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AIMS Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.g. aneurysmal bone cysts, non-ossifying fibromas, chondroblastomas, brown tumours, and giant-cell-rich osteosarcomas. Our aim was to analyse the clinical history, imaging, molecular pathology and histology of three H3F3A-mutated bone tumours without detectable giant cells. None of the patients received denosumab therapy. METHODS AND RESULTS Diagnostic material was obtained by curettage or resection and/or biopsy. Common histomorphological features of all three reported lesions were fibrocytic, oval cells in a background of osteoid and an absence of multinuclear giant cells as confirmed with CD68 immunohistochemistry. We used immunohistochemistry and Sanger sequencing to demonstrate positivity for the H3.3 p.G34W mutation. Differential diagnoses were systematically excluded on the basis of histomorphology, immunohistochemistry, and fluorescence in-situ hybridisation. The imaging (radiography, computed tomography, and magnetic resonance imaging) for all three cases is presented and discussed. CONCLUSIONS We believe that these GCTBs without giant cells expand one end of the heterogeneous range of GCTB. Because of the lack of giant cells, correct diagnosis of GCTB is challenging or even impossible on histological grounds alone. In these cases, detection of the characteristic H3F3A mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful for diagnosing those lesions without giant cells as giant cell tumours of bone.

Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare thesein vitrofindings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients.

To establish a chordoma tissue cohort (n = 43) and to correlate localization, size, metastasis, residual disease (R-status), recurrences, histological subtype, matrix content, and Ki-67 proliferation index with patients’ overall survival (OS). We used routine histopathology supplemented by immunohistochemistry. In our patient cohort (median age 69 years, range 17 to 84 years) the median OS was 8.25 years. 24 chordomas were localized in the sacrum, 6 in lumbar vertebrae, 7 in thoracic and cervical vertebrae, 5 were limited to the clivus, and one was localized in the nasal septum. Ten patients had metastases, with pulmonary, nodal, and hepatic involvement. 23 patients had recurrent disease. 23 chordomas were classified as ‘not otherwise specified’ (NOS). Besides NOS, we found the following differentiation patterns: renal cell cancer like in six cases, chondroid in four cases, hepatoid differentiation in three cases, and anaplastic morphology in six cases. Ki-67 index of ≥10 %, presence of metastasis, and the low content of extracellular matrix were statistically linked to poor OS (p

To explore the diagnostic value of MRI-based 3D texture analysis to identify texture features that can be used for discrimination of low-grade chondrosarcoma from enchondroma. Eleven patients with low-grade chondrosarcoma and 11 patients with enchondroma were retrospectively evaluated. Texture analysis was performed using mint Lesion: Kurtosis, entropy, skewness, mean of positive pixels (MPP) and uniformity of positive pixel distribution (UPP) were obtained in four MRI sequences and correlated with histopathology. The Mann-Whitney U-test and receiver operating characteristic (ROC) analysis were performed to identify most discriminative texture features. Sensitivity, specificity, accuracy and optimal cut-off values were calculated. Significant differences were found in four of 20 texture parameters with regard to the different MRI sequences (p

Aims Giant cell tumour of the bone (GCTB) is a neoplasm predominantly of long bones characterized by the H3F3A mutation G34W. Conventional diagnosis is challenged by the tumour's giant cell-rich morphology, which overlaps with other giant cell-containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell-containing lesions. Methods and results We used the antibody for analysis of 22 H3F3A-mutated GCTB, including two patients with recurrences; for comparison we analysed a cohort of 36 H3F3A wild-type giant cell-rich lesions of the bone and soft tissue, containing one brown tumour, six aneurysmal bone cysts (ABC), six chondroblastomas, five non-ossifying-fibromas, two fibrous dysplasias, nine tenosynovial giant cell tumours, one giant cell-rich sarcoma and six osteosarcomas. Furthermore, among the 22 mutated cases, we included one GCTB with two recurrences and lung metastases; the patient was treated with the anti-receptor activator of nuclear factor κB (RANK) ligand denosumab. We show that all 22 H3F3A-mutated GCTB display strong nuclear H3.3 G34W staining in the neoplastic component, while the osteoclastic giant cells are negative. 36 H3F3A wild-type lesions are negative. The GCTB treated with denosumab revealed a reduction in the H3.3 G34W-positive tumour cells and a decrease in osteoclastic giant cells accompanied by matrix and osteoid formation. Conclusions We conclude that positive H3.3 G34W staining is a specific and sensitive method for detection of H3F3A-mutated GCTB. Denosumab treatment leads to a pathomorphosis of the lesion characterized by matrix and osteoid producing H3.3 G34W-negative stromal cells.

