastic diseases. This report describes a typical case of metastatic chordoma: the age at first diagnosis, the site of the primary tumor, and the slow growth of the cardiac metastasis were all typical features. Surgical excision of the mass from the right ventricular outflow tract is described together with echocardiographic, radiologic, and histopathologic characteristics of the metastatic chordoma.

Dedifferentiated Chordoma: Clinicopathologic and Molecular Characteristics With Integrative Analysis.

Dedifferentiated chordoma is a rare chordoma subtype characterized by a high-grade sarcoma juxtaposed to conventional chordoma. We identified a series of dedifferentiated chordomas, reviewed clinicopathologic features, performed next-generation sequencing in select cases, and analyzed all related English-language publications. Our series included 7 men and 3 women (age 15 to 80 y [median: 54 y]; <1% of >1000 chordomas surveyed). The tumor (2.8 to 24.5 cm [median: 5.8 cm] in size) presented de novo or as recurrence (including postradiotherapy) in sacrum (n=5), skull base (n=2), lumbar spine (n=1), thoracic/mediastinum (n=1), and lung (n=1; as metastasis). Histologically, the dedifferentiated component (3% to 95% [median: 60%]) was pleomorphic-to-fibrosarcomatous, juxtaposed to conventional (n=8) or chondroid (n=2) component. By immunohistochemistry, the conventional/chondroid component consistently expressed cytokeratin and brachyury, whereas the dedifferentiated component showed loss of both. We identified a sacral conventional chordoma with INI1 loss, with one of the lung metastases showing biphasic histology with loss of cytokeratin and brachyury in the dedifferentiated component. Sequencing identified tumor suppressor mutations in 4 tumors, including TP53 mutations in the dedifferentiated component in 3 tumors. Of 7 patients with follow-up, 6 developed metastases; 4 died at 15 to 99 months (median: 24 mo) after dedifferentiated chordoma diagnosis. Collectively, of 87 dedifferentiated chordoma patients described in 1913-2020 (including 10 herein), the median overall survival was 20 months. In summary, dedifferentiated chordoma involves diverse sites and presents de novo, postradiotherapy, or as recurrence/metastasis months-to-years after initial diagnosis. The dedifferentiated component shows loss of brachyury and cytokeratin staining and harbors recurrent TP53 mutations, implicating tumor suppressor dysregulation in chordoma dedifferentiation.

Cutaneous Metastasis from Cervical Spinal Chordoma: Case Report and Literature Review.

BACKGROUND: Chordomas are rare primary tumors of the bone that arise from embryonic notochord. They are locally aggressive tumors with a high tendency for postsurgical recurrence. On the other hand, distant metastases are rare. When they occur, they involve lungs, liver, lymph nodes, and bones. Skin and subcutaneous tissue involvement is even rarer and usually occurs by direct extension of the primary tumor or by local recurrence. Distant cutaneous metastasis from chordoma is an exceptional finding, with fewer than 20 cases reported in the literature. All the cutaneous metastases described derive from sacral chordomas, except for 2 cases in which the source of metastasis is skull-base chordomas. CASE DESCRIPTION: We report the case of a 55-year-old man with skin metastasis from a cervical chordoma. CONCLUSIONS: Metastasis has to be taken into account in the differential diagnosis when a new skin lesion appears in a patient with a past medical history of chordoma. To the best of our knowledge, this is the first case of cutaneous metastasis from spinal cervical chordoma. A systematic literature review was performed.

The role of TNF-α in chordoma progression and inflammatory pathways.

