Benign Tumors and Tumorlike Conditions of Bone



Benign Tumors and Tumorlike Conditions of Bone


Frank E. Chiarappa, MD

James H. Flint, MD, FACS, FAAOS


Dr. Flint or an immediate family member serves as a board member, owner, officer, or committee member of American Academy of Orthopaedic Surgeons. Neither Dr. Chiarappa nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter.





Introduction

It is important for orthopaedic surgeons to be aware of relevant epidemiology, pathophysiology, presentation, imaging, histology, treatment, and potential for recurrence/transformation of benign tumors and tumor-like conditions of bone. A review of the most current literature will provide information relevant to the diagnosis and management of these challenging conditions.


Cystic Lesions


Unicameral Bone Cyst

Unicameral bone cysts (UBCs), also known as simple or solitary bone cysts, are frequently seen in the metaphysis of skeletally immature patients, with a predilection for the proximal humerus and proximal femur. These lesions are most commonly identified in the first or second decade of life, and there is a 2:1 male:female distribution. UBCs are rarely found in adults, suggesting resolution during or after skeletal maturity. Lesions abutting the physis are classified as active, whereas those not directly adjacent are considered latent. The pathophysiology of UBC is thought to be related to a local increase in pressure due to venous obstruction; therefore this lesion represents a reactive condition rather than a true neoplasm. This is corroborated by histologic analysis of the cyst lining, which shows a bland fibrous lining without endothelial cells. The fluid contained within the cyst is proteinaceous, containing interleukins, prostaglandins, and matrix metalloproteinases. UBCs are often found incidentally or after a pathologic fracture. Radiographs are usually diagnostic. Occasionally, after a fracture, a pathognomonic fallen leaf sign (a small piece of cortical bone floating within the cyst) can be appreciated.

Treatment is based on the size and location of the lesion, as well as the age of the patient. Patients with symptomatic or high-risk lesions are generally treated with injection (sometimes requiring serial injections) or curettage and autologous bone grafting. According to a 2020 study, aspiration and injection of bioresorbable bone cements (porous beta-tricalcium phosphate and hydroxyapatite/calcium sulfate) have been investigated with good healing and a low reoperation rate,1 but there are no data showing a clinical advantage of these materials over conventional treatments. Fractures can usually be managed nonsurgically, although internal fixation may be appropriate in some locations, such as the proximal femur. Some lesions will resolve after fracture; if they persist and remain at risk for repeat fracture, prophylactic surgical treatment as mentioned previously should be considered.



Aneurysmal Bone Cyst

Aneurysmal bone cysts (ABCs) are seen in the metaphysis of children typically between 8 and 14 years of age, with a slight female preponderance. Although most lesions occur in the proximal humerus or about the knee, ABCs are also seen in the spine, pelvis, and clavicle. Unlike UBCs, which are not wider than the adjacent physis, ABCs expand and thin the cortex and can become quite large, as the name aneurysmal suggests. There are often septations appreciated on radiographs and fluid-fluid levels on MRI. However, it is important to note that fluid-fluid levels are not pathognomonic and may be seen in other conditions including telangiectatic osteosarcoma. ABCs can be primary or secondary, arising from another lesion. The pathophysiology is related to a translocation causing upregulation of USP-6, which in turn increases matrix metalloproteinases via nuclear factor kappa B.

Treatment consists of observation, injections (such as doxycycline, which demonstrates inhibition of matrix metalloproteinases), or surgery. The mainstay of surgical treatment is thorough curettage and grafting, with or without an adjuvant such as argon beam, ethanol, or phenol. Some lesions require internal fixation or even resection if they become extremely large. Approximately one-third of these lesion may recur, likely related to inadequate surgical treatment, aggressive biology, or a combination of both factors. A 2019 review of 65 patients treated with curettage with or without phenol suggests that phenol use does not decrease the risk of local recurrence as previously concluded.2 A 2021 review of the literature suggested that primary and secondary ABCs may have a different clinical course and concluded that polidocanol (a local anesthetic and sclerosing agent) injection is an effective minimally invasive treatment for primary ABCs.3


Chondroid Lesions


Osteochondroma

Osteochondromas are among the most common bone tumors. The true incidence is unknown as many lesions are asymptomatic. Osteochondromas often present as firm, painless masses and can be pedunculated or sessile. They often present with discomfort related to muscle, tendon, or nerve irritation; contact with the bone prominence; or fracture of the pedunculated stalk. More rarely, they can cause deformity or limb-length discrepancy by interfering with normal skeletal growth. The pathophysiology is thought to be a physeal aberrancy or extrusion. Like the normal physis, these lesions will continue to grow until skeletal maturity is reached. Osteochondromas appear to grow away from the joint; however, the adjacent joint is actually growing away from the base of the osteochondroma. Imaging and histology reveal a confluence of medullary contents between the bone itself and the tumor. Osteochondromas have a cartilage cap within which endochondral ossification occurs. If the cartilage cap exceeds 2 cm, transformation into chondrosarcoma should be considered.

Asymptomatic lesions do not require treatment. Surgical resection is indicated for symptomatic lesions, or those causing growth disturbances, such as angular deformity or limb-length discrepancy. Occasionally they may require treatment in adulthood if late symptoms such as impingement or an inflamed bursa overlying the lesion develop. Multiple hereditary exostosis is an autosomal dominant condition affecting 1:50,000 individuals because of mutations in genes EXT1, EXT2, or EXT3. Multiple hereditary exostosis results in numerous osteochondromas, which are often much more severe and debilitating than isolated lesions. A recent study evaluated full-body MRI as a screening method for assessing malignant transformation in multiple hereditary exostosis and enchondromatosis.4 It was concluded that MRI may be an effective screening tool but caution that long-term follow-up and cost analysis need to be performed before recommending this for all patients.2


Enchondroma and Other Chondromas


Enchondroma

Enchondromas are benign cartilaginous bone tumors. Approximately half occur in the hands and feet, but they are also found in the central portion of the metaphysis of long bones, particularly about the knee and proximal humerus. Most are painless, incidental findings without risk of fracture or malignancy. Pain can be a sign of malignant transformation, but a thorough examination should rule out other sources, such as rotator cuff symptomology. Imaging findings that may suggest potential malignancy include eccentric location, cortical breakthrough, large lucent areas, periosteal reaction, soft-tissue mass, or perilesional edema. Histologically, enchondromas cannot be readily distinguished from low-grade chondrosarcoma; therefore, biopsy is not performed routinely.

Treatment of enchondromas without concerning features generally consists of observation. When surgery is required, curettage and grafting with or without internal fixation is effective with a low rate of local recurrence. Local recurrence should raise concern for chondrosarcoma.


Periosteal Chondromas

Also known as juxtacortical chondromas, these surface-based benign chondral tumors arise from the periosteum. Surgical treatment consisting of curettage is indicated for symptomatic lesions.



Enchondromatosis (Ollier Disease and Maffucci Syndrome)

Ollier disease is a disfiguring condition resulting from numerous enchondromas (Figure 1) and is usually first diagnosed in childhood. Maffucci syndrome is even more rare and is characterized by extensive enchondromas as well as soft-tissue angiomas. Both conditions carry an approximately 30% risk of malignant transformation of enchondroma to chondrosarcoma. However, the risk of development of a malignancy by early adulthood, including visceral malignancies and leukemia, in patients with Maffucci syndrome is almost 100%.5


Chondroblastoma

Chondroblastoma is a benign-aggressive cartilaginous tumor arising in the epiphysis of long bones. Patients present at a mean age of 18 years (range, 8 to 48 years).6 Involvement of the femoral head is rare (4.5%) and occurs in slightly younger patients (mean age, 13.9 years).6 Patients often present with pain and occasionally joint stiffness or effusion. Radiographs reveal a well-marginated lucent lesion usually abutting the subchondral surface. There may be central mineralization and/or cortical destruction. A representative magnetic resonance image is shown in Figure 2, with the corresponding histology slide of a subsequent biopsy in Figure 3.

Treatment usually consists of extended curettage and local adjuvant treatment with bone grafting, with an effort being made to spare the physis. Although this lesion is benign, like giant cell tumor of bone, it can be associated with risk of local recurrence and, very rarely, pulmonary metastasis. A 2019 single-center review of 177 cases revealed 14% local recurrence at an average of 10 months.6 Another single-institution retrospective review of 38 cases showed a higher proportion of recurrence (11.8%) with curettage and hydrogen peroxide compared with curettage and grafting alone.7 This study was not randomized, and there is potential for selection bias for peroxide use based on surgeon preference, tumor size, and tumor location.







