Musculoskeletal Neoplastic Disorders

Hee-Kyung Kim

Jung-Eun Cheon

Sara O. Vargas

Hye-Kyung Yoon

INTRODUCTION

During the past several decades, improved early and accurate diagnosis along with development of new therapeutic regimens for managing childhood musculoskeletal neoplasms have resulted in substantially improved outcomes for pediatric patients with various bone and soft tissue neoplasms. However, musculoskeletal neoplasms continue to cause substantial mortality and morbidity in the pediatric population.¹,²,³ Imaging evaluation plays an essential role in the initial detection, staging, and follow-up assessment of musculoskeletal neoplasms in infants and children. In this chapter, currently available imaging modalities with up-to-date imaging techniques, clinical presentations, imaging findings, and management of benign and malignant childhood bone and soft tissue neoplasms as classified by the World Health Organization (WHO) are discussed (Table 23.1).⁴

IMAGING TECHNIQUES

Radiography

Radiography is usually the first imaging modality for evaluating bone and soft tissue neoplasms in children. In general, aggressive lesions on radiographs are malignant, and nonaggressive lesions are benign tumors. Osteosarcoma and Ewing sarcoma comprise 90% of malignant bone tumors in children and have an aggressive appearance such as an ill-defined border with a broad zone of transition, periosteal new bone formation, and cortical destruction on radiographs. However, an aggressive radiographic appearance can also be seen with nonmalignant entities such as Langerhans cell histiocytosis (LCH), osteomyelitis, and occasionally with a fracture undergoing the healing process in the pediatric population.⁵ Therefore, further evaluation using computed tomography (CT) or magnetic resonance imaging (MRI) may be needed for clarification.

Ultrasound

Ultrasound is often used as the first imaging study in evaluation of palpable mass and useful to differentiate solid from cystic masses. The utilized ultrasound technique usually depends on the depth of the lesions. While superficial masses are often evaluated with high frequency linear transducers (12 to 17 MHz), deep masses are evaluated with lower frequency curved array transducers (5 to 9 MHz) with better soft tissue penetration.⁶ Color Doppler imaging is useful for evaluating vascular masses especially vascular malformations and identification of solid masses. However, in most cases, sonographic imaging findings of soft tissue masses are nonspecific and often require further evaluation and characterization with MRI.

Computed Tomography

CT is useful to detect mineralization associated with malignant osseous tumors and nidus in osteoid osteoma. Although CT and MRI have comparable accuracy in local staging of bone and soft tissue tumors, MRI is superior to CT due to its excellent tissue contrast.⁷ In addition to evaluation of the primary malignant bone and soft tissue lesions, evaluation of metastases should be also performed. Twenty percent of children with osteosarcoma and 25% of patients with Ewing sarcoma have metastases at presentation.⁸ Because the lung is the most common site of metastases, chest CT is currently recommended as a part of initial evaluation and staging.

TABLE 23.1 World Health Organization (WHO) Classification of Bone Tumors

Bone Tumor Origin	Benign	Intermediate	Malignant
Chondrogenic	Osteochondroma Enchondroma Subungual exostosis Synovial chondromatosis	Chondromyxoid fibroma Atypical cartilaginous tumor (chondrosarcoma grade I) Chondroblastoma	Chondrosarcoma (grade II, grade III) Mesenchymal chondrosarcoma
Osteogenic	Osteoma Osteoid osteoma	Osteoblastoma	Osteosarcoma
Fibrogenic	Desmoplastic fibroma of bone		Fibrosarcoma of bone
Fibrohistiocytic	Nonossifying fibroma
Hematopoietic			Primary lymphoma of bone
Osteoclastic giant cell rich		Giant cell tumor of bone
Notochordal	Benign notochordal tumor		Chordoma
Vascular	Hemangioma	Epithelioid hemangioma	Epithelioid hemangioendothelioma Angiosarcoma
Miscellaneous			Ewing sarcoma Adamantinoma
Undefined neoplastic nature	Simple bone cyst Fibrous dysplasia Osteofibrous dysplasia	Aneurysmal bone cyst Langerhans cell histiocytosis
Adapted from: Fletcher CDM, Bridge JA, Hogendoorn PCW, et al., eds. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon, France: IARC; 2013.

Magnetic Resonance Imaging

MRI has been used as a standard care imaging modality in evaluation of malignant bone and soft tissue tumors. Staging of malignant bone and soft tissue tumors is summarized in Table 23.2.⁹ MRI is an essential step in the preoperative workup because it provides critical information regarding (1) intra- and extraosseous tumor involvement, (2) the extent of bone marrow involvement and skip lesions, (3) invasion of the epiphysis, (4) involvement of the neurovascular or joint structures, and (5) documentation of viable tumor and mineralized matrix to guide biopsy.

Skip metastases are areas of tumor within the bone marrow of the affected bone but separate from the primary lesion. They are associated with an increased incidence of local recurrence and subsequent metastases after ablative surgery. Therefore, MRI with T1-weighted and/or short tau inversion recovery (STIR) sequences should be performed through the entire involved bone to detect skip metastases. In contrast to bone marrow edema from benign entities such as osteomyelitis or trauma, malignant bone tumors typically demonstrate a clear demarcation between normal marrow and tumor involved marrow. The signal intensities of primary bone lesions depend on the tissue components of the tumors. Enhancement after intravenous contrast administration is useful to differentiate peritumoral edema from tumor and to assess tumor necrosis after treatment. At least two planes of postcontrast T1-weighted MR images with fat-suppression are required for a complete assessment.

Nuclear Medicine

Technetium 99m-methylene diphosphonate (MDP) bone scintigraphy can be used to assess the presence of bone metastases and skip lesions, which are represented by increased uptake. Single-photon emission computed tomography (SPECT) can improve sensitivity of the examinations. Whole-body (WB) FDG-PET imaging can be used to detect metastases, assess chemotherapeutic response, and detect tumor recurrence.¹⁰ Whole-body (WB) MRI is currently used in oncology patients. Using a moving tabletop in the scanner and software with automatic direct realignment of the sequential achieved images, imaging the entire body is enabled in a short time. WB MRI is useful to assess tumor extent, follow-up of therapeutic response, as well as detection of complications. Accuracy of WB MRI in detection of skeletal and extraskeletal metastasis is even higher than bone scintigraphy or CT.¹¹ Integrating WB MRI and PET scan has been recently carried out and enabled metabolic-anatomic combined imaging. This technique might be beneficial to tumor staging with improved accuracy in pediatric oncologic patients.¹²

SPECTRUM OF PEDIATRIC MUSCULOSKELETAL NEOPLASMS

Tumors Arising from Bone

Benign Osseous Tumors

Although the exact incidence is not known, the majority of bone tumors in children are benign.¹³ It is common for benign bony lesions to be found incidentally on radiographs obtained for evaluation of traumatic injury or joint pain. For benign bone lesions, such as benign fibrous cortical defects (FCDs), or nonossifying fibromas (NOFs), radiography alone is sufficient for diagnosis, and there is no need for further imaging studies or biopsy.

TABLE 23.2 TNM Classification of Bone and Soft Tissue Tumors

Category Domain	Category Item	TNM Classification of Bone Tumors		TNM Classification of Soft Tissue Tumors
Primary tumor (T)	TX	Primary tumor cannot be assessed		Primary tumor cannot be assessed
	T0	No evidence of primary tumor		No evidence of primary tumor
	T1	Tumor ≤8 cm in greatest dimension		Tumor ≤5 cm in greatest dimension^b
					T1a: superficial tumor T1b: deep tumor
	T2	Tumor >8 cm in greatest dimension		Tumor >5 cm in greatest dimension^b
					T2a: superficial tumor T2b: deep tumor
	T3	Discontinuous tumors in the primary bone site
Regional lymph nodes (N)	NX	Regional lymph nodes cannot be assessed^a		Regional lymph nodes cannot be assessed^a
	N0	No regional lymph node metastasis		No regional lymph node metastasis
	N1	Regional lymph node metastasis		Regional lymph node metastasis
Distant metastasis (M)	MX	Distant metastasis cannot be assessed
	M0	No distant metastasis		No distant metastasis
	M1	Distant metastasis		Distant metastasis
			M1a: lung M1b: other distant sites
^aRegional node involvement is rare, and cases in which nodal status is not assessed either clinically or pathologically could be considered N0 instead of NX. ^bSuperficial tumor is located exclusively above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath the superficial fascia or superficial to the fascia with invasion of or through the fascia. Retroperitoneal, mediastinal, and pelvic sarcomas are classified as deep tumors.
Edge S, Byrd DR, Compton CC, et al. eds. AJCC Cancer Staging Manual. 7th ed. Chicago, IL: American Joint Commission on Cancer; 2010.