PURPOSE: Chordomas are highly therapy-resistant primary bone tumors that exhibit high relapse rates and may induce local destruction. Here, we evaluated the effects of tumor necrosis factor-alpha (TNF-α) on chordoma progression and clinical outcome. METHODS: Chordoma cells were treated with TNF-α after which its short- and long-term effects were evaluated. Functional assays, qRT-PCR and microarray-based expression analyses were carried out to assess the effect of TNF-α on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, invasion and cancer stem cell-like properties. Finally, relationships between TNF-α expression and clinicopathological features were assessed in a chordoma patient cohort. RESULTS: We found that TNF-α treatment increased the migration and invasion of chordoma cells. Also, NF-κB activation was observed along with increased EMT marker expression. In addition, enhanced tumor sphere formation and soft agar colony formation were observed, concomitantly with increased chemo-resistance and CD338 marker expression. The TNF-α and TNFR1 expression levels were found to be significantly correlated with LIF, PD-L1 and Ki67 expression levels, tumor volume and a short survival time in patients. In addition, a high neutrophil to lymphocyte ratio was found to be associated with recurrence and a decreased overall survival. CONCLUSIONS: From our data we conclude that TNF-α may serve as a prognostic marker for chordoma progression and that tumor-promoting inflammation may be a major factor in chordoma tumor progression.

Analysis of prognostic factors for survival in patients with primary spinal chordoma using the SEER Registry from 1973 to 2014.

BACKGROUND: Spinal chordomas are rare primary osseous tumors that arise from the remnants of the notochord. They are commonly considered slow-growing, locally invasive neoplasms with little tendency to metastasize, but the high recurrent rate of spinal chordomas may seriously affect the survival rate and quality of life of patients. The aim of the study is to describe the epidemiological data and determine the prognostic factors for decreased survival in patients with primary spinal chordoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry database, a US population-based cancer registry database, was used to identify all patients diagnosed with primary spinal chordoma from 1973 to 2014. We utilized Kaplan-Meier method and Cox proportional hazards regression analysis to evaluate the association between patients overall survival and relevant characteristics, including age, gender, race, disease stage, treatment methods, primary tumor site, marital status, and urban county background. RESULTS: In the data set between 1973 and 2014, a total of 808 patients were identified with primary spinal chordoma. The overall rate of distant metastatic cases in our cohort was only 7.7%. Spinal chordoma was more common occurred in men (62.6%) than women (37.3%). Majority of neoplasms were found in the White (87.9%), while the incidence of the Black is relatively infrequent (3.3%). Three hundred fifty-seven spinal chordomas (44.2%) were located in the vertebral column, while 451 patients' tumor (55.8%) was located in the sacrum or pelvis. Age ≥ 60 years (HR = 2.72; 95%CI, 1.71 to 2.89), distant metastasis (HR = 2.16; 95%CI, 1.54 to 3.02), and non-surgical therapy (HR = 2.14; 95%CI, 1.72 to 2.69) were independent risk factors for survival reduction in analysis. Survival did not significantly differ as a factor of tumor site (vertebrae vs sacrum/pelvis) for primary spinal chordoma (HR = 0.93, P = 0.16). Race (P = 0.52), gender (P = 0.11), marital status (P = 0.94), and urban background (P = 0.72) were not main factors which affected overall survival rate. CONCLUSION: There was no significant difference in overall survival rate between chordomas located in the sacrum and vertebral column. Spinal chordoma patients with an elderly age (age ≥ 60), performing non-surgical therapy, and distant metastasis were associated with worse overall survival. Performing surgery was an effective and reliable treatment method for patients with spinal chordoma, and public health efforts should pay more attention to the elderly patients with spinal chordoma prior to distant metastasis.

Multifocal metastatic chordoma to the soft tissues of the fingertips: a case report including sonographic features and a review of the literature.

Chordoma is a rare, locally aggressive tumor which commonly metastasizes, most often to the lung, liver, and spine. In this case report, a 59-year-old male with history of sacral chordoma and pulmonary metastases presented to the emergency department with swelling and discoloration of multiple left fingertips. The initial radiographs led to a presumptive diagnosis of gout, which did not respond to medical therapy. An ultrasound demonstrated multiple solid masses with vascular hyperechoic septations which were subsequently biopsied and proven to be metastatic chordoma. Metastatic disease to the hand is a well documented but rare manifestation of many malignancies. The clinical presentation and radiographic features of multifocal hand metastases may mimic entities such as systemic deposition and granulomatous diseases. To the best of our knowledge, this is the first case report of soft tissue chordoma metastases to the fingertips as well as the first reported sonographic description of chordoma metastases.

