Bone Lesions

Clinical Features.

Osteomas are most frequently diagnosed in the second to fourth decades of life, being uncommon in the first decade. The average patient age has varied from 25 to 35 years. Paranasal sinus osteomas are more common in male patients.

Osteoma is frequently an incidental finding in radiologic evaluations for other problems of the head and neck. Symptoms may be quite diverse depending on the lesion’s location and include chronic sinusitis, local pain, headache, nasal obstruction, a painful or painless mass, exophthalmos, focal facial asymmetry, difficulty opening the mouth, meningitis, and hearing loss or a sensation of ear plugging. Surface lesions that protrude from the bone are more likely to cause symptoms than those confined within the central medullary cavity.

The most common site of origin is the paranasal sinuses, with the frontal sinus ( Fig. 8.1A ) the most frequent location and the ethmoid, maxillary, and sphenoid sinuses involved in descending order of frequency. Osteomas also arise from either the inner or outer tables of the cranial bones, including the mastoid, and middle ear, and the jaw bones ( Fig. 8.1B ), especially the mandible. Extraskeletal osteomas occur in the buccal mucosa, tongue, and nasal cavity. However, these are not true neoplasms and are termed choristomas.

Radiologically, an osteoma typically appears as a dense, opaque, sharply defined mass that is usually broad based and ranges from less than 1 to 8.5 cm in maximum size. An important clinical feature of head and neck osteomas is their association with Gardner syndrome and familial adenomatous polyposis. In this association, the osteomas tend to be multiple and most frequently arise in the mandible, especially at the mandibular angle, and in the maxilla. Osteomas may be the first manifestation of these syndromes and occur as early as 10 years before the discovery of the intestinal polyps.

Pathologic Features

Histologically, most osteomas are composed of hard, dense, compact lamellar bone, similar to cortical bone, in which Haversian systems are present ( Fig. 8.2 ). Cement lines may be prominent, with densely stained parallel accretion lines at the peripheral margin. These so-called ivory or compact osteomas have little stroma, and that which is present consists of bland fibrous tissue. Osteomas may also be composed predominantly of mature lamellar trabecular bone between which fat and marrow elements are found. Osteomas on the surfaces of the bones forming the paranasal sinuses bulge into the sinus cavity covered by sinus mucosa.

Treatment and Prognosis.

Osteomas found incidentally in asymptomatic patients need not be removed because follow-up studies frequently have shown no increase in size over several years’ duration. For symptomatic lesions, local excision is curative in almost all cases, although rare recurrences after several years are reported.

Clinical Features

Most patients with osteoid osteoma are in the second decade of life, with approximately 75% between the ages of 5 and 30 years; mean and median ages range from 12 to 17 years. Male patients outnumber female patients in a ratio of 2:1 to 3:1 ; in spinal osteoid osteomas, this ratio is 6:1.

In the head and neck, the cervical spine is the most common site, with other locations, including the mandible, maxilla, and various skull bones. Overall, however, osteoid osteoma is uncommon in the head and neck. Among 861 cases in four series, only 18 (2.1%) were so situated. In the spine, the tumor usually arises from the posterior elements, with the base of the transverse process, the lamina, and the pedicle being the most common sites; the vertebral body is only rarely involved.

Pain is virtually a universal symptom in patients with osteoid osteoma, with only rare cases being painless. The pain is usually most severe at night and is frequently dramatically relieved by aspirin. Patients with cervical spine involvement may have limitation of neck movement or a scoliosis associated with torticollis. Neurologic symptoms and signs with reflex changes and muscle atrophy also occur. First-bite syndrome, excruciating pain felt at the first bite of each meal, has been described in temporal bone lesions. In the absence of abnormal radiologic studies, the duration of symptoms before diagnosis may be quite long, with some patients having symptoms for several years. Patients have been referred for psychiatric evaluation because of their persistent complaint of unexplained pain. Osteoid osteoma should be considered in any young patient who has persistent neck pain or painful scoliosis, and appropriate radiologic studies should be instituted.

Conventional radiographs of osteoid osteoma in its active proliferative phase show a lucent, round to oval area, the nidus, surrounded by a zone of dense bone ( Fig. 8.3 ). The size of the lesion is determined by the size of the nidus, not including the surrounding sclerotic bone. Although most osteoid osteomas are 1 cm or less in maximum size, some authors have accepted lesions as large as 1.5 to 2 cm as osteoid osteoma. This radiographic pattern, combined with the clinical presentation, is virtually diagnostic of osteoid osteoma. However, routine radiographic studies may either fail to show the lesion or show a lesion without the typical pattern. Bone scans are the most sensitive method for discovering the lesion, with increased radionuclide uptake found in all cases ; computed tomography (CT) scans are also more sensitive and accurate than routine radiographs for locating the lesion and showing its extent. Over time, the nidus becomes increasingly calcified and ossified and eventually may become completely opaque.

The nidus may be located within the cancellous bone or cortex or beneath the periosteum. An intracortical location is most frequent, and here the nidus expands to reach the periosteum, where it induces the production of extensive, and highly dense, new bone that surrounds and extends for a considerable distance on either side of the nidus. Osteoid osteomas confined to the spongiosa may have little or no reactive bone about them, a situation often found in vertebra-based lesions.

Pathologic Features

In its active growth phase, in which there is considerable vascularity, osteoid osteoma grossly appears as a discrete, round to oval lesion marked by a cherry-red or reddish-brown color. In this phase, it is quite granular and friable and easily displaced from the adjacent bone. In its mature phase, in which there are more calcification and bone production, the lesion is hard and gritty and blends with the bone around it.

Histologically, the nidus consists of active new bone, in various stages of maturity, within a loose fibrous stroma that contains numerous dilated thin-walled blood vessels ( Fig. 8.4 ). Seams of osteoid are present that are lined with plump osteoblasts, lacking pleomorphism or atypia (see Fig. 8.4B ). Occasionally, osteoblasts are found that have large hyperchromatic nuclei in association with brisk, but normal, mitotic activity. The osteoid gradually undergoes calcification and conversion to woven and mature bone. Active osteoclastic activity is also present, so that one may find simultaneous new bone production and bone resorption, which eventually results in bone that has a mosaic, pagetoid appearance.