Chondromyxoid Fibroma

Chondromyxoid fibroma is an extremely rare bone tumor. It is often misdiagnosed and in some cases is a diagnosis of exclusion.8 This lesion is usually found in the metaphysis of patients in the second and third decades of life. Radiographs reveal an eccentric lucent lesion with well-defined sclerotic borders. MRI is useful in identifying the juxtaposed chondroid and myxoid components of this lesion. The mainstay of treatment includes curettage and grafting, with a 15% to 20% risk of local recurrence.


Fibrous Lesions


Nonossifying Fibroma

Nonossifying fibromas (NOFs), also known as fibrous cortical defects or fibroxanthomas, are among the most common bone tumors. It has been suggested that one-third of skeletally immature individuals have a nonossifying fibroma, although the true prevalence is unknown because most lesions are asymptomatic and thus found incidentally. NOFs are rarely seen in adults, and when they are incidentally identified in this population, they appear sclerotic rather than lucent. Radiographs will show a cortically based lucent lesion with well-defined sclerotic borders and often a soap bubble appearance without aggressive features. NOFs were previously thought to represent a reactive condition (such as UBC), but new data show activation of the RAS-MAPK pathway in 80% of cases, suggesting a true neoplastic etiology.9 The postpubertal regression remains enigmatic. Biopsy is not necessary as the diagnosis can be made radiographically. Surgery is rarely indicated, generally being reserved for lesions that become large enough to cause pain or fracture risk, particularly in young patients with significant skeletal growth remaining.


Fibrous Dysplasia

Fibrous dysplasia is a developmental abnormality that can be either monostotic (80%) or polyostotic, most commonly involving the femur. The monostotic variety usually presents before the age of 40 years, most
commonly in the second decade, and is often identified incidentally. Patients with more extensive skeletal disease may present at a younger age with pain or deformity. Radiographs reveal a central lesion of the diaphysis or metaphysis with variably defined borders, ground-glass intramedullary matrix, cortical thinning/expansion, and possible skeletal deformity such as varus (ie, shepherd’s crook) of the proximal femur. The MRI appearance is heterogeneous and therefore, in the absence of plain radiographs, can be misleading for a malignant condition. Histology reveals a pathognomonic lack of osteoblastic rimming adjacent woven bone. Observation is the mainstay of treatment for asymptomatic patients. Diphosphonates may be used for symptomatic lesions that do not require surgery or cannot be managed surgically. Surgical treatment is indicated for stabilization of impending or actual pathologic fractures, particularly in high-risk areas such as the femoral neck, or for correction of severe deformity.10 Of note, autologous bone graft is not beneficial because it will be quickly converted to dysplastic fibrous tissue. Although rare, there is a slight (1%) risk of malignant transformation into secondary bone sarcoma. There are some rare associated conditions. McCune-Albright syndrome consists of unilateral polyostotic fibrous dysplasia, café-au-lait spots (irregular “coast of Maine” borders), and precocious puberty.11 Mazabraud syndrome is a combination of polyostotic fibrous dysplasia and numerous soft-tissue myxomas. The true incidence of these syndromes is unknown with estimates of approximately 1 in 1,000,000. However,
the incidence of Mazabraud syndrome among patients with fibrous dysplasia is about 2%.












Giant Cell Tumor of Bone

Giant cell tumor (GCT) of bone is a benign-aggressive tumor of bone. GCT typically presents in the third or fourth decade of life, most commonly adjacent to the knee or in the distal radius. Pulmonary metastasis can occur in 1% to 2% of patients, but these are considered benign. A rare, malignant variant of GCT also exists; this, as well as giant-cell-rich osteosarcoma, should be ruled out during evaluation. Symptoms consist of progressive pain, particularly with weight bearing, and sometimes local swelling or a soft-tissue mass. Radiographs reveal an eccentric, geographic lesion with cortical destruction, located in the subchondral bone, directly adjacent to a joint. GCTs may form an expanded pseudocortex, but even this is often destroyed as the tumor grows larger.

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May 1, 2023 | Posted by in ORTHOPEDIC | Comments Off on Benign Tumors and Tumorlike Conditions of Bone

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