Benign Radiolucent Lesions
John A. Abraham, MD, FAAOS, FACS
Dr. Abraham or an immediate family member serves as a paid consultant to or is an employee of CarboFix and Osteocentric and has stock or stock options held in CarboFix and Osteocentric.
ABSTRACT
Benign cystic lesions include simple (also called unicameral) bone cysts, aneurysmal bone cysts, and cystic fibrous dysplasia. Certain location-specific benign radiolucent diagnoses exist as well, specifically calcaneal simple cysts and liposclerosing myxofibrous tumor, a solid benign tumor that has a marked predilection for the proximal femur. Malignant tumors can have cystic regions because of central necrosis and can be confused for an aneurysmal bone cyst. Telangiectatic osteosarcoma is an example of a malignant bone lesion that is expected to have fluid-filled areas evident on imaging. For this reason, care must be taken in the diagnosis and management of these lesions. Nonneoplastic conditions that have a cystic appearance include bone abscesses and intraosseous ganglions, otherwise known as geodes. Humeral pseudocyst is an example of a normal variant that has a radiolucent appearance on plain radiographic imaging and can be confused with a lesion if incorrectly identified.
Keywords:
benign; bone cyst; fibrous dysplasia; hemangioma
INTRODUCTION
Diagnosis of any bone lesion, including cystic lesions, relies on an accurate history and physical examination, as well as an accurate and clear understanding of the patient’s imaging. For all bone lesions, plain radiographic imaging is the starting point for evaluation. When plain radiographs of a bone lesion are evaluated, several features are considered, including size, location, the zone of transition or borders of the lesion, and, importantly, the matrix identified within the lesion. Radiolucent lesions of bone can be divided into benign, malignant, and nonneoplastic conditions. Generally, lesions that appear lucent on radiography are lesions that are made up of either a cystic or a fibrous matrix. Other matrices, such as bone and cartilage, have a distinct radiographic appearance that distinguishes them from radiolucent lesions, aiding in initial differential diagnosis.
BENIGN CYSTIC LESIONS
Unicameral Bone Cysts
Unicameral bone cyst (UBC) is the most common bone lesion found in the immature skeleton, as discussed in a 2022 study.1 This lesion is also referred to as a simple cyst or a solitary cyst and is most commonly seen in the proximal humerus and proximal femur (Figure 1). Although the etiology is not completely elucidated, it is thought that increased pressure in the region of the cyst at development leads to necrosis of local bone and then accumulation of fluid.2 UBC may thus be more of a reactive lesion than a true neoplasm. The fluid contained in the cyst is proteinaceous and straw colored and is not bloody except in patients with pathologic fracture. This characteristic distinguishes UBC from aneurysmal bone cyst (ABC), which has grossly bloody fluid. The cyst has been shown to contain prostaglandins, interleukins, and metalloproteinases.3 As discussed in a 2021 study, these lesions typically occur in the first 2 decades of life with an approximate 3:1 male predominance.4 The lesions may be painless, but pathologic fracture can occur in up to two-thirds of patients and can cause significant pain (Figure 2). Lesions large enough to present an impending risk for fracture are also painful. In some instances, fracture can precipitate healing, although this only occurs in fewer than 10% of cases.5 Most lesions become evident during childhood and may grow or be painful. It was previously widely held that these lesions generally heal spontaneously with skeletal maturity, but longer follow-up studies demonstrate that may not be the case.6 As discussed in a 2020 study, the lesions are seen infrequently in adults, in whom they are usually found in less common locations such as the calcaneus or ilium.7
 FIGURE 1 Radiograph shows the unicameral bone cyst of the proximal femur. Note the mild expansion of bone and the radiolucent center of the lesion. |
 FIGURE 2 A, Radiograph shows the unicameral bone cyst of the proximal humerus. Note the small cortical defect in the cortex. B, Radiograph shows that the bone is expanded to the width of the physis but not beyond. |
Imaging
Plain radiography of UBC is usually diagnostic. The UBC lesion is a lucent cystic lesion at the metaphysis of the bone and has one chamber, but occasionally may have a multichamber appearance because of partial internal septations within the lesion. The UBC lesion is central in the bone and may expand the contour of the bone slightly, but not to the extent seen in ABC and usually not wider than the width of the adjacent physis. The cortex is also thinned, but no areas of cortical perforation or soft-tissue mass are present. Pathologic fracture, however, can occur and is a common form of UBC presentation, as discussed in a 2022 study.8 In some instances, a small portion of the cortical wall breaks off and becomes suspended in the cystic cavity, giving rise radiographically to the classically described fallen leaf sign. This finding is considered pathognomonic for UBC and is a radiographic confirmation that there is no tissue within the cavity, but rather only fluid that allows the cortical fragment to drift throughout the cavity. Periosteal reaction is not seen unless in response to a fracture. UBCs are classified as active or latent on the basis of the relationship to the physis.9 Historically, lesions within 1 cm of the physis were defined as active, and those farther into the diaphyseal region were called latent. Over time, a lesion may seem to move toward the diaphysis. This appearance of movement is due to the new bone growth stemming from the physis and, in the case of a latent lesion, exceeding the growth of the cyst, thereby pushing it farther into the diaphysis. Latent lesions more than 2 cm from the epiphyseal plate have demonstrated improved outcomes with treatment, with 43% of these patients experiencing complete healing, as opposed to only 6% of patients with lesions within 2 cm of the physis experiencing complete healing.10 As discussed in a 2022 study, increased cystic fluid tartrate-resistant acid phosphatase levels may be helpful for evaluating the risk of postoperative recurrence in patients with UBCs.11
CT will show thinned cortical bone and may better define fallen fragments or pathologic fractures. MRI
will show homogenous fluid signal within the cavity. In the absence of fracture, fluid-fluid levels are usually not seen because of the absence of blood in the cavity. If bone scanning is performed, it shows peripheral uptake with central photopenia.
will show homogenous fluid signal within the cavity. In the absence of fracture, fluid-fluid levels are usually not seen because of the absence of blood in the cavity. If bone scanning is performed, it shows peripheral uptake with central photopenia.
Histology
Histology of the lesion shows a thin, fibrous lining. The lesion has no epithelial or endothelial component. The cells are fibroblastic, and the lining can also contain scattered giant cells, mesenchymal cells, and lymphocytes, all with bland appearance. The lining is not typically bloody unless pathologic fracture has occurred, so the large lakes of red blood cells seen in ABCs are absent. Eosinophilic fibrinous material known as cementum is sometimes seen.
Management
Optimal management of UBCs is a controversial topic, with several surgical procedures (with or without adjuncts) and minimally invasive techniques being recently studied.1,12,13,14 A 2020 survey of European Paediatric Orthopaedic Society and Pediatric Orthopaedic Society of North America members demonstrated wide discordance between the groups, not only in which lesions should be treated but also regarding the best treatment methods.15 Many lesions are painless and found incidentally. If imaging confirms a low level of concern for pathologic fracture, these lesions can be observed, although even for these lesions some recommend restriction from sports and activities, which may precipitate fracture. In the setting of a painful lesion or concern for pathologic fracture, treatment is generally considered. The most common procedures include corticosteroid injection, autologous bone marrow injection, curettage with or without grafting (using autologous bone graft, bone graft substitutes, or bone morphogenetic protein), and percutaneous decompression with or without intramedullary nailing. Currently, the optimal method of treatment is unknown; however, combination therapies may prove beneficial with further research.12,14 In the case of an actual pathologic fracture in the upper extremity, the fracture is generally allowed to heal before surgical intervention for the cyst itself is considered. Following fracture healing, the lesion can then be managed surgically or can be observed to see if the fracture will precipitate healing. In most cases, occurrence of a pathologic fracture is a reasonable indication for treatment of the cyst, because in general the occurrence of fracture does not lead to complete involution of the cyst. In the weight-bearing lower extremity, in particular the proximal femur, depending on the age of the patient and the size of the lesion, a more aggressive approach may be taken with prophylactic curettage, grafting, and internal fixation to avoid hip fracture.
