Text B Sarcomasof Soft Tissueand Bone

Definition

Sarcomas are a very heterogeneous group of malignant neoplasms of connective tissues，including bone and soft tissue．Sarcomas，as well as other putatively“nonmalignant”neoplasms that affect soft tissue and bone，share a mesenchymal cell of origin with aberrant differentiation and growth potential． Mesenchymal cells（derived from mesoderm），as well as neural crest cells（from ectoderm），are critical for the normal structure and function of humans because they give rise to the connective tissues that hold the organism together and also provide critical functions such as support and nourishment of neural tissues．When the growth，differentiation，or survival of these cells is aberrant， tumors arise．Sarcomas include a vast array of tumor types related to muscle， stromal tissue，adipose tissue，blood and lymphatic vessels，nerves and nerve sheaths，cartilage，bone，and other fibrous tissues．

Epidemiology

True sarcomas represent a very uncommon subset of human malignancies， accounting for less than 1％of cancers in adults but a disproportionately large number of cancers in the pediatric population（approximately 15％of pediatric cancers）．The overall incidence of sarcomas of soft tissue and bone is approximately 15，000cases per year in the United States．Given the fact that there are no sarcoma－specific disease diagnostic codes，however，such numbers must be viewed as rough approximations at best．Nonetheless，it is clear that sarcomas are uncommon compared with carcinomas．The prevalence of sarcomas significantly exceeds the incidence，because sarcomas can be cured with expert multidisciplinary care．This makes it critical that the initial evaluation and management of patients suspected of having sarcomas be performed by an experienced team with relevant expertise and interdisciplinary capabilities （including pathology diagnostic capabilities，surgical specialization，and radiotherapeutic experience and judgment，as well as access to the latest systemic therapy agents and data on their use）．Certain patients are at high risk of developing sarcomas，most notably individuals in families with Li－Fraumeni syndrome and those with neurofibromatosis（at risk for malignant peripheral nerve sheath tumors and GISTs）or familial polyposis（at risk for intra－abdominal desmoid tumors）．1 Other risk factors include exposure to radiation （including radiation therapy for other cancers，such as patients with prior irradiated breast cancer or survivors of retinoblastoma）．Chemical carcinogens can also increase the risk of sarcoma development，such as the increased risk of sarcomas in Vietnam veterans exposed to Agent Orange or the greatly increased risk of hepatic angiosarcomas associated with occupational exposure to polyvinyl chloride．2 However，the vast majority of sarcomas appear to be sporadic，with no evident inciting risk factors．

Clinical Manifestations and Diagnosis

Given the broad range of sarcomas，it is understandable that the clinical course can range from rapidly evolving and immediately life－threatening cancers（such as most Ewing's sarcomas）to indolent lesions that can take decades to evolve（such as atypical lipomatous tumors，also known well－differentiated liposarcomas）．Most patients with sarcomas present with a mass，often nontender，with a history of abnormal growth over time．For extremity tumors of soft tissues，it is important to note that many benign tumors（e．g． lipomas）cannot be easily distinguished from more worrisome neoplasms or even from frankly malignant sarcomas．Therefore，it is important to include sarcoma in the differential diagnosis of any mass．

The initial biopsy or surgical approach to a sarcomatous lesion is often the important，and a poorly oriented biopsy or a suboptimal surgical procedure can make the difference between cure with full limb function and disease recurrence with the need for amputation or mutilating surgical resection．The National Comprehensive Cancer Network（NCCN）has developed expert consensus guidelines for clinical practice that emphasize the importance of expert management from the moment a suspected sarcoma presents．The initial diagnosis includes appropriate imaging studies of relevant anatomic areas，including plain radiographs，computed tomography，or magnetic resonance imaging to define the anatomic area of the mass and surrounding tissue，as well as systemic staging because sarcomas can spread in well－defined patterns to distal sites such as the lung or liver．The decision to proceed to diagnostic biopsy，with optimal orientation，is an important one，and for certain lesions，forgoing incisional biopsy and proceeding directly to expertly planned surgical excision may be justified．The most important consideration is to make the correct diagnosis，and there must be sufficient amounts of properly prepared and expertly oriented tissues for optimal diagnosis analysis．In certain tumors with pathognomonic molecular markers（such as the translocation between chromosomes X and 18 that characterizes synovial sarcoma，or the balanced translocation between chromosomes 12 and 16 that defines myxoid and round cell liposarcoma），molecular analyses such as fluorescence in situ hybridization（FISH）may help make the diagnosis．

The diagnosis of a soft tissue or bone tumor is made by evaluating biopsy material in the clinical context，which includes understanding the tumor's anatomic location and imaging characteristics．Such contextual diagnostics are key to understanding whether a lesion may represent a primary sarcoma or whether it may be the first presentation of metastases from an occult primary tumor located elsewhere．Given the broad spectrum of sarcomas，the diagnostic considerations are quite far－reaching，especially because many benign pathophysiologic conditions can mimic sarcomas．For example，it may be very difficult for an inexperienced pathologist to distinguish among normal fat，inflammatory infiltrates，and liposarcoma．Similarly，certain fibroblastic neoplasms might simulate inflammation or scar．Therefore，a broad differential diagnosis is needed when considering any neoplasm of soft tissue or bone．

