Biomedical subjects

Jean-Michel Coindre

Publications and source records attributed to Jean-Michel Coindre.

At least 19 recordsLinked to original sources

PubMed2025

Deciphering Pseudoendocrine Sarcoma: A Clinicopathological, Molecular, and Epigenetic Study Suggesting Biological Links With Solid Pseudopapillary Neoplasm of the Pancreas.

Pseudoendocrine sarcoma (PS) is a recently described neoplasm of uncertain differentiation, characterized by recurrent CTNNB1 mutations, frequent paravertebral location, and a neuroendocrine-like histomorphology. In this study, we report the clinicopathologic, immunohistochemical, transcriptomic, and epigenetic findings of 12 PS cases. The tumors affected 7 men and 5 women with a median age of 66 years and were located in the paraspinal/paravertebral region (n = 11) and the thigh (n = 1). Median tumor size was 82 mm (range, 32-170 mm). Histologically, the tumors comprised sheets and nests of epithelioid-to-ovoid cells with uniform nuclei and speckled chromatin, frequently associated with extracellular hyaline globules and fibrovascular cords/septa. Uncommon findings included microcalcifications, myxoid stroma, pseudopapillary, pseudoglandular, microcystic or corded architecture, and lumen and rosette-like structures. Necrosis was absent, and mitotic activity was low. On immunohistochemistry, the tumors showed aberrant nuclear staining for beta-catenin (8/8) and expression of CD56 (7/7), S100 (8/8), desmin (2/6), and androgen receptor (1/4). Pankeratin (AE1/AE3), progesterone receptor, synaptophysin, chromogranin, and INSM1 were negative. All tested cases harbored CTNNB1 mutations. Using a customized cohort, methylation profiling revealed that PS formed a common cluster with solid pseudopapillary neoplasm of the pancreas (SPNP), distinct from all methylation classes from the Heidelberg sarcoma classifier and a subset of paragangliomas. Transcriptomic analysis showed that PS formed an independent cluster from a control group of tumors (including SPNP). Differential gene expression analysis showed enrichment in genes of the Wnt signaling pathway (HALLMARK gene sets) and biological processes related to sensory perception, among others (gene ontology - biological process [GO-BP]). Additionally, upregulated genes were related to various fetal cell types from the cell type signature data set (MSigDB), particularly of neuronal and epithelial lineage. Immunohistochemical assessment of potential markers identified through gene expression analysis revealed focal-to-diffuse expression of GLUT1 (6/6) and focal/multifocal expression of Brachyury (4/9) and HuD (3/7). Follow-up information, available for 10 cases (median duration of 18 months; range, 7-69 months), showed local recurrences and metastatic spread in 2 patients each. Evidence of response to radiotherapy was documented in one tumor. Altogether, this study expands knowledge on PS and suggests biological links with SPNP, including a potential shared cell of origin.

Humans↗

PubMed2006

Genetic polymorphisms of the XPG and XPD nucleotide excision repair genes in sarcoma patients.

There are more than 50 subtypes of soft tissue sarcomas, among which 30% are associated with specific genetic alterations, including translocations. Several studies have reported associations between cancer risk and polymorphisms of DNA repair genes from the nucleotide excision repair (NER) pathway. NER involves more than 20 proteins whose inactivation leads to xeroderma pigmentosum (XP) or cockayne syndrome (CS), among which XPD, a helicase allowing DNA strand excision by the endonuclease XPG. DNA from 93 patients with synovial sarcomas, myxoid liposarcomas, dermatofibrosarcomas protuberans (DFSP), malignant fibrous histiocytomas and leiomyosarcomas were genotyped for both XPD Lys751Gln and XPG Asp1104His polymorphisms. Departure from Hardy-Weinberg was highly significant for the XPG polymorphism with an excess of heterozygotes in synovial sarcomas (p = 1.5 x 10(-5)), myxoid liposarcomas (p = 1.5 x 10(-4)) and to a lesser extent in DFSP (p = 0.028). In the case of XPD, a significant deviation was observed in synovial sarcomas (p = 3 x 10(-6)) and DFSP (p = 0.0014). When tumors were pooled according to their genetic alterations, the proportion of carriers of the variant XPG allele was significantly increased in sarcomas with specific translocations as compared to sarcomas with complex genetics (p < 10(-9)). No difference was found for XPD. Genotyping of the tumor samples in synovial sarcomas and myxoid liposarcomas revealed frequent loss of heterozygosity for XPG, mostly due to the loss of the frequent allele. 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.

