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Copy right t 9144 b The Journal of Bot .a, id Joint .Surgert . It corp()r(It.

VOL 66-A, NO. I . JANUARY 954 53

Dedifferentiated Parosteal Osteosarcoma

BY LESTER E. WOLD, M.D.*, KRISHNAN K. UNNI, M.D.*, JOHN W. BEABOUT, M.D.*, FRANKLIN H. SIM, M.D.*.

AND DAVID C. DAHLIN, M.D.*, ROCHESTER, MINNESOTA

From the Section of Surgical Pathology and the Departments of Diagnostic Radiology and Orthopedics.

Maw Clinic and Mayo Foundation, Rochester

ABSTRACT: Parosteal osteosarcoma is an uncom-

mon malignant tumor of bone, and in a review of Mayo

Clinic records we identified eleven cases of so-called de-

differentiated parosteal osteosarcoma. Ten of the eleven

patients had had a long history of treatment for multiple

recurrences of the tumor as a low-grade parosteal os-

teosarcoina and then for a definite recurrence as a high-

grade undifferentiated osteosarcoma. The prognosis in

this group of patients was similar to that in patients with

conventional osteosarcoma.

Parosteal osteosarcoma was first described as a distinct

clinicopathological entity in 195 1 , but it was called parosteal

osteoma8. Since that time, there has been a general con-

sensus in the literature that the tumor is of low-grade ma-

lignancy, as pointed out in reports of several small series72.

Although most of the parosteal osteosarcomas described in

the present report were found by a review of the records of

tumors occurring on the surface of bone - that is, tumors

that lack medullary involvement - not all of the surface

lesions in our series were low-grade parosteal osteosarcoma.

A variety of other tumors develop on the surface of bone,

including periosteal chondroma , periosteal osteosarcoma,

and various surface tumors that extend into the medullary

areas of bone and have the histological appearance of either

intramedullary osteosarcoma or osteochondroma . Even such

reactive conditions as ossifying or calcifying hematomas

can occur on the surface of bone and extend toward the

marrow.

Previous studies of parosteal, or juxtacortical, tumors

have included mention of the occasional occurrence of high-

grade anaplastic tumors that do not fit the usual patterns that

are associated with parosteal osteosarcoma579#{176}24. In

most of these reports a low-grade parosteal osteosarcoma

dedifferentiated , after multiple recurrences, to high-

grade tumor. In 1979, Dunham et al. reported on a patient

with a large parosteal osteosarcoma that had transformed

into a high-grade osteosarcoma. This had previously been

reported from the Mayo Clinic; such a so-called transfor-

mation had been noted in three of fifteen5 and seven of

I 2 patients with parosteal osteosarcoma.

The present series consisted of eleven Mayo Clinic

* Mayo Clinic. 200 First Street SW. , Rochester. Minnesota 55905.

Please address reprint requests to Dr. Wold.

patients in whom dedifferentiation of parosteal osteosar-

coma was evident. We undertook this study to define the

clinical and prognostic correlates of histologically high-

grade malignant tumors that coexist with or are derived from

the usual low-grade parosteal osteosarcoma.

Clinical Observations

We identified eleven cases ofdedifferentiated parosteal

osteosarcoma in fifty-five patients who were treated at the

Mayo Clinic for parosteal osteosarcoma. These eleven pa-

tients comprised perhaps 1 per cent of the approximately

1 ,200 patients who were seen with osteosarcoma. Gross

specimens of the high-grade recurrence were available for

review for six of the eleven patients. and multiple histo-

logical sections were available for review for all patients

(including sections of the original tumor in five of them).

When necessary, additional histological material was sub-

milled for evaluation, in particular to document the presence

or absence of evidence of medullary involvement. Clinical

data and follow-up information were obtained from the pa-

tients charts and from letters from the referring physicians.

There were seven female and four male patients. At

the time of the onset of symptoms or at the first attempt at

therapy, six were in their teen-age years. three were in their

twenties, and two were in their thirties. The initial symptoms

were those most commonly associated with neoplasia of

bone - that is, pain or a mass, or both. The distribution

of these tumors was equivalent to that associated with or-

dinary low-grade parosteal osteosarcoma: eight tumors were

in the distal part of the femur: two, in the proximal part of

the humerus; and one, in the proximal part of the tibia. Of

the eleven patients, one had coexistent low-grade parosteal

osteosarcoma and high-grade dedifferentiation when first

seen.

Dedifferentiation was documented in three patients at

the time of the first recurrence. in five at the time of the

second, and in two at the time of the third recurrence.

The interval from the onset of symptoms or the tinie

of the first operation to the time of dedifferentiation ranged

from thirty-one to 396 months, with a mean of I 53 months

(Table I). At the time of dedifferentiation. six patients had

a minimum amount (less than one centimeter) of medullary

involvement.

Radiographs or photographic copies of radiographs

were available for seven of the eleven patients. Interpre-

Fio. 1-A FIG. 1-B

54 L. E. WOLD, K. K. UNNI, J. W. BEABOUT, F. H. SIM, AND D. C. DAHLIN

THE JOURNAL OF BONE AND JOINT SURGERY

Figs. 1-A. I-B. and I-C: Dedifferentiated parosteal osteosarcoma in the distal part of the finiur.Fig. I-A: Preoperative radiograph showing a typical broad-based. heavily mineralized parosteal osteosarcoma with lobulation. The tubulation of the

femur is altered.Fig. 1-B: Appearance one year after the tumor was shaved off the surface of the femur.

tations of the radiographs were available for the remaining

patients, and all indicated that the tumor was on the surface

of the bone.

Radiographs made before any surgical procedure had

been performed were available for five patients. All of the

tumors were located on the surface of the bone and had the

typical characteristics of parosteal osteosarcoma. None had

any evidence of medullary involvement. Serial radiographs

showing the entire course of the tumor were available for

two patients (Figs. 1-A, 1-B, and 1-C). In both of them the

parosteal osteosarcoma was originally thought to be a benign

tumor (Fig. 1-A). Follow-up radiographs showed postop-

erative changes (Fig. 1 -B) and then a mass appeared on the

surface of the bone or in the adjacent soft tissues (Fig.

1-C) at the site ofthe previous operation. In all five patients

for whom preoperative radiographs could be compared with

radiographs made at the time ofdedifferentiation, the degree

of mineralization of the tumor matrix was consistently less

in the dedifferentiated tumor than it had been in the initial

parosteal osteosarcoma.

All patients except one (Case 1 1 ) had biopsy or excision

as the initial treatment. At the time ofdedifferentiation, nine

patients were treated with amputation; one. with disarticu-

lation; and one. with forequarter amputation. In general,

the gross appearance of the tumor at the time of dediffer-

entiation was somewhat similar to that of a usual low-grade

parosteal osteosarcoma (Fig. 2). The general characteristics

included areas of dense hard tumor, a broad base, a bos-

selated surface with or without a cartilage cap. and infiltra-

tion of surrounding skeletal muscle. Areas that were proved

histologically to be dedifferentiated were grossly softer. His-

tologically these tumors often had areas of low-grade par-

osteal osteosarcoma, characterized by parallel arrays of

irregularly shaped osseous trabeculae with an intervening

spindle-cell component (Fig. 3). Adjacent to these areas

were anaplastic high-grade foci, often with spindle-cell dif-

ferentiation and the fine lacelike osteoid of conventional

high-grade intramedullary osteosarcoma (Fig. 4). These

areas had less well formed, dense osteoid production than

did the adjacent low-grade portions of the tumor. The an-

aplasia within these foci was considered to be grade 3 or 4

according to Broders method. Six of the tumors involved

the medullary cavity at the time of dedifferentiation (Fig.

5). In two patients the medullary component was minimum

and in four there was gross medullary involvement.

Follow-up information was available for nine of the

FIG. 1-C

A tumor of the distal part of the femur that recurred twice in a twenty-three-year period. Although a large portion of the neoplasm is on the surfaceof the bone. this dedifferentiated parosteal osteosarcoma now also involves the medullary cavity. The patient died of pulmonary metastases three yearsafter amputation.

DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA 55

Three years and three months after operation. a poorly mineralized four-centimeter mass is seen on the surface of the bone. indicating a recurrenttumor.

eleven patients. Five had died of the disease and four pa-

tients were alive (Table I). Ofthe six patients with medullary

involvement, three had died of the disease, two were alive

and free of disease, and one could not be followed. Of the

five patients without medullary involvement, two were alive

and free of disease, two had died of the disease. and one

could not be followed.

Discussion

The 20 per cent incidence of dedifferentiation of low-

grade parosteal osteosarcomas in patients at the Mayo Clinic

is evidence of the importance of correct diagnosis and treat-

ment when the lesion is first seen. This incidence is higher

than that reported in other series but this may be due to a

selection bias at our institution. Seven of the patients in this

study were referred to the Mayo Clinic at the time that

dedifferentiation was documented. Three patients (Cases 1,

2, and 3; Table I) who were treated initially at the Mayo

Clinic were seen before parosteal osteosarcoma was rec-

ognized as a clinicopathological entity. Inadequate initial

surgical treatment thus allowed for recurrence and dedif-

ferentiation. Parosteal osteosarcomas are generally low-

grade malignant tumors at the onset but have a tendency to

become more anaplastic with recurrence354. Although they

may maintain a low-grade malignant potential, with each

recurrence there is potential for dedifferentiation.

One must have a high index of suspicion with regard

to dedifferentiation because there may be no significant din-

ical clues to distinguish a true recurrence of a parosteal

osteosarcoma from a recurrence with dedifferentiation . On

the other hand, rapid growth of a lesion or severe pain

suggests dedifferentiation. Also, radiographic lyric defects

within tumors that have the classic appearance of low-grade

parosteal osteosarcoma may be helpful in identifying pa-

tients with dedifferentiation. At the time of recurrence, the

high-grade component of these tumors is the most important

prognostic indicator.

A similar risk of dedifferentiation has been noted for

FIG. 3

56 1.. 1. WOI.D. K. K. UNNI, J. W. BEABOUT, F. H. SIM, AND D. C. DAHLIN


TABLE

ClINICAL

Case

Site of

Lesion Sex. A.e

( Yr. I

Initial Operation First Recurrence Second Recurrence

Date Type Date Treatment Date Treatment

I I)kt. piO (I

femur

Ni. lS 4 18 27 Excision I 1/8/28 Amputation

2 Prox. part of

humerus

F. 3() 62835 Biopsy 9/4/35 Excision 10/29/35 Excision

3 I)ist. part of

fentum

F. 14 4,547 Excision 9/18/48 Excision I 1/21/49 Disartic.

4 I)ist. part of

fetiwr

NI. 2() 1971 Excisiont 1974 Amputation

5 Prox. part of

humerus

M. 19 1945 Excision 1958 Subtotal

removall

2/78 Amputation

6 1)1st. part of

femur

F. 3(1 1964 Excisioni I 1/1/78 Aniputation

7 I)ist. part of

fetitur

F. I I 1971 Biopsy 1975 Excisions 8/17/81 Amputation

S Dist. part of

femur

F. 24 1932 Excisionl 1934 Biopsyl 1936 Biopsyl

9 1)1st. part of

fermium

F. 16 1956 Excision 1956 Excision 7/22/70 Amputation

It) I)ist. part of

femur

F. 15 1927 Incomplete

removall

1933 Incomplete

removaI

1937 Amputation

I I Prox. metaph.

of tibia and

NI. 28 4/29/81 Amputation

fibula

* At the onset of svmptonls or at the initial operation.

. Symptoms preceded the first operation by nine years.

1: Performed elsewhere.

well dedifferentiated intra-osseous osteosarcoma; in the se-

ries of Unni et al.5. three of eleven tumors that recurred

had changed from a low-grade to a highly undifferentiated

tumor.

Because of the potential for dedifferentiation of these

lesions, an aggressive surgical approach to the initial lesion

is imperative. This has been emphasized by Enneking et

al. , who indicated that the most important factors in the

prognosis are the surgical stage of the lesion and the ade-

quacy of the surgical procedure.

.istn area of mesidual lots gmade parosteal osteosarcotita s ith parallel bone trabeculae and intervening hypercellular fibrous connective tissue (hematoxylinand eosin. X 2 It)).

FIG. 4


VOL. 66-A, NO. 1. JANUARY 1984

DATA

Third Recurrence MedullaryInvolvement

Follow-upTime from

Onset to

Dedifferentiation

(Mos.)

Time from

Dedifferentiation to

Last Follow-up

(Mos.)

