Aggressive Local Recurrence Research Articles

N6-methyladenosine-modified circTEAD1 stabilizes Yap1 mRNA to promote chordoma tumorigenesis.

Chordoma, a rare bone tumour with aggressive local invasion and high recurrence rate with limited understanding of its molecular mechanisms. Circular RNAs (circRNAs) have been extensively implicated in tumorigenesis, yet their involvement in chordoma remains largely unexplored. N6-methyladenosine (m6A) modification holds a crucial function in regulating protein translation, RNA degradation and transcription. Initially, screening and validation of circTEAD1 in chordoma were conducted by high-throughput sequencing. Subsequently, sh-circTEAD1 and an overexpression plasmid were constructed. Colony formation assays, cell counting kit-8, Transwell and wound healing assays were utilized to validate the function of circTEAD1 in vitro. RNA pull-down assays identified the binding proteins of circTEAD1, which underwent verification through RNA immunoprecipitation (RIP). Methylated RIP assays were conducted to detect the m6A binding sites. Following this, luciferase assay, RT-qPCR, RIP and Western blotting analyses were conducted, revealing that Yap1 was the direct target of circTEAD1. Afterwards, the same methods were utilized for the validation of the function of Yap1 in chordoma in vitro. Finally, the regulatory relationship between circTEAD1 and Yap1 in chordoma was verified by an in vivo tumour formation assay. CircTEAD1 was identified as an upregulated circRNA in chordoma specimens, with heightened circTEAD1 expression emerging as a prognostic indicator. In vitro experiments convincingly demonstrated that circTEAD1 significantly promoted chordoma cell invasion, migration and aggressiveness. Furthermore, the analysis revealed that methyltransferase-like 3-mediated m6A modification facilitated the cytoplasmic export of circTEAD1. The circTEAD1/IGF2BP3/Yap1 mRNA RNA-protein ternary complex not only bolstered the stability of Yap1 mRNA but also exerted a pivotal role in driving chordoma tumorigenesis. In this study, the role of m6A-modified circTEAD1 in chordoma was identified. The findings offer novel insights into the potential molecular targets for chordoma therapy, shedding light on the intricate interplay between circRNAs, m6A modification and Yap1 mRNA in chordoma pathogenesis.

Association of MDM2 Overexpression in Ameloblastomas with MDM2 Amplification and BRAFV600E Expression.

Ameloblastoma is a rare tumor but represents the most common odontogenic neoplasm. It is localized in the jaws and, although it is a benign, slow-growing tumor, it has an aggressive local behavior and high recurrence rate. Therefore, alternative treatment options or complementary to surgery have been evaluated, with the most promising one among them being a targeted therapy with the v-Raf murine sarcoma viral oncogene homologue B (BRAF), as in ameloblastoma the activating mutation V600E in BRAF is common. Studies in other tumors have shown that the synchronous inhibition of BRAF and human murine double minute 2 homologue (MDM2 or HDM2) protein is more effective than BRAF monotherapy, particularly in the presence of wild type p53 (WTp53). To investigate the MDM2 protein expression and gene amplification in ameloblastoma, in association with BRAFV600E and p53 expression. Forty-four cases of ameloblastoma fixed in 10% buffered formalin and embedded in paraffin were examined for MDM2 overexpression and BRAFV600E and p53 expression by immunohistochemistry, and for MDM2 ploidy with fluorescence in situ hybridization. Sixteen of forty-four (36.36%) cases of ameloblastoma showed MDM2 overexpression. Seven of sixteen MDM2-positive ameloblastomas (43.75%) were BRAFV600E positive and fifteen of sixteen MDM2-positive ameloblastomas (93.75%) were p53 negative. All MDM2 overexpressing tumors did not show copy number alterations for MDM2. Overexpression of MDM2 in ameloblastomas is not associated with MDM2 amplification, but most probably with MAPK activation and WTp53 expression. Further verification of those findings could form the basis for the use of MDM2 expression as a marker of MAPK activation in ameloblastomas and the trial of dual BRAF/MDM2 inhibition in the management of MDM2-overexpressing/BRAFV600E-positive/WTp53 ameloblastomas.