Adolescent↗

PubMed2006

Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues: clinicopathologic and molecular analysis of 44 patients from the French sarcoma group.

BACKGROUND: Clear cell sarcoma (CCS) is a rare tumor with a very poor prognosis that occurs predominantly in the distal extremities of young adults. Most patients bear the t(12;22) reciprocal translocation, which involves the EWS and ATF1 genes. 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. METHODS: Forty-four patients with CCS and 14 conventional melanomas were examined for the presence of EWS-ATF1 transcripts by using real-time polymerase chain reaction (PCR) analysis on paraffin embedded tissues, including frozen samples for 9 CCS samples and 9 melanoma samples. Prior to molecular analysis, the diagnosis of CCS was considered certain in 35 patients and as probable in 9 patients on the basis of location, histologic features, and immunohistochemical profile. Treatment modalities and follow-up were available for 41 patients with CCS. RESULTS: EWS-ATF1 fusion transcripts were detected in 38 paraffin embedded CCS tissues (86% of all samples; 93% of interpretable samples), 3 samples (7%) were negative, and 3 samples (7%) were considered uninterpretable. Fusion transcripts were detected in 7 of 9 samples for which the diagnosis of CCS was considered probable. EWS-ATF1 transcripts were not detected in the 14 samples of melanoma. Results from frozen tissues were concordant with those from all corresponding paraffin embedded samples. Twenty-eight of 41 patients (68%) experienced lymph node and/or distant metastasis, and the 5 year-survival rate was 44%. Mitotic index and histologic grade were predictive of survival and distant metastasis. CONCLUSIONS: The results of this study showed that the molecular detection of EWS-ATF1 fusion transcript by real-time PCR on paraffin embedded tissues is a sensitive and specific method for the diagnosis of CCS. It is an efficient tool for the diagnosis of unusual tumors, especially with regard to its distinction from melanoma. The current results also confirmed the poor prognosis for patients with this tumor type. Mitotic index and grade were predictive factors for survival and distant metastasis.

Adolescent↗

PubMed2006

Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis.

Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide. Antitumor activity has been observed for gemcitabine and docetaxel combination. We conducted a retrospective study on 133 patients (58 males/75 females) with unresectable or metastatic soft-tissue sarcoma. The median age at diagnosis was 51.7 (18-82), with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes. The initial localizations were limb (44), uterine (32), retroperitoneal (23) and organs or bone (34). Patients received 900 mg/m2 of gemcitabine (days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel (day 8), intravenously every 21 days. Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4% and with no clear statistical difference between leiomyosarcomas and other histological subtypes (24.2% versus 10.4% (p=0.06)). No difference was found between uterine soft-tissue sarcomas versus others. The median overall survival was 12.1 months (1-28). Better overall survival was correlated with leiomyosarcoma (p=0.01) and with the quality of the response, even for patients with stable disease (p<10(-4)). No statistical difference was found for the initial localization. Response to treatment and overall survival were better for patients in World Health Organization (WHO) performance status classification (PS) 0 at baseline versus patients in WHO PS-1, 2 or 3 (p=0.023 and p<10(-4), respectively). Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma, especially for patients in WHO PS-0 at baseline. For the other histological subtypes, the response was not encouraging, but the survival for patients in response or stable suggests further investigation.

Adolescent↗

PubMed2006

Retroperitoneal liposarcomas: follow-up analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocytomas.

BACKGROUND: Dedifferentiated liposarcoma (DDL) juxtapose components of well-differentiated liposarcoma (WDL) and nonlipogenic sarcoma. Malignant fibrous histiocytoma (MFH) is no longer considered a homogeneous entity, but rather as the common morphologic appearance of various subtypes of sarcomas. 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. METHODS: Between 1974 and 2001, 86 patients with retroperitoneal liposarcoma (61 patients) or MFH (25 patients) underwent surgery at Institut Bergonie in Bordeaux, France. Histologic review was performed and tumors reclassified as WDL or DDL were retained for further clinicohistologic study. Subsequently, initial presentation and all recurrences were analyzed. RESULTS: The 61 liposarcomas consisted of 21 WDLs and 35 DDLs; 17 MFHs were reclassified as DDL. In all, approximately half of the retroperitoneal liposarcomas and MFHs were found to be DDLs. The DDLs presented with a smaller size (20 cm vs.30 cm; P = .05) but a lower rate of complete resection (72% vs.90%; P = .015) and remission (72% vs. 100%; P = .0015). Dedifferentiated recurrence was evidenced in 7 WDLs. Ten DDLs presented with metastatic evolution. DDLs demonstrated a tendency toward lower rates of 5-year overall survival (55% vs. 82%; P = .075). CONCLUSIONS: Most occurrences of retroperitoneal liposarcomas and MFHs are in fact DDLs and dedifferentiated recurrence of WDLs is frequent. Retroperitoneal DDLs present a lower rate of complete remission than WDLs and a risk of metastatic recurrence. Therefore, extensive histologic analysis of WDLs is required to identify an undifferentiated component and avoid misdiagnosis of DDL.

