- Email: [email protected]
Osteosarcoma
Osteosarcoma By Beth
Edeiken-Monroe,
Jack
Edeiken,
T
HE ADVENT OF chemotherapy for the treatment of osteosarcoma has changed the prognosis significantly. Furthermore, limb salvage procedures preserve function. Since the variations of histologic types are treated differently, the classification of these neoplasms has become more than an intellectual exercise. Osteosarcoma can be divided into a number of clinical types and grouped by site and histologic variations with differences in prognosis.’ In order of frequency, they are: (1) classical central osteosarcoma; (2) mandibular osteosarcoma; (3) secondary osteosarcoma (Paget’s Disease and radiation); (4) parosteai sarcoma (parosteal osteosarcoma and juxtacortical osteosarcoma) and dedifferentiated parosteal osteosarcoma; (5) telangiectatic osteosarcoma; (6) periosteal osteosarcoma; (7) poorly differentiated (high-grade) surface osteosarcoma; (8) extraosseous osteosarcoma; (9) intraosseous well-differentiated (lowgrade) central osteosarcoma; (10) small cell osteosarcoma; (11) osteoblastoma-osteosarcoma complex; (12) sclerosing osteosarcomatosis (multicentric osteosarcoma); and (13) intracortical osteosarcoma (Table 1). Raymond et al* propose a classification that serves to emphasize the common histologic elements of these tumors (Table 2). Osteosarcomas, radiographically, produce all varieties of bone change, from nearly normal, to extremely dense, to almost total destruction, and to varying admixtures. The totally osteolytic osteosarcoma may be a telangiectatic osteosarcoma. It cannot be distinguished radiographically from an osteolytic osteosarcoma of the classical histologic pattern. Purely lytic osteosarcoma is reported in 13.7% of 305 patients in one series3 The roentgenographic diagnosis rests on the abnormal skeletal response, whether homogenous or heterogeneous, regular or irregular, clearly defined or totally lacking in margination; the nature of the cortical response; the presence or absence of a perifocal soft tissue mass; and many other factors.
Seminars
in Roenrgeno/ogy,
Vol XXIV,
No 3 (July),
1989:
pp 153-l
and
Harold
G. Jacobson
With osteosarcoma the periosteal response is extremely important radiologically because it is almost always highly irregular and interrupted. The sunburst and onion-peel types are classic examples. In contrast, in benign processes the periosteal reaction may be more uniformly homogeneous and solid. With benign lesions the segments of the cuff of newly formed periosteal bone appear all of the same age, as though in response to a single event, and are morphologically uniform throughout, with their superficial portions similar in all radiographic structure to the deeper ones. In osteosarcoma, the periosteal cuff is totally irregular, with different types of periosteal reaction observed at different sites. The structural composition of the periosteal cuff usually appears to represent events occurring at different times and responding differently to the ever-present irritant. These variations are not always unmistakably present, nor is it possible to always distinguish benign from malignant periosteal responses. However, as a working rule these generalities do prove helpful in differential diagnosis. For years, the Codman triangle has been considered invariably reliable in the roentgenographic recognition of malignant bone tumors. It is not. The Codman triangle is not a pathognomanic feature, since it may occur in benign
From the Department of Radiology, M.D. Anderson Cancer Center, University of Texas System. Houston; Department of Radiology. Health Science Medical School, University of Texas, Houston; and Division of Diagnostic Radiology, Montefiore Hospital and Medical Center, Bronx, NY, respectively. Beth Edeiken-Monroe: Department of Radiology, University of Texas Health Science Medical School, Houston; Harold G. Jacobson: Division of Diagnostic Radiology, Montejiore Hospital and Medical Center, Bronx. NY; Jack Edeiken: Department of Radiology, M.D. Anderson Cancer Center, University of Texas System, Houston. Address reprint requests to Jack Edeiken. MD, Department of Radiology, Box 57. M.D. Anderson Cancer, University of Texas System, 1515 Holcombe Blvd. Houston, TX 77030. 0 I989 by W.B. Saunders Company. 0037-I 98X/89/2403-0002$5.0000/0
73
153
154
EDEIKEN-MONROE,
Table
1. Types
of Osteosarcoma No. of Cases
Tvw Conventional Others
Osteosarcoma
Osteosarcoma Osteosarcoma
in jaw in Paget’s
Postradiation Osteosarcoma Telangiectatic Periosteal High-grade
933 281 84 43 52
Disease
osteosarcoma in benign conditions osteosarcoma
8 44
osteosarcoma surface osteosarcoma
22 9 16
Low-grade osteosarcoma Multicentric osteosarcoma Parosteal osteosarcome Dedifferentiated Total
3 56
chondrosarcoma
Classification Clinic.’
system
43 1,373
for osteosarcoma
developed
at the Mayo
disorders, particularly those that are aggressive in their behavior (eg, infection). The presence of a soft-tissue mass immediately adjacent to the diseased bone from which it obviously arose is highly informative. With osteosarcoma, nests of tumor bone, varying radiographically in density, may appear as individual Table
2. Osteosarcoma
Classificstion
System
Conventional Osteoblastic Chondroblestic
in jaw
well-differentiated resembling
conditions
osteosarcoma osteoblastoma
Telangiectatic osteosarcoma Small cell osteosarcoma ? Dedifferentisted chondrosarcoma
(CENTRAL)
OSTEOSARCOMA
Proposed modification of the osteosarwma tem. All elements of the Mayo Clinic system serva to emphasize the diverse group. Modified
Classical osteosarcoma, primarily a disease of young adults, is rare before the age of 10 years; 70% to 80% of the tumors appear before the age of 30 years.7-9 We have evaluated 181 consecutive patients with osteosarcoma; and 70% were females, except with de novo tumors after age 50, when the reverse is true.” Roentgenographic Features
? Malignant fibrous histiocytoma Surface Parosteal osteosarcoma Dedifferentieted parosteal osteosarcoma Pariosteal osteosarcoma High-grade surface osteoearcoma
The minor additions within this otherwise aLz
JACOBSON
Clinical Features
Postradiation osteosarcoma Paget’s osteosarcoma Multifocal osteosarcoma Osteosarcome in other benign Morphologic lntraosseous Osteosarcoma
AND
islets or coalescing groups of islets. These mineralized islets often contain trabeculae and haversian canals, pathognomonic of tumor bone, but just as often the mineral may be homogeneous without a trabecular pattern. Calcified tumor cartilage has a distinctive roentgenogrpahic appearance, described variously as extremely dense or of a snow-flake character. On many occasions, calcified tumor cartilage resembles small nests of bone infarcts seeded throughout the spongy portions of bone. Sometimes the tumor bone and tumor cartilage obscure, radiographically, the true nature of the sarcoma, and since osteosarcomas are more common than chondrosarcomas, the pragmatic tendency is to call such uncharacteristic tumors osteosarcomas, particularly where the age group suggests them. Metastases to bone, lung, lymph nodes, liver, soft tissues, and brain may contain tumor new bone and may be identified by the increased density of the metastases.4 With the advent of chemotherapy, intravenous or intraarterial responses can be followed by routine radiography. Medullary sclerosis, periosteal new bone formation, and disappearance of soft-tissue masses reflect a positive response to treatment.5*6 CLASSICAL
Fibroblastic Variants Clinical Osteosarcoma
EDEIKEN,
classification syshave been retained. common elements from Raymond et
Before describing the distinctive roentgenographic features of osteosarcoma, brief mention must be made of the general responses of bone and soft tissues to irritants. All bone reacts to inflammatory or neoplastic irritants in either an osteoblastic or an osteolytic way. Osteoblastic responses are generally referred to as reactive bone, new bone formation, or just increased bone density, appellations as nonspecific as their roentgenographic appearances.
OSTEOSARCOMA
Benign bone responses are usually sharply demarcated (short transition zone) and easily differentiated from their surroundings. Malignant neoplastic responses usually lack this differentiation, their borders blending imperceptibly with surrounding bone (wide transition zone) (Fig 1). Sometimes osteoblastic responses display characteristic bone patterns, with trabeculae and haverSian canals, and may very properly be called new bone formation. New bone formations may be benign or malignant; radiographically they are
Fig 1. Central osteosarcoma. An osteoblastic reaction is present in a large tumor that extends from the head of the femur to the shaft. The transition zone is long and blends inperceptively with the host bone.
155
differentiated by their density and margins: the less uniform the density and the less definitive the margins, the greater the likelihood of malignancy. However, exceptions do occur. The transition zone may be short and suggest a benign process. A sclerotic margin may form at the transition zone (Fig 2), and a benign lesion may be considered, but within the lesion, tumor new bone (eburnated bone) will usually be present. This occurs with fibroblastic osteosarcomas, often with
156
Fig 2. suggests
EDEIKEN-MONROE,
High-grade osteosarcoma of the a benign process. (A) Antero-posterior
tibia.
