吉林大学学报(医学版)  2019, Vol. 45 Issue (03): 697-700     DOI: 10.13481/j.1671-587x.20190339

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田艳华, 苏凯, 王三春, 童卫芳, 张旭, 魏明雪, 冯青杰
TIAN Yanhua, SU Kai, WANG Sanchun, TONG Weifang, ZHANG Xu, WEI Mingxue, FENG Qingjie
咽喉部肉瘤样癌5例报告及文献复习
Sarcomatoid carcinoma of throat: A report of 5 cases and literature review
吉林大学学报(医学版), 2019, 45(03): 697-700
Journal of Jilin University (Medicine Edition), 2019, 45(03): 697-700
10.13481/j.1671-587x.20190339

文章历史

收稿日期: 2019-01-25
咽喉部肉瘤样癌5例报告及文献复习
田艳华 , 苏凯 , 王三春 , 童卫芳 , 张旭 , 魏明雪 , 冯青杰     
吉林大学第二医院耳鼻咽喉-头颈外科, 吉林 长春 130041
[摘要]: 目的: 探讨5例咽喉部肉瘤样癌患者的临床特征、病理学表现、治疗方法和预后。方法: 回顾性分析5例经病理检查证实的咽喉部肉瘤样癌患者的临床资料,并进行相关文献复习。结果: 5例咽喉部肉瘤样癌患者中,4例患者为男性,1例患者为女性;发病年龄为55~77岁;3例患者有长期吸烟史,2例患者有长期饮酒史。患者均表现为咽痛、咽部异物感、声音嘶哑及呼吸困难等,5例患者均行电子喉镜检查,1例患者表现为菜花样肿物,其余患者表现为较光滑肿物。2例患者行CT检查,肿物表现为软组织密度影,无骨质破坏。5例患者均行手术治疗,2例患者行术后辅助性放疗,1例患者行术后化疗;术后组织病理学检查及免疫组织化学染色结果显示5例患者均诊断为肉瘤样癌;术后随访1~36个月,随访率为100%,其中1例患者存活,4例患者死亡。结论: 咽喉部肉瘤样癌无特异的临床特点,多呈息肉状生长,易误诊,其恶性程度高于鳞状细胞癌,易复发,晚期易转移,预后差,确诊依靠组织病理学检查,治疗首选手术切除。
关键词: 肉瘤样癌    咽喉部    梭形细胞癌    组织病理学    免疫组织化学    
Sarcomatoid carcinoma of throat: A report of 5 cases and literature review
TIAN Yanhua , SU Kai , WANG Sanchun , TONG Weifang , ZHANG Xu , WEI Mingxue , FENG Qingjie     
Department of Otorhinolaryngology and Head-Neck Surgery, Second Hospital, Jilin University, Changchun 130041, China
[ABSTRACT]: Objective: To investigate the clinical features, pathological features, treatment methods and prognosis of 5 patients with sarcomatoid carcinoma of throat. Methods: The clinical data of 5 patients with sarcomatoid carcinoma of throat confirmed by pathology were retrospectively analyzed, and the relevant literatures were reviewed. Results: Among 5 patients with sarcomatoid carciroma of throat, 4 patients were male and 1 patient was female, with the onset age from 55 to 77 years old. Among them, 3 patients had a long-term smoking history and 2 patients had a long-term drinking history.The chief complaints of the patients were pharyngeal pain, foreign body sensation in the pharynx, hoarseness and dyspnea, etc.All 5 patients underwent electronic laryngoscope examination, and 1 case presented cauliflower mass, while the other patients presented smooth mass.CT examination was performed in 2 patients, and the mass showed soft tissue density shadow without bone destruction. All 5 patients received surgical treatment, including 2 cases of adjuvant radiotherapy after operation and 1 case of chemotherapy after operation.The postoperative histopathological examination and immunohistochemical staining results showed that the diagnosis of 5 patients was sarcomatoid carcinoma.The postoperative follow-up time was 1-36 months, and the follow-up rate was 100%;among 5 patients, 1 case survived and 4 cases died. Conclusion: Sarcomatoid carcinoma of throat has no specifically clinical characteristics, and mainly present polypoid growth and is easy to be misdiagnosed.Its malignant degree is higher than that of squamous cell carcinoma, and it is easy to relapse and metastasis in the late stage. Its prognosis is poor, the diagnosis depends on the pathological examination, and surgical resection is preferred.
KEYWORDS: sarcomatoid carcinoma     throat     spindle cell carcinomas     histopathology     immunohistochemistry    

肉瘤样癌又称梭形细胞癌,由上皮成分和间质成分共同构成, 可发生在子宫、膀胱、乳腺、肺和支气管等全身各个部位,发生于咽喉部较罕见[1-6],其构成比约占全身肉瘤样癌的1%[7]。自1864年OLSEN等[8]首次描述该疾病以来,已经使用了许多替代名称,如梭形细胞癌、假性肉瘤、鳞状细胞癌梭形样变和多形细胞癌等,截至2010年,国内外仅报道410例喉肉瘤样癌患者[9]。本文作者收集5例咽喉部肉瘤样癌患者的临床资料,并结合相关文献报道如下。

