Case Report Cordoma
Content
CASE REPORT
Patient Identity Name Age Sex RM Date of admission : Tn. DB : 43 years old : Male : 551616 : June 12th 2012
History Taking Chief Complains: Low Back Pain History of Disease: Suffered since + 10 months ago but became severe in last 1 month before admitted into Hospital. Initialy he felt pain at the buttock which spread to the soles of the feet, pain felt such as stabbing sensation. The pain is intermitten, not affected by the activity. Pain is also the same in both time of day or night. 1 month ago pain more severe. Patient is currently only able to walk about 10 meters. There is bladder dysfunction and constipation since 2 months ago. There is sexual dysfunction since 4 months ago. History of chronic cough (-), ATD comsuption (-), fever (-), sweat (-), tremor (-),weight loss (-), bloody stool (-). History tumor disease and family history (-). History of trauma (-), diabetic (-) and hypertension (-).
General Status Moderate/well nourished/conscious Vital Sign BP RR : 120/80 mmHg : 16 tpm HR Temp. : 88 bpm, regular : 36.5C
Local Status: Vertebra Region : I: deformity (-), gibbus (-) P: lump (+) size 2x2cm, irregular surface, soft consistency, immobile, ill defined, tenderness (+), lymph enlargement (-).
Clinical Appereance
Motoric Examination : within in normal limit Sensory Examination : within in normal limit Physiologic Reflex: R Biceps Triceps Achilles Patellar (+) (+) (+) (+) L (+) (+) (+) (+)
Phatologic Reflex: R Babinski Chadock Openheim (-) (-) (-) L (-) (-) (-)
Laboratory Findings
WBC RBC HGB HCT PLT Ureum Creatinin GDS SGOT SGPT
6.000 /uL 4.920.000 /Ul 12.7 g/dl 38.7% 329.000/uL 19 mg/dl 0,9 mg/dl 117 mg/dl 18 U/L 22 U/L
Na K Cl HBsAg(rapid) CT BT PT APTT CEA PSA
139 4.0 103 Negative 7’00” 3’00” 11,7 Kontrol 11,2 25,6 kontrol 23,6 8,48 0,676
Lumbosacral X-Ray AP/LAT (June 14th 2012)
MRI lumbosacral (June 7th 2012)
Histopatology : Microscopic : preparations of tumor tissue showed the sheets or elongated cords of clear cells with multiple intracytoplasmic vacuoles, so-called physaliphorous (“soap bubble”) cells, some cell show eosinophilic cytoplasmic, there is tumor cells within mucin bluish mass, focal necrose and there is little bleeding with little bone trabekel them. Conclusion: Suitable for chordoma Resume : A man 43 years old with chief complain low back pain suffered since 10 months ago and more severe at this 1 month last. There have bladder dysfunction and constipation since 2 month ago and sexual dysfunction since 4 months ago. From physical examination found lump at sacral region with size 2x2cm, irregular surface, soft consistency, immobile, ill defined, and tenderness. From the thoracolumbal X-Ray found litic lesion at sacral region. From lumbosacral MRI found T1 Isointense mass and T2 hiperintense heterogeneous at level CV S2- coccygeus which destruction bone and push rectum susp. Chordoma. From histopathology biopsy found the preparation suitable for Chordoma.
Diagnosis: Sacral Chordoma Treatment : Analgesic Wide en-bloc excision
CHORDOMA
BACKGROUND Chordomas are relatively rare, slow-growing, primary malignant bone tumors. They are thought to arise from notochordal remnants and thus they occur along the midline from the skull base to the sacrum. Because of their indolent and low-grade nature, chordomas are typically diagnosed at a late stage and therefore, often cause significant damage through local bone destruction and compromise of neurologic structures. The goal of treatment is to achieve surgical en bloc excision with tumor-free margins to maximize local tumor control and overall survival. Radiation therapy is often used postoperatively when tumor-free margins cannot be achieved. Prognosis in terms of both overall survival and prevention of local recurrence is highly dependent on the adequacy of initial surgical margins.
EPIDEMIOLOGI Chordomas comprise 1% to 4% of all primary bone tumors. The age adjusted incidence rate in the general population is 0.8 per 1,000,000 people. These tumors affect men nearly twice as frequently as women, and they are most commonly diagnosed in middle-aged persons. Although chordoma can occur in the pediatric population, particularly at the skull base, this is rare and accounts for <5% of all chordomas. The median age at diagnosis is 58.5 years, and the incidence increases with age. Chordomas occur only one fourth as frequently in blacks as in whites. Chordomas are found in the midline of the neuraxis, where they arise from intraosseous notochordal remnants within spinal segments from the clivus to the coccyx. The anatomic distribution has been commonly reported to be approximately 50% sacrococcygeal and 35% sphenooccipital, with15% occurring in the mobile spine, although this distribution varies by case series.3 In the largest published series to date (400 cases), McMaster et al2 reported that chordomas appeared in sacral, sphenooccipital, and spinal locations with approximately equal frequency. Boriani et al4 observed that chordomas that affect the mobile spine involve the lumbar spine most frequently (57% to 66%), followed by the cervical spine (24% to 29%) and the thoracic spine (10% to 13.5%). Chordomas are the most common primary bone tumors found in the mobile spine and the sacrum.