Benign bone lesions are typically well-demarcated, having a narrow transition zone with sclerotic rim and no cortical bone breakdown or soft tissue extension. In some cases, the lesions can have an aggressive radiographic appearance that may mimic malignant bone tumor or osteomyelitis, requiring further evaluation.¹⁴ CT is superior to radiography or MRI in visualizing matrix calcification or ossification and associated fracture. MRI is excellent for showing the cross-sectional intraosseous and extraosseous extent of bone tumors, internal characteristics such as necrosis, hemorrhage, or fluid-fluid levels, adjacent marrow edema, and enhancement pattern.

Benign bone tumors have a tendency to be found in certain bones (Schematic A), in specific locations (epiphysis, metaphysis, and diaphysis, Schematic B), and in different depths (Schematic D) within the bones. Because skeletal growth is ongoing in the pediatric population, benign bone lesions such as bone cysts in the metaphysis may appear to migrate away from the physis. In addition, benign slow-growing tumors can cause substantial deformity of the involved bone or the adjacent joint, for example, Madelung deformity in multiple exostoses and “shepherd crook” deformity in fibrous dysplasia.

Osteochondroma

Osteochondroma, also known as an osteocartilaginous exostosis, is a cartilage-capped bony excrescence that arises from the external surface of the bone and contains a medullary cavity that is continuous with that of the parent bone¹⁵ (Fig. 23.1). It is the most common benign bone tumor, accounting for 20% to 50% of benign bone tumors and affecting 1% of the general population.¹ In most cases, osteochondromas present as a solitary bone lesion (86% of cases) and occur in the first three decades of life with slight male predilection (male: female 1.6 to 3.4:1).¹ They most commonly arise from the metaphyses of the long bones, particularly the distal femur, proximal tibia, and proximal humerus. Less commonly involved locations are the radius, fibula, and flat bones including the ileum, scapula, and ribs. Involvement of small bones of the hand or the foot is seen in 10% of osteochondromas.¹⁶

Multiple osteochondromas account for 14% of cases and occur in the setting of hereditary multiple exostoses (HME). In ˜80% of solitary osteochondromas, homozygous mutations in the EXT1 gene can be found in the cartilaginous cap. In HME, also known as familial osteochondromatosis or diaphyseal aclasis, germline mutations in the EXT1 or EXT2 gene are commonly identified.¹⁷ HME most commonly

affects the distal and proximal bones of the lower extremities, and involvement is typically bilateral and symmetrical. Nearly 2% of patients with HME eventually develop a chondrosarcoma.¹⁷

A: Benign Bone Tumors in Characteristic Locations in the Peripheral and Axial Skeletons.

B: Characteristic Locations of Benign Bone Tumors.

C: Characteristic Locations of Malignant Bone Tumors.

D: Characteristic Locations of Superficial Benign and Malignant Bone Tumors.

FIGURE 23.1 Solitary osteochondroma in the humerus of a 13-year-old boy. A: The outer surface shows knobby cartilaginous protrusions. B: The cut surface shows the relationship between the cartilaginous cap and the underlying trabecular bone. C: Microscopically, there is a thin fibrous perichondrium overlying a cap of disorganized hyaline cartilage, with enchondral ossification and underlying bone (hematoxylin and eosin, original magnification, 40×).

Osteochondroma is the most common tumor in irradiated skeletons; 6% to 12% of patients who underwent previous radiation at a young age develop osteochondromas, and latent periods are variable with a range of 3 to 16 years.¹⁸,¹⁹ Imaging findings and histologic features are the same as those of primary osteochondroma.

In the immature skeleton, osteochondromas continue to increase in size by endochondral ossification occurring at the base of the cartilage cap, which is equivalent to the epiphyseal physis, and growth ceases after skeletal maturation (physeal closure). Spontaneous regression of osteochondromas has been reported after skeletal maturation. In many cases, osteochondromas are asymptomatic and found incidentally, but affected pediatric patients can present with pain and other symptoms. Complications of osteochondromas include fracture, bursa formation, bursitis, vascular injury, and neurologic compromise. Complications and osseous deformities are more common in HME.

FIGURE 23.2 Pedunculated osteochondroma in an 11-year-old boy. A: Frontal radiograph of the left knee shows a solitary osteochondroma (arrow) arising from the proximal tibia. The medullary and cortical portions of the lesion are continuous with those of the parent bone. There is bowing of the proximal fibula. B: Axial fat-suppressed T2-weighted MR image demonstrates a hyperintensity cartilaginous cap (arrow) over the bony mass of the proximal tibia.

The imaging findings of osteochondromas are characteristic and include pedunculated or sessile lesions. Pedunculated osteochondromas have a long and slender appearance with a bony excrescence arising from the surface of the bone (usually long bone metaphyses). Pedunculated osteochondromas grow in the direction of tendon pulling (Fig. 23.2). Sessile osteochondromas have a broad-based and flat appearance. Typically, the medullary portion of the osteochondroma merges into the bone marrow of the parent bone, and the bony cortex and periosteum continuously outline both parent bone and osteochondroma. In contrast to osteochondroma, juxtacortical osteosarcoma
has interposed periosteum and cortex between tumor and parent bone.

Imaging findings of individual osteochondromas in HME and solitary osteochondromas are the same. Besides multiple osteochondromas, HME is characterized by abnormal modeling of developing bone, including metaphyseal widening, growth disturbance, and deformities of the joints. Radiographic evaluation is required to delineate the dramatic bone changes.²⁰ The affected bone is abnormally wide due to failure of normal tubulation. The cartilage cap is not visualized on radiographs except when irregular zones of calcification occur in the cartilage cap. Small stippled calcifications are compatible with a benign growth of the cartilage cap.²¹ Osteochondromas arising from the innominate bone tend to be especially large and may exert mass effect, displacing adjacent structures.

Both CT and MRI can show the continuity of the medullary bone between the parent bone and the lesion. MRI is superior to CT in demonstrating the cartilaginous cap, which has a curvilinear area of fluid-like signal intensity (low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted MR images), and can allow accurate measurement of the thickness of the cartilage cap (Fig. 23.2). In children and adolescents, the cartilage cap can be as thick as 3 cm.²² In adults, the cartilage cap is usually <1 cm in thickness or can be entirely absent. In skeletally mature patients, a cartilage cap presenting with more than 1.5 cm in thickness raises the possibility of underlying malignant change.²³

Malignant transformation to chondrosarcoma can occur in the cartilage cap and is reported in <1% of solitary osteochondromas and in nearly 2% of HME (Fig. 23.3).²⁴ Imaging features suggesting malignant transformation include growth of the lesion in a skeletally mature patient or after physeal closure, irregular or indistinct lesion surface, focal areas of radiolucency in the base of the lesion, erosion or destruction of the adjacent bone, and new soft tissue formation with extensive or irregular calcification (Fig. 23.3).²⁴ Malignant transformation of osteochondroma to chondrosarcoma before the age of 20 years is unusual. Malignant transformation of osteochondroma to osteosarcoma, which usually occurs in the osteochondroma stalk, is even rarer.

Small asymptomatic osteochondromas do not require treatment. Surgical resection is reserved for large solitary lesions or lesions with complications. In pediatric patients with HME, treatment is complex to correct deformities as well as to resect lesions, and often multiple surgical procedures are required.

Osteochondroma Variants

Dysplasia epiphysealis hemimelica (DEH), also known as Trevor disease, is a rare developmental disorder characterized by osteochondromas arising from the epiphysis. DEH is nonhereditary and more commonly seen in boys. The lower extremity is usually affected, and tarsal or carpal bones are also involved in some cases.²⁵ DEH is caused by asymmetric overgrowth of the medial or lateral aspect of the epiphyseal cartilage or epiphyseal equivalent. Three different types are observed: localized (single epiphyseal involvement), classical (involvement of more than one epiphysis of the same limb), and generalized (involvement of the entire limb).²⁶

Radiographs usually demonstrate the characteristic appearance of asymmetric epiphyseal cartilage overgrowth with multiple stippled, irregular, and dense calcifications in the epiphysis.²⁷ The lesion is more likely to be medial than lateral in a given bone part, and CT can clearly show the continuity of the mass with the mother bone (Fig. 23.4). MRI is helpful for defining epiphyseal overgrowth, which is mainly cartilaginous before ossification. On MRI, the osteochondroma appears incorporated into the epiphysis, and the lesion has the same signal intensity as normal cartilage and may contain internal low signal spots from calcified foci.

