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Clinical and Pathologic Review of 48 Cases of Chordoma

TYVIN A. RICH, MD..t ALAN SCHILLER, MD,* HERMAN D. SUIT, MD, PHD. AND HENRY J. MANKIN, MD9

The results of treatment of 48 patients with the diagnosis of chordoma during the period 1931 to 1981at the Massachusetts General Hospital were reviewed. Fourteen patients were treated with surgeryalone: eight patients with primary tumors in the sacrococcygeal region were treated with radical surgeryand four are alive with no evidence of disease (NED) with follow-up of 8 to 20 years. Recurrent tumorsin six patients were treated with surgery alone resulting in long palliation (3-25 years). The actuarialsurvival rate a t 5 years for all patients treated with surgery was 76%. Radiation therapy was used inpatients after either a biopsy (15), partial excision (17). or before radical excision in 2 patients. Toachieve a worthwhile level of palliation, doses greater than 4000 c G y were required. Highdose levels(>6500 cCy) were achieved in nine case s,by a combination of photon and 160 MeV proton beams.The results to date of this approach for lesions of the base of skull and cervical vertebral body areencouraging: high local control and low morbidity. The 5-year actuarial survival rate of all patientstreated with radiation was 50%.

Cancer 56:182-187, 1985.

HORDOMAS are rare tum ors that arise from rests ofC notochord cells along the spinal axis. Th e anatom icdistribution of these tumors is: sacrococcygeal, approx-imately 50%; vertebral, approximately 15%; an d basioc-ciput, approximately35%.- Chordomas grow slowly,producing local destructionof bone, and frequentlyextend to adjacent soft tissue. The most com mon s y m ptom is pain secondary to destructionof bone and/or topressure effects o n nervesor adjacent organs. The radio-logic featuresof chordomas have been well de ~ ri be d. ~ .Metastases are not seen except in those patients whosetumor has reached massive proportions as occurs com-monly in patients with tumors of the sacrococcygealand vertebral site^.^.'.^

Radical resection for lesions of the distal sacrum(S3-S S ) and coccyx may be curative, as total removal isoften achieved. In contrast, complete resection of chor-dom as of the base of skullor vertebra is rarely successfulbecause of the inability to achieve good surgical mar-g i n ~ . . ~Eradicationof chordomas by conventional radia-tion therapy alone is uncommon becauseof the large

size and/or the limitation on dose imposed by thesensitivity of adjacent structures. Where small lesions

From the Departmentsof *Radiation Medicine. $Pathology, andOrthopedic Surgery, Massachusetts General Hospital, HamardMedicalSchool, Boston, Massachusetts.

Address for reprints: Tyvin A.Rich, MD. Departmentof Radio-therapy, Universityof Texas System Cancer Center, M. D. AndersonHospital and Tumor Institute. 6723 Bertner Drive, Houston,TX77030.

Accepted for publication July13, 1984.

can be treated to high dose levels, long-term control canbe expected in a substantial number of patients.

Th is article presents an assessmentof the criteria forhistologic diagnosis of chordoma based upon a reviewof the clinical and pathologic featuresof tumors diag-nosed as chordoma at the Massachusetts GeneralHos-pital from 1931 to 1981. We then describe the surgicaland radiotherapeutic approaches employed in the treat-ment of these patients an d the results achieved.

Clinical Material

Th e clinical records of53 patients who were listed inour tumor registry with the diagnosis of chordoma werereviewed. Five cases were excluded because of a changeof diagnosis an d the rem aining 48 cases are reported.

The age, sex, and anatomic distributions are shownin Figures 1 and 2. A history of significant trauma tothe sacrum was recorded in2 of 19 patients withsacrococcygeal lesions.In both, this antedated the diag-nosis by about5 years. Table I lists the symptoms andrange of durat ion of sy mp tom s before diagnosis forchordom as at the basiocciput, vertebral,or sacrococcygealregions.For the 34 vertebral column and sacral patients,pain was the most frequent symptom. Of 14 patientswith chord om a of the base of the skull, diplopia was themost frequent symptom. Four of the baseof skullchordomas were of the chondroid variety (tumors con-taining featuresof either chondrosarcomaor chondroma,e . g , the stroma resembled hyaline cartilage with neo-plastic cells in lacunae).The mean durations of symp-

18 2


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CHORDOMA

n

0FornoloYolo

n

10-20 30-39 40-49 50.59 -69 70-79

Age

FIG. 1. Age and sex distribution o f patients with chordoma.

toms were 15.6 and 28.5 months for the regular and thechondroid chordomas of the base of skull, respectively.