In some lesions, the nidus consists entirely of osteoid arranged in broad sheets with focal calcification; other lesions contain calcium and woven bone. The center is usually the most highly mineralized portion of the lesion. The periphery of the nidus may have mature bone trabeculae that form an anastomotic or interlacing network that fuses with either the normal cortical bone or, if present, adjacent sclerotic compact bone. In intramedullary osteoid osteomas that lack adjacent compact bone, the nidus is separated from the adjacent cancellous bone by a zone of vascular connective tissue.

Differential Diagnosis

The distinction between osteoid osteoma and osteoblastoma cannot be made based on histology alone because both tumors are morphologically similar. Osteoblastoma is larger than osteoid osteoma, usually greater than 2 cm in maximum size and, unlike osteoid osteoma, which has a limited growth potential and rarely exceeds 1 cm, is a progressive and expansive lesion. Clinically, the pain associated with osteoblastoma is also less often relieved by aspirin. Osteoid osteoma is distinguished from osteosarcoma by its radiologic pattern, strict histologic circumscription, and lack of significant cytologic atypia, abnormal mitotic figures, or malignant cartilage.

Treatment and Prognosis

Almost all osteoid osteomas are cured by complete en-bloc excision of the nidus. Although some patients are cured even when no nidus is histologically found, recurrences may develop in such individuals. Recent innovations have involved the destruction of the nidus by percutaneous drilling or the use of radiofrequency techniques.

Clinical Features

Approximately 75% to 90% of osteoblastomas occur in patients younger than 30 years of age, with only occasional cases in older patients. It most frequently arises in the vertebral column. Across all body sites, there is a male to female ratio of 2:1 However, a female predominance is reported in those lesions located in the jaws and temporal bone.

In the head and neck, the cervical spine is the most common location. Other sites include the facial and skull bones, including the temporal bone; occipital bone; and ethmoid, frontal and sphenoid bones; the orbit supraorbital region; mandible; and maxilla. There are approximately 67 reported cases involving the mandible and maxilla. The mandible is more commonly affected than the maxilla, with a ratio ranging from 2 to 3.8:1.

The incidence of skull involvement among all cases of osteoblastoma has varied from 2% to 20%. In the vertebrae, osteoblastoma arises mainly from the posterior elements ; an origin in the vertebral body is uncommon.

Patients with osteoblastoma are frequently symptomatic, with pain present in as many as approximately 90% of cases. In the jawbones, osteoblastoma may present as a swelling that may be painless; 50% of patients in a recent series were pain free. Osteoblastomas of the spine and base of the skull frequently produce neurologic symptoms because of their extension into the spinal canal. Those in the cervical vertebrae may, similar to osteoid osteoma, be associated with scoliosis and torticollis. Symptoms may be present for as short a time as 1 to 2 months or for several years before diagnosis, especially in patients with spinal lesions in whom plain radiographs often fail to demonstrate the lesion. However, even osteoblastomas of the jaw have been present for long periods before diagnosis.

Radiologically, osteoblastoma is usually a lucent, well-circumscribed, expansive defect ( Fig. 8.5 ) that may contain focal calcification and radiopaque areas. Cortical destruction may occur and be associated with periostitis and expansion into the soft tissue (see Fig. 8.5B ), such that the radiologic pattern suggests an aggressive process. Plain radiographs may not demonstrate the lesion, especially in vertebral cases, but bone scans are invariably positive and are a sensitive and accurate means of finding the lesion. CT scans are also of great value in determining the precise location and extent of the lesion.

Osteoblastoma may have a periosteal, cortical, or medullary location, with the last most frequent; however, a periosteal location is more common for osteoblastomas in the facial and cranial bones, especially the maxilla. Intracortical osteoblastoma is associated with surrounding sclerotic bone, which is absent in medullary lesions.

The nidus of osteoblastoma is greater than 2 cm, with most ranging from 4 to 7 cm in maximum size. Unlike osteoblastoma of the long bones, which seldom extends into the soft tissue, vertebral osteoblastoma frequently spreads into the epidural space and the paraspinal tissues and may extend to involve adjacent vertebrae.

Pathologic Features

On gross examination, osteoblastoma appears fairly well delimited within either the cortex or cancellous bone. The tumor is hemorrhagic and is purple to reddish-brown and has a gritty or granular consistency, with occasional cystic regions. Within the head and neck, osteoblastoma may reach a surprisingly large size (>5 cm), with vertebral lesions as large as 15 cm reported.

The basic histologic pattern of osteoblastoma is similar to that of osteoid osteoma ( Fig. 8.6 ), consisting of a well-vascularized connective tissue stroma containing widely dilated capillaries in which there is active production of osteoid and primitive woven bone. However, there is considerable variation in this pattern from tumor to tumor. In the less mature lesion, there is an abundance of connective tissue stroma in which osteoclast-type giant cells and small foci of osteoid are present, some in a lacelike pattern. With maturation, there is progressive mineralization of the osteoid with conversion to trabeculae of coarse woven bone, rimmed by plump osteoblasts. The trabeculae may fuse to form an anastomosing, netlike pattern. The osteoblasts usually lack any significant atypia, having round to oval regular nuclei, often with prominent nucleoli. Mitotic activity is infrequent.

The most mature portion of osteoblastoma is located at its periphery, where lamellar bone is found. Here, the interface between the tumor and the adjacent normal bone is usually sharp, with little or no evidence of infiltration into the normal bone.

Osteoclasts are present and frequently found to be actively resorbing (remodeling) the newly formed bone trabeculae. The combination of bone production and resorption leads to the formation of pagetoid-appearing bone with prominent cement lines. Some osteoblastomas contain large sheets of osteoid with little or no stroma and few osteoblasts. The intertrabecular stroma in osteoblastoma is loosely arranged with its content of thin-walled blood vessels and lacks the crowding and sheetlike grouping of atypical cells that occurs in osteosarcoma.

