Nanopore DNA Sequencing Detected Chromothripsis-Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma.

An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood-filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high-grade surface osteosarcoma. A 10-year-old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid-fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm2) and lace-like osteoid formation, which was diagnosed as a high-grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as "possibly osteoblastoma." The patient was disease-free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement. The fusion gene was further validated using reverse transcription-polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non-ossifying fibroma using t-distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis.

Aneurysmal bone cysts: A UK wide tumor center experience.

BACKGROUND AND OBJECTIVES: This multicenter retrospective series of consecutive extra-spinal aneurysmal bone cysts aims to identify risk factors for treatment failure. METHODS: Aneurysmal bone cysts treated within seven collaborating centers with over 12-months follow-up were eligible for inclusion. Survival analyses were performed to identify variables associated with recurrence using log-rank tests and Cox proportional hazard regression. RESULTS: One hundred and fifteen (M:F 60:55) patients were included. Median age at presentation was 13 years and median follow-up was 27 months. Seventy-five patients underwent surgical curettage and 27% of these required further intervention for recurrence. Of the 30 patients who underwent biopsy with limited percutaneous curettage as initial procedure, 47% required no further treatment. Patients under 13 years (log-rank p = 0.006, HR 2.3, p = 0.011) and those treated who had limited curettage (log-rank p = 0.001, HR 2.7, p = 0.002) had a higher risk of recurrence/persistence. CONCLUSIONS: There is a high risk of recurrence following surgical treatment for aneurysmal bone cysts and this risk is higher in young patients. However, the cyst heals in a substantial number of patients who have a limited curettage at the time of biopsy.

A rare case of aneurysmal bone cyst of the anterior clinoid process in an 18-year-old female mimicking optic neuritis.

BACKGROUND: Aneurysmal bone cyst (ABC) is an uncommon, benign, vascular multicystic bony lesion that most frequently develops in the first two decades of life. The metaphysis of long bones, pelvic, and vertebral column are the most common locations. The precise underlying pathophysiology of ABCs formation remains unclear; however, it is believed that reactive processes subsequent to trauma or vascular disturbance may play an important role. Involvement of the skull base rarely occurs with a prevalence of up to 5% of intracranial ABCs. CASE PRESENTATIONS: An 18-year-old adolescent female with a history of progressive blurred vision since three months ago presented to our office. The brain and orbital MRI demonstrated no abnormal findings. After three months of glucocorticoid treatment with the diagnosis of multiple sclerosis, the visual impairment of the left eye deteriorated abruptly. The patient underwent an MRI and the imaging study demonstrated a well-defined 30 × 22 × 20-mm lesion at the anterior clinoid process with an extension to the optic canal and ethmoid sinus. The patient underwent pterional craniotomy, and the tumor was resected. The histopathological examination was suggestive of ABC. CONCLUSION: ABC and other conditions should be considered in young-age people with an early unilateral decline in vision and imaging studies should be obtained in early stages and during follow-ups.

Unusual presentation of aneurysmal bone cyst (ABC) in children: pediatric intracranial osteosarcoma with secondary ABC.

A 13-year-old female patient presented with painless vision loss and proptosis for 18 months. Imaging findings were highly suggestive of a supraorbital aneurysmal bone cyst (ABC) for which she underwent complete surgical excision. Postoperatively, she developed left hemiparesis. Computed tomography angiography (CTA) revealed right complete internal carotid arterial (ICA) thrombosis. This was managed conservatively, and she improved in hemiparesis over the next 3 weeks. Histopathology report revealed osteosarcoma with secondary ABC, for which she was referred for radiotherapy. At 1.5 months follow-up, the patient's left lower limb power improved to 4 + /5. She was walking without support, and her left upper limb power was 4/5.

Adjunct role of liquid absolute alcohol intralesional sclerotherapy during the surgical management of spinal primary aneurysmal bone cyst in a child: a technical case report.

