Nonosseous sarcomas in a military hospital

This is a retrospective review of 67 patients with soft tissue or visceral sarcomas treated during 1973-1982. There were 40 males and 27 females. The mean age was 36 with a range of 1 to 77 years of age. The most common histologic subtypes were rhabdomyosarcoma (19%), malignant fibrohistiocytoma (13%), fibrosarcoma, leiomyosarcoma, dermatofibrosarcoma protuberans (12% each), and liposarcoma (10%). Among the 42 soft tissue sarcomas 33% occurred in the trunk, 35% and 21% in the lower and upper extremities, and 10% in the head and neck region. Among the 25 visceral sarcomas, 16% were in the thorax, 56% involved abdominal or retroperitoneal organs, and 28% were in the head and neck region. Overall, 33 of the 54 patients with early sarcomas were treated by surgical resection alone while 21 others had postoperative adjuvant radiotherapy and/or chemotherapy. Factors influencing survival are presented and patterns of metastasis discussed. Overall, 45% of the patients showed metastatic disease either at diagnosis (15%) or during the follow-up period (30%). The lung was involved in two-thirds of the cases and was the most common site of spread. In patients with rhabdomyosarcoma and malignant fibrohistiocytoma, regional lymph node metastasis was noted in 36% and 17%, respectively.     

Apport des analyses moléculaires à la classification anatomopathologique des sarcomes

Conventional histology and immunohistochemistry remain the basic tools for the diagnosis and classification of sarcomas. However, molecular biology can enrich the pathologists analysis: the identification of a specific molecular abnormality can confirm diagnosis, rule out a differential diagnosis, and sometimes provide prognostic information. About 15% of sarcomas bear a specific translocation, such as rearrangements of SS18 (SYT) [synovial sarcoma], DDIT3 (CHOP) [myxoid liposarcoma], FUS (TLS) [low-grade fibromyxoid sarcoma, myxoid liposarcoma], FOXO1 (FHKR) [alveolar rhabdomyosarcoma], PDGFB (dermatofibrosarcoma protuberans), and ALK (inflammatory myofibroblastic tumor). Rearrangements of the EWSR1 gene are less specific as found in many sarcomas (Ewing sarcoma, desmoplastic round cell tumor, clear cell sarcoma, myxoid liposarcoma, andmyoepithelioma). The search for an amplification of MDM2 gene is a sensitive and specific tool for the diagnosis of atypical lipomatous tumors/welldifferentiated liposarcomas and dedifferentiated liposarcomas (ALT/WDL). The same molecular abnormality can be observed in several tumor types, emphasizing the importance of integrating the results of any molecular study within clinical, morphological, and immunohistochemical context: ASPSCR1 (ASPL)-TFE3 translocation can be observed in alveolar soft tissue sarcoma but also in juvenile renal carcinomas, ETV6 (TEL)-NTRK3 (TRKC) translocation in infantile fibrosarcoma and secretory breast carcinoma, ALK rearrangements in inflammatory myofibroblastic tumors, anaplastic lymphomas, and lung adenocarcinomas. In some cases immunochemistry can highlight the consequence of a molecular abnormality: MDM2 overexpression in ALT/WDL, loss of INI1 expression in rhabdoid tumors and epithelioid sarcoma, and overexpression of ALK in inflammatory myofibroblastic tumors.     

Incidence, épidémiologie des sarcomes et biologie moléculaire. Résultats préliminaires de l’étude EMS en Rhône-Alpes