The transition zone projection. (Bj Lateral
elements of nonosteogenic fibroma. The short transition zone or the sclerotic margin has no bearing on the prognosis. Malignant reactive new bone formation may be either primary or secondary and, when it is confined within the normal limits of the bone and defined by the normal cortex, it is difficult to classify from roentgenographic appearances alone. Under such circumstances, the clinical story is of paramount importance. For a 70year-old man whose prostatic carcinoma shows reactive new bone deposits, the diagnosis would be different from that suggested for a teenager with similar bone densities. Important as are the roentgenographic mani-
is short projection.
and
surrounded
EDEIKEN,
by a sclerotic
AND
JACOBSON
margin
which
festations of these new bone formations, even more important are the soft tissue masses that may lie adjacent to the bone, particularly those that are obviously extensions of processes, apparently primary in bone. (Figs 3-5) This type of new bone formation may very properly be called tumor bone. Invariably associated with new bone formation within the parent bone, tumor bone in parosseous soft tissue masses is a cardinal roentgenographic feature of primary osteosarcoma of bone. Osteosarcomas usually arise in the metaphyseal portion of long bones, most frequently at the distal end of the femur and the proximal ends of the tibia and the humerus. They do not always,
OSTEOSARCOMA
157
Fig 3. Osteosarcoma of the femur. Osteoblastic bone is present within the distal end of the femur. The homogeneous appearance suggest tumor new bone but it is possible that it is reactive bone. However, the soft-tissue mass contained homogeneous calcification indiiting osteoid tumor new bone formation (arrows). There is also perioaeaf reaction.
however, arise in the metaphysis, and they may affect any part of the bone, or arise in the soft tissues (see EXTRAOSSEOUS OSTEOSARCOMA). Osteosarcomas occur more frequently in the cylindrical bones of patients under 30 and in the flat bones, particularly the ilium, of those over 50.8,‘o OSTEOSARCOMA
OF THE JAW
Osteosarcoma of the jaw (mandible and maxilla) has an incidence 1 to 15 years later than the classical osteosarcoma”V’2of 24 de novo osteo-
sarcomas of the jaw studied at M.D. Anderson Hospital, I2 12 were present in the maxillary bone and 11 in the mandible. Roentgenographic Features A soft tissue massis always present and most contain calcifications and/or bone (Fig 6). SECONDARY OSTEOSARCOMA TO PAGET’S DISEASE AND OTHER CONDITIONS
In patients over 35, most osteosarcomasare secondary to preexisting bone conditions, such as Paget’s disease. However, another peak inci-
158
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 4. Osteoaarcoma of the distal end of the femur. Mixed osteolytic and osteoblastic destruction is present in the distal end of the femur. The osteoblastic reaction could represent reactive new bone, rather than tumor new bone, but the soft-tissue mass contained a homogeneous calcific density characteristic of tumor oateoid new bone formation (arrows).
dence in the fifth decade cannot be completely attributed to preexisting lesions. Severe pain, intermittent at first and later becoming constant, is the outstanding clinical complaint; it has usually been less than 2 months in duration at the initial examination. Osteosarcoma accounts for about 90% of sarcomas developing in pagetoid bone.‘4’4 Approximately 5% of osteogenic sarcomas are associated with monostotic or polyostotic Paget’s disease. The median age is 64 years, with male predomi-
nance. The most frequent areas are the pelvic bones, humerus, femur, and craniofacial bones.i4 Pain and swelling are the most common presenting symptoms, with pathological fractures occurring in one quarter of the patients. In approximately two thirds of cases, the radiologic appearance is a lytic destructive lesion, while in the minority a sclerotic, mixed, or permeative pattern is present. The tumors are large, bulky, soft-tissue masses and periosteal reaction is infrequent (Fig 7). l3
OSTEOSARCOMA
159
Fig 5. High-grade central osteosarcoma of the femur. The soft-tissue mass contains considerable tumor new bone formation. There ara alao islanda of tumor new bone extending to the neck of the femur. The characteristics of the density indicate a bone forming tumor.
PAROSTEAL SARCOMA (PAROSTEAL OSTEOSARCOMA OR JUXTACORTICAL OSTEOSARCOMA)
Parosteal sarcoma7 develops from the periosteum, grows outward from the bone, and tends to surround the host bone, unlike central osteosarcoma, which begins within the bone and later breaks out.
Roentgenographic Features Recognition of classical parosteal sarcomas usually_ -presents no difficulty. Found most commonly in the lower end of the femur, either end of the tibia, and proximal end of the humerus, they present as dense massesof homogeneous new bone extending away from the bone cortex. They are rare in bones other than long bones. The
160
Fig 6. Osteosarcoma of the manidbls. Ostaoblastic reaction is present in the anterior portion of the mandible. There was a soft-tissue mass with calcification within indicating the correct diignosis.
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
it,
periphery is usually lobulated and round; small bone trabeculae may be found within the lesion. Highly characteristic in the early stages is a fine radiolucent line separating the dense mass of tumor bone from the cortex, except at the site of the central stalk attachment (Fig 8). Running parallel to the shaft of the bone, this line probably represents the thickness of the periosteum, lying between the cortex and the tumor. The stalk grows with the tumor, eventually attaching along its entire extent, and as it grows the radiolucent line is shortened and eventually obliterated (Fig 9).“*” Small areas of new bone, either adjoining the periosteum or seemingly unattached, may be the only early evidence of parosteal sarcoma. Later, as these masses grow, the linear radiolucent periosteal defect that separates cortex and tumor disappears and all contrast between them is obscured. The inner portions and stalk are homogeneously dense, and the periphery less dense. The tumor bone nearest the cortex is thickest and most mature and is therefore slightly denser than at the periphery. The cortex of the bone remains intact until very late in the disease. Later, additional round deposits of new bone may form, separated from the main mass of tumor, and have
Fig 7. Paget’s disease with secondary osteosarcoma. The characteristic changes of Pagat’s disease is present the medial aspect of the distal femur extending proximally into the shaft. On the lateral border there is a soft-tissue mass which extends exterior to the bone and was proven be an osteosarcoma.
on
to
been known to exceed 10 cm in diameter (Fig 10). Occasionally, these tumors metastasize early, with new bone formation within the lymph node metastasis; however, they may grow slowly for years before metastasis occurs. Usually the tumor can be differentiated from other cortical lesions such as osteochondroma and myositis ossificans. With osteochondroma, the cortex of the host bone is continuous with the lesion itself, so that cortex and medulla of tumor and host bone are indistinguishable from each other. Myositis ossificans appears in two forms, either as feathery bone that follows fascial planes, or as rounded, ossified masses less dense in the center than parosteal sarcoma and with sclerotic
OSTEOSARCOMA
Fig 8. Parosteal sarcoma. The dense osteoblastic bone which tends to fade in the periphery zonal sign characteriatic of parosteal osteosarcoma. The radiolucant line separates the tumor from the tibia.
margins. This zonal sign is most useful in distinguishing the lesion from parosteal osteosarcoma. Juxtacortical hematomas occasionally reveal periosteal reactions not unlike those of early parosteal sarcoma. Extraosseous osteosarcomas are not in intimate contact with bone. Dedifferentiation of low-grade parosteal osteosarcomas is reported; rapid growth or severe pain suggests dedifferentiation, as does development of new lytic areas following treatment. At the time of recurrence, the high-grade component is the most important prognostic indicator.‘*
DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA
Dedifferentiated parosteal osteosarcoma occurs in 10% to 20% of parosteal osteosarcomas,‘7 and the prognosis is similar to that for conventional osteosarcoma. In one series, 10 of 11 patients had a long history of treatment for multiple recurrences of low-grade parosteal osteosarcoma before the high-grade undifferentiated osteosarcoma occurred.17 In our experience, however, 12 of 13 patients demonstrated dediffer-
162
EDEIKEN-MONROE,
Fig 9. Parosteal osteosarooma blastic bone is denser in the toward the periphery, especially tumor has anached to the bone therefore, no fine line separates
of the femur. The osteocenter of the lesion than at the inferior margin. The along its entire extent and it from the normal bone.
entiation on the first examination. Such lesions are most often reported in the femur, but have occurred in the humerus, tibia, and the fibula (Fig 1l).” Roentgenographic
Features
Usually evidence exists of a characteristic parosteal osteosarcoma with dense new bone formation, most frequently at the posterior surface of the distal end of the femur. The tumor new bone is denser in the center and fades at the periphery of the tumor (zonal sign). With dedifferentiation one of three different radiographic patterns appears: (1) a characteristic parosteal osteosarcoma, with round osteolytic areas measuring 1 to 2 cm present within the tumor new bone; (2) large, soft-tissue masseswith spotty calcifica-
EDEIKEN,
AND
JACOBSON
Parosteal osteosarcoma. The dense tumor bone Fig 10. is on the surface of the tumor. There are several separate islands of calcification. The tumor density is greatest in the center of the tumor and fades at the periphery.