ICAM-1 Activates Platelets and Promotes Endothelial Permeability through VE-Cadherin after Insufficient Radiofrequency Ablation.

Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) often leads to aggressive local recurrence and increased metastasis, and vascular integrity and platelets are implicated in tumor metastasis. However, whether interactions between endothelial cells and platelets induce endothelial permeability in HCC after insufficient RFA remains unclear. Here, significantly increased CD62P‐positive platelets and sP‐selectin in plasma are observed in HCC patients after RFA, and tumor‐associated endothelial cells (TAECs) activate platelets and are susceptible to permeability after heat treatment in the presence of platelets in vitro. In addition, tumors exhibit enhanced vascular permeability after insufficient RFA in mice; heat treatment promotes platelets‐induced endothelial permeability through vascular endothelial (VE)‐cadherin, and ICAM‐1 upregulation in TAECs after heat treatment results in platelet activation and increased endothelial permeability in vitro. Moreover, the binding interaction between upregulated ICAM‐1 and Ezrin downregulates VE‐cadherin expression. Furthermore, platelet depletion or ICAM‐1 inhibition suppresses tumor growth and metastasis after insufficient RFA in an orthotopic tumor mouse model, and vascular permeability decreases in ICAM‐1−/− mouse tumor after insufficient RFA. The findings suggest that ICAM‐1 activates platelets and promotes endothelial permeability in TAECs through VE‐cadherin after insufficient RFA, and anti‐platelet and anti‐ICAM‐1 therapy can be used to prevent progression of HCC after insufficient RFA.

A Case Report of Huge Sacrum Undifferentiated Pleomorphic Sarcoma Treated with Two Separate Surgeries of Decompression and Stabilization

Primary sacrum undifferentiated pleomorphic sarcoma (UPS) is an extremely rare malignant lesion. Furthermore, sacral tumor is often an uncontrollable condition, because the first diagnosis is usually made at advanced stage in the patients of sacral tumors. In this article, we report a patient with sacrum UPS, who showed aggressive local recurrence and early progression of multiple metastases in major organs after palliative surgery, resulting in the occurrence of a U-shaped sacrum pathological fracture requiring stabilization from the fourth lumbar to the ilium. An 87-year-old male patient showed progressively worsening gait difficulty following bladder and bowel dysfunction because of the presence of a sacrum tumor. Palliative surgery (laminectomy) from the first to the third sacrum (S) and tumor excision were performed. His neurological dysfunction tended to recover after surgery. However, a U-shaped sacrum pathological fracture occurred. Percutaneous stabilization from the fourth lumbar to the ilium was performed during the second postoperative week. The findings were consistent with those of a UPS. The patient was able to transfer from the bed to a wheel chair. However, his general condition deteriorated, with multiple organ metastases, and he expired because of respiratory insufficiency caused by the UPS 2 months after stabilization. Sacral stabilization should be considered for patients with an invaded S1–2 pedicle because of the potential occurrence of S1 pedicle and sacrum fractures. Palliative treatment with only radiation and analgesic agents after needle biopsy might have been another option, considering the age and the biological nature of sacral UPS.

Rare leiomyosarcoma in a burn scar

Leiomyosarcomas presenting as a cutaneous malignancy in a burn scar are rare due to scarce mesenchymal elements within the cutaneous tissues. We here present a case of a 73-year-old woman with a past history of burns, came with a recurrent ulceroproliferative lesion in the right lumbar region over previous burn scar. She had a history of a similar lesion in the same region 1 year ago, for which wide local excision and grafting were done, and histopathology revealed as sarcomatoid carcinoma. Examination revealed multiple right axillary lymph nodes. Evaluation was done with contrast-enhanced computed tomography to rule out systemic metastasis. She was managed surgically with wide local excision, right axillary dissection, and split skin grafting. She had aggressive local recurrence along with lung metastasis within 6 months and was lost to follow-up. This report presents the second case of leiomyosarcoma arising in a burn scar on the right flank.

