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.

Analysis of Diagnosis and Treatment Strategies for Primary Juvenile Psammomatoid Ossifying Fibroma Complicated With Primary Aneurysmal Bone Cyst.

BACKGROUND: Juvenile Psammomatoid Ossifying Fibroma (JPOF) is a type of noncancerous bone tumor that usually affects adolescents in the craniomaxillofacial area. Clinical manifestations are usually symptoms caused by the tumor's invasive compression of surrounding tissues. Aneurysmal Bone Cyst (ABC) is also a benign bone tumor, and it typically occurs in long bones and the spine. Only 2% to 3% of cases occur in the head and neck. Due to the rarity of this combination of clinical cases, clinicians face difficulties in comprehensively understanding this complex lesion. Therefore, a comprehensive review of the clinical manifestations and characteristic imaging findings is necessary for surgeons. CASE PRESENTATIONS: On April 6, 2019, a 13-year-old boy presented with left maxillofacial bulge and pain for 1 month. Magnetic resonance imaging of the paranasal sinuses showed an irregular hive-like mass signal in the left maxillary sinus, and cystic changes with fluid levels were seen in the lesion. After the initial diagnosis of JPOF with primary ABC, we decided to perform a facial mid-facial resection of maxillary sinus tumor to remove the tumor tissue. Finally, after 3 recurrences and 4 operations, there was no tumor recurrence for 20 months after the last operation, and the patient was still under continuous follow-up. CONCLUSIONS: This case provided a reference for the diagnosis and treatment of JPOF combined with ABC. In particular, a new understanding of the association between the two diseases and the management of recurrence were proposed, which had the potential to improve clinical understanding of this complicated condition.

[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.

Aneurysmal bone cyst: Is selective arterial embolization effective as curettage and bone grafting?

INTRODUCTION: Aneurysmal bone cyst (ABC) is a lytic benign bone lesion representing about 1% of all primary bone tumors. Method to treat ABC's have developed over time. The standard of care cure for ABC has been curettage with or without bone grafting of the defect but is burdened by recurrence rates of approximately 25%-31%. Based on the assumption that ABCs usually supplied by one or more pathological feeding arteries, selective arterial embolization has been described as an adjuvant preoperative procedure to reduce intra-operative hemorrhage, and as primary treatment for lesions in difficult surgical access. In the current study, we therefore asked whether (1) a single or a repeat selective arterial embolization (SAE) for treating ABCs would produce comparable healing rates compared with curettage and bone grafting; (2) evaluated the relationship of recurrence in relation to the site of the cyst, the age, and gender of the patients; and (3) the two techniques differ in term of long-term complication. MATERIAL AND METHODS: We retrospectively reviewed 265 patients who underwent curettage and bone grafting or SAE performed at our institute from 1994 to 2018. The diagnosis of ABC was always established with percutaneous CT-guided biopsy or open biopsy. Patients were followed clinically with plain radiographs or CT scan at 3, 6, 9, and 12 months then annually in the absence of symptoms. Treatment success was determined evaluating pre- and postprocedural imaging according to Chang classification. RESULTS: Two hundred and nineteen were treated with curettage and bone grafting (curettage group), and 46 with SAE Group. Of the 219 patients treated with Curettage and bone grafting (curettage group), 165 out of 219 (75.3%) experienced bone healing, while local recurrence was observed in 54 cases (24.7%) after 12 months on average (range: 3-120 months) from surgery. After the first SAE, bone ossification was seen in 27 (58.7%), without needing any further treatment. Eleven recurred patients were treated with SAE (four patients need two while seven need three SAE to heal), and eight patients with curettage and bone grafting. Thirty-eight out of 46 (82%) patients experienced bone ossification regardless the number of SAE. The overall rate of local recurrence for all patients was 26.7%. SAE group presented a lower complication rate (6%) where two patients experienced skin necrosis, and one limb-length discrepancies (2% of all cohort). DISCUSSION: The use of SAE is an attractive option to treat ABC as it combines on one hand a lower complication rate than curettage and bone grafting, on the other it can be carried out in case of nonresectable ABCs, significantly reducing the size of viable ABC lesions, fostering bone remodeling and mineralization, and most importantly, significantly improving the patient's quality of life.

The treatment of aneurysmal bone cysts.