Treatment

The most important element of treatment is expert multidisciplinary care． The range of options is too broad to categorize simply，and the specific details of each patient's anatomy，comorbidities，functional status，and personal preferences must be taken into account when defining treatment options and management plans．Therefore，the care of virtually all sarcoma patients should be managed by an expert multidisciplinary team with expertise in advanced surgical and／or orthopedic oncology techniques，radiation therapy，reconstructive surgery，physical therapy and rehabilitation medicine，systemic therapies such as conventional cytotoxic chemotherapy，hormonal therapy，and modern molecularly targeted therapy with agents such as kinase inhibitors，as well as psychosocial support and specialized nursing care．Sarcomas represent such a complex family of diseases that referral to academic centers makes good sense for patients as well as for the health care system overall．Therefore，appropriate referral to obtain expert opinion and to define the diagnostic and treatment options for patients with suspected sarcomas is exceedingly important．

For most primary localized masses in which sarcoma is in the differential diagnosis，the first step is to obtain the correct diagnosis in a manner that does not compromise patient outcome or function．The need for biopsy must be considered first，because some small，localized sarcomas are best approached through definitive surgical excision following careful staging and expert review of imaging studies．For suspected sarcomas in deeper locations，such as deep within muscle compartments，or for large visceral lesions，biopsy may be necessary to ascertain the process is in fact a sarcoma，as well as to fully characterize the histopathologic subtype．This may make the difference between initial management with chemotherapy，as might be appropriate for a highly chemosensitive disease such as Ewing's sarcoma，versus surgery，which might be appropriate for a less chemosensitive disease such as differentiated liposarcoma．3

In general，expert surgical resection is first－line therapy for localized sarcomas．Preoperative or postoperative systemic chemotherapy is standard for most common forms of osteosarcoma，as well as for Ewing's sarcoma and certain rhabdomyosarcomas．Traditional cytotoxic chemotherapy is dramatically effective at increasing disease control and cure rates for certain sarcomas （especially those most prevalent in pediatric patients，such as osteosarcoma， Ewing's sarcoma and rhabdomyosarcoma）．It appears to be somewhat less effective in improving long－term cure rates for patients with other forms of soft tissue and bone sarcomas，such as liposarcoma，leiomyosarcoma，synovial sarcoma，and other subtypes．Nonetheless，appropriate use of chemotherapy can lead to objective responses in certain patients and can palliate metastatic disease with disease control and prolongation of progression－free survival．

For soft tissue sarcomas other than GIST，radiation therapy can play a meaningful role in preventing disease recurrence，especially for lesions that arise in the extremities．Radiation therapy can also provide significant palliation of unresectable disease，and it can be surprisingly effective in certain tumors such as desmoids tumor．However，radiation－associated sarcomas are increasingly common after therapeutic radiation therapy（e．g．in patients cured of breast cancer with radiation therapy），and an increasing incidence of poorly differentiated sarcomas or vascular sarcomas has been reported in patients following irradiation for other diseases．