tions separate from or invading the original tumor (Fig 11); and (3) hypervascular areas demonstrated by arteriography. Parosteal osteosarcomas are usually hypovascular but in the absence of dedifferentiation they may contain small hypervascular areas that must undergo biopsies. TELANGIECTATIC
OSTEOSARCOMA
Classical osteosarcomas can have areas of telangiectasia, but the presence of more than 90% of tissue of telangiectatic features indicates the special variant, telangiectatic osteogenic sarcoma. Radiographically, the lesion is purely lytic,
with minimal internal sclerosis (Figs 12, 13). The most characteristic appearance is that of an expansile lesion, often lacking periosteal reaction and displaying a well-demarcated radiolucency, so that differentiation from aneurysmal bone cyst may be difficult (Fig 13). PERIOSTEAL OSTEOSARCOMA (PERIOSTEAL OSTEOGENIC SARCOMA)
Periosteal osteosarcoma is distinct from the conventional (medullary) osteosarcoma, and the less aggressive parosteal sarcoma, for which it may be mistaken.18M20 Roentgenographic Features
The appearance is so characteristic that the correct diagnosis is easily made in the majority of lesions. The lesion appears as a sessile elliptic growth on the periosteal aspect of the cortex of the diaphysis of a long bone, but may often cause irregular destruction of the cortex. Short spicules of bone at right angles to the shaft are intermingled with small areas of rounded bone density (Figs 14, 15). The periosteal reaction may be lamellated. The lesion is rarely over 7 to 12 cm in length and 2 to 4 cm in width. A small, uncalcified soft-tissue component often appears beyond the calcification. The base of the tumor is usually closely attached to the cortex over the entire extent of the tumor, unlike a parosteal sarcoma, with its short pedicle attachment and radiolucent line between the remainder of the tumor and the cortex. The enlargement of the bone is almost exclusively from the periosteal aspect, but in rare cases endosteal cortical thickening may encroach on the medullary cavity. Cortical destruction and invasion of the medullary canal should not occur in this tumor. The exclusive diaphyseal origin is unusual for mesenchymal tumors, which occur most frequently in metaphyseal areas of long bones. The proximal end of the diaphysis of the tibia and distal end of the diaphysis of the femur are the most frequent sites, especially at the medial and/or anterior aspects. 2oThey also are reported in the humerus, fibula, and ilium.2’ A conventional osteosarcoma is occasionally indistinguishable radiographically from periosteal osteosarcoma, but invasion of the medul-
Fig 11. Parosteal osteosarcoma with dedifferentiation. The dense tumor new bone on the surface suggests the diagnosis of psrostesl osteosarcoms. However, the softtissue extension without signifioant calcification (srrows) suggest either the dediierentiation of a parosteal sarcoma or perhaps s high-grade aggressive surface sarcoms.
lary cavity should indicate the correct diagnosis. Parosteal osteosarcomas most frequently occur at the posterior aspect of the distal metaphysis of the femur, and are much larger and denser than periosteal osteosarcomas. Ewing’s sarcoma occasionally presents as a sessile tumor on the periosteum with spiculated periosteal reaction, which may make it indistinguishable from periosteal osteosarcoma; however, such an appearance is unusual in Ewing’s sarcoma, since involvement of the cortex cortical and medullary canal is usually evident. On occasion, because of the presence of malignant chondrocytes, a periosteal osteosarcoma
164
EDEIKEN-MONROE,
Telangiectatic Fig 12. amount of calcific debris mass with calcification.
osteosarooma. in the soft-ti8se
(A) An osteolyic mass. (B) One month
may erroneously be diagnosed histologically chondrosarcoma. HIGH-GRADE
as a
SURFACE OSTEOSARCOMA
High-grade surface osteosarcomas are rare juxtacortical tumors that account for ~1% of osteosarcomas.22 The age range is between 9 and 62 years, with a mean of 25 years at the time of diagnosis. The symptom is usually a mass, with or without pain, occurring most commonly in the femur, although reported in the humerus, radius, and interosseous membrane of the tibia and the fibula.22
lesion after
destroys arterial
EDEIKEN,
the proximal end of the fibula cis-platinum there is organization
AND
JACOBSON
with only a small of the soft-tissue
Radiographically, the appearance is similar to a periosteal osteosarcoma, arising from the surface of bone and being attached to the cortex (Fig 16). Superficial cortical destruction is typical, the amount of periosteal new bone formation is variable. EXTRAOSSEOUS
OSTEOSARCOMA
This uncommon neoplasm usually occurs in the soft tissues of the thighs,23-28 but it is reported in the soft tissues of the retroperitoneum,29-32 the buttock and back,26733W36 the orbit, submental region, 36q37 the face,38the upper and lower extrem-
165
OSTEOSARCOMA
tous tissue of malignant osteoid and/or bone; and (3) the ready exclusion of osseous origin.42 The histologic features are the same as for intraosseous osteosarcoma. This tumor must be distinguished from malignant mesenchymoma, which is a combination of osteosarcomatous and other malignant elements (liposarcoma). Osteosarcomas with fibromatous and/or chondromatous elements are not excluded from the diagnosis. 42 Extraosseous osteogenic sarcoma is associated with previous radiation therapy in 10% of cases.23 Roentgenographic
Features
The typical lesion is usually a large soft-tissue mass, not always adjacent to bone. Somewhat more than 50% have calcifications,25 which may lead to the proper diagnosis, but otherwise the appearance is nonspecific (Fig 17). Soft-tissue osteosarcoma may be mistaken for myositis ossificans, but osteosarcoma causes production of mineral more in the center of the lesion, fading off toward the periphery. The periphery of the lesion will be irregular. With myositis ossificans, on the other hand, the mineral is densest at the periphery and fades off towards the center (the zonal sign). INTRAOSSEOUS WELL-DIFFERENTIATED OSTEOSARCOMA (CENTRAL OSTEOSARCOMA OF LOW-GRADE MALIGNANCY)
This well-differentiated malignant tumor43*44 may be confused with fibrous dysplasia, osteofibrous dysplasia, osteoblastoma, and the sclerosing variant of conventional osteosarcoma. Roentgenographic Features Fig 12. (Cont’d). (C) Three months Inter, after several courses of intraarterial chemotherapy, there is almost complete organization of the tumor. These tumors are very responsive to chemotherapy and a better prognosis may be expected than central osteosarcoma.
ities, the axilla, 25 the abdomen, the neck,25 the kidney, 39the liver,40 and the breast (Fig 14).41 The diagnostic criteria are: (1) the uniform morphologic pattern of sarcomatous tissue, excluding the possibility of mixed malignant mesenchymal tumor; (2) the production by sarcoma-
The tumor is usually localized within the bone, with minimal areas of sclerosis. Its frequently observed sclerotic margin suggests a slowgrowing nature (Fig 18). Usually there is some endosteal cortical destruction of a permeative nature, and when this is present lesions such as fibrous dysplasias or infarcts must be excluded. This tumor may be upgraded on repeated biopsies over several years.43*44 Although few cases are noted in the literature, metastasis to the lung has occurred only with inadequate or delayed treatment. No reports of recurrence exist
166
EDEIKEN-MONROE,
Fig 14. bone occur smell areas Fig 13. Telangiectatic osteosarcoma. An osteolytic tumor is present in the midshaft of the tibia w’iih a fairly well-defined transition zone and slight expansion of bone. The appearance may suggest a benign lesion such as an aneurysmal bone cyst, but this proved to be a telangietactic osteosarcoma.
after an en bloc resection or amputation initial procedure.45 SMALL-CELL
as the
OSTEOSARCOMA
Small-cell osteosarcomahas the histologic and radiologic features of osteosarcomaand Ewing’s sarcoma. Synonyms are multipotential primary sarcoma of bone, and polyhistiocytoma.
Periosteal at right of round
Roentgenographic
osteosarcoma. angles to the bone density.
EDEIKEN,
shaft
AND
JACOBSON
Short spicules intermingled
of with
Features
The distal end of the femur is the most frequent site and the humerus, pelvis, tibia, and fibula follow in order of frequency.46 The roentgenographic appearance is variable and cannot be absolutely distinguished from central osteosarcoma, although certain features are rather constant and may suggest the diagnosis. In the long bones, long lesionsusually affect one third to two thirds of the shaft, and generally arise in the metaphysis. Most lesions have an osteoblastic component and the dense,eburnated tumor osteoid formation is concentrated in the
167
Fig 16. Periosteal osteosarcoma. The tumor is situated on the external cortex and consists of a soft-tissue mass with spicules of periosteal reaction extending at right angles from the anterior surface of the tibia.
metaphysis or one end of the lesion. The majority show a considerable soft-tissue component. Periosteal new bone formation occurs in one half of the cases.46 Occasionally, the tumor is completely lytic, with a geographic destructive pattern (Figs 19, 20),46 or blastic without a permeative pattern and confined to the metaphysis and junction of the metaphysis and diaphysis. The lesion also may be
Fig 16. High-grade surface osteoaarcoma. The leaion is situated on the external cortex and there are apicules of perioateal reaction with some tumor new bone at the inferior margin of the lesion. This lesion oan easily be mistaken for parosteal oateosarcoma or periosteal oateosarcoma but the histologic pattern is high-grade oateosarcoma.
confined to the shaft of the affected long bone with only periosteal reaction.46 OSTEOSARCOMA RESEMBLING OSTEOBLASTOMA
Bertoni, et a147report 17 patients with osteosarcoma that histologically resembled osteoblastoma. The male-female ratio was almost equal, with the age range 11 to 58 years. The radio-
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 17. Extraoaaeous osteosarcoma. (A) An intraperitonaal osteosarcoma with dense tumor new bone is present in the left upper abdomen. (B) Metastases to soft tissues of the forearm. (C) Metastases to the lymph nodes of the abdomen, 1 year after removal of the primary tumor.