Pathology

Grossly, this tumor appears nodular with dense fibroustrabeculae surrounding cystic or gelatinous tumor. Apushing margin can be seen associated with osteolysisand replacement of bone by diffuse tumor infiltration.The fresh specimens have frequently been described ashaving a deep reddish or purple color and containgrossly hemorrhagic zones. Soft tissue masses are fre-quently surrounded by a pseudocapsule.

Five of the original 53 cases of chordoma wereexcluded. The diagnosis was changed to metastatic ad-enocarcinoma in two cases that were reticulin negativeand had an unusual clinical course for chordoma. Intwo other cases, benign chordoma was found in thedura at the base of the skull on routine autopsy. Theselesions were clinically silent, and there was no evidenceof invasion of adjacent structures grossly or microscopically. In one case no tumor was found on histologicreview. The histopathologic slides were available for

review in 32 of the 48 cases. Detailed study of theseslides revealed that mitoses and necrosis were rarelyfound. Reticulin stains were performed on recut materialavailable in 24 cases; in 22, reticulin fibers formed aloose network around large cells with bubbly cytoplasm(the so-called physaliferous cells). In 16 of 48 cases,histologic material was unavailable but the clinical courseand radiographic features confirmed the diagnosis ofchordoma.

The incidence of metastasis was 18% (9/48) and onlyoccurred late in the course of disease, ( 5 sacrococcygeal,4 vertebral). Metastases were found in bones, lymph

. Rich et al.Percen t of

Total

28%

34 K

38 T o

B a s e ofSkull

Cervical

Thoracic

Lumbar

Sacro-C o c c y g a a l

183

MALE FEMALE

I I

FIG. 2. Sex and site distribution o f patients with chordom a.

nodes, brain, lungs, and abdominal viscera. The histo-logic pattern of the metastases was not different from

that of its primary lesion. The cause of death usually

TABLE I . Sympto ms of Patients With Chordoma

sacral ( 19)

Vertebral ( 15)

Base of Skull (14)

No . of patients withbase of skullchordoma

104

~ ~~~~~

Range, 2-24 moSacral pain 14Incontinence 2Constipation IRange, 2-48 moPain 16Bladder dysfunction 1Hoarseness 1Dysphagia 2Pharyngeal bleeding ILower extremity weakness 4

Range, 3-72 moDiplopia 10Headache 3Blindness IPtosis IGait disturbance 1Tinnitus/vertigo 1Hoarseness/dysphagia IDecreased visual acuity I

Average duration ofsymptoms

15.6 (1-48) Chordoma28.5 (6-72) Chondroid chordoma

(range in m o) Pathology


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184 C ANCERJuly 1 1985 Vol. 56

TABLE2. Treatment of Patients With Chordoma According to Site

Base of sacro-skull Vertebral coccygeal Total

Surgery 4 2 8 14Surgery (partial exci- 5 10 2 17

sion or total grossremoval) and post-operative radiation

Biopsy and radiation 5 3 7 15

Preoperative radiation - - 2 2and radical excision

48

was related to the consequence of the local effect ofrelentless growth of the primary lesion.

Treatment

T he use of surgery alone (1 4 cases)or in combinationwith radiation (34 cases) according to a natom ic site issummarized in Table 2. In the surgery alone group,eight patients with tumors located in the distal sacrumand coccyx had complete resection. One of these eightpatients was treated by total extirpation of the coccyxand the lower sacrum for recurrent disease, six hadlimited resection of the coccyx and a portionof thesacrum, and one had a hemi-pelvectomy for a massivetum or of the lower sacrum that extended laterally bencaththe sciatic notch. The morbidity of radical surgery (eightcases) was directly related to the location and extent ofthe tumor. Tumors in the distal sacrococcygeal regionwere totally removed withoutloss of anal or urogenitalfunction in six cases. In two cases more proximal therewas anal dysfunction resulting from the sacrifice of highsacral roots. In patients with more advanced tumors inthe sacrococcygeal region treated by radiation therapy,five had permanent neurologic damage affecting thebladder and seven had anal dysfunction before treatme nt.

