CASE REPORT

Patient Identity

Name : Tn. DB

Age : 43 years old

Sex : Male

RM : 551616

Date of admission : 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 : 120/80 mmHg HR : 88 bpm, regular

RR : 16 tpm Temp. : 36.5°C

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 L

Biceps (+) (+)

Triceps (+) (+)

Achilles (+) (+)

Patellar (+) (+)

Phatologic Reflex:

R L

Babinski (-) (-)

Chadock (-) (-)

Openheim (-) (-)

Laboratory Findings

WBC 6.000 /uL Na 139

RBC 4.920.000 /Ul K 4.0

HGB 12.7 g/dl Cl 103

HCT 38.7% HBsAg(rapid) Negative

PLT 329.000/uL CT 7’00”

Ureum 19 mg/dl BT 3’00”

Creatinin 0,9 mg/dl PT 11,7 Kontrol 11,2

GDS 117 mg/dl APTT 25,6 kontrol 23,6

SGOT 18 U/L CEA 8,48

SGPT 22 U/L PSA 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 high-

grade 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 soft-

tissue 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 follow-

up 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.