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New Words and Phrases

putatively［'pjuːtətɪvlɪ］ad． 一般认定地；推定地

mesenchymal［mes'eŋkɪməl］a． 间叶细胞的；间充质的

mesoderm［'mesədзːm］n． 中胚层

neural［'njʊərəl］a． 神经的；神经系统的

crest［krest］n． 嵴

ectoderm［'ektədзːm］n． 外胚层

stromal［'strəʊməl］a． 间质的

adipose［'ædɪpəʊs］a． 动物脂肪（似）的

lymphatic［lɪm'fætɪk］a． 淋巴的

sheath［ʃiːθ］n． 鞘

fibrous［'faɪbrəs］a． 纤维的，纤维状的

pediatric［,piːdɪ'ætrɪk］a． 儿科的

carcinoma［,kɑːsɪ'nəʊmə］ 癌

（［复］carcinomas／carcinomata）n．

neurofibromatosis［,njʊərəʊfaɪ,brəʊmə'təʊsɪs］n． 神经纤维瘤病

polyposis［,pɒlɪ'pəʊsɪs］n． 息肉病

breast cancer 乳腺癌

carcinogen［kɑː'sɪnədʒən］n． 致癌物

angiosarcoma［,ændʒɪəʊsɑː'kəʊmə］n． 血管肉瘤

polyvinyl chloride［,pɒlɪ'vaɪnɪl'klɔːraɪd］ 聚氯乙烯

indolent［'ɪndələnt］a． 懒惰的；不活跃的

atypical［,eɪ'tɪpɪkəl］a． 非典型的

lipomatous［lɪ'pɒmətəs］a． 脂肪瘤的

liposarcoma［,lɪpəʊsɑːkəʊmə］n． 脂肪肉瘤

lipoma［lɪ'pəʊmə］（［复］lipomata／lipomas）n． 脂肪瘤

sarcomatous［sɑː'kəʊmətəs］a． 肉瘤样的

mutilate［'mjuːtɪleɪt］v． 切断（手足等）

forgo［fɔː'ɡəʊ］v． 放弃，抛弃

incisional［ɪn'sɪʒənəl］a． 切入的，切开的

excision［ek'sɪʒən］n． 切除（术）

pathognomonic［pə,θɒɡnə'mɒnɪk］a． 特殊（病症）的，能确定诊断的

synovial［sɪ'nəʊvɪəl，saɪ－］a． 滑液的；分泌滑液的

myxoid［'mɪksɒɪd］a． 黏液样的

fluorescence［flʊə'resəns］n． 荧光，荧光性

occult［ə'kʌlt，'ɒkʌlt］a． 超自然的，神秘的

infiltrate［'ɪnfɪltreɪt］v． （使）渗透，（使）渗入n． 渗透物

fibroblastic［,faɪbrəʊ'blæstɪk］a． 成纤维细胞的

comorbidity［,kemɔː'bɪdɪtɪ］n． 并存疾病；复合病变

oncology［ɒŋ'kɒlədʒɪ］n． 肿瘤学

rehabilitation［'riːhə,bɪlɪ'teɪʃən］n． 修复，恢复

hormonal［hɔː'məʊnəl］a． 激素的，荷尔蒙的

kinase［'kɪneɪs］n． 激酶

psychosocial［,saɪkəʊ'səʊʃəl］a． 社会心理的

referral［rɪ'fзːrəl］n． 转交，转送；转诊患者

rhabdomyosarcoma［'ræbdəʊ,maɪəʊsɑː'kəʊmə］n． 横纹肌肉瘤

leiomyosarcoma［,laɪəʊ,maɪəʊsɑː'kəʊmə］n． 平滑肌肉瘤

palliate［'pælɪeɪt］v． 减轻，缓和（痛苦、疾病等）

Notes

1．Certain patients are at high risk of developing sarcomas，most notably individuals in families with Li－Fraumeni syndrome and those with neurofibromatosis（at risk for malignant peripheral nerve sheath tumors and GISTs）or familial polyposis（at risk for intra－abdominal desmoid tumors）．

参考译文：某些患者是肉瘤的高发人群，最值得注意的是一些有Li－Fraumeni综合征家族史及患有神经纤维瘤病（存在恶性外周神经鞘肿瘤和胃肠道基质肿瘤危险）或家族性息肉病（存在腹内硬纤维瘤危险）的患者。

GIST：gastrointestinal stromal tumor（胃肠道基质肿瘤）

2．Chemical carcinogens can also increase the risk of sarcoma development， such as the increased risk of sarcomas in Vietnam veterans exposed to Agent Orange or the greatly increased risk of hepatic angiosarcomas associated with occupational exposure to polyvinyl chloride．

参考译文：化学致癌物也会增加肉瘤发生的危险。例如，接触过橙剂的越南退伍军人患肉瘤的危险增加，而职业性接触聚氯乙烯者肝血管肉瘤的发病危险则更高。

Agent Orange：橙剂、落叶剂，是一种含有微量毒药的除草剂，在越南战争中被用来使森林地区的树木落叶。

3．This may make the difference between initial management with chemotherapy， as might be appropriate for a highly chemosensitive disease such as Ewing's sarcoma，versus surgery，which might be appropriate for a less chemosensitive disease such as differentiated liposarcoma．

参考译文：这种检查（活组织检查）对确定初始治疗采用化疗还是实施手术可能至关重要。前者也许适合于尤因肉瘤这类具有高度化学敏感性的肿瘤，而

后者则或许适合于分化性脂肪肉瘤这类对化学敏感性较低的肿瘤。

make the（a）difference：有差别；产生影响；起作用。as引导非限制性定语从句，修饰chemotherapy。which引导的非限制性定语从句修饰surgery。

Exercises

Ⅰ．Answer the following questions．

1．What is critical for the normal structure and function of humans？

2．How is the diagnosis of a soft tissue or bone tumor made？

3．What might simulate inflammation or scar？

4．What must be taken into account when defining treatment options and management plans？

5．What can play a meaningful role in preventing disease recurrence， especially for lesions that arise in the extremities？

Ⅱ．Decide whether the following statements are True or False．

1．Most patients with sarcomas present with a mass，often tender，with a history of abnormal growth over time．

2．The diagnosis of a soft tissue or bone tumor is made by evaluating biopsy material in the clinical context，which includes understanding the tumor's anatomic location and imaging characteristics．

3．Given the broad spectrum of sarcomas，the diagnostic considerations are quite far－reaching，especially because many benign pathophysiologic conditions can't mimic sarcomas．

4．For most primary localized masses in which sarcoma is in the differential diagnosis，the first step is to obtain the biopsy in a manner that does not compromise patient outcome or function．

5．Traditional cytotoxic chemotherapy is dramatically effective at increasing disease control and cure rates for certain sarcomas（especially those most prevalent in pediatric patients，such as osteosarcoma，Ewing's sarcoma and rhabdomyosarcoma）．