Sarcomas comprise a heterogeneous group of mesenchymal neoplasms. They can be grouped into 3 general categories, soft tissue sarcoma, visceral and primary bone sarcoma, which have different staging and treatment approaches. Soft tissue sarcomas are typically classified on the basis of genetic alterations and light-microscopic examination of hematoxylineosin-stained tissue, in which recognizable morphological characteristics of normal tissues are identified. Sarcomas are further characterized by histologic grade. The 3 most important prognostic variables are grade, size, and location of the primary tumor. This review includes a discussion of both soft tissue sarcomas (unclassified sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, dermatofibrosarcoma protuberans, angiosarcoma, Kaposi sarcoma, gastrointestinal stromal tumor, rhabdomyosarcoma, …) and primary bone sarcomas (osteosarcoma, Ewing sarcoma and chondrosarcoma). The approach to a patient with a sarcoma begins with a biopsy that obtains adequate tissue for diagnosis without interfering with subsequent optimal definitive surgery. Subsequent treatment depends on the specific type of sarcoma. Due to the absence of clear knowledge for incidence rate, we conducted in 2005 and 2006 an exhaustive analysis of all diagnosed cases in the Rhône-Alpes region. Because sarcomas are relatively uncommon yet comprise a wide variety of different entities, second opinion was systematically performed for all included cases.     

肢体软组织肉瘤34例外科治疗体会

目的探讨肢体软组织肉瘤的诊断与手术疗效。方法回顾性分析外科手术治疗并经病理证实的34例肢体软组织肉瘤患者的诊治资料。结果术后病理:韧带样瘤型纤维瘤病4例,纤维肉瘤5例,浅表型纤维瘤病1例,隆突性皮肤纤维肉瘤4例,恶性纤维组织细胞瘤4例,脂肪肉瘤5例,平滑肌肉瘤5例,恶性周围神经鞘膜瘤2例,滑膜肉瘤2例,原始神经外胚层瘤2例。28例获术后随访1～4 a,4例(14.3%)复发,复发时间12～26个月,平均20个月。结论外科手术是肢体软组织肉瘤最重要的治疗手段,合理应用综合治疗和个体化治疗可提高切除率、降低复发率。     

Management of sarcomas of the head and neck

Soft tissue and bone sarcomas in the head and neck are rare tumors. The 1000 to 1500 yearly cases in the United States are distributed among at least 10 main histologies and multiple head and neck subsites. Although this makes structured studies difficult to perform and high-level evidence-based treatment algorithms difficult to find, basic treatment recommendations can be made from the existing literature for most histologies and subsites. This paper discusses the epidemiology, natural history, and treatment approaches for several of the most common head and neck sarcomas, including the “adult soft tissue sarcomas,” osteosarcoma, chondrosarcoma of the larynx, angiosarcoma, rhabdomyosarcoma, desmoid tumors, and dermatofibrosarcoma protuberans.     

Signal transduction pathways in sarcoma as targets for therapeutic intervention.

Investigations into the molecular alterations in sarcomas have made substantial progress during the past decade. Classical linkage analysis and the direct sequencing of chromosomal translocation fusions have identified candidate genes in many different sarcomas. A large group of these genes participate in signal transduction pathways and represent potential sites of disease intervention with targeted therapies. This review will discuss five types of sarcoma that display aberrant tyrosine kinase pathway signaling: gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, congenital fibrosarcoma and mesoblastic nephroma, dermatofibrosarcoma protuberans, and desmoplastic small round cell tumor; one sarcoma predisposition syndrome with specific dysregulation of the ras pathway--neurofibromatosis--will also be discussed.     

Management of adult soft tissue sarcomas of the head and neck

Adult soft tissue sarcoma of the head and neck are rare and represent a heterogeneous group of tumours of different histological variants. Management of these neoplasms presents a great challenge. Malignant fibrous histiocytoma, fibrosarcoma, angiosarcoma and malignant peripheral nerve sheath tumour are the most frequently found sarcoma types in the head and neck. Although traditional morphological assessment is the foundation of clinical decision making, the role of immunohistochemistry and molecular biology are useful for diagnosis, prognosis and identification of possible targets for molecular therapy. The most frequently involved tumour sites are scalp/face, sinonasal tract/anterior skull base and parotid/neck. The management of soft tissue sarcomas in the head and neck is primarily surgical. Since it is difficult to obtain wide margins during surgical treatment in head and neck sarcomas, because of anatomic constraints, most patients undergo post-operative irradiation. Survival varies from 50 to 80%. Prognostic factors are tumour grade, margin status and tumour size. With further insight into the biology of soft tissue sarcoma, modern imaging techniques and new treatment options, we will most certainly be able to improve clinical outcome in patients with soft tissue sarcoma in the upcoming years.     

