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.

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.

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.

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.

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.

[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.

Resources Required for Semi-Automatic Volumetric Measurements in Metastatic Chordoma: Is Potentially Improved Tumor Burden Assessment Worth the Time Burden?

The Response Evaluation Criteria in Solid Tumors (RECIST) is the current standard for assessing therapy response in patients with malignant solid tumors; however, volumetric assessments are thought to be more representative of actual tumor size and hence superior in predicting patient outcomes. We segmented all primary and metastatic lesions in 21 chordoma patients for comparison to RECIST. Primary tumors were segmented on MR and validated by a neuroradiologist. Metastatic lesions were segmented on CT and validated by a general radiologist. We estimated times for a research assistant to segment all primary and metastatic chordoma lesions using semi-automated volumetric segmentation tools available within our PACS (v12.0, Carestream, Rochester, NY), as well as time required for radiologists to validate the segmentations. We also report success rates of semi-automatic segmentation in metastatic lesions on CT and time required to export data. Furthermore, we discuss the feasibility of volumetric segmentation workflow in research and clinical settings. The research assistant spent approximately 65 h segmenting 435 lesions in 21 patients. This resulted in 1349 total segmentations (average 2.89 min per lesion) and over 13,000 data points. Combined time for the neuroradiologist and general radiologist to validate segmentations was 45.7 min per patient. Exportation time for all patients totaled only 6 h, providing time-saving opportunities for data managers and oncologists. Perhaps cost-neutral resource reallocation can help acquire volumes paralleling our example workflow. Our results will provide researchers with benchmark resources required for volumetric assessments within PACS and help prepare institutions for future volumetric assessment criteria.

Sorafenib in patients with locally advanced and metastatic chordomas: a phase II trial of the French Sarcoma Group (GSF/GETO).

BACKGROUND: There is no consensual treatment of locally advanced or metastatic chordomas. PATIENTS AND METHODS: We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. RESULTS: Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30-86) years. There were 17 men and 10 women. Twelve patients had been previously treated with chemotherapy and molecularly targeted agents. The maximum toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27 [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free rate of 73.0% (95% CI 46.1-88.0) and a 12-month overall survival rate of 86.5% (95% CI 55.8-96.5). Survival curves were similar in pretreated and not pretreated patients. DISCUSSION: Additional clinical trials further exploring sorafenib as a treatment of locally advanced or metastatic chordomas are warranted.

Diffuse skeletal muscle metastases from sacral chordoma.

Chordomas are rare, slow-growing tumors arising from cellular remnants of the notochord. They account for 1-4% of primary malignant bone tumors and usually occur in the axial skeleton, most commonly the sacrum. Although typically locally recurrent, chordoma metastasis rates as high as 10-42% have been reported. While spread to multiple organ systems has been documented, metastatic disease to skeletal muscle is extremely rare. We present a case of extensive, multifocal skeletal muscle metastases developing in the setting of recurrent sacral chordoma. Our literature search found only one additional case of metastatic chordoma to a single skeletal muscle.

Unusual location of chordoma metastasis.

BACKGROUND: Chordoma is a rare tumor originating from the remnants of the notochord. The tumor is known as locally aggressive with a strong tendency for recurrence rather than metastasis. CASE REPORT: We reported on a case of a 47-year-old Caucasian male with a history of sacral chordoma with metastasis to the cicatrix. CONCLUSIONS: Skin involvement in chordoma is uncommon but, according to literature, possible. Nevertheless, to our knowledge, there were no reports on incisional chordoma.

Phase II study on lapatinib in advanced EGFR-positive chordoma.

BACKGROUND: To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. PATIENTS AND METHODS: From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phospho-arrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) ≥ 6 months). RESULTS: All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. CONCLUSIONS: This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29.

Maxillary surgical seeding of a clival chordoma.

Seeding on surgical pathway is a rare form of clival chordoma treatment failure. We report the case of a 42-year-old male with a clival chondroid chordoma removed by a sublabial transsphenoidal approach followed by proton beam radiotherapy, who developed a maxillary bone recurrence 3 years after surgery.