Subungual exostosis is a neoplastic overgrowth of cartilage and trabecular bone in the nail bed of the phalanx. Bizarre parosteal osteochondromatous proliferation (BPOP), also known as Nora lesion, is a benign proliferation of bone and cartilage that arises from the bone surface in the hand or foot, or less commonly the long bones. BPOP presents with a nodular mineralized mass arising from the hand and foot bones (Fig. 23.5).²⁴

Simple Bone Cyst

A simple bone cyst (SBC), also known as a unicameral cyst, solitary bone cyst, or juvenile bone cyst, is an intramedullary membrane-lined, fluid-filled cavity in the bone. In most cases, SBC remains asymptomatic and is discovered incidentally. However, SBC may present with pain and swelling when there is a pathologic fracture. SBC is most commonly found in the proximal humerus (over two-thirds of cases), followed by the proximal femur. SBC usually involves the metaphysis and is centered in the medullary cavity, in contrast to the eccentric location of a typical aneurysmal bone cyst (ABC). As the child grows, SBC appears to gradually migrate away from the physis into the diaphysis.

On radiograph, SBC appears as a well-demarcated radiolucent lesion with or without septations. There is no or little expansion of the bone. A “fallen-fragment” sign, representing a fractured bone fragment dislodged in the dependent portion of the cyst, is pathognomonic for SBC with pathologic fracture (Fig. 23.6).²⁸ On MRI, the bone cyst appears as a high signal intensity fluid-filled lesion on T2-weighted MR images and low to iso-signal intensity on T1-weighted MR images. There may be rim or cyst wall enhancement after administration of gadolinium. When complicated by a pathologic fracture, fluid-fluid levels are often demonstrated within a SBC. If the SBC occurs in the calcaneus, mostly in adults, it is typically located near the neck of the calcaneus.²⁹ Calcaneal pseudocyst and intraosseous lipoma may have a

similar radiographic appearance with well-demarcated radiolucent lesions.

FIGURE 23.3 Malignant transformation of multiple hereditary exostoses to chondrosarcoma in a 15-year-old boy who presented with a rapidly growing mass. A: Frontal radiograph of the pelvis shows multiple sessile and bizarre-shaped bony masses and deformities. A calcified mass (arrows) is seen arising from the right pelvis. B: Axial T2-weighted MR image demonstrates a heterogeneous high-signal mass arising from the right pelvic bones. Multiple areas of dark signal represent calcifications (arrowheads). C: Gross specimen demonstrates chondrosarcoma arising from the right pelvic bones.

FIGURE 23.4 Dysplasia epiphysealis hemimelica (Trevor disease) in a 9-year-old girl. A: Lateral view of the left ankle joint radiograph shows an exuberant bony mass (arrowheads) projecting through the calcaneus and talus. B: Coronal CT image also demonstrates bony masses (arrows) protruding from the medial aspects of the talus and calcaneus around the talocalcaneal joint.

FIGURE 23.5 Bizarre parosteal osteochondromatous proliferation in a 15-year-old boy. A: Frontal radiograph of the index finger demonstrates a mineralized mass (arrow) arising from the proximal phalanx. B, C: Coronal T1-weighted (B) and axial fat-suppressed T2-weighted (C) MR images demonstrate an intermediate T1, heterogeneous high T2 signal mass (arrow) arising from the cortex of the proximal phalanx.

FIGURE 23.6 Simple bone cyst with a fracture in a 17-year-old boy. A, B: Frontal radiograph of the proximal left humerus (A) and axial CT image (B) show an osteolytic bony lesion in the proximal left humerus associated with a pathologic fracture. A detached bone fragment is seen within the bone cyst (arrows), which is known as the “fallen fragment” sign.

FIGURE 23.7 Aneurysmal bone cyst (ABC) with an associated fracture in a 16-year-old boy. A: Frontal radiograph of the left hip shows an expansile bony lesion with a soap-bubble appearance in the left femoral neck. There is a radiolucent line crossing the bony lesion (arrow) with angulation representing an associated fracture. B: Axial fat-suppressed T2-weighted MR image demonstrates a multilocular cystic mass with fluid-hemorrhage levels, characteristic of an ABC.

The current treatment of SBC includes steroid injection after cyst aspiration, sclerotherapy, and curettage with cement engrafting. Posttreatment radiography may show a more complex appearance of the no longer “simple” cyst with sclerosis and deformity.

Aneurysmal Bone Cyst

ABC is a benign bone neoplasm composed of blood-filled spaces separated by multiple thin fibrous septa. Lesions with histologic features of ABC can arise de novo (primary), which accounts for 70% of cases, or they may occur adjacent to other benign or malignant bone tumors (secondary) in the remaining 30%.⁴ ABC is most common during the first two decades of life with no gender predilection. The most commonly affected sites are the metaphyses of the long tubular bones, the femur, tibia and humerus, and the posterior aspect of the spine. Typical clinical presentations include pain and swelling and neurologic symptoms in cases of spinal involvement.

Radiographs usually show a well-delineated and expansile osteolytic lesion with thin walls and septa creating a “ soap-bubble” appearance. In the long bones, ABC is usually eccentric in location, and the outer cortex is markedly thin (Fig. 23.7). CT and MRI can reveal fluid-fluid levels due to blood products; this finding is nearly diagnostic of ABC (Fig. 23.7). It is important to recognize that secondary ABC components with fluid-fluid levels can be found in various other benign bone lesions such as osteoblastoma, chondroblastoma, giant cell tumor (GCT), NOF, cystic fibrous dysplasia, and SBC. In addition, some of malignant bone lesions such as osteosarcoma, either telangiectatic or even conventional type, can also have an ABC component. Fat-suppressed T2-weighted MR images are best at clearly showing fluid-fluid levels. The bone cortex is preserved in most cases of ABC unless it is associated with a pathologic fracture. The radiologic differential diagnosis of ABC includes GCT, low-grade osteosarcoma, and telangiectatic osteosarcoma in the pediatric population.

FIGURE 23.8 Aneurysmal bone cyst (ABC). A: Fibular ABC in a 12-year-old boy who presented with an expansile mass shows a cystic cut surface. B: Tibial ABC in an 11-year-old girl shows the characteristic fibrous septa with interspersed giant cells. Cytogenetic analysis revealed t(1;17), confirming the diagnosis (hematoxylin and eosin, original magnification, 400×).

Solid-variant ABC, also known as giant cell reparative granuloma when it occurs in the head and neck, is a rare type of ABC that is primarily seen in the craniofacial bones and small tubular bones of the hand and foot. It is uncommonly seen in the long tubular bones.³⁰ This variant has a wide spectrum of imaging features, from similar to ABC at one end to having aggressive features such as permeative bone destruction and periosteal reaction simulating malignancy at the other end. One-third of the solid-variant ABC lesions are not expansile (nonaneurysmal).³¹ MRI shows a persistent solid component with heterogeneous high T1 and T2 signal intensity in an
expansile cystic lesion. Occasional perilesional bone marrow edema can be also observed in the solid-variant ABC.³⁰

Grossly and histologically, ABC typically shows blood-filled cysts with intervening septa that contain fibroblasts, multinucleate giant cells, and variable numbers of admixed osteoblasts and inflammatory cells (Fig. 23.8). Chromosomal rearrangement involving the USP6 gene at chromosome 17p13 is seen in primary ABC, illustrating a relationship between ABC and nodular fasciitis, another fibroblastic proliferation characterized by USP6 rearrangement.³¹ ABC is treated with surgical removal of the entire lesion with bone graft if it is required. Local recurrences after resection are rare.³²

Osteoid Osteoma

Osteoid osteoma is a benign bone-forming tumor that is characterized by a relatively small-sized lesion with disproportionally severe pain. Osteoid osteomas account for 10% to 12% of all benign bone neoplasms and 2% to 3% of all primary bone tumors.⁴ Most cases (over 75%) occur between ages 5 and 24 years with male predilection (3:1).⁴ In more than 50% of cases, the femur or tibia is affected, and the proximal femur including the femoral neck is the single most common site.⁴ Other locations include the midshaft or metadiaphysis of the long bones and less commonly the tarsal bones, hand phalanges, and the spine. Osteoid osteomas are subclassified into three subtypes based on location: cortical, medullary, or subperiosteal. Of these, cortical osteoid osteomas are the most common, and subperiosteal ones are the least common.³³

FIGURE 23.9 Osteoid osteoma in an 8-year-old boy who presented with nocturnal pain. A: Frontal radiograph shows fusiform cortical thickening and solid periosteal new bone formation (arrow) involving the mid- to distal shaft of the left tibia. A radiolucent nidus is not demonstrated on this study. B: Coronal reformatted CT image clearly depicts diffuse cortical thickening and a radiolucent nidus (arrow). C: Coronal postcontrast fat-suppressed T1-weighted MR image shows a central enhancing nidus (arrow) with diffuse enhancement of the adjacent bone marrow and soft tissue. The nidus is usually more conspicuous on CT than on MRI, as it is in this case.