抑癌基因 P~(53)蛋白在78例软组织肉瘤的表达

本研究应用Ｐ５３蛋白单克隆抗体对７８例软组织肉瘤行免疫组化染色，并对各种软组织肉瘤组织中Ｐ５３蛋白的表达进行了分析研究，结果发现全部病例Ｐ５３总阳性率为４３．５％，在脂肪肉瘤（４７．０％）中阳性率较高，而平滑肌肉瘤（７．１４％）中阳性率较低。Ｐ５３蛋白阳性表达与肉瘤组织分化程度有关，分化愈低其阳性率愈高，且在不同类型肉瘤中有一定差别，说明Ｐ５３抑癌基因突变在软组织肉瘤发生发展过程中起着重要作用。     

Soft-tissue sarcoma: initial characteristics and prognostic factors in patients with and without metastatic disease

Five hundred and sixty-five patients with soft-tissue sarcoma were admitted to Memorial Sloan-Kettering Cancer Center from July 1, 1982 to July 1, 1985. Clinical and pathologic factors were analyzed to identify initial characteristics and to determine factors associated with prognosis and the development of metastasis. In decreasing order of frequency, the most common sites of primary tumor were the extremity (51.1%), retroperitoneum/viscera (28.8%), trunk (15.9%), head and neck (3.7%) and breast (0.4%). The most common histologic types were liposarcoma (21.4%), malignant fibrous histiocytoma (20.2%), leiomyosarcoma (20.0%), fibrosarcoma (11.0%), and tendosynovial sarcoma (9.6%). One hundred and twenty-eight patients (22.7%) had metastases in a median follow-up period of 19 months. Metastasis was more common in patients with retroperitoneal and visceral sarcomas than in patients with extremity sarcomas. Patients with leiomyosarcomas were more likely to develop metastases than those with other histologic types. Fibrosarcoma and liposarcomas were the least likely to develop metastases in this time frame. Tumors greater than 5 cm in diameter occurred more frequently in patients with metastases. Actuarial survival was related to the site of primary tumor and the histologic type and grade of malignancy. Multivariate analysis indicated that patients with low-grade sarcomas, extremity sarcomas, and fibrosarcomas and patients without metastatic disease demonstrated significantly improved survival. In patients with metastases, disease-free interval (less than 365 or greater than or equal to 365 days) was significantly related to overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sarcomas of the head and neck region

PURPOSE OF REVIEW: This review discusses the classification, etiology, diagnosis, evaluation, treatment, and prognosis of sarcoma of the head and neck region. RECENT FINDINGS: Sarcomas account for less than 1% of all malignancies in the United States with only 5 to 15% of these sarcomas occurring in the head and neck region. However, about 1 in 3 pediatric sarcomas will occur in the head and neck region. Occasionally, these tumors are associated with genetic syndromes or previous radiation exposures, but, most commonly, no clear etiology exists. Pathologic classification is critical to the ultimate treatment and prognosis of sarcoma of the head and neck. Osteosarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, and angiosarcoma are the most common types of sarcoma to occur in the head and neck region; however, up to 20% of head and neck sarcomas will remain unclassified. Surgery has been central to the management of these malignancies with some exceptions in the pediatric population. Adjuvant chemotherapy is being utilized and/or studied for most high-grade sarcomas and adjuvant radiotherapy is important for disease control in high-grade soft-tissue sarcomas. Prognosis is clearly related to tumor grade and margin status. SUMMARY: Sarcomas of the head and neck region are rare malignancies often without a clear etiology. Expert pathologic review and classification is critical, as are quality imaging and multidisciplinary management.     

