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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 443 - 443
1 Jul 2010
Albertini U Piana R Gino G Boux E Marone S Boffano M Linari A Faletti C del Prever EB
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Giant cell tumor (GCT) of bone is an aggressive tumor with high rate of recurrence. Bad prognosis factors were inquired, without a definite identification: type of treatment, soft tissue invasion, high proliferation rate at histology, pathologic fracture.

From January 2000 to February 2008, 38 patients affected by GCT were treated in a regional reference centre, 17 male, mean age 32 (range 16–69, median 29); one patient had 2 localizations (tarsal bone and proximal tibia); 3 were recurrences previously treated in other hospitals. Seven cases were in upper limb, 1 case in the sacrum, 30 in lower limb (20 around the knee); fracture at presentation was present in 6 cases; bone aneurismal cyst (ABC) was associated in 4 cases. Five cases in stage 3 were treated by bone resection followed in 4 cases by allograft and/or prosthesis (no reconstruction in 1 proximal fibula excision); 33 cases were treated by curettage, local chemical (phenole) and mechanical adjuvants (burring), filling with bone grafts in 13 cases, cement in 8 cases, cement and allografts in subchondral area in 11 cases. The sacral lesion was only curetted.

Seven patients developed a local recurrence, in 2 patients twice, for a total of 9 recurrences (19% of treatments). Recurrences occurred in 2 proximal tibia, in 2 distal femurs, in 1 proximal femur, in 1 distal radius and in 1 proximal fibula. The first treatment was bone grafts in 3 cases (23% of recurrence), bone cement and grafts in 2 cases (18% of recurrence), cement in 1 case (12% of recurrence), resection in the proximal fibula with severe soft tissue invasion. Two patients with associated ABC developed a recurrence and two with fracture at presentation.

In this study, increased rate of recurrences occurred with pathologic fracture at presentation, soft tissue invasion and ABC association.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 465 - 465
1 Jul 2010
Berta M Cistaro A Defilippi C Linari A Pagano M Garrone E Postini A Albertini U Mancini M Fagioli F del Prever AB
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PET/CT is successfully used in metabolic characterization of lung nodules in adult patients. An SUV max of 2.5 is generally accepted to distinguish benign from malignant lesions; for small solitary lung nodules some authors recommend visual evaluation rather than only SUV, suggesting that classical SUV criterion of 2.5 is inappropriate.

In pediatric patients interpretation of nodular opacity is still a clinical problem: specificity of CT in a pulmonary nodule, especially when small, is still limited.

Aim of this prospective study was to evaluate PET/ CT for non invasive characterization of pulmonary nodules in pediatric bone sarcomas.

Materials and methods: 56 whole-body PET-CT exams were performed in 19 patients with OS (14 female, 5 male) and 9 with ES (4 female and 5 male); median age at the first PET/CT exam was 14 years 8 months. PET/ CT results have been correlated with conventional imaging (CI), hystologic findings and clinical follow-up.

Results: PET/CT correctly identified pulmonary metastases, according with CI, in 33/56 exams (59%), PET/ CT revealed correctly “understaging” in 15 exams (27%) (10 in ES, 5 in OS) and incorrect “understaging” in 8 (14%) exams (4 in OS, 4 in ES). There were no false positive in either groups.

Conclusion: Correct diagnosis of a pulmonary opacity is fundamental for prognosis and choice of treatment in patients with doubtful lung lesions. Our preliminary results suggest the feasibility of a correct characterization by PET/CT in paediatric bone sarcoma patients. In particular PET/CT seems accurate and sensitive for lung nodules higher than 5 mm: an SUV max (and SUV ratio) higher than 1 seems to be significant when size is higher than 5 mm, while no significant SUV max (and SUV ratio) differences were found for smaller lesions.

Prospective studies are needed to clarify benefit of PET/CT in management of these patients.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 275 - 275
1 May 2009
Pulerà F Linari A Forni M Gino G De Marchi A del Prever EB
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Background: Chromosomal translocation are frequently observed in leukemias and sarcomas; these translocations break specific genes in the involved chromosomes and create novel chimeric genes that encode a fusion protein. Advances in these techniques have increased knowledge of the genes involved in tumoral development; molecular techniques have enabled more precise diagnosis as well as identification of new prognostic factors.

Aims: To explore the use of Reverse-Transcriptase Poly-merase Chain Reaction (RT-PCR) assay for detecting fusion transcripts in a series of Soft Tissue Sarcomas (STS) and compare the results with histopathologic diagnosis.