Indication of Amputation after Tumoral Arthroplasty

Abstract Introduction. After a time when amputation was the only treatment option for musculoskeletal malignancies, a major breakthrough was the tumoral arthroplasty with limb preservation. Material and method. The study included a group of 28 patients, of whom 20 had pelvic limb tumor formation. Malignant bone tumors were present in 18 patients and benign tumors in 10 patients. The most commonly encountered was osteosarcoma in 12 patients, Ewing sarcoma in 4 patients and giant cell tumor in 3 patients. Patient follow-up was conducted within 4 years (with an average of 3-5 years). Results. 5 of our patients developed pulmonary metastases 8 months after surgery and, for 4 of the patients, pulmonary determinations were extirpated without subsequent relapse. The survival rate was 75% at the last follow-up (6 of 12 patients with osteosarcoma, 1 of 4 patients with Ewing’s sarcoma has died), and 32% had local tumor recurrence. The infection remains an inherent danger by using implants in immunosuppressed patients. 18% of the patients had amputations secondary to long-term complications involving the following prosthesis causes: vascular compromise, aseptic loosening, periprosthetic fractures, and metallosis. Sarcoma was associated with a higher infection rate. Radiotherapy and chemotherapy (not in combination) were statistically associated with an increased infection. Debridement with retention of the implant has reached a remission of the infection rate of 70%, 62% for two-step treatment to 100% in the case of amputations. Conclusions. Regardless of the stage of the tumor, amputation has a narrower indication nowadays, the goal being the retention of the limb and reconstruction. The amputation post-tumoral arthroplasty is of a primary intention in the case of aggressive local recurrences and massive infections. Staphylococcus aureus remains the bacterium with the highest incidence of infection complications.

Multiple cutaneous metastasis of sacral chordoma, mimicking neurofibromas clinically

Chordoma is a rare primary bone tumor of notochordal origin, constituting 1-4% of malignant primary bone tumors. Chordomas are slow growing tumors and show aggressive local extension, multiple recurrences and metastasis. Cutaneous metastasis of chordoma is very rare. We report a case of a 61-year-old man presenting with multiple cutaneous metastasis of primary sacral chordoma.DOI:10.21276/APALM.1753

Genome-Wide Transcriptome Profiling of the Neoplastic Giant Cell Tumor of Bone Stromal Cells by RNA Sequencing.

Giant cell tumor of bone (GCTB) is the most common non-malignant primary bone tumor reported in Hong Kong. Failure of treatment in advanced GCTB with aggressive local recurrence remains a clinical challenge. In order to reveal the molecular mechanism underlying the pathogenesis of this tumor, we aimed to examine the transcriptome profiling of the neoplastic stromal cells of GCTB in this study. RNA-sequencing was performed on three GCTB stromal cell samples and one bone marrow-derived MSC sample and 174 differentially expressed genes (DEGs) were identified between these two cell types. The top five up-regulated genes are SPP1, F3, TSPAN12, MMP13, and LGALS3BP and further validated by qPCR and Western Blotting. Knockdown of SPP1 was found to induce RUNX2 and OPG expression in GCTB stromal cells but not the MSCs. Ingenuity pathway analysis (IPA) of the 174 DEGs revealed significant alternations in 23 pathways; variant calling analysis revealed 1915 somatic variants of 384 genes with high or moderate impacts. Interestingly, four canonical pathways were found overlapping in both analyses; from which VEGFA, CSF1, PLAUR, and F3 genes with somatic mutation were found up-regulated in GCTB stromal cells. The STRING diagram showed two main clusters of the DEGs; one cluster of histone genes that are down-regulated in GCTB samples and another related to osteoblast differentiation, angiogenesis, cell cycle progression, and tumor growth. The DEGs and somatic mutations found in our study warrant further investigation and validation, nevertheless, our study add new insights in the search for new therapeutic targets in treating GCTB. J. Cell. Biochem. 118: 1349-1360, 2017. © 2016 Wiley Periodicals, Inc.

Epithelial–mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation

We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial–mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA.

Recurrent feature after radiofrequency ablation therapy for hepatocelluar carcinoma: Risk of increasing malignant behavior.