graphic appearance suggests malignancy in most; ossification with bone formation is more common than pure osteolysis (Fig 21). Aggressive osteoblastoma and malignant osteoblastoma are used to describe the lesion, but Bertoni et al consider it an osteosarcoma, resembling osteoblastoma; it behaves like osteosarcoma.47
OSTEOSARCOMATOSIS
Osteosarcomatosisis a rare condition in which multiple skeletal sites are involved simultaneously.48-51 Synonyms include sclerosing osteogenic sarcoma, osteoblastic osteogenic sarcoma, sclerosing osteogenic sarcomatosis, multicentric
OSlEO6ARCOMA
169
Fig 18. Intraosseous welldifferentiated osteossrcoma. An osteolytic tumor is present at the distal end of the femur. lt extends outside of the cortex and has a calcific rim. The transition zone is short and there is no osteoid production. The appearance is fairly characteristic, however, or some osteolytic high-grade central osteosarcomas or telangiectatic osteosarcomas may have this appearance.
osteosarcomata, and multifocal osteosarcoma. Although the multiple foci may simply represent metastatic lesions, it is clear clinically that osteosarcomatosis is a separate disease entity.52 Roentgenographic Features The diangosis of osteosarcomatosis can be made with confidence from the roentgenograms alone. Simultaneous densely opaque lesions are found in the metaphyses of multiple long bones.53 The sclerosis correlates with heavy production of osteoid and bone (osteoblastic). The tumors are
bilateral and symmetrical: they may occur in a few bones, or every bone of the body. Early lesions present intense radiopacities, confined to bone and varying in size depending on their age. In the early stage, the lesions may appear to be innocuous bone islands, (Fig 22) but their persistent and rapid growth soon indicates the diagnosis. Eventually, the entire metaphysis of the bone fills with markedly sclerotic lesions, which frequently break through the cortex to produce soft tissue tumors with new bone formation. The tumors may extend into the epiphyseal plate
170
Fig lg. Small-cell osteosarcoma. There is a geographical destructive area in the distal end of the femur. On the lateral portions of the distal femur there are some osteoblastic reactions. This tumor has the characteristic of small-cell lesion that can be mistaken for Ewing’s but production of tumor osteoid makes the correct diagnosis of small-cell osteosarcoma.
from the metaphysis, or begin in the epiphysis and present as multiple rounded densities. Usually the lesions are all of the same size, strongly suggesting that they originate at the same time. Occasionally, a single primary osteosarcoma will ‘metastasize early and extensively to bone, and all the metastatic lesions may be of the same size. In such cases the primary lesion is usually larger than the metastases, which helps distinguish such a disorder from multicentric osteosarcoma. Metastic deposits in the lung are common, and, because they contain new bone, often appear as densely opaque, rounded lesions.
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 20. Smell-cell osteosarcoma. There is a destructive lesion at the distal end of the femur on the medial size with spiculated periosteel reaction. There is one area of osteoid tumor new bone formation adjacent to the epiphysis which should aid in the diagnosis (arrows). The initial histologic appearance was that of a small-cell tumor and the diegnosis was believed to be a Ewing’s sarcoma; the presence of tumor osteoid indicated a small-cell osteosarcome.
Early localized metaphyseal lesions are distinguished from the linear densities of heavy metal poisoning by their rounded or oval appearance. Other osteoblastic focal lesions such as sclerosing osteitis, progressive diaphyseal dysplasia, melorheostosis, osteopoikilosis, and bone infarction do not have a malignant appearance, nor are they usually painful. Osteopetrosis, a more generalized form of osteosclerosis, should not be confused with osteosarcoma.
171
OSTEOSARCOMA
Fig 21. Osteosarcoma resembling osteoblastoma. The destructive lesion has caused enlargement of the bone and endosteal cortical thickening. The transition zone is short and there is tumor new bone formation within the osteolytic area. The histologic diagnosis was atypical osteoblastoma but eventually it proved to be a conventional osteosarcoma. The histologic diagnosis of atypical osteoblastoma almost always indicates an osteosarcoma with histologic elements of osteoblastoma.
INTRACORTICAL
OSTEOSARCOMA
Intracortical osteosarcomasare indolent, and have a much better prognosisthan other forms of osteosarcoma.54’55 Approximately 50% will sur
vive 5 years. Radiographically, the lesion begins as a small area of destruction within the cortex, and may be mistaken for benign disease (eg, osteoid osteoma, Brodie’s abscess).
172
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 22. Osteosarcomatosis. Areas of dense bone are present in the metastases of the tibia, the proximal fibula. and the distal femur. (A) Small osteoblastic densities are present in the metastases of the right humerus adjacent to the epiphyseal plate. (B) Small densities were present in all the long bones and the patient died within a year of widespread matastases.
REFERENCES 1. Dahlin DC Bone Tumors, 4th ed. Springfield, IL: 7. Jaffe HL: Tumors and Tumorous Conditions of the Thomas, 1986 Bones and Joints. Philadelphia: Lea & Febiger, 1958 2. Raymond AK, Chawla SP, Carrasco CH, et al: Osteo8. Dahlin DC: Bone Tumors. Springfield, IL: Thomas, sarcoma chemotherapy effect: A prognostic factor. Semin 1957 Diagn Path01 1987;4:212-236 9. Cade S: Osteogenic sarcoma. J R Co11 Surg Edinb 3. de Santos LA, Edeiken B: Purely lytic osteosarcoma. 1955;1:79-83 Skeletal Radio1 1982;9:1-7 10. de Santos LA, Rosengren JE, Wooten WB, et al: 4. Danziger J, Wallace S, Handel SF, et al: Metastatic Osteogenic sarcoma after the age of 50: A radiographic osteogenic sarcoma to the brain. Cancer 1979;43:707-10 evaluation. AJR 1978;131:481-4 5. Smith J, heelan RT, Huvos AG, et al: Radiographic 11. Finkelstein JB: Osteosarcoma of the jaw bones. Radio/ changes in primary osteogenic sarcoma following intensive Clin North Am 1970;8:425-443 chemotherapy. Radiology 1982;143:355-360 6. Chuang VP, Benjamin R, Jaffe N, et al: Radiographic 12. Lee YY, Van Tassel P, Nauert C, et al: Craniofacial and angiographic changes in osteosarcoma after intraarterial osteosarcomas: Plain film, CT, and MR findings in 46 cases. chemotherapy. AJR 1982;139:1065-9 AJNR March/April 1988;9:379-385
OSTEOSARCOMA
13. Smith J, Botet JF, Yeh SDJ: Bone sarcomas in Paget disease: a study of 85 patients. Radiology 1984;152:583-590 14. Huvos AG, Butler A, Bretsky SS: Osteogenic sarcoma associated with Paget’s disease of bone. Cancer 1983; 52:1489-1495 15. Smith J, Ahuja SC, Huvos AG, et al: Parosteal (juxtacortical) osteogenic sarcoma: A roentgenological study of 30 patients. JCan Assoc Radio1 1918;29:167-114 16. Edeiken J, Farrell C, Ackerman LV, et al: Parosteal sarcoma. AJR 1971;111:579-84 17. Dahlin DC: Bone Tumors, 2nd ed. Springfield, II: Thomas, 1967;176-185 18. Wold LE, Unni KK, Beabout JW, Sim FH, Dahlin DC. Dedifferentiated parosteal osteosarcoma. J Bone Joint Surg 1984;66A(1):53-59 19. Spjut HJ, Dorfman HD, Fechner RE, et al: Tumors of bone and cartilage. In: Atlas of Tumor Pathology, fascicle 5. Washington, DC: U.S. Armed Forces Institute of Pathology, 1971;166-174 20. de Santos LA, Murray JA, Finklestein JB, et al: The radiographic spectrum of periosteal osteosarcoma. Radiology 1978;127:123-9 21. Unni KK, Dahlin DC, Beabout JW: Per&teal osteogenic sarcoma. Cancer 1976;37:2476-2485 22. Wold LE, Unni KK, Beabout JW, et al: High-grade surface osteosarcomas. Am JSurg Path01 1984;8:181-6 23. Sordillo PP, Hajdu SI, Magi11 GB, et al: Extraosseous osteogenic sarcoma: A review of 48 patients. Cancer 1983; 511121-734 24. Rao
U, Cheng A, Didolkar MS: Extraosseous osteogenicsarcoma. Cancer 1978;48:1488-1496 25. Allan CJ, Soule EH: Osteogenic sarcoma of the somatic soft tissues: Clinicopathologic study of 26 cases and review of literature. Cancer 27:1121-33, 1971 26. DeBoer WGRM, Oldhoff J, Stam H: Extraosseous ossifying sarcoma localized in the soft tissues. Arch Chir Neurol1964;16:217-24 27. Gupta DN, Aga V: Soft tissue osteogenic sarcoma (a case report). Indian J Path01 Bacterial 1965;8:59-62 28. Das Guptz TK, Hajdu SI, Foote FW Jr: Extraosseous osteogenicsarcoma.AnnSurg1968;168:1011-15 29. Jarvi OH, Kvist HTA, Vainio PV: Extraskeletal retroperitoneal osteosarcoma probably arising from myositis ossiticans. Acta Path01 Microbial Stand 1968;14:11-16 30. Lowry K Jr, Haynes CD Osteogenic sarcoma of extraskeletal soft tissues: A case report. Am Surg 1964; 30:97-100
3 1. Rachman R, Massa EV: Pelvic extraskeletal osteosarcoma associated with prostatic adenocarcinoma. Am J Clin Path01 1965;44:556 32. Boyer CW Jr, Navin JJ: Extraskeletal osteogenic sarcoma: A late complication of radiation therapy. Cancer 1965;18:628 33. Salm R: A case of primary osteofenic sarcoma of extraskeletal soft tissue. Br J Cancer 1959;13:614
173
34. Sheikh MA, Koten JW: A case of primary osteogenic sarcoma of connective tissue. East Aji hfed J 1968;45:760 35. Kauffman SL, Stout AP: Extraskeletal osteogenic sarcomas and chondrosarcomas in children. Cancer 1963; 16:432 36.
