Patients with primary localized high-grade sarcomas of the digestive tract excluding GIST : a retrospective study from the French sarcoma group.

INTRODUCTION: The natural history of localized high-grade sarcomas of the digestive tract (SDT) excluding GIST has been rarely considered owing to their low incidence and heterogeneity. We describe the histoclinical characteristics of SDT and correlate them with patients' outcomes. METHODS: We retrospectively collected medical files from a European database covering connective tissue tumors listed in Europe for about twenty years. Only untreated localized primary high-grade SDT were included. A central histological review was performed for each case. Patients' characteristics were compared and correlated with clinical outcomes. RESULTS: A total of 45 patients were identified. Leiomyosarcomas (LMS) and undifferentiated sarcomas (UDS) were predominant, the former having better overall survival (OS) and progressionfree survival (PFS) while the latter having a worse outcome than the other histological types. Complete remission was obtained in 34 patients (75%) and was associated with male sex, age over 40 years and monofocal tumor. Complete surgery and LMS histology were associated with a better prognosis without any significant difference in baseline characteristics or in treatment modalities. CONCLUSION: Complete surgery and histological type seem to be prognostic indicators of SDT. These results suggest the importance of treating these patients in a reference center.

Does aggressive local treatment have an impact on survival in children with metastatic rhabdomyosarcoma?

PURPOSE: Due to the extensive initial distant tumour spread in metastatic rhabdomyosarcoma, the importance of local treatment is sometimes underestimated. A retrospective study was conducted to identify the prognostic value of aggressive local treatment in paediatric metastatic rhabdomyosarcoma. PATIENTS: Patients with metastatic rhabdomyosarcoma aged 1-21 years treated in France from 1998 to 2011 according to European protocols MMT-4-89, 4-91, 98 and recent national guidelines were selected. Survival comparison were performed between patients with 'aggressive local treatment' (surgery and radiotherapy) and exclusive surgery or radiotherapy, after exclusion of patients with early progression. End-points were event-free and overall survival (OS). RESULTS: A total of 101 children, median age 9 years, with majority of primaries in unfavourable sites (73 patients, pts), T2 tumours (66 pts), alveolar subtypes (65 pts) and large tumours (>5 cm, 83 pts) received various chemotherapy regimens. On univariate and multivariate analyses, OS was better after 'aggressive local treatment' (49 pts; 44.3 ± 8%), than after exclusive surgery (10 pts; 18.8% ± 15.5%) or exclusive radiotherapy (29 pts; 16.1 ± 7.2%, P < 0.006). Moreover, OS was better in the case of surgery with complete resection (41.1 ± 10.2%) or microscopic residue (56.4 ± 14.9%) than macroscopic residue (20.0 ± 12.6%; P < 0.03). CONCLUSIONS: In this large retrospective analysis, OS appeared to be better for patients receiving 'aggressive local treatment' even after adjustment for the initial patient and tumour characteristics. Isolated debulking surgery is associated with a very poor outcome and should be avoided. Aggressive local treatment in patients with rhabdomyosarcoma, even with metastasis, should be seriously considered.

High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.

BACKGROUND: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome. METHODS: Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). RESULTS: Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). CONCLUSION: A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

Angiosarcomas, a heterogeneous group of sarcomas with specific behavior depending on primary site: a retrospective study of 161 cases.

BACKGROUND: Angiosarcomas are rare, heterogeneous and a retrospective study was conducted to describe their natural history. PATIENTS AND METHODS: We reviewed 161 files of angiosarcoma treated in three institutions of the French Sarcoma Group from 1980 to 2004. Survival and prognostic factors for survival were analyzed. RESULTS: Median age was 52 years. Primary sites were the breast (35%), skin (20%) and soft tissues (13%). At initial diagnosis, 31 (19%) had metastases. Surgery was the first treatment in 121 (75%) patients combined with chemotherapy or radiotherapy in 34 and 32, respectively. Ninety (74%) of these 121 patients relapsed, mostly locally (50). With an average time since initial diagnosis of 8.1 years, 123 (76%) patients progressed and 76 (47%) died. Median survival was 3.4 years [95% confidence interval (CI) 2.4-5.8], and the 5-year overall survival (OS) rate was 43% (95% CI 33-53). In multivariate analysis, liver primary site [relative risk (RR) = 12.62], performance status (PS) of two or more (RR = 3.83), presence of metastases at diagnosis (RR = 2.50), soft tissue tumor (RR = 0.31) were correlated to OS. PS, liver and soft tissue tumors were identified as independent prognostic factors for progression-free survival. CONCLUSIONS: Angiosarcomas have an overall poor outcome, but with a clearly distinct prognosis depending on the primary site.

Sarcomas and malignant phyllodes tumours of the breast--a retrospective study.

