Welcome to Visited Lingnan Modern Clinics In Surgery, Today is

Lingnan Modern Clinics in Surgery ›› 2019, Vol. 19 ›› Issue (06): 694-700.DOI: 10.3969/j.issn.1009-976X.2019.06.010

Previous Articles     Next Articles

Diagnosis and treatment of solitary fibrous tumors?a single?center retrospective study

JIN Shaowen, HE Maoqin, SUN Qing, WANG Kaimei   

  1. 1. Department of Gastrointestinal Surgery, Sun Yat?Sen Memorial Hospital, Sun Yat?Sen University, Guangzhou, China 510120; 2. Department of Pathology, Sun Yat?Sen Memorial Hospital, Sun Yat?Sen University, Guangzhou, China 510120; 3. Department of Pediatrics, Sun Yat?Sen Memorial Hospital, Sun Yat?Sen University, Guangzhou, China 510120

孤立性纤维性肿瘤的诊断和治疗--单中心回顾性研究

金少文, 何茂钦, 孙情, 王开美   

  1. 中山大学孙逸仙纪念医院1.胃肠外科,2.院病理科,3.儿科;广州 510120
  • 通讯作者: 金少文

Abstract: Objective To explore the diagnosis, treatment and follow?up of solitary fibrous tumors (SFT). Methods The clinical data for seven and a half years in our institution of solitary fibrous tumors, which were surgically resected and pathologically diagnosed, were collected, and epidemiological characteristics, diagnosis, therapies and follow?up of SFT were analyzed and summed up. Results There was no significant difference in the ratio of male to female of 60 SFT patients and the median age was 46 years old. Pelvic and abdominal cavities were the most common site, followed by intracranial space, otolaryngology and oral cavity. About half of patients came to the hospital with specialized symptoms. All cases were surgically resected and confirmed by histopathology and immunohistochemical staining. 45% of the patients were reexamined and followed up postoperatively almost in one year. Recurrence was found in 4 of the 27 patients at follow?up. Conclusion Solitary fibrous tumors are mostly benign or low?grade malignant and grow slowly. Its diagnosis depends on histopathology and immunohistochemical staining. Complete surgical resection is the main treatment, and follow?up should be carried out regularly.

Key words: solitary fibrous tumors, follow up, spindle cell tumors, diagnosis, therapy

摘要:

孤立性纤维性肿瘤的诊断和治疗
——单中心回顾性研究

金少文1*, 何茂钦1, 孙情2, 王开美3

[摘要] 目的 探讨孤立性纤维性肿瘤的诊断、治疗方法和随访。方法 回顾我院7年半收治的经手术切除并病理确诊为孤立性纤维性肿瘤的病例资料,就其流行病学特点、诊断、治疗方法和随访进行总结与分析。结果 60例孤立性纤维性肿瘤患者,男女比例无明显差异,中位年龄为46岁。盆腹腔为最常见的发病部位,其次为颅内、耳鼻喉口腔。约一半的患者出现专科症状而就诊。所有病例均行手术切除,并经病理组织学检查和免疫组化染色确诊。27例(45%)患者术后进行了复查随访,且多为1年内。27例中有4例在复查随访时发现复发。结论 孤立性纤维性肿瘤大多为良性或低度恶性,生长较缓慢,诊断主要依赖组织学和免疫组化染色确诊,手术完整切除是其主要治疗手段,术后应定期进行随访复查。

[关键词] 孤立性纤维性肿瘤;梭形细胞肿瘤;诊断;治疗;随访

孤立性纤维性肿瘤(solitary fibrous tumor,SFT)是一种较少见的间叶来源的肿瘤。最初由Klemperer和Rabin于1931年首次报道,被认为来源于胸膜间皮细胞,现认为起源于一种CD34+的树突状间叶细胞,可发生于任何部位,如胸膜、腹膜、脑膜、椎管、口鼻腔、眼眶、支气管、胃肠道、膀胱、前列腺等[1,2]。由于其组织学的复杂性和多样性,发生部位广泛,较少见且往往缺乏对该病的认识,临床上极易与其他肿瘤相混淆[2]。现就我院过去7年半收治的60例SFT患者的临床资料,并结合国内外研究报道,总结并探讨SFT的流行病学特点、临床病理学特征、诊断、治疗和随访。