Material and methods: We studied 80 biopsies performed at Orthopaedic Oncology and Reconstructive Surgery Department, CTO-CFR-M.Adelaide Hospital Turin Italy, with clinical suspect of STS. Histological diagnosis was obtained contemporary to evaluation of chimeric transcripts detected by RT-PCR. cDNA were PCR amplified using primer specific for each sarcoma. Paraffin-embedded tissue samples were not used because the poor quality of the extracted RNA may give wrong positive results. Results Histology confirmed 21 Ewing Sarcoma (ES), 14 Synovial sarcoma (SS), 7 Mixoid liposarcoma (M-LPS), 4 Extraskeletal Myxoid Chondrosarcoma (E-MCDS), 4 Dermatofibrosarcoma protuberans (DFSP), 10 Rhabdo-myosarcoma, 10 Leiomyosarcoma. Of the 21 tumors diagnosed as ES, 21 (100%) expressed EWS-FLI1 chimeric transcripts. All 14 SS were positive for SYT-SSX fusion transcripts. Of the 7 cases with diagnosis of M-LPS, six were positive for EWS-CHOP transcripts; of the four cases of E-MCS 3 were positive for EWS-CHN fusion transcripts. All 4 DFSP were positive for COL1A1-PDGFB transcripts. Expression of Myo-D1, tested in ten cases of Rhabdomyosarcoma, was positive while in ten cases of Leiomyosarcoma no expression of Myo-D1 was detected by RT-PCR Ten cases were non sarcoma and negative for molecular biology.

Conclusion These results demonstrate a strong concordance between the standard histopathological diagnosis and molecular results. These techniques could be a useful method to increase the quality of histologic diagnosis in difficult cases.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 269 - 269
1 May 2009
Comandone A Foglione A Berardengo E Bernardi A Bergnolo P Linari A Forni M Chiadò Cutin S Gino G del Prever EB
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Aims: Angiogenesis is a multistep phenomenon, critical for tumor growth and prognosis in many solid neoplasms. Microvessels density (MVD) is a method of assessing angiogenesis and adversely affects DFS and OS in breast, lung and colorectal cancer. Few data are available in STS in which stage and grading are until now fundamental.

Methods: Our perspective study determined the level of MVD in a series of STS and correlated these results with DFS and OS, comparing its prognostic value with grading and stage. MVD was determined with CD 31 immunostains in formalin fixed, paraffin embedded tissues. Intratumoral MVD was assessed by light microscopic analysis. Hot spots defined the positive areas. The study included 45 patients, 35 with localized and 10 with metastatic disease at diagnosis. All tumors were located in upper or lower extremities. Histology were: 13 liposarcoma,11 MFH, 5 leiomiosarcoma, 5 PNST, 3 rabdo, 3 synovialsarcoma, 3 undifferentiated and 2 fibrosarcoma. Following Coindre classification 23 pts had low grade and 22 high grade STS.

Results: median follow up is 23 months (2–84). At present 20 pts (44.4%) are alive and DF, 11 (24.4%) alive with disease, 14 (31.1%) dead. Median survival is 75 months. Median MVD of all specimens is 62 microvessels/mm2 (7–161). 32 pts (71.1%) have low MVD (group A) and 13 pts (29.9%) high MVD (group B). Mean survival is 62.7 mo in group A (median 75) and 36 mo in group B (median not reached) (p 0.01); median DFS respectively 24 mo and 15 mo (p 0.01). There is also a significant association with histological grade and survival: 75 mo in low grade and 34 mo in high grade tumors (p 0.05) and presence of metastasis at diagnosis (median survival: M+23 mo, M−75 mo). Unfortunately no relationship between angiogenesis and grading is found.

Conclusions: Our study confirms the prognostic importance of grade and staging in pts with STS. Moreover the role of MVD in prognosis is well defined and should be used as a routine marker in STS histological diagnosis.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 269 - 269
1 May 2009
Pulerà F Linari A Forni M Gino G De Marchi A del Prever EB
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Backgroud: Leiomyosarcoma (LMS) is characterized by malignant smooth muscle cells. LMS are principally tumours of adult life, children rarely develop these tumours. The cause of LMS is not understood, however the genetic alterations are thought to be important, if not inciting, in the formation and progression of sarcoma. The silencing of tumour suppressor genes by promoter hypermethylation is a common feature among many types of malignancies; it has been proposed that DNA methylation provides an alternative pathway to gene mutation.

Aims: To evaluate the promoter methylation in LMS: two tumour-related genes (MGMT and RASSF1A) were studied.

Materials and methods: 14 LMS specimens were obtained from patients treated at Orthopaedic Oncology and Reconstructive Surgery Department, CTO-CFR-M.Adelaide Hospital, Turin. Genomic DNA was extracted from paraffin sections and frozen samples according to standard protocols. Transformation of the methylations patterns in the CpG island of RASSF1A and MGMT of DNA were determined by chemical modification. To analyzed the role of aberrant DNA in LMS, methylation status by SP-PCR was evaluated. PCR products were amplified by unmethylated (U) and methylated (M)-specific primers.

Results: The RASSF1A promoter was methylated in 4 (29%) LMS, MGMT promoter was methylated in 2 (15 %); 1 of these patients with methylation had both RASSF1A and MGMT. Eight LMS samples did not show any methylation.

Conclusions: Our data indicate that inactivation of RASSF1A is a common event in LMS. Aberrant methylation of the RASSF1A promoter region is one of the most frequent epigenetic inactivation events detected in human cancer and leads to silencing of RASSF1A; moreover inactivation of RASSF1A was usually associated to poor prognosis. According to recent reports, that demonstrated that promoter hypermethylation of the MGMT gene is not a frequent event in LMS, the present study detected MGMT in 2 (15%) tumour samples.