BACKGROUND: Although most breast cancers are adenocarcinomas of the mammary gland, primary breast sarcomas may also arise from mammary gland mesenchymal tissue. The annual incidence of primary breast sarcoma is low and has been estimated at 45 new cases per 10 million women. These tumours are at high risk of recurrence and are known to have poor prognosis. Phyllodes tumours represent a specific subset of these breast soft tissue tumours. They are composed of a connective tissue stroma and epithelial elements. Pathological presentation ranges from grade I to malignant phyllodes tumours (grade III) where the stromal component clearly exhibits a sarcoma pattern. MATERIALS AND METHODS: SAPHYR (SArcoma and PHYllode Retrospective) is a retrospective study of the experience of Leon Bérard Cancer Centre (Lyon, France) from 1966 to August 2004. SAPHYR aims to describe the characteristics of primary breast sarcomas and to define potential survival factors to be evaluated in future prospective studies. RESULTS: We included 70 patients. Half of them presented at least one recurrence (35/70). Median disease-free-survival (DFS) was 1.15 years. At 3 years, median overall survival had not been reached and more than 61% of the patients were alive. Quality of surgical resection was significantly (p=0.036) different whether patients were in the R0 group (72%) or not (38%). No survival difference was found between malignant phyllodes (grade III) and other primary breast sarcomas (angiosarcomas excluded). Histology revealed three significantly (p=0.0003) different prognostic groups: phyllodes grade I and II (DFS=57%), angiosarcomas (DFS=7%) and phyllodes grade III and other primary breast sarcomas (DFS=45%). DISCUSSION: Phyllodes tumours and primary breast sarcomas are totally different from epithelial breast cancers and should be considered as a distinct group of rare tumours. The first goal of treatment is to achieve negative margins (R0). We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival. As further prospective studies are needed, European oncology groups must join their forces to create a prospective Rare Cancer Network.

Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group.

BACKGROUND: Histologic grade is said to be the most important prognostic factor in adult soft tissue sarcomas (STS), but most grading systems have been tested in the overall sarcoma group and the predictive value of histologic grade needs to be assessed specifically for each of the histologic categories. METHODS: From 1980 to 1994, 1240 nonmetastatic patients were entered in the French STS database. The following parameters were studied: patient's age and gender, previous history, tumor location, size and depth, neurovascular or bone involvement (NBI), histologic type and subtype, and grade (the French Federation of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88 months; only 5% of patients were lost to follow-up. The authors performed univariate and multivariate analyses for metastasis-free survival for the overall sarcoma group and for every main histologic type. RESULTS: In order of importance, parameters were respectively retained as independent predictors of metastasis as follows: grade, tumor size, NBI and tumor depth for the overall group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size, histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n = 125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n = 158). No parameter was significant for malignant schwannomas (n = 72) or for rhabdomyosarcomas (n = 60). CONCLUSION: In this study, histologic grade appeared as an independent predictor of metastasis development in the main histologic types of adult STS, with the exception of malignant schwannomas and rhabdomyosarcomas.

Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients.

PURPOSE: To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. PATIENTS AND METHODS: Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. RESULTS: The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location. CONCLUSION: These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors.

Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes. The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%). In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.

Desmoid tumor arising in a cesarean section scar during pregnancy: monitoring and management.

Desmoid tumors (DTs) are frequently associated with either surgical trauma, like scars, or physiologic trauma, like pregnancy. A DT arising in a cesarean scar during pregnancy shows both correlations. A case of DT that grew gradually in a cesarean scar during the first trimester of a subsequent pregnancy is presented. After initial MR imaging, the lesion was biopsied and carefully monitored; immediate surgical removal was considered at any time if indicated by the follow-up results. No increase in the tumor size was observed during the following 6 months of gestation, and the lesion was extirpated with mesh replacement of the abdominal defect at the time of cesarean section.

Primary cardiac sarcomas: an immunohistochemical and grading study with long-term follow-up of 24 cases.

AIMS: Primary cardiac sarcomas are rare and aggressive tumours. The aims of this study were to precisely classify cardiac sarcomas according to their pathology, and to determine their clinicopathological features and prognosis. METHODS AND RESULTS: Twenty-four primary cardiac sarcomas were studied. Clinical features and follow-up of all patients were collected. Histological diagnoses were obtained by combining both morphological features as described in soft tissue counterparts and the immunoprofile of the tumours. The 24 cases were classified as undifferentiated sarcoma (nine cases), angiosarcoma (six cases all located in the right atrium), leiomyosarcoma (six cases), malignant fibrous histiocytoma (one pleomorphic and one giant cell type) and synovial sarcoma (one case). Patients included 14 men and 10 women, with a mean age of 46 years. Clinical manifestations were protean, often delaying the diagnosis. Dyspnoea resulting from obstruction of the cardiac chambers was the most common symptom. Echocardiography and magnetic resonance imaging were useful respectively to detect and to evaluate tumour extension. Complete macroscopic resection was possible in only 33% of patients. The most common cause of death was local recurrence of the tumours (50%), even in the cases of complete macroscopic resection. Whatever the treatment, the prognosis was poor with a mean survival of 16.5 months after diagnosis. CONCLUSIONS: All types of sarcomas may be observed in the heart with a predominance of undifferentiated sarcomas. Histological grading, unlike histological type, seems to correlate with survival which remains extremely poor.

Case report: a preterm infant with an extradural myxopapillary ependymoma component of a teratoma and high levels of alpha-fetoprotein.

The sacrococcygeal region may be the origin of germinal tumors, of paragangliomas, and, rarely, of extradural myxopapillary ependymomas (MPE) in the newborn and child. A case is presented of a preterm child with an abdominal tumor, originating from the precoccygeal area, that turned out to be a teratoma with a component of an MPE. The high levels of alpha-fetoprotein in this preterm baby were initially misleadingly interpreted as a tumoral marker. The differential diagnosis and the difficulties in interpreting tumoral markers in infants are discussed.