In six other patients with tumors of the base of skull(four) or vertebral body (two), resection alone wassubtotal and usually achieved some relief of symptoms.There was one postoperative death secondary to sepsis

after incomplete removalof tum or from the basiocciput.Thirty-four patients were treated with radiation. In

17 patients radiation was given postoperatively after apartial excision (1 6) and after radical excision but withtumor spillage ( I ) . Partial excision means that grossdisease was left in the patient. This combined approachwas most frequently used in patients with tumors of thevertebral column where surgical removalof the tumorwas first attempted. Fifteen other patients were treatedwith radiation alone after biopsy. In seven patients(radiation alone [two],or partial excision and radiation[five]), residual disease remained after radiation and

further surgery was performed( 1-8 additional opera-tions). In two patients with extensive tumors of thesacrum, preoperative radiation was used before radicalexcision.

Physical characteristics of the radiation equipmentused varied markedly and included: 280 kvp x-ray,1 t o10 MeV x-ray,6oCo, an d 160 MeV protons. Iodine 125seeds were placed in the tum or bed along the pedicle ofthe second cervical vertebra in one case. The doses ofradiation vaned over the period studied. Treatment wasusually given as five treatm ents of 180 to 200 cGy pe rweek. In the earlier years dosesof orthovoltage radiationwere usually below 4500 cGy (eight patients). Fourteenother patients received doses between 4500 and 6000cGy (1-2 MeV). Three patients received total dosesgreater than 6000 cGy with only photons (6100-6300cGy). Nine patients have received combined pho ton a nd

160 MeV proton doses of 6490 to8040 cGyE (60Coc G y equivalent, 6oCo cG y + proton c G y X relativebiologic effectiveness [RBE]). For this clinical study, th eRBE of 160 mv protons is accepted asl.10.9 In twocases treated with orthovoltage the details of radiationdose were not available.

Results

Palliative radiation doses (6000 cGy except for one of the twopatients who received preoperative radiation( 5 0 0 0 cGy).Nine patients are NE D after high-dose radiation therapyand eight of these nine patients have received a boostdose of radiation with 160 MeV protons. Table 4summarizes the types of treatment for patients aliveafter either radical surgeryor radiation.

T he survival of all patients has been analyzed accord-ing to treatm ent modality (surgery alonevrrszis radiation)


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No. I CHORDOMA Rich et al. 185

TA B L E3. Patient Status According to T reatment a nd RadiationDose Level

Cause of failure~

TreatmentNo. of Local

Surgery Radiation patients NE D AW D Local -+ DM DM ID Lost

Radical excision None 8 4 0 2 0 0Palliative excision None 6 0 0 4 I 0Partial excision >6000 cG y 5 4 0 0 1 0

~ 6 0 0 0cG y 12 0 3 6 2 0Biopsy >6000 cG y 9 5 2 0 I 0


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186 CANCERJuly 1 1985 Vol. 56

logically similar to the malignant tumors but they donot invade surrounding structures,i.e., the distinctionbetween benign and malignantis not based simply uponcellular features of the tumor. The two cases in thisstudy were associated with other solid tumors but acorrelation between notochord rests and other malig-nancies has not been established.

The histologic review was designed to examine for acorrelation between on e or mo re histologic features andsurvival. N o correlation was detected between cellularpleomorphism, mitotic figures or hyperchromatic nuclei(rarely found), and survival. In three cases, multinucle-ated giant cells and nuclear inclusion cysts were seenbut the significance of this cytologic finding is unclear.Reports from earlier literature can be found that bothupp port^*^ and deny13 the correlation of histologic ob-servations with prognosis.

The only histologic correlation with survival in thisstudy was the presence of chondroid elements in thetumor. Chordomas with chondroid elements tend tofollow a relatively indolent course.A report from theMayo Clinic3 described average survival of15.8 yearsin 19 patients with chondroid chordoma arising in thebase of the skull as compared with 4.1 years for 36patients with pure chordom a. In our series, the patientswith chondroid chordomas generally had a longer du-ration of symptoms and were treated onlyb y surgery.T he relatively low biologic aggressiveness of these tum orsis reflected in t he survival (n ot disease-free) of4.8 to 8.7years for the chondroid variant in these patients treatedby surgery alone. In contrast, the maximum survival forthe ten patients with nonchondroid chordoma of thebase of the skull treated by partial excision and postoperative irradiation is3.7 years.

Although chondroid chordomas apparently behaveless aggressively and have a long natural history, thecourse of disease ultimately leads to tumor recurrenceand death. W e therefore recommend the use of radiationtherapy for these tumors when surgical removalisincomplete.

