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1、Malignant peripheral nerve sheath tumors(恶性外周神经鞘瘤)-Malignant peripheral nerve sheath tumors(MPNST) are an uncommon but devastating tumor of peripheral nerve, representing only about 10 percent of tumors encountered by a peripheral nerve surgeon43. The incidence of MPNSTs in the general population is
2、 0.001 percent. MPNSTs, which are classified as malignant soft tissue sarcomas, can arise from pre-existing plexiform 丛状neurofibromas or perineuriomas(神经束膜瘤) or normal nerves. They do not arise form schwannomas(神经鞘瘤). MPNSTs also occur as secondary neoplasms 10 to 20 years after radiation therapy. A
3、ccounting for up to 10 percent of ?。Photo5MPNSTs4, From 22 to 50 percent of MPNSTs occur in patients with neurofibromatosis多发性神经纤维瘤type1 (NF1), the rest being sporadic2.43,44.The risk of developing a MPNST in a patient with NF1 is between 8 and 13 percent45, with most, if not all, arising from pre-e
4、xisting plexiform neurofitbromas(丛状神经纤维瘤（plexiform neurofibroma）：此瘤主要由神经轴柱组成，多见于面部、颈后、上睑等处，肿瘤可沿神经及其分支向各方面发展，累及范围广，并可沿脊神经进入脊髓)46. In patients with NF1,the presence of an internal plexiform neurofitbroma is associated with a 20-fold increased risk of developing a MPNST compared with the risk in those
5、lacking an internal plexiform neurofitbroma46. MPNSTs tend to present at an earlier age in patients with NF1(third or fourth decade of life, versus seventh decade in patients who do not have NF1)45. MPNSTs are most commonly found on the extremities and trunk, and less often on the head and neck47. T
6、he clinical picture临床现象 is characterized by rapid change, whether in pain, size of tumor mass, or progression of neurologic deficit(神经缺陷,神经痛), especially when occurring in a pre-existing peripheral 周围nerve tumor2. In particular, frequent sites of involvement43,but a nerve of origin is often not evid
7、ent2.The diagnosis of malignant恶性 versus benigh良性 tumor requires biopsy活检, which should be open and involve multiple sections of the tumor6.43. Conventional radiographic imaging may help but cannot reliably differentiate between malignant and benign, large tumor size(5 cm) , heterogeneity, ill-defin
8、ed margins不清晰的边界, invasion of fat planes脂肪层, and surrounding edema（病理 水肿（等于oedema）；瘤腺体） all suggest MPNST7(image2). At lease some data suggest that PET imaging can be helpful in distinguishing an MPNST from a neurofibroma. (See “clinical presentation histopathology. Diagnostic evaluation and staging
9、 of soft tissue sarcome”, section on PET and PET/CT). Photo4Radiographic imaging (typically chest imaging to evaluate of pulmonary metastases) is also important as part of a metastaic(医（癌细胞的）转移性的) evaluation. (See” clinical presentation临床表现 histopathology组织病理学, diagnostic evaluation and staging of s
10、oft tissue sarcoma”. Section on “Evaluation for metastatic disease”). By gross inspection肉眼检查, MPNSTs tend to be targe. Firm tumors, containing areas of necrosis and hemorrhage26. Microscopically, most MPNSTs are highly cellular, comprised of spindle cells (梭形细胞（spindle cells）) reminiscent of Schwan
11、n cells(雪旺细胞(Schwann cells)是周围神经的主要结构和功能细胞,在神经再生过程中起重要作用,是周围神经组织工程的核心). The cells are mitotically active(picture 7). The cells are weakly S100 positive, consistent with dedifferentiation(去分化) from schwann cells. Variations include malignant triton tumor(蝾螈瘤(triton tumor)：该瘤为恶性外周神经鞘瘤陪横纹肌肉瘤)(malignant
12、 peripheral nerve外周神经 sheath tumor with rhabdomyosarcomatous(rhabdomyosarcoma横纹肌肉瘤) differentiation分化)，a highly malignant tumor containing embryonic striated muscle横纹肌components48.49In all NF1-associated MPNSTs and most sporadic MPNSTs. Both NF1 alleles are lost. However, homozygous loss of NF1 is n
13、ot sufficient to generate a MPNST and additional genetic hits are necessary.Such as mutations突变 in p53 and deletions in CDKN2A29. Positive p53 staining is very common in MPNSTs and intense immunoreactivity to p53 may be an indicator of malignancy26,50.Treatment of MPNSTs - MPNSTs are staged and trea
14、ted as malignant soft tissue saroomas, Because of their rarity and the frequent need for multimodal treatment. The evaluation and management of MPNSTs ideally should be carried out in a center with expertise in the treatment of sarcomas, including surgical, orthopedic整形外科的, medical, and radiation on
15、cology射线肿瘤学.(See “treatment of locally recurrent and unresectable, locally advanced soft tissue sarcoma of the extremities”, section on “Importance of multidisciplinary evaluation and management”)For limb primaries,surgical resection alone with a sufficient wide margin to achieve a potentially curat