纤维肉瘤超微结构的研究

Ultrastructure of 9 cases of fibrosarcoma was observed and compared with that of fibrous connective tissue of 4 human embryos and 9 cases of spindle cell sarcoma, including 3 each of leiomyosarcoma, neurofibrosarcoma and dermatofibrosarcoma protuberans. Ultrastructurally, fibrosarcoma consisted of well-differentiated fibroblast-like cells, poorly differentiated fibroblast-like cells (embryonic fibroblast-like cells), myofibroblast-like cells and primitive mesenchymal cells. It is suggested that fibrosarcoma may arise from primitive mesenchymal cells which are capable of differentiating into fibroblast and myofibroblast. There were two special cases of fibrosarcoma in this series. One was a congenital fibrosarcoma with ultrastructure resembling adult and the other was a sarcoma of myofibroblast. Diagnosis and differential diagnosis between fibrosarcoma and leiomyosarcoma, neurofibrosarcoma, dermatofibrosarcoma protuberans are discussed.     

Surgery of soft tissue sarcomas in children

Surgery of soft tissue sarcomas in children has been modified by the introduction of multidisciplinary treatment so that major amputation and exenterations are now rare in the management of these tumors in children. Surgery must still be well planned for total removal of the tumor with preservation of limbs and, in most instances, the function of pelvic organs. The commonest soft tissue sarcomas in children are embryonal rhabdomyosarcoma (RMS), fibrosarcoma, and synovial sarcoma. Treatment of embryonal RMS can now achieve a 2-year survival of 80% at all sites. Surgery and irradiation are used to control the primary tumor and multidrug chemotherapy to control metastases or prevent dissemination of localized tumor. Fibrosarcoma in children, usually a low-grade, extra-abdominal desmoid lesion, does not respond to radiation treatment or chemotherapy, and management is by surgery alone. It shows a marked tendency to local recurrence, and multiple local resections may be necessary for cure. Ninety percent of the children with this tumor can be salvaged by surgery and careful follow-up. The management of synovial sarcoma is surgical and similar to that of RMS. Although not radiosensitive as is RMS, this tumor has responded well to multidisciplinary treatment. Adequate resection is now followed by a chemotherapy protocol similar to that used in osteogenic sarcoma. The smaller numbers of these tumors and their varied natural history make evaluation of treatment difficult. Other soft tissue sarcomas seen with extreme rarity in children are liposarcoma, angiosarcoma, and neurosarcoma. These tumors are treated with the same protocol as that of RMS.     

Head and neck soft tissue sarcomas of adult: prognostic value of surgery in multimodal therapeutic approach

Adult head and neck soft tissue sarcomas (AHNSTS) are rare, and data concerning treatment results are spare. To assess clinico-pathological characteristics, management prognostic factors, and survival of AHNSTS, we reviewed our experience of 28 recent successive new cases. Data were collected from a retrospective database (1997-2002). Aggressive fibromatosis, dermatofibrosarcoma, Kaposi sarcoma, chondrosarcoma and osteogenic sarcoma were excluded. Univariate analysis for prognostic factors was performed with chi2 test with Yates correction. The median age was 45.7 years (range: 18-86). The male/female ratio was 15/13. The most common subtypes was rhabdomyosarcoma (seven cases). Twenty-two patients presented with previous inadequate resection performed elsewhere before admission. The most common location was neck muscles (11 cases). Nineteen patients had surgery (complete resection in 13 cases). Associated treatments were neoadjuvant chemotherapy, adjuvant chemotherapy and postoperative radiotherapy in respectively, 4, 3 and 10 cases. The 2-year overall survival was 56%. Rhabdomyosarcomas (p = 0.005) and inadequate resection (p = 0.04) were associated with poor outcome. Large resection of AHNSTS in a multimodality approach may afford the best chance of disease control.     