BACKGROUND: Aneurysmal bone cyst is composed of variable -sized cystic blood-filled spaces separated by connective tissue septae. First-line surgical resection of spinal aneurysmal bone cyst in a child with limited total blood volume can lead to massive intraoperative bleeding, thus limiting extent of resection. Our Centre's has good experience of using absolute alcohol as an effective immediate devascularizing agent during vertebral hemangioma surgery in children. MATERIAL AND METHODS: We report the first case of pediatric lumbar primary aneurysmal bone cyst in which completely blood-less piecemeal total resection of the lesion was performed after intraoperative absolute alcohol intralesional sclerotherapy. RESULTS: Completely blood-less piecemeal total resection of the lumbar aneurysmal bone cyst was performed after intraoperative absolute alcohol intralesional sclerotherapy. CONCLUSION: Intraoperative absolute alcohol intralesional sclerotherapy is a very effective devascularizing adjunct for complete piecemeal resection of spinal aneurysmal bone cyst in children with limited blood volume.

[Pediatric neurosurgical treatment of aneurysmal bone cyst at the level of thoracic spine]. / Aneurysmás csontcysta gyermek-idegsebészeti megoldása a háti gerinc magasságában.

Aneurysmal bone cysts are benign but locally aggressive bone tumours, most often affecting children and young adults. In this case report, we present the clinical  picture of a 15-year-old boy with progressive, chronic back pain. An MRI of thoracic spine  confirmed a T2 cystic spinal tumour. After considering potential options surgical removal was our choice and gross total removal was achieved with T1-3 short-segment fixation. Aneurysmal bone cysts are often rapidly expanding lesions with vascular  transformation. In order to avoid irreversible damage, in addition to early diagnosis, it is necessary to carefully consider the therapeutic options, perform surgical removal and stabilization as necessary. In case of the presented patient, extensive surgical removal and short-segmentation were performed. At 18 months of follow-up, he had no complaints and was asymptomatic. Follow-up imaging studies showed no residual or recurrent tumour to date.

Denosumab in Giant Cell Rich Tumors of Bone: An Open-Label Multicenter Phase II Study.

BACKGROUND: Since giant cell tumors of bone (GCTB) and other giant cell rich tumors of bone (GCRTB) share the histological presence of osteoclastic giant cells and expression of RANK/RANKL, we hypothesized that GCRTB will respond similarly to denosumab as GCTB. The primary objective of this study was to determine the efficacy of denosumab in patients with GCRTB that have recurred or require morbid surgery. METHODS: In this open-label, multicenter, phase II trial, patients with GCRTB were included (June 2018-March 2020). Recruitment was stopped because of low accrual. Patients received denosumab (120 mg) subcutaneously (SC) on day 1 of every 4-week cycle with a loading dose of 120 mg SC on days 8 and 15. RESULTS: Three patients were enrolled. One withdrew consent before start of study. The remaining patients had central giant cell granuloma of the jawbone (CGCG). Median treatment duration was 15 cycles (range 12-18). In both subjects, improvement in ossification of lesions was seen. Median follow-up was 28.5 months (range 20-37). One patient developed a recurrence for which surgery was performed. CONCLUSION: Due to critical emerging real-world data of denosumab in GCRTBs, the study was prematurely stopped and not supportive of use of denosumab for this indication. (ClinicalTrials.gov Identifier: NCT03605199).

The role of vascular surgeons in the management of pediatric bone tumors.

OBJECTIVES: The objective of this study was to review the outcomes of a multidisciplinary approach to the surgical management of pediatric bone tumors with blood vessel involvement over a 14- year period. METHODS: A retrospective review was conducted of all pediatric bone tumor resections performed with the assistance of vascular surgery at our institution between January 2006 and January 2021. Inclusion criteria for the study included the presence of a vascular surgeon at the operative resection and radiographic evidence of major blood vessel involvement. RESULTS: From 2006 to 2021, 117 patients underwent a bone tumor resection by a single orthopedic surgeon/vascular surgeon team. Sixty were malignant tumors, and 57 were benign. Of the 117 procedures, 5.1% (6/117) required reconstruction of an artery; five in malignant cases and one in benign. No venous reconstructions were undertaken in this study. Ligation of a major artery without reconstruction was performed in 8.8% (5/57) of malignant and 1.7% (1/60) of benign resections. Despite this vessel-sparing approach, microscopic margins were clear in all cases. Local recurrence occurred in a single patient in the malignant group at 61 months. CONCLUSIONS: The ideal management of pediatric bone tumors with major blood vessel involvement remains poorly defined. Our results demonstrate that even in the setting of radiographic evidence of vessel involvement, a multidisciplinary team of vascular and orthopedic surgeons can employ a vessel-sparing approach with minimal blood loss, excellent limb salvage, and minimal local recurrence.

Giant cell tumor of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence.

BACKGROUND: Fluid-fluid levels (FFLs) is found in 10%-16% of giant cell tumor of bone (GCTB), and the presence of FFLs raises the suspicion of GCTB with secondary aneurysmal bone cyst (ABC), which can lead to increased intraoperative bleeding and, blurring the operative field, be associated with a risk of local recurrence. The first objective of this study is to determine whether secondary ABC is associated with a higher risk of local recurrence after curettage in patients with GCTB of the extremities. The second objective of this study is to investigate the sensitivity, specificity, positive predictive value, and negative predictive value of the presence of FFLs detected on magnetic resonance imaging (MRI) to diagnose secondary ABC associated with GCTB. METHODS: Two hundred and eighty patients with GCTB of the extremities who underwent curettage at the authors' institutions between 1980 and 2021 were included in this study. RESULTS: Secondary ABC was found in 36 of 280 patients (12.9%) and local recurrence occurred in 66 of 280 patients (23.6%). Multivariate analysis showed no significant correlation between secondary ABC and local recurrence (hazard ratio [HR]: 1.87 (95% confidence interval [CI]: 1.00-3.53]; p = 0.051). Preoperative MRI revealed FFLs in 13 of 82 patients (15.9%). Sensitivity, specificity, positive predictive value, and negative predictive value of FFLs detected on preoperative MRI to diagnose secondary ABC were 36.8%, 90.5%, 53.8%, and 82.6%, respectively. CONCLUSION: The results of this study showed that secondary ABC does not increase the risk of local recurrence after curettage in patients with GCTB of the extremities. Although rare, FFLs were present in patients with GCTB and half of those with FFLs detected on preoperative MRI had secondary ABC.

Frequency of translocation of USP-6 in the aneurysmal bone cyst of the jaw.

BACKGROUND: This study aims to detect USP6 translocation in aneurysmal cysts located in the jaw and to give an overview of demographic data. METHODS: The present retrospective cohort study includes 10 patients who underwent surgery due to an aneurysmal cyst of the jaw in our hospital between 2002 and 2021. Unstained formalin-fixed and paraffin-embedded tissue sections cut at 4 µm thickness were subjected to USP6 FISH testing. RESULTS: All patients underwent surgical treatment. In four of ten patients (40%) USP-6-translocations have been found. CONCLUSION: Based on the study, it is hypothesized that the aneurysmal bone cyst of the jaw bone may be subject to a different pathomechanism than that of the long bones. Therefore, it seems conceivable that the primary cause of aneurysmal bone cysts in the jaw might differ.

Benign Brain and Spinal Tumors Originating from Bone or Cartilage.

Benign osseocartilaginous tumors of the spine are overall uncommon, representing between 1 and 13% of all primary bone tumors and less than 10% of all spinal tumors. Tumors in this category include osteoblastic lesions such as the related osteoid osteoma and osteoblastoma, and cartilage-forming lesions including osteochondroma, chondroma, and chondroblastoma. Aneurysmal bone cysts, giant cell tumors of bone, and eosinophilic granulomas also comprise benign tumors of the spine arising from bone. There is significant heterogeneity in the epidemiology, molecular biology, imaging features, and optimal treatment of these lesions. For example, osteoid osteoma is characterized by high expression of the cyclooxygenase enzymes, making it amenable to treatment with anti-inflammatory drugs initially, whereas other lesions such as osteoblastoma may require intralesional curettage or en bloc resection sooner. Generally, en bloc resection is preferred when possible to minimize risk of recurrence. Further, some tumors may arise in the setting of syndromic conditions, such as multiple chondromas arising in Ollier disease or Maffucci syndrome, or as part of genetic disorders, such as osteochondromas in the context of hereditary multiple exostosis. These lesions may present with local pain, cause neurological compromise or be discovered incidentally on routine imaging. The Enneking classification and Weinstein-Boriani-Biagini system are routinely used to classify lesions and assist in surgical planning. More novel techniques such as radiofrequency ablation and laser photocoagulation have been applied for the treatment of osteoid osteoma and may have utility in the treatment of other lesion types. A multidisciplinary approach is critical in the management of benign lesions of the spine, and both chemotherapeutic and surgical approaches are routinely used.