Iatrogenic seeding of skull base chordoma following endoscopic endonasal surgery.

OBJECTIVE: Iatrogenic tumor seeding after open surgery for chordoma has been well described in the literature. The incidence and particularities related to endoscopic endonasal surgery (EES) have not been defined. METHODS: The authors retrospectively reviewed their experience with EES for clival chordoma, focusing on cases with iatrogenic seeding. The clinical, radiographic, pathological, and molecular characterization data were reviewed. RESULTS: Among 173 EESs performed for clival chordomas at the authors' institution between April 2003 and May 2016, 2 cases complicated by iatrogenic seeding (incidence 1.15%) were identified. The first case was a 10-year-old boy, who presented 21 months after an EES for a multiply recurrent clival chordoma with a recurrence along the left inferior turbinate, distinct from a right petrous apex recurrence. Both appeared as a T2-hypertintense, T1-isointense, and heterogeneously enhancing lesion on MRI. Resection of the inferior turbinate recurrence and debulking of the petrous recurrence were both performed via a purely endoscopic endonasal approach. Unfortunately, the child died 2 years later due progression of disease at the primary site, but with no sign of progression at the seeded site. The second patient was a 79-year-old man with an MRI-incompatible pacemaker who presented 19 months after EES for his clival chordoma with a mass involving the floor of the left nasal cavity that was causing an oro-antral fistula. On CT imaging, this appeared as a homogeneously contrast-enhancing mass eroding the hard palate inferiorly, the nasal septum superiorly, and the nasal process of the maxilla, with extension into the subcutaneous tissue. This was also treated endoscopically (combined transnasal-transoral approach) with resection of the mass, and repair of the fistula by using a palatal and left lateral wall rotational flap. Adjuvant hypofractionated stereotactic CyberKnife radiotherapy was administered using 35 Gy in 5 fractions. No recurrence was appreciated endoscopically or on imaging at the patient's last follow-up, 12 months after this last procedure. In both cases, pathological investigation of the original tumors revealed a fairly aggressive biology with 1p36 deletions, and high Ki-67 levels (10%-15%, and > 20%, respectively). The procedures were performed by a team of right-handed surgeons (otolaryngology and neurosurgery), using a 4-handed technique (in which the endoscope and suction are typically passed through the right nostril, and other instruments are passed through the left nostril without visualization). CONCLUSIONS: Although uncommon, iatrogenic seeding occurs during EES for clival chordomas, probably because of decreased visualization during tumor removal combined with mucosal trauma and exposure of subepithelial elements (either inadvertently or because of mucosal flaps). In addition, tumors with more aggressive biology (1p36 deletions, elevated Ki-67, or both) are probably at a higher risk and require increased vigilance on surveillance imaging and endoscopy. Further prospective studies are warranted to evaluate the authors' proposed strategies for decreasing the incidence of iatrogenic seeding after EES for chordomas.

[Pulmonary Metastasis of Sacral Chordoma Fifteen Years after Resection of Primary Site;Report of a Case].

A 71-years-old man, who had undergone resection for sacral chordoma 15 years before, was admitted to our hospital to treat a nodule in the right middle lobe detected by computed tomography. The nodule was resected and was histologically diagnosed as lung-metastasis of chordoma.

Metastatic clival chordoma: a case report of multiple extraneural metastases following resection and proton beam radiotherapy in a 5-year old boy.

The authors report the case of a 5-year-old boy in whom extraneural metastases developed 5 years after he underwent an occipitocervical fusion and transoral approach to treat a clival chordoma without local recurrence. Following primary resection, the patient's postoperative course was complicated by recurrent meningitis secondary to CSF leak, which responded to antibiotics, and communicating hydrocephalus, for which a ventriculoperitoneal shunt was placed. The patient then underwent postoperative proton beam radiotherapy. Five years following his initial presentation, surveillance imaging revealed a new asymptomatic lung mass for which the patient underwent thoracotomy and resection of the mass. Histological examination of the lung mass revealed findings consistent with a de-differentiated chordoma, confirming extraneural metastasis from the original tumor without evidence of local recurrence. Chest wall and scalp metastases subsequently developed, and the patient was started on an adjuvant chemotherapy regimen that included imatinib and rapamycin followed by subsequent nivolumab and an EZH2 inhibitor for recurrent, disseminated disease. Despite this patient's remote and distant metastases, primary gross-total resection for chordoma remains a critical treatment objective, followed by proton beam radiotherapy. This case illustrates the importance of interval posttreatment imaging and the emerging potential to treat chordoma with molecularly targeted therapies.