PRESENTATION Although the presentation of these lesions varies by location, pain is reported to be the most common presenting symptom regardless of location, in particular, pain with a gradual and insidious onset. Chordomas often encroach on the spinal canal, and they may cause compression of the spinal cord, cauda equina, or nerve roots. This is reflected in a wide range of neurologic symptoms, including weakness, sensory deficits, bowel and bladder incontinence, and sexual dysfunction. Regional extension dictates symptomatology, including symptoms not directly attributable to spinal cord or nerve root compromise. Chordomas involving the cervical region may obstruct the airway, give rise to a retropharyngeal mass, or cause dysphagia, dysphonia, or Horner syndrome. In the sacral region, presacral extension of chordomas can lead to rectal dysfunction, including obstipation, constipation, tenesmus, and hemorrhoids, as well as gluteal masses or masses that are palpable on rectal examination. Because of their slow growth rate and the often nonspecific nature of their symptoms, chordomas often evade diagnosis until late in the disease course. The mean duration of symptoms in reported series ranges from 4 to 40 months.
ADVANCED IMAGING Chordoma classically appears as an osteolytic lesion centered in the midline and in association with a large soft-tissue mass. Osteosclerotic areas or areas of mixed osteolytic and osteosclerotic bone destruction may be seen on CT scan. Amorphous intratumoral calcification can be detected on CT imaging in 30% to 90% of cases. In >50% of cases, a higherattenuation fibrous pseudocapsule can be seen surrounding the lowerattenuation soft-tissue mass. Compared with muscle, chordomas range from isointense to hypointense on T1-weighted MRI scans and are hyperintense on T2-weighted images. Chordomas are well-defined extramedullary masses that may be seen to compress and sometimes to encase adjacent neurovascular structures. These tumors commonly invade the intervertebral disk space as they extend between adjacent vertebral bodies. Chordomas may appear heterogeneous on T2-weighted MRI scans; they have internal hypointense foci on T1-weighted images because of intralesional calcification, cystic changes, and hemorrhage. They display prominent contrast enhancement on both CT and MRI scans.
HISTOLOGY Chordomas consist of lobulated tumor cell nests separated by fibrous septae, often within an overlying pseudocapsule. Sheets or elongated cords of clear cells with multiple intracytoplasmic vacuoles, so-called physaliphorous (“soap bubble”) cells, are a pathognomonic feature of these tumors. The nuclei are small, round, and darkly staining, and they display a mild to moderate amount of nuclear pleomorphism, with few mitotic figures. Mucin is abundant both intracellularly and extracellularly in the surrounding myxoid stroma. Necrotic areas are infrequently seen within chordomas; areas of calcification, hemorrhage, and resultant hemosiderin deposition are more common. The mucinous stroma may contain prominent sarcomatous elements, whether fibrous, chondroid, or osteoid, in dedifferentiated chordomas. These dedifferentiated chordomas are comparatively aggressive, tend to exhibit highgrade behavior, and carry a poor prognosis. In the well-described variant, chondroid chordoma, areas of bland-appearing hyaline cartilage make up a substantial component of the specimen. Benign notochordal cell tumors, also known as notochordal rests, are benign intraosseous lesions that often are mistaken for chordomas. The anatomic distribution of notochordal rests is the same as that of chordomas, and it has been suggested that these lesions may be precursors of chordomas. Benign notochordal rests are made up of sheets of vacuolated cells mixed with less vacuolated cells. It is important to note that benign notochordal rests lack the surrounding myxoid stroma characteristic of chordomas and have no mitotic figures or necrotic areas.
DIFFERENTIAL DIAGNOSIS Although chordomas are the most frequently occurring primary malignantbone tumor in both the sacrum and the mobile spine, metastatic lesions and multiple myeloma make up the overwhelming majority of sacral and spinal neoplasms.9 Chordomas may be confused with plasmacytoma because of their lytic appearance, but chordomas demonstrate positive scintigraphy. Osteomyelitis and lymphoma are also difficult to distinguish radiographically, but they can be distinguished from one another because of their distinct clinical courses. Benign notochordal rests do not display the bony destruction, cortical disruption, or associated softtissue masses seen in chordomas. Clinically, they are indolent and usually asymptomatic. Chordomas can be distinguished from chondrosarcoma and metastatic tumors on radiographic evaluation because chordomas lack the associated soft-tissue mass.
Other primary sacral tumors include benignlesions (eg, giant cell tumor, aneurismal bone cyst, osteoid osteoma, osteoblastoma, hemangioma, nerve sheath tumor) and malignant lesions (eg, Ewing sarcoma, primitive neuroectodermal tumor, osteosarcoma, Paget’s sarcoma, multiple myeloma, plasmacytoma). The differential diagnosis for primary vertebral lesions includes all of these entities as well as teratoma and dermoid. Myxopapillary ependymomas, which are lesions that arise from the filum terminale, are also occasionally mistaken for chordomas. Immunohistochemical analysis is one method of distinguishing chordomas from other lesions that are histologically similar, including choroid meningioma, chondroma, chondrosarcoma, melanoma, and metastatic adenocarcinoma. Most chordomas display S-100 immunoreactivity, thus distinguishing them from metastatic adenocarcinoma and meningioma, as well as epithelial membrane antigen immunoreactivity, thus distinguishing them from chondroma,
chondrosarcoma, and melanoma. Positive cytokeratin CAM 5.2 immunoreactivity is a highly sensitive but nonspecific means of detecting chordoma.