1 临床资料

1.1 一般资料

收集我院2012年1月至2019年6月,经手术切除、病理及IHC明确诊断孤立性纤维性肿瘤,排除穿刺标本、未经IHC明确诊断、外院会诊等病例,共收集60例SFT患者的临床资料。其中男26例,女34例,年龄10月龄~70岁,中位年龄46岁。所有病例均行手术切除,手术切除标本经10%福尔马林固定,石蜡包埋、常规切片,行HE染色和免疫组化染色以明确诊断。

1.2 临床表现

本组病例多为出现专科症状(34/60=56.7%),如头晕头痛、视物模糊、一侧肢体乏力、一侧耳疼、鼻腔出血、鼻塞、腹痛腹胀、咳嗽咳痰等,进一步检查发现的。23.3%的病例为体检时意外发现。另外20%病例自行发现或扪及包块而就诊。

1.3 诊断和治疗

所有病例的肿瘤均行手术切除,肿瘤部位:盆腹腔11例,其中腹膜后4例;肝脏4例,肾1例,前列腺1例;甲状腺1例,躯干、四肢9例;耳鼻喉、口腔10例;肺、纵膈6例;颅内14例,椎管内3例。除颅内、椎管内肿瘤为分块切除外,大多为整块切除。术后均行病理检查和免疫组化染色检查,由2名病理科医师共同确诊为孤立性纤维性肿瘤。

2 结果

2.1 病理检查

2.1.1 大体检查 肿瘤最大37.5 cm×22 cm×11 cm,最小 0.6 cm×0.5 cm×0.4 cm,中位直径约 5 cm。大部分肿瘤界限较清楚,可见到部分或完整包膜;肿瘤切面多为灰白色、灰黄色,少数为灰褐色;质韧或稍硬,多为实性,少数可见胶冻状、小囊性改变,偶可见坏死及浸润周围组织。

2.1.2 镜检 肿瘤细胞多呈梭形、短梭形或卵圆形。多数无明显异型性,少数为轻度异型性,极少数亦可表现为异型性明显。核分裂像多为罕见、偶见或少见,极少数核分裂像可达10~15个/10HPF。肿瘤细胞多呈细胞稀疏区与细胞致密区交替排列,表现为束状、席纹状、血管外皮瘤样或不规则排列;间质中可见粗大的胶原纤维,常伴有玻璃样变性;肿瘤组织内可见较多血管。

2.2 免疫组化染色

除组织学形态外,IHC染色对SFT的确诊至关重要。CD34、STAT6、Bcl-2、CD99、Vimentin和CK、Actin、Desmin、S-100、EMA是诊断SFT常用的分子标志物。其检查情况详见表1。

2.3 随访

60例病例中有27例进行术后复查随访。随访最短1个月,最长90个月,平均随访半年。27例中有4例在复查随访时发现复发。

3 讨 论

SFT多发生于成年的各个年龄段,平均发病年龄50岁,无明显性别差异[3]。本组病例中位年龄46岁,男女比例无明显差异,与之报道相一致。值得一提的是,本组病例中最小年龄为10月龄,尚未见更低年龄病例报道。研究报道[4]胸腔为最常见SFT肿瘤发病部位,其次为腹腔,约30%出现在胸膜以外的部位。我中心报道与此差异较大,胸腔SFT肿瘤仅占10%(6/60),盆腹腔(25%)为最常见部位,其次为颅内(23%)、耳鼻喉口腔(17%),这可能与东西方人种差异有关。Brian Davanzo等[5]学者认为大多SFT肿瘤患者无症状或者为非特异性症状,通常进行影像学检查时偶然发现,与我中心的数据存在差异。我们的数据显示约56%患者出现专科症状,如头晕头痛、视物模糊、一侧肢体乏力、鼻塞、腹痛腹胀等,另外44%患者为体检意外发现或者自行扪及包块。这可能与发病部位不同有关。

