Summary USP6 (also known as TRE17) is a ubiquitin-specific protease that was identified as an oncogene in transfection experiments with Ewing sarcoma DNA 2 decades ago. Until recently, little was ...known about USP6 function and mechanisms of oncogenic activation. The identification of USP6 fusion genes in aneurysmal bone cyst (ABC) and, more recently, in nodular fasciitis led to a better understanding of the pathogenesis of these lesions. Furthermore, the detection of USP6 genomic rearrangements or USP6 fusion genes may be used as a diagnostic tool for these lesions. In this review, we discuss the clinicopathologic features, molecular pathology, and pathogenesis of ABC and nodular fasciitis. We also discuss the possible line of differentiation of ABC and its relationship to nodular fasciitis and other lesions.
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.
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.
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.
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.
Differentiating osteoclast-rich lesions of bone (giant cell tumor of bone GCTB, chondroblastoma CBA, and aneurysmal bone cyst ABC) can be challenging, especially in small biopsies or fine-needle ...aspirations. Mutations affecting codons 34 and 36 of either H3 Histone Family Member 3A (H3F3A) and/or 3B (H3F3B) are characteristically seen in GCTB and CBAs. We devised a simple assay to identify these mutations and evaluated its applicability for routine clinical diagnosis. One hundred twenty-four tissue specimens from 108 patients (43 GCTBs, 38 CBAs and 27 ABCs) were collected from the archives of the Calgary Laboratory Services/University of Calgary and Vanderbilt University Medical Center. Histology was reviewed by an expert orthopedic pathologist. A single base extension assay (SNaPshot) is used to interrogate each nucleotide in codons 34 and 36 of H3F3A and codon 36 of H3F3B. Final diagnoses were generated after re-reviewing cases and incorporating molecular findings. Of 43 GCTBs, 38 (88%) had an H3F3A G34W mutation; 35 of 38 CBAs (92%) had a K36M mutation in either H3F3B (N = 31; 82%) or H3F3A (N = 4; 11%); none of 27 ABCs had a tested mutation. Molecular findings changed the histomorphologic diagnosis in 5 cases (3 GCTB changed to ABC, and 2 ABC changed to GCTB). These findings support the diagnostic utility of mutational analysis for this differential diagnosis in certain challenging cases when clinicoradiologic and histomorphologic features are not definitive, particularly for distinguishing cellular ABC versus GCTB with secondary ABC.
•We devised a simple assay to identify H3F3A G34W and H3F3A/B K36M mutations.•We tested 124 archived osteoclast-rich bone tumors and performed histologic review.•88% of giant cell tumors of bone had an H3F3A G34W mutation.•92% of chondroblastomas had a H3F3A/B K36M mutation.•The test is most valuable in cases when radiology and histology are not definitive.
Aneurysmal bone cysts (ABCs) mostly occur in the metaphysis of long bones. Primary paranasal ABCs are extremely rare, and most reported cases reveal typical histopathological features including ...cystic space with fibrous septa and hemorrhage. Solid-variant ABCs or solid ABCs lacking cyst formation may be histologically indistinguishable from giant cell reparative granulomas, giant cell tumor of bone, and brown tumor. Here we report the case of a 24-year-old woman with a paranasal mass diagnosed as USP6-rearranged solid ABC, mimicking giant cell reparative granuloma, giant cell tumor of bone, and brown tumor. For paranasal sinus bone or soft tissue tumors containing numerous giant cells, molecular analysis including the USP6 gene may serve as a useful diagnostic tool to distinguish solid ABCs from other giant cell–rich lesions.
•Solid aneurysmal bone cysts (ABCs) of the paranasal sinus are extremely rare.•Solid ABCs are histologically indistinguishable from giant cell reparative granulomas and giant cell tumors.•USP6 FISH can distinguish solid ABCs from other giant cell–rich lesions of the head and neck.
Myositis ossificans is defined as a self-limiting pseudotumor composed of reactive hypercellular fibrous tissue and bone.
USP6 rearrangements have been identified as a consistent genetic driving ...event in aneurysmal bone cyst and nodular fasciitis. It is therefore an integral part of the diagnostic workup when dealing with (myo)fibroblastic lesions of soft tissue and bone. Two cases of myositis ossificans with USP6 rearrangement were published so far.
We determine herein the incidence of USP6 rearrangement in myositis ossificans using USP6 fluorescence in situ hybridization analysis (FISH). Of the 11 cases included, seven patients were female and four were male. Age ranged from 6 to 56 years (mean 27 years). Lesions were located in the thigh (n = 5), knee (n = 1), lower leg (n = 1), lower arm (n = 1), perineum (n = 1), gluteal (n = 1) and thoracic wall (n = 1).
All assessable cases except one (8/9) showed rearrangement of USP6 providing evidence that myositis ossificans is genetically related to nodular fasciitis and aneurysmal bone cyst.
•We have identified USP6 rearrangements in a series of myositis ossificans cases.•We therefore argue that this entity belongs to the group of clonal transient neoplasms also including nodular fasciitis and aneurysmal bone cyst.