MANAGEMENT Surgery remains the mainstay of management of chordomas. However, adjuvant therapies are currently under investigation. Given the lowgrade nature of these lesions, wide en bloc excision is mandatory for curative treatment. The importance of obtaining wide tumor-free margins when possible cannot be underestimated. Numerous studies demonstrate a direct correlation between the extent of surgical resection and the length of recurrence-free survival. Sacral chordoma resection involves amputation of a portion of the distal sacrum or removal of the entire sacrum. A portion of the adjacent bony pelvis may also be removed to achieve an adequate margin. These procedures often involve the intentional sacrifice of one or more sacral nerve roots to achieve wide resection of the lesion. This may result in motor, sensory, sphincter, or sexual dysfunction. The resections can be classified based on the location of the highest segment removed or according to the highest level of nerve root sacrificed. We herein define sacral amputations as low (sacrifice of at least one S4 nerve root or any level below), middle (sacrifice of at least one S3 nerve root), or high (sacrifice of at least one S2 nerve root). Total sacrectomy is performed when both S1 nerve roots must be sacrificed. In general, ipsilateral resection of sacral nerve roots leads to ipsilateral motor and sensory deficits corresponding to the levels sacrificed; however, bowel and bladder function are usually
entirely preserved. Lowsacral amputations commonly result in complete preservation of sphincter function, although perineal numbness and sexual dysfunction are common. Midsacral amputations result in a variable degree of functional loss. Most patients are left with saddle anesthesia and reduced sphincter control but retain intact motor function. Preservation of at least one S3 root will result in normal bowel and bladder function in most patients. Limited functional urinary and fecal continence may be preserved when at least one S2 nerve root is spared, although most patients will have abnormal sphincter function. High sacral amputation and total sacrectomy with resection of the S1 nerve root frequently results in postoperative motor deficits, particularly in ankle plantar flexion. This can impair the patient’s ability to ambulate without external support, even if only temporarily. Patients undergoing high sacral amputation or total sacrectomy usually experience complete loss of sphincter control as well as saddle anesthesia and sexual dysfunction. Surgical management of sacral chordomas is challenging because of the complex regional anatomy, the often advanced stage of tumor growth, and the proximity to and encroachment on surrounding tissues. Accordingly, it is appropriate to bring together a multidisciplinary surgical team whose members may include specialists in surgical oncology, neurosurgery, orthopaedic surgery, vascular surgery, and plastic surgery. Adequate exposure of the lesions often requires a staged operation in which standard anterior, posterior, perineal, and lateral approaches are used in combination. Following tumor excision, advanced techniques in instrumentation (eg, iliac screws, transiliac bars) may be required to prevent spinopelvic instability, particularly for patients who require high amputation or total sacrectomy. In addition, soft-tissue reconstruction with rotational gluteal flaps or transpelvic vertical rectus abdominis myocutaneous flaps is recommended to promote wound healing and obliterate dead space. For vertebral body chordomas, en bloc resection with tumor-free margins remains the goal of surgical treatment. Numerous studies have demonstrated that intralesional excision leads to a high rate of local recurrence and negatively affects overall survival. To avoid this, en bloc spondylectomy, or removal of the entire vertebral body in one block, is performed (Figure 7). This procedure often requires a combination of posterior and anterior approaches, including thoracoabdominal and retroperitoneal abdominal as well as transpleural thoracotomy). En bloc removal of alL posterior elements of the vertebra is performed, followed by en bloc resection of the anterior portion. Spinal reconstruction is necessary. Excellent results have been obtained with
these surgical techniques. Wide en bloc resection is not always possible, either because of the size or extent of the tumor or because such resection would lead to excessive morbidity. Even though the margins are intralesional in these cases, an effort is made to perform extracapsular excision of the chordoma, which involves removal of the specimen without penetration of its surrounding pseudocapsule. Often these patients then receive adjuvant radiation therapy to provide local control over any residual disease.Chordomas in the upper cervical vertebrae require special consideration. Like sacral chordomas, these are in a region with complex anatomy and many sensitive structures. These tumors may extend into the retropharyngeal space or may spread epidurally, causing spinal cord compression. Multidisciplinary teams may be involved, including ear, nose, and throat specialists and plastic surgeons. The anterior phase of these procedures often consists of transglossal or transmandibular approaches (as opposed to transoral approaches). These approaches provide adequate visualization of the tumor pseudocapsule and allow for extracapsular excision. Radiation therapy can be used as an adjuvant treatment for chordomas with incomplete resection or positive margins; however, the efficacy of such treatment is unproved. Their proximity to sensitive neurologic tissues make chordomas difficult to treat with standard radiation therapy. These tumors are relatively radiation-resistant and thus are thought to require doses of ≥60 to 70 Gy, which may surpass the doses safely tolerated by the spinal cord.35 Moreover, metal hardware associated with spinal reconstructive surgery may produce artifacts that interfere with accurate targeting of the tumor volume during radiation therapy. Conventional photon-beam radiation therapy is used as an adjuvant treatment in patients undergoing subtotal excision. However, reports vary as to whether additional survival benefit is derived.36 Conventional treatments with doses of 40 to 60 Gy have produced 5-year local control rates of 10% to 40%.35 It is difficult to interpret and apply results given the rarity of the disease as well as the variability in surgical procedure, completeness of excision, and the timing and method of delivery of radiotherapy. However, radiation treatments are improving with recent advances in photon-beam therapy, including the use of intensity-modulated radiation therapy and stereotactic radiosurgery. Improved accuracy of tumor targeting can be achieved with both of these techniques, allowing for an increased tumor dose with reduced collateral damage to surrounding tissues.