Rare osteoblastomas contain an abundant number of large cells, with bizarre, atypical, hyperchromatic nuclei and large nucleoli, in combination with osteoid and bone production. Such lesions, which have been described as “malignant” osteoblastoma and aggressive osteoblastoma, may easily be histologically confused with conventional osteosarcoma. Common to these tumors is the presence of numerous large, epithelioid-like osteoblasts that rim the bone trabeculae or are focally arranged in large sheets (see Fig. 8.6B ). Numerous osteoclast-type giant cells are also present. Highly calcified tumor bone, intensely stained with hematoxylin and termed spiculated tumor bone , was found in the cases. Aggressive osteoblastoma may focally contain areas that cannot be distinguished histologically from osteosarcoma, but an important feature is their lack of atypical mitotic figures, necrosis, malignant cartilage, or peripheral permeation at the interface between the lesion and the adjacent normal cancellous bone.

Complicating this issue, Bertoni and colleagues reported examples of osteosarcoma that histologically resembled osteoblastoma and suggested that these were similar to the lesions described as malignant and aggressive osteoblastoma. Although both aggressive and malignant osteoblastomas were reported to have a greater tendency than conventional osteoblastomas for local recurrence, none had metastasized. Other investigators, however, found no difference between these tumors and classic osteoblastoma in their clinical behavior.

A few genetic aberrations, including hypoploidy, hyperploidy, and deletions, have been reported in osteoblastoma. However, none of these changes is a consistent finding.

Differential Diagnosis

The histologic distinction between osteoblastoma and osteosarcoma is one of the most difficult diagnostic problems in orthopedic tumor pathology. The problem is compounded by the fact that osteoblastoma may, on occasion, have an aggressive-appearing radiologic pattern, and osteosarcoma may contain foci that are histologically indistinguishable from osteoblastoma. With an adequate amount of tissue, the most critical histologic feature that allows separation of osteoblastoma from an osteoblastoma-like osteosarcoma is the sharp, noninfiltrative margin found in osteoblastoma, in contrast to the characteristically peripheral infiltrative pattern of osteosarcoma. However, when only small biopsy specimens are available, the peripheral margin may not be represented, and it may not be possible to distinguish between these two tumors. Conventional osteoblastic osteosarcoma is distinguished from osteoblastoma by its atypical pleomorphic stromal cells and osteoblasts with their sheetlike intertrabecular grouping, atypical mitotic figures, necrosis, and malignant cartilaginous areas. Although osteoblastoma lacks cartilage in most cases, foci of mature or immature chondroid may occur, but, unlike the cartilage in osteosarcoma, this chondroid lacks cytologic atypia.

The distinction between osteoid osteoma and osteoblastoma is not possible histologically, and the diagnosis rests on the size of the lesion and the clinical setting. Osteoid osteoma is rarely larger than 1.5 cm and, unlike osteoblastoma, is rarely progressive. Although the pain associated with osteoblastoma may, as in osteoid osteoma, be more prevalent at night, it is rarely as sharply intense as in osteoid osteoma and not as frequently relieved by aspirin. Osteoblastoma is far more frequent in the vertebrae, jawbones, and skull than is osteoid osteoma.

Some advocate use only of the term osteoblastoma for benign jaw lesions that are composed of osteoblasts that form osteoid and bony trabeculae. This is largely on the basis that the smaller lesions, which by size criteria would be classified as osteoid osteoma, are only infrequently associated with the pathognomonic sign of nocturnal pain relieved by aspirin. As a highly imaged part of the skeleton, it seems likely that jaw osteoblastomas could be picked up more readily at a smaller size.

In the jaw bones, it may be difficult, on histologic grounds alone, to distinguish osteoblastoma from cementoblastoma. The latter is an odontogenic tumor that is intimately associated with the cementum of the tooth root.

Treatment and Prognosis

Complete en-bloc resection of osteoblastoma is usually curative ; depending on its location, however, this procedure is not always possible and marginal resection or curettage procedures must be used. In such cases, local recurrence rates of 10% to 20% are reported. Death caused by local extension of the tumor may occur, as well as from surgical complications of its treatment. Malignant transformation of osteoblastoma is reported as usually, but not always, occurring only after local recurrence. However, some of these cases may represent an underdiagnosed osteoblastoma-like osteosarcoma.

Clinical Features

Osteosarcoma occurs in patients of all ages; however, 70% to 95% of patients are in the first two decades of life, with a peak incidence in the second decade. At Memorial Sloan–Kettering Hospital in New York, 10% of all osteosarcomas occurred in patients older than 60 years of age, more than one-half of whom had some underlying condition, such as Paget disease. Older patients (older than 50 years of age) have a higher incidence of craniofacial involvement than younger patients, with this site accounting for 13% to 33% of osteosarcomas in this age group. In general, osteosarcoma is more common in male patients, with male-to-female ratios of 1.3:1 to 2:1.

Radiologically, osteosarcoma has an aggressive appearance with extensive cancellous and cortical bone destruction with tumor extension into the soft tissues. Depending on the proportion of bone produced by the tumor, it will appear either totally lytic or densely sclerotic or, in the majority of cases, have a mixed lytic-sclerotic pattern.

Pathologic Features

On gross examination, there is good correlation with the radiologic pattern with extensive bone destruction being present and, in more than 90% of cases, an associated soft-tissue mass. The tumor’s appearance and consistency vary considerably depending on the proportion of cartilage, soft tissue, and bone present. It may be pink to gray-white, with a “fish flesh” appearance or gray to blue-gray associated with firm, white fibrous nodular masses. In tumors with abundant bone production, the tumor may be quite hard and require a saw to section. Yellow to yellow-white calcific foci are usually found throughout the lesion, as well as areas of hemorrhage, necrosis, and cystic change. In most osteosarcomas, even those with abundant bone formation, the peripheral soft-tissue margins usually contain highly cellular regions that are soft enough to section with a scalpel blade, and it is from such regions that tissue should be obtained whenever frozen-section biopsy material is needed.