Metastatic chordoma of the tongue: Case report.

Chordomas are rare bone tumors that arise from notochord remnants. They most commonly occur in the sacrum, but they also can be seen in the skull base, cervical spine, and thoracolumbar vertebrae. Chordomas account for 1 to 4% of all primary skeletal tumors. They are usually indolent, locally growing tumors. Distant metastasis has been reported in 3 to 48% of cases. When metastasis occurs, it is usually observed in the lung, bone, and liver. To the best of our knowledge, no case of a chordoma metastasis to the tongue has been previously reported in the literature. We report such a case in a 61-year-old man.

Cutaneous Metastasis From Sacral Chordoma.

Chordoma is a rare primary bone malignancy of notochord origin, representing 1-4% of malignant bone tumors., Typically, chordomas follow a slow progressive course with aggressive local extension, multiple recurrences, and metastases. Of particular interest to this case, cutaneous metastasis is exceedingly rare. Diagnosis of this entity can be a challenge due to the rarity of chordoma, as well as the infrequent presentation of distant cutaneous metastasis and non-specific clinical skin findings. We report a case of a 61-year-old male with a history of sacral chordoma treated by wide local excision 8 years prior to presentation developed a nodule on his scalp for 6 weeks. Physical examination revealed a 1 cm rubbery, pink, shiny dome-shaped nodule on his left occipital scalp. Hematoxylin and eosin sections revealed a lobular dermal proliferation of small ovoid cells and larger physaliferous cells with hyperchromatic, displaced nuclei and finely vacuolated "soap-bubble" cytoplasm in a myxoid stroma. Immunohistochemistry of tumor cells showed positivity for both S-100 protein and pancytokeratin (AE1/AE3), while smooth muscle actin (SMA), P63, and CK7 were negative. Additionally, tumor cells stained positive for brachyury. The medical history, clinical presentation, histopathological appearance and immunohistochemical profile are consistent with cutaneous metastasis from sacral chordoma, known as chordoma cutis. This case illustrates the integral role of dermatopathology in the diagnosis of a rare and critical condition.

What Are the Conditional Survival and Functional Outcomes After Surgical Treatment of 115 Patients With Sacral Chordoma?

