Benign Bone Tumors

Introduction and Classification

Benign bone tumors are clonal neoplastic proliferations of bone-derived or matrix- producing cells that, in contrast to malignant tumors, demonstrate limited growth potential, no metastatic capacity, and — in most cases — predictable natural histories. The classification used throughout this chapter follows the World Health Organization framework as elaborated in Apley & Solomon’s, Miller’s Review, and Tachdjian’s: tumors are grouped by their predominant matrix or cell of origin, with separate categories for bone-forming (osteogenic), cartilage-forming (chondrogenic), fibrogenic, vascular, notochordal, and miscellaneous lesions. A complementary biological framework — Enneking’s grading of benign tumors as latent (Stage 1), active (Stage 2), or aggressive (Stage 3) — provides the conceptual link between histology and treatment: latent lesions are observed, active lesions are curetted, and aggressive lesions require extended intralesional surgery or even wide resection. The reader will recall from the previous chapter that several entities classified historically as benign tumors — notably the aneurysmal bone cyst — are now understood as neoplasms with characteristic translocations; the convention in this text is to follow the traditional clinical groupings, since they correspond more closely to the radiographic and treatment categories used in practice. The principal benign bone tumors discussed are: osteoid osteoma and osteoblastoma; osteochondroma (solitary and hereditary multiple exostoses); enchondroma and the enchondromatoses (Ollier and Maffucci); periosteal chondroma; chondroblastoma and chondromyxoid fibroma; giant cell tumor of bone; intraosseous hemangioma; and the rare entities of intraosseous lipoma, neurilemmoma of bone, and the locally aggressive but non- metastasizing adamantinoma. The presentation of each follows the same framework — epidemiology, pathology, clinical features, radiographic findings, differential diagnosis, treatment, complications — to permit direct comparison.

Osteoid Osteoma

Epidemiology and Pathology Osteoid osteoma is a small, benign, bone-forming tumor characterized by a central vascular nidus of osteoid and woven bone surrounded by a halo of reactive sclerosis. It accounts for approximately 10-12% of benign bone tumors. The peak incidence is in the second decade, with a male predilection of roughly 2-3:1. Histologically the nidus consists of interlacing trabeculae of woven bone and osteoid lined by plump osteoblasts within a richly vascular, loose connective tissue stroma; the reactive bone surrounding the nidus is dense lamellar bone. The nidus rarely exceeds 1.5 cm — a critical size cutoff, since lesions larger than this are by definition osteoblastomas. Recent molecular work has demonstrated FOS rearrangements in both osteoid osteoma and osteoblastoma, supporting their classification as a single neoplastic spectrum.