Date Treatment Date Condition

No 9/13/30 Died 127 22

9i24l Disartic. No 12843 Died 75 15

Yes 10 1381 No evidence of disease 31 384

No 12 1 1 8 1 No evidence of disease 36 84

Yes 4:781 Died 396 36

Yes 180

No 120

7646 Amputation Yes 5 52 Died 168 71

Slight 220/80 No evidence of disease 168 120

Slight I 1343 Died 228 72

No 6 9:82 No evidence of disease 0 14

In our series ten ofthe initial lesions would be classified

as stage lB , according to the staging system of Enneking

et al. , because they were of low grade and did not extend

into the underlying marrow or penetrate the overlying mus-

cle - that is, the lesion occupied the potential paraosseous

space. In the remaining patient (Case 1 1 , Table I), who had

areas of high-grade tumor when first seen, the lesion would

be classified as stage hA.

Awareness of the potential for dedifferentiation of a

parosteal osteosarcoma should stimulate increased interest

in initial control of the primary lesion by effective surgical

treatment. In this series, all ten patients who had a parosteal

osteosarcoma when they were first seen had a standard mar-

ginal excision, as advocated by Enneking et al. For local

A region adjacent to that shown in Fig. 3. Other areas of these tumors were histologically identical to conventional high-grade intramedullaryosteosarcoma (hematoxylin and eosin. x 825).

FIG. 5

58 L. E. WOLD. K. K. UNNI, J. W. BEABOUT, F. H. SIM, AND D. C. DAHLIN


Permeation of the medullary cavity b a residual low-grade osteosarcoma. Note that the pre-existing benign bone trabeculae are broader than thethin intervening neoplastic trabeculae (hematoxylin and eosin. x 80).

control of the tumor and prevention of recurrence with po-

tential dedifferentiation, our current approach is wide local

resection to obtain a wide surgical margin that includes an

envelope of surrounding normal tissue. Unfortunately, if

the parosteal lesion dedifferentiates into a stage-Il lesion -

that is, a tumor with extracompartmental extension - the

potential for a successful limb-salvage procedure is lost.

Few of these tumors are small enough to be treated ade-

quately with resection, and treatment for dedifferentiated

parosteal osteosarcoma is similar to that for conventional

high-grade osteosarcoma and generally involves amputa-

tion.

Although the incidence of dedifferentiation to high-

grade osteosarcoma in patients with recurrent parosteal os-

teosarcoma is significant, recognition of the coexistence of

low-grade and high-grade tumor is rare when a patient is

first seen. Such coexistence was seen in only one patient in

this series. This emphasizes the necessity of adequate sam-

pling of a parosteal osteosarcoma initially to be certain that

dedifferentiation has not already occurred. In this series, in

which many of the patients were treated elsewhere before

being referred to the Mayo Clinic, one must question

whether the initial sampling of the tumor was adequate to

rule out the possibility that some areas of high-grade ma-

lignant tumor were present from the onset. In addition to

the patient with coexistent low-grade and high-grade surface

osteosarcoma, slides were available for adequate sampling

of the primary lesion in five patients. In the five remaining

patients, the original histological material was not available

for review and the historical information was not sufficient

to confirm that there was no coexistent high-grade tumor at

the time that the patient was originally treated. In these five

patients, however, the intervals from the time of initial

treatment to the time of dedifferentiation were ten, thirty-

three, fifteen, ten, and fourteen years; if high-grade osteo-

sarcoma had coexisted with the original lesions, recurrence

would probably have been much earlier. Moreover, ade-

quate sampling of the dedifferentiated tumor is generally

not a problem because the dedifferentiated areas are grossly

recognizable and different from the usual parosteal osteo-

sarcoma. The usual low-grade parosteal osteosarcoma is

densely ossified; in contrast, the areas of dedifferentiation

are often softer and less densely ossified.

The survival rate of patients with dedifferentiated par-

osteal osteosarcoma has been worse than that of patients

with the usual parosteal osteosarcoma. The prognosis for

our patients appears to be similar to that for patients with

high-grade intramedullary osteosarcoma . Medullary in-

volvement does not appear to indicate a poorer prognosis.

A variety of histologically different osteosarcomas can

develop on the surface of bone. Because of differences in

prognosis, these tumors should be considered distinct din-

icopathological entities. As a group, parosteal osteosarco-

mas can be associated with a good prognosis if the diagnosis

is restricted to surface tumors that lack medullary involve-

ment and that are histologically low-grade (Fig. 4). Simi-

larly, periosteal osteosarcomas form a less common but

equally distinct group with specific prognostic implications

if the diagnosis is restricted to surface tumors that lack

medullary involvement and that are lobulated and predom-

inantly chondroblastic.