It is important to emphasize that the finding of unequivocal osteoid or tumor bone formed by malignant-appearing stromal cells establishes the diagnosis of osteosarcoma, regardless of the quantity of matrix present. The pattern and amount of tumor osteoid or bone vary considerably, not only from tumor to tumor but also from area to area within the tumor. Osteoid may be found as thin, eosinophilic strands of hyaline-like material interspersed between the malignant stromal cells, producing a lacelike pattern ( Fig. 8.7A ). These strands may fuse to form larger, irregular seams or trabeculae. The osteoid may also occur in broad sheet-like masses in which the malignant stromal cells become “choked off” and eventually disappear. Of diagnostic importance, the osteoid trabeculae are not rimmed by an orderly layering of osteoblasts as in benign reactive bone. Also, unlike reactive new bone formation, in which the stroma between the bone trabeculae contains dilated capillaries and loosely arranged bland stromal cells, in osteosarcoma this space is usually packed with malignant stromal cells ( Fig. 8.7C ). Under polarized light, osteoid has a woven or mat-like appearance, unlike the more orderly longitudinal fiber array found in collagen. However, at times, the light microscopic distinction between collagen and osteoid may be problematic, with the diagnosis depending on the experience of the pathologist. To convert to bone, osteoid must undergo calcification, such that the presence of fine granules of calcification within the eosinophilic strands or trabeculae is a helpful clue to identify the osteoid.

A further histologic problem is distinguishing osteoid from chondroid. Contrary to common belief, chondroid, like osteoid, stains pink with conventional hematoxylin-eosin stains and not blue like hyaline cartilage. Chondroid usually occurs as well-defined islands, usually sharply set off from the surrounding cellular stroma, and has a less fibrillar appearance than does osteoid.

Immunohistochemical stains for the noncollagenous bone proteins, osteocalcin and osteonectin, have been used in an attempt to distinguish osteosarcoma from other malignant bone tumors. Although osteonectin is found in osteosarcoma, its presence in a variety of other tumors makes it unreliable as a diagnostic marker. Reactivity for osteocalcin has been used by some authors for distinguishing osteosarcoma from pleomorphic undifferentiated sarcoma (MFH) and fibrosarcoma, but it has been found to occur in chondroblasts as well.

As the osteoid in osteosarcoma becomes calcified to form tumor bone, it may be deposited on residual normal trabeculae. This tumor bone has an irregular appearance, is strongly hematoxylinophilic, and, by polarized light, has a woven or basket-weave pattern, unlike the uniform lamellar pattern of normal bone. Within this tumor bone, the now-incorporated stromal cells (malignant osteoblasts) lie within lacunar spaces. These “osteocytes” have small hyperchromatic and irregularly shaped nuclei.

Histologic Subtypes

Although the majority of osteosarcomas produce an abundance of osteoid and tumor bone and are thus classified as osteoblastic, others contain a predominance of malignant cartilage (chondroblastic type) or fibrous spindle cell areas (fibroblastic/fibrohistiocytic type) where osteoid or tumor bone may be scarce and require examination of many sections. Additional other histologic subtypes of osteosarcoma have been reported, including telangiectatic, chondroblastoma-like, chondromyxoid fibroma–like, osteoblastoma-like, clear cell, epithelioid, and malignant fibrous histiocytoma-like ; however, with the exception of the last subtype, all the others are exceptionally rare.

The abundant tumor bone produced by osteoblastic osteosarcoma may be so extensive that it obscures much of the intervening stroma, such that it may be difficult to find stromal cells directly producing osteoid or bone. Despite this, the general permeative growth pattern and the quality and abundance of the irregular tumor bone serve to establish the diagnosis of osteosarcoma. Chondroblastic osteosarcomas contain an abundance of malignant-appearing cartilage arranged in lobules or islands with cells within lacunar spaces. The periphery of the lobules tends to be more cellular, and the cells frequently assume spindle shapes. Calcification with enchondral ossification may be present. It is important to note that enchondral ossification can also be found is chondrosarcomas; the distinction being that the malignant cells in osteosarcoma must also directly produce osteoid. Fibroblastic osteosarcoma contains large areas composed of spindle cells that may assume a herringbone pattern indistinguishable from fibrosarcoma. Fibrohistiocytic osteosarcomas have abundant large pleomorphic tumor cells with bizarre enlarged nuclei and abnormal spindle-shaped cells. Multinucleated tumor giant cells with an abundant glassy eosinophilic cytoplasm are frequent, as are smaller histiocyte-like cells having a fine granular cytoplasm. A storiform pattern may be found in the spindle cell areas, the overall pattern appearing identical to that of soft-tissue pleomorphic undifferentiated sarcoma (MFH). Small biopsies may not contain obvious osteoid or tumor bone, and the diagnosis of osteosarcoma must be presumptive, pending further sectioning or examination of a resection specimen. Most conventional intramedullary osteosarcomas express a wide spectrum of histologic patterns and contain a mixture of elements, from areas showing osteoid or tumor bone to those with cartilaginous, fibrosarcomatous, or fibrohistiocytic foci (see Fig. 8.7B ).

All forms of osteosarcoma are characterized by a permeative growth pattern with tumor invading between and entrapping existing normal bone trabeculae. More than one-fourth of osteosarcomas contain scattered benign osteoclast-type giant cells that at times may be so numerous as to simulate a giant cell tumor (GCT). Such cells may be frequent in osteosarcomas arising in Paget disease. Distinguishing a GCT with bone formation from an osteoclast-rich osteosarcoma may be difficult, especially on biopsy tissue. However, with adequate tissue, the bone in true GCT is frequently at the periphery of the lesion, rather than scattered haphazardly throughout the tumor as in osteosarcoma, and it is rimmed by an orderly array of plump osteoblasts as in reactive bone as opposed to the unlined bone of conventional osteosarcoma. Malignant cartilage is absent in GCT, and osteoclast-rich osteosarcoma will invariably have foci diagnostic of conventional osteosarcoma elsewhere. Osteosarcomas that arise in association with Paget disease or radiated bone are most frequently of the fibrosarcomatous or fibrohistiocytic type, as are those osteosarcomas that occur in patients older than the age of 60 years.