213 Background: Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). However, several reports demonstrated the aggressive local recurrence after RFA, suggesting the induction of further malignant transformation of HCC. Methods: Eighty-eight patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for the HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and patient’s prognosis after hepatectomy were compared between the two groups. Expression levels of HIF-1, EpCAM, CD44, VEGF and EMT markers mRNA in the tumor tissues were examined. We also investigated miR-34a and miR-200c expressions in the two groups. Results: RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p &lt; 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p &lt; 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p &lt; 0.05). The expressions of TGF-β, Twist and Snail-1 in RFA group were significantly higher than those in non-RFA group (P &lt; 0.05), and Vimentin expression in RFA group tended to be higher than that in non-RFA group (P = 0.07). Regarding to miRNA, miR-200c and miR-34a expressions in RFA group were significantly lower than those in non-RFA group (miR-200c: P = 0.04, miR-34a: P &lt; 0.01). Conclusions: Recurrent HCC after RFA showed the highly malignant potential through the expressions of HIF-1, cancer stem cell and EMT markers.

Dermatofibrosarcoma Protuberans: A Case Report and Review of Surgical Management

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous neoplasm with low to intermediate grade malignancy. While it rarely metastasizes, it is characterized by aggressive local infiltration and high recurrence. The etiology of DFSP remains unknown, but current research has shown that DFSP has specific histologic, immunohistochemical, and cytogenetic findings. We report a unique case of a 29-year-old female who presented with a dry, shallow ulcerated right posterior shoulder mass diagnosed as DFSP, and describe our surgical management. J Curr Surg. 2016;6(2):57-59 doi: http://dx.doi.org/10.14740/jcs302w

Giant cell tumor in first metacarpal bone: A rare entity

Giant cell tumors (GCT) commonly occur at the ends of long bones. However in rare cases, they can occur in bones of hands and feet. We here report a case of giant cell tumor of first metacarpal bone in a 33-year-old male to highlight the importance of occurrence of such a common bone tumor in extremely rare location. Diagnosis of giant cell tumor should not be missed even in extremely rare location as GCT is well known for its aggressive behavior and local recurrence.

Juvenile Aggressive Trabecular Ossifying Fibroma of Mandible: A Rare Case Report

ABSTRACTFibroosseous lesions of the jaws, including juvenile ossifying fibroma (JOF), pose diagnostic and therapeutic difficulties due to their clinical, radiological, and histological variability. There are two histological varieties of it, one as psammomatoid type and second as trebacular type; here, we present a trebacular type, which is a rare variety. After the clinical examination, radiological and histological analysis, it was diagnosed as juvenile trebacular ossifying fibroma. Although JOF is an uncommon clinical entity, its aggressive local behavior and high recurrence rate means that it is important to make an early diagnosis, apply the appropriate treatment, and, especially, follow-up the patient over the long term.How to cite this articleGhule AS, Achath DD, Kanchan- Talreja P, Bhatnagar S. Juvenile Aggressive Trabecular Ossifying Fibroma of Mandible: A Rare Case Report. J Contemp Dent 2016;6(1):45-51.

Refractory Status Epilepticus in a Pregnant Woman Affected by Clivus Chordoma

Status epilepticus (SE) is a rare but potentially life threatening complication that women with epilepsy may experience during pregnancy. Refractory status epilepticus (RSE) is defined as an epileptic status which is unresponsive to early standard antiepileptic medical treatments; it has been reported that in pregnant women affected by other diseases (systemic lupus erythematosus, porphyria, vitamin B6 deficiency and cavernous angioma) this status spontaneously resolved only after delivery. We report the case of a primigravida 29-year-old epileptic woman who was admitted to the Emergency Room at 25 weeks of gestation with RSE and a confused mental state. Her Electroencephalography documented repeated seizures not controlled by medical treatments, for this reason she was then sent to the Intensive Care Unit. The patient had no known risk factors. Her cranial magnetic resonance revealed a clivus chordoma, a rare, slow-growing neoplasm, characterized by locally aggressive growth patterns and high local recurrence rates. Spontaneous premature delivery at 26 weeks and three days brought an almost immediate cessation of seizures.