Clinical Features The cardinal symptom is pain — characteristically nocturnal, progressively severe, and dramatically relieved by aspirin or other non-steroidal anti-inflammatory drugs. This response to NSAIDs is so consistent that it has been considered virtually diagnostic, and it reflects the high concentration of prostaglandins (particularly PGE2) within the nidus, which mediate both the pain and the surrounding vascular and bony reaction. The lesion can arise in any bone but has a strong predilection for the diaphysis and metaphysis of long bones, with the proximal femur, tibia, fibula, and humerus most commonly affected. Spinal lesions occur in approximately 10% of cases, most often in the posterior elements of the lumbar spine, and are an important cause of painful scoliosis in children and adolescents: the scoliotic curve is concave on the side of the lesion, the tumor sits at or near the apex, and the curve is at least partially reversible if the lesion is treated before structural changes occur. Intra-articular osteoid osteomas, particularly in the hip and elbow, can produce synovitis with painful effusion and a clinical picture mimicking inflammatory arthritis. Imaging Plain radiographs may demonstrate the classic appearance of a small radiolucent nidus surrounded by a zone of dense reactive sclerosis, often within or adjacent to the cortex of a long bone. In cortical lesions, the sclerotic reaction can be intense and the nidus difficult to visualize; in cancellous or intra-articular locations, sclerosis is often less marked. Computed tomography is the imaging modality of choice for confirming the diagnosis: thin- section CT identifies the nidus as a well-defined, round or oval lucent area, sometimes with central mineralization, surrounded by sclerotic bone. Magnetic resonance imaging often shows extensive bone-marrow and soft-tissue edema disproportionate to the size of the nidus, which can be misleading and has historically led to misdiagnosis as a malignant or infectious lesion when the diagnostic CT is omitted. The bone scan is universally hot and is useful in localizing a suspected lesion when initial imaging is non-diagnostic. Treatment Although natural-history studies of untreated osteoid osteoma show that the lesion eventually burns out over several years, the severity of the pain and the duration required for spontaneous resolution make conservative management with chronic NSAID therapy unattractive for most patients. The historic surgical treatment is en-bloc excision or wide curettage of the nidus, which is curative but at the cost of substantial cortical bone removal and the need for internal fixation in many long-bone cases. Since the mid-1990s, percutaneous radiofrequency ablation under CT guidance has become the treatment of choice for accessible lesions outside the spinal canal and major nerves. Under general or regional anesthesia, a radiofrequency probe is advanced to the center of the nidus and heated to 90 °C for several minutes, producing complete coagulative necrosis of the lesion. Reported success rates exceed 90% with minimal morbidity, no need for postoperative immobilization, and same-day discharge in most centers. The chief contraindications are lesions within 1 cm of the spinal cord or major nerves and lesions in subcutaneous bones (digits) where thermal injury to overlying skin is a concern; in these cases open surgical excision remains the standard.

Osteoblastoma

Osteoblastoma is a benign bone-forming tumor that resembles osteoid osteoma histologically but differs in three important respects: it is larger (>1.5 to 2 cm), it lacks the surrounding intense reactive sclerosis, and it is more likely to behave aggressively with local recurrence. Half of all osteoblastomas occur in the spine, with a predilection for the posterior elements, and another quarter occur in the long bones. The clinical presentation is dull aching pain that, in contrast to osteoid osteoma, is less consistently relieved by NSAIDs and is less commonly nocturnal. Spinal osteoblastomas can produce nerve-root compression, painful scoliosis, or — when large — myelopathy. Radiographically the lesion appears as a relatively well-defined expansile lytic lesion, sometimes with internal mineralization, and may demonstrate a “blow-out” expansion of the cortex with a thin periosteal shell. The differential diagnosis includes osteoid osteoma (smaller, more sclerotic), aneurysmal bone cyst (which often coexists or arises within osteoblastomas, particularly in the spine), Langerhans cell histiocytosis, and — most critically — the aggressive osteoblastoma-like osteosarcoma. Treatment is surgical: extended intralesional curettage with high-speed burring and adjuvant therapy (phenol, polymethylmethacrylate cement, cryotherapy) is the standard, with reported recurrence rates of 10-20%. En-bloc resection is reserved for aggressive lesions, lesions with significant soft-tissue extension, or those in expendable bones. Preoperative selective arterial embolization is sometimes useful in reducing intraoperative blood loss for large spinal or pelvic lesions.

Osteochondroma

Solitary Osteochondroma (Exostosis) The solitary osteochondroma — also called osteocartilaginous exostosis — is the commonest benign tumor of bone, accounting for perhaps 35-50% of all benign bone tumors and arising in approximately 1-2% of the general population. It is best understood as a developmental lesion: a fragment of physeal cartilage herniates through the perichondrial fibrocartilaginous ring of LaCroix during skeletal growth, gives rise to a bony outgrowth covered by a cartilaginous cap, and is continuous with the medullary cavity of the underlying bone — the latter feature being the radiographic hallmark that distinguishes the osteochondroma from any surface neoplasm. The lesion grows by enchondral ossification at its cartilaginous cap and ceases to grow at skeletal maturity. Continued growth of an osteochondroma after closure of the growth plates, or the development of pain in a previously asymptomatic lesion in an adult, must raise concern for malignant transformation to secondary chondrosarcoma. The lesion arises in the metaphysis of any long bone formed by enchondral ossification, with a strong predilection for the distal femur, proximal humerus, proximal tibia, and proximal fibula. Two morphological subtypes are recognized: the pedunculated (stalked) osteochondroma, which classically points away from the adjacent joint because of the directionality imparted by physeal growth; and the sessile (broad-based) osteochondroma. The cartilaginous cap is typically 1-3 mm thick in adults; a cap greater than 1-2 cm in adulthood is a worrisome feature suggestive of chondrosarcomatous transformation. Apley