Mitotic activity is easily found in all forms of conventional osteosarcoma, with frequent abnormal forms. The absence of mitotic activity should give one pause in making a diagnosis of osteosarcoma and suggests the possibility of a pseudosarcomatous tumor. Hemorrhage and necrosis are also frequent. Such spontaneous necrosis may involve 40% to 70% of the total tumor. The degree of tumor necrosis induced by chemotherapy has been correlated with prognosis, with patients classified as good responders when the necrosis involves 90% or more of the tumor and poor responders when there is a lesser degree of necrosis; patients with a good therapeutic response have significantly better 5-year survival rates. However, these data are based almost entirely on the results obtained for appendicular osteosarcomas.

Although some experienced bone tumor pathologists attempt to grade conventional intramedullary osteosarcomas, the extensive variability from area to area that exists in the majority of these tumors makes such grading suspect, as well as the fact that, with the exception of the well-differentiated intraosseous form of osteosarcoma, grading of head and neck tumors appears to have little prognostic value.

Clinical Features

In as many as one-half of cranial osteosarcomas, the tumor arises secondary to some underlying condition, most commonly Paget disease, FD, or in irradiated bone. Although the age range is considerably wider, most patients are in the fourth and fifth decades of life, an older age than for those with osteosarcoma of the appendicular skeleton. This reflects the component of patients with cranial osteosarcoma who have Paget disease or radiation sarcoma, conditions that most often occur in older patients. Such secondary osteosarcomas occur in patients approximately 20 to 30 years older than those with primary cranial osteosarcoma. Unlike the male predominance in osteosarcoma of the long bones, the male-to-female ratio in osteosarcoma of the skull is roughly equal.

Any of the skull bones may be involved, with reported cases in the calvarium and skull base; the occipital, parietal, frontal, and temporal bones; the orbit; the ethmoid, sphenoid, and maxillary sinuses; the nasal fossa; the zygoma; and the sella area. In some cases, the tumor may be so large that its exact site of origin cannot be established.

Clinically, the dominant symptom is that of a painless mass, although cranial nerve symptoms, epistaxis, and eye displacement may occur, reflecting the location of the tumor. Most cases are diagnosed within 6 months of the onset of symptoms.

Pathologic Features

Osteoblastic osteosarcoma is the most common type encountered in the skull, but chondroblastic, fibroblastic, fibrohistiocytic, small cell, telangiectatic, and well-differentiated subtypes also occur.

Treatment and Prognosis

In a review of 201 patients with craniofacial osteosarcoma, 61 of whom had cranial lesions, the best overall and disease-free survival rates were associated with complete surgical removal of the tumor and the use of chemotherapy, the latter improving survival even in those patients with incomplete resections.

The prognosis for osteosarcoma of the skull and facial bones is generally poor, with the reported results influenced by the number of secondary osteosarcomas in the series. The 5-year survival rate is approximately 10%, with only a few long-term survivors ; metastases develop in approximately 45% of cases. By contrast, of the 276 patients with skull/facial bone osteosarcomas reported by the National Cancer Data Base in the United States, 57% survived 5 years and only 10.5% experienced distant metastasis, but lesions affecting the maxilla were included in the skull/facial bone group. Patients with osteosarcoma secondary to Paget disease have a very poor prognosis, with almost all dying of the tumor.

Clinical Features

The jaws constitute 5% to 13% of all cases of osteosarcoma. The ratio of mandibular to maxillary cases varies in the literature, with the mandible accounting for 44% to 73% of cases and the maxilla for 27% to 56%. Within the mandible, the body is the most common location, accounting for 55% to 75% of cases followed in order of frequency by the angle, the ramus, and the symphysis. In the maxilla, the alveolar ridge is the most common site.

Although cases occur in children, this is uncommon; most patients are in the third to fourth decades of life, generally one decade older than patients with osteosarcoma of the long bones and the gender distribution is roughly equal or slightly favoring males.

Clinically, the majority of patients report a swelling or mass that is often, but not always, painless ; pain alone may also occur. Numbness or paresthesia of the lip or chin reflects tumor involvement of the inferior alveolar nerve and is an important clue to the diagnosis of an aggressive lesion. Loosening of the teeth may be the first or even dominant manifestation of the disease, such that the dentist may be the one the patient first sees for medical attention. Other symptoms include nasal obstruction, epistaxis, or visual disturbances secondary to antral involvement. Although a history of symptoms for as long as 30 years is recorded, most patients seek medical attention within 6 months of the onset of symptoms.

Osteosarcoma of the jaw bones may develop as a consequence of predisposing conditions, the most common of which is previous radiation therapy to the region; in approximately 10% of cases, tumors also develop secondary to Paget disease, FD, and chronic osteomyelitis.

Radiologically, osteosarcoma of the jaw has a purely lytic and destructive pattern ( Fig. 8.8A ) in 35% to 45% of cases, a sclerotic pattern in 5% to 65% of cases, and a mixed pattern of lysis and sclerosis in 22% to 50% of cases. A sunburst pattern, with radiating spicules of bone ( Fig. 8.8B ) is considered a characteristic feature of osteosarcoma of the jaw, especially in mandibular lesions ; however, it is not frequent, occurring in 7% to 27% of cases. Extraosseous soft-tissue extension is radiologically evident in 30% to 100% of cases. An important radiologic feature of osteosarcoma of the jaws is symmetric widening of the periodontal membrane space that may also be associated with loss of the lamina dura (see Fig. 8.8B ). Although not specific for osteosarcoma, its occurrence is suggestive of an aggressive process.

Pathologic Features

Osteosarcomas of the jaw bone have ranged from 2 to 10 cm in maximum size. The histologic type has varied in different series, with some reporting a predominance of osteoblastic tumors and others reporting a chondroblastic or fibroblastic predominance. In addition to parosteal and periosteal osteosarcomas (see subsequent discussion), examples of telangiectatic, small cell, well-differentiated, and high-grade surface osteosarcoma are reported.

