High-Grade Uterine Sarcoma with BCOR Internal Tandem Duplication Presenting With Total Uterine Inversion

AUTHORS

T J Greenwell, S Kumar, C Hysell

ABSTRACT

High-grade uterine sarcomas are rare mesenchymal tumors in which the underlying genetics of many have been recently elucidated. BCOR internal tandem duplications are present in a subset of high-grade uterine sarcomas. We report a diagnostically challenging case of a high-grade uterine sarcoma with a BCOR internal tandem duplication presenting with total uterine inversion. The case is that of a 24 year old G0P0 female with a four month history of intermittent diffuse abdominal pain and abnormal uterine bleeding. Pelvic examination revealed a mass protruding to the hymenal ring. The patient was suspected of having a prolapsed fibroid through the cervix, and a myomectomy was planned. During the procedure, total uterine inversion was noted as a result of a submucosal mass emanating from the uterine apex. The mass was removed off a broad base using sharp dissection, and the uterus was reverted in a subsequent procedure. Grossly, the mass was polypoid, rubbery, and measured 7 cm in greatest dimension. It was grey-white to red-brown, variegated, and fibrotic with focal hemorrhagic areas.

Histologically, the neoplasm had variable cellularity with spindle cells and a myxoid background. There was diffuse mild to moderate cytologic atypia and areas of increased mitotic activity. Tongue-like growth was present at the interface of the tumor with the normal myometrium. The neoplastic cells showed strong immunoreactivity for cyclin D1, BCOR, and TRK. There was focal immunoreactivity for CD10, and ALK was negative. Next-generation sequencing was performed and demonstrated an insertion into the BCOR gene, consistent with a diagnosis of high- grade uterine sarcoma with BCOR internal tandem duplication. In conclusion, we report an interesting presentation of a high-grade uterine sarcoma with BCOR internal tandem duplication causing total uterine inversion. The morphologic features and immunohistochemical profile suggested the possibility of the entity, and next generation sequencing confirmed the diagnosis.

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The effect of polyethylenglycol gel on the delivery and osteogenic differentiation of homologous tooth germ–derived stem cells in a porcine model

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The aim of this study was to investigate if bone regeneration can be promoted by homologous transplantation of STRO-1 sorted (STRO-1+) porcine tooth germ mesenchymal stem cells (TGSCs) with the combination of polyethylenglycol (PEG)-based hydrogel and biphasic calcium phosphate (BCP) scaffolds.

Collagen XII mediated cellular and extracellular mechanisms regulate establishment of tendon structure and function

Tendons have a uniaxially aligned structure with a hierarchical organization of collagen fibrils crucial for tendon function. Collagen XII is expressed in tendons and has been implicated in the regulation of fibrillogenesis. It is a non-fibrillar collagen belonging to the Fibril-Associated Collagens with Interrupted Triple Helices (FACIT) family. Mutations in COL12A1 cause myopathic Ehlers Danlos Syndrome with a clinical phenotype involving both joints and tendons supporting critical role(s) for collagen XII in tendon development and function.

Anti‐Interleukin‐6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head

Legg‐Calvé‐Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin‐6 (IL‐6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL‐6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis.

Cell and Tissue Response to Polyethylene Terephthalate Mesh Containing Bone Allograft in Vitro and in Vivo

AUTHORS

D. Joshua Cohen, Lisa Ferrara, Marcus B. Stone, Zvi Schwartz and Barbara D. Boyan

ABSTRACT

Background Extended polyethylene terephthalate mesh (PET, Dacron) can provide containment of compressed particulate allograft and autograft. This study assessed if PET mesh would interfere with osteoprogenitor cell migration from vertebral plates through particulate graft, and its effect on osteoblast differentiation or the quality of bone forming within fusing vertebra during vertebral interbody fusion.

Methods The impact of PET mesh on the biological response of normal human osteoblasts (NHOst cells) and bone marrow stromal cells (MSCs) to particulate bone graft was examined in vitro. Cells were cultured on rat bone particles +/− mesh; proliferation and osteoblast differentiation were assessed. The interface between the vertebral endplate, PET mesh, and newly formed bone within consolidated allograft contained by mesh was examined in a sheep model via microradiographs, histology, and mechanical testing.

Results Growth on bone particles stimulated proliferation and early differentiation of NHOst cells and MSCs, but delayed terminal differentiation. This was not negatively impacted by mesh. New bone formation in vivo was not prevented by use of a PET mesh graft containment device. Fusion was improved in sites containing allograft/demineralized bone matrix (DBM) versus autograft and was further enhanced when stabilized using pedicle screws. Only sites treated with allograft/DBM+screws exhibited greater percent bone ingrowth versus discectomy or autograft. These results were mirrored biomechanically.

Conclusions PET mesh does not negatively impact cell attachment to particulate bone graft, proliferation, or initial osteoblast differentiation. The results demonstrated that bone growth occurs from vertebral endplates into graft material within the PET mesh. This was enhanced by stabilization with pedicle screws leading to greater bone ingrowth and biomechanical stability across the fusion site.

Improved bone regeneration using bone anabolic drug conjugates (C3 and C6) with deproteinized bovine bone mineral as a carrier in rat mandibular defects

AUTHORS

Zeeshan Sheikh, Mohamed-Nur Abdallah, Faik Al-Jaf, Gang Chen, Nader Hamdan, Robert N. Young, Marc D. Grynpas, Michael Glogauer

ABSTRACT

Background

Deproteinized bovine bone mineral (DBBM) has been extensively studied and used for bone regeneration in oral and maxillofacial surgery. However, it lacks an osteoinductive ability. We developed two novel bone anabolic conjugated drugs, known as C3 and C6, of an inactive bisphosphonate and a bone activating synthetic prostaglandin agonist. The aim was to investigate whether these drugs prebound to DBBM granules have the potential to achieve rapid and enhanced bone regeneration.

Methods

Bilateral defects (4.3 mm diameter circular through and through) were created in mandibular angles of 24 Sprague-Dawley rats were filled with DBBM Control, DBBM with C3 or DBBM with C6 (n = 8 defects per group/ each timepoint). After 2 and 4 weeks, postmortem samples were analyzed by microcomputed tomography followed by backscattering electron microscopy and histology.

Results

DBBM grafts containing the C3 and C6 conjugated drugs showed significantly more bone formation than DBBM control at 2 and 4 weeks. The C6 containing DBBM demonstrated the highest percentage of new bone formation at 4 weeks. There was no significant difference in the percentage of the remaining graft between the different groups at 2 or 4 weeks.

Conclusions

DBBM granules containing conjugated drugs C3 and C6 induced greater new bone volume generated and increased the bone formation rate more than the DBBM controls. This is expected to allow the development of clinical treatments that provide more predictable and improved bone regeneration for bone defect repair in oral and maxillofacial surgery.