and Miller agree that risk of malignant transformation in a solitary osteochondroma is approximately 1%. Most osteochondromas are asymptomatic and discovered incidentally. Symptomatic lesions may produce a painless or painful palpable bony mass, mechanical impingement on tendons or neurovascular structures (especially in the popliteal fossa, where popliteal artery pseudoaneurysm has been reported), bursitis overlying the cap, or fracture through the stalk of a pedunculated lesion. Indications for surgical excision are persistent pain, mechanical or neurovascular impingement, cosmetic concern, fracture, and any concern for malignant transformation. Excision must include the bony stalk, the entire cartilaginous cap, and the overlying perichondrium to avoid recurrence; piecemeal removal leaving cartilaginous remnants predictably leads to local recurrence. Hereditary Multiple Exostoses (HME, Multiple Osteochondromatosis) Hereditary multiple exostoses, also known as multiple hereditary osteochondromatosis or diaphyseal aclasis, is an autosomal-dominant disorder characterized by the development of multiple osteochondromas throughout the metaphyses of the long bones. Causative mutations have been identified in the EXT1 gene on 8q24, the EXT2 gene on 11p11, or, less commonly, EXT3; these genes encode glycosyltransferases involved in heparan sulfate proteoglycan synthesis in the cartilaginous matrix. Patients typically present in childhood with multiple palpable bony lumps, often associated with short stature, limb-length discrepancy, forearm deformity (most characteristically a short ulna with bowing of the radius, a Madelung-like wrist, and ulnar deviation of the hand), genu valgum, ankle valgus, and occasional spinal deformity. The risk of malignant transformation to chondrosarcoma is significantly higher than in solitary disease — quoted variably between 1% and 10% lifetime, with EXT1 mutations carrying a higher risk than EXT2. Management involves surveillance, excision of symptomatic individual lesions, correction of secondary skeletal deformities (forearm osteotomies, hemiepiphysiodesis for genu valgum), and lifelong monitoring for the development of pain or growth in a previously stable lesion.

Enchondroma and the Enchondromatoses

Solitary Enchondroma Enchondroma is a benign cartilaginous tumor arising within the medullary cavity of bone, accounting for approximately 10% of benign bone tumors. The pathogenesis is thought to involve a focus of cartilage that fails to undergo normal enchondral ossification during growth. The lesion has a particular predilection for the short tubular bones of the hands — the metacarpals and phalanges — where it is the commonest primary bone tumor; it also arises commonly in the proximal humerus, distal femur, and proximal tibia. Histologically the lesion consists of lobules of mature hyaline cartilage with bland chondrocytes in lacunae, surrounded by a thin shell of cortical bone. Most enchondromas in the long bones are asymptomatic and discovered incidentally. In the hand, presentation may be with pathological fracture through the lesion. On plain radiographs the enchondroma appears as a well-defined lytic lesion, often with characteristic “rings and arcs” of internal calcification, scalloped endosteal cortex, and

