Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

Background: Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings: We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance: These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context

Rare agressive form of giant-cell granuloma: a three years follow-up case report and discussion about medical therapeutic solutions

Introduction: Central giant cell granuloma (CGCG) is a rare and benign intraosseous lesion that usually occurs in the mandible and the maxilla. It might be aggressive. Nowadays, several treatments exist. Observation: This case report, with a three years follow-up, was about an aggressive and recurring form of CGCG exclusively managed by surgical approach. Comments: Several pharmacologic approaches are possible (intralesional injections of glucocorticoids, administration of calcitonin, alpha-2a interferon, denosumab) and could be an interesting alternative or complement to the surgical management when CGCG is aggressive, recurring, or non resectable. Conclusion: Surgical approach is the gold standard for the treatment of CGCG but sometimes, pharmacologic approaches could be proposed. According to the scientific literature, denosumab appears as a reliable and effective treatment but more prospective studies are needed

Juvenile ossifying fibroma: case report and literature review. Management and differential diagnosis

Introduction: Juvenile ossifying fibroma (JOF) is a rare neoplasm characterized by the replacement of the normal bone matrix with osteo-fibrous tissue. It has the tendency to be locally aggressive despite its benign character and to have a strong tendency for recurrence. Observation: In this case report, the patient is a young man, aged 16, with rapidly advancing maxillary swelling. We describe the diagnostic procedure, the surgical procedure and the differential diagnosis to be eliminated. Discussion: The clinical presentation of JOF, and its rapid growth, can cause fear of other pathologies such as osteosarcoma. The radiological characteristics should reassure the practitioner and a histological examination confirmed the diagnosis. Conclusion: JOF is a benign tumor. It should be operated on at an early stage because of its rapid growth. In its clinical and histological presentation, its trabecular form may mimic an osteosarcoma

Exercise-Induced Vasculitis: A Review with Illustrated Cases

International audienceAlthough exercise-induced vasculitis (EIV) is usually misdiagnosed, it is not uncommon. Occurring mostly after prolonged exercise, especially in hot weather, EIV is an isolated cutaneous vasculitis with stereotypical presentation. This article reviews the clinical characteristics, treatments, and outcomes of EIV based on the published literature. We report 99 patients who developed EIV after walking, dancing, swimming, or hiking especially during hot weather, including the records of 16 patients with EIV treated at our hospital from 2007 to 2015. Erythematous or purpuric plaques arise on the lower legs, without the involvement of compression socks or stockings. Symptoms include itch, pain, and a burning sensation. EIV is an isolated cutaneous vasculitis. Lesions resolve spontaneously after 10 days. When triggering conditions persist, relapses are frequent (77.5 %). Histopathology demonstrates leukocytoclastic vasculitis in 95 % of cases with C3 or immunoglobulin M deposits in 88 and 46 % of cases, respectively. Blood investigations are negative. EIV appears to be a consequence of venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation. Both appear after prolonged and unusual exercise in hot weather. Treatment is not codified; topical corticosteroids may reduce symptoms and wearing light clothes might limit lesion occurrence

Selective CD28 antagonist prevents Aldara-induced skin inflammation in non-human primates

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Selective CD28 antagonist blunts memory immune responses and promotes long-term control of skin inflammation in nonhuman primates

International audienceNovel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are longlived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1–dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell–mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation

A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.

In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide-binding protein/α subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive management