劉振軒臺灣大學：獸醫學研究所涂央昌Tu, Yang-ChangYang-ChangTu2007-11-282018-07-092007-11-282018-07-092005http://ntur.lib.ntu.edu.tw//handle/246246/59999收集犬周邊神經鞘膜瘤共36例，包括組織病理學診斷23例惡性及13例良性病例。以品種分析，好發品種為混種犬（mongrel）佔51.5％，年齡以7歲到14歲的發生率最高佔86.7％；就性別比較，雌犬（54.8％）的發生略高於雄犬（41.2％）；以發生部位統計，四肢的發生率最高（75.6%）。組織病理學特徵，周邊神經鞘膜瘤由梭形或S型的細胞，構成波浪狀、柵欄狀、束狀交織及旋渦狀的列，細胞間因腫瘤細胞的彎曲型，而有裂隙的產生。惡性周邊神經鞘膜瘤的腫瘤細胞，呈現肥胖梭形或圓形至類上皮形態，偶見多核巨大細胞出現，有2例惡性病例伴隨有軟骨細胞的化生，另有6例腫瘤區域出現嚴重的壞死，其中有3例伴隨廣泛血栓的形成。此外，14例良性病例有9例許旺氏細胞瘤及5例神經纖維瘤，而9例許旺氏細胞瘤中，只有2例組織病理形態具有典型Antoni type A and B的特徵；神經纖維瘤的腫瘤細胞密度低且細胞間存在多量的膠原纖維。超顯微結構下腫瘤細胞膜上可見到雙層連續的basal lamina，細胞突起（processes）且互相交織（intertwining processes），細胞間存在大量的膠原纖維。免疫組織化學染色的結果，vimentin有100％，laminin有93.3％，S-100有87.8％，NGFR（nerve growth factor receptor）有84.8％，neurofilament有51.58％，NSE（neuron-specific enolase）有30.3％，α-SMA（α-smooth muscle actin）有6.1％，及desmin有3.0％，而cytokeratin，factorⅧ及GFAP （glial fibrillary acidic protein）均呈陰性。神經纖維瘤對neurofilament抗體染色，大部分呈陽性（4/5; 80.0%），而laminin對良性或惡性的許旺氏細胞瘤會呈陽性。雖然血管周細胞瘤對S-100有71.4％的陽性率，但血管周細胞瘤對α-SMA有71.4％的陽性率，但配合laminin及NGFR抗體染色，可進一步區別兩者。綜合研究結果，梭形細胞瘤於組織病理形態學下，即可初步推測其組織來源，配合免疫組織化學染色S-100，vimentin，α-SMA（＋），neurofilament，laminin，NGFR及NSE的結果，可將周邊神經鞘膜瘤與其他組織學類似的梭形細胞瘤區別。A total of 36 canine peripheral nerve sheath tumors (PNSTs), 23 malignant PNSTs (MPNSTs), and 13 benign PNSTs (BPNSTs) were diagnosed by histological features and immunohistochemical results. In this study, the affected dogs were 17 (54.8%) females and 14 (41.2%) males. The peak incidence of the PNSTs was between 7 to 14 years of age (26/30; 86.7%). Breed at the highest risk was mongrel dogs (17/33; 51.5%). The limbs were the most common site (25/33; 75.6%), followed by the trunk (5/33; 15.2%), genital (2/33; 6.1%), and head (1/33; 3.0%). Microscopically, PNSTs were composed of spindle or S shape cells arranged in wavy bundles, palisading, storiform, and whorl fashions. The predominant tumor cells of MPNSTs were either plump spindle or round in shape with epithelioid characteristics, mixed with multinucleated giant cells occasionally. There were two MPNSTs with cartilaginous metaplasia, and six MPNSTs presented with extensive necrotic foci accompanied with thrombosis in 3 of 6 cases. Regarding to 13 BPNSTs, all exhibited a typical feature of either schwannoma or neurofibroma. Only 2 of 9 schwannomas had typical Antoni type A and B features. The 4 neurofibromas presented with extensive collagen deposition likened to shredded carrots appearance, which tumor cells arranged in hypocellularity. Ultrastructurally, the tumor cells were long, thin, intertwining processes, a duplicated external basal lamina covering the cells, and long spacing collagen. Immunohistochemically, the expression of vimentin (100%), laminin (93.3%), S-100 (87.8%), nerve growth factor receptor (NGFR, 84.8%), neurofilament (51.58%), neuron-specific enolase (NSE, 30.3%), α-SMA (α-smooth muscle actin, 6.1%), and desmin (3.0%) were found in PNSTs. PNSTs failed to demonstrate expression of cytokeratin, factorⅧ, and glial fibrillary acidic protein (GFAP). On conclusion, PNSTs often occur in the skin soft tissue of dogs that share histological similarities with other spindle cell tumors. Comprehensive studies on microscopical findings and immunohistochemical characterization provide a useful and practical method to differentiate PNSTs from other spindle cell tumors.