PURPOSE OF REVIEW: Aneurysmal bone cysts are rare, locally aggressive bone tumors. Optimal treatment of ABCs is still matter of debate as therapies including sclerotherapy, selective arterial embolization and systemic treatment with denosumab are increasingly utilized, in addition to or instead of traditional curettage. The purpose of this review is to discuss current concepts and difficulties in diagnosing and treating primary ABCs, based on latest available literature. RECENT FINDINGS: In diagnostics, multiple new fusion partners of USP-6 have been described on next-generation sequencing specifically for primary ABCs. In a recent systematic review, failure rates of percutaneous injections and surgery were comparable. In a literature review, the use of denosumab seemed effective but resulted in multiple cases of severe hypercalcemia in children. SUMMARY: Accurately diagnosing primary ABC is crucial for treatment decisions. Curettage remains a valid treatment option, especially with adjuvant burring, autogenous bone grafting and phenolization. Percutaneous sclerotherapy represents a solid alternative to surgery, with polidocanol showing good results in larger studies. Systematic therapy with denosumab exhibits favorable results but should be reserved in the pediatric population for unresectable lesions, as it may result in severe hypercalcemia in children. When selecting a treatment option, localization, stability and safety should be considered.

Aneurysmal Bone Cyst of the Orbit With USP6 Gene Rearrangement.

PURPOSE: Aneurysmal bone cyst (ABC) of the orbit is a very rare tumor, occurring mostly in the pediatric population, and can result in sight threatening complications and disfigurement. This review discusses previously reported cases with a focus on evolving treatment options and molecular genetics. METHODS: We report the youngest case of an orbital ABC with a confirmed gene fusion: a 17-month-old girl, with confirmed FGFR-UPS6 (Fibroblast Growth Factor Receptor 1-ubiquitin specific peptidase 6/tre-2). A literature search for relevant publications on the topic was performed via Medline and PubMed, with the appropriate data extracted. RESULTS: Thirty-two cases of orbital aneurysmal bone cyst were identified in the literature. Presentations are varied and can include pain, proptosis, decreased vision, and extraocular motility disturbance. Typical imaging and histopathology findings are discussed, in particular the usefulness of identifying USP6 gene arrangements. Treatment modalities are reviewed including surgery, embolization, and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors. Recurrences can occur, usually within 2 years. CONCLUSIONS: Orbital ABC is a neoplasm that presents unique diagnostic and treatment challenges. Gene rearrangements can confirm primary ABC and rule out other underlying pathology. Disfigurement and sight threatening complications can occur due to both the disease process and with treatment. Outcomes may be improved with the use of systemic therapy.

Large skull osteoblastoma presented as aneurysmal bone cyst (ABC).

Aneurysmal bone cysts (ABCs) are rare benign vascular bony lesions mostly encountered in young patients. These cysts can occur as primary lesions or, less frequently, secondary to other pathologies such as osteoblastomas. Skull ABCs are rare and can extend intracranially, presenting with hydrocephalus and bleeding. Here we illustrate the case of a 9-year-old male who presented with headache, nausea, and vomiting, without neurological deficit. Radiological investigations showed a soap-bubble lesion with mass effect over the right cerebellum. The patient underwent right sub-occipital craniotomy with marginal wide resection of the cystic lesion. The patient had excellent outcomes. The histopathological report was consistent with osteoblastoma with an aneurysmal bone cyst.

[Giant cell-containing tumors of bone and differential diagnoses]. / Riesenzell-haltige Tumoren des Knochens und Differenzialdiagnosen.

Osteoclastic giant cells represent a common cellular component of lesions arising in bone. Highlighting this morphological finding, the current WHO classification of bone tumors defines a diagnostic group comprising aneurysmal bone cyst, giant cell tumor of bone and non-ossifying fibroma, which may display morphologic similarities while being distinct with regard to molecular and biological features. Starting with these tumors - putting a focus on lesions arising in bone - this article gives a survey of other (chondrogenic and osteogenic) tumors that frequently contain osteoclastic giant cells, which may, particularly in small biopsies, enter differential diagnosis. Overlapping features with selected giant cell-containing soft tissue tumors, which may be of differential diagnostic relevance in daily routine, are discussed.

Aneurysmal bone cyst with an unusual clinical presentation and a novel VDR-USP6 fusion.