Initial surgical management, particularly in the upper extremity, often consists of cyst aspiration and injection. It is unclear what the best injection material is; various agents have been tested. These agents include methylprednisolone acetate (historically used) as well as autogenous bone marrow, cancellous allograft, demineralized bone matrix, calcium sulfate, high-porosity hydroxyapatite, and fibrosing agents. One report described the use of platelet-rich plasma.16 Although no agent has been shown to be clearly superior, administering a combination of intralesional autologous bone marrow concentrate and equine-derived demineralized bone matrix led to better healing than using each of these agents in isolation.13 If a first injection fails, with failure defined as no radiographic signs of healing in a 3-month period, then a second or third injection may precipitate healing. If three injections fail, curettage and bone grafting with or without internal fixation may be considered. In general, the use of bone allograft is associated with adequate healing, so autogenous bone graft harvest is usually not necessary, although it is sometimes used. Some studies have also investigated cyst decompression and flexible intramedullary nailing without grafting.17,18
Calcaneal Bone Cysts
Simple calcaneal bone cysts occur fairly commonly, although pathologic fracture through this lesion is quite uncommon. Although the exact incidence is unknown because most are identified incidentally, several series of simple bone cysts show that the calcaneal variety accounts for anywhere from 2% to 11% of simple cysts. The precise algorithm for management of these lesions remains undefined because their clinical relevance is debated. For asymptomatic lesions under normal loading conditions, it is unclear if there is a risk of pathologic fracture; biomechanical studies have suggested that the strength of the calcaneus remains unchanged even in the presence of a cyst.19 Other clinical studies present series of pathologic fractures in patients with these lesions, although these fractures usually occur in previously painful lesions, or during sports or impact activities. Pathologic fractures of these cysts can be extremely difficult to manage because of the intrinsic complexity of any calcaneal fracture, along with the intra-articular nature of the fractures, which highlights the need for an accurate method of predicting which lesions are at risk of fracture. A subset of patients, predominantly adults, will have a variable amount of fat within the cyst, leading to the postulation of a corollary diagnosis of calcaneal intraosseous lipoma, but the relationship between these lesions is unknown.20,21
Imaging
Lesions are found in the anterior-central portion of the calcaneus, typically below the sulcus calcanei and the posterior articular facet of the talus. A well-circumscribed lucent area devoid of any trabeculae is seen on plain radiographic imaging (Figure 3, A). CT may show some thinning of the cortex in regions where the cyst abuts the endosteal surface. Frequently, extensive sclerosis is evident around the tumor, presumably relating to the remodeling to accommodate load throughout the calcaneus. MRI shows a fluid signal within the cyst (Figure 3, B), although some fat signal may be seen as well.
 FIGURE 3 A, Radiographic appearance of a calcaneal cyst demonstrates its purely lytic nature with no intralesional mineralization. B, T2-weighted magnetic resonance image shows the high water content of the lesion (arrow). |
Histology
Histologically, as with other simple cysts, a thin cyst wall is seen with fibrous lining, scattered giant cells, and thin, scattered trabeculae. Fat seen histologically usually has the appearance of marrow fat.