目錄 目錄------------------------------------------------------------------------------------ Ⅰ 圖次------------------------------------------------------------------------------------ Ⅳ 表次------------------------------------------------------------------------------------ Ⅶ 中文摘要------------------------------------------------------------------------------ Ⅷ 英文摘要------------------------------------------------------------------------------ Ⅹ 第一章 前言------------------------------------------------------------------------- 1 第二章 文獻探討------------------------------------------------------------------ 3 第一節 周邊神經系統的組成------------------------------------- 3 第二節 周邊神經鞘膜瘤的分類---------------------------------- 3 2.2.1世界衛生組織（WHO）分類---------------------- 3 2.2.2犬PNSTs的分類------------------------------------- 4 第三節 人與動物周邊神經鞘膜瘤的研究---------------------- 4 2.3.1犬周邊神經鞘膜瘤之臨床表現------------------- 5 2.3.2人及犬周邊神經鞘膜瘤之病理特徵------------- 6 2.3.3其他動物周邊神經鞘膜瘤的研究---------------- 8 第四節 免疫組織化學染色技術---------------------------------- 9 2.4.1免疫組織化學染色技術的方法及原理---------- 9 2.4.2免疫組織化學染色法之腫瘤診斷---------------- 12 2.4.3周邊神經鞘膜瘤之免疫組織化學染色應用---- 14 第五節 周邊神經鞘膜瘤之超微結構---------------------------- 16 第六節 其他常見梭形細胞瘤------------------------------------- 17 2.6.1血管周細胞瘤---------------------------------------- 17 2.6.2平滑肌瘤及其肉瘤---------------------------------- 18 2.6.3纖維瘤及纖維肉瘤---------------------------------- 18 2.6.4惡性纖維組織細胞瘤------------------------------- 19 2.6.5黏液瘤及黏液肉瘤---------------------------------- 19 2.6.6橫紋肌瘤及其肉瘤---------------------------------- 20 2.6.7其他梭形細胞瘤------------------------------------- 20 第三章 材料與方法--------------------------------------------------------------- 22 第一節 實驗設計與流程------------------------------------------- 22 第二節 材料來源---------------------------------------------------- 23 第三節 形態病理學檢查------------------------------------------- 23 3.3.1肉眼病理學檢查------------------------------------- 23 3.3.2組織病理學檢查------------------------------------- 24 3.3.3組織化學染色---------------------------------------- 28 3.3.4改良式免疫組織化學染色------------------------- 33 3.3.5穿透式電子顯微鏡檢查---------------------------- 40 第四章 結果------------------------------------------------------------------------- 47 第一節 周邊神經鞘膜瘤------------------------------------------- 47 4.1.1臨床資料---------------------------------------------- 47 4.1.2肉眼病理學檢查------------------------------------- 48 4.1.3組織病理形態學------------------------------------- 49 4.1.4免疫組織化學---------------------------------------- 51 4.1.5穿透式電子顯微鏡下的超微構造---------------- 52 第二節 血管周細胞瘤---------------------------------------------- 52 第三節 其他梭形細胞瘤------------------------------------------- 53 4.3.1纖維細胞腫瘤---------------------------------------- 53 4.3.2平滑肌瘤---------------------------------------------- 54 4.3.3纖維平滑肌瘤--------------------------------------- 55 4.3.4惡性纖維組織細胞瘤------------------------------- 55 4.3.5脂肪瘤肉瘤------------------------------------------- 56 4.3.6橫紋肌瘤---------------------------------------------- 56 4.3.7黏液瘤------------------------------------------------- 56 第五章 討論---------------------------------------------------------- 85 第六章 參考文獻---------------------------------------------------- 93 圖次 Fig 3.1 實驗流程圖----------------------------------------------------------------- 22 Fig 3.2 TEM製備簡易流程圖---------------------------------------------------- 46 Fig 4.1 BPNST, Case 2------------------------------------------------------------- 58 Fig 4.2 BPNST, Case 2------------------------------------------------------------- 58 Fig 4.3 BPNT, Case 4--------------------------------------------------------------- 58 Fig 4.4 BPNT, Case 4--------------------------------------------------------------- 