1 临床资料 1.1 一般资料

回顾性分析2012年2月—2018年4月于本科经手术治疗的5例咽喉部肉瘤样癌患者的临床资料,其中男性4例,女性1例,发病年龄为55~77岁,3例有长期吸烟史,2例有饮酒史,均无术前咽喉部放疗史。发生在扁桃体1例,下咽2例,喉2例。患者主诉:咽痛、咽部异物感、声音嘶哑及呼吸困难等。5例患者术前均行电子喉镜检查,病例1表现为菜花样肿物,其余4例患者表现为较光滑肿物(图 1,见封三)。2例患者行CT检查,肿物表现为软组织密度影, 无骨质破坏(图 2)。

图 1 喉肉瘤样癌患者的电子喉镜图像 Fig. 1 Electronic laryngoscope image of patient with sarcomatoid carcinoma of throat
图 2 喉肉瘤样癌患者的CT影像 Fig. 2 CT image of patient with sarcomatoid carcinoma of throat
1.2 手术方法

5例患者均行手术治疗。病例1行右侧扁桃体扩大射频消融术+右侧软颚重建术+右侧Ⅱ、Ⅲ区颈淋巴结清扫,术后辅以放射治疗;病例2行双侧颈廓清+气管切开术+喉及下咽部分切除术+下咽重建术,术后辅以放疗及化疗;病例3行支撑喉镜下右侧声带肿物切除术;病例4行双侧颈廓清+气管切开术+部分下咽全喉切除+会厌瓣、舌根瓣、下咽重建术+颈前气管悬吊术;病例5行全喉切除术+气管切开术。

1.3 术后病理

病例1病理:(右侧扁桃体)梭形细胞癌,浸润横纹肌;免疫组织化学:CD34(-),CD31(-),CK(AE1/AE3)(+), CK5/6(-), p40(灶状+),Vimentin(+)。病例2病理:(下咽)低分化鳞状细胞癌(部分区域呈梭形细胞癌特征),切缘未见癌;免疫组织化学:CK5/6(灶状+),p63(+),Ki67(阳性率10%),S-100(-),SMA(-),CD34(-),CD68(-)。病例3病理:(右侧声带)符合肉瘤样癌;免疫组织化学:CK(AE1/AE3)(-), EMA(-), Vimentin(+), p63(部分+),p40(部分+),CK5/6(部分+), SMA(-), Desmin(-), HMB45(-), Ki67(阳性率70%),S-100(-)(图 3,见封三)。病例4病理:(下咽)肉瘤样癌,伴鳞状细胞癌及乳头状癌成分;免疫组织化学:CK(AE1/AE3)(部分+), Vimentin(部分+), Desmin(-),SMA(-), H-Caldesmon(-), Myogenin(-), Myoglobin(-), S-100(-), MelanA(-), HMB45(-), p63(部分+),CK5/6(部分+), Ki67(阳性率40%),CD31(部分+),CD34(血管+),CK19(+),BRAF V600E突变特异性抗体(VE1)(Ventana免疫组织化学增强扩增试剂盒)(++),HBME-1(部分+),Galectin-3(+), TG(+), TTF-1(+)。病例5病理:(喉)肉瘤样癌(中分化鳞状细胞癌,伴梭形细胞肉瘤成分),浸润软骨及横纹肌组织,骨组织内未见浸润,各切缘未见癌;免疫组织化学:CK(AE1/AE3)(+),CK5/6(+)、Ki67(阳性率40%),Vimentin(+), p63(+)。

A: HE staining; B: CK5/6(part +); C: Vimentin(+); D: Ki67. 图 3 喉肉瘤样癌患者肿瘤组织术后病理组织形态表现(免疫组织化学,×100) Fig. 3 Pathomorphology of tumor tissue of patient with sarcomatoid carcinoma of throat (Immunohistochemistry, ×100)
1.4 术后随访

5例患者均经电话随访,获得完整随访资料,无失访病例。随访时间1~36个月,术后1例患者存活,4例患者死亡。病例1为扁桃体肉瘤样癌,术后1年患者出现颈部淋巴结转移及肺内多发转移癌,再次行放疗后1年死亡。病例2为下咽肉瘤样癌,存活3年后因骨转移癌死亡。病例3为喉肉瘤样癌,仅行声带肿物切除术,未扩大切除,患者拒绝行术后辅助放疗,患者随访10个月,现恢复良好。病例4为下咽肉瘤样癌,术后1个月因局部感染和恶病质死亡。病例5为喉肉瘤样癌,随访2年后患者死亡。

