Osteosarcoma resembling osteoblastoma

Osteosarcoma Resembling Osteoblastoma FRANC0 BERTONI, MD,’ KRISHNAN

K. UNNI, MB, BS,t RICHARD A. MCLEOD, MD,$ AND DAVID C. DAHLIN, M D t

A series of 17 patients with osteosarcomas that histologically resembled osteoblastomas was studied. The ages of the 9 male and 8 female patients ranged from 11 to 58 years. The roentgenographic appearance was suggestive of malignancy in most cases. Two histologic features seemed most important in differentiatingosteosarcoma from osteoblastoma. I n the former, there is permeation of surrounding tissues and lack of “maturation” toward the edges, whereas osteoblastoma tends to show maturation peripherally and is circumscribed. Osteoblastoma-like osteosarcoma should be considered to be a malignant tumor because 7 of the 17 patients died of their disease. The authors believe that malignant osteoblastoma and aggressive osteoblastoma are really osteosarcomas that resemble osteoblastomas. Cancer 55416-426, 1985.

0

STEOBLASTOMA is

generally considered to be the Results benign counterpart of osteosarcoma. Although Clinical Findings they probably are unrelated conditions, osteoblastoma Most patients presented with pain, usually of short has been reported to undergo malignant transand for some tumors, the question of duration. Four tumors involved the tibia, three the ver“benign” versus “malignant” is difficult to a n ~ w e r . ~ , ~ tebrae, two the sacrum, two the fibula, and one each the This problem has been previously addressed under the scapula, cuboid, femur, ilium, maxilla, ethmoid, and terms “malignant oste~blastoma”~~~ and “aggressive temporal bone (Fig. 1); one patient had two tumors. 0steob1astoma.”~- We have reviewed our experience with 17 cases in which the differential diagnosis was Roentgenographic Findings between osteoblastoma and osteosarcoma. Roentgenograms were available for study in 13 cases. The appearances at presentation varied. Materials and Methods Malignancy was correctly suggested in 9 of the 13 Slides from more than 1200 osteosarcomas in the cases. Ossification was present in six of the nine maligMayo Clinic files were reviewed. In addition, all consulnant-appearing lesions, allowing the radiologist to cortation cases in which a diagnosis of low-grade osteosarrectly suggest a diagnosis of osteosarcoma (Figs. 2A and coma and osteosarcoma resembling osteoblastoma was 2B, and Fig. 3). The other three lesions were purely lytic rendered were reviewed. Seventeen cases of well-differ- and, though malignant in appearance, were otherwise entiated osteosarcomas that resembled osteoblastomas nonspecific in presentation. One tumor that was considwere identified: 5 from the Mayo Clinic files and 12 from ered an osteosarcoma had an equivocal appearance, and the consultation files. The ordinary osteoblastomas were not reviewed because they did not pose a significant problem in differential diagnosis. Of the 17 patients, 9 1 1 17 Patients--18 tumors were males and 8 were females, with ages ranging from 1 1 to 58 years (Table 1). Preoperative roentgenogramsof 15 Males 9 13 patients were available, and follow-up information Females 8 Total 17 was obtained from clinic charts and the referring physi10 cians. No of

416

5 -

n

--

i’I 2

cases

From the Departments of ?Surgical Pathology and .$Diagnostic Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. * Visiting Surgical Pathologist from USL 28 Ospdale M. Malpighi, Serviziodi Anatomia ed Istologia Patologica, and the Rizzoli Institute, Bologna, Italy. Address for reprints: Krishnan K. Unni, MB, BS, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Accepted for publication January 16, 1984.

I

10

. 20

.

.

.

30 40 50 Age In decades

.

.

60

70

2

FIG.1. Age of patients and skeletal distribution of osteosarcomas.

OSTEOSARCOMA RESEMBLING OSTEOBLASTOMABertoni et al.

No. 2

FIGS.2A

AND

417

2B. Osteosarcoma of femur. (A, left) Anteroposterior and (B, right) lateral views show classic presentation of osteosarcoma.

osteoblastoma had to be considered in the differential diagnosis (Figs. 4A and 4B). In 4 of the 13 cases, the roentgenographic appearance erroneously indicated a benign lesion. In three, osteoblastoma was the suggested diagnosis (Fig. 5 ) , while in one, the tumor was considered to be a typical osteoid osteoma (Figs. 6A and 6B). One tumor believed to be an osteoblastoma was considered to have a borderline appearance, and osteosarcoma had to be included in the differential diagnosis (Fig. 7 ) .