absent periosteal reaction. The distinction between an enchondroma and a low-grade central chondrosarcoma is one of the most difficult problems in bone pathology, and is based on a combination of clinical, radiographic, and histological features: a low-grade chondrosarcoma is typically larger (>5 cm), causes deep endosteal scalloping (>two-thirds of cortical thickness), exhibits cortical penetration or a soft-tissue mass, demonstrates more aggressive imaging features (increased uptake on bone scan, mineralization changes), and is more likely to be symptomatic in an adult. Histologically the distinction relies on cellularity, the presence of binucleate cells, and permeation of host bone — features that pathologists with limited experience in bone tumors frequently misinterpret. Treatment of asymptomatic long-bone enchondromas is observation with serial imaging. Symptomatic lesions, pathological fractures, and lesions where the diagnosis cannot be confidently distinguished from low-grade chondrosarcoma require curettage with bone grafting; in the hand, curettage with or without bone grafting achieves consistently good results. Ollier Disease and Maffucci Syndrome Multiple enchondromatosis — Ollier disease — is a non-hereditary developmental disorder characterized by multiple enchondromas, often with marked asymmetry of distribution. Presentation in childhood is with multiple palpable bony swellings, limb-length discrepancy, deformity, and pathological fracture. Maffucci syndrome combines multiple enchondromas with multiple soft-tissue hemangiomas (often visible as bluish phleboliths on radiographs). Both syndromes carry a markedly elevated risk of malignant transformation to chondrosarcoma — quoted as 25-30% in Ollier disease and approaching 100% over a lifetime in Maffucci syndrome, with an additional risk of non-skeletal malignancies including ovarian and pancreatic cancers and brain gliomas. Surveillance is therefore essential, with low threshold for biopsy of any painful or growing lesion in adulthood.

Chondroblastoma and Chondromyxoid Fibroma

Chondroblastoma Chondroblastoma — historically called Codman tumor for its predilection for the proximal humerus — is a benign cartilaginous tumor with a strong predilection for the epiphyses of long bones in the immature skeleton. It accounts for approximately 1% of benign bone tumors. Most patients are aged 10-25 years with an open or recently closed physis. Common sites are the proximal humerus, proximal and distal femur, and proximal tibia; less commonly the talus, calcaneus, and apophyses (greater trochanter, lesser trochanter, tibial tuberosity). Histologically the lesion consists of polygonal chondroblastic cells with characteristic longitudinal nuclear grooving, scattered multinucleated giant cells, focal chondroid matrix, and a characteristic “chicken-wire” calcification pattern; the H3F3B K36M mutation is characteristic. Clinically the patient presents with persistent joint pain, sometimes with effusion, and an antalgic gait. Radiographically the lesion is a well-defined, round-to-oval, eccentric, lytic epiphyseal lesion, often with internal stippled mineralization, a thin sclerotic margin, and minimal expansion. The bone scan is hot. Treatment is

curettage with high-speed burring and either bone grafting or polymethylmethacrylate cementation; recurrence rates are 10-25%. Pulmonary metastases — rare and indolent — have been described, particularly after intralesional surgery, and remain a topic of speculation regarding the true biological nature of this otherwise benign lesion. Chondromyxoid Fibroma Chondromyxoid fibroma is a rare benign tumor, the rarest of the chondrogenic tumors, accounting for less than 1% of benign bone tumors. The lesion has a predilection for the metaphyses of long bones in the second and third decades, particularly the proximal tibia, distal femur, and small bones of the foot. The pain is mild and slowly progressive. Radiographically the lesion is eccentric, lytic, multilobulated, and well-defined, often with a sclerotic margin and a characteristic septation pattern; cortical expansion is common, and the lesion can be misinterpreted as a more aggressive tumor. Histologically the tissue consists of stellate or spindle-shaped cells in a chondroid or myxoid matrix arranged in lobules with sharp boundaries. Treatment is extended curettage with bone grafting, and recurrence rates approach 15-25%.

Giant Cell Tumor of Bone

Epidemiology and Pathology Giant cell tumor of bone (GCT) is a benign but locally aggressive tumor, classified in the WHO scheme as an intermediate (rarely metastasizing) lesion. It accounts for approximately 5% of primary bone neoplasms. The age distribution is unusual: GCT arises after physeal closure, with peak incidence in the third and fourth decades, and is rare in skeletally immature patients. A slight female predominance is noted in most series. The pathology is characterized by sheets of mononuclear stromal cells, which are the actual neoplastic component, interspersed with abundant osteoclast-like multinucleated giant cells; the giant cells are reactive and the stromal cells carry an activating H3F3A G34W or G34V mutation. The discovery that the stromal cells overexpress RANKL has been clinically transformative, since it has provided the basis for denosumab therapy.