2 讨论

肉瘤样癌可发生在子宫、膀胱、乳腺、肺和支气管等处,发生于咽喉部者较罕见,咽喉部肉瘤样癌多在成年发病,平均发病年龄为65岁,男女比例约为10:1,以过度吸烟、嗜酒的老年男性较多,也有文献[10]报道该病发生与接触放射线有关。肿瘤原发部位:声门区占72%、下咽区占14%、声门上区占12%、声门下区占2%[9]。本研究5例患者中,男性患者4例,有吸烟史者3例,与文献报道相符。肉瘤样癌病因未明,关于其起源,目前有3种学说:①碰撞学说,即肉瘤样癌来源于2个不同胚层间的相互浸润;②成分学说,即肉瘤样癌中的肉瘤样成分是癌成分所诱导形成的间质不典型增生反应;③单克隆学说,即肿瘤中的上皮成分和间质成分来源于共同的多能干细胞,朝着两个不同的方向发展,肉瘤样成分来自癌的化生[11]

咽喉部肉瘤样癌极易误诊为声带息肉,赵玮等[12]曾报道1例喉肉瘤样癌患者误诊为声带息肉,行支撑喉镜下声带息肉切除术,术后经免组织化学检测得以确诊,再次行右垂直半喉切除及右颈部淋巴结清扫术,术后随访1年未复发。咽喉部肉瘤样癌误诊主要原因:①喉肉瘤样癌较为罕见,仅占肉瘤样癌1%,男女比例约为10:1,以过度吸烟、嗜酒的老年男性较多,女性且无吸烟饮酒史者少见。②喉肉瘤样癌大部分表现为息肉型,仅有少数表现为深部浸润型[9]。本研究中病例3喉镜检查及术中探查显示瘤体呈息肉样生长,且表面光滑,符合声带息肉的临床特点。③未行免疫组织化学染色。肉瘤样癌患者的临床表现和影像学表现无明显特异性,与鳞状细胞癌相似,因此确诊需依靠病理学检查。光学显微镜下肉瘤样癌表现为同一肿瘤中既有癌成分又有肉瘤成分,其间质常由杂乱无章或交织束状排列的梭形细胞构成,细胞异型性明显,核分裂活跃。免疫组织化学检测结果显示:上皮性标志物呈阳性表达,如细胞角蛋白CK和EMA;间叶性标志物呈阳性表达,如Vimentin及S-100等[13]。本研究中5例患者的临床资料和免疫组织化学结果显示符合肉瘤样癌的诊断。④肉瘤样癌具有独特的组织学特点,由上皮成分及间质成分共同组成,取检时应多处取材,若只取检到间质成分,则易误诊为鳞状细胞癌,若只取检到上皮成分,则易误诊为平滑肌肉瘤等。肉瘤样癌需要与以下肿瘤进行鉴别:①恶性纤维组织细胞瘤。后者细胞成分复杂呈多形性,以成纤维细胞和组织细胞为主,细胞呈车辐状排列,一般不表达CK[14]。②平滑肌肉瘤。后者细胞较大,排列紧密,核分裂象多见,且免疫组织化学表达DES和ACT, 不表达CK。③恶性神经鞘瘤。后者瘤细胞呈长梭形,细胞核呈波浪状或逗点状,异型性不显著,免疫组织化学检测中S100蛋白、Leu-7蛋白和髓鞘碱性蛋白等呈阳性。

肉瘤样癌的恶性程度和死亡率高于鳞状细胞癌,且其复发率较高,甚至在早期复发,其晚期转移率较高。OLSEN等[8]对34例喉及下咽肉瘤样癌临床资料分析表明:首次治疗后患者3年生存率为56.8%,且角蛋白阳性对总生存率有不良影响,下咽肉瘤样癌患者的生存率明显低于喉部肉瘤样癌患者;对于喉肉瘤样癌而言,患者5年生存率排序为声门型80%,声门上型65%,声门下型40%。LEVENTON等[15]发现:患者存活率与肿瘤入侵深度有关,肿瘤浸润较深的患者生存率较低,而肿瘤浸润较浅的患者生存前景较好。咽喉部肉瘤样癌的治疗原则与头颈部鳞状细胞癌的治疗原则相同,以手术治疗为首选。肿瘤的部位和分期是影响肿瘤预后的主要因素[16]。SU等[17]通过对18例口腔肉瘤样癌患者的研究发现:肿瘤的切缘对复发无影响,但为了提高手术疗效,仍建议于肿瘤边缘处扩大2 cm进行切除。一般来说,对于T2期及更早期的声门区肿瘤,建议行保守治疗,即局部放疗,其效果较好,且长期并发症较少[18-19]。对于T3和T4期肿瘤,建议行喉部分切除或全喉切除术[20],对于下咽肿瘤,应行下咽部分切除术,伴有淋巴结转移者,应同时行颈部淋巴结清扫术[18-19]。有学者认为放疗对肉瘤样癌的疗效无明显影响,但OLSEN等[8]报道1例T1期声门癌患者单独行放疗后效果良好,49个月后仍未复发。AMPIL等[23]报道4例肉瘤样癌患者中2例患者受益于手术与放疗的联合作用。SU等[17]报道1例手术切缘阳性患者行辅助放疗后效果良好。因此,放疗可能有助于改善手术切缘阳性患者的生存质量。因本文作者收集病例数较少,尚无法明确放疗与患者预后的关系,需要后续进一步研究。

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