Gross Appearance 0n:ly two specimens had gross features that could be evaluated: one from the ethmoid and one from the ilium. Neither had the “fish-flesh” appearance of conventional osteosarcoma. The specimen from the ethmaid was red and granular, and the lesion from the was markedly cystic.

FIG. 3. Osteosarcoma of ilium. CT scan shows features typical of osteosarcoma, with large partially ossified soft tissue mass on either side of ilium.

-

-

-

F/17

MI29

2

F/19

MI58

Fl53

MI26

MI15

MI14

4

5

6

I

8

9

Severe pain

loss

Pain, R foot, swelling; 9. I kg weight

4-5

-

-

1

Pain, L pelvis and L lower extremity

-

1-1.25

Back pain, Bilat leg weakness

-

-

-

MI13

1

3

Duration (mo)

Symptoms

Sex/age (Yr)

Case

Upper tibia

R cuboid

R upper fibula

Sacrum

T-1 I

R scapula

R tibia, distal - diaphysis

C-3 spinous process

R tibia, distal diaphysis; R fibula, upper end

Site

Intralesional excision (3-2 1-78)

lntralesional excision (6-28-78), midthigh amputation (4-3079), wide amputation

No evidence of disease, May 1981 (13 mo); no evidence of disease (3 Y r)

I

Alive, November 1974 (1 1 mo); walking, returned to limited employment Radiotherapy

Lower lumbar sacral laminectomy, subtotal removal of tumor (intralesional excision) (11-73)

No evidence of disease, June 1975 (3 mo)

Resection (wide excision) (8-772), soft tissue recurrence (marginal excision) (12-74), soft tissue recurrence (marginal excision) (3-75)

No follow-up available

Died, August 1970 (7 mo), metastasis to lungs

Died, October 1963 (6 mo), massive tumor

Died, May 1963 (8 mo), metastasis to lungs and bones

Follow-up (from last treatment)

Recurrence removed (marginal excision) (12-7-68), subcutaneous recurrence removed (marginal excision) (8-69), subcutaneous recurrence removed (marginal excision) (10-20-69), soft tissue recurrence removed (marginal excision) (4-29-70)

Radiotherapy (4-5-63), curettage

Midthigh amputation (lytic defect in distal femur), wide amputation (1 1-8-62)

Further treatment (date)

-

Intralesional excision (4-7-71)

Intralesional excision ( 12-17-62) Intralesional excision (3-29-62)

Intralesional excision (9-28-62)

Initial treatment (date)

TABLE1. Clinical Data on 17 Patients With Osteosarcomas Resembling Osteoblastomas

f

vI

\D 00

c

bl

k.

-2

Q

E

3

3

Qia

Pz

03

Decompressive hemilaminectomy, tumor not completely removed, bone graft C-5 to C-2 (1-78)

C-6

Migratory pain, weakness and numbness of fingers

Pain, R hard palate, R tonsil, R ear

F/32

MI20

16

17

L left; R: right: Bilat: bilateral: CT: computerized tomographic.

2

8

Intralesional excision (7-31-80)

Biopsy (4-7-81)

L ilium

12

Tiredness of legs, pain, superficial varicosities

F/3 I

15

R maxilla

Biopsy (9-26-72)

L lower femur

1.5

Pain, swelling

F/11

R maxillectomy (wide excision) (8-7-80)

Recurrence, biopsy (10-78), chemotherapy (4-2-79), radiotherapy (6-9-79). R anterior cervical decompression, tumor not completely removed (1 1-8-80), malignant esophageal fistula (1-12-8 I )

Wide L hemipelvectomy (4-158 I), wedge resection of multiple lung metastases (7-9-82)

Radiation therapy (3-30-73), pulmonary metastasis, chemotherapy

No evidence of disease (19 mo)

Died, June 1981 ( 5 mo), tumor invaded bony spinal canal and engulfed cervical cord in midcervical to C-7 level (tiny nodule in R upper lung, ? metastatic deposit)

