Malignant peripheral nerve sheath tumors(恶性外周神经鞘瘤).doc

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 surgeon[43]. The incidence of MPNSTs in the general population is 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. Accounting for up to 10 percent of ???。

Photo5MPNSTs[4], 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 sporadic[2.43,44].The risk of developing a MPNST in a patient with NF1 is between 8 and 13 percent[45], with most, if not all, arising from pre-existing 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 lacking an internal plexiform neurofitbroma[46]. 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 neck[47]. The 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 tumor[2]. In particular, frequent sites of involvement[43],but a nerve of origin is often not evident[2].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 tumor[6.43]. Conventional radiographic imaging may help but cannot reliably differentiate between malignant and benign, large tumor size(>5 cm) , heterogeneity, ill-defined 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 MPNST[7](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 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 soft 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 hemorrhage[26]. Microscopically, most MPNSTs are highly cellular, comprised of spindle cells (梭形细胞（spindle cells）) reminiscent of Schwann 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 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components[48.49]In all NF1-associated MPNSTs and most sporadic MPNSTs. Both NF1 alleles are lost. However, homozygous loss of NF1 is not 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 malignancy[26,50].Treatment of MPNSTs ---- MPNSTs are staged and treated 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 oncology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 curative 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 structures[6,43,51]. Nerve grafting is not appropriate due to the proximal nature of the remaining nerve. The use of adjuvant radiation therapy and the natural history of MPNSTs. AT other sites(eg. The head and neck), wide 。