High-grade osteosarcomas may involve the surface of

bone in three ways. First, a typical intramedullary high-

grade osteosarcoma may permeate the cortex and form a

predominantly extra-osseous tumor. We believe that such a

tumor should be considered an ordinary type of high-grade

osteosarcoma. Second, on rare occasions a high-grade os-

teosarcoma develops on the surface of a bone without med-


ullary involvement. Such a tumor appears to have a forpatients with a usual parosteal osteosarcoma and appears

prognosis similar to that of an ordinary intramedullary high- to be similar to that for patients with an intramedullary high-

grade tumor. Finally, a high-grade osteosarcoma on the grade tumor. Therefore, not all surface osteosarcomas are

surface of bone can coexist with or be a recurrence of a low-grade (stage-I) lesions. A proportion of them present

usual parosteal osteosarcoma. This group ofdedifferentiated as high-grade tumors, and a significant number of low-grade

parosteal osteosarcomas is the subject of this report. The lesions may dedifferentiate to become high-grade tumors

prognosis for patients with these tumors is worse than that after inadequate excision.

References

I . BOWMAN, W. E. ,and Sist. F. H. : Limb Salvage in Primary Malignant Bone Tumors of the Pelvis. Orthop. Trans. , 7: 74, 1983.2. BRODERS, A. C.: Squamous-Cell Epithelioma of the Lip. A Study of Five Hundred and Thirty-seven Cases. J. Am. Med. Assn. . 74: 656-664.

1920.

3. DAHLIN. D. C.: Bone Tumors: General Aspects and Data on 3,987 Cases. Ed. 2, pp. 176-185. Springfield. Illinois. Charles C Thomas. 1967.4. DUNHAM. W. K. ; WII.B0RN. W. H. ; and ZARZOUR. R. J.: A Large Parosteal Osteosarcoma with Transformation to High-Grade Osteosarcoma.

A Case Report. Cancer. 44: 1495-1500, 1979.5. DWINNELL, L. A. ; DAHLIN, D. C. ; and GHORMLEY. R. K. : Parosteal (Juxtacortical) Osteogenic Sarcoma. J. Bone and Joint Surg. ,36-A: 732-

744. July 1954.6. ENNEKING, W. F. : SPANIER. S. S. ; and GOODMAN. M. A.: A System for the Surgical Staging of Musculoskeletal Sarcoma. Clin. Orthop. , 153:

106-120, 1980.7. FARR, G. H., and Huvos, A. G.: Juxtacortical Osteogenic Sarcoma. An Analysis of Fourteen Cases. J. Bone and Joint Surg.. 54-A: 1205-12 16,

Sept. 1972.8. GESCHICKTER, C. F., and COPELAND, M. M.: Parosteal Osteoma of Bone. A New Entity. Ann. Surg., 133: 790-806, 1951.9. LICHTENSTEIN, LOUIS: Tumors of Periosteal Origin. Cancer, 8: 1060-1069, 1955.

10. SCAGLIETTI, 0. , and CALANDRIELLO. B. : Ossifying Parosteal Sarcoma. Parosteal Osteoma or Juxtacortical Osteogenic Sarcoma. J. Bone and JointSurg. , 44-A: 635-647, June 1962.

1 1. SIM, F. H.; IviNs, J. C.; and PRITCHARD, D. J.: Surgical Treatment of Osteogenic Sarcoma at the Mayo Clinic. Cancer Treat. Rep., 62: 205-21 1,1978.

12. UNNI. K. K.; DAHLIN. D. C.; BEABOUT. J. W.: and IvINs, J. C.: Parosteal Osteogenic Sarcoma. Cancer, 37: 2466-2475, 1976.13. UNNI. K. K.; DAHLIN, D. C.: MCLEOD, R. A.; and PRITCHARD, D. J.: Intraosseous Well-Differentiated Osteosarcoma. Cancer. 40: 1337-1347,

1977.14. VAN DER HEUL. R. 0. , and VON RONNEN, J. R. : Juxtacortical Osteosarcoma. Diagnosis, Differential Diagnosis, Treatment, and an Analysis of

Eighty Cases. J. Bone and Joint Surg. . 49-A: 415-439, April 1967.

VOL. 66-A, NO. I. JANUARY 1984

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