The use of radiosensitizing agents to enhance response to photon-beam therapy has been reported in a small number of patients. Hadron therapy, which makes use of protons or charged particles such as carbon ions, helium, and neon, is another promising treatment modalityfor chordomas. Because of the ballistic properties of these particles, hadron dose deposition is limited to a sharply defined Bragg peak, which provides a steep gradient between the target dose and that delivered to the surrounding tissues. Thus, hadron therapy permits delivery of highdose radiation to the target tissue that, in principle, could surpass even the most sophisticated photon radiation delivery techniques while minimizing damage to nearby sensitive structures. Additionally, certain hadron particle beams may offer superior tumor kill properties. Hadron therapy may be used in combination with conventional photon beam therapy, or it may be given alone. Proton-beam therapy appears to offer an improvement in chordoma treatment, with reported local control rates of 50% to 60% at 5 years. However, there is no level I or II evidence to support this. Most of these studies are smaller case series, and they often combine data related to patients with chondrosarcoma and those with chordoma. More data are needed to evaluate the true short- and long-term efficacy of hadron therapy and to better determine the scenarios inwhich it will be useful as an adjunct treatment for chordoma. Chordomas have proved to be highly resistant to chemotherapy. This modality may have some impact on the rare, high-grade dedifferentiated chordoma. However, the development of newer molecularly targeted agents has led to renewed interest in the use of chemotherapy. One such agent, imatinib, an inhibitor of platelet-derived growth factor receptor-β (PDGFR-β), was used to treat chordomas in 18 patients.43 Many of these patients demonstrated symptomatic improvement and a tumor response evidenced by a reduction in contrast enhancement, with effects lasting for 1 year. These results are promising, especially in light of the recent report of a series of 31 chordomas, all of which displayed overexpression and activation of PDGFR-β.44 Clinical trials are ongoing, and other drugs are under investigation for chordoma, including antiangiogenic agents and epidermal growth factor receptor inhibitors.
PROGNOSIS Current studies suggest that the prognosis for patients with chordoma has improved dramatically with the adoption of aggressive surgical treatments. Older studies reported 5-year survival rates of 50% to 68% and 10-year survival rates of 28% to 40%,2,4 whereas newer case
series report 5-year survival rates of 73% to 86% and 10-year survival rates of 49% to 71%. Although chordomas are considered to be slow-growing neoplasms, they do have the propensity to metastasize. Metastases have been found in up to 5% of patients at the time of diagnosis and in up to 65% at autopsy; the most common sites of metastasis are the lungs, soft tissues, bone, skin, pancreas, heart, and brain. Most surgeons agree, however, that local recurrence is the most important determinant of long-term survival and that local control is the key to successful treatment. Bergh et al3 report a 21-fold increase in risk of tumor-related death in those with recurrent local disease. Several studies have confirmed that the recurrence rate is greatly increased for patients with intralesional excision compared with those who had adequate margins. Local control is difficult to achieve without en bloc excision and tumor-free margins regardless of the use of adjuvant radiotherapy. Thus, the current standard of care for chordomas remains aggressive en bloc surgical resection whenever possible to achieve optimal local control and survival. With the high rate of recurrence and the resulting poor prognosis, extended followup and surveillance is necessary for chordoma patients. At our institution, patients undergo CT scan of the resection bed immediately postoperatively, and MRI scanning is done within 48 hours. After release from the hospital, surveillance MRI scans are obtained every 3 months in the first year following resection, every 6 months in the second year, and annually thereafter.
SUMMARY Chordomas can appear at any location along the spine and often show advanced growth at the time of diagnosis. Such tumors are minimally responsive to radiation and chemotherapy; thus, surgical resection remains the mainstay of treatment. Local control and overall survival have been linked with the ability to perform radical resection. However, given the propensity for such lesions to become intimately associated with neural, vascular, and visceral structures, specifically at the skull base and sacrum, surgical morbidity may be substantial. For this reason, treatment of patients with chordomas should involve a multidisciplinary team consisting of doctors in the fields of surgical oncology, radiation oncology, neurosurgery, orthopaedic surgery, general surgery, and plastic surgery, as needed, to provide the best chance for an optimal outcome.