Adult↗

PubMed2006

Detection of a new mutation in KIT exon 9 in a gastrointestinal stromal tumor.

Gastrointestinal stromal tumors are mesenchymal tumors arising in the stomach and small bowel and more rarely in the rectum, esophagus, peritoneum and retroperitoneum. These tumors are characterized by KIT or PDGFRA mutations. KIT mutations are all in frame and lead to constitutive tyrosine kinase domain activation without ligand binding. Mutations concern four exons (9, 11, 13 and 17) but mainly exon 11. We report a new mutation in exon 9, since only AY 502-503 duplication/insertion, FAF 506 insertion and P456S substitution have been previously reported. This mutation consists of a large deletion of 43 nucleotides and an insertion of 25 nucleotides. 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.

Aged↗

PubMed2006

alpha-fetoprotein expression in a dedifferentiated liposarcoma.

Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. We describe a unique case of relapsing retroperitoneal dedifferentiated liposarcoma with biochemical, immunohistochemical, and molecular evidence of alpha-fetoprotein (AFP) ectopic production. The lesion was associated to elevated AFP plasma levels that subsided after tumor removal. Immunohistochemical studies showed AFP production by a minority of tumor cells and reverse transcriptase polymerase chain reaction confirmed AFP mRNA expression. Finding of MDM2 and CDK4 iperexpression by immunohistochemistry confirmed the diagnosis of dedifferentiated liposarcoma.

Aged↗

PubMed2006

Pseudosarcomatous myofibroblastic proliferations of the bladder: a clinicopathologic study of 42 cases.

Inflammatory pseudotumor or pseudosarcomatous fibromyxoid tumor and postoperative spindle cell nodule of the bladder are unusual lesions of uncertain pathogenesis which share overlapping, if not identical, histologic features. We present our experience with 42 cases, the largest series to date, to study the etio-pathogenesis, histologic features, biologic behavior and relationship to "inflammatory myofibroblastic tumor" of childhood. Patients ranged in age from 7 to 77 years (mean 47 y) and males predominated (3.2:1). Most patients presented with hematuria (31/42). Common associations were smoking (10/30) and previous instrumentation or surgery (9/42). The clinicopathologic features of patients having or not having prior instrumentation were identical. Grossly the lesions were polypoid or nodular and involved any portion of bladder wall, most commonly the dome (9/27) and measured 1 to 10 cm (mean 4 cm). They were composed of spindled and stellate cells arranged in a myxoid background with numerous inflammatory cells. Myxoid hypocellular areas were more pronounced near the mucosal surface with greater cellularity and a fascicular arrangement in the deep aspect of the lesion. "Atypical" features included mitotic activity (0 to 20/10 HPF; mean 2/10 HPF; median 1/10 HPF; none atypical), necrosis (22/42), and extension into muscularis propria (28/32) or perivesicular fat (3/8). Lesions were positive for cytokeratin (31/33), SMA (23/34), desmin (21/35), and Alk-1 protein (12/26). FISH confirmed the Alk-1 translocation in 4/6 cases. Treatment included transurethral resection (30/42), partial cystectomy (9/42), and total cystectomy (3/42). Initial diagnostic error resulted in radiotherapy and chemotherapy in 3 patients. Follow-up was available in 28 patients. (range 3 to 93 mo; median 25 mo). Three patients developed recurrences, but none had metastases. Because the clinicopathologic features of lesions associated with and without instrumentation were similar and inseparable, we believe they are essentially the same entity, and propose the term pseudosarcomatous myofibroblastic proliferation. The preponderance of evidence which includes the extravesical growth, local recurrence, and Alk-1 gene translocation in some cases suggests perhaps a neoplastic process with limited growth potential. Even in the face of atypical histologic features (muscle invasion and necrosis) the prognosis is excellent. Despite the Alk-1 gene translocation, there continues to be sufficient evidence for regarding these as distinct from the so-called inflammatory myofibroblastic tumor of childhood.