The clinical presentation of an osteoid osteoma is characteristic. Affected pediatric patients experience pain that worsens at night and dramatically improves with salicylates. Unfortunately, the pain is often referred to the adjacent joint and occasionally to a site distant from the lesion, resulting in misdirecting of radiographic studies and incorrect clinical diagnosis.³⁴

The characteristic imaging findings of osteoid osteomas include a nidus (core) that is usually located in the cortex and contains a variable degree of mineralization, associated adjacent cortical thickening, and reactive sclerosis in a long bone shaft (Fig. 23.9).³³ The nidus appears as a central radiodense
area that is surrounded by a lucent rim or a radiolucent focus because it is located in the center of an area of reactive sclerosis.

The nidus is round or oval and usually less than 2 cm in size.³³ CT best delineates the nidus; it has a target appearance with a well-defined round or oval area of lucency and a central mineralized area.³⁵ MRI shows a low to intermediate T1 and variable T2 signal intensity nidus, depending on the mineralization of the central osteoid. The mineralized nidus has a target appearance on T2-weighted MR images; there is a central dark spot (mineralized) surrounded by peripheral high signal (unmineralized area). The nidus may show strong enhancement after administration of gadolinium (Fig. 23.9). With intravenous contrast administration, dynamic CT or MR perfusion imaging technique enables the nidus to be more conspicuously visualized.³⁶ MRI can also show associated bone marrow edema and surrounding soft tissue changes. With recent advances in MRI techniques, current MRI would be comparable or even better than CT for evaluating osteoid osteoma and has the advantage of showing additional findings such as marrow edema, reactive soft tissue changes, and abnormalities of adjacent joints without associated ionizing radiation exposure.³⁶

Intra-articular osteoid osteoma is rare, but somewhat challenging in clinical and imaging diagnosis. An osteoid osteoma near or within the joint typically presents with joint effusion and pain mimicking arthritis. In contrast to osteoid osteoma in usual locations, reactive cortical thickening may be minimal or absent in intra-articular osteoid osteoma. A high level of suspicion is often required, especially when the nidus is small and associated reactive bone changes are minimal.³⁷,³⁸

Occurrence in an atypical anatomic location may complicate the diagnosis of osteoid osteomas. Spinal osteoid osteoma, most commonly occurring in the neural arch of the lumbar spine, presents with scoliosis and radicular pain. CT or MRI is required in most cases to detect the nidus in the pedicle and lamina. Imaging and clinical findings of osteoid osteoma in the carpal and tarsal bones may mimic infection or inflammatory arthritis.

The differential diagnosis of an osteoid osteoma includes stress fracture, intracortical abscess, and other tumors such as intracortical hemangioma, osteoblastoma, and compensatory hypertrophy of the pedicle. Osteoid osteoma has a round nidus, as opposed to a stress fracture, which has a linear cortical break in the center of the cortical thickening. On bone scintigraphy, an osteoid osteoma demonstrates the “double density” sign with intense uptake in the nidus and surrounding moderate uptake. In contrast, a stress fracture typically shows linear intense uptake of the tracer.³⁹ An intracortical osteoid osteoma has a smooth margin with strong enhancement of the nidus; this contrasts with an intracortical abscess or sequestrum, which usually has an irregular shape and margin with peripheral rim enhancement at contrast-enhanced CT.⁴⁰ Differentiation between osteoid osteoma and intracortical hemangioma is difficult based on imaging features, although intracortical hemangioma is extremely rare. Compensatory hypertrophy of the vertebral pedicle is seen in unilateral spondylolysis and mimics spinal osteoid osteoma. Lack of a nidus and presence of contralateral spondylolysis in compensatory hypertrophy of the pedicle can differentiate it from spinal osteoid osteoma. The differences between osteoid osteoma and osteoblastoma are discussed in the following section.

Grossly and microscopically, osteoid osteoma shows a nidus rich in osteoblasts and poorly mineralized woven bone (Fig. 23.10). A variably sclerotic bony rim surrounds the nidus. The current treatment of choice for osteoid osteoma is complete excision, which is curative with en bloc resection. Recently, percutaneous radiofrequency ablation of the nidus has become a treatment of choice almost replacing surgical excision. Radiofrequency ablation effectively relieves pain in most cases with few complications and a low recurrence rate.⁴¹

Osteoblastoma

Osteoblastoma is a rare benign bone-forming neoplasm. It is characterized by loose woven bone bordered by prominent osteoblasts with reactive bone formation. Osteoblastoma is relatively rare, accounting for 3% of all benign bone tumors.⁴ It affects patients in the second to fourth decades of life with male predilection (2.5:1).⁴²

Histologically, osteoblastomas are identical to osteoid osteomas, but they are quite different regarding imaging findings and clinical manifestations. Compared to osteoid osteoma, osteoblastoma is less painful and less responsive to medication. Osteoblastoma is more expansile, larger (often arbitrarily distinguished from an osteoid osteoma by a measurement of more than 2 cm; mostly in the 3 to 10 cm range), and has less reactive adjacent bone change.⁴³ Unlike osteoid osteomas that more commonly involve the long tubular bones, osteoblastomas are most frequently found in the spine or flat bones⁴³; long tubular bone involvement is seen in 35% of cases, mostly in the diaphysis.

Radiographic features of osteoblastomas are nondiagnostic in most cases; the lesions may appear purely osteolytic or purely osteosclerotic or may demonstrate a combination of the two. In the long tubular bones, osteoblastomas may have an intramedullary or cortical origin. The appearance is usually that of an expansile, predominantly osteolytic lesion with an ossified matrix and reactive sclerosis. While CT is best for showing the calcified matrix and outer bony cortex (Fig. 23.11), MRI is excellent at discriminating the tumor from associated marrow edema and showing soft tissue changes. Osteoblastomas are highly vascularized and demonstrate a dense capillary blush on angiogram. Bone scintigraphy can help pinpoint the tumor site, especially in those occurring in the posterior vertebral column, and shows increased uptake of the radionuclide in the lesion.⁴⁴

Some osteoblastomas, in particular those arising from the posterior elements of the spine, have an ABC-like appearance. In other locations, the appearance of osteoblastoma is variable, and the differential diagnosis includes osteoid osteoma, SBC, ABC, eosinophilic granuloma, enchondroma, chondromyxoid fibroma, and fibrous dysplasia.

FIGURE 23.10 Osteoid osteoma of the distal femoral epiphysis in a 9-year-old boy. A: The en bloc resection specimen shows a nidus surrounded by a bony rim. B: The zonal architecture is appreciable microscopically (hematoxylin and eosin, original magnification, 40×). C: In the center, the nidus consists of abundant osteoblasts and a poorly mineralized osteoid matrix (hematoxylin and eosin, original magnification, 600×).

Curettage or en bloc surgical resection is the current management of choice for osteoblastomas.

Fibrous Cortical Defect/Nonossifying Fibroma

Fibrous cortical defects (FCDs) and nonossifying fibromas (NOFs) are benign fibrous lesions of bone and are histologically identical to each other. FCD is confined to the cortex of the bone and is smaller than 2 cm in size. NOF, also known as fibroxanthoma, has an eccentric location with medullary extension and is equal or larger than 2 cm in size. FCD is essentially a normal variant and is seen in children during skeletal maturation at age 4 to 8 years. Most (>70%) NOFs occur in teenagers.⁴ FCD and NOF are the most common benign bone lesions, seen in up to 40% of children.⁴

FIGURE 23.11 Osteoblastoma in an 11-year-old girl. A: Frontal rib radiograph shows an expansile bony mass (asterisk) involving the posterior arc of the left seventh rib near the costovertebral junction. There is right convex thoracic scoliosis, which could be pain related. B: Axial CT image demonstrates an ill-defined expansile bony lesion (arrow) with mixed lucencies and ossified matrix in the left-sided rib. No cortical breakdown is seen.

FIGURE 23.12 Fibrous cortical defect (FCD) versus nonossifying fibroma (NOF). A: FCD: A small cortical-based elongated radiolucent lesion is noted in the distal femur medially. The lesion is confined to the cortex suggesting a FCD (arrow). B: NOF: A radiolucent lesion with a well-demarcated thin sclerotic rim is seen in the distal femur. The lesion has an eccentric location with medullary extension suggesting a NOF (arrow). There is no periosteal reaction or cortical break.