Patient Identity Name Age Sex RM Date of admission : Tn. DB : 43 years old : Male : 551616 : June 12th 2012
History Taking Chief Complains: Low Back Pain History of Disease: Suffered since + 10 months ago but became severe in last 1 month before admitted into Hospital. Initialy he felt pain at the buttock which spread to the soles of the feet, pain felt such as stabbing sensation. The pain is intermitten, not affected by the activity. Pain is also the same in both time of day or night. 1 month ago pain more severe. Patient is currently only able to walk about 10 meters. There is bladder dysfunction and constipation since 2 months ago. There is sexual dysfunction since 4 months ago. History of chronic cough (-), ATD comsuption (-), fever (-), sweat (-), tremor (-),weight loss (-), bloody stool (-). History tumor disease and family history (-). History of trauma (-), diabetic (-) and hypertension (-).
General Status Moderate/well nourished/conscious Vital Sign BP RR : 120/80 mmHg : 16 tpm HR Temp. : 88 bpm, regular : 36.5C
Local Status: Vertebra Region : I: deformity (-), gibbus (-) P: lump (+) size 2x2cm, irregular surface, soft consistency, immobile, ill defined, tenderness (+), lymph enlargement (-).
Clinical Appereance
Motoric Examination : within in normal limit Sensory Examination : within in normal limit Physiologic Reflex: R Biceps Triceps Achilles Patellar (+) (+) (+) (+) L (+) (+) (+) (+)
Phatologic Reflex: R Babinski Chadock Openheim (-) (-) (-) L (-) (-) (-)
Laboratory Findings
WBC RBC HGB HCT PLT Ureum Creatinin GDS SGOT SGPT
6.000 /uL 4.920.000 /Ul 12.7 g/dl 38.7% 329.000/uL 19 mg/dl 0,9 mg/dl 117 mg/dl 18 U/L 22 U/L
Na K Cl HBsAg(rapid) CT BT PT APTT CEA PSA
139 4.0 103 Negative 7’00” 3’00” 11,7 Kontrol 11,2 25,6 kontrol 23,6 8,48 0,676
Lumbosacral X-Ray AP/LAT (June 14th 2012)
MRI lumbosacral (June 7th 2012)
Histopatology : Microscopic : preparations of tumor tissue showed the sheets or elongated cords of clear cells with multiple intracytoplasmic vacuoles, so-called physaliphorous (“soap bubble”) cells, some cell show eosinophilic cytoplasmic, there is tumor cells within mucin bluish mass, focal necrose and there is little bleeding with little bone trabekel them. Conclusion: Suitable for chordoma Resume : A man 43 years old with chief complain low back pain suffered since 10 months ago and more severe at this 1 month last. There have bladder dysfunction and constipation since 2 month ago and sexual dysfunction since 4 months ago. From physical examination found lump at sacral region with size 2x2cm, irregular surface, soft consistency, immobile, ill defined, and tenderness. From the thoracolumbal X-Ray found litic lesion at sacral region. From lumbosacral MRI found T1 Isointense mass and T2 hiperintense heterogeneous at level CV S2- coccygeus which destruction bone and push rectum susp. Chordoma. From histopathology biopsy found the preparation suitable for Chordoma.
Diagnosis: Sacral Chordoma Treatment : Analgesic Wide en-bloc excision
CHORDOMA
BACKGROUND Chordomas are relatively rare, slow-growing, primary malignant bone tumors. They are thought to arise from notochordal remnants and thus they occur along the midline from the skull base to the sacrum. Because of their indolent and low-grade nature, chordomas are typically diagnosed at a late stage and therefore, often cause significant damage through local bone destruction and compromise of neurologic structures. The goal of treatment is to achieve surgical en bloc excision with tumor-free margins to maximize local tumor control and overall survival. Radiation therapy is often used postoperatively when tumor-free margins cannot be achieved. Prognosis in terms of both overall survival and prevention of local recurrence is highly dependent on the adequacy of initial surgical margins.
EPIDEMIOLOGI Chordomas comprise 1% to 4% of all primary bone tumors. The age adjusted incidence rate in the general population is 0.8 per 1,000,000 people. These tumors affect men nearly twice as frequently as women, and they are most commonly diagnosed in middle-aged persons. Although chordoma can occur in the pediatric population, particularly at the skull base, this is rare and accounts for <5% of all chordomas. The median age at diagnosis is 58.5 years, and the incidence increases with age. Chordomas occur only one fourth as frequently in blacks as in whites. Chordomas are found in the midline of the neuraxis, where they arise from intraosseous notochordal remnants within spinal segments from the clivus to the coccyx. The anatomic distribution has been commonly reported to be approximately 50% sacrococcygeal and 35% sphenooccipital, with15% occurring in the mobile spine, although this distribution varies by case series.3 In the largest published series to date (400 cases), McMaster et al2 reported that chordomas appeared in sacral, sphenooccipital, and spinal locations with approximately equal frequency. Boriani et al4 observed that chordomas that affect the mobile spine involve the lumbar spine most frequently (57% to 66%), followed by the cervical spine (24% to 29%) and the thoracic spine (10% to 13.5%). Chordomas are the most common primary bone tumors found in the mobile spine and the sacrum.