Adolescent↗

PubMed2006

Reproducibility of MDM2 and CDK4 staining in soft tissue tumors.

MDM2 and CDK4 immunostaining can be useful adjuncts in diagnosing liposarcoma among soft tissue neoplasms. We examined the reproducibility of MDM2 and CDK4 staining between 2 laboratories and between tissue microarrays and whole tissue sections. Sixty-two soft tissue tumors were immunostained at the Bergonié Institute, Bordeaux, France, and the Curie Institute, Paris, France. We also examined 203 soft tissue neoplasms on standard tissue sections and tissue microarrays. There was high concordance of results obtained from the 2 laboratories (with 2 different pathologists) for MDM2 (kappa, 0.93) and CDK4 (kappa, 0.8) staining. There also was excellent concordance between results on tissue microarray and on whole tissue sections for MDM2 (kappa, 0.80) 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.

Biomarkers, Tumor↗

PubMed2006

Grading of soft tissue sarcomas: review and update.

CONTEXT: Histologic grading is the most important prognostic factor and the best indicator of metastatic risk in adult soft tissue sarcomas. The most commonly used systems are the French grading and the National Cancer Institute grading. Both are 3-grade systems and are mainly based on histologic type and subtype, tumor necrosis, and mitotic activity. Rules for using grading should be strictly respected and limitations of grading should be known to obtain the best performance. The most controversial point is the respective values of histologic typing and grading. Histologic typing should be clearly defined before any attempt at grading, and grading should not be used on tumors of intermediate malignancy such as atypical fibroxanthoma and on some sarcomas such as dedifferentiated liposarcoma. 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. OBJECTIVE: To review the current value and limitations of histologic grading in soft tissue sarcomas. DATA SOURCES: The reviews on grading and original studies on prognostic factors in soft tissue sarcomas were analyzed. CONCLUSIONS: Grading is the best predictor of metastasis outcome in adult soft tissue sarcomas and should be part of the pathologic report. Grading should be adapted to the modern management of patients and complemented by radiologic and molecular parameters.

Biopsy, Fine-Needle↗

PubMed2005

Primary clear cell sarcoma of the ileum: an uncommon and misleading site.

A clear cell sarcoma, arising primarily in the ileum of a 35-year-old man, is reported. Histologically, the neoplasm infiltrated the full thickness of the intestinal wall. It consisted of strands and sheets of round to spindle-shaped cells with clear to eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. Vascular invasion was present at diagnosis. Tumour cells expressed S-100 protein, melan-A and tyrosinase. They were negative for HMB45, CD117, cytokeratins, epithelial membrane antigen, smooth muscle actin, desmin, CD31, CD34, chromogranin and synaptophysin. Reverse transcription-polymerase chain reaction analysis performed on paraffin-embedded tissue showed EWS-ATF1 fusion transcripts representative of the t(12;22) (q13;q12) clear cell sarcoma reciprocal translocation. The patient, who developed liver metastases 2 months after diagnosis, died of disease at 15 months. 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.

Adult↗

PubMed2005

[Digitalized imaging pathology: application to quality control in cancer diagnosis].

OBJECTIVES: To test a double histology reading system based on digitalized imaging for cancer diagnosis. MATERIAL AND METHODS: Pathology images of cancer diagnosis material were produced in real time by a digital imaging system integrated into the laboratory data processing system. Over a 30-day period, second readings were performed using the digitalized images. Cases with second readings were classified according to the aspect on the digitalized images as malignant tumor with histological type, malignant tumor with no other precision, and doubtful malignancy. RESULTS: During the study period, 204 cases of cancer were diagnosed, including 178 with digitalized imaging (87%). Among the digitalized cases, 119 (67%) were classified as malignant tumor with histological type, 53 (30%) as malignant tumor with no other precision, and 6 (3%) as doubtful malignancy. The histology material of these latter cases were reviewed and corresponded to malignant tumors. Approximately 2 hours per week were devoted to the second readings. CONCLUSION: A integrated digitalized imaging system can participate in quality control of cancer diagnosis by allowing rapid efficacious second readings.

Clinical Laboratory Information Systems↗

PubMed2005

[Gastrointestinal stromal tumors: definition, histological, immunohistochemical, and molecular features, and diagnostic strategy].