Clinical Features and Radiographic Findings The most common locations are the distal femur, proximal tibia, distal radius, and proximal humerus — the so-called “ends of the long bones around the knee, wrist, and shoulder” — with the sacrum and vertebral bodies as further sites. Presentation is with pain, swelling, and limited joint motion; pathological fracture is the presenting feature in 5-10%. Radiographically the lesion is an eccentric, expansile, purely lytic lesion of the epiphysis and metaphysis (extending to the subchondral bone in adults whose growth plates have closed), with a narrow zone of transition, no matrix mineralization, no periosteal reaction, and absent or minimal sclerotic margin — the so-called “geographic, purely lytic” pattern that helps distinguish GCT from other tumors. The Campanacci radiographic grading (I-III) reflects increasing extent of cortical destruction and is correlated with treatment recommendations.

Treatment Extended intralesional curettage with high-speed burring and adjuvant therapy (phenol, hydrogen peroxide, cryotherapy, or polymethylmethacrylate cement, which provides both mechanical stabilization and a local cytotoxic effect from the heat of polymerization) is the standard treatment, achieving local control in 70-90% of cases. Wide en-bloc resection is reserved for Campanacci III lesions, lesions with extensive soft-tissue extension, recurrent disease in expendable bones, and lesions in the distal radius or proximal fibula where resection is well tolerated. Denosumab, a monoclonal antibody against RANKL, has revolutionized the medical management of GCT: it stops the osteolytic process driven by the recruited osteoclasts and switches the balance toward bone formation. It is used preoperatively to facilitate resection of difficult lesions, as a primary medical treatment for unresectable spinal and pelvic lesions, and occasionally in metastatic disease. Side effects include hypocalcemia, osteonecrosis of the jaw, and atypical fractures. The “denosumab dilemma” of recurrence after discontinuation in primary tumors has prompted protocols of short preoperative courses followed by definitive surgery rather than prolonged primary medical therapy. Approximately 2% of GCTs metastasize, almost always to the lung as slow-growing, biologically benign “benign pulmonary metastases” that often respond to local resection or even observation.

Hemangioma of Bone

Hemangioma of bone is a benign vascular lesion that occurs most commonly in the vertebral bodies (where it accounts for the great majority of incidentally noted vertebral lesions) and the skull. The lesion consists of thin-walled vascular channels — capillary, cavernous, or mixed — within bone. In the spine, the characteristic radiographic appearance is a vertebral body with prominent vertical trabeculae (“corduroy” or “honeycomb” appearance on plain radiographs, “polka-dot” appearance on axial CT); on MRI the lesion typically demonstrates high signal on both T1 and T2 sequences because of the fat content. The vast majority are asymptomatic and require no treatment. Symptomatic or aggressive hemangiomas — characterized by extra-osseous extension, soft-tissue mass, or neurological compression — can be treated with vertebroplasty (which obliterates the vascular spaces and provides mechanical reinforcement), embolization, or — rarely — radiotherapy.

Other Benign Lesions

Intraosseous Lipoma Intraosseous lipoma is a rare benign tumor of fat within bone. The commonest locations are the calcaneus and the intertrochanteric region of the proximal femur. The lesion is usually asymptomatic. Radiographically the lesion is a well-defined lytic area, sometimes with a central calcification; MRI is diagnostic by demonstrating fat signal. Treatment is observation; symptomatic lesions can be curetted and grafted.