In our study the reticulin stain was found t o be usefulin differentiating chordomas from other tumors, partic-

ularly adenocarcinom a. In two excludedcases the clinicalcourse was rapidly fatal and the original diagnosis ofchordoma was questionable. In these two cases thehistologic appearance was more consistent with adeno-carcinoma and reticulin could not be found, whereas inall other 22 cases studied that had a clinical courseconsistent with chordoma reticulin was observed. Thereis supporting evidence for this histologic finding fromin vitro studies that chordom a cells produce extracellularr e t i c ~ l i n . ' ~ ~ ' ~The positive staining reaction found in thisstudy differs from a previous report that found thereticulin stain of no value in the diagnosis of chordom a.'6

Chord oma is considered a relatively radiation-resistant

tumor. Although there have been occasional cases ofrapid regression13*'7-20total doses of radiation of6000t o 7000 cGy, fractionated at200 cGy per day, appearto be required to achieve worthwhile palliation. Tumoreradication requires doses in excess of6500 to 7000cGy, but this can only be achieved in selected circum-stances when treatment volumes are small and includeminimal amounts of normal tissue. In this series wehave been able to achieve such dose levels in ninepatients treated by combinationsof photon and protonbeam technique for lesions in the base of the skull(seven patients, doses from6500 to 7550 c G y in 38fractions) and the second cervical vertebrae (two patients,7660 to 8040 cGy in 37 to 38 fractions). Eight of thesepatients a re free of disease from10 months to3.0 years;to date there has been no radiation morbidity.

In our opinion, surgery has been and remains the

primary treatment modality where it is technically fea-sible. Sufficient studies exist with long enough follow-up which demonstrate that cure by surgery canbeachieved with good functional results in patients withs a c r o c o c c y g e a l t ~ r n o r s . ~ * ~ . ~ * * * ~ ' * ~ ~T he role for radiationtherapy isless defined, but appears useful in combinationwith surgery where margins are involved with tumor orin small inoperable tumors.

Our approach has been modified by the use of com-puterized tomography, which now provides much moreprecise determination of tumor extent.A carefullyplanned effort between the surgeon and radiation ther-apist is likely to improve the local control by optimizingthe planned utilization of both modalities from thebeginning of treatment.Based on o ur study and a reviewof the literature the following recommendations aresuggested to maximize the results of radical surgery,high-dose radiation therap y, or the com bination of thesetwo m odalities.

SacrumTotal extirpation alon e where this is technically feasible

offers the best chance for cure. In selected cases wheretum or lies close to or involves the second sacral segments,treatment with a combination of surgery and radiation

is indicated because surgical margins will be close orthere may be cut-through of the tumor. There is majormorbidity associated with removal of bothS2 or partialSI sacral segments,e.g.,pelvicinstability, lumba r descent,and anal or bladder dysfunction. In an effort to reducethis morbidity, two .yatients have been treated withpreoperative radiation followed by sacrococcygeal resec-tion. Microscopic tumor was present at the resectionmargins in both patients: one patient has recurredlocally and the other is NED at48 months sincetreatment.

Repeated palliative operations have sometimes beensuccessful in prolonging survival. In our series one


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No. 1 CHORDOMA - Rich et ul. I87

patient lived 25 years with eleven local recurrences thatwere treated by surgery alone. Patients with large recur-rent and primary tumors of the sacrum treated withhigh-dose radiation therapy often achieved a usefulpalliation and survived 2. 5 to 10.5 years.

Vertebra and Base of Skull

In these sites total surgical extirpation is unlikelyexcept for very small lesions because of severe anatomicconstraints. Postoperative radiation is recommended inall cases with residual disease. In nine cases, high-doseprecision radiotherapy has been used for nonresectableor only partially resectable lesions with the proton beamand results to date are satisfactory (Table 4).

Survival longer than 10 years in patients with chor-domas has been reported. 1*3*5-73.21.23*24 Average survivalranges from 5.0 to 6.4 years and survival rates of 50%at 5 years have been reported by the Mayo Clinic.3 Thebest survival figures have been achieved for those patientswhose lesions could be treated by radical surgery, somepatients reportedly living free of disease 18 to 20 years.Four patients in our series are alive 8 to 20 years afterradical excision of a sacrococcygeal chordoma. Thesurvival at 5 years of the patients treated with surgeryalone is 71%. The patients treated with radiation had a50% survival at 5 years, and although some patientssurvived as long as 1 1 years, nearly all eventually diewith recurrence.

In conclusion, this review indicates that for large

lesions treatment by surgery with or without radiationmay achieve an occasional long-term disease-free sur-vival. For small lesions that are not resectable, high-dose precision therapy can achieve good results in somepatients. Our preference is to employ surgery wherefeasible and to combine this with radiation therapy inall situations where there is concern that the surgicalmargin will not be ample.

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