Jean Michel Coindre

....

..The respective roles of immunohistochemistry and molecular biology are underlined...

..These tumors are the most frequent LPS. This paper reviews the molecular pathology, general clinical and imaging features, histopathology, new diagnostic tools, and prognosis of ALT-WDLPS and DDLPS...

....

....

..Leiomyosarcomas, pleomorphic rhabdomyosarcomas, pleomorphic liposarcomas, myxofibrosarcomas, poorly differentiated sarcomas (so-called MFH and fibrosarcomas) belong to this category and show no specific molecular abnormality...

..Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas...

....

..The diagnosis of CCS usually is easy but may be challenging in unusual sites, and the detection of EWS-ATF1 fusion transcripts is helpful to rule out a metastatic melanoma...

..However, grading is useful in more than 90% of adult soft tissue sarcomas and has been adapted to pediatric nonrhabdomyosarcomatous sarcomas. Current grading is not suitable for core needle biopsies...

..In conclusion, adult-type RMS is a rare sarcoma occurring mainly in the extremities and trunk wall with 2 main histologic patterns, spindle cell, and pleomorphic patterns, which represent the end of the spectrum of a single entity...

..With this definition, the authors attempted to evaluate the clinical significance of microinvasion...

..Moreover, DLPS with a myogenic component have a low metastatic potential, similar to conventional DLPS and significantly lower to the metastatic potential of leiomyosarcomas...

..The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years...

....

..We present the results of the largest series of sporadic desmoid tumors ever published to determine the prognostic factors of these rare tumors...

....

..We describe the clinical characteristics of a large series of S-STS (N=367) from the French Sarcoma Group (GSF-GETO) database and analyse the prognostic factors affecting outcome...

..Tissue fixation with the MF is an important improvement for molecular pathologic diagnosis, enabling a combination of routine pathologic diagnoses and current molecular diagnoses if they are carried out near the processing time...

..Data about the prognostic factors of soft-tissue leiomyosarcomas and their correlation with molecular profile are limited...

..We propose here that MED12 alterations could be implicated in the development of smooth muscle tumor and that its expression could be inhibited in malignant tumors...

....

..Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited...

....

..Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals...

..Loss of expression of INI1 is frequent in the conventional and large cell subtypes of ES and can be used as a diagnostic marker, but it has no prognostic impact...

..Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology...

..To test a double histology reading system based on digitalized imaging for cancer diagnosis...

..For XPD, both alleles were lost with a similar frequency. Our results raise the potential implication of the XPG Asp1104His polymorphism in the occurrence of chromosomal translocations associated with specific subtypes of sarcomas...

....

..Endothelial cells are the primary target of metronomic chemotherapy. We report the safety and the efficacy of metronomic chemotherapy in metastatic STS patients...

..To evaluate the place of conservative surgery in locally recurrent soft tissue sarcoma of the extremities and the trunk wall...

..Further investigations of the phosphoinositide 3-kinases/PTEN/Akt/mTOR pathway are needed to explore the role of mTOR inhibitors, either alone or in combination, in patients with advanced sarcoma...

..Genotyping and accurate detection of KIT/PDGFRA mutations in GIST are becoming increasingly useful for clinicians in the management of the disease...

..The positive detection of the SYT-SSX1 fusion transcripts with reverse-transcription polymerase chain reaction in formalin-fixed and paraffin-embedded tissue confirmed the synovial sarcoma diagnosis...

..A better understanding of the pathogenetic pathways in the initiation and progression of desmoid tumors requires studies of 8q and 20q gains, as well as of 6q and 5q losses, and study of the Wnt/beta-catenin pathway...

....

....

..More surprisingly, the sequence inserted corresponds to the complementary sequence of the wild allele but in the opposite sense. To our knowledge, this mutation has never been previously described...

..The goal of this work was to evaluate the impact of expert pathological second opinion on the diagnosis and management of patients with cancer, in a French region (Aquitaine) and with an economic point of view...

..Finally, and may be more importantly, HMGA2 is useful for the diagnosis of benign fibrous histiocytoma, nodular fasciitis and vulvovaginal benign mesenchymal tumors...

..Our goal was to determine whether the absence of CDK4 amplification was (a) correlated to a specific clinico-histopathologic profile; and (b) compensated by another genomic anomaly involving the CCND1/CDK4/P16INK4a/RB1/E2F pathway...

....

..Although RT-PCR analysis appears not to possess diagnostic value in tumors with < 50% tumor cell immunopositivity, it is strongly recommended for the diagnosis of tumors containing > 50% myogenin-positive cells...

..The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma (AS)...

....

..Proper understanding and utilisation of the diagnostic criteria and classification of GIST by pathologists are essential for good patient management...

..The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist...

..Epithelial atypia could be more a risk marker of concomitant than subsequent cancer...