Aneurysmal bone cyst is a benign bone neoplasm that most commonly arises from the metaphyses of long bones in the first and second decades of life. Here, we describe a case of an aneurysmal bone cyst that occurred in the distal tibial diaphysis of a 72-year-old female that was concerning for malignancy on imaging, demonstrating cortical breakthrough and soft tissue extension. Histologically, the tumor showed the characteristic morphologic features of aneurysmal bone cyst. Fluorescence in situ hybridization was positive for USP6 rearrangement, and RNA sequencing revealed a USP6 gene fusion with VDR, a novel partner that encodes the vitamin D receptor and that has not been implicated previously in human neoplasia. This case highlights the diagnostic challenges presented by aneurysmal bone cyst in elderly adults, and it expands the genetic spectrum of USP6 rearrangements.

Clinicopathological and molecular characterisation of USP6-rearranged soft tissue neoplasms: the evidence of genetic relatedness indicates an expanding family with variable bone-forming capacity.

AIMS: USP6 rearrangement underpins self-limiting fibroblastic/myofibroblastic neoplasms, including nodular fasciitis (NF), myositis ossificans (MO), aneurysmal bone cyst (ABC), and related variants. The aim of this study was to characterise UPS6 and fusion partners in order to delineate the clinicopathological, genetic and bone-forming features in such lesions of soft tissue (ST). METHODS AND RESULTS: Break-apart fluorescence in-situ hybridisation (FISH) validated USP6 rearrangement in 31 of 35 NF [comprising three of three fasciitis ossificans (FO) cases, seven of eight cellular variant of fibroma of tendon sheath (C-FTS), four of six MO, three of three ST-ABC, and two of two fibro-osseous pseudotumours of digits (FOPD)]. As determined with FISH and reverse transcription polymerase chain reaction, MYH9-USP6 was the commonest fusion in four C-FTS and 20 NF, including one intravascular case and two infantile (one retroperitoneal) cases. The presence of MYH9-USP6 confirmed the diagnosis of two NFs> 50 mm with prominent ischaemic necrosis. COL1A1-USP6 was predominant in ossifying lesions, including all FO, MO, ST-ABC and FOPD with identified partner genes, and was also present in non-ossifying head and neck NF (HN-NF) and C-FTS in two cases each. A cervical NF of a 14-month-old girl harboured the novel COL1A2-USP6. Ossifying lesions showed considerable genetic and morphological overlaps. Sharing COL1A1-USP6, FO and FOPD showed similar central or haphazard bone matrix deposition. Besides zonation of outward bone maturation, four COL1A1-USP6-positive MO had incipient to sieve-like pseudocysts reminiscent of ST-ABC. CONCLUSION: MYH9-USP6 is present in some C-FTS and most NF, including rare variants, but is unrelated to bone formation. All bone-forming USP6-rearranged lesions adopt COL1A1 as the 5' partner, indicating close genetic kinships. However, COL1A1/COL1A2 also contributes to the pathogenesis of minor subsets of non-ossifying USP6-rearranged HN-NF and C-FTS.

Chondroblastoma of the patella with secondary aneurysmal bone cyst, an easily misdiagnosed bone tumor:a case report with literature review.

BACKGROUND: Chondroblastoma (CB) is a rare, primary, benign bone tumor that commonly affects men aged 15-20 years. It is usually detected in the epiphysis of the long bones, such as the proximal femur, humerus, and tibia. The patella is an infrequent site. CB with secondary aneurysmal bone cyst (ABC) is extremely rare in the patella, which can be easily confused with other common bone tumors of the patella. Thus, it is necessary to make the right diagnosis to get a good outcome. CASE PRESENTATION: We have presented here the case of a 30-year-old man who was suffering from anterior knee pain for the past 6 months that had aggravated 2 weeks before the presentation. Osteolytic bone destruction in the patella could be detected in both his X-ray and computed tomography (CT) examinations, while the magnetic resonance imaging (MRI) detected a fluid level. Accordingly, secondary ABC was presumed. We diagnosed the condition as giant cell tumor (GCT) with secondary ABC and, accordingly, performed curettage inside the focus region with autogenous bone grafting following the patient's medical history, physical manifestations, results of physical and ancillary examinations, and the disease characteristics. However, the intraoperative and postoperative outcomes indicated that the patient's histopathology was consistent with that of typical CB, suggesting a definitive error in diagnosis. Accordingly, the patient was finally diagnosed with patella CB along with secondary ABC. CONCLUSIONS: Past studies have demonstrated that the 3 commonest bone tumors affecting the patella are GCT, CB, and ABC. CB with secondary ABC can be easily misdiagnosed as GCT with secondary ABC or ABC. Performing incision biopsy or excision biopsy and conducting histological examination may be the most effective method for suspected CB with secondary ABC.