Jussawalla DJ, Desani JG: Primary osteogenic sarcoma arising in extraskeletal soft tissues of the neck. Br J Surg 1964;51:504 37. Shanoff LB, Spira M, Hardy SB: Myositis ossificans evolution of osteogenic sarcoma: Report of a histologically verified case. Am JSurg 1967;113:537 38. Stout AP, Lattes R: Tumors of the soft tissues. In: Atlas of Tumor Pathology, fascicle 1, Ser. 2. Washington, DC: U.S. Armed Forces Institute of Pathology, 1967;162-3 39. Axelrod R, Naidech HJ, Myers J, et al: Primary osteosarcoma of the kidney. Cancer 1978;41:724-7 40. Dalinka MK, Fiveash A, Aston JK: Metastatic extracsseous osteosarcoma to the liver: Report of a case demonstrated by s5Sr and 99mTc-sulfur colloid scanning. J Nucl Med 1911:154-9 41. Watt AC, Haggar AM, Krasicky GA: Extraosseous osteogenic sarcoma of the breast: Mammographic and pathologic findings. Radiology 1984;150;34 42. Stout AP: Mesenchymoma, the mixed tumor of mesenchymal derivatives. Ann Surg 1948;127:278 43. Unni KK, Dahlin DC, McLeod RA, et al: Intraosseous well-differentiated osteosarcoma. Cancer 1977;40:1337-1347 44. Campanacci M, Bertoni F, Campanna R, et al: Central osteosarcoma of low grade malignancy. Ztal J 0rthop Traumatol1981;7:71-8 45. Xipell JM, Rush J: Case report 340. Skeletal Radio1 1985;14:312-316 46. Edeiken J: Small cell osteosarcoma. Znt Skeletal Radiology, 1987;16:621-8 47. Bertoni F, Unni KK, McLeod RA, et al: Gsteosarcoma resembling osteoblastoma. Cancer 1985;55:416-426 48. Parham DM, Pratt CB, Parvey LS, et al: Childhood multifocal osteosarcoma: Clinicopathologic and radiologic correlates. Cancer 1985;55:2653-8 49. Morse D Jr, Reed JO, Berstein J: Sclercsing osteogenic sarcoma. AJR 196&88:491-g 50. Geschickter CF. Copeland MM: Tumors of Bone, 2nd ed. Philadelphia: Lippincott, 1949 5 1. Moseley JE, Bras MH: Sclerosing osteogenic sarcomatosis; radiologic entity. Radiology 1956;66:41-52 52. Edeiken J: Roentgen Diagnosis of Diseases of Bone, 3rd ed. Baltimore: Williams & Wilkins, 1981 53. Singleton EB, Rosenberg HS, Dodd GD, et al: Sclerosing osteogenic sarcomatosis. AJR 1962;88:483 54. Vigorita VJ, Jones JK, Ghelman B, et al: Intracortical osteosarcoma. Am JSurg Path01 1984;8:65-71 55. Picci P, Gherlinzoni F, Guerra A: Intracortical osteosarcoma: Rare entity or early manifestation of classical osteosarcoma? Skeletal Radio1 1983;9:255-8
Edeiken-Monroe,
Jack
Edeiken,
T
HE ADVENT OF chemotherapy for the treatment of osteosarcoma has changed the prognosis significantly. Furthermore, limb salvage procedures preserve function. Since the variations of histologic types are treated differently, the classification of these neoplasms has become more than an intellectual exercise. Osteosarcoma can be divided into a number of clinical types and grouped by site and histologic variations with differences in prognosis.’ In order of frequency, they are: (1) classical central osteosarcoma; (2) mandibular osteosarcoma; (3) secondary osteosarcoma (Paget’s Disease and radiation); (4) parosteai sarcoma (parosteal osteosarcoma and juxtacortical osteosarcoma) and dedifferentiated parosteal osteosarcoma; (5) telangiectatic osteosarcoma; (6) periosteal osteosarcoma; (7) poorly differentiated (high-grade) surface osteosarcoma; (8) extraosseous osteosarcoma; (9) intraosseous well-differentiated (lowgrade) central osteosarcoma; (10) small cell osteosarcoma; (11) osteoblastoma-osteosarcoma complex; (12) sclerosing osteosarcomatosis (multicentric osteosarcoma); and (13) intracortical osteosarcoma (Table 1). Raymond et al* propose a classification that serves to emphasize the common histologic elements of these tumors (Table 2). Osteosarcomas, radiographically, produce all varieties of bone change, from nearly normal, to extremely dense, to almost total destruction, and to varying admixtures. The totally osteolytic osteosarcoma may be a telangiectatic osteosarcoma. It cannot be distinguished radiographically from an osteolytic osteosarcoma of the classical histologic pattern. Purely lytic osteosarcoma is reported in 13.7% of 305 patients in one series3 The roentgenographic diagnosis rests on the abnormal skeletal response, whether homogenous or heterogeneous, regular or irregular, clearly defined or totally lacking in margination; the nature of the cortical response; the presence or absence of a perifocal soft tissue mass; and many other factors.
Seminars
in Roenrgeno/ogy,
Vol XXIV,
No 3 (July),
1989:
pp 153-l
and
Harold
G. Jacobson
With osteosarcoma the periosteal response is extremely important radiologically because it is almost always highly irregular and interrupted. The sunburst and onion-peel types are classic examples. In contrast, in benign processes the periosteal reaction may be more uniformly homogeneous and solid. With benign lesions the segments of the cuff of newly formed periosteal bone appear all of the same age, as though in response to a single event, and are morphologically uniform throughout, with their superficial portions similar in all radiographic structure to the deeper ones. In osteosarcoma, the periosteal cuff is totally irregular, with different types of periosteal reaction observed at different sites. The structural composition of the periosteal cuff usually appears to represent events occurring at different times and responding differently to the ever-present irritant. These variations are not always unmistakably present, nor is it possible to always distinguish benign from malignant periosteal responses. However, as a working rule these generalities do prove helpful in differential diagnosis. For years, the Codman triangle has been considered invariably reliable in the roentgenographic recognition of malignant bone tumors. It is not. The Codman triangle is not a pathognomanic feature, since it may occur in benign
From the Department of Radiology, M.D. Anderson Cancer Center, University of Texas System. Houston; Department of Radiology. Health Science Medical School, University of Texas, Houston; and Division of Diagnostic Radiology, Montefiore Hospital and Medical Center, Bronx, NY, respectively. Beth Edeiken-Monroe: Department of Radiology, University of Texas Health Science Medical School, Houston; Harold G. Jacobson: Division of Diagnostic Radiology, Montejiore Hospital and Medical Center, Bronx. NY; Jack Edeiken: Department of Radiology, M.D. Anderson Cancer Center, University of Texas System, Houston. Address reprint requests to Jack Edeiken. MD, Department of Radiology, Box 57. M.D. Anderson Cancer, University of Texas System, 1515 Holcombe Blvd. Houston, TX 77030. 0 I989 by W.B. Saunders Company. 0037-I 98X/89/2403-0002$5.0000/0
73
153
154
EDEIKEN-MONROE,
Table
1. Types
of Osteosarcoma No. of Cases
Tvw Conventional Others
Osteosarcoma
Osteosarcoma Osteosarcoma
in jaw in Paget’s
Postradiation Osteosarcoma Telangiectatic Periosteal High-grade
933 281 84 43 52
Disease
osteosarcoma in benign conditions osteosarcoma
8 44
osteosarcoma surface osteosarcoma
22 9 16
Low-grade osteosarcoma Multicentric osteosarcoma Parosteal osteosarcome Dedifferentiated Total
3 56
chondrosarcoma
Classification Clinic.’