Multimodality imaging features of USP6-associated neoplasms.

Since the discovery of USP6 gene rearrangements in aneurysmal bone cysts nearly 20 years ago, we have come to recognize that there is a family of USP6-driven mesenchymal neoplasms with overlapping clinical, morphologic, and imaging features. This family of neoplasms now includes myositis ossificans, aneurysmal bone cyst, nodular fasciitis, fibroma of tendon sheath, fibro-osseous pseudotumor of digits, and their associated variants. While generally benign and in many cases self-limiting, these lesions may undergo rapid growth, and be confused with malignant bone and soft tissue lesions, both clinically and on imaging. The purpose of this article is to review the imaging characteristics of the spectrum of USP6-driven neoplasms, highlight key features that allow distinction from malignant bone or soft tissue lesions, and discuss the role of imaging and molecular analysis in diagnosis.

Primary aneurysmal bone cyst of hands and feet: A series of 14 cases.

Aneurysmal bone cyst (ABC) is a relatively rare, benign bone tumor that occurs exceptionally in the hands and feet. The objective of this article is to present clinical, radiological, histopathological features and management of a series of 14 primary ABC cases in these unusual locations. Eight cases occurred in hands and six in feet. We present the first reported subungual case to occur in the hand. The average age of the patients was 26 years (range 7 to 49), with half being over the age of twenty at diagnosis. The male to female ration was 9:5. In radiological terms, ABC appeared as an expansive lesion with internal septa and without cortical disruption. Twelve cases displayed the classic multicystic morphology and two cases were of the solid variant. "Blue bone" was detected in 50 % of the specimens. Treatment consisted of curettage, excision, or amputation in all cases. Recurrence rate was observed in 35 % of the cases, with the similar ABC morphology as the original samples. New therapeutic options have been proposed on their own or in combination with surgery to reduce local recurrence rates.

Total en bloc spondylectomy of thoracic giant cell tumor with secondary aneurysmal bone cyst: case reports and review of literature.

Spinal giant cell tumor (GCT) combined with secondary aneurysmal bone cyst (ABC) is a locally aggressive primary bone tumor. Total en bloc spondylectomy has never been reported to treat thoracic GCT combined with secondary ABC. We retrospectively reviewed two cases of spinal GCT combined with secondary ABC. A 41-year-old male patient was presented with back pain due to irregular expansive bone destruction involving the T6 vertebral body and intraspinal space-occupying lesion. Total en bloc spondylectomy of T6 vertebra was performed with good neurological status after the surgery. A 29-year-old female patient was presented with right scapular region pain due to irregular expansive bone destruction involving the T5 vertebral body and intraspinal space-occupying lesion. Total en bloc spondylectomy of T5 vertebra was performed with good neurological status after the surgery. Adjuvant radiation therapy was applied after the surgery without local recurrence at the 12-month or 24-month follow-up. Spinal GCT combined with secondary ABC appears to have a high local recurrence rate. Therefore, total en bloc spondylectomy should be applied to treat thoracic GCT combined with secondary ABC.

Solid-variant aneurysmal bone cysts in the craniofacial skeleton: the role of genomic analysis.

BACKGROUND: Solid variant aneurysmal bone cysts (SVABCs) are a rare but well-described subtype of ABCs. While classic ABCs are readily identified radiographically, SVABCs lack these characteristic radiographic features and thus have a wide differential diagnosis on presentation (including Ewing sarcoma, Langerhans cell histiocytosis, osteosarcoma, metastasis, and giant cell tumor). Genomic/molecular analyses are often necessary for the diagnosis of SVABCs, with USP6 rearrangements being a characteristic finding. We present two cases in which genomic analysis was critical in the diagnosis of SVABCs and revealed unique gene fusions that may provide insight into SVABC pathogenesis. CASE DESCRIPTIONS: Two 13-year old male children presented to our institution with new mass lesions involving the craniofacial skeleton. Magnetic resonance imaging (MRI) in both cases revealed predominantly solid, avidly enhancing masses, one of the squamous portion of the temporal bone, and the other arising from the sphenopalatine foramen with extension into the ipsilateral maxillary and ethmoid sinuses. Histopathology displayed predominantly solid morphology, and next generation sequencing (NGS) revealed a FAT1-USP6 gene fusion in the temporal lesion, and a MIR22HG-USP6 gene fusion in the maxillofacial lesion, the latter of which was not identified on fluorescence in situ hybridization (FISH). These findings were most consistent with a diagnosis of SVABC in each case. CONCLUSIONS: These two cases highlight novel gene fusions in atypically located SVABCs and emphasize the ability of NGS to more accurately and consistently identify USP6 gene fusions, particularly in SVABCs that may otherwise be indistinguishable from alternative pathologies.

Aneurysmal bone cyst of the pelvis and sacrum: a single-center study of 17 cases.

BACKGROUND: The aneurysmal bone cyst (ABC) is a benign, but locally aggressive cystic lesion of the bone. It usually occurs in the metaphysis of long bones of adolescents and young adults but can also affect the pelvis. METHODS: This single-center study is a retrospective review of 17 patients with primary ABCs of the pelvis. It examines the importance of polidocanol instillations as minimally invasive treatment option for ABCs of the pelvis compared to intralesional curettage or marginal resection. RESULTS: Seventeen patients with the diagnosis of a primary ABC of the pelvis were included in the study. Six patients were male (35%) and 11 patients female (65%); the mean age was 18 (9-49) years. The mean follow-up time was 50 months (12-136 months). The most common location of manifestation was the pubis (6; 35%), followed by the ilium (6; 35%), the sacrum (3; 18%) and the ischium (2; 12%). Eight patients were treated by intralesional curettage with the use of adjuvants, one patient by marginal resection, seven by sequential instillation of polidocanol and one patient by simple observation. Five patients received an additional transarterial embolization. After intralesional curettage local recurrence was detected in 4/8 cases (50%). After instillation therapy six patients (86%) had a stable disease without recurrence, only one patient (14%) had a persistent disease with need of additional treatment and was therefore converted to intralesional curettage without local recurrence in the follow-up. CONCLUSIONS: Sequential instillations of polidocanol are a promising, minimally invasive treatment method for ABCs of the pelvis and can be well combined with transarterial embolization.

Doxycycline sclerotherapy of cervical spine aneurysmal bone cysts: single-institution 13-year experience.

BACKGROUND: Aneurysmal bone cysts (ABCs) are benign, locally aggressive neoplasms that typically affect patients during their first two decades of life. Curettage with or without bone grafting or adjuvants is the current standard treatment; however, other surgical and medical treatments, such as sclerotherapy, have been reported. Treatment options for cervical spine ABCs are more limited because the proximity of ABCs to critical structures leads to greater risk of spontaneous or treatment-related adverse events, including death. OBJECTIVE: To retrospectively review all children and young adults with cervical spine ABCs treated with doxycycline sclerotherapy at one referral center to assess its viability as a standalone treatment. MATERIALS AND METHODS: We retrospectively reviewed the clinical notes and imaging of 16 patients treated with doxycycline sclerotherapy for pathologically proven cervical spine ABCs at our institution between May 2008 and March 2021. All patients underwent image-guided percutaneous doxycycline sclerotherapy to ablate the ABC and stimulate bone formation. We assessed clinical outcomes through chart review and described post-treatment imaging outcomes using modified Neer scoring. RESULTS: Of the 16 total children and young adults treated, 2 were lost to follow-up, leaving 14 patients with a median age of 14.5 years. Twelve of these 14 patients were successfully treated with doxycycline sclerotherapy for a success rate of 86%. One patient experienced one treatment-related complication (Society of Interventional Radiology [SIR] adverse event classification D), before ultimately being successfully treated. Doxycycline treatment failed in two patients, who then underwent surgical management. Post-treatment imaging of successfully treated cases had a mean modified Neer score of 1.3, whereas post-treatment imaging in failed cases had a mean score of 3.5. CONCLUSION: Doxycycline sclerotherapy is a viable standalone treatment for cervical spine ABCs because it is safe and effective while avoiding the morbidity associated with open surgical treatments.

Percutaneous image-guided treatment of aneurysmal bone cysts: is there a superior treatment option?