FCDs are typically asymptomatic and detected incidentally; they spontaneously regress in most cases. NOFs are asymptomatic in most cases, but can present with pain associated with pathologic fractures. Although most NOFs present as a solitary lesion, there have been reported cases of multiple NOFs. Multiple NOFs along with café-au-lait skin lesions and other extraskeletal congenital malformations (mental retardation, ocular anomalies, cardiovascular malformations, hypogonadism) are known as Jaffe-Campanacci syndrome.⁴⁵ Some authors have proposed that it could be a different manifestation of neurofibromatosis type 1.⁴⁶,⁴⁷

Radiography is usually sufficient for the diagnosis of FCDs and NOFs. Both FCDs and NOFs most commonly develop in the metaphyses of the long bones of the lower extremities with a predilection for the posterior cortex. FCD and NOF demonstrate a well-defined and cortex-based (FCD) or eccentrically located (NOF) osteolytic lesion with an adjacent sclerotic rim. In general, the lesions are not accompanied by substantial periosteal reaction. The larger lesions tend to have a more elongated and multiloculated appearance with slight expansion and cortical thinning (Fig. 23.12). Main differential diagnoses include chondromyxoid fibroma, fibrous dysplasia, osteoid osteoma, bone abscess, and periosteal chondroma. FCDs and NOFs located in the metaphyses appear to migrate into the diaphysis with skeletal growth.

CT and MRI are not usually indicated, although CT may be useful in the cases of associated fracture. On MRI, the lesions are well-demarcated, typically in eccentric cortical locations, with low signal intensity on both T1- and T2-weighted MR images with enhancement depending on the evolving stage. As expected, an early active lesion appears hyperintense on T2-weighted MR images and enhances, while a regressing lesion shows a low signal on T2-weighted MR images with a lack of enhancement.⁴⁸ Whereas most NOFs can heal spontaneously with reactive sclerosis, some may persist into adulthood with a potential risk of developing a pathologic fracture.

Microscopically, FCD and NOF lesions are characterized by fibroblasts that are arranged in a storiform pattern, along with interspersed multinucleate giant cells and histiocytes (Fig. 23.13). Hemosiderin and lipid may accumulate within the histiocytes. No treatment is required for noncomplicated NOF or FCD.

Fibrous Dysplasia

Fibrous dysplasia is a benign fibroosseous lesion involving the medullary cavity of the bone. It affects children and young adults with an equal gender distribution. Fibrous dysplasia has monostotic and polyostotic forms; the monostotic type accounts for 70% to 80% of cases.⁴⁹ The facial bones, in particular the jaw bone, are most commonly affected; other affected sites include the skull, ribs, and long bones including the femur and tibia. The polyostotic form, also known as fibrocartilaginous dysplasia or generalized fibrocystic disease of bone, can be associated with syndromes, such as McCune-Albright syndrome (precocious puberty, cutaneous café-au-lait lesions, unilateral polyostotic fibrous dysplasia) (Fig. 23.14)⁵⁰,⁵¹ and Mazabraud syndrome (intramuscular myxomas, fibrous dysplasia).⁵²

FIGURE 23.13 Multiple nonossifying fibromas (NOFs) in the femur of an 11-year-old girl with neurofibromatosis type 1. Histologically, the NOFs show spindle-shaped fibroblasts in a storiform growth pattern; collections of macrophages with pale vacuolated cytoplasm represent lipidization (hematoxylin and eosin, original magnification, 200×).

FIGURE 23.14 Fibrous dysplasia in a 17-year-old girl with McCune-Albright syndrome. A, B: Frontal radiographs of the lower extremities show multiple bony lesions with a ground-glass matrix in the right femur, tibia, fibula, and talus. There are associated bony expansions, endosteal scalloping, and mild deformity, especially in the right proximal femur. This girl had a past history of precocious puberty and café-au-lait skin lesions.

On radiographs and CT, fibrous dysplasia demonstrates characteristic findings of a well-demarcated intramedullary lesion in a long bone with a ground-glass or hazy matrix. There is also endosteal scalloping with or without bone expansion (Fig. 23.14). “Shepherd crook deformity” is a result of repeated fractures and varus deformity of the proximal femur. There is no periosteal reaction unless it is fractured. Bone scintigraphy may help identify multiple lesions. On MRI, fibrous dysplasia has similar signal intensity to that of muscle on T1-weighted MR images and variable signal on T2-weighted MR images depending on the component (although showing T2 hyperintensity in most cases). After administration of gadolinium-based contrast material, the lesions usually enhance heterogeneously (Fig. 23.15).⁵³

FIGURE 23.15 Fibrous dysplasia in a 13-year-old boy. A: Frontal radiograph of right femur shows a well-demarcated ovoid radiopaque lesion (arrow) in the right proximal femur with a ground-glass matrix and a thin sclerotic rim. B, C: Coronal T2-weighted (B) and postcontrast fat-suppressed T1-weighted (C) MR images demonstrate an intramedullary hyperintense lesion with homogeneous enhancement (asterisk). Several smaller hyperintense T2 lesions are also noted surrounding the larger lesion representing foci of fibrous dysplasia (arrows).

Microscopically, fibrous dysplasia shows delicate spindled to stellate fibroblasts with variable amounts of admixed thin bony trabeculae without substantial osteoblastic rimming (Fig. 23.16). The prognosis for this benign disease is excellent.
However, affected pediatric patients can occasionally be left with deformities such as leg length discrepancy or bowing. Malignant transformation is exceptionally rare.

FIGURE 23.16 Fibrous dysplasia involving the femur of a 10-year-old girl who presented with a pathologic fracture. Microscopically, elongate and curvilinear bone spicules lie within a background of spindle to stellate fibroblasts (hematoxylin and eosin, original magnification, 100×).

FIGURE 23.17 Osteofibrous dysplasia in a 10-year-old girl. A: Lateral radiograph of tibia shows a mixed radiolucent and radiodense lesion (arrow) in the anterior aspect of the left proximal tibia, which presents with a sclerotic rim and bone expansion. Anterior bowing of the tibia is seen. B-D: Sagittal T1 (B), fat-suppressed T2-weighted (C) and axial postcontrast fat-suppressed (D) MR images demonstrate an expansile bony lesion (arrows) confined to the anterior aspect of the cortex of the tibia. The cortex is thinned out anteriorly, but no definite extraosseous soft tissue mass is formed. Diffuse enhancement of the tumor is seen.

Osteofibrous Dysplasia

Osteofibrous dysplasia is a benign fibroosseous lesion of bone. It is confined almost exclusively to the tibia. It occurs mostly during infancy and childhood and is rare after the age of 15 years. Osteofibrous dysplasia shares imaging features with adamantinoma, which has a progressive and malignant nature.⁵⁴,⁵⁵ It has been suggested that osteofibrous dysplasia may represent a precursor to, an incomplete sampling of, or a regression of adamantinoma.⁵⁶

On radiographs, osteofibrous dysplasia is typically seen as a relatively well-circumscribed complex radiolucent lesion with marginal sclerosis involving the anterior cortex of the tibia. There is typically associated cortical thickening and anterior bowing (Fig. 23.17). The eccentric cortical location differentiates it from fibrous dysplasia, which has a medullary location.
In contrast to adamantinoma, which often has a soft tissue component, osteofibrous dysplasia typically is not accompanied by a soft tissue mass. Pathologic fractures and congenital pseudoarthrosis can be associated with osteofibrous dysplasia. CT and MRI show the extent of the lesions and the degree of narrowing of the medullary cavity as well as the thinned outer cortex. MRI signal intensity of osteofibrous dysplasia is not specific; it is of low to intermediate signal on T1-weighted MR images and high signal on T2-weighted MR images with a varying degree of sclerosis seen as a low signal rim. There is usually strong intralesional enhancement after contrast administration (Fig. 23.17).

Microscopically, osteofibrous dysplasia contains delicate fibroblasts that produce wispy collagen (Fig. 23.18). Bony trabeculae are embedded within the fibrous proliferation. Occasional keratin-positive cells, occurring singly and not well visualized on routine stains, may be highlighted by immunohistochemical stains. Most osteofibrous dysplasias undergo spontaneous healing or regression. In rare cases, they may progress to adamantinoma.

Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH), previously known as eosinophilic granuloma or histiocytosis X, is a neoplastic proliferation of Langerhans cells. LCH is a spectrum of histiocytic disorders in which immature Langerhans cells proliferate in certain parts of the body. The skeletal system is affected in up to 80% of cases.⁴ LCH may occur at any age but is mostly seen under the age of 5 years.⁵⁷ Systemic involvement is seen in infants and younger pediatric patients. The prognosis is poor in children younger than 2 years.

FIGURE 23.18 Osteofibrous dysplasia in a 14-year-old boy with long-standing tibial bowing. A: The tibia is bowed, with a cut surface showing pale soft tissue with areas of cystification. B: Microscopically, bony spicules with variably prominent osteoblastic rimming lie within a background of fibroblasts and delicate wispy collagen (hematoxylin and eosin, original magnification, 400×).

Traditionally, LCH was divided into three categories according to clinical manifestations: eosinophilic granuloma (skeleton solely involved), Hand-Schuller-Christian disease (cranial lesions, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (disseminated form that occurs in infants and very young children). More practically, it can be categorized into a restricted (monostotic or polyostotic) or an extensive (visceral organ involvement) form. Clinical symptoms vary with involved organs, and affected pediatric patients often present with low-grade fever and raised inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein.

The skull is most frequently involved, although any of the axial or appendicular bones can be affected by LCH. A punched-out lytic lesion with a beveled edge is characteristic of the skull lesions. Beveled edges are explained by differential destruction of the inner and outer table of the skull (Fig. 23.19). When LCH involves the maxilla or mandible, it can result in “floating teeth.” This is the description given to the appearance on imaging of teeth “hanging in the wind” as a result of underlying alveolar bone destruction around the root of the teeth in patients with
LCH. LCH lesions of the mastoid bone cause ear symptoms. Therefore, the affected children are prone to treatment for otomastoiditis before being diagnosed with LCH. LCH is the most common cause of “vertebra plana” in children (Fig. 23.19). For spinal LCH lesions, MRI is needed to assess the presence of an epidural mass and cord compression. In long tubular bones, the lesions typically develop in the metaphysis or diaphysis. LCH involving uncommon locations such as the clavicle and small tubular bones has also been reported.⁵⁸

FIGURE 23.19 Multifocal Langerhans cell histiocytosis in a 6-month-old infant boy. A: Lateral skull radiograph shows multiple small punched-out bony lesions (arrows). B: Lateral thoracic spine radiograph shows a midthoracic vertebra plana (arrow).

FIGURE 23.20 Langerhans cell histiocytosis (LCH) in a 3-year-old boy. A: Frontal right femur radiograph shows a small ill-defined round to ovoid osteolytic lesion (arrow) with a relatively wide transition zone. The lesion is intramedullary and diaphyseal in location with multilayered periosteal reaction mimicking a malignant bone tumor such as Ewing sarcoma. B: Coronal fat-suppressed T2-weighted MR image demonstrates extensive marrow edema surrounding the femoral lesion. Hyperintense T2 soft tissue edema is noted circumferentially. These findings mimic osteomyelitis.

A skeletal survey is the first step to be used to investigate bone involvement of LCH despite some controversy regarding its sensitivity in comparison with bone scintigraphy, which is a radiation bearing.⁵⁹,⁶⁰ In children with multiple bone lesions, LCH should be included in the diagnostic considerations. Although radiological findings vary with the stage and disease activity, most LCH bone lesions are well-defined (“punched out”) and purely osteolytic with endosteal scalloping (Fig. 23.19). Sometimes, a permeative and aggressive pattern of bone destruction is present in association with either a single or multilayered periosteal reaction (Fig. 23.20), which may mimic findings of malignant bone tumors or osteomyelitis. Spontaneous regression is not
unusual in LCH, and involuting lesions appear more sclerotic and remodeled.

Cortical breakdown and soft tissue extension of LCH can be well demonstrated on CT; the margins are irregular and tend to be more sharply delineated as compared to those in Ewing sarcoma. On MRI, the bone lesions and soft tissue masses of LCH appear with low signal intensity on T1-weighted MR images, high signal intensity on T2-weighted MR images, and enhance with gadolinium. A soft tissue mass is present in about one-third of lesions. The associated inflammatory reaction causes bone and soft tissue edema, which enhance and may mimic osteomyelitis (Fig. 23.20). Involuting lesions can show low signal intensity on both T1- and T2-weighted MR images. WB MRI using the STIR sequence can provide valuable information in the initial workup as well as for patient monitoring and has many advantages over radiography and bone scintigraphy.⁶¹

Pathological evaluation of LCH shows sheets of Langerhans-type “histiocytes” as well as variable numbers of admixed eosinophils. LCH localized to the skeletal system carries a favorable prognosis. “Vertebra plana” tends to restore its height, and the involved bones remodel themselves after treatment. Reactivations are relatively common, occurring in about a quarter of the patients with systemic disease. LCH is treated by low-dose chemotherapy in extensive cases.

Chondroblastoma

Chondroblastoma is a benign cartilaginous neoplasm that affects exclusively the epiphyses or apophysis of long bones. It is most common in the second and third decades of life, and almost half of the lesions occur prior to physeal closure.⁶² Chondroblasts, chondroid matrix, giant cells, and foci of calcifications are seen on microscopic examination. Chondroblastomas can have a component of ABC. There are two main benign bone lesions that affect the epiphyses: chondroblastoma prior to skeletal maturation and GCT after physeal closure (Schematic B). The differential diagnosis for an epiphyseal lesion in a child can also include infectious osteomyelitis (Brodie abscess), which was discussed in Chapter 22.

FIGURE 23.21 Chondroblastoma in a 17-year-old girl. A: Frontal left ankle mortise view radiograph shows a well-demarcated osteolytic lesion (arrow) with a thin sclerotic rim in the lateral aspect of the left talus. B: A lytic bony lesion is more clearly seen on the coronal CT image (asterisk), which presents with surrounding reactive sclerosis. C: Axial T2-weighted MR image demonstrates a talar lesion with a fluid-fluid level (arrow) representing secondary aneurysmal bone cyst changes.

Chondroblastoma typically presents as an eccentric well-defined osteolytic lesion with a sclerotic rim in the epiphysis or apophysis (epiphysis equivalent) on radiographs (Fig. 23.21). Approximately one-third of cases show calcified chondroid matrix, which is best shown by CT⁶³,⁶⁴. Surrounding inflammatory changes are usually pronounced, resulting in adjacent bone marrow and soft tissue edema. Periosteal reaction is common due to an associated inflammatory response.⁶³ In contrast to most cartilaginous tumors, which are usually hyperintense on T2-weighted MR imaging, chondroblastoma can present with low- to intermediate-signal intensity on T2-weighted MR images. An ABC component can show cystic areas with or without fluid-fluid levels (Fig. 23.21). Chondroblastoma shows a low signal intensity rim on MRI. The bone marrow edema, soft tissue changes, and/or joint effusions can be pronounced. These findings can be important for differentiating chondroblastoma from other benign tumors. Chondroblastomas variably enhance, while Brodie abscesses typically show enhancement of the granulation tissue around the nonenhancing central abscess. The various signal intensities on T2-weighted MR imaging and enhancement patterns of chondroblastomas correlate well with their underlying histopathologic features, depending on the various amounts of chondroid matrix, calcifications, ABC components, and others.⁶⁴

Microscopically, chondroblastomas show sheets variably mature chondrocytes, often individually outlined by a rim of calcium (so-called “chicken-wire calcification”). Admixed osteoclast-like giant cells are frequently seen. Simple curettage
is curative in the majority of patients, although recurrence may be observed in 14% to 18%.⁶⁵

Chondromyxoid Fibroma

Chondromyxoid fibroma is a relatively rare benign cartilaginous tumor that usually involves the metaphyses of the extremity bones.⁶⁶ The proximal tibia is the most common location, followed by the fibula and the calcaneus.⁶⁷ Lesions involving the upper extremity bones, pelvis, and spine have also been described. It is more common in males in the second or third decades of life.⁶⁸

On radiographs, chondromyxoid fibroma shows an eccentric osteolytic lesion with a sclerotic margin in the metaphysis; its elongated shape parallels the axis of the long tubular bone. In small tubular bones, it can occupy the entire width of the medullary cavity with bony expansion and cortical thinning (Fig. 23.22). Calcifications are not usually present. MR signal characteristics are nonspecific and vary depending on the internal composition, but usually show low signal on T1- and high signal on T2-weighted MR images (Fig. 23.22).

FIGURE 23.22 Chondromyxoid fibroma in a 21-year-old woman. A: Lateral left elbow radiograph shows a well-circumscribed and expansile osteolytic lesion (arrow) in the proximal radius. B, C: Coronal T1-weighted (B) and fat-suppressed T2-weighted (C) MR images demonstrate an expansile lesion (arrow) with cortical thinning.

The current management of choice for chondromyxoid fibroma is surgical resection. Chondromyxoid fibromas can recur after surgical excision, but there is no known risk of malignant transformation.