Alive, October 1982 (tiny lung metastasis versus healing reaction on CT scans): January 1982, no new nodules

Died, May 1974 (13 mo), metastasis to lungs

Died, September 1978 ( 3 mo): autopsy, metastasis to lungs and brain, extension of tumor into frontal, ethmoid, sphenoid bones bilaterally

14

Recurrence (4-13-77), cobalt therapy (6-10-77), intralesional excision of recurrent tumor of ethmoid bone R nose, basifrontal dura, and intradural tumor (8-5-77), intralesional excision of recurrent orbital tumor (3-3-78), chemotherapy (4-1 1-78, 5-19-78, 6-9-78)

Excision of tumor infiltrating ethmoid, labyrinthine, bulging into orbit and choana, 5 X 3 X 2 cm ( 1 2-2-76)

R ethmoid

1

Obstruction of nose with PUS

€132

13

Alive with no metastasis (2 mo)

lntralesional excision (5-12-82)

Intralesional excision (2-17-81)

R maxilla

2

Pain, low back and sacrum

MI25

12

Patient alive, September 1982

lntralesional excision (9-78), wide excision with bone graft (4-79), midthigh amputation (4-80). chemotherapy

Intralesional excision (4-27-78)

R tibia, midshaft

Painful swelling

MI19

11

24

Tumor stable on chemotherapy, January 198 1 ( 5 mo): “dying,” summer 1981 (? local tumor)

lntralesional excisions ( I 977, 1979), radiotherapy (5-79), chemotherapy (7-79)

lntralesional excision ( 1976)

L temporal bone

36

Drainage and blocking, L ear swelling, tender L mastoid

Fl17

10

N

z ?

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OSTEOSARCOMA RESEMBLING OSTEOBLASTOMA Bertoni et al.

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Microscopic Appearance The tumors were selected primarily because of their resemblance to osteoblastomas. The tumors were found to permeate bone, particularly when the material for review included the edge of the tumor (Figs. 8A and 8B). Under low-power microscopy, abundant bone production was evident as well-formed bony trabeculae (Fig. 8C). Trabeculae were rimmed with plump cells that had eosinophilic cytoplasm and round nuclei. The nuclei usually had prominent nucleoli, and the cells had pink cytoplasm, making them appear to be “epithelioid” (Fig. 8D). Mitotic figures were abundant. In addition to rimming the bony trabeculae, the tumor cells were present between the trabeculae, giving the lesion a cellular appearance (Fig. 8D). In addition, some of the tumors showed areas that were more typical of conventional osteosarcomas, having small inconspicuous cells in a heavily ossified matrix or having spindle cells with lacelike osteoid.

Treatmenl and Survival Because the study is retrospective, our definitions of the treatment modalities employed are arbitrary. We have no information about the treatment of three patients (Cases 5 , 7, and 8) (Table l). Of the 1 1 patients who underwent excision primarily, 1 (Calse 6) received postoperative radiotherapy and was alive without disease at 1 I months, at which time she was lost to follow-up. Three of the other 10 patients underwent amputation for recurrent tumor. Two (Cases 9 and 1 1) of the three patients were alive without disease, one 2 years, and the other 3 years later. The third patient (Case 1) died 8 months after amputation, with metastasis to the lungs and bones. The remaining seven patients were treatled with combinations of surgery, radiotherapy, and chemotherapy. Two (Cases 4 and 12) of the seven were alive without disease at last follow-up (2 and 3 months, respectively), and the other five (Cases 2, 3, 10, 13, and 16) were dead or dying 6 , 7 , 10,3, and 5 months, respectively, after the last treatment, with local extension ofthe tumor in three, lung metastasis in one, and local extension and lung and brain metastasis in one. Of the other three patients, one (Case 14) received radiotherapy after biopsy and was given chemotherapy after pulmonary metastasis was detected. She died 13 months later of disease. One patient (Case 17), with a maxillary lesion, underwent maxillectomy and was alive without disease at 19 months. A third patient (Case 15) underwent hemipelvectomy for an iliac lesion. Fifteen months later, she had resection of multiple metastatic lesions in the lung and was alive 6 months later with no progression of disease.