Current topics in the diagnosis and treatment of malignant fibrous histiocytoma

Malignant fibrous histiocytoma (MFH) is a tumor about which much remains unknown. The cell origin, molecular mechanism of pleomophism and mechanism of pleomorphic change in a cell undergoing malignant change have not been elucidated. MFH-like histological changes are observed in many bone and cartilage sarcomas, and some renal cell carcinomas and malignant lymphomas. These changes occur in many subtypes of sarcomas such as osteogenic sarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and liposarcoma. MFH has been regarded as one tumor classification from its special histopathological features. In clinical pathological studies these tumors are divided into low-grade fibrous tumors and fibrous histiocytic tumors. With the establishment of molecular biological diagnostic methods, MFH-like histological features can be seen in changes in cellular differentiation of many sarcomas. Patients with MFH often have repeated recurrences before a diagnosis is made, and the tumor is partially resected. Furthermore, distance metastasis develops and the prognosis is poor. The sensitivity of MFH to radiotherapy and chemotherapy is insufficient, and evidence is lacking for adjuvant treatment. Rescue following initial treatment failure is extremely difficult. Local control of 70% to 90% can be achieved if a correct diagnosis is made, and a curative wide resection or salvage wide resection are done early. For treatment of bone and soft tissue sarcoma, a correct diagnosis and initial treatment are extremely important. MFHs are rare tumors that occur in every part of the body. Many cases need to be accumulated in joint clinical studies across fields according to organ and specialty, and effective treatment method developed. We need to advance the standardization of treatment for MFH, and eliminate wrong initial treatment through the active provision of information.     

Clinicopathologic assessment of postradiation sarcomas: KIT as a potential treatment target.

PURPOSE: Postradiation sarcoma, a sarcoma developing in a previously irradiated field, is a rare tumor. Surgery appears to be the only curative treatment option. In general the prognosis is poor, and new treatments options are needed. One study reported the expression of KIT receptor tyrosine kinase in two postradiation angiosarcomas. Success of inhibition of KIT in malignant gastrointestinal stromal tumors with imatinib mesylate seems mutation-dependent, with a favorable response in the presence of exon 11 mutations. Experimental Design: We performed a clinical, immunohistochemical, and genetic assessment of postradiation sarcomas, including angiosarcomas. Archival tumor tissue was available from 16 patients diagnosed with a postradiation sarcoma between 1978 and 2001. Data on the first and secondary tumor, treatment, and follow-up was documented. KIT expression was assessed by immunohistochemistry. For comparison, 23 spontaneous soft tissue sarcomas of similar histological types were analyzed. Exon 11 of the c-kit gene was analyzed by direct DNA sequencing. RESULTS: Fifteen patients received initial irradiation for malignant disease and 1 patient for a benign condition. The median delivered dose was 50 Gy. The median latency period between irradiation and diagnosis of postradiation sarcomas was 222 months. Histological types included: angiosarcoma, fibrosarcoma, malignant fibrous histiocytoma, osteosarcoma, rhabdomyosarcoma, and unspecified sarcoma. In concordance with the literature, patients had a poor outcome. Only 3 of 16 patients were disease-free 43, 60, and 161 months after being diagnosed of postradiation sarcoma, all 3 having favorable tumor and treatment characteristics. Fourteen of 16 tumor samples were KIT-positive (88%). In 8 cases >80% of tumor cells stained positively. Five of 23 (22%) spontaneous soft tissue sarcomas of comparable histological types, including 2 angiosarcomas, were KIT-positive. Molecular genetic analysis of exon 11 of the c-kit gene was attainable for 13 of the 16 postradiation sarcomas. No mutations were found. CONCLUSIONS: Postradiation sarcomas are aggressive malignancies, seldom amenable to curative treatment. A majority of the analyzed tumors showed extensive expression of the KIT protein, but no mutations in exon 11 of the c-kit gene were found. Still, without the availability of effective therapies, treatment with the KIT inhibitor imatinib mesylate might be considered for patients with postradiation sarcomas.     

Malignant fibrous histiocytoma: an analysis of 200 cases.