Atypical Presentation of Navicular Aneurysmal Bone Cyst in a Symptomatic Pediatric Flatfoot Deformity: A Case Report.

Aneurysmal bone cysts (ABCs) are rare in the foot, accounting for 4% to 6.3% of all ABCs found in the body. Approximately 80% of patients diagnosed with an ABC are in the second decade of life. While benign, pain and deformity are often the presenting symptoms. This report's objective is to describe, to our knowledge, the first reported case of a pediatric navicular ABC in association with pediatric flatfoot deformity that was successfully treated with curettage and bone grafting. An additional goal of the report is to highlight how the diagnosis of these osseous tumors can easily be missed given the overlap in symptoms with pediatric flatfoot deformity. An 11-year-old female presented to clinic with a chief complaint of painful, flatfoot deformity and discomfort to the medial midfoot after walking for more than 2 city blocks. The patient was conservatively treated for pediatric flatfoot deformity at an outside institution and advised that a surgical flatfoot reconstruction would be necessary to relieve her symptomology. On examination, the patient exhibited focal pain to the medial aspect of the navicular. Radiographs revealed an ill-defined, expansile, sclerotic lesion of the navicular, and MRI demonstrated a multicystic lesion filling the navicular, consistent with an ABC. Treatment included curettage and packing with allograft. At 1-year follow-up, the patient is well, with minimal pain and return to full activity without functional limitations. Local recurrence of an aneurysmal bone cyst following curettage and bone grafting is as high as 22% with patient age and lesion size comprising the main risk factors. This report demonstrates successful curettage of an ABC within the navicular and preservation of osseous articulations in a pediatric patient. At 1-year follow-up, the patient had minimal pain with no evidence of recurrence.

Pathologic evaluation of the solid variant of aneurysmal bone cysts with USP6 rearrangement with an emphasis on the frequent diagnostic pitfalls.

The solid variant of aneurysmal bone cyst (SVABC) is very uncommon and frequently misdiagnosed. We reevaluated and summarized the clinicopathologic features of 17 SVABCs and further discussed the use of this nomenclature to differ SVABCs from extragnathic giant cell reparative granuloma (GCRG) in the setting of the USP6 rearrangement era. The immunohistochemical markers included α-SMA, SATB2, AE1/AE3, Ki67, S100, CD68 and P63. USP-6 status was detected by fluorescence in situ hybridization using a break-apart probe. The 17 patients with SVABCs comprised 10 males and 7 females ranging in age from 4 to 70 years. The involved locations included the long bone (n = 11), hand (n = 4), rib (n = 1) and vertebra (n = 1). The lesions were characterized by proliferated spindle cells with scattered giant cells and hemorrhages with variable positive α-SMA, SATB2, CD68 and Ki-67 expression. All patients had USP6 rearrangements without H3F3A glycine 34 mutations. Our study reveals that SVABC shares similar clinical and histologic features with other bone lesions, which may lead to an erroneous diagnosis. The presence of an USP-6 rearrangement contributes to the diagnosis SVABC; SVABC and most of the previously documented extragnathic GCRGs may be considered within the umbrella of primary aneurysmal bone cysts.

Primary aneurysmal bone cyst of the scapula in adult patient: two case reports and a review of the literature.

Aneurysmal bone cyst (ABC) is a rare, benign but locally aggresive bone tumor of unknown origin tumor. It commonly affects children and usually occurs at the metaphysis of long bones. Scapula is a very rare location and ABCs of the scapula have been sparsely described in the literature. Differential diagnosis can be challenging as it shares common radiological and clinicopathological features with other benign and malignant bone tumors. The degree of diagnostic difficulty increases even more when an unusual tumor site has to be taken into account. Here, we describe rare and challenging cases of a primary ABC located at the scapula that was surgically treated. This is the first case report of ABC involving the scapula in adult patient.