SFT 肿瘤病理组织学特点[1,2]如下:①大体病理:多为界限清楚的肿块,多为孤立性,部分有纤维性假包膜,可呈分叶状或哑铃状;肿瘤切面多呈灰白或淡褐色,质韧,少数可呈黏液样,或出血及囊性病变;②组织学:梭形或短梭形肿瘤细胞呈束状、席纹状、血管外皮瘤样或不规则排列,细胞丰富区域和细胞稀疏区域相间分布,间质中可见粗大的胶原纤维,常伴有玻璃样变性。SFT的确诊主要依赖病理组织学和免疫组织化学染色。其中恶性较少见,约占10%~15%。多位学者提出了恶性SFT的肿瘤特征标准,更广为接受的为England等[6]学者提出:①肿瘤大于10 cm;②肿瘤坏死或出血;③细胞多形性;④核分裂像增多,≥4/10 HPF。本组病例有14例考虑恶性SFT,恶性率为23%,稍高于一般所报道的10%~15%[4]。免疫组化染色有助于诊断和鉴别诊断。肿瘤细胞常表达CD34、STAT6、Vimentin、CD99和 Bcl-2,而结蛋白(Desmin)、细胞角蛋白(CK)、EMA、Actin、S-100、CD68、CD117一般呈阴性。其中CD34和STAT6对SFT的诊断意义重大,CD34弥漫强阳表达、STAT6核强阳表达是SFT的免疫表型特点之一。然而,CD34表达缺乏特异性,在一些其他间叶源性肿瘤如胃肠道间质瘤(GIST)亦可表达,可通过CD117和DOG1分子标志物加以鉴别[7]。本研究中CD34阳性率为85.0%(51/60),STAT6阳性率为86.2%(25/29)。Vimentin(95.2%)、CD99(73.5%)和Bcl-2(90.6%)也有助于诊断。SFT分子遗传学重大进展之一就是NAB2-STAT6基因融合被证实对SFT诊断具有高度敏感性和特异性[8]。由于需要设计特殊的引物探针,且需要基因二代测序仪,成本较高。STAT6核强阳表达可作为一种替代工具来辅助证实存在NAB2-STAT6融合基因,同样可以可靠地将SFT与其他软组织肿瘤等鉴别[9]。免疫组化染色有助于本病与以下几种疾病鉴别[10]:神经鞘瘤、神经纤维瘤、恶性间皮瘤、滑膜肉瘤、胃肠道间质瘤等。

表1 各分子标志物在孤立性纤维性肿瘤中的表达

检测分子CD34 STAT6 Vimentin CD99 Bcl-2检测阳性病例数51 25 40 25 48检查病例数60 29 42 34 53阳性率/%85.0 86.2 95.2 73.5 90.6检测分子CK Actin EMA Desmin S-100检测阴性病例数37 53 31 47 48检查病例数39 56 37 48 54阴性率/%94.9 94.6 83.8 97.9 88.9

由于难以设计随机对照试验,目前尚未制定针对SFT的全球公认的治疗策略。手术完整切除肿瘤即获得足够的阴性切缘,为SFT最主要的治疗手段。能否彻底清除肿瘤是预防SFT复发的关键。对于腹膜后孤立性纤维性肿瘤,由于腹膜后巨大潜在间隙,便于肿瘤膨胀性生长,同时往往具有丰富的血供,有多支扩张血管进入,肿瘤可能与邻近重要血管粘连或将其包绕,因此手术难度大的关键在于术中控制大出血[11]。放疗并不推荐用于肿瘤得到完整切除的病例。多个回顾性研究评估了以阿霉素为基础的化疗方案疗效不佳,因而更多的研究转向靶向治疗[5]。研究显示[12]替莫唑胺和贝伐单抗有79%部分缓解率。此外,多靶点抗血管生成药物如舒尼替尼也显示出抗SFT效果。

由于SFT有部分表现为恶性,且良性SFT也有恶变可能,因此长期随访十分重要[13]。一般建议术后3年内每3~6个月随访1次,以后每年复查1次。本研究中,60例病例有27例(45%)进行术后复查随访,且大多在术后1年内随访1~2次便不再随访。因此,大多数医护人员和患者对本病的认识还有待提高。

参考文献

[1] Demicco EG,Park MS,Araujo DM,et al.Solitary fibrous tumor:a clinicopathological study of 110 cases and proposed risk assessment model[J].Mod Pathol,2012,25(9):1298-1306.

[2] Thway K,Ng W,Noujaim J,et al.The Current Status of Solitary Fibrous Tumor:Diagnostic Features,Variants,and Genetics[J].Int JSurg Pathol,2016,24(4):281-292.

