Central giant cell granulomas of the jaws stromal cells harbour mutations and have osteogenic differentiation capacity, in vivo and in vitro.

BACKGROUND: Central giant cell granulomas (CGCG) of the jaws are osteolytic lesions that may behave aggressively and respond poorly to surgery. Microscopically, in addition to giant cells, there is a mononuclear cell population composed of macrophage/monocytic cells and spindle-shaped cells of mesenchymal origin. Seventy two percent of these tumours harbour mutually exclusive TRPV4, KRAS and FGFR1 mutations. We aimed to assess the mutational status of mononuclear and giant cells and the osteogenic potential of stromal cells in vitro and in vivo. METHODS AND RESULTS: We screened CGCG for signature mutations and used laser-capture microdissection to demonstrate that the mutations are restricted to the mononuclear cells. Additionally, we established CGCG primary cell culture and observed that the cells retained the mutations throughout passages. By flow cytometry, we observed predominance of CD14- CD51- CD61- cells, consistent with the expected profile for stromal cells. Considering the mesenchymal origin of stromal cells, we assessed the osteogenic differentiation potential of CGCG cells in culture by cytochemistry (von Kossa and alizarin red staining), alkaline phosphatase (ALP) activity assay and gene expression of osteogenic markers. CGCG cells presented self-capacity to increase ALP levels in a time-dependent manner and under osteogenic induction presented increasing number of calcium deposits, and overall higher expression of osteocalcin, RUNX2, ALPL and osteopontin than cells without osteogenic induction. A patient-derived xenograft model for CGCG was established, and osteoid material deposition was observed. CONCLUSION: Collectively, the results confirm that the signature mutations are restricted to stromal cells in CGCG, and the in vitro and in vivo results support that these cells have the capacity to differentiate into osteoblasts, in line with the bone formation often observed in the stroma of these lesions.

Correlação citológica e histopatológica do osteossarcoma rico em células gigantes em felino / Cytological and histopathological correlation of feline giant cell-rich osteosarcoma

Background: Primary bone tumours are uncommon and poorly reported in cats but osteosarcoma (OSA) is the most frequent, mostly inelderly animals. Giant cell-rich OSA is considered rare in the literature representing 3% of all OSA in humans. The mitotic index seemsto have a significant effect on the survival time of cats affected by OSA as well as the tumour histopathological grade. The objective ofthis study was to report the cytological and histopathological findings of a giant cell rich OSA in a 4-year-old cat with persistent felineleukaemia virus (FeLV) antigenaemia.Case: A 4-year-old male neutered cat was referred with a history of persistent FeLV viraemia and pelvic limb lameness with a firmswelling. Previous radiographs of the affected limb revealed bone lysis in the third and fourth metatarsals and increased soft tissueradiopacity in the tarsal region. The referral veterinary assumed it to be osteomyelitis and initiated clinical treatment with antibiotic andanti-inflammatory. The cat was referred after there was no response to medical treatment. The cat was presented with a 5cm diameterulcerated mass, with putrid odor in the pelvic limb. Complementary exams were performed, and abnormalities were found, includingincreased urea, creatinine, calcium and potassium, and decreased sodium and phosphorus. A new radiograph showed exuberant boneproliferation, with increased radiopacity involving tarsal, metatarsal, distal third of tarsal I and II, and distal diaphysis of metatarsal V,without compromising the metaphyseal region of distal diaphysis of metatarsal IV. Chest radiographs and abdominal ultrasound wereunremarkable. Fine-needle aspiration was performed for cytological analysis and revealed a moderate amount of pleomorphic mesenchymal cells with moderate adhesion, cytoplasm with a format ranging from fusiform to stellate, pronounced...(AU)

Correlação citológica e histopatológica do osteossarcoma rico em células gigantes em felino / Cytological and histopathological correlation of feline giant cell-rich osteosarcoma

Background: Primary bone tumours are uncommon and poorly reported in cats but osteosarcoma (OSA) is the most frequent, mostly inelderly animals. Giant cell-rich OSA is considered rare in the literature representing 3% of all OSA in humans. The mitotic index seemsto have a significant effect on the survival time of cats affected by OSA as well as the tumour histopathological grade. The objective ofthis study was to report the cytological and histopathological findings of a giant cell rich OSA in a 4-year-old cat with persistent felineleukaemia virus (FeLV) antigenaemia.Case: A 4-year-old male neutered cat was referred with a history of persistent FeLV viraemia and pelvic limb lameness with a firmswelling. Previous radiographs of the affected limb revealed bone lysis in the third and fourth metatarsals and increased soft tissueradiopacity in the tarsal region. The referral veterinary assumed it to be osteomyelitis and initiated clinical treatment with antibiotic andanti-inflammatory. The cat was referred after there was no response to medical treatment. The cat was presented with a 5cm diameterulcerated mass, with putrid odor in the pelvic limb. Complementary exams were performed, and abnormalities were found, includingincreased urea, creatinine, calcium and potassium, and decreased sodium and phosphorus. A new radiograph showed exuberant boneproliferation, with increased radiopacity involving tarsal, metatarsal, distal third of tarsal I and II, and distal diaphysis of metatarsal V,without compromising the metaphyseal region of distal diaphysis of metatarsal IV. Chest radiographs and abdominal ultrasound wereunremarkable. Fine-needle aspiration was performed for cytological analysis and revealed a moderate amount of pleomorphic mesenchymal cells with moderate adhesion, cytoplasm with a format ranging from fusiform to stellate, pronounced...

Magnetic resonance imaging aspects of giant-cell tumours of bone.

INTRODUCTION: This study aimed to describe the magnetic resonance imaging (MRI) features of giant-cell tumours of bone. METHODS: We analysed the clinical and MRI features of patients diagnosed with giant-cell tumours of bone confirmed by histopathology at our institution between 2010 and 2012. RESULTS: The peak incidence was between the second and third decades of life. There was no gender predominance. The most frequent locations were the knee and wrist. Pain and swelling were the prevailing symptoms. Fifty-one per cent of the patients were found to have associated secondary aneurysmal bone cysts on histopathology. On MRI, lesions demonstrated signal intensity equal to that of skeletal muscle on T1-weighted images and low signal intensity on T2-weighted images in 90% of cases. In gadolinium-enhanced T1-weighted images, 76.6% of cases demonstrated heterogeneous enhancement. We observed cystic components involving more than 50% of the lesion in 17 cases (56.6%). There was extra-osseous involvement in 13 cases (43.3%). CONCLUSION: MRI offers a valuable diagnostic tool for giant-cell tumours of bone. Contrast-enhanced MRI can distinguish between cystic and solid components of the tumour. MRI is also the imaging modality of choice for evaluation of soft-tissue involvement, offering a complete preoperative diagnosis.