Enchondroma

Enchondroma is a type of chondroma that involves the medullary cavity. It is composed of benign hyaline cartilage.
Chondromas may also occur in a juxtacortical or periosteal location. The peak age of juxtacortical chondromas is slightly younger than that of enchondromas.⁶⁹ Enchondromas commonly occur in the metaphyses or metadiaphyses of the small tubular bones of the hands and feet of children and adults. Enchondroma protuberans has been described as a variant of enchondroma that protrudes outward from one side of the affected bone mimicking an osteochondroma or juxtacortical chondroma.⁶⁴

FIGURE 23.23 Multiple enchondromatosis (Ollier disease) in an 11-year-old boy. Frontal hand radiograph shows multiple central and eccentric lytic lesions involving the metacarpal and phalangeal bones of the right third and fourth fingers.

FIGURE 23.24 Maffucci syndrome in a 21-year-old woman. Multiple bizarre, expansile lesions are noted involving the bones of both hands, which present with associated soft tissue calcifications (phleboliths) in the right wrist and right second and third fingers representing vascular lesions. Both ulnae are short and deformed, which is a common finding in multiple enchondromatosis.

Ollier disease and Maffucci syndrome are the most common subtypes of endochondromatosis, in which enchondromas can affect both sides of the body, but are random and asymmetric; generally, one side of the body is almost exclusively or more predominantly affected.⁷⁰ Enchondromas that arise in the metaphysis near the growth plates may impair physeal bone growth resulting in deformity and limb shortening. The risk of malignant transformation to chondrosarcoma is also a potential complication. Maffucci syndrome refers to multiple enchondromas in association with spindle cell hemangioma (Fig. 23.24). Both Ollier disease and Maffucci syndrome are known to be nonhereditary, usually sporadic disorders. The enchondromas and spindle cell hemangiomas usually harbor somatic mutations in the IDH1 or IDH2 gene.⁷¹

Radiographic evaluation is often sufficient to make a diagnosis of enchondroma. Typical radiographic findings include multiple expansile, radiolucent lesions with well-defined bony margins in the metaphyses of long bones and small tubular bones. Enchondromas develop in close proximity to the growth plate and then migrate toward the diaphysis (Figs. 23.23 and 23.24). In the long bones, they commonly show longitudinal streaks in the metaphysis that parallel the long bone axis. Metaphyseal widening by clustered enchondromas and variable shortening of metacarpal or phalangeal bones are seen in the hands (Figs. 23.23 and 23.24). On both radiography and CT, punctuate or chondroid calcifications can be seen. On MRI, signal intensity follows that of the cartilage at all sequences, revealing predominantly high signal intensity on T2-weighted MR images. Enhancement after gadolinium administration varies, and some lesions show enhancement in a peripheral, ring-and-arc pattern.

FIGURE 23.25 Periosteal chondroma in a 9-year-old boy. A: Lateral radiograph of the femur shows a saucerized cortical defect (arrow) with buttresses of solid periosteal new bone and reactive sclerosis. B: Sagittal fat-suppressed T2-weighted MR image demonstrates marked hyperintensity of the cortical/periosteal lesion (arrow) in keeping with hyaline cartilage in this case of juxta-cortical (periosteal) chondroma.

Periosteal Chondroma

Periosteal or juxtacortical chondroma is a distinctive benign cartilaginous tumor that affects the metaphyseal surface of tubular bones beneath the periosteum. The tumor occurs in children as well as adults younger than 30 years of age.⁷² It is a slow-growing tumor that causes erosion and sclerosis at the underlying bony cortex. Because it develops outward from the cortical surface of tubular bones, it can sometimes mimic osteochondroma or other benign or even malignant surface tumor.

The radiographic appearance of periosteal chondroma is often characteristic. A protruding bony mass with or without chondroid matrix is seen causing pressure erosion and remodeling at the cortex (saucerization) (Fig. 23.25). CT shows mineralization of the matrix. The interface between the tumor and the underlying bony cortex helps differentiate periosteal chondroma from sessile osteochondroma. The MRI appearance is similar to that of other cartilaginous tumors with low to iso-signal on T1-weighted MR images and foci of bright high signal on T2-weighted MR images (Fig. 23.25). Peripheral enhancement is typically noted after gadolinium administration (50).

Giant Cell Tumor of Bone

GCT is a benign but locally aggressive bone tumor. It accounts for 4% to 5% of all primary bone tumors and usually affects patients from 20 to 45 years of age with a female predilection.⁷³,⁷⁴ Uncommonly, younger pediatric patients are affected. The tumor typically involves the long tubular bones, specifically the distal femur and proximal tibia. Spinal involvement is described in a mainly adult population.⁷⁵ Although GCT is rare in skeletally immature patients, GCT can develop in the distal metaphysis and involve the epiphysis before the physis is closed. The tumor is located at the epimetaphysis in most cases, and tumor extension through growth plates may reflect its aggressiveness. Purely metaphyseal GCT has been observed only in the distal radius.⁷⁶ Pulmonary “ metastasis” occurs rarely; it is indolent, thought to represent tumor emboli rather than true metastasis.

Radiographically, GCT is typically a geographic, expansile, osteolytic lesion with ill-defined or sclerotic margins seen in the epimetaphysis of the tubular bones (Fig. 23.26). Matrix calcification is not a finding in GCT. In cases of expansile bone lesions, there can be cortical breakdown with soft tissue extension. No periosteal reaction is identified unless complicated by a pathologic fracture. MRI shows diverse findings depending on whether the tumor is mainly solid or cystic. A solid tumor shows intermediate signal intensity on both T1- and T2-weighted MR images with diffuse enhancement. There can be associated intratumoral hemorrhage and intratumoral ABC components. Fluid-fluid levels can be demonstrated on both CT and MRI.

Microscopically, GCT of bone shows numerous large multinucleate giant cells embedded in a background of mononuclear fibrohistiocytic cells (Fig. 23.27). En bloc resection is preferred over curettage due to the high recurrence rate of the latter procedure. Local recurrent is not common.

Malignant Osseous Tumors

Malignant bone tumors have a tendency to be found in the specific locations within the bones: the epiphysis, metaphysis, and diaphysis (Schematic C).

Osteosarcoma

Osteosarcoma is the most common primary malignant bone tumor in the pediatric population with an overall incidence of 5 per million patients under age 20 years.⁷⁷,⁷⁸ Osteosarcoma is slightly more common in males, and the peak incidence occurs in the 10 to 14 year age range, at the age of the growth
spurt.⁷⁷,⁷⁸ The most commonly affected sites are the metaphyses of the long bones, particularly about the knee (42% in femur, 19% in tibia) and the humerus (10%).⁷⁷,⁷⁸ Less commonly affected locations include the skull or jaw (8%) and pelvis (8%).⁷⁷,⁷⁸ Diaphyseal origin is less common, and epiphyseal origin is extremely rare.

FIGURE 23.26 Giant cell tumor in a 25-year-old man. A, B: Lateral knee radiograph (A) and sagittal CT image (B) show an expansile osteolytic lesion (arrow) in the proximal tibia involving the epimetaphysis. The outer cortex is thinned out with endosteal scalloping. Septa-like trabecular structures are noted on radiograph.

The current WHO classification categorizes osteosarcoma into eight subtypes: (1) conventional (chondroblastic, fibroblastic, or osteoblastic), (2) telangiectatic, (3) small cell, (4) low-grade central, (5) parosteal, (6) periosteal, (7) high-grade surface, and (8) secondary osteosarcomas.⁴ Conventional osteosarcoma is the most common high-grade type of osteosarcomas. Other high-grade variants include telangiectatic osteosarcoma, small cell osteosarcoma, high-grade surface osteosarcoma, and secondary osteosarcoma. Periosteal osteosarcoma is an intermediate-grade variant. Low-grade variants include low-grade central osteosarcoma and parosteal osteosarcoma.⁷⁸,⁷⁹ Among these eight subtypes of osteosarcoma, parosteal, periosteal, and high-grade surface osteosarcomas are juxtacortical osteosarcomas, which originate from the bone surface.

FIGURE 23.27 Giant cell tumor of bone involving the distal femoral epiphysis in a 17-year-old boy. A: Grossly, the curetted sample shows soft yellow-tan tissue admixed with blood. B: Microscopically, mononuclear cells are admixed with numerous multinucleate giant cells (hematoxylin and eosin, original magnification, 600×).

A few inherited risk factors for osteosarcoma account for a small minority of cases. These include retinoblastoma, Li-Fraumeni, Baller-Gerold, Bloom, McCune-Albright, OSLAM, Rothmund-Thomson, and Werner syndromes.⁸⁰,⁸¹ Rarely, multicentric osteosarcomas can occur at multiple skeletal sites spontaneously (synchronous) or subsequently that develop at multiple locations after a solitary lesion (metachronous).⁸² Extraskeletal osteosarcoma is extremely rare in children.⁸³ Localized pain and swelling are the most common presentations of osteosarcoma, and pathologic fracture can be the first presenting sign.

Curative treatment for high-grade osteosarcomas consists of surgery and chemotherapy. Most recent protocols for high-grade osteosarcomas include preoperative chemotherapy. The degree of histologic tumor response to preoperative chemotherapy offers the most important prognostic

information. Research protocols using diffusion-weighted MR images and dynamic contrast-enhanced MRI allow quantification of tumor necrosis and viable residual tumor.⁸⁴ Increased numeric values in apparent diffusion coefficient maps reflect tumor necrosis.⁸⁵ Low-grade variants, such as low-grade central or parosteal osteosarcomas, are treated by surgery only. Surgical removal is the primary treatment for metastatic and recurrent osteosarcomas as well. Pulmonary metastases occur most commonly and are seen in 10% to 20% of patients.⁷⁷

FIGURE 23.28 Variable radiographic findings of osteosarcoma. A, B: Pure osteolytic appearance. C, D: Mixed osteolytic and sclerotic appearances (arrows). E, F: Pure sclerotic pattern (arrows).

FIGURE 23.29 Classic radiographic appearances of osteosarcoma (A, B) and associated pathologic fracture. A: Osteosarcoma with “sunburst” appearance (black arrows) and osteoid matrix formation (white arrows). B: Codman triangle (arrows). C: Pathologic fracture (arrow).

Among eight subtypes of osteosarcoma, seven subtypes including conventional, telangiectatic, secondary, small cell, low-grade central, parosteal, periosteal, and high-grade surface osteosarcomas are further discussed in the following section; small cell type, which is exceedingly rare, is omitted in this chapter.

Conventional Osteosarcoma

Conventional osteosarcoma, also known as central high-grade intramedullary osteosarcoma, is the most common subtype and accounts for 80% to 90% of all osteosarcomas. Based on the predominant cell type, conventional osteosarcoma is divided into three subtypes: osteoblastic, chondroblastic, and fibroblastic osteosarcoma.

The radiographic appearance of conventional osteosarcoma varies from purely osteolytic to mixed osteolytic and sclerotic to purely sclerotic (Fig. 23.28). Osteoblastic osteosarcoma is the predominant type seen in 50% to 80% of all cases of osteosarcomas.⁸⁶ It demonstrates characteristic osteoid matrix with fluffy or cloud-like calcification in 90% of cases.⁸⁶ The chondroblastic type shows predominantly osteolytic lesions. The typical appearance of conventional osteosarcoma is a poorly defined intramedullary mass with metaphyseal origin and mixed osteolysis and sclerosis (Fig. 23.28). Additional radiographic features include cortical destruction, aggressive periosteal reaction such as onion skin, a Codman triangle, and sunburst appearance (Fig. 23.29), features that can also be appreciated upon gross examination of resected tumors (Fig. 23.30). Pathologic fractures are present in 15% to 20% of cases⁸⁶ (Fig. 23.29). The radiologic appearance of osteosarcomas in other rare locations is similar to that of long bone osteosarcomas.

MRI of conventional osteosarcoma primarily shows intermediate signal on T1-weighted MR images and areas of high signal intensity on water-sensitive sequences (Fig. 23.31). Epiphyseal extension through an open physis is often seen in metaphyseal osteosarcomas in children (Fig. 23.31).⁸⁷ Skip metastases have been reported in 6.5% of osteosarcomas and are associated with a poor prognosis.
Areas of necrosis with low T1- and high T2-weighted signal and hemorrhage with high signal on both T1- and T2-weighted MR images are common. Intravenous contrast administration typically shows heterogeneous enhancement of tumor. Mineralized matrix is represented by low-signal intensity on both T1- and T2-weighted MR images. In some cases, differentiation of intra- and extraosseous tumor extension from peritumoral edema is difficult, and tumor enhancement with intravenous contrast can be helpful for differentiation.⁸⁶

FIGURE 23.30 Conventional osteosarcoma, involving the proximal humerus in a 16-year-old boy. Tumor occupies the medullary space, lifts the periosteum (Codman triangle), destroys the cortex, and extends into the soft tissues.

FIGURE 23.31 Conventional osteosarcoma in a 13-year-old girl. A: Radiograph demonstrates mixed osteolytic and sclerotic lesions in the distal femur associated with “sunburst” appearance representing periosteal reaction (arrows). B: Coronal T1-weighted MR image demonstrates cortical disruption (black arrow). Epiphyseal extension of tumor (white arrows) is seen. C: Axial fat-suppressed T2-weighted MR image shows heterogeneous high T2 signal mass replacing bone marrow and an associated extraosseous mass formation (*). D: Sagittal postcontrast fat-suppressed T1-weighted MR image shows tumor necrosis (arrow).

Telangiectatic Osteosarcoma

Telangiectatic osteosarcoma is a rare subtype accounting for 2.5% to 12% of all osteosarcomas.⁸⁸ The lesion most commonly occurs in the metaphyses of the femur and tibia. Grossly, telangiectatic osteosarcoma is composed predominantly of large blood-filled cavities separated by septations as in an ABC⁸⁸ (Fig. 23.32). Therefore, the imaging appearance of a telangiectatic osteosarcoma often simulates an ABC. However, in telangiectatic osteosarcoma, high-grade sarcomatous cells line the septa.

FIGURE 23.32 Telangiectatic osteosarcoma involving the distal femur in a 15-year-old boy. This expansile tumor with large blood-filled cysts mimics aneurysmal bone cyst grossly.

On radiographs, geographic bone destruction without appreciable sclerosis and a wide zone of transition are the most common findings (Fig. 23.33). Expansile bone remodeling is observed, and this osseous expansion is often associated with pathologic fractures at initial presentation. Other common findings are aggressive periosteal reaction, cortical destruction, and soft tissue mass formation. Bone scintigraphy and FDG-PET CT demonstrate marked heterogeneous uptake with central photopenia called “donut sign,” which is seen in up to 65% of cases (Fig. 23.33).

In all cases, MR imaging evidence of hemorrhage, either as fluid levels or as areas of high signal intensity on both T1- and T2-weighted MR images, is observed. In fact, areas of hemorrhage reflected by high-signal intensity on T1-weighted MR images are seen in 52% of cases of telangiectatic osteosarcoma⁸⁸ (Fig. 23.33), but are highly unusual in other types of primary osseous neoplasm in the pediatric population. There are imaging features that favor telangiectatic osteosarcoma as opposed to benign ABCs. The first of these is thick, solid nodular tissue in the septa, which can be best depicted with postcontrast T1-weighted MR images. The second is matrix mineralization in the lesion, recognized in 58% of radiographs, and the third imaging feature is soft tissue formation and cortical destruction reflecting more aggressive growth (Fig. 23.33).⁸⁸ Despite these often helpful imaging features, biopsy is required to definitively differentiate telangiectatic osteosarcoma from ABC.

Low-Grade Central Osteosarcoma

Low-grade central osteosarcoma is a rare subtype accounting for 1.9% of all osteosarcomas. Imaging findings are variable; small lesions mimic benign fibrous lesions, and larger lesions display an aggressive nature on radiographs. Low-grade central osteosarcoma can be purely osteolytic or have a mixed appearance with osteolytic and sclerotic portions.⁸⁹ MRI typically shows cortical disruption and extraosseous mass formation, but imaging diagnosis is still challenging and requires confirmation with bone biopsy.⁹⁰,⁹¹

Parosteal Osteosarcoma

Parosteal osteosarcoma is the most common type of juxtacortical osteosarcoma and accounts for 4% of all
osteosarcomas.⁹² The long bone metaphysis is the primary site with the posterior aspect of the distal femur being most commonly involved. Histologically, parosteal osteosarcoma is usually low grade, but dedifferentiation mixed with high-grade disease is reported in 16% to 43% of cases.⁹³ Parosteal osteosarcoma originates from the outer layer of the periosteum.

FIGURE 23.33 Telangiectatic osteosarcoma in a 15-year-old boy. A: Frontal radiograph demonstrates an osteolytic lesion (arrows) with cortical disruption in the distal femur. B, C: Coronal T1- (B) and axial fat-suppressed T2-weighted (C) MR images demonstrate multicystic lesions with fluid-fluid levels (arrows, C). (Continued)

FIGURE 23.33 (Continued) D: Axial postcontrast fat-suppressed T1-weighted MR image demonstrates thick septal enhancement (arrows). E: FDG-PET image demonstrates peripheral increased tracer uptake, called “donut” sign (arrow).

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