Adamantinoma Adamantinoma is a rare, locally aggressive, low-grade malignant epithelial tumor of bone with a strong predilection for the anterior diaphyseal cortex of the tibia. Although low- grade and slow-growing, it has metastatic potential and is therefore not strictly a benign tumor; it is included here for the radiographic differential, since it shares many features with osteofibrous dysplasia and fibrous dysplasia. The radiograph shows a multifocal, lobulated, lytic lesion with sclerosis and cortical expansion of the anterior tibial cortex. Wide en-bloc resection with reconstruction is the standard treatment because of the malignant potential and the high recurrence rate after intralesional surgery. Neurilemmoma (Schwannoma) of Bone Primary intraosseous neurilemmoma is rare and occurs most commonly in the mandible, sacrum, and vertebral bodies. The lesion is typically a well-defined, expansile, lytic lesion; histologically the picture is that of a soft-tissue schwannoma with Antoni A and B areas. Treatment is curettage; recurrence is uncommon.

Principles of Surgical Management for Benign Bone Tumors

The surgical management of benign bone tumors follows a hierarchy based on Enneking grading and the specific behavior of each lesion. Observation is appropriate for latent (Stage 1) lesions that are asymptomatic, mechanically stable, and demonstrate no concerning radiographic features — for example, the typical incidentally discovered osteochondroma in an adult or the small enchondroma of the proximal humerus. Intralesional curettage — the historic mainstay — is appropriate for active Stage 2 lesions such as enchondroma, chondroblastoma, and chondromyxoid fibroma; the lesion is debulked through a window in the cortex, the cavity is examined and aggressively curetted, and the cavity is filled with autogenous or allogeneic bone graft. Extended intralesional curettage — the standard for aggressive Stage 3 benign lesions, particularly giant cell tumor — adds high-speed burring of the cyst walls (to remove the macroscopically invisible fringe of viable tumor cells extending into trabecular bone) and a local adjuvant, typically either polymethylmethacrylate cement (whose exothermic polymerization produces a thermal kill zone of several millimeters) or chemical (phenol, alcohol) or thermal (cryotherapy, argon-beam coagulation) ablation. Wide en-bloc resection, with margins of normal bone and soft tissue, is reserved for Campanacci III GCT with cortical destruction, recurrent aggressive lesions in expendable bones, suspected low-grade chondrosarcoma masquerading as enchondroma, and adamantinoma. Adjuvant therapies include preoperative selective arterial embolization for large or vascular lesions, percutaneous radiofrequency ablation for osteoid osteoma, denosumab for GCT, bisphosphonates for fibrous dysplasia, and — historically — radiotherapy, which is now used only for surgically unresectable lesions because of the risk of secondary sarcoma. Reconstruction after benign tumor surgery ranges from simple bone-graft packing in small contained defects, through structural allograft or vascularized fibular autograft for larger segmental defects, to endoprosthetic replacement for periarticular defects where joint salvage is not possible. The biological principles of host bone-graft incorporation —

creeping substitution for cancellous autograft, slower remodeling for allograft, primary union for vascularized autograft — govern the choice of reconstruction and the postoperative rehabilitation protocol.

Summary and Take-Home Points

The benign bone tumors are a diverse family unified by their limited growth potential and the predictability of their natural histories when correctly identified. The key clinical recognition points are: the nocturnal pain relieved by aspirin of an osteoid osteoma; the painful scoliosis of a posterior-element spinal osteoblastoma; the painless metaphyseal bony lump pointing away from the joint of an osteochondroma; the incidental “rings and arcs” appearance of an enchondroma in a phalanx; the epiphyseal lytic lesion in a skeletally immature patient of a chondroblastoma; the geographic, purely lytic epi-metaphyseal lesion around the knee in an adult of a giant cell tumor; and the polka-dot vertebral body of a vertebral hemangioma. The unifying principles of management — observation of latent lesions, extended intralesional curettage with adjuvant for active and aggressive lesions, wide resection for Campanacci III GCT and for any lesion whose diagnosis cannot be confidently distinguished from a malignancy — reflect the constant tension between achieving local control and preserving function. The single most consequential pitfall remains the misdiagnosis of a low-grade chondrosarcoma as an enchondroma, particularly in adult patients with newly painful or growing cartilaginous lesions; the orthopedic surgeon must always entertain the possibility of malignancy in any cartilaginous lesion of adult onset and pursue the diagnosis with imaging, expert pathology review, and, when indicated, definitive surgical resection.