system
43 1,373
for osteosarcoma
developed
at the Mayo
disorders, particularly those that are aggressive in their behavior (eg, infection). The presence of a soft-tissue mass immediately adjacent to the diseased bone from which it obviously arose is highly informative. With osteosarcoma, nests of tumor bone, varying radiographically in density, may appear as individual Table
2. Osteosarcoma
Classificstion
System
Conventional Osteoblastic Chondroblestic
in jaw
well-differentiated resembling
conditions
osteosarcoma osteoblastoma
Telangiectatic osteosarcoma Small cell osteosarcoma ? Dedifferentisted chondrosarcoma
(CENTRAL)
OSTEOSARCOMA
Proposed modification of the osteosarwma tem. All elements of the Mayo Clinic system serva to emphasize the diverse group. Modified
Classical osteosarcoma, primarily a disease of young adults, is rare before the age of 10 years; 70% to 80% of the tumors appear before the age of 30 years.7-9 We have evaluated 181 consecutive patients with osteosarcoma; and 70% were females, except with de novo tumors after age 50, when the reverse is true.” Roentgenographic Features
? Malignant fibrous histiocytoma Surface Parosteal osteosarcoma Dedifferentieted parosteal osteosarcoma Pariosteal osteosarcoma High-grade surface osteoearcoma
The minor additions within this otherwise aLz
JACOBSON
Clinical Features
Postradiation osteosarcoma Paget’s osteosarcoma Multifocal osteosarcoma Osteosarcome in other benign Morphologic lntraosseous Osteosarcoma
AND
islets or coalescing groups of islets. These mineralized islets often contain trabeculae and haversian canals, pathognomonic of tumor bone, but just as often the mineral may be homogeneous without a trabecular pattern. Calcified tumor cartilage has a distinctive roentgenogrpahic appearance, described variously as extremely dense or of a snow-flake character. On many occasions, calcified tumor cartilage resembles small nests of bone infarcts seeded throughout the spongy portions of bone. Sometimes the tumor bone and tumor cartilage obscure, radiographically, the true nature of the sarcoma, and since osteosarcomas are more common than chondrosarcomas, the pragmatic tendency is to call such uncharacteristic tumors osteosarcomas, particularly where the age group suggests them. Metastases to bone, lung, lymph nodes, liver, soft tissues, and brain may contain tumor new bone and may be identified by the increased density of the metastases.4 With the advent of chemotherapy, intravenous or intraarterial responses can be followed by routine radiography. Medullary sclerosis, periosteal new bone formation, and disappearance of soft-tissue masses reflect a positive response to treatment.5*6 CLASSICAL
Fibroblastic Variants Clinical Osteosarcoma
EDEIKEN,
classification syshave been retained. common elements from Raymond et
Before describing the distinctive roentgenographic features of osteosarcoma, brief mention must be made of the general responses of bone and soft tissues to irritants. All bone reacts to inflammatory or neoplastic irritants in either an osteoblastic or an osteolytic way. Osteoblastic responses are generally referred to as reactive bone, new bone formation, or just increased bone density, appellations as nonspecific as their roentgenographic appearances.
OSTEOSARCOMA
Benign bone responses are usually sharply demarcated (short transition zone) and easily differentiated from their surroundings. Malignant neoplastic responses usually lack this differentiation, their borders blending imperceptibly with surrounding bone (wide transition zone) (Fig 1). Sometimes osteoblastic responses display characteristic bone patterns, with trabeculae and haverSian canals, and may very properly be called new bone formation. New bone formations may be benign or malignant; radiographically they are
Fig 1. Central osteosarcoma. An osteoblastic reaction is present in a large tumor that extends from the head of the femur to the shaft. The transition zone is long and blends inperceptively with the host bone.
155
differentiated by their density and margins: the less uniform the density and the less definitive the margins, the greater the likelihood of malignancy. However, exceptions do occur. The transition zone may be short and suggest a benign process. A sclerotic margin may form at the transition zone (Fig 2), and a benign lesion may be considered, but within the lesion, tumor new bone (eburnated bone) will usually be present. This occurs with fibroblastic osteosarcomas, often with
156
Fig 2. suggests
EDEIKEN-MONROE,
High-grade osteosarcoma of the a benign process. (A) Antero-posterior
tibia.
The transition zone projection. (Bj Lateral
elements of nonosteogenic fibroma. The short transition zone or the sclerotic margin has no bearing on the prognosis. Malignant reactive new bone formation may be either primary or secondary and, when it is confined within the normal limits of the bone and defined by the normal cortex, it is difficult to classify from roentgenographic appearances alone. Under such circumstances, the clinical story is of paramount importance. For a 70year-old man whose prostatic carcinoma shows reactive new bone deposits, the diagnosis would be different from that suggested for a teenager with similar bone densities. Important as are the roentgenographic mani-
is short projection.
and
surrounded
EDEIKEN,
by a sclerotic
AND
JACOBSON
margin
which
festations of these new bone formations, even more important are the soft tissue masses that may lie adjacent to the bone, particularly those that are obviously extensions of processes, apparently primary in bone. (Figs 3-5) This type of new bone formation may very properly be called tumor bone. Invariably associated with new bone formation within the parent bone, tumor bone in parosseous soft tissue masses is a cardinal roentgenographic feature of primary osteosarcoma of bone. Osteosarcomas usually arise in the metaphyseal portion of long bones, most frequently at the distal end of the femur and the proximal ends of the tibia and the humerus. They do not always,
OSTEOSARCOMA
157
Fig 3. Osteosarcoma of the femur. Osteoblastic bone is present within the distal end of the femur. The homogeneous appearance suggest tumor new bone but it is possible that it is reactive bone. However, the soft-tissue mass contained homogeneous calcification indiiting osteoid tumor new bone formation (arrows). There is also perioaeaf reaction.
however, arise in the metaphysis, and they may affect any part of the bone, or arise in the soft tissues (see EXTRAOSSEOUS OSTEOSARCOMA). Osteosarcomas occur more frequently in the cylindrical bones of patients under 30 and in the flat bones, particularly the ilium, of those over 50.8,‘o OSTEOSARCOMA
OF THE JAW
Osteosarcoma of the jaw (mandible and maxilla) has an incidence 1 to 15 years later than the classical osteosarcoma”V’2of 24 de novo osteo-
sarcomas of the jaw studied at M.D. Anderson Hospital, I2 12 were present in the maxillary bone and 11 in the mandible. Roentgenographic Features A soft tissue massis always present and most contain calcifications and/or bone (Fig 6). SECONDARY OSTEOSARCOMA TO PAGET’S DISEASE AND OTHER CONDITIONS
In patients over 35, most osteosarcomasare secondary to preexisting bone conditions, such as Paget’s disease. However, another peak inci-
158
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 4. Osteoaarcoma of the distal end of the femur. Mixed osteolytic and osteoblastic destruction is present in the distal end of the femur. The osteoblastic reaction could represent reactive new bone, rather than tumor new bone, but the soft-tissue mass contained a homogeneous calcific density characteristic of tumor oateoid new bone formation (arrows).
dence in the fifth decade cannot be completely attributed to preexisting lesions. Severe pain, intermittent at first and later becoming constant, is the outstanding clinical complaint; it has usually been less than 2 months in duration at the initial examination. Osteosarcoma accounts for about 90% of sarcomas developing in pagetoid bone.‘4’4 Approximately 5% of osteogenic sarcomas are associated with monostotic or polyostotic Paget’s disease. The median age is 64 years, with male predomi-
nance. The most frequent areas are the pelvic bones, humerus, femur, and craniofacial bones.i4 Pain and swelling are the most common presenting symptoms, with pathological fractures occurring in one quarter of the patients. In approximately two thirds of cases, the radiologic appearance is a lytic destructive lesion, while in the minority a sclerotic, mixed, or permeative pattern is present. The tumors are large, bulky, soft-tissue masses and periosteal reaction is infrequent (Fig 7). l3
OSTEOSARCOMA
159
Fig 5. High-grade central osteosarcoma of the femur. The soft-tissue mass contains considerable tumor new bone formation. There ara alao islanda of tumor new bone extending to the neck of the femur. The characteristics of the density indicate a bone forming tumor.
PAROSTEAL SARCOMA (PAROSTEAL OSTEOSARCOMA OR JUXTACORTICAL OSTEOSARCOMA)
Parosteal sarcoma7 develops from the periosteum, grows outward from the bone, and tends to surround the host bone, unlike central osteosarcoma, which begins within the bone and later breaks out.
Roentgenographic Features Recognition of classical parosteal sarcomas usually_ -presents no difficulty. Found most commonly in the lower end of the femur, either end of the tibia, and proximal end of the humerus, they present as dense massesof homogeneous new bone extending away from the bone cortex. They are rare in bones other than long bones. The
160
Fig 6. Osteosarcoma of the manidbls. Ostaoblastic reaction is present in the anterior portion of the mandible. There was a soft-tissue mass with calcification within indicating the correct diignosis.