Aneurysmal Bone Cysts: Do Simple Treatments Work? Reddy, Krishna I. A.; Sinnaeve, F.; Gaston, Czar Louie ...
Clinical orthopaedics and related research,
06/2014, Letnik:
472, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Background
Primary aneurysmal bone cysts (ABCs) are benign, expansile bone lesions commonly treated with aggressive curettage with or without adjuvants such as cryotherapy, methacrylate cement, or ...phenol. It has been reported that occasionally these lesions heal spontaneously or after a pathologic fracture, and we observed that some ABCs treated at our center healed after biopsy alone. Because of this, we introduced a novel biopsy technique we call “curopsy,” which is a percutaneous limited curettage at the time of biopsy, obtaining the lining membrane from various quadrants of the cyst leading to consolidation (curopsy = biopsy with intention to cure).
Questions/purposes
We asked whether (1) a curopsy results in comparable likelihood of healing of the ABC compared with more aggressive approaches involving curettage, (2) the two approaches differ in terms of the likelihood of recurrence after treatment, and (3) the two approaches differ in terms of complications after surgery.
Methods
Between January 1, 1999 and June 30, 2012, 221 patients with a diagnosis of primary ABC were registered in our oncology database. Patients presenting with a pathologic fracture and those seeking a second opinion were excluded. One hundred ninety patients were included in the study. One hundred two (54%) were treated with curopsy and 88 (46%) were treated with curettage after a core needle biopsy. Complete followups were available for 88% (90 of 102) and 93% (80 of 88) of patients in those groups, respectively. During that period, a curopsy was performed for all patients with benign bone lesions with imaging suggestive of classic primary ABCs and for whom the core needle biopsy simply showed blood with no solid component. Curettage after a core needle biopsy was reserved for histologically confirmed primary ABCs, lesions with impending fractures, large lesions, if the ABC was thought to be a secondary disorder, and patients for whom the curopsy failed. All patients were followed up until consolidation of the lesion (mean, 9.6 weeks, range, 3–25 weeks, 95% CI, 8.32–10.9 for curopsy; mean, 11.4 weeks, range, 8–32 weeks, 95% CI, 10.6–12.3 for curettage). The median followup for all patients was 14 months (range, 6–36 months).
Results
Of the 102 patients who had curopsy and observation, 83 (81%) required no additional treatment and the lesion resolved. Of the 88 patients who underwent curettage (with or without adjuvant therapy) after core needle biopsy, the success rate was 90% (79 of 88). Local recurrences in both groups (curopsy or curettage) were treated successfully with additional curettage in all but one case. Curopsy in comparison to curettage provided a mean shorter healing time (9.6 versus 11.4, p = 0.01) but there was a higher local recurrence and need for additional intervention rate (18.6% versus 10.2%, p = 0.04). There were no differences in the complications between the treatment groups.
Conclusions
A curopsy is a novel biopsy technique that was successful in resolving ABCs in 81% of the patients in our study. Curopsy, as a biopsy technique, for ABCs needs consideration as it potentially minimizes the number of patients needing a second procedure (a core needle biopsy being the first) as is the current practice. Furthermore, it does not disadvantage the patient or surgeon should additional intervention be needed in the form of curettage with or without adjuvants.
Level of Evidence
Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.
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.
Background
Minimally invasive approaches such as sclerotherapy have been introduced to treat aneurysmal bone cysts. Sclerotherapy has been associated with reasonable healing rates during the past two ...decades. However, it is unclear whether sclerotherapy compares with the more traditional extended curettage and bone grafting.
Questions/purposes
We therefore compared the healing rates and functional scores in patients having percutaneous repetitive sclerotherapy using polidocanol (Group 1) with those with intralesional excision (extended curettage with a high-speed burr) and bone grafting (Group 2) for treatment of aneurysmal bone cyst.
Patients and Methods
We randomly divided 94 patients into two treatment groups. We assessed healing rates (primary outcome measure), pain relief, time to healing and recurrence, hospital stay, and the Enneking functional score. Forty-five patients from Group 1 and 46 from Group 2 were available for study. The minimum followup was 3.2 years (mean, 4.4 years; range, 3.2–6.1 years).
Results
At last followup, 93.3% in Group 1 and 84.8% in Group 2 had achieved healing. Complications in Group 1 were minor and resolved. In Group 2, three patients had deep infections and five had superficial infections, and two had growth disturbances. Although the healing rates were similar, we found higher rates of clinically important complications, worse functional outcomes, and higher hospital burden associated with intralesional excision.
Conclusions
Repetitive sclerotherapy using polidocanol is a minimally invasive, safer method of treatment for aneurysmal bone cysts compared with intralesional excision and bone grafting. In this preliminary study, we found similar recurrence rates for the two treatment methods, however, this will require confirmation in larger studies.
Level of Evidence
Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses.
Fourteen cases of SBC were collected at the Department of Pathology, ...the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis.
There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur (
4), humerus (
5) and iliac bone (
5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional
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