PRESENTATION Although the presentation of these lesions varies by location, pain is reported to be the most common presenting symptom regardless of location, in particular, pain with a gradual and insidious onset. Chordomas often encroach on the spinal canal, and they may cause compression of the spinal cord, cauda equina, or nerve roots. This is reflected in a wide range of neurologic symptoms, including weakness, sensory deficits, bowel and bladder incontinence, and sexual dysfunction. Regional extension dictates symptomatology, including symptoms not directly attributable to spinal cord or nerve root compromise. Chordomas involving the cervical region may obstruct the airway, give rise to a retropharyngeal mass, or cause dysphagia, dysphonia, or Horner syndrome. In the sacral region, presacral extension of chordomas can lead to rectal dysfunction, including obstipation, constipation, tenesmus, and hemorrhoids, as well as gluteal masses or masses that are palpable on rectal examination. Because of their slow growth rate and the often nonspecific nature of their symptoms, chordomas often evade diagnosis until late in the disease course. The mean duration of symptoms in reported series ranges from 4 to 40 months.
ADVANCED IMAGING Chordoma classically appears as an osteolytic lesion centered in the midline and in association with a large soft-tissue mass. Osteosclerotic areas or areas of mixed osteolytic and osteosclerotic bone destruction may be seen on CT scan. Amorphous intratumoral calcification can be detected on CT imaging in 30% to 90% of cases. In >50% of cases, a higherattenuation fibrous pseudocapsule can be seen surrounding the lowerattenuation soft-tissue mass. Compared with muscle, chordomas range from isointense to hypointense on T1-weighted MRI scans and are hyperintense on T2-weighted images. Chordomas are well-defined extramedullary masses that may be seen to compress and sometimes to encase adjacent neurovascular structures. These tumors commonly invade the intervertebral disk space as they extend between adjacent vertebral bodies. Chordomas may appear heterogeneous on T2-weighted MRI scans; they have internal hypointense foci on T1-weighted images because of intralesional calcification, cystic changes, and hemorrhage. They display prominent contrast enhancement on both CT and MRI scans.
HISTOLOGY Chordomas consist of lobulated tumor cell nests separated by fibrous septae, often within an overlying pseudocapsule. Sheets or elongated cords of clear cells with multiple intracytoplasmic vacuoles, so-called physaliphorous (“soap bubble”) cells, are a pathognomonic feature of these tumors. The nuclei are small, round, and darkly staining, and they display a mild to moderate amount of nuclear pleomorphism, with few mitotic figures. Mucin is abundant both intracellularly and extracellularly in the surrounding myxoid stroma. Necrotic areas are infrequently seen within chordomas; areas of calcification, hemorrhage, and resultant hemosiderin deposition are more common. The mucinous stroma may contain prominent sarcomatous elements, whether fibrous, chondroid, or osteoid, in dedifferentiated chordomas. These dedifferentiated chordomas are comparatively aggressive, tend to exhibit highgrade behavior, and carry a poor prognosis. In the well-described variant, chondroid chordoma, areas of bland-appearing hyaline cartilage make up a substantial component of the specimen. Benign notochordal cell tumors, also known as notochordal rests, are benign intraosseous lesions that often are mistaken for chordomas. The anatomic distribution of notochordal rests is the same as that of chordomas, and it has been suggested that these lesions may be precursors of chordomas. Benign notochordal rests are made up of sheets of vacuolated cells mixed with less vacuolated cells. It is important to note that benign notochordal rests lack the surrounding myxoid stroma characteristic of chordomas and have no mitotic figures or necrotic areas.
DIFFERENTIAL DIAGNOSIS Although chordomas are the most frequently occurring primary malignantbone tumor in both the sacrum and the mobile spine, metastatic lesions and multiple myeloma make up the overwhelming majority of sacral and spinal neoplasms.9 Chordomas may be confused with plasmacytoma because of their lytic appearance, but chordomas demonstrate positive scintigraphy. Osteomyelitis and lymphoma are also difficult to distinguish radiographically, but they can be distinguished from one another because of their distinct clinical courses. Benign notochordal rests do not display the bony destruction, cortical disruption, or associated softtissue masses seen in chordomas. Clinically, they are indolent and usually asymptomatic. Chordomas can be distinguished from chondrosarcoma and metastatic tumors on radiographic evaluation because chordomas lack the associated soft-tissue mass.
Other primary sacral tumors include benignlesions (eg, giant cell tumor, aneurismal bone cyst, osteoid osteoma, osteoblastoma, hemangioma, nerve sheath tumor) and malignant lesions (eg, Ewing sarcoma, primitive neuroectodermal tumor, osteosarcoma, Paget’s sarcoma, multiple myeloma, plasmacytoma). The differential diagnosis for primary vertebral lesions includes all of these entities as well as teratoma and dermoid. Myxopapillary ependymomas, which are lesions that arise from the filum terminale, are also occasionally mistaken for chordomas. Immunohistochemical analysis is one method of distinguishing chordomas from other lesions that are histologically similar, including choroid meningioma, chondroma, chondrosarcoma, melanoma, and metastatic adenocarcinoma. Most chordomas display S-100 immunoreactivity, thus distinguishing them from metastatic adenocarcinoma and meningioma, as well as epithelial membrane antigen immunoreactivity, thus distinguishing them from chondroma,
chondrosarcoma, and melanoma. Positive cytokeratin CAM 5.2 immunoreactivity is a highly sensitive but nonspecific means of detecting chordoma.