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
it,
periphery is usually lobulated and round; small bone trabeculae may be found within the lesion. Highly characteristic in the early stages is a fine radiolucent line separating the dense mass of tumor bone from the cortex, except at the site of the central stalk attachment (Fig 8). Running parallel to the shaft of the bone, this line probably represents the thickness of the periosteum, lying between the cortex and the tumor. The stalk grows with the tumor, eventually attaching along its entire extent, and as it grows the radiolucent line is shortened and eventually obliterated (Fig 9).“*” Small areas of new bone, either adjoining the periosteum or seemingly unattached, may be the only early evidence of parosteal sarcoma. Later, as these masses grow, the linear radiolucent periosteal defect that separates cortex and tumor disappears and all contrast between them is obscured. The inner portions and stalk are homogeneously dense, and the periphery less dense. The tumor bone nearest the cortex is thickest and most mature and is therefore slightly denser than at the periphery. The cortex of the bone remains intact until very late in the disease. Later, additional round deposits of new bone may form, separated from the main mass of tumor, and have
Fig 7. Paget’s disease with secondary osteosarcoma. The characteristic changes of Pagat’s disease is present the medial aspect of the distal femur extending proximally into the shaft. On the lateral border there is a soft-tissue mass which extends exterior to the bone and was proven be an osteosarcoma.
on
to
been known to exceed 10 cm in diameter (Fig 10). Occasionally, these tumors metastasize early, with new bone formation within the lymph node metastasis; however, they may grow slowly for years before metastasis occurs. Usually the tumor can be differentiated from other cortical lesions such as osteochondroma and myositis ossificans. With osteochondroma, the cortex of the host bone is continuous with the lesion itself, so that cortex and medulla of tumor and host bone are indistinguishable from each other. Myositis ossificans appears in two forms, either as feathery bone that follows fascial planes, or as rounded, ossified masses less dense in the center than parosteal sarcoma and with sclerotic
OSTEOSARCOMA
Fig 8. Parosteal sarcoma. The dense osteoblastic bone which tends to fade in the periphery zonal sign characteriatic of parosteal osteosarcoma. The radiolucant line separates the tumor from the tibia.
margins. This zonal sign is most useful in distinguishing the lesion from parosteal osteosarcoma. Juxtacortical hematomas occasionally reveal periosteal reactions not unlike those of early parosteal sarcoma. Extraosseous osteosarcomas are not in intimate contact with bone. Dedifferentiation of low-grade parosteal osteosarcomas is reported; rapid growth or severe pain suggests dedifferentiation, as does development of new lytic areas following treatment. At the time of recurrence, the high-grade component is the most important prognostic indicator.‘*
DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA
Dedifferentiated parosteal osteosarcoma occurs in 10% to 20% of parosteal osteosarcomas,‘7 and the prognosis is similar to that for conventional osteosarcoma. In one series, 10 of 11 patients had a long history of treatment for multiple recurrences of low-grade parosteal osteosarcoma before the high-grade undifferentiated osteosarcoma occurred.17 In our experience, however, 12 of 13 patients demonstrated dediffer-
162
EDEIKEN-MONROE,
Fig 9. Parosteal osteosarooma blastic bone is denser in the toward the periphery, especially tumor has anached to the bone therefore, no fine line separates
of the femur. The osteocenter of the lesion than at the inferior margin. The along its entire extent and it from the normal bone.
entiation on the first examination. Such lesions are most often reported in the femur, but have occurred in the humerus, tibia, and the fibula (Fig 1l).” Roentgenographic
Features
Usually evidence exists of a characteristic parosteal osteosarcoma with dense new bone formation, most frequently at the posterior surface of the distal end of the femur. The tumor new bone is denser in the center and fades at the periphery of the tumor (zonal sign). With dedifferentiation one of three different radiographic patterns appears: (1) a characteristic parosteal osteosarcoma, with round osteolytic areas measuring 1 to 2 cm present within the tumor new bone; (2) large, soft-tissue masseswith spotty calcifica-
EDEIKEN,
AND
JACOBSON
Parosteal osteosarcoma. The dense tumor bone Fig 10. is on the surface of the tumor. There are several separate islands of calcification. The tumor density is greatest in the center of the tumor and fades at the periphery.
tions separate from or invading the original tumor (Fig 11); and (3) hypervascular areas demonstrated by arteriography. Parosteal osteosarcomas are usually hypovascular but in the absence of dedifferentiation they may contain small hypervascular areas that must undergo biopsies. TELANGIECTATIC
OSTEOSARCOMA
Classical osteosarcomas can have areas of telangiectasia, but the presence of more than 90% of tissue of telangiectatic features indicates the special variant, telangiectatic osteogenic sarcoma. Radiographically, the lesion is purely lytic,
with minimal internal sclerosis (Figs 12, 13). The most characteristic appearance is that of an expansile lesion, often lacking periosteal reaction and displaying a well-demarcated radiolucency, so that differentiation from aneurysmal bone cyst may be difficult (Fig 13). PERIOSTEAL OSTEOSARCOMA (PERIOSTEAL OSTEOGENIC SARCOMA)
Periosteal osteosarcoma is distinct from the conventional (medullary) osteosarcoma, and the less aggressive parosteal sarcoma, for which it may be mistaken.18M20 Roentgenographic Features
The appearance is so characteristic that the correct diagnosis is easily made in the majority of lesions. The lesion appears as a sessile elliptic growth on the periosteal aspect of the cortex of the diaphysis of a long bone, but may often cause irregular destruction of the cortex. Short spicules of bone at right angles to the shaft are intermingled with small areas of rounded bone density (Figs 14, 15). The periosteal reaction may be lamellated. The lesion is rarely over 7 to 12 cm in length and 2 to 4 cm in width. A small, uncalcified soft-tissue component often appears beyond the calcification. The base of the tumor is usually closely attached to the cortex over the entire extent of the tumor, unlike a parosteal sarcoma, with its short pedicle attachment and radiolucent line between the remainder of the tumor and the cortex. The enlargement of the bone is almost exclusively from the periosteal aspect, but in rare cases endosteal cortical thickening may encroach on the medullary cavity. Cortical destruction and invasion of the medullary canal should not occur in this tumor. The exclusive diaphyseal origin is unusual for mesenchymal tumors, which occur most frequently in metaphyseal areas of long bones. The proximal end of the diaphysis of the tibia and distal end of the diaphysis of the femur are the most frequent sites, especially at the medial and/or anterior aspects. 2oThey also are reported in the humerus, fibula, and ilium.2’ A conventional osteosarcoma is occasionally indistinguishable radiographically from periosteal osteosarcoma, but invasion of the medul-
Fig 11. Parosteal osteosarcoma with dedifferentiation. The dense tumor new bone on the surface suggests the diagnosis of psrostesl osteosarcoms. However, the softtissue extension without signifioant calcification (srrows) suggest either the dediierentiation of a parosteal sarcoma or perhaps s high-grade aggressive surface sarcoms.
lary cavity should indicate the correct diagnosis. Parosteal osteosarcomas most frequently occur at the posterior aspect of the distal metaphysis of the femur, and are much larger and denser than periosteal osteosarcomas. Ewing’s sarcoma occasionally presents as a sessile tumor on the periosteum with spiculated periosteal reaction, which may make it indistinguishable from periosteal osteosarcoma; however, such an appearance is unusual in Ewing’s sarcoma, since involvement of the cortex cortical and medullary canal is usually evident. On occasion, because of the presence of malignant chondrocytes, a periosteal osteosarcoma
164
EDEIKEN-MONROE,
Telangiectatic Fig 12. amount of calcific debris mass with calcification.
osteosarooma. in the soft-ti8se
(A) An osteolyic mass. (B) One month
may erroneously be diagnosed histologically chondrosarcoma. HIGH-GRADE
as a
SURFACE OSTEOSARCOMA
High-grade surface osteosarcomas are rare juxtacortical tumors that account for ~1% of osteosarcomas.22 The age range is between 9 and 62 years, with a mean of 25 years at the time of diagnosis. The symptom is usually a mass, with or without pain, occurring most commonly in the femur, although reported in the humerus, radius, and interosseous membrane of the tibia and the fibula.22
lesion after
destroys arterial
EDEIKEN,
the proximal end of the fibula cis-platinum there is organization
AND
JACOBSON
with only a small of the soft-tissue
Radiographically, the appearance is similar to a periosteal osteosarcoma, arising from the surface of bone and being attached to the cortex (Fig 16). Superficial cortical destruction is typical, the amount of periosteal new bone formation is variable. EXTRAOSSEOUS
OSTEOSARCOMA
This uncommon neoplasm usually occurs in the soft tissues of the thighs,23-28 but it is reported in the soft tissues of the retroperitoneum,29-32 the buttock and back,26733W36 the orbit, submental region, 36q37 the face,38the upper and lower extrem-
165
OSTEOSARCOMA
tous tissue of malignant osteoid and/or bone; and (3) the ready exclusion of osseous origin.42 The histologic features are the same as for intraosseous osteosarcoma. This tumor must be distinguished from malignant mesenchymoma, which is a combination of osteosarcomatous and other malignant elements (liposarcoma). Osteosarcomas with fibromatous and/or chondromatous elements are not excluded from the diagnosis. 42 Extraosseous osteogenic sarcoma is associated with previous radiation therapy in 10% of cases.23 Roentgenographic
Features
The typical lesion is usually a large soft-tissue mass, not always adjacent to bone. Somewhat more than 50% have calcifications,25 which may lead to the proper diagnosis, but otherwise the appearance is nonspecific (Fig 17). Soft-tissue osteosarcoma may be mistaken for myositis ossificans, but osteosarcoma causes production of mineral more in the center of the lesion, fading off toward the periphery. The periphery of the lesion will be irregular. With myositis ossificans, on the other hand, the mineral is densest at the periphery and fades off towards the center (the zonal sign). INTRAOSSEOUS WELL-DIFFERENTIATED OSTEOSARCOMA (CENTRAL OSTEOSARCOMA OF LOW-GRADE MALIGNANCY)
This well-differentiated malignant tumor43*44 may be confused with fibrous dysplasia, osteofibrous dysplasia, osteoblastoma, and the sclerosing variant of conventional osteosarcoma. Roentgenographic Features Fig 12. (Cont’d). (C) Three months Inter, after several courses of intraarterial chemotherapy, there is almost complete organization of the tumor. These tumors are very responsive to chemotherapy and a better prognosis may be expected than central osteosarcoma.