..Soft tissue sarcoma should also be treated in specialised centres. Surgery quality depends on obtained margins that are determined best by close collaboration between the surgeon and the pathologist...

..Nine cases have been previously described in the literature. In this retrospective study, we report six cases reviewed in the department of pathology at the Bergonié Institute between 01/01/1987 and 31/12/2009...

..80) and CDK4 (kappa, 0.93). Immunostaining for MDM2 and CDK4 is a reproducible technique that may be exported to different laboratories for routine use. Tissue microarray is indicated for studying large series...

..These results suggest the possibility of a newly defined subgroup of primitive round cell sarcomas characterized by CIC rearrangements, distinct from Ewing sarcoma family of tumors...

..Usually, the lesion is small and shows a myopericytic differentiation. The cells are short, fusiform and arranged concentrically around small vascular lumen. We reported here the second case of arterial mural myopericytoma...

..The LNA-1 anti-HHV-8 antibody is a reliable marker of all variants of KS. Because KS mimickers are consistently negative for this marker, its use for diagnostic purposes is recommended...

..Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion...

..Some of these intermediary forms may correspond to a genomic premalignant condition while some may have no malignant potential...

..This case demonstrates that the gastrointestinal tract is a potential site for primary clear cell sarcoma of soft tissues, and, furthermore, that cytogenetics and/or molecular techniques play a central role in the diagnosis...

..In conclusion, intrathoracic SS are rare but aggressive tumors with poor prognosis. In this unusual location, the detection of SYT-SSX fusion transcripts is a valuable diagnostic adjunct...

..The characterization of common gene alterations in both tumor groups would suggest a closer relationship between these two types of soft tissue sarcomas...

..To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS)...

..These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors...

..However, the high rate of local relapses (especially in field of radiation) does not demonstrate the usefulness of radiotherapy at the level of dose used and further preferably randomized studies should be planned...

..The role of immunohistochemistry and molecular pathology in the identification and delineation of these new entities is emphasized...

..We conclude that synovial sarcoma has to be added to the list of radiation-associated soft-tissue sarcomas...

..Finding of MDM2 and CDK4 iperexpression by immunohistochemistry confirmed the diagnosis of dedifferentiated liposarcoma...

..For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation...

..The objectives of the current retrospective study were: 1( to analyze the relation between DDLs and tumors previously diagnosed as MFHs; 2) to trace the evolution of liposarcomas, and 3) to assess the consequences of dedifferentiation...

..On the basis of cytogenetic and molecular findings, some SCL may constitute an independent entity rather than being regarded as variants of WDLPS...

..In addition, the t(X;18) can be detected not only on frozen but also on paraffin-embedded tumor samples...

..We also found a frequent amplification and overexpression of YEATS4, an oncogene that inactivates P53, suggesting that YEATS4 might play an important role together with MDM2 in WDLPS/DDLPS oncogenesis...

..In conclusion, we recommend that the evaluation of MDM2-CDK4 amplification using FISH or Q-PCR be used to supplement IHC analysis when diagnosis of adipose tissue tumors is not possible based on clinical and histologic information alone...

..The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related...

..Of great importance is the determination of such genetic markers as additional tools for the differential diagnosis between benign and malignant forms of adipose tumors, and to avoid erroneous diagnoses...

..Few STSs that showed a TRF pattern suggestive of alternative lengthening of telomeres (ALT) may contain ALT subpopulations...

..We confirm by cellular and xenograft mouse models recapitulating these sarcoma genetics that the failure to differentiate is dependent upon JUN amplification/overexpression...

..It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome...

..Laboratories that use PCR-based techniques for diagnostic purposes would benefit from quality assurance programs...

..This case analysis demonstrated the utility of molecular genetics as a powerful tool for the diagnosis of atypical forms of dermatofibrosarcoma protuberans...

..In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression...

..We confirm our preliminary CGH results and demonstrate that two main clusters of tumors are present in the series analyzed...

..The search for rearrangement of ALK by fluorescence in situ hybridization (FISH) is a useful complementary tool for IMT diagnosis...

..A national consensus meeting was therefore organized in order to identify the optimal management procedures for patients with GIST in localized and advanced stages...

..It has to be differentiated from extraskeletal myxoid chondrosarcoma, parachordoma and synovial sarcoma. Most of myoepitheliomas are benign. However, metastasis may occur in a minority of cases...

..2 were disrupted by this rearrangement. Although rare, the existence of cases of DFSP negative for the COL1A1-PDGFB fusion has to be taken in consideration when performing molecular diagnosis for a tumor suspected to be a DFSP...

....

..It can hopefully regarded as an example for targeted therapies, which may come with a better understanding of the molecular mechanisms triggered by the fundamental, specific genetic alterations shown in sarcoma...