Primary malignant bone tumors--recent developments.

Primary malignant bone tumors are rare sarcomas with an estimated frequency of about 2900 new cases per year; they constitute less than 0.2% of all cancers diagnosed in the United States. The diagnosis and management of these neoplasms require a team approach, which includes orthopaedic surgeons, radiologists, pathologists, and oncologists. With this approach and current treatment modalities, the 5-year survival for the most common malignant bone tumors, osteosarcoma and Ewing sarcoma, are 70% and 60%, respectively. This review will summarize recent developments and advances in molecular pathogenesis of the more common primary malignant bone neoplasms.

Intraneural parachordoma of the arm with regional metastases.

Parachordoma is a rare tumor, with fewer than 100 cases reported. We present an unusual presentation of a long tumor tracking along the median nerve, with regional metastasis to the axillary nodes in a 67-year-old woman. The tumor extended from the wrist proximally along the forearm to the elbow, coursing intraneurally along the median nerve. We present this case due its rarity, interesting radiographic appearance, and atypical presentation.

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.

Surgical margins and local control in resection of sacral chordomas.

BACKGROUND: The treatment of choice in sacral chordoma is surgical resection, although the risk of local recurrence and metastasis remains high. The quality of surgical margins obtained at initial surgery is the primary factor to improve survival reducing the risk of local recurrence, but proximal sacral resections are associated with substantial perioperative morbidity. QUESTIONS/PURPOSES: We considered survivorship related to local recurrence in terms of surgical margins, level of resection, and previous surgery. METHODS: We retrospectively reviewed 56 patients with sacral chordomas treated with surgical resection. Thirty-seven were resected above S3 by a combined anterior and posterior approach and 19 at or below S3 by a posterior approach. Nine of these had had previous intralesional surgery elsewhere. The minimum followup was 3 years (mean, 9.5 years; range, 3-28 years). RESULTS: Overall survival was 97% at 5 years, 71% at 10 years, and 47% at 15 years. Survivorship to local recurrence was 65% at 5 years and 52% at 10 years. Thirty percent of patients developed metastases. Wide margins were associated with increased survivorship to local recurrence. We found no differences in local recurrence between wide and wide-contaminated margins (that is, if the tumor or its pseudocapsule was exposed intraoperatively, but further tissue was removed to achieve wide margins). Previous intralesional surgery was associated with an increased local recurrence rate. We observed no differences in the recurrence rate in resections above S3 or at and below S3. CONCLUSIONS: Surgical margins affect the risk of local recurrence. Previous intralesional surgery was associated with a higher rate of local recurrence. Intraoperative contamination did not affect the risk of local recurrence when wide margins were subsequently attained.

Cytologic diagnosis of chordoma in a peritoneal effusion: a case report.

BACKGROUND: Chordoma, a distinct malignant neoplasm arising from the remnants of the notochord, occurs mostly in patients in the fifth to seventh decade of life. Metastasis occurs in 20-30% of cases. The most common metastatic sites are lungs and, less commonly, other bones and visceral organs. The cytologic features of chordoma in both primary and metastatic foci have been described for specimens obtained by fine needle aspiration biopsy. A few cases have been reported in the sputum and the cerebrospinal fluid. CASE: A 57-year-old man presented with metastatic chordoma diagnosed in a peritoneal effusion. Cytospin slides of the effusion showed numerous individual and clusters of polygonal, round epithelial cells with a background of myxoid chondroid substance, which stained metachromatic on Diff-Quik slides. Many diagnostic physaliphorous cells were present and characterized by abundant intracytoplasmic vacuoles of various sizes. The nuclei were monotonous, with minimal anisonucleosis. The nuclei had evenly dispersed chromatin with occasional small, eosinophilic nucleoli. The nuclear membranes were smooth, with focal indentation. The differential diagnosis included an adenocarcinoma and metastatic chordoma. Immunohistochemistry applied to the cell block showed that the neoplastic cells were positive for cytokeratin and S-100 protein. CONCLUSION: The clinical history with immunohistochemical profiles helped confirm the diagnosis of metastatic chordoma.