FIG.5. Osteosarcoma of tibia. Roentgenographic appearance suggestive of osteoblastoma.

In summary, 7 of the 17 patients are known to have died of the tumor and 7 have survived; however, the longest follow-up was only 3 years. Discussion We have been impressed with the rare case in which the differentiation of osteosarcoma from osteoblastoma was difficult. The problem seems to be most common with spinal lesions. The 17 cases in this series were chosen on the basis of the histologic appearance of the lesion, that is, osteosarcoma that resembled osteoblastoma on low-power microscopic examination. In the past, this problem has been addressed under the terms “aggressive osteoblastoma”’ and “malignant osteoblastoma.”8 We recognized only 5 such cases in the Mayo Clinic files, which include more than 1200 osteosarcomas, in-

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dicatiing the rarity of this problem. Their relative abundancle in the consultation files attests to the difficulty in diagnosing them. The clinical features are not remarkable except for the relatively high incidence in the vertebral column ( 5 / 17), including the sacrum. This incidence is higher than for conventional osteosarcoma. A roentgenographic presentation that is typical of malignancy or shows the classic features of osteosarcoma is quite useful (8/ 13). However, some tumors are initially seen with an equivocal roentgenographic picture of osteosarcoma versus typical osteoblastoma (2/ 13). The roentgenographic appearance may be misleading when typical of a benign process (3/ 13). This difficult problem is further complicated because about 25% of osteoblastomas initially have a roentgenographic appearance suggestive of malignancy.12 The gross appearance also does not appear to be helpful. The typical osteosarcoma is white and fleshy, whereas the typical osteoblastoma is red and granular. However, osteoblastoma-like osteosarcomas are also red and granular. Thus, the distinction probably has to be made on histologic findings alone. The distinguishing features that we believe are helpful are given in Table 2. Two of these features are most useful. First, the edge of osteoblastoma will tend to show maturation or zonation -thlat is, the presence of peripheral, well-formed bony trabeculae -whereas the edge of the osteoblastoma appears to be well-rounded, with no tendency for the tumor to permeate the surrounding bone (Fig. 9A). Second, the inteitrabecular tissue of an osteoblastoma is loose and vascular (Fig. 9B), whereas that of an osteosarcoma is solicl and cellular (Fig. 8D). The differential diagnosis is impossible to make with limited tissue, for example, from a needle biopsy, and may be impossible even with adequate tissue. Two rare variants of osteoblastoma have to be considered in the differential diagnosis: pseudomalignant osteoblastoma and multifocal osteoblastoma. Pseudomalignant oste~blastoma~~ has bizarre cells similar to those seen in neurilemmoma. However, the cells do not show

423

FIG.7. Osteosarcomaof tibia. Sharp margin and sclerotic rim favor diagnosis of osteoblastoma. Osteosarcoma included in differential diagnosis because of cortical destruction.

mitotic activity (Figs. 1OA and IOB). Such bizarre cells are not seen in osteoblastoma-like osteosarcomas. Multifocal osteoblastoma has multiple small foci of osteoblasts that permeate reactive bone and produce a large total mass. However, the foci appear to be in the intertrabecular spaces and do not destroy tissue. They are not apposed to the trabeculae and, hence, do not appear to

TABLE2. Differential Histologic Features of Osteoblastoma and Osteoblastoma-LikeOsteosarcoma Feature

Osteoblastoma

Cytoairchitectural organization

Trabeculae of osteoid rimmed by osteoblasts; spindle cells, osteoclasts, and capillary vessels between trabeculae

Mitolic rate Atypical mitosis Zonal phenomenon Permeating bone growth Margins Sheets of cells without bone production

Generally low No Yes No; sometimes multifocal Well defined No

Osteosarcoma Large cells with abundant deep-staining cytoplasm, large nucleus with big nucleolus, and osteoclasts may be present between trabeculae of osteoid Generally high May be present No Yes Permeation and infiltration Yes

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FIGS.8A-8D. Osteosarcoma simulating osteoblastoma. (A, top left) Edge of tumor is irregular, with destruction of bone (H & E, original magnification X 5). (B, top right) Permeation between bone trabeculae at edge (H & E, original magnification X 250). (C, bottom left) Low power shows pattern of osteoblastoma(H & E, original magnificationX 64). (D, bottom right) Higher power showsthe plump cells and lack of vascularity (H & E, original magnification X 250).