BACKGROUND: Conditional survival is a measure of prognosis for patients who have already survived for a specific period of time; however, data on conditional survival after sacrectomy in patients with sacral chordoma are lacking. In addition, because sacral tumors are rare and heterogeneous, classifying them in a way that allows physicians to predict functional outcomes after sacrectomy remains a challenge. QUESTIONS/PURPOSES: (1) What is the overall survival and disease-free survival in patients treated by sacrectomy for chordoma? (2) What is the conditional survival probability and how do prognostic factors change over time in patients undergoing surgical resection for sacral chordoma? (3) What is the local recurrence rate after surgery, how was it treated, and what factors impact on local recurrence? (4) What is the postoperative motor, sensory, bowel, and bladder function by level of resection as determined by using a newly designed scoring method? METHODS: Between 2003 and 2012, our center treated 122 patients surgically for sacral chordoma. Of those, two died and five were lost before a minimum followup of 1 year was achieved, leaving 115 patients available for analysis in this retrospective study at a mean of 4.9 years (range, 1.3-10.8 years). Basically, single posterior or combined approaches were chosen based on the most cephalad extent of the tumor and resection level was normally at half or one sacral vertebrae above the tumor. The 5-year conditional survival rate was calculated based on Kaplan-Meier survival analysis. The effect of prognostic factors on conditional survival was also explored. A newly designed score method was proposed and adopted in the current study to critically evaluate the functional outcome after resection of the sacrum. Inter- and intraobserver reliability was tested by a preliminary study using kappa statistics and Spearman rank correlation coefficients. Significant interobserver (p < 0.01) and intraobserver agreement (κ > 0.75) were found in nine items between each observer. RESULTS: The estimated 5-year overall survival rate was 81% (95% confidence interval [CI], 72%-90%) at diagnosis. The 5-year disease-free survival rate was 52% (95% CI, 43%-63%). The 5-year conditional overall survival decreased with each additional year in the first 4 years (81% at diagnosis versus 60% at the fourth year, p < 0.0001) and increased slightly in the fifth year. Patients with adequate surgical margins displayed a higher 5-year survival than those with an inadequate margin (86% [95% CI, 76%-95%] versus 67% [95% CI, 48%-85%], p = 0.01) at diagnosis. Conditional survival estimates for patients who received operations elsewhere were lower than that of newly diagnosed patients treated by us at diagnosis (64% [95% CI, 46%-83%] versus 90% [95% CI, 82%-99%], p = 0.012), but with the numbers we had, we could not detect a difference in conditional survival between those treated elsewhere first compared with those initially treated by us at 5 years. The proposed score system for function evaluation was able to distinguish different levels of resection. The overall functional results for the preservation of bilateral S1, S2, and S3 were 40 ± 8%, 60 ± 12%, and 82 ± 11%, respectively. Patients who had preservation of only one S3 nerve root had more severe incontinence (1.99 ± 0.79 versus 2.60 ± 0.63, p = 0.01) and more sensory loss (1.88 ± 0.82 versus 2.31 ± 0.59, p = 0.02) than those patients with preservation of bilateral S3 nerve roots. CONCLUSIONS: The 5-year conditional survival for sacral chordoma decreased with each additional year and began to improve after the fourth year. In addition, the effect of the surgical margin and influence of previous surgery on conditional survival were not linear over time. The level of nerve root resections corresponded with the overall function scores according to the proposed scoring method. This information and scoring system should be valuable in discussing outcomes of sacrectomy in patients with chordoma who are considering this operation and serve as the basis for further study. LEVEL OF EVIDENCE: Level III, therapeutic study.

The role of diffusion-weighted MRI (DWI) in the differentiation of benign from malignant skeletal lesions of the pelvis.

PURPOSE: To evaluate the utility of Diffusion-weighted MRI in the differentiation of benign from malignant skeletal lesions of the pelvis. MATERIALS AND METHODS: In this retrospective study 33 patients with indeterminate skeletal lesions of the pelvis were evaluated with DWI. Minimum, mean, maximum ADC-values of the skeletal lesions were measured followed by qualitative assessment of DWI. All patients underwent histological confirmation using CT-guided biopsy or surgical resection. The histology of the skeletal lesions was correlated with the findings on DWI. RESULTS: There were 13 malignant lesions and 20 benign lesions. The mean, minimum and maximum ADC values (×10-6mm2/s) for benign skeletal lesions was higher than the mean ADC-values for malignant lesions (1422.2 vs 1263.7; 780.4 vs 771.8; 1969.6 vs 1676.8 respectively). These differences were however not statistically significant (P-values=0.29; 0.94; 0.149 respectively). The sensitivity, specificity, positive predictive value and negative predictive value for qualitative assessment of Diffusion-weighted MRI in the differentiation of benign from malignant skeletal lesions were: 53.9%, 85%, 70%, 73.9% respectively. Qualitative assessment of DWI (restricted diffusion versus non-restricted diffusion) allowed differentiation of benign from malignant skeletal lesions (P-value=0.0259). CONCLUSIONS: Qualitative assessment of DWI may aid in the differentiation of benign skeletal lesions from malignant skeletal lesions of the pelvis. Although DWI has a low sensitivity in the distinction of the two disease entities, it may be a useful adjunct due to its relatively high specificity. This is of particular importance in lymphoma where biopsy may only show chronic inflammatory cells and hence may be false negative.