Synchronous Juvenile ossifying Fibroma in maxilla and mandible- A case report

Juvenile ossifying fibroma (JOF), one of the fibroosseous lesions is an uncommon clinical entity and involving both jaw is even rarer. Here, we present the case of a 15-year-old female patient with synchronous occurrence of JOF in the right sided maxilla and in the periapical area of mandibular right premolar molar region. After the clinical, radiographical and histopathological examination, the surgical treatment was carried out and the patient was kept under long term follow up. Owning to its aggressive local behaviour and high recurrence, early diagnosis, appropriate treatment and long term regular follow up are of prime importance. DOI: http://dx.doi.org/10.3126/jcmc.v4i2.10867 Journal of Chitwan Medical College 2014; 4(2): 54-57

Hypoxia After Liver Surgery Imposes an Aggressive Cancer Stem Cell Phenotype on Residual Tumor Cells

To assess the contribution of hypoxia and bone marrow-derived cells to aggressive outgrowth of micrometastases after liver surgery. Liver surgery generates a microenvironment that fosters aggressive tumor recurrence. These areas are characterized by chronic hypoxia and influx of bone marrow-derived cells. The contribution of hematopoietic cell types was studied in mice lacking specific components of the immune system and in irradiated mice lacking all bone marrow-derived cells. Tumor cells were derived from colorectal cancer patients and from a metastatic tumor cell line. Hypoxia-induced changes in stem cell and differentiation marker expression, clone-forming potential, and metastatic capacity were assessed. The effect of vascular clamping on cancer stem cell (CSC) characteristics was performed in mice bearing patient-derived liver metastases. Immune cells and bone marrow-derived cells were not required for aggressive outgrowth of micrometastases in livers treated with surgery. Rather, hypoxia was sufficient to promote invasion and accelerate metastatic outgrowth. This was associated with a rapid loss of differentiation markers and increased expression of CSC markers and clone-forming capacity. Likewise, metastases residing in ischemia-reperfusion-injured liver lobes acquired CSC characteristics. Despite their renowned general resistance to chemotherapy, clone-forming CSCs were readily killed by the hypoxia-activated prodrug tirapazamine. Surgery-generated hypoxia in the liver causes rapid dedifferentiation of tumor cells into immature CSCs with high clone- and metastasis-forming capacity. The results help explain the phenomenon of aggressive local tumor recurrence after liver surgery and offer a potential strategy to kill aggressive CSCs by hypoxia-activated prodrugs.

Expressions of Hypoxia-Inducible Factor-1 and Epithelial Cell Adhesion Molecule are Linked with Aggressive Local Recurrence of Hepatocellular Carcinoma After Radiofrequency Ablation Therapy

Radiofrequency ablation (RFA) is a widely used therapy for hepatocellular carcinoma (HCC). Several reports have demonstrated the aggressive local recurrence of HCC after RFA, suggesting that induction of further malignant transformation of HCC has occurred. Eighty-eight (88) patients with HCC who underwent hepatic resection were included in this study. Hepatectomy was indicated for local recurrence of HCC after RFA (n = 10, RFA group) and for HCC without prior RFA (n = 78, non-RFA group). Clinicopathological data and the patient's prognosis after hepatectomy were compared between the two groups. Expression levels of hypoxia-inducible factor-1 (HIF-1), epithelial cell adhesion molecule (EpCAM), CD44, and vascular endothelial growth factor messenger RNA (mRNA) in the tumor tissues were also examined. The RFA group showed higher frequency of portal vein invasion and less tumor differentiation compared with the non-RFA group (p < 0.05). Overall and disease-free survival rates in the RFA group were significantly worse than those in the non-RFA group (p < 0.05). HIF-1 and EpCAM mRNA expression levels in the RFA group were significantly higher than those in the non-RFA group (p < 0.05). These results suggest that local HCC recurrence after RFA shows an aggressive tumor phenotype and poor prognosis through the enhanced expressions of HIF-1 and EpCAM in the residual HCC tumors after insufficient or sub-lethal treatment by RFA.