FIciS. 1OA AND 10B. Osteoblastoma with bizarre nuclei. Nuclear details are blurred, and cells are similar to those seen in “chemotherapy” effect (H & E, original magnification X 250).

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permeate bone, as do the foci of osteoblastoma-like osteosarcoma. We prefer to think of the lesions as osteosarcomas.We believe that the lesion we refer to as osteoblastoma-like osteosarcoma is identical to that described by Schajowicz and Lemos7s8as malignant osteoblastoma and by Dorfman1p9as aggressive osteoblastoma. Whatever the term used, it is important to recognize this small group of osteoblast-rich lesions that resemble osteoblastomas but behave like osteosarcomas. ADDENDUM After this manuscript was submitted, we learned that Case 9 was reportedI4as osteoid osteoma transforming to an aggressive (low-grade malignant) osteoblastoma. REFERENCES 1. Dorfman HD. Malignant transformation of benign bone lesions.

Proc Natl Cancer Conf 1972; 7:901-913. 2. Mayer L. Malignant degeneration of so-called benign osteoblastoma. Bull Hosp Joint Dis 1967; 28:4- 13. 3. Merryweather R, Middlemiss JH, Sanerkin NG. Malignant transformation of osteoblastoma. J Bone Joint Surg [Br] 1980; 62:381-384. 4. Seki T, Fukuda H, Ishii Y et al. Malignant transformation of

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benign osteoblastoma: A case report. J Bone Joint Surg [Am] 1975; 57~424-426. 5. Dahlin DC. Bone Tumors: General Aspects and Data on 622 1 Cases, ed. 3. Springfield, IL: Charles C Thomas, 1978; 283. 6. Jackson JR, Bell MEA. Spurious “benign osteoblastoma”:A case report. J Bone Joint SurgIAm] 1977; 59:397-401. 7. Schajowicz F, Lemos C. Osteoid osteoma and osteoblastoma: Closely related entities of osteoblastic derivation. Acta Orthop Scund 1970 41:272-291. 8. Schajowicz F, Lemos C. Malignant osteoblastoma. JBone Joint Surg[Br] 1976; 58:202-21 I . 9. Dorfman HD. Case records ofthe MassachusettsGeneral Hospital (Case 40-1980). N Engl JMed 1980; 303:866-873. 10. Revell PA, Scholtz CL. Aggressive osteoblastoma. J Pathol 1979; 127~195-198. 11. Spjut HJ, Fechner RE, Ackerman LV. Tumors of bone and cartilage. In: Hartmann WH, ed. Atlas of Tumor Pathology, series 2, fascicle 5, supplement. Washington D.C.: Armed Forces Institute of Pathology, 198I . 12. McLeod RA, Dahlin DC, Beabout JW. The spectrum of osteoblastoma. Am JRoentgenol 1976; 126:321-335. 13. Mirra JM, Kendrick RA, Kendrick RE. Pseudomalignant osteoblastoma versus arrested osteosarcoma:A case report. Cancer 1976; 37~2005- 2014. 14. Pieterse AS, Vernon-Roberts B, Paterson DC et al. Osteoid osteoma transforming to aggressive (low grade malignant) osteoblastoma: A case report and literature review. Histopathology 1983; 7:789- 800.

American Board of Internal Medicine 1985 Subspecialty Examination in Medical Oncology Registration period: Examination date:

January I , 1985-April I , 1985 November 19, 1985

Physicians certified in internal medicine who completed 2 years of acceptable subspecialty training in hematology, medical oncology, or hematology/oncology in June 1975 or before will fullfill the Board’s training requirements for admission to the examinations in Hematology and Medical Oncology only through 1986. Therefore, such Diplomates must be admitted to the 1985 Medical Oncology or to the 1986 Hematology Examination to achieve certification in both subspecialties. After these examinations, all candidates must have had at least 3 years of acceptable training to be certified in both subspecialties. For further information and application forms please contact: American Board of Internal Medicine, 3624 Market Street, Philadelphia, PA 19104 (215) 243-1500.

(Note: Examination date has been changed from November 12, 1985)