Treatment and Prognosis

Marginal excision of osteosarcoma of the jaw leads to local recurrence in 36% to 100% of cases. Such recurrences carry a poor prognosis because most patients die of local recurrence. The rate of local recurrence in maxillary osteosarcoma has varied from 29% to 60% and in mandibular lesions from 43% to 66%. Distant metastases occur, although there is considerable variation in the literature as to its incidence, with reported rates of 6% to 52%. Metastases from mandibular osteosarcoma are more frequent than maxillary lesions, with mandibular lesions ranging from 33% to 71% and of maxillary lesions from 13% to 20%. Gnathic osteosarcomas metastasize at a considerably lower rate than those in long bone.

Historically, the overall 5-year survival rates range from 23% to 47%, with most series reporting rates of 35% to 45%. Radical excision yields the best prognosis, with 5-year survival rates for maxillary lesions of 25% to 63% and for mandibular lesions of 24% to 71%, but overall 5-year survival rates of 70% are currently being reported. Some authors express the view that mandibular lesions have a better prognosis than maxillary tumors.

The role of neoadjuvant chemotherapy in the outcomes in patients with osteosarcoma of the head and neck needs further study. The authors of one study showed an obvious improvement in the 5-year local control, distant metastasis, and overall survival compared with historical cohorts. However, no outcome advantage was reported for chemotherapy in the largest series of gnathic osteosarcomas reported to date and the 496 cases reported from the US National Cancer Data Base of Head and Neck lesions also disclosed no outcome advantage for chemotherapy.

Clinical Features

Most vertebral osteosarcomas arise secondary to some other condition, most notably Paget disease or after radiation therapy to the region, with de novo cases being uncommon. In 1994 Kebudi and colleagues found only 45 cases of vertebral osteosarcoma in the absence of Paget disease or radiation therapy in the American and European medical literature since 1904. Despite the high incidence of spinal involvement in Paget disease, the actual occurrence of vertebral osteosarcoma in such patients is quite uncommon.

Patients with vertebral osteosarcoma have ranged from 3 to 70 years of age and are older, on average, than those with appendicular osteosarcoma, reflecting the inclusion of older adults with Paget disease and radiation-induced tumors. Virtually all patients with vertebral osteosarcoma present because of pain that is frequently associated with neurologic symptoms, sensory, as well as motor. Those with osteosarcoma of the cervical vertebrae may have pain that radiates to the upper extremity. The presence of a palpable mass is uncommon.

Radiologically, vertebral osteosarcoma is a destructive, usually nonexpansive lesion with soft-tissue extension found in the majority of cases ( Fig. 8.9 ). Within the vertebra, the body is involved in almost all cases, although the tumor frequently extends to involve the posterior elements as well; primary origin in the posterior elements is uncommon.

Pathologic Features

Most cases of vertebral osteosarcoma are osteoblastic, although cases of chondroblastic, fibroblastic, and fibrohistiocytic subtypes occur. Distinguishing osteoblastoma from osteosarcoma is a major problem because cases of vertebral osteosarcoma have been misdiagnosed as osteoblastoma on biopsy tissue. Perhaps contributing to this problem is the knowledge that the spine is a common site for osteoblastoma, but an uncommon location for osteosarcoma. As mentioned earlier, the most helpful histologic feature that separates osteoblastoma from osteosarcoma is the peripheral permeative pattern in osteosarcoma, in contrast to the sharp interface of the nidus of osteoblastoma with the host bone at its periphery. Rare cases will be found where the distinction between these tumors may be histologically impossible, and only the course of the disease unmasks the true nature of the lesion.

Treatment and Prognosis

The prognosis in vertebral osteosarcoma is dismal, with almost all patients dying of the tumor, usually within 1 year of diagnosis. This no doubt reflects the difficulty in adequately resecting tumors in this region. In none of the 10 patients with vertebral osteosarcoma treated at Memorial Hospital could the tumor be completely resected. Of 27 patients with vertebral osteosarcoma reported from the Mayo Clinic, there was only one survivor (3.7%); all those with cervical vertebral lesions died. The poor prognosis in vertebral osteosarcoma may also be a reflection of the number of older patients with Paget disease or radiation-induced tumors. However, the prognosis in the 45 patients with primary vertebral osteosarcoma, reported by Kebudi and colleagues, was also poor, with 36 (80%) dying of the tumor, two (4.4%) alive with tumor, and only seven (15%) alive without tumor, only two of whom were long-term survivors.

Clinical Features

Patients with parosteal osteosarcoma are generally older than those with conventional osteosarcoma, with 80% older than 20 years of age; most patients are in the third and fourth decades of life.

In the head and neck, a painless swelling is the most common symptom, although the lesion may be tender. The tumor typically grows slowly, and although in some patients the tumor is detected within a few days to several months of symptom onset, other patients have had a mass for as long as 10 years before diagnosis.

Parosteal osteosarcoma arises on the surface of the bone and forms a coarsely lobulated or bosselated, usually broad-based mass that rests on and bulges from the cortical surface. Radiologically, the underlying cortex is frequently thickened, and a radiolucent cleavage plane may be seen between the tumor and the underlying cortex. The base of the lesion is usually more densely ossified than the periphery. Radiolucent zones may be found within the tumor that represent entrapped normal soft tissue, low-grade cartilage, fibrous tissue, or areas of dedifferentiated tumor. Occasionally, invasion into the underlying bone is seen. The central portion of parosteal osteosarcoma is not in direct continuity with the medullary cavity of the underlying bone. Even in the confined space of the head and neck, some parosteal osteosarcomas have been as large as 16 cm, although most are between 3 and 5 cm.

Pathologic Features

Grossly, parosteal osteosarcoma appears well delimited and typically grows to envelop the external aspect of the bone. Medullary involvement is infrequent, and its development appears correlated with the length of time that the tumor has been present, with long-standing tumors eventually invading the underlying cortex which varies from 1.3% to 59%.