ities, the axilla, 25 the abdomen, the neck,25 the kidney, 39the liver,40 and the breast (Fig 14).41 The diagnostic criteria are: (1) the uniform morphologic pattern of sarcomatous tissue, excluding the possibility of mixed malignant mesenchymal tumor; (2) the production by sarcoma-
The tumor is usually localized within the bone, with minimal areas of sclerosis. Its frequently observed sclerotic margin suggests a slowgrowing nature (Fig 18). Usually there is some endosteal cortical destruction of a permeative nature, and when this is present lesions such as fibrous dysplasias or infarcts must be excluded. This tumor may be upgraded on repeated biopsies over several years.43*44 Although few cases are noted in the literature, metastasis to the lung has occurred only with inadequate or delayed treatment. No reports of recurrence exist
166
EDEIKEN-MONROE,
Fig 14. bone occur smell areas Fig 13. Telangiectatic osteosarcoma. An osteolytic tumor is present in the midshaft of the tibia w’iih a fairly well-defined transition zone and slight expansion of bone. The appearance may suggest a benign lesion such as an aneurysmal bone cyst, but this proved to be a telangietactic osteosarcoma.
after an en bloc resection or amputation initial procedure.45 SMALL-CELL
as the
OSTEOSARCOMA
Small-cell osteosarcomahas the histologic and radiologic features of osteosarcomaand Ewing’s sarcoma. Synonyms are multipotential primary sarcoma of bone, and polyhistiocytoma.
Periosteal at right of round
Roentgenographic
osteosarcoma. angles to the bone density.
EDEIKEN,
shaft
AND
JACOBSON
Short spicules intermingled
of with
Features
The distal end of the femur is the most frequent site and the humerus, pelvis, tibia, and fibula follow in order of frequency.46 The roentgenographic appearance is variable and cannot be absolutely distinguished from central osteosarcoma, although certain features are rather constant and may suggest the diagnosis. In the long bones, long lesionsusually affect one third to two thirds of the shaft, and generally arise in the metaphysis. Most lesions have an osteoblastic component and the dense,eburnated tumor osteoid formation is concentrated in the
167
Fig 16. Periosteal osteosarcoma. The tumor is situated on the external cortex and consists of a soft-tissue mass with spicules of periosteal reaction extending at right angles from the anterior surface of the tibia.
metaphysis or one end of the lesion. The majority show a considerable soft-tissue component. Periosteal new bone formation occurs in one half of the cases.46 Occasionally, the tumor is completely lytic, with a geographic destructive pattern (Figs 19, 20),46 or blastic without a permeative pattern and confined to the metaphysis and junction of the metaphysis and diaphysis. The lesion also may be
Fig 16. High-grade surface osteoaarcoma. The leaion is situated on the external cortex and there are apicules of perioateal reaction with some tumor new bone at the inferior margin of the lesion. This lesion oan easily be mistaken for parosteal oateosarcoma or periosteal oateosarcoma but the histologic pattern is high-grade oateosarcoma.
confined to the shaft of the affected long bone with only periosteal reaction.46 OSTEOSARCOMA RESEMBLING OSTEOBLASTOMA
Bertoni, et a147report 17 patients with osteosarcoma that histologically resembled osteoblastoma. The male-female ratio was almost equal, with the age range 11 to 58 years. The radio-
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 17. Extraoaaeous osteosarcoma. (A) An intraperitonaal osteosarcoma with dense tumor new bone is present in the left upper abdomen. (B) Metastases to soft tissues of the forearm. (C) Metastases to the lymph nodes of the abdomen, 1 year after removal of the primary tumor.
graphic appearance suggests malignancy in most; ossification with bone formation is more common than pure osteolysis (Fig 21). Aggressive osteoblastoma and malignant osteoblastoma are used to describe the lesion, but Bertoni et al consider it an osteosarcoma, resembling osteoblastoma; it behaves like osteosarcoma.47
OSTEOSARCOMATOSIS
Osteosarcomatosisis a rare condition in which multiple skeletal sites are involved simultaneously.48-51 Synonyms include sclerosing osteogenic sarcoma, osteoblastic osteogenic sarcoma, sclerosing osteogenic sarcomatosis, multicentric
OSlEO6ARCOMA
169
Fig 18. Intraosseous welldifferentiated osteossrcoma. An osteolytic tumor is present at the distal end of the femur. lt extends outside of the cortex and has a calcific rim. The transition zone is short and there is no osteoid production. The appearance is fairly characteristic, however, or some osteolytic high-grade central osteosarcomas or telangiectatic osteosarcomas may have this appearance.
osteosarcomata, and multifocal osteosarcoma. Although the multiple foci may simply represent metastatic lesions, it is clear clinically that osteosarcomatosis is a separate disease entity.52 Roentgenographic Features The diangosis of osteosarcomatosis can be made with confidence from the roentgenograms alone. Simultaneous densely opaque lesions are found in the metaphyses of multiple long bones.53 The sclerosis correlates with heavy production of osteoid and bone (osteoblastic). The tumors are
bilateral and symmetrical: they may occur in a few bones, or every bone of the body. Early lesions present intense radiopacities, confined to bone and varying in size depending on their age. In the early stage, the lesions may appear to be innocuous bone islands, (Fig 22) but their persistent and rapid growth soon indicates the diagnosis. Eventually, the entire metaphysis of the bone fills with markedly sclerotic lesions, which frequently break through the cortex to produce soft tissue tumors with new bone formation. The tumors may extend into the epiphyseal plate
170
Fig lg. Small-cell osteosarcoma. There is a geographical destructive area in the distal end of the femur. On the lateral portions of the distal femur there are some osteoblastic reactions. This tumor has the characteristic of small-cell lesion that can be mistaken for Ewing’s but production of tumor osteoid makes the correct diagnosis of small-cell osteosarcoma.
from the metaphysis, or begin in the epiphysis and present as multiple rounded densities. Usually the lesions are all of the same size, strongly suggesting that they originate at the same time. Occasionally, a single primary osteosarcoma will ‘metastasize early and extensively to bone, and all the metastatic lesions may be of the same size. In such cases the primary lesion is usually larger than the metastases, which helps distinguish such a disorder from multicentric osteosarcoma. Metastic deposits in the lung are common, and, because they contain new bone, often appear as densely opaque, rounded lesions.
EDEIKEN-MONROE,
EDEIKEN,
AND
JACOBSON
Fig 20. Smell-cell osteosarcoma. There is a destructive lesion at the distal end of the femur on the medial size with spiculated periosteel reaction. There is one area of osteoid tumor new bone formation adjacent to the epiphysis which should aid in the diagnosis (arrows). The initial histologic appearance was that of a small-cell tumor and the diegnosis was believed to be a Ewing’s sarcoma; the presence of tumor osteoid indicated a small-cell osteosarcome.
Early localized metaphyseal lesions are distinguished from the linear densities of heavy metal poisoning by their rounded or oval appearance. Other osteoblastic focal lesions such as sclerosing osteitis, progressive diaphyseal dysplasia, melorheostosis, osteopoikilosis, and bone infarction do not have a malignant appearance, nor are they usually painful. Osteopetrosis, a more generalized form of osteosclerosis, should not be confused with osteosarcoma.
171
OSTEOSARCOMA
Fig 21. Osteosarcoma resembling osteoblastoma. The destructive lesion has caused enlargement of the bone and endosteal cortical thickening. The transition zone is short and there is tumor new bone formation within the osteolytic area. The histologic diagnosis was atypical osteoblastoma but eventually it proved to be a conventional osteosarcoma. The histologic diagnosis of atypical osteoblastoma almost always indicates an osteosarcoma with histologic elements of osteoblastoma.
INTRACORTICAL
OSTEOSARCOMA
Intracortical osteosarcomasare indolent, and have a much better prognosisthan other forms of osteosarcoma.54’55 Approximately 50% will sur
vive 5 years. Radiographically, the lesion begins as a small area of destruction within the cortex, and may be mistaken for benign disease (eg, osteoid osteoma, Brodie’s abscess).
172
EDEIKEN-MONROE,
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JACOBSON
Fig 22. Osteosarcomatosis. Areas of dense bone are present in the metastases of the tibia, the proximal fibula. and the distal femur. (A) Small osteoblastic densities are present in the metastases of the right humerus adjacent to the epiphyseal plate. (B) Small densities were present in all the long bones and the patient died within a year of widespread matastases.
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