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have resulted in the delineation of a treatment that has become a model of targeted therapy in oncology. GISTs are defined as tumors of the gastrointestinal tract, but also of the mesentery and peritoneum, constituted by a proliferation of usually spindle-shaped, rarely epithelioid cells, usually, but not consistently expressing the KIT protein. Most GISTs are associated with molecular abnormalities in two target genes: KIT (which encodes the KIT protein) and PDGFRA (which encodes the A chain of the PDGF receptor). The diagnosis of GIST relies on histological arguments (proliferation of spindle-shaped cells in 70% of cases, of epithelioid cells in 20%; histological variants are rare and sometimes misleading) and on immunohistochemical arguments (expression of KIT in 95%, usually associated with CD34 expression in 60%-70% of cases). The demonstration of mutations in target genes is required only in cases that are histologically suggestive but KIT-negative; beyond this indication, this is only undertaken in research protocols. The differential diagnosis of GIST includes the other mesenchymal tumors of the gastrointestinal tract, such as leiomyomas and leiomyosarcomas, and the digestive locations of some sarcomas; it relies on both histological and immunohistochemical arguments. The evaluation of the prognosis is essential. According to the current concept, every GIST carries a risk of malignancy, which may vary from very low to very high. Prognosis is based on a simple algorithm using two histoprognostic parameters, i.e., tumor size and mitotic index. The treatment of localized GIST is surgical resection, which must be complete; that of advanced or unresectable GIST is based on the use of a targeted therapy, imatinib, which is a pharmacological antagonist of the KIT protein. Proper understanding and utilisation of the diagnostic criteria and classification of GIST by pathologists are essential for good patient management.

Adult↗

PubMed2005

Myxoid malignant fibrous histiocytoma and pleomorphic liposarcoma share very similar genomic imbalances.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma. Nevertheless, the validity of this heterogeneous pathological entity has been recurrently questioned by pathologists. Recently, analyses by comparative genomic hybridization (CGH) of a large series of MFHs suggested that MFHs consist of morphologic modulation of other poorly differentiated sarcomas like leiomyosarcomas (LMS) or dedifferentiated liposarcomas (DLPS). We report here an analysis by CGH of 22 myxoid MFHs (mMFH), one of the five histological subtypes of MFH, and of nine pleomorphic liposarcomas (pLPS), a rare poorly differentiated LPS. The chromosome imbalances encountered in the series of mMFH were very similar to those observed in the series of pLPS studied in the laboratory and in the series of 14 pLPS published in the literature. The most frequent gains involved chromosome subregions: pericentromeric regions of 1, 5p, 19p, 19q and 20q. Losses found in the chromosomal arms 1q, 2q, 3p, 4q, 10q, 11q and 13q were also recurrent. The use of a clustering software did not separate the two pathological groups (mMFH and pLPS) on the basis of genomic data. Moreover, pLPS-mMFH represented, according to the clustering software results, an entity clearly distinguished from other soft tissue sarcomas, LMS in particular, with which they share common genetic aberrations. Additional studies are needed to identify genes targeted by these genomic aberrations, and implicated in the oncogenesis of these tumor subtypes. The characterization of common gene alterations in both tumor groups would suggest a closer relationship between these two types of soft tissue sarcomas.

Adult↗

PubMed2005

Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene.

Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. 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.

Adolescent↗

PubMed2005

Primary intrathoracic synovial sarcoma: a clinicopathologic study of 40 t(X;18)-positive cases from the French Sarcoma Group and the Mesopath Group.

Synovial sarcoma (SS), an aggressive neoplasm accounting for up to 14% of soft tissue sarcomas, was recently recognized as a primary tumor in the lung and pleura. SS is characterized by the chromosomal translocation t(X;18)(SYT-SSX) found in more than 95% of the tumors. We report a cooperative study from the French Sarcoma Group and the Mesopath Group on 40 t(X;18)(SYT-SSX)-positive primary intrathoracic SS. There were 22 males and 18 females, whose age ranged from 16 to 79 years (median, 47 years). Neoplasms were mostly circumscribed and of large size (median, 7.5 cm; range, 2-16 cm). Thirty-nine tumors were monophasic SS, including 24 (60%) monophasic fibrous and 15 (37.5%) poorly differentiated cases, and one lesion was a biphasic SS. A larger proportion of poorly differentiated tumors were observed among intrathoracic SS as compared with soft tissue SS. Immunohistochemically, 90% of the cases reacted with at least one epithelial marker. CD34 was focally expressed in 3 cases. SYT-SSX1 fusion transcripts were detected in 22 cases (56.4%) and SYT-SSX2 fusion transcripts in 17 cases. Median and 5-year disease-specific survival in 33 patients was 50 months and 31.6%. Median and 5-year disease-free survival was 24 months and 20.9%. Patient sex, age, tumor size, histologic subtype, grade, and SYS-SSX fusion type had no significant impact on outcome. 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.