A fibrous capsule or a cartilaginous cap may be found at the tumor’s peripheral margin. Despite this seemingly gross circumscription, microscopically, the tumor may invade and incorporate the adjacent skeletal muscle and fat. The consistency of the tumor varies depending on the proportion of fibrous, osseous, and cartilaginous tissue present. The periphery may be soft and fleshy and easily cut with a scalpel, but the basal portion is usually hard, requiring a saw to section. Here, the cut surface shows white to yellow-white chalklike areas of calcification and ossification. In long-standing tumors, the entire lesion may be rock hard because of extensive bone formation.

Histologically, parosteal osteosarcoma may be difficult to diagnose, especially on small biopsy specimens, if careful attention is not given to the clinical and radiologic features. The stromal and osseous elements in parosteal osteosarcoma usually lack clear evidence of cytologic malignancy or that which is present may be so scarce, as to require many sections to discover. The tumor is composed of a fibrous stroma in which reside irregular spicules and trabeculae of bone ( Fig. 8.10A ). The stroma varies in its cellularity; some cases are relatively hypocellular with the stroma containing abundant collagen separating bland-appearing spindle cells ( Fig. 8.10B ); in others, the stroma is more cellular, containing plumper and more atypical cells, creating a fibrosarcoma-like pattern. Mitotic figures may be scarce. The bone trabeculae are irregular, being of a woven or lamellar type, and frequently arranged in parallel arrays (see Fig. 8.10A ). Unlike conventional osteosarcoma, a layer of plump but benign-appearing osteoblasts may rim the trabeculae. In other areas, the bone arises directly by metaplastic transformation of the fibrous stroma as in FD. It is at the peripheral margin of the tumor that one finds more cellular zones composed of primitive-appearing cells that have enlarged and irregular nuclei and that form osteoid. Here, direct invasion of skeletal muscle and fat is found. The base of the lesion consists of densely compact woven or lamellar bone in contrast to its more fibrous, spindle cell peripheral component. Cartilaginous foci, of variable size, occur in 50% to 80% of cases. These foci may have cytologic features of low-grade chondrosarcoma, with increased cellularity and atypia and show enchondral ossification. The amount of cartilage varies from tumor to tumor, but it is never the dominant element as it is in periosteal osteosarcoma.

Foci of dedifferentiation in which areas of high-grade sarcoma, usually pleomorphic undifferentiated sarcoma (MFH), fibrosarcoma, or conventional osteosarcoma are found, may occur in an otherwise typical parosteal osteosarcoma. Such dedifferentiated areas usually develop only after several local recurrences, but may be found at the time of initial presentation. The incidence of dedifferentiation varies from 16% to 43%. Dedifferentiated lesions have occurred in the head and neck region.

In the literature, some osteosarcomas listed as parosteal type have been histologically graded numerically from I to III, a grade III lesion being an overtly malignant tumor with features of conventional osteosarcoma. However, such a tumor is best classified as a high-grade surface osteosarcoma rather than a parosteal osteosarcoma because it has a considerably worse prognosis than does true parosteal osteosarcoma.

Differential Diagnosis

The differential diagnosis of parosteal osteosarcoma includes sessile osteochondroma, myositis ossificans, and periosteal osteosarcoma. Unlike parosteal osteosarcoma, the radiologic pattern of osteochondroma shows continuity between the lesion and the underlying parent bone. Histologically, osteochondroma has a cartilage cap composed of benign rather than malignant cartilage; the cancellous bone is of the lamellar type, and the central portion of the lesion contains marrow fat or hematopoietic elements and lacks the fibrous stroma of parosteal osteosarcoma. Periosteal osteosarcoma has more abundant and more atypical cartilage than parosteal osteosarcoma, and its spindle cell elements are larger and more atypical than the spindle cells of parosteal osteosarcoma. Essentially, periosteal osteosarcoma is an intermediate-grade surface chondroblastic osteosarcoma, in contrast to the low-grade fibroosseous character of parosteal osteosarcoma.

Myositis ossificans is the lesion most likely to be histologically confused with parosteal osteosarcoma. The clinical and radiographic features may enable one to easily separate the two conditions, provided there is a history of recent trauma to the involved site, followed by the rapid appearance of a soft-tissue mass that gradually ossifies over time. However, such a history may be lacking, the patient reporting only a slowly enlarging mass. Radiologically, myositis ossificans usually appears separate from the underlying bone, although in some long-standing cases, it may continue to grow and ultimately attach itself to the bone and thus radiologically simulate parosteal osteosarcoma. The classic histologic feature of myositis ossificans is its zonal pattern, in which the periphery of the growing lesion shows the most mature degree of bone differentiation, with the more central and basal aspects composed of a stroma of immature, and sometimes atypical, cells in which there is primitive (woven) bone production. This contrasts with parosteal osteosarcoma, in which the periphery of the lesion shows the least mature elements and the basal or central regions contain more mature bone. In the fully developed form of myositis, the lesion may become totally ossified, being composed of mature compact lamellar bone so as to resemble an osteoma; such a degree of organization is never found in parosteal osteosarcoma.

Unlike conventional osteosarcoma, parosteal osteosarcoma is characterized by one or more supernumerary ring chromosomes, often as the sole alteration. Mutations in RB1 have not been found to be present in parosteal osteosarcoma. Parosteal osteosarcoma shows similar MDM2 and CDK4 overexpression as LGO.

Treatment and Prognosis

In general, parosteal osteosarcoma has an excellent prognosis after complete surgical excision, with a 5-year survival rate of approximately 80%. However, 10-year survival rates are somewhat lower, owing to the appearance of late metastases in some patients. The course of parosteal osteosarcoma in the head and neck region is not well established because of its rarity, with only a few reports containing long-term follow-up information. At the time of these reports, however, almost all the patients were alive and well. Dedifferentiated parosteal osteosarcoma has a poor prognosis, with metastases in approximately 50% of patients at 5 years. Whenever possible, a wide local complete excision should be done for parosteal osteosarcoma to prevent local recurrence and the possibility of dedifferentiation.