RNA sequencing identifies a novel USP9X-USP6 promoter swap gene fusion in a primary aneurysmal bone cyst.

Primary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the noncoding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full-length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell-rich primary bone tumors. In this report, we present a case of a 16-year-old male with a primary ABC of the left distal femur. USP6 break apart fluorescence in situ hybridization was positive for a rearrangement and conventional chromosome analysis identified a reciprocal X;17 translocation. In order to identify the putative USP6 fusion partner, we performed RNA sequencing and uncovered a novel USP9X-USP6 promoter swap fusion. This result was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and by mate pair sequencing thus showing the utility of these alternative methodologies in identifying novel fusion candidates. Ubiquitin-specific protease 9X (USP9X), like USP6, encodes a highly conserved substrate-specific deubiquitylating enzyme. USP9X is highly expressed in a number of tissue types and acts as both an oncogene and tumor suppressor in several human cancers. We conclude that oncogenic activation of USP6 via USP9X promoter exchange represents a novel driver of primary ABC formation.

Total Calcanectomy and Bilateral Iliac Bone Autograft Reconstruction for the Treatment of Calcaneal Chondroblastoma Involving a Secondary Aneurysmal Bone Cyst: A Case Report and Literature Review.

Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.

Cystic bone tumors of the foot and ankle.

Bone tumors are relatively rare in the foot and ankle region. Many of them present as cystic lesions on plain films. Due to the relative rarity of these lesions and the complex anatomy of the foot and ankle region, identification of such lesions is often delayed or they get misdiagnosed and mismanaged. This review discusses the most common cystic tumors of the foot and ankle including their radiographic features and principles of management.

Denosumab: a potential treatment option for aneurysmal bone cyst of the atlas.

PURPOSE: Aneurysmal bone cysts (ABCs) of spine are conventionally treated with en-bloc resection or intralesional excision/curettage and reconstruction or filling of defects with bone cement. For the treatment of upper cervical ABCs, en-bloc resections are often not desirable considering the risk/benefit ratio while the risk of recurrence after intralesional excision is high. Hence, alternative management options are often necessary. We describe our clinical experience with one such treatment alternative-denosumab for the treatment of ABC of Atlas. METHODS AND RESULTS: We present a case of 16-year-old boy who presented with neck pain and restriction of neck movements. A large lytic lesion with multiple fluid-fluid interfaces involving vertebral arch of atlas was identified on further imaging. There was destruction of right lateral mass and the lesion was found encasing the right vertebral artery. Core needle biopsy confirmed the diagnosis of ABC. With no visible CT response after first session of intra-lesional injection of Calcitonin and Methylprednisolone, the patient was treated with denosumab (120 mg SC once-a-month) for a period of 12 months. His symptoms resolved within 7 months of onset of treatment and serial CT scans over 12-month treatment period showed complete ossification of the lesion. Further there was no evidence of recurrence at 12 months after completion of treatment. CONCLUSION: Our case report contributes to the accruing evidence on the effectiveness of denosumab for the treatment of spinal ABCs. However, long-term safety, risk of recurrence, optimal duration of treatment and consistency of denosumab are yet to be determined.

Surgical treatment of a lumbar aneurysmal bone cyst using percutaneous endoscopic lumbar discectomy.

PURPOSE: Aneurysmal bone cysts of the lumbar spine are usually treated by curettage followed by bone or bioactive ceramics grafting. Here, we present the first case of an aneurysmal bone cyst of the lumbar spine treated by percutaneous endoscopic lumbar discectomy (PELD). METHODS: We describe the clinical characteristics of the patient including the radiological and pathological findings of the tumor and the surgical technique used. RESULTS: A 15-year-old boy presented with low back pain, and he was diagnosed with an aneurysmal bone cyst of the L3 vertebra based on radiological findings, including plain radiograph, computed tomography, and magnetic resonance imaging. The technique and equipment of PELD were used to perform curettage of the tumor cavity and fill it with hydroxyapatite granules. The skin incision was only 8 mm. The patient was discharged 1 day postoperatively and could walk without assistance. The postoperative course was uneventful and the symptoms improved following surgery. CONCLUSION: Endoscopic surgery via PELD can be a treatment option for ABCs of the lumbar spine.