MANAGEMENT Surgery remains the mainstay of management of chordomas. However, adjuvant therapies are currently under investigation. Given the lowgrade nature of these lesions, wide en bloc excision is mandatory for curative treatment. The importance of obtaining wide tumor-free margins when possible cannot be underestimated. Numerous studies demonstrate a direct correlation between the extent of surgical resection and the length of recurrence-free survival. Sacral chordoma resection involves amputation of a portion of the distal sacrum or removal of the entire sacrum. A portion of the adjacent bony pelvis may also be removed to achieve an adequate margin. These procedures often involve the intentional sacrifice of one or more sacral nerve roots to achieve wide resection of the lesion. This may result in motor, sensory, sphincter, or sexual dysfunction. The resections can be classified based on the location of the highest segment removed or according to the highest level of nerve root sacrificed. We herein define sacral amputations as low (sacrifice of at least one S4 nerve root or any level below), middle (sacrifice of at least one S3 nerve root), or high (sacrifice of at least one S2 nerve root). Total sacrectomy is performed when both S1 nerve roots must be sacrificed. In general, ipsilateral resection of sacral nerve roots leads to ipsilateral motor and sensory deficits corresponding to the levels sacrificed; however, bowel and bladder function are usually
entirely preserved. Lowsacral amputations commonly result in complete preservation of sphincter function, although perineal numbness and sexual dysfunction are common. Midsacral amputations result in a variable degree of functional loss. Most patients are left with saddle anesthesia and reduced sphincter control but retain intact motor function. Preservation of at least one S3 root will result in normal bowel and bladder function in most patients. Limited functional urinary and fecal continence may be preserved when at least one S2 nerve root is spared, although most patients will have abnormal sphincter function. High sacral amputation and total sacrectomy with resection of the S1 nerve root frequently results in postoperative motor deficits, particularly in ankle plantar flexion. This can impair the patient’s ability to ambulate without external support, even if only temporarily. Patients undergoing high sacral amputation or total sacrectomy usually experience complete loss of sphincter control as well as saddle anesthesia and sexual dysfunction. Surgical management of sacral chordomas is challenging because of the complex regional anatomy, the often advanced stage of tumor growth, and the proximity to and encroachment on surrounding tissues. Accordingly, it is appropriate to bring together a multidisciplinary surgical team whose members may include specialists in surgical oncology, neurosurgery, orthopaedic surgery, vascular surgery, and plastic surgery. Adequate exposure of the lesions often requires a staged operation in which standard anterior, posterior, perineal, and lateral approaches are used in combination. Following tumor excision, advanced techniques in instrumentation (eg, iliac screws, transiliac bars) may be required to prevent spinopelvic instability, particularly for patients who require high amputation or total sacrectomy. In addition, soft-tissue reconstruction with rotational gluteal flaps or transpelvic vertical rectus abdominis myocutaneous flaps is recommended to promote wound healing and obliterate dead space. For vertebral body chordomas, en bloc resection with tumor-free margins remains the goal of surgical treatment. Numerous studies have demonstrated that intralesional excision leads to a high rate of local recurrence and negatively affects overall survival. To avoid this, en bloc spondylectomy, or removal of the entire vertebral body in one block, is performed (Figure 7). This procedure often requires a combination of posterior and anterior approaches, including thoracoabdominal and retroperitoneal abdominal as well as transpleural thoracotomy). En bloc removal of alL posterior elements of the vertebra is performed, followed by en bloc resection of the anterior portion. Spinal reconstruction is necessary. Excellent results have been obtained with
these surgical techniques. Wide en bloc resection is not always possible, either because of the size or extent of the tumor or because such resection would lead to excessive morbidity. Even though the margins are intralesional in these cases, an effort is made to perform extracapsular excision of the chordoma, which involves removal of the specimen without penetration of its surrounding pseudocapsule. Often these patients then receive adjuvant radiation therapy to provide local control over any residual disease.Chordomas in the upper cervical vertebrae require special consideration. Like sacral chordomas, these are in a region with complex anatomy and many sensitive structures. These tumors may extend into the retropharyngeal space or may spread epidurally, causing spinal cord compression. Multidisciplinary teams may be involved, including ear, nose, and throat specialists and plastic surgeons. The anterior phase of these procedures often consists of transglossal or transmandibular approaches (as opposed to transoral approaches). These approaches provide adequate visualization of the tumor pseudocapsule and allow for extracapsular excision. Radiation therapy can be used as an adjuvant treatment for chordomas with incomplete resection or positive margins; however, the efficacy of such treatment is unproved. Their proximity to sensitive neurologic tissues make chordomas difficult to treat with standard radiation therapy. These tumors are relatively radiation-resistant and thus are thought to require doses of ≥60 to 70 Gy, which may surpass the doses safely tolerated by the spinal cord.35 Moreover, metal hardware associated with spinal reconstructive surgery may produce artifacts that interfere with accurate targeting of the tumor volume during radiation therapy. Conventional photon-beam radiation therapy is used as an adjuvant treatment in patients undergoing subtotal excision. However, reports vary as to whether additional survival benefit is derived.36 Conventional treatments with doses of 40 to 60 Gy have produced 5-year local control rates of 10% to 40%.35 It is difficult to interpret and apply results given the rarity of the disease as well as the variability in surgical procedure, completeness of excision, and the timing and method of delivery of radiotherapy. However, radiation treatments are improving with recent advances in photon-beam therapy, including the use of intensity-modulated radiation therapy and stereotactic radiosurgery. Improved accuracy of tumor targeting can be achieved with both of these techniques, allowing for an increased tumor dose with reduced collateral damage to surrounding tissues.