The clinicopathologic findings in 200 cases of malignant fibrous histiocytoma (MFH) with follow-up information are presented. This tumor occurred principally as a mass on an extremity (lower extremity 49%, upper extremity 19%) or in the abdominal cavity or retroperitoneum (16%) of adults (peak incidence 61-70 years of age). It typically involved deep fascia (19%) or skeletal muscle (59%) and only rarely was confined to the subcutis without fascial involvement (7%). The MFH had variable morphologic features and frequently showed transitions from areas having a highly ordered storiform pattern to less differentiated areas having a pleomorphic appearance. The rate of local recurrence of the tumor was 44%, and of metastasis, 42%. Metastasis was most frequently to the lung (82%) and lymph nodes (32%). Factors that influenced the rate of metastasis included depth, size, and inflammatory component of the tumor. Tumors that were small, superficially located, or had a prominent inflammatory component metastasized less frequently than larger, more deeply located tumors. In our experience the MFH is the most common soft tissue sarcoma of late adult life, and many tumors previously diagnosed as pleomorphic variants of liposarcoma, fibrosarcoma, or rhabdomyosarcoma are probably examples of MFH. Although the histogenesis of this neoplasm remains controversial, we feel it is best regarded as a primitive and pleomorphic sarcoma showing partial fibroblastic and histiocytic differentiation, as reflected by collagen production and occasional phagocytosis.     

Soft tissue sarcomas in Osaka, Japan (1962-1985): review of 290 cases

Two hundred and ninety patients with soft tissue sarcomas (STS) in Osaka, Japan, were reviewed. The patients' ages ranged from one month to 84 years (mean 51 years) with a male to female ratio of 1.23:1. The tumors were located in the extremities (120 cases), the trunk (76 cases), the abdominal cavity (40 cases), and the head and neck (43 cases). Histologically the tumors were classified as malignant fibrous histiocytoma (101 cases, 34.8%), liposarcoma (28 cases, 9.7%), synovial sarcoma (24 cases, 8.3%), rhabdomyosarcoma (23 cases, 7.9%), neurogenic sarcoma (20 cases, 6.9%), fibrosarcoma (16 cases, 5.5%), leiomyosarcoma (16 cases, 5.5%) and others. From the present study, it appears that there are no significant differences between STS in Japan and Western countries with regard to the distributions of histological type and primary site.     

Emerging therapies for adult soft tissue sarcoma

Soft tissue sarcoma (STS) are a broad group of rare tumors. Cornerstone of treatment is surgery. Complementary radiotherapy is recommended in high-risk STS arising from extremities. Doxorubicine ± ifosfamide based cytotoxic chemotherapy, explored in few randomized trials, showed a certain degree of activity, playing an established role only in unresectable disease. Since peculiar chemosensitivity towards alternative drugs was described for different metastatic subtypes in second or further lines, the modern concept of ‘histology-driven chemotherapy’ has been accepted and employed: gemicitabine ± dacarbazine, trabectedin and taxanes used respectively in patients with leiomyosarcoma, solitary fibrous tumor, myxoid/round cell liposarcoma, angiosarcoma. Recent discoveries about molecular pathways involved in STS tumorogenesis led to develop molecular targeted agents such as imatinib used in advanced dermatofibrosarcoma protuberans (DFSP) or metastatic DFSP-related fibrosarcoma, pazopanib, approved as second line regimen in advanced non-adipocitic STS and recently sunitinib in solitary fibrous tumors, alveolar soft part sarcoma and extraskeletal myxoid chondrosarcoma.     

原发性256例软组织肉瘤手术治疗的临床分析

目的：探讨软组织肉瘤的诊断、手术治疗方法及其疗效。方法：对256例原发性软组织肉瘤患者的治疗情况进行回顾性分析。行局部广泛切除及根治切除术,对侵犯骨组织的软组织肉瘤则按微波原位灭活保肢手术处理。切除肿瘤后,行血管修复重建、带血管蒂游离皮瓣转移、局部皮瓣转移、肌腱移位、肌皮瓣移位。结果：发病年龄为20-70岁,占62.11%（159/256）,常见的病理类型为滑膜肉瘤、恶性纤维组织细胞瘤、脂肪肉瘤、横纹肌肉瘤、纤维肉瘤,占65.23%（167/256）。Kaplan-Meier法计算5年生存率为63.28%。结论：诊断采用CT、MRI为主的影像学,治疗以手术为主,辅助放疗和化疗。