Management
As discussed in a 2023 study, management of calcaneal bone cysts is controversial, with three major courses to choose from: observation, injection, and surgery.22 However, selection of which course to pursue is difficult because there are no clear parameters that define cysts with pathologic fracture risk. One series of 50 patients suggested the following criteria as determinants of a critical lesion size: completely filling the calcaneus in the coronal plane, and occupying more than 30% of the transverse plane. In that series, 8 of the 17 patients who met the criteria were successfully treated nonsurgically. Below this critical size, however, none of the patients sustained pathologic fracture and none progressed. This finding suggests that these parameters may be used as a reasonable lower-limit threshold of nonsurgical management.23
Once the decision for surgical management has been made, several treatment options are available. These options include steroid, demineralized bone matrix or bone marrow aspirate injections, and curettage with or without bone grafting or bone graft substitute. Internal fixation may be necessary in the presence of fracture. Both open and minimally invasive or endoscopic procedures have been described.24 Most reported procedures have results comparable but not superior to open treatment. Reported success rates for open curettage and bone grafting procedures are approximately 60%.25
Aneurysmal Bone Cysts
ABC is a cystic neoplasm of bone generally affecting patients younger than 30 years (median age, 13 years) and has a slight female predominance (male-to-female ratio of 1:1.16). These lesions are usually found in the metaphyses of long bones, most commonly the proximal humerus, distal femur, and proximal tibia, as discussed in a 2020 study.26 ABCs also occur in locations such as the ilium, sacrum, and spine in 15% to 20% of patients,
which may present difficult anatomic challenges for treatment.4 Spinal lesions are generally located in the posterior elements and may extend into the vertebral body. The clinical presentation is usually one of pain that is mild to moderate and may be associated with swelling. Lesions in the spine may cause radiculopathy, vertebral collapse, scoliosis, and neurologic deficits. Pathologic fracture can occur as a result of an ABC and can cause exacerbation of pain. ABCs can also develop as a secondary lesion within another bone lesion in approximately 30% of cases.27 Osteoblastoma, chondroblastoma, giant cell tumor, fibrous dysplasia, or other bone lesion may be the primary lesion. In these secondary cases, a specific translocation, as discussed later, is not identified.
which may present difficult anatomic challenges for treatment.4 Spinal lesions are generally located in the posterior elements and may extend into the vertebral body. The clinical presentation is usually one of pain that is mild to moderate and may be associated with swelling. Lesions in the spine may cause radiculopathy, vertebral collapse, scoliosis, and neurologic deficits. Pathologic fracture can occur as a result of an ABC and can cause exacerbation of pain. ABCs can also develop as a secondary lesion within another bone lesion in approximately 30% of cases.27 Osteoblastoma, chondroblastoma, giant cell tumor, fibrous dysplasia, or other bone lesion may be the primary lesion. In these secondary cases, a specific translocation, as discussed later, is not identified.
ABC can be seen as a primary lesion or as a secondary component of another bone lesion. Once thought to potentially be a reactive lesion secondary to local circulatory disturbance, primary ABCs are now known to be a result of the translocation of USP6 (also known as TRE17) leading to its upregulation, whereas secondary ABCs are not associated with USP6 dysregulation.28,29 The induction of matrix metalloproteinase 9 in response to the presence of the upregulated ubiquitin-specific protease fusion protein is thought to be responsible for the pathogenesis of ABCs.30
Imaging
Plain radiography of an ABC shows an eccentric lucent bone lesion at the metaphysis of the bone, bounded by a thin cortical rim (Figure 4, A and B). Even in the most extensive cases, a thin bony rim, or at least a portion of one, can be seen at the periphery of the cyst. The width of the cyst may be wider than that of the metaphysis; this feature distinguishes ABCs from UBCs, which generally do not expand wider than the adjacent physis.31 The cyst may have multiple fluid-filled or blood-filled chambers separated by bony septa. Periosteal elevation and new bone formation can be seen at the junction of the cyst with normal host bone. MRI or CT shows multiloculated fluid-filled or blood-filled chambers, and fluid-fluid levels are a characteristic, but not diagnostic, feature (Figure 4, C). A soft-tissue mass can arise from the lesion and extend beyond the bone into the adjacent tissues. Bone scan will show uptake in the region of the lesion and may have an area of decreased uptake centrally.
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