The use of radiosensitizing agents to enhance response to photon-beam therapy has been reported in a small number of patients. Hadron therapy, which makes use of protons or charged particles such as carbon ions, helium, and neon, is another promising treatment modalityfor chordomas. Because of the ballistic properties of these particles, hadron dose deposition is limited to a sharply defined Bragg peak, which provides a steep gradient between the target dose and that delivered to the surrounding tissues. Thus, hadron therapy permits delivery of highdose radiation to the target tissue that, in principle, could surpass even the most sophisticated photon radiation delivery techniques while minimizing damage to nearby sensitive structures. Additionally, certain hadron particle beams may offer superior tumor kill properties. Hadron therapy may be used in combination with conventional photon beam therapy, or it may be given alone. Proton-beam therapy appears to offer an improvement in chordoma treatment, with reported local control rates of 50% to 60% at 5 years. However, there is no level I or II evidence to support this. Most of these studies are smaller case series, and they often combine data related to patients with chondrosarcoma and those with chordoma. More data are needed to evaluate the true short- and long-term efficacy of hadron therapy and to better determine the scenarios inwhich it will be useful as an adjunct treatment for chordoma. Chordomas have proved to be highly resistant to chemotherapy. This modality may have some impact on the rare, high-grade dedifferentiated chordoma. However, the development of newer molecularly targeted agents has led to renewed interest in the use of chemotherapy. One such agent, imatinib, an inhibitor of platelet-derived growth factor receptor-β (PDGFR-β), was used to treat chordomas in 18 patients.43 Many of these patients demonstrated symptomatic improvement and a tumor response evidenced by a reduction in contrast enhancement, with effects lasting for 1 year. These results are promising, especially in light of the recent report of a series of 31 chordomas, all of which displayed overexpression and activation of PDGFR-β.44 Clinical trials are ongoing, and other drugs are under investigation for chordoma, including antiangiogenic agents and epidermal growth factor receptor inhibitors.
PROGNOSIS Current studies suggest that the prognosis for patients with chordoma has improved dramatically with the adoption of aggressive surgical treatments. Older studies reported 5-year survival rates of 50% to 68% and 10-year survival rates of 28% to 40%,2,4 whereas newer case
series report 5-year survival rates of 73% to 86% and 10-year survival rates of 49% to 71%. Although chordomas are considered to be slow-growing neoplasms, they do have the propensity to metastasize. Metastases have been found in up to 5% of patients at the time of diagnosis and in up to 65% at autopsy; the most common sites of metastasis are the lungs, soft tissues, bone, skin, pancreas, heart, and brain. Most surgeons agree, however, that local recurrence is the most important determinant of long-term survival and that local control is the key to successful treatment. Bergh et al3 report a 21-fold increase in risk of tumor-related death in those with recurrent local disease. Several studies have confirmed that the recurrence rate is greatly increased for patients with intralesional excision compared with those who had adequate margins. Local control is difficult to achieve without en bloc excision and tumor-free margins regardless of the use of adjuvant radiotherapy. Thus, the current standard of care for chordomas remains aggressive en bloc surgical resection whenever possible to achieve optimal local control and survival. With the high rate of recurrence and the resulting poor prognosis, extended followup and surveillance is necessary for chordoma patients. At our institution, patients undergo CT scan of the resection bed immediately postoperatively, and MRI scanning is done within 48 hours. After release from the hospital, surveillance MRI scans are obtained every 3 months in the first year following resection, every 6 months in the second year, and annually thereafter.
SUMMARY Chordomas can appear at any location along the spine and often show advanced growth at the time of diagnosis. Such tumors are minimally responsive to radiation and chemotherapy; thus, surgical resection remains the mainstay of treatment. Local control and overall survival have been linked with the ability to perform radical resection. However, given the propensity for such lesions to become intimately associated with neural, vascular, and visceral structures, specifically at the skull base and sacrum, surgical morbidity may be substantial. For this reason, treatment of patients with chordomas should involve a multidisciplinary team consisting of doctors in the fields of surgical oncology, radiation oncology, neurosurgery, orthopaedic surgery, general surgery, and plastic surgery, as needed, to provide the best chance for an optimal outcome.