Clinical Features

The age range for periosteal osteosarcoma is quite broad, with approximately 60% to 75% of patients in the second decade of life; it is uncommon in the first decade. In the few head and neck cases, patients have ranged from 20 to 65 years of age. Periosteal osteosarcomas of the mandible and maxilla are usually small, ranging from 2.7 to 3.5 cm.

Although the radiologic appearance of periosteal osteosarcoma in the long bones usually shows a radiating pattern of osseous spicules that extend outward from the cortex, the few cases reported in the jaws have not, with an occasional exception, demonstrated this pattern.

Pathologic Features

On gross examination, periosteal osteosarcoma rests on a thickened cortex, which may be minimally invaded by the tumor, and appears well delimited by the periosteum. On section, the periphery of the tumor is soft and well-rounded and has a distinct chondroid appearance with glistening gray to gray-white lobules that contain white to yellow streaks of calcification or ossification.

Microscopically, periosteal osteosarcoma consists of lobules of high-grade malignant cartilage that are separated by spindle-shaped mesenchymal cells, in which eosinophilic lacelike ribbons of osteoid are found. However, these osteoid areas may be quite sparse and difficult to find and are best seen at the peripherally growing margin of the lesion. In some cases, fibroblastic or even osteoblastic foci may be found and even predominate, such that the tumor may be difficult to distinguish from a conventional high-grade surface osteosarcoma.

Complex karyotypic patterns were identified in three cases of periosteal osteosarcoma, and in one case, trisomy 17 was the only change.

Differential Diagnosis

Unlike parosteal osteosarcoma, large seams of parallel-oriented osteoid or tumor bone do not occur in periosteal osteosarcoma, nor does it have the abundant fibroblastic stroma of parosteal osteosarcoma.

The scarcity of osteoid in some cases of periosteal osteosarcoma has led to diagnostic confusion with juxtacortical chondrosarcoma, a problem further compounded by the fact that the eosinophilic ribbons that occur in periosteal osteosarcoma are considered by some as representing collagen and not osteoid. In contrast to periosteal osteosarcoma, however, juxtacortical chondrosarcoma is composed of low-grade hyaline cartilage and lacks atypical spindle cell elements. Conventional high-grade OSs can occur on the surface of a bone and have been designated as surface high-grade osteosarcomas. They behave as conventional OSs.

Treatment and Prognosis

In the long bones, periosteal osteosarcoma has a prognosis that is intermediate between that of parosteal osteosarcoma and conventional osteosarcoma, with a lower incidence of metastases than conventional osteosarcoma. The few patients with periosteal osteosarcoma of the jaw were all alive and well at the time of the reports.

Clinical Features

Extraskeletal osteosarcoma accounts for only 2% to 5% of all osteosarcomas. It occurs in older patients. The mean and median ages are in the sixth decade of life, only 5% to 10% of patients are younger than 30 years of age.

The majority of extraskeletal osteosarcomas occur in the lower extremity, with the head and neck region involved in less than 5% of cases. Here, extraskeletal osteosarcoma has occurred in the soft tissues of the face, neck, floor of the orbit, larynx, and tongue. Extraskeletal osteosarcoma has developed secondary to previous radiation therapy, including cases in the head and neck.

Pathologic Features and Differential Diagnosis

With only rare exceptions, extraskeletal osteosarcomas are high-grade lesions whose varied morphologic pattern mirrors that of conventional intraosseous osteosarcoma. However, other malignant epithelial and mesenchymal tumors may contain focal bone formation and pose diagnostic problems. Surface osteosarcomas of bone may invade soft tissue. Before a diagnosis of extraskeletal osteosarcoma is made, therefore other soft-tissue tumors with bone formation must be excluded and radiologic studies done to exclude an origin in adjacent bone.

Important in the differential diagnosis is the distinction of extraskeletal osteosarcoma from myositis ossificans. In its fully developed and mature form, myositis ossificans is composed of compact lamellar bone residing within a fibrous stroma, resembling an osteoma. However, in its evolving early stages, the central portion of myositis ossificans contains immature stromal fibroblasts and myofibroblasts, which may show nuclear atypia, frequent mitotic figures, and florid new bone and osteoid formation, such that it may be impossible to distinguish it from extraskeletal osteosarcoma when only a small amount of biopsy tissue is available. The well-delimited mature, new bone formation at the peripheral margin of a more mature myositis ossificans is in contrast to the invasive, anaplastic, spindle cell periphery of extraskeletal osteosarcoma that lacks bone maturation. It is imperative that when there is a strong clinical likelihood that the lesion represents a developing myositis ossificans, the pathologist be made aware of such information.

Treatment and Prognosis

Extraskeletal osteosarcoma is highly aggressive, with a high incidence of local recurrence after surgical excision and distant metastases, with most patients dying of the tumor within 2 to 3 years of diagnosis.

Clinical Features

Most patients with chondromas are in the second to fourth decades of life ; those with head and neck lesions have ranged in age from the first to the eighth decades of life. Chondromas of the head and neck are reported in patients in Ollier disease and Maffucci syndrome.

Chondromas may develop within bone or the soft tissues. Those in the cranial bones usually originate in the base of the skull, with the origin in the sella, clivus, parasellar area, and posterior fossa. Other sites include the nasal cartilage, cervical vertebrae, soft palate, paranasal sinuses, nasopharynx, region of the foramen magnum, eustachian tube, tongue, gingiva, cheek and buccal mucosa, and larynx. Soft-tissue chondromas of the oral cavity are believed to be choristomas rather than true neoplasms.

Chondromas of the cervical spine frequently cause cord or nerve compression with neurologic impairment, including Horner syndrome; respiratory difficulty may be produced by direct pressure on airway passages. Intracranial chondromas produce a variety of signs and symptoms caused by compression of cranial nerves, with resulting nerve palsies, or increased intracranial pressure, with headache, diplopia, visual loss, tinnitus, hearing loss, and facial numbness among the most frequent symptoms, as well as pituitary dysfunction and optic nerve atrophy. Laryngeal chondromas are most frequently associated with hoarseness or dyspnea. Owing to the slow growth of chondromas, it is not uncommon for patients either to know of the presence of a mass or to have symptoms for several years before diagnosis.