58 Fig 4.5 BPNST, Case 5------------------------------------------------------------- 58 Fig 4.6 MPNST; Case 20----------------------------------------------------------- 58 Fig 4.7 MPNST; Case 26----------------------------------------------------------- 59 Fig 4.8 MPNST; Case 24----------------------------------------------------------- 59 Fig 4.9 MPNT; Case 22------------------------------------------------------------- 59 Fig 4.10 BPNST, Case 2------------------------------------------------------------- 59 Fig 4.11 BPNT, Case 4--------------------------------------------------------------- 59 Fig 4.12 BPNT, Case 4--------------------------------------------------------------- 59 Fig 4.13 BPNST, Case 2------------------------------------------------------------- 60 Fig 4.14 BPNST, Case 5------------------------------------------------------------- 60 Fig 4.15 BPNST, Case 5------------------------------------------------------------- 60 Fig 4.16 BPNST, Case 5------------------------------------------------------------- 60 Fig 4.17 BPNST; Case 7------------------------------------------------------------- 60 Fig 4.18 MPNST; Case 16----------------------------------------------------------- 60 Fig 4.19 BPNST; Case 12----------------------------------------------------------- 61 Fig 4.20 BPNST; Case 12----------------------------------------------------------- 61 Fig 4.21 BPNST; Case 12----------------------------------------------------------- 61 Fig 4.22 BPNST; Case 12----------------------------------------------------------- 61 Fig 4.23 BPNST; Case 11----------------------------------------------------------- 61 Fig 4.24 MPNST; Case 16----------------------------------------------------------- 61 Fig 4.25 MPNST; Case 16----------------------------------------------------------- 62 Fig 4.26 MPNST; Case 22----------------------------------------------------------- 62 Fig 4.27 MPNST; Case 20----------------------------------------------------------- 62 Fig 4.28 MPNST; Case 16----------------------------------------------------------- 62 Fig 4.29 MPNST; Case 16----------------------------------------------------------- 62 Fig 4.30 MPNST; Case 24----------------------------------------------------------- 62 Fig 4.31 MPNST; Case 20----------------------------------------------------------- 63 Fig 4.32 MPNST; Case 16----------------------------------------------------------- 63 Fig 4.33 MPNST; Case 16----------------------------------------------------------- 63 Fig 4.34 MPNST; Case 26----------------------------------------------------------- 63 Fig 4.35 MPNST; Case 26----------------------------------------------------------- 63 Fig 4.36 MPNST; Case 27----------------------------------------------------------- 63 Fig 4.37 MPNST; Case 27----------------------------------------------------------- 64 Fig 4.38 BPNST, Case 2------------------------------------------------------------- 64 Fig 4.39 BPNST, Case 5------------------------------------------------------------- 64 Fig 4.40 MPNST; Case 20----------------------------------------------------------- 64 Fig 4.41 MPNST; Case 26----------------------------------------------------------- 64 Fig 4.42 BPNT, Case 4--------------------------------------------------------------- 64 Fig 4.43 BPNST, Case 5------------------------------------------------------------- 65 Fig 4.44 MPNST; Case 16----------------------------------------------------------- 65 Fig 4.45 MPNST; Case 16----------------------------------------------------------- 65 Fig 4.46 MPNST; Case 20----------------------------------------------------------- 65 Fig 4.47 BPNT, Case 4--------------------------------------------------------------- 65 Fig 4.48 BPNST, Case 2------------------------------------------------------------- 65 Fig 4.49 MPNST; Case 20----------------------------------------------------------- 66 Fig 4.50 MPNST; Case 16----------------------------------------------------------- 66 Fig 4.51 MPNST; Case 27----------------------------------------------------------- 66 Fig 4.52 BPNST; Case 7------------------------------------------------------------- 66 Fig 4.53 BPNST; Case 7; TEM----------------------------------------------------- 66 Fig 4.54 BPNST; Case 7; TEM----------------------------------------------------- 66 Fig 4.55 HP; Case 55----------------------------------------------------------------- 67 Fig 4.56 HP; Case 55----------------------------------------------------------------- 67 Fig 4.57 HP; Case 59----------------------------------------------------------------- 67 Fig 4.58 HP; Case 55----------------------------------------------------------------- 67 Fig 4.59 HP; Case 59----------------------------------------------------------------- 67 Fig 4.60 HP; Case 55----------------------------------------------------------------- 67 Fig 4.61 Fibrosarcoma; Case 73---------------------------------------------------- 68 Fig 4.62 Fibrosarcoma; Case 73---------------------------------------------------- 68 Fig 4.63 Leiomyosarcoma; Case 73------------------------------------------------ 68 Fig 4.64 Leiomyosarcoma; Case73------------------------------------------------- 68 Fig 4.65 Leiomyosarcoma; Case 73------------------------------------------------ 68 Fig 4.66 MFH; Case 87-------------------------------------------------------------- 68 Fig 4.67 MFH; Case 87-------------------------------------------------------------- 69 Fig 4.68 Liposarcoma; Case 73----------------------------------------------------- 69 Fig 4.69 Liposarcoma; Case 73----------------------------------------------------- 69 Fig 4.70 Myxoma; Case 93---------------------------------------------------------- 69 Fig 4.71 Myxoma; Case 93---------------------------------------------------------- 69 Fig 4.72 Myxoma; Case 93---------------------------------------------------------- 69 Fig 5.1 A flowchart for pathology and IHC identification of spindle cell tumor in dogs. -------------------------------------------------------------- 92 表次 Table 3.1 Source and working dilutions of the antisera used to evaluate neoplasms of spindle cell tumors----------------------------------------- 39 Table 4.1 Clinical data of canine PNSTs-------------------------------------------- 70 Table 4.2 Histologic features of BPNSTs------------------------------------------- 73 Table 4.3 Histologic features of MPNSTs------------------------------------------ 74 Table 4.4 Immunohistochemical results of each case with BPNST, MPNST, and other spindle cell tumor examined---------------------------------- 77 Table 4.5 Immunohistochemical results in canine BPNSTs and MPNSTs----- 80 Table 4.6 Clinical data of canine other spindle cell tumor------------------------ 8134578240 bytesapplication/pdfen-US犬周邊神經鞘膜瘤免疫組織化學染色DogImmunohistochemistryPeripheral Nerve Sheath Tumorsthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/59999/1/ntu-94-R92629002-1.pdf