Intracranial Hemangiopericytomas: A Wolf in Sheep's Clothing

Hemangiopericytomas (HPCs) are extraordinarily rare tumors and comprise less than 1% of all intracranial neoplasms (3). HPCs resemble meningiomas, but they are derived from fibrohistiocytic precursor cells and exhibit molecular changes that are distinct from meningiomas. In their seminal work on meningiomas, Cushing and Eisenhardt (2) described an angioblastic meningioma with a predilection for aggressive behavior and local recurrence. Later, Stout and Murray (10) coined the term hemangiopericytoma to describe a malignant and vascular tumor of the soft tissues, and this tumor was noted to be comprised of capillary pericytes. Begg and Garret (1) subsequently published the first case of a primary intracranial HPC in 1954. HPCs often share radiographic features and clinical presentations of the much more commonly observed meningioma. A neurosurgeon will not quickly forget the experience of finding an HPC at the time of a tumor resection instead of the much more manageable World Health Organization grade I meningioma. The significant vascularity of HPCs and their frequent involvement with adjacent dural sinus and cranial osseous components can make surgical extirpation a harrowing experience. These tumors can thus be the neurosurgical metaphor of the Biblical wolf in sheep’s clothing. In the article by Melone et al. (5) in the March/April issue of WORLD NEUROSURGERY, they describe their extensive experience spanning 30 years with the management of 36 patients with HPC whowerefollowedforamediandurationof118months.Thestudy presentsadetailedanalysisofthesuccessesofcontemporaryHPC management and the challenges that remain. All patients were treated with initial surgical resection. The median overall survival (OS) was 84 months, and the actuarial survival rates at 5 and 10 yearswere 94%and72%,respectively.Preoperativeembolization was performed in 28% of tumors. Gross total resection (GTR) during theinitial treatment phase wasachieved in 70% of patients. Postoperative external beam radiotherapy (EBRT) was performed in 37% and 78% of patients who had GTR and subtotal resection (STR), respectively. Patients who underwent STR also received adjuvant treatment with gamma knife radiosurgery (50%) and proton beam therapy (50%). The overall and recurrence-free survival durations of the patients with GTR was significantly longer than those with STR (P ¼ 0.047 and P ¼ 0.0025, respectively). In a similar study of 63 patients with HPC treated at M.D. Anderson Cancer Center during a 30-year span, Ghia et al. (4) found GTR to be an independent predictor of improved local control (P ¼ 0.008) but not of OS. In a systematic review by the University of California San Francisco group, treatment outcomes for intracranial HPC, the rates of GTR alone, GTR and EBRT, STR alone, and STR and EBRT were 54%, 25%, 12%, and 9%, respectively (7). The OS of patients who underwent GTR was significantly longer than in those who had STR (P < 0.01). In addition, the OS of patients who underwent GTR alone was superior to those who underwent combined STR and EBRT (P < 0.0001). Postoperative EBRT for patients with GTR did not significantly improved OS. Although GTR cannot always be safely achieved in a portion of HPCs, attaining it appears to confer a reasonable survival benefit. Selection biases, differences in patient and tumor attributes, and variations in treatment algorithms could contribute to the differing findings regarding impact of GTR on OS. Nevertheless, surgical resection should intuitively proceed to the point of maximal safe reduction in tumor volume, yet preserving neurological function.

Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the bony containment, mostly located intracortically in the proximal radius. The diagnosis of a periosteal ABC was confirmed by FISH demonstrating USP6 gene rearrangement on the initial biopsy. Function conserving surgery could be performed, enabling reconstruction of the affected bone. Inhibition of RANKL with denosumab may offer therapeutic option for patients not only with giant cell tumors but also with ABCs.

Aggressive angiomyxoma of the vulva: A case report

Aggressive angiomyxoma (AA) is an unusual mesenchymal tumor. AA occurs most commonly in women of reproductive age and is located in the perineal or pelvic region. This is a distinct soft tissue tumor that has a prominent myxoid matrix and numerous thin-walled blood vessels and may have an aggressive local recurrence. The tumors have the characteristics of large size (usually greater than 10 cm) and slow growth, and are not painful. The standard treatment for AA is total excision and close follow-up. We announce a case of a 35 year-old female presenting with a pedunculated AA on the right labium majora that has not relapsed for seven years.