16、ive operation may require amputation of the limb proximal to the tumor, or disarticulation of a shoulder or hip,with sacrifice of nerves, nerve trunks, and adjacent soft-tissue structures6,43,51. Nerve grafting is not appropriate due to the proximal nature of the remaining nerve. The use of adjuvant
17、 radiation therapy and the natural history of MPNSTs. AT other sites(eg. The head and neck), wide excision may be impossible due to the constraints of the local anatomy(See “Head and neck sarcomas”, section on “Other adult soft tissuePhoto3 Sarcomas and “Head and neck sarcomas”. Section on “Surgical
18、 principles” and “Local treatment for primary soft tissue sarcoma of the extremities and chest wall”,section onResection)Although the rarity of these tumors has precluded any definitive efficacy trial4, as with other adult-type soft tissue sarcomas, adjunctive radiation therapy (RT) can provide an o
19、pportunity for limb salvage(保肢). And also improve local control where the attainment of wide excision margins by surgery alone is difficult. Adjunctive RT may be administered preoperatively(术前) or postoperatively. (See “Local treatment for primary soft tissue sarcoma of the extremities and chest wal
20、l”. Section on “limb salvage” and “Local treatment for primary soft tissue sarcoma of the extremities and chest wall” , section on “Benefit of RT” and “Local treatment for primary soft tissue sarcoma of the extremities and chest wall”, section on “Preoperative术前 versus postoperative术后 RT”)。Mangement
21、 of locally advanced 晚期or locally recurrent 复发tumors is challenging. Initial RT or chemoradiotherapy may permit some initially unresectable(不可切除的) tumors to undergo later limb-sparing保肢 surgery. Where available. Isolated limb perfusion(隔离肢体热灌注). Isolated limb infusion. Or regional hyperthermia with
22、systemic chemotherapy represent potentially limb-preserving options, but expertise is limited, and these procedures are not in widespread use in the United states (See “Treatment of locally recurrent and unresectable,loaclly advanced soft tissue sarcomas of the extremities(四肢)”) 第二页Chemotherapy（化疗）t
23、reatment for advanced disease is discussed eisewhere（别处）（see“systemic treatment of metastatic soft tissue sarcoma”.） Prognosis- Even with aggressive surgical and radiation treatment. The prognosis is not good. Poor prognostic signs include tumors exceeding 5 cm in size. Higher tumor grade. Associati
24、on with neurofibromatosis(多发性神经纤维瘤) type1 (NF1). Older age. Distant metastases (远处转移) at the time of diagnosis, and inability to achieve tumor-free margins2.6.47.52.53. in various studies, five-year survival ranged from 34 to 64 percent2.6.43.52.53. The variable outcomes among these repotrs may be d
25、ue in part to differences in treatment protocols(治疗方案) and to the proportion of NF1-associated MPNSTs, Which often present at a later stage with larger tumors than sporadic(散发) MPNSTs54. A survival meta-analysis of 28 studies published form 1963 through 2011 demonstrated worse survival for NF-1- ass
26、ociated tumors compared with sporadic tumors(hazard ratio危险率 HR 1.39, 95% CI 1.10-1.72); however, in an analysis limited to series pulished since 2001, the pooled HR was smaller and no longer significant (HR 1.19.95% CI 0.85-1.66 )，suggesting that observed differences in outcome between NF-1 and spo
27、radic tumors may be lessening over time53.One of the largest studies evaluating MPNSTs was a single-center retrospective review of 175 cases seen over a 25-year period47. The median age was 44, and one-third of MPNSTs arose in the setting of NF1. The extremities(四肢) were the most common site（45 perc
28、ent）followed by the trunk(躯干)(34 percent) and head and neck （19 percent）. At presentation, 84 percent had locoregional (限于局部的) disease, while 16 percent had distant metasasses. A complete (R0) resection was accomplished in 69 percent of cases, and the majority had adjuvant(辅助) treatment with radiati
29、on therapy, chemotherapy, or both. At a median follow-up of 74 months, the local recurrence(局部复发) rate was 22 percent, and the 5 and 10-year disease-specific survival rates were 60 and 45 percent，respectively，On multivariate analysis（多变量分析），highter tumor grade, size 25cm, truncal(躯干的) location and l
30、ocal recurrence were associated with a significantly worse prognosis. Patients with NF-1 presented with larger tumors(median 9.9 versus 6.6 cm for sporadic tumors), and there was a statistically nonsignificant trend toward worse 5-year disease-specific survival(54 versus 75 percent for sporadic cases).家父得此病，收集的一些资料，希望能对大家有用，望科技进步，解决这个医学难题 -