Adolescent↗

PubMed2005

[Recommendations for the management of GIST patients].

BACKGROUND: The management of gastrointestinal stromal tumors (GIST) has evolved very rapidly in the last years. A national consensus meeting was therefore organized in order to identify the optimal management procedures for patients with GIST in localized and advanced stages. METHODS: A panel of different specialties, including pathology, molecular biology, imaging, surgery, gastroenterology, medical oncology reviewed the current literature, in particular the recent Lugano conference, to identify consensus points and topics for future research in four different working groups: pathology and molecular biology, early management of small tumors and imaging, surgery, and medical treatment. Consensus points were categorized according to the Standard Options Recommendations (SOR) of the French Federation of Cancer Centers. RESULTS: The standard histological examination with immunohistochemical analysis using CD117, CD34, PS100, desmin and smooth muscle actin is considered standard. Molecular biology for the identification of KIT and PDGFRA mutation is advisable for GIST with negative CD117 staining, and otherwise is considered a research procedure. Complete tumor resection with negative tumor margins is the standard surgical treatment. Adjuvant imatinib after optimal tumor resection as well as neo-adjuvant imatinib remain experimental approaches to be performed within prospective clinical studies. Imatinib should be started at the date of diagnosis of metastatic relapse and given until development of intolerance or progressive disease. Resection of metastases is also considered as an experimental procedure which can not be recommended routinely. The criteria for tumor response to imatinib should include not only tumor size reduction or disease stabilization, but also reduction of tumor density (Hounsfield units) on computed tomography, metabolic activity (i.e. reduction of FDG uptake on positron emission tomography), and reduction of vascularisation of the tumors using contrast enhanced ultrasound evaluation. An increase in tumor size may be associated with pathologic response to imatinib therapy, and available survival data indicate that the survival of these patients is similar to that of patients with conventional tumor response. CONCLUSIONS: Consensus points in clinical management of GIST in this national conference adopted the majority of consensus points published in the Lugano conference. This multidisciplinary work will be published in the reference oncology, gastroenterology, and pathology journals in French languages.

Antineoplastic Agents↗

PubMed2004

Rhabdomyosarcoma: value of myogenin expression analysis and molecular testing in diagnosing the alveolar subtype: an analysis of 109 paraffin-embedded specimens.

BACKGROUND: Identification of the alveolar subtype of rhabdomyosarcoma (ARMS) is important, because the poor prognosis associated with this subtype necessitates a modified therapeutic regimen. At present, ARMS diagnoses are made on the basis of histologic findings and the extent of myogenin immunopositivity. Nonetheless, the absence of an alveolar pattern in the solid variant, the low degree of differentiation in certain embryonal rhabdomyosarcomas (ERMS), and the increasing use of microbiopsy samples make the diagnosis of ARMS somewhat difficult. Two specific translocations have been found in ARMS, and fusion transcripts can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of paraffin-embedded tissue (PET). METHODS: To assess the value of myogenin staining and molecular testing in the diagnosis of rhabdomyosarcoma, the authors examined 109 rhabdomyosarcoma samples (45 ARMS samples and 64 ERMS samples). Real-time RT-PCR analysis of PET was performed in all 109 rhabdomyosarcomas, and RT-PCR analysis of frozen material was performed in 24 cases. RESULTS: PAX fusion transcripts were present in 44 cases (39 ARMS and 5 ERMS) and absent in 52 cases (2 ARMS and 50 ERMS). In 13 cases (4 ARMS and 9 ERMS), the results were not interpretable. Results were concordant between paired frozen and fixed tumor samples. All 35 interpretable ERMS samples that contained < 50% myogenin-positive cells failed to yield detectable PAX fusion transcripts. Of the 61 interpretable tumor samples (41 ARMS and 20 ERMS) that contained > 50% myogenin-positive cells, 44 (39 ARMS and 5 ERMS) yielded detectable PAX fusion transcripts. CONCLUSIONS: The current study demonstrates that molecular detection of PAX fusion transcripts via real-time RT-PCR analysis of PET is a sensitive and specific method for the diagnosis of ARMS and that immunohistochemical analysis of myogenin expression can be used to select cases for such molecular testing. 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.

Adolescent↗