BACKGROUND: Aneurysmal bone cysts (ABCs) are often treated with intralesional surgery (curettage) with or without adjuvant treatments. Side effects and conflicting results regarding recurrence rates do not suggest one clearly superior therapy. Percutaneous therapeutic options including sclerotherapy and thermal ablation have gained popularity as potential alternatives. OBJECTIVE: The purpose of this retrospective review is to report this institution's experience and results of various image-guided minimally invasive treatments in a single institution series of cases referred to interventional radiology by orthopedic surgery after surgical failure or in patients with anatomically challenging ABCs. MATERIALS AND METHODS: This study identified all patients ≤18 years old who received percutaneous therapy for an ABC, including cryoablation, doxycycline sclerotherapy, microwave ablation or a combination of these modalities. Procedural details, complications, imaging follow-up and clinical follow-up were analyzed. RESULTS: A total of 21 patients received 41 procedures, with major complications seen in 7.7% (3/39) of procedures involving cryoablation or doxycycline sclerotherapy. Patients receiving cryoablation required an average of 1.7 procedures (median: 1 procedure, range: 1-4 procedures) while patients receiving doxycycline sclerotherapy required an average of 3 procedures (median: 2 procedures, range: 1-6 procedures). Patients were followed clinically and with computed tomography or magnetic resonance imaging (average: 23.9 months, range: 3.9-68.3 months). Follow-up imaging demonstrated improvement in 17 (85%) patients. Clinically, 93.8% (15/16) of patients who presented with fracture or pain had markedly reduced or absent pain as well as no fractures. CONCLUSION: Percutaneous image-guided treatment of ABCs demonstrates a favorable efficacy and safety profile. Adding cryoablation may lead to fewer total procedures than using doxycycline sclerotherapy alone.

Update on aneurysmal bone cyst: pathophysiology, histology, imaging and treatment.

Aneurysmal bone cyst (ABC) is a benign but locally aggressive lesion that predominantly affects children and young adults. ABC, which accounts for approximately 70% of the cases, is now recognized to be a true neoplasm, whereas ABC-like changes associated to other bone neoplasms (also referred in the literature as secondary ABC) accounts for the remaining 30%. The solid variant of ABC is also considered a true neoplasm but is rare. ABC can involve any bone in the body, and although it has a metaphyseal preference, it can involve any part of a bone and soft tissues. As with any bone tumor, the initial evaluation of ABCs should be done with radiographs followed by magnetic resonance imaging or less frequently computed tomography for further characterization. The imaging appearance of ABC is variable; however, a lytic and expansile lesion with fluid-fluid levels is the most common presentation. The main differential diagnosis of an ABC in the pediatric population is unicameral bone cyst (UBC) and telangiectatic osteosarcoma, therefore a biopsy is recommended before treatment. The therapeutic options of ABC range from curettage with or without adjuncts such as phenol, liquid nitrogen, argon laser and bone grafting or bone substitutes to more recently employed alternatives such as image-guided sclerotherapy with various sclerosing agents and monoclonal antibodies (e.g., Denosumab).

Epithelioid osteoblastoma with secondary aneurysmal bone cyst and FOS gene rearrangement.

Epithelioid osteoblastoma, sometimes equated with aggressive osteoblastoma, is a variant of osteoblastoma that typically demonstrates more worrisome imaging and pathological features compared to conventional osteoblastoma. These more aggressive features can overlap with those seen in osteosarcoma, creating a diagnostic challenge for radiologists and pathologists. Recent identification of FOS and FOSB gene rearrangements in osteoid osteoma and osteoblastoma has allowed for greater diagnostic confidence following biopsy, but careful radiological-pathological correlation remains a key component for guiding appropriate management. Although the imaging features of conventional osteoblastoma have been previously described, there are limited examples in the literature of the imaging appearance of epithelioid osteoblastoma, and none with secondary aneurysmal bone cyst. In this case report, we detail the clinical, imaging, and histological characteristics of a proximal femoral epithelioid osteoblastoma which was pathologically confirmed by FOS and FOSB genetic testing. The initial imaging impression favored a malignancy, but when the biopsy results were correlated in a multidisciplinary fashion with the imaging, epithelioid osteoblastoma became the leading diagnosis which was subsequently genetically confirmed. This case emphasizes the value of multidisciplinary radiology-pathology correlation in routine practice.