The purpose of this study was to evaluate prospectively, whether integrated 2-deoxy-2-[(18)F]fluoro-D: -glucose positron emission tomography-computed tomography (FDG-PET-CT) is more accurate for determination musculoskeletal tumors compared with separate interpretation of CT and FDG-PET, because most of the current clinical data come from patients studied with PET.Eighty patients with newly diagnosed musculoskeletal tumors underwent FDG-PET-CT. CT, FDG-PET, and FDG-PET-CT were interpreted separately to determine the performance of each imaging modality.Assuming that equivocal lesions are benign, performance of diagnostic tests was as follows: sensitivity, specificity and accuracy for CT alone was 81, 84, 83%, for PET 71, 82, 76, and for PET-CT 80, 83 and 86%. Assuming that equivocal lesions are malignant, sensitivity, specificity, and accuracy for CT was 61, 100, 70%, for PET 69, 100, 79, and for PET-CT 69, 100 and 79%.Combined FDG-PET-CT reliably differentiates soft tissue and bone tumors from benign lesions. The value of the information provided by FDG-PET-CT for planning surgical procedures must be evaluated in further studies.

Die aneurysmatische Knochenzyste ist eine seltene tumorahnliche Erkrankung, die jeden Skelettabschnitt involvieren kann und sich uberwiegend im Kindes- oder Jugendlichenalter manifestiert. Differentialdiagnostische Schwierigkeiten bei der Abgrenzung gegenuber bestimmten benignen und malignen primaren Knochentumoren erfordern neben dem Einsatz differenzierter bildgebender Verfahren haufig die histopathologische Beurteilung durch ein Knochentumorregister. Bedingt durch eine sehr heterogene biologische Aktivitat und den Umstand, das die Erkrankung uberwiegend das wachsende Skelett betrifft, mus bei der chirurgischen Therapie sowohl hinsichtlich der Resektion als auch der Defektrekonstruktion auf ein breites Spektrum an Behandlungsmasnahmen zuruckgegriffen werden konnen. In einer retrospektiven Studie wurden die Behandlungsergebnisse bei 41 operierten Tumoren, davon 31 aktive und jeweils 5 latente bzw. aggressive Lasionen, untersucht. Wahrend die therapieassoziierte Morbiditat auch bei ausgedehnteren Destruktionen sowie aufwendigeren Rekonstruktionen vergleichsweise gering war, lag die Rezidivrate bei 19,5%. Die Analyse der Lokalrezidive zeigte, das– unter Berucksichtigung der biologischen Aktivitat des Primartumors – jeweils ein inadaquates Resektionsverfahren zu Grunde lag. Der Umstand, das das Lokalrezidivrisiko sowohl mit der Aggressivitat der Primarlasion als auch mit der chirurgischen Radikalitat korreliert, macht ein praoperatives Staging und eine stadiengerechte Therapie erforderlich.

Im Rahmen einer prospektiven Studie an 168 Patienten mit Weichteil- oder Knochentumoren, darunter 71 Sarkomen, wurde unter farbdopplersonographischer Kontrolle eine Vollschnittbiopsie mit dem Hochgeschwindigkeitssystem Autovac® gewonnen. Das Ultraschallmonitoring erlaubte eine gezielte Punktion auch von kleinen oder tiefer gelegenen Lasionen und ermoglichte im Falle des Vorliegens von Nekrosen das Aufsuchen vitaler Tumoranteile. Eine adaquate histologische Beurteilung einschlieslich Tumortypisierung und Grading war bei der grosen Mehrzahl der Weichteilsarkome, Weichteilmetastasen, malignen Lymphome, Plasmocytome und osteolytischen Skelettmetastasen moglich. Benigne Weichteil- und Knochentumoren waren dagegen nur zu 66 % diagnostizierbar. In der Gruppe der ossaren Sarkome war trotz histologischem Malignitatsnachweis eine exakte Tumortypisierung aufgrund zu geringer Materialmenge haufig nicht moglich. Mit einer Genauigkeit von 97 % fur das Kriterium Malignitat und von 94 % fur die Diagnose Weichteilsarkom liefert die Methode Ergebnisse, die denen der Incisionsbiopsie, dem Standardverfahren bei Weichteil- und Knochentumoren unklarer Dignitat, vergleichbar sind. In Anbetracht der bekannten Nachteile und onkologischen Risiken des offenen Verfahrens stellt die Nadelbiopsie – bei Einhaltung der fur die Incisionsbiopsie geltenden Kautelen – fur Weichteiltumoren und osteolytische Skelettlasionen die Methode der Wahl dar.

In April 2010, a 19-year-old soccer player presented with a 4-week history of pain after a tap against his right knee. Medical and family histories were unremarkable and no abnormalities were found on physical examination. A radiograph of the right knee showed osteolytic lesions in the distal femur and the head of the tibia. On magnetic resonance imaging, the epiphyseal lesions were visualized as cystic and nonsclerotic and extended to the articular surface of the distal femur and proximal tibia (Figure 1). Soft tissue extension was suspected from the tibia. Laboratory test results showed normal blood cell count, renal function, and concentration of C-reactive protein. Aneurysmatic bone cysts were suspected and a biopsy was performed. Histopathological examination detected spindle cell infiltrates with hemorrhages, fragmented trabecular bone, and numerous osteoclastic giant cells proliferating at a rate of 10% suggesting an aggressive giant cell lesion. Since it was still not determined whether the lesions were malignant, flourodeoxyglucose F 18positron emission tomography/computed tomographywasperformedand foundadditional lesions in the left distal femur and the leftmandible. Biopsyof themandible showed the same type of tissue as seen in the right femur and tibia. Quiz at jamasurgery.com A B