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      Current strategies for the treatment of solitary and aneurysmal bone cysts: A review of the literature

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          Highlights

          • SBCs can mostly be treated conservatively.

          • In ABCs a biopsy is compulsory.

          • ABCs can be treated by polidocanol instillations adequately.

          Abstract

          This review of the literature aims to compare the etiology, the pathogenesis, the clinical diagnostics and the relevant treatment options of two different types of cystic bone lesions: the solitary bone cyst (SBC) and the aneurysmal bone cyst (ABC). Whereas the clinical symptoms and the radiographic appearance can be similar, the diagnostic pathway and the treatment options are clearly different.

          The solitary bone cyst (SBC) represents a tumor-like bone lesion, occurring most frequently in the humerus and femur in children and adolescents. Pain caused by intercurrent pathological fractures is often the first symptom, and up to 87% of the cysts are associated with pathological fractures. In the majority of cases SBCs can be treated conservatively, especially in the upper extremity. However, if a fracture is completely dislocated, joint affecting, unstable or open, surgical treatment is necessary. Pain under weight bearing or regaining the ability to mobilize after fracture timely can necessitate surgical treatment in SBCs affecting the lower extremity. Spontaneous resolution can be seen in rare cases.

          The aneurysmal bone cyst (ABC) is a benign, locally aggressive tumor that occurs in childhood and early adulthood. It usually affects the metaphysis of long bones but can also occur in the spine or the pelvis. ABC can be primary but also secondary to other bone pathologies. The diagnosis has to be confirmed by biopsy and histopathological examinations. With cytogenetic studies and the detection of specific translocations of the ubiquitin-specific protease (USP) 6 gene primary ABCs can be differentiated from secondary ABCs and other bone lesions. Among various modalities of treatment i.e. en bloc resection, intralesional curettage with adjuvants, embolization or the systemic application of denosumab, intralesional sclerotherapy using polidocanol is an effective and minimally invasive treatment of primary ABCs.

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          Most cited references71

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          USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts.

          Aneurysmal bone cyst (ABC) is a locally recurrent bone lesion that has been regarded as a reactive process. Recently, a neoplastic basis in primary ABC was evidenced by demonstration of clonal chromosome band 17p13 translocations that place the USP6 (TRE2 or TRE17) oncogene under the regulatory influence of the highly active CDH11 promoter. Herein, we report CDH11 and/or USP6 rearrangements in 36 of 52 primary ABCs (69%), of which 10 had CDH11-USP6 fusion, 23 had variant USP6 rearrangements without CDH11 rearrangement, and three had variant CDH11 rearrangements without USP6 rearrangement. USP6 and CDH11 rearrangements were restricted to spindle cells in the ABC and were not found in multinucleated giant cells, inflammatory cells, endothelial cells, or osteoblasts. CDH11 and USP6 rearrangements did not correlate with recurrence-free survival, or with other clinicopathological features. CDH11 and USP6 rearrangements were not found in any of 17 secondary ABC associated with giant cell tumor, chondroblastoma, osteoblastoma, and fibrous dysplasia. These findings demonstrate that primary ABC are mesenchymal neoplasms exhibiting USP6 and/or CDH11 oncogenic rearrangements. By contrast, secondary ABC lack CDH11 and USP6 rearrangements, and although morphological mimics of primary ABC, appear to represent a non-specific morphological pattern of a diverse group of non-ABC neoplasms.
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            Bone cysts: unicameral and aneurysmal bone cyst.

            Simple and aneurysmal bone cysts are benign lytic bone lesions, usually encountered in children and adolescents. Simple bone cyst is a cystic, fluid-filled lesion, which may be unicameral (UBC) or partially separated. UBC can involve all bones, but usually the long bone metaphysis and otherwise primarily the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC) is an expansive and hemorrhagic tumor, usually showing characteristic translocation. About 30% of ABCs are secondary, without translocation; they occur in reaction to another, usually benign, bone lesion. ABCs are metaphyseal, excentric, bulging, fluid-filled and multicameral, and may develop in all bones of the skeleton. On MRI, the fluid level is evocative. It is mandatory to distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve spontaneously between adolescence and adulthood; the main concern is the risk of pathologic fracture. Treatment in non-threatening forms consists in intracystic injection of methylprednisolone. When there is a risk of fracture, especially of the femoral neck, surgery with curettage, filling with bone substitute or graft and osteosynthesis may be required. ABCs are potentially more aggressive, with a risk of bone destruction. Diagnosis must systematically be confirmed by biopsy, identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra-lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and in aggressive lesions with a risk of fracture, surgical treatment should be preferred, possibly after preoperative embolization. The risk of malignant transformation is very low, except in case of radiation therapy.
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              Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts.

              Aneurysmal bone cysts (ABCs) are expansive and destructive lesions positive for osteoclast markers, resembling benign giant cell tumors (GCTs). Treatment options include surgical resection, curettage and cavity filling, embolization, injection of fibrosing agents, or radiotherapy. Particularly in children and adolescents with spinal ABCs, these options may be unsatisfactory, and innovative forms of treatment are needed. Denosumab is a human monoclonal antibody that inhibits osteoclast function by blocking the cytokine receptor activator of the nuclear factor-kappa B ligand. Satisfactory results with denosumab in treating GCTs and immunohistochemical similarities suggest that it may also have positive effects on ABCs. This report is the first description of the therapeutic use of denosumab in two patients with spinal ABCs. Two boys (aged 8 and 11) had recurrent ABCs at C5 after surgery with intralesional tumor resection. Treatment options were discussed by the interdisciplinary tumor board. Arterial embolization was attempted, but failed due to an absence of appropriate afferent arteries. After the families had received extensive information and provided written consent, denosumab therapy was initiated as an individualized treatment, despite the absence as yet of scientific evidence. After the start of denosumab therapy, both patients recovered from pain and neurologic symptoms significantly and are now in a healthy condition with no severe side effects. Magnetic resonance imaging check-ups after 2 or 4 months of denosumab treatment, respectively, showed tumor regression in both patients. Longer follow-up and clinical studies are warranted to establish the value of denosumab in the treatment of ABCs.
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                Author and article information

                Contributors
                Journal
                J Bone Oncol
                J Bone Oncol
                Journal of Bone Oncology
                Elsevier
                2212-1366
                2212-1374
                20 July 2021
                October 2021
                20 July 2021
                : 30
                : 100384
                Affiliations
                [a ]Department of Orthopedics and Tumororthopedics, University Hospital Munster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany
                [b ]Department of Pediatric Orthopaedics, Deformity Reconstruction and Foot Surgery, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany
                Author notes
                [* ]Corresponding author. niklas.deventer@ 123456ukmuenster.de
                [1]

                Niklas and Nils Deventer contributed equally to this work.

                Article
                S2212-1374(21)00039-7 100384
                10.1016/j.jbo.2021.100384
                8326748
                34367902
                fd72f47b-b4cb-4521-934c-8b2a32687789
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 23 May 2021
                : 5 July 2021
                : 12 July 2021
                Categories
                Review Article

                abc, aneurysmal bone cyst,sbc, solitary bone cyst,aneurysmal bone cyst,solitary bone cyst,simple bone cyst,juvenile bone cyst

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