[3] Suehisa H,Yamashita M,Komori E,et al.Solitary fibrous tumor of the mediastinum[J].Gen Thorac Cardiovasc Surg,2010,58(4):205-208.

[4] Gold JS,Antonescu CR,Hajdu C,et al.Clinicopathologic correlates of solitary fibrous tumors[J].Cancer,2002,94(4):1057-1068.

[5] Davanzo B,Emerson RE,Lisy M,et al.Solitary fibrous tumor[J].Transl Gastroenterol Hepatol,2018,3:94.

[6] England DM,Hochholzer L,Mccarthy MJ.Localized benign and malignant fibrous tumors of the pleura.A clinicopathologic review of 223 cases[J].Am JSurg Pathol,1989,13(8):640-658.

[7] Miettinen M,Felisiak-Golabek A,Wang Z,et al.GIST manifesting as a retroperitoneal tumor:clinicopathologic immunohistochemical,and molecular genetic study of 112 cases[J].Am J Surg Pathol,2017,41(5):577-585.

[8] Robinson DR,Wu YM,Kalyana-Sundaram S,et al.Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing[J].Nat Genet,2013,45(2):180-185.

[9] Cheah AL,Billings SD,Goldblum JR,et al.STAT6 rabbit monoclonal antibody is a robust diagnostic tool for the distinction of solitary fibrous tumour from its mimics[J].Pathology,2014,46(5):389-395.

[10]高杰,汪欣,尹洪芳,等.盆腔孤立性纤维性肿瘤的诊断及治疗[J].北京大学学报(医学版),2013,45(6):960-964.

[11]艾中立.腹膜后肿块的临床特征[J].腹部外科,2002,15(4):200-201.

[12]Park MS,Patel SR,Ludwig JA,et al.Activity of temozolomide and bevacizumab in the treatment of locally advanced,recurrent,and metastatic hemangiopericytoma and malignant solitary fibrous tumor[J].Cancer,2011,117(21):4939-4947.

[13]朱磊,林琳,郭大伟,等.孤立性纤维性肿瘤的诊断及外科治疗[J].中国普外基础与临床杂志,2012,19(1):99-101.

Diagnosis and treatment of solitary fibrous tumors-a single-center retrospective study

JIN Shaowen1,HE Maoqin1,SUNQing2,WANGKaimei3
1.Department of Gastrointestinal Surgery,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,China 510120;2.Department of Pathology,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,China 510120;3.Department of Pediatrics,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,China 510120

[Abstract] Objective To explore the diagnosis,treatment and follow-up of solitary fibrous tumors(SFT).Methods The clinical data for seven and a half years in our institution of solitary fibrous tumors,which were surgically resected and pathologically diagnosed,were collected,and epidemiological characteristics,diagnosis,therapies and follow-up of SFT were analyzed and summed up.Results There was no significant difference in the ratio of male to female of 60 SFT patients and the median age was 46 years old.Pelvic and abdominal cavities were the most common site,followed by intracranial space,otolaryngology and oral cavity.About half of patients came to the hospital with specialized symptoms.All cases were surgically resected and confirmed by histopathology and immunohistochemical staining.45%of the patients were reexamined and followed up postoperatively almost in one year.Recurrence was found in 4 of the 27 patients at follow-up.Conclusion Solitary fibrous tumors are mostly benign or low-grade malignant and grow slowly.Its diagnosis depends on histopathology and immunohistochemical staining.Complete surgical resection is the main treatment,and follow-up should be carried out regularly.

[Key words] solitary fibrous tumors;spindle cell tumors;diagnosis;therapy;follow up

doi:10.3969/j.issn.1009-976X.2019.06.010

中图分类号:R734.3

文献标识码:A

基金项目:广东省自然科学基金博士启动项目(2016A03031 0183);国家自然科学基金青年基金项目(81602125)

作者单位:中山大学孙逸仙纪念医院1.胃肠外科,2.院病理科,3.儿科;广州 510120

通讯作者:金少文,Email:jinshw3@mail.sysu.edu.cn

Correspondence author:JIN Shaowen,jinshw3@mail.sysu.edu.cn

(收稿日期:2019-10-11)

关键词: 孤立性纤维性肿瘤, 诊断, 随访, 梭形细胞肿瘤, 治疗

CLC Number: