Asian Case Reports in Oncology
Vol. 08  No. 02 ( 2019 ), Article ID: 30576 , 7 pages
10.12677/ACRPO.2019.82003

Adult Solid Alveolar Rhabdomyosarcoma: A Case Report and Literature Review

Jie Peng1,2, Wei Wang1, Renya Zhang1, Wen Cui3*

1Department of Pathology, Affiliated Hospital of Jining Medical University, Jining Shandong

2College of Clinical Medicine, Jining Medical University, Jining Shandong

3Center of Forensic Science, Jining Medical University, Jining Shandong

Received: May 5th, 2019; accepted: May 24th, 2019; published: May 31st, 2019

ABSTRACT

Objective: To investigate the pathological features, treatment and differential diagnosis of adult solid alveolar rhabdomyosarcoma (ARMS). Methods: The pathological features and immunophenotype of 1 case of solid alveolar rhabdomyosarcoma were observed and the related literatures were consulted. Results: The tumor was located in the left groin, and the tumor consisted of solid tumor cell nests with no obvious alveolar structure. Some tumor cells are rich in glycogen, similar to renal clear cell carcinoma or soft tissue clear cell sarcoma, called clear cell variant. Immunohistochemical staining showed that tumor cells desmin, Myoglobin, MyoD1, CD99, CD56 all (+), Syn, CgA, Fli-1, LCA, TTF-1, CK, CD20 all (−), tumor cell Ki-67 proliferation index of about 70%. Conclusion: ARMS is a malignant tumor from embryonic mesenchymal tissue [1] , which occurs in deep soft tissues of the extremities. It is morphologically characterized by a vesicular structure. It needs to be associated with malignant lymphoma, clear cell sarcoma, and Ewing’s sarcoma (ES)/primitive neuroectodermal tumor (PNET) and other identification [2] .

Keywords:Alveolar Rhabdomyosarcoma, Metastasis, Pathological Features, Immunohistochemistry

成人实体型腺泡状横纹肌肉瘤1例并文献复习

彭洁1,2,王卫1,张仁亚1,崔文3*

1济宁医学院附属医院病理科,山东 济宁

2济宁医学院临床医学院,山东 济宁

3济宁医学院司法鉴定中心,山东 济宁

收稿日期:2019年5月5日;录用日期:2019年5月24日;发布日期:2019年5月31日

摘 要

目的:研究成人实体型腺泡状横纹肌肉瘤(alveolar rhabdomyosarcoma, ARMS)的病理学特征、治疗以及鉴别诊断。方法:观察1例实体型腺泡状横纹肌肉瘤的病理学特征及免疫表型,并查阅相关文献。结果:肿物位于左侧腹股沟,肿瘤由实性瘤细胞巢组成,腺泡状结构不明显。部分瘤细胞因富含糖原透明,类似肾透明细胞癌或软组织透明细胞肉瘤,称为透明细胞变型。免疫组化示肿瘤细胞desmin Myoglobin, MyoD1, CD99, CD56均(+), Syn, CgA, Fli-1, LCA, TTF-1, CK, CD20均(−),瘤细胞Ki-67增殖指数约70%。结论:ARMS是发生自胚胎间叶组织的恶性肿瘤 [1] ,多发生于四肢深部软组织,形态学上以腺泡状结构为特征,需与恶性淋巴瘤、透明细胞肉瘤、尤文氏肉瘤(ES)/原始神经外胚层肿瘤(PNET)等鉴别 [2] 。

关键词 :腺泡状横纹肌肉瘤,转移性,病理学特征,免疫组织化学

Copyright © 2019 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

1. 引言

腺泡状横纹肌肉瘤 [3] (alveolar rhabdomyosarcoma, ARMS)常见于10~25岁的青少年,男多于女。ARMS在成人中并不常见,超过60%的成年患者在初诊时有局部或远处转移 [4] ,预后很差,好发四肢,也可发生于躯干。主要症状是痛性或无痛性肿块,手术、化学疗法 [5] 和放射疗法 [6] 是有效的治疗方法并可降低转移率。最常使用的药物是长春新碱和环磷酰胺 [7] ,本文将结合文献对1例实体型腺泡状横纹肌肉瘤 [8] 的临床及病理学特征、免疫表型进行分析,旨在提高对其诊断水平。

2. 材料与方法

2.1. 临床资料

中年男性,48岁,6天前发现左侧腹股沟肿物,质硬,无触痛,活动可,期间服用头孢进行治疗,效果不佳,近2天左侧腹股沟区疼痛,无发热、无乏力等不适,查体:T36.5℃,P89次/分,R20次/分,BP138/90 mmHg,神志清,精神可,给予手术完整切除。

2.2. 方法

1) 标本经规制片

2) HE染色

将已脱蜡后的切片放入苏木素溶液中染色10 min–流水冲洗5~10 s–分化液1~3 s–流水冲洗3~5 s–氨水返蓝5~10 s–流水冲洗15~30 s–伊红染色液染色1 min–流水冲洗3~5 s–70%、90%和100%酒精依次脱水各5 min–二甲苯透明10 min–中性树胶封固。

3) 免疫组化染色

石蜡切片,烤片30 min以上(46℃)–二甲苯15 min–100%、95%和80%乙醇各5 min–去离子水洗1 min–抗原修复EGTA (50×) 5 ml与250 ml去离子水混合H1沸腾5 min、加入切片标本80℃ 7 min、60℃ 7 min–隔水降至室温–去离子水3 min–缓冲液冲洗6 min–Hydrogen Peroxide Block孵育10~15 分钟–缓冲液洗5 min/2次–滴加一抗工作液37℃孵育2小时。(具体孵育时间和温度由试验者最终决定)–缓冲液洗5 min/2次–Primary Antibody Enhancer (增强子),在室温下孵育20分钟–缓冲液洗5 min/2次–HRP Polymer (酶标二抗),在室温下孵育30分钟。(注:HRP Polymer对光敏感,应避免不必要的光暴露并储存在不透明的小瓶中。)–缓冲液洗5 min/2次。向1 ml DAB Plus Substrate (或AEC Plus Substrate)中滴加1~2滴DAB Plus Chromogen,混匀后滴加到切片上,孵育3~5分钟。(具体时间由染色深浅决定。)–自来水充分冲洗,复染,脱水,透明,封片。

3. 结果

3.1. 眼观

结节样物一枚,大小2.2 × 1.7 × 1 cm,切面灰白质韧。

3.2. 镜检

瘤细胞呈片状或巢状排列,呈实性(图1),腺泡状结构不明显,镜下见肿瘤由比较幼稚的横纹肌母细胞组成,呈圆形、卵圆形或小多边形,核深染,核仁不明显。部分瘤细胞因富含糖原淡染或透明,类似肾透明细胞癌或软组织透明细胞肉瘤,称为透明细胞变型(图2)。

Figure 1. Tumor cells are round, oval, and the structure of the acinus is not obvious

图1. 肿瘤细胞呈圆形、卵圆形,腺泡结构不明显

Figure 2. Part of the tumor cell cytoplasm is transparent, mitotic figures are more common

图2. 部分肿瘤细胞胞质透明,核分裂象多见

3.3. 免疫表型

肿瘤细胞Myoglobin (图3)、desmin (图4)弥漫强阳性,MyoD1 (图5)、CD99、CD56阳性,Syn、CgA、Fli-1、LCA、TTF-1、CK(图6)、CD20均呈阴性,瘤细胞Ki-67增殖指数约70%。

Figure 3. Myogenin is diffusely strongly positive in tumor cells, EnVision method

图3. 肿瘤细胞中Myogenin呈弥漫强阳性,EnVision法

Figure 4. Desmin is strongly diffusely positive in tumor cells, EnVision method

图4. 肿瘤细胞中desmin呈弥漫强阳性,EnVision法

Figure 5. Myo D1 is diffusely strongly positive in tumor cells, EnVision method

图5. 肿瘤细胞中Myo D1呈弥漫强阳性,EnVision法

Figure 6. CK is negative in tumor cells and positive in normal tissues, EnVision method

图6. 肿瘤细胞中CK呈阴性,正常组织中呈阳性,EnVision法

3.4. 病理诊断

腺泡状横纹肌肉瘤。

4. 讨论

4.1. 临床特征

横纹肌肉瘤是婴儿和儿童最常见的软组织肿瘤,根据肿瘤的临床特点、病理和分子遗传 学特征,分为4型:腺泡状横纹肌肉瘤、胚胎型横纹肌肉瘤、梭形细胞横纹肌肉瘤、葡萄状横纹肌肉瘤 [1] 。ARMS好发于四肢,尤其是前臂和上臂,也可发生于颈部及躯干处,肿瘤边界不清,常浸润周围软组织。ARMS有许多不同的临床表现,类似于淋巴瘤,白血病等全身性疾病。成人ARMS局部淋巴结转移率高 [6] 。本例表现为左侧腹股沟肿物,质硬,无触痛。免疫组织化学染色:肿瘤细胞desmin、Myoglobin弥漫强阳性,MyoD1、CD99、CD56阳性,Syn、CgA、p40、TTF-1、Fli-1、CK均呈阴性,瘤细胞Ki-67增殖指数约70%。

4.2. 病理学特征

ARMS根据病理学特征分为经典型、实体型和胚胎性–腺泡状混合型三种。经典型肿瘤细胞为圆形和椭圆形,胞质呈嗜酸性、核深染 [9] ,镜下可以看到裂隙样腔隙或更典型的肺泡模式区域。小部分可有横纹肌细胞分化的形态学证据,包括带状细胞和多核成肌细胞,另外,细胞核位于胞质周边的多核巨细胞也可存在。实体型ARDS瘤细胞呈实性排列,无明显纤维血管性间隔及腺泡状结构,有时还可见透明细胞变型。胚胎性–腺泡状混合型除了包括经典型区域,还有胚胎性横纹肌肉瘤的形态。本例肿瘤由实性瘤细胞巢组成,腺泡状结构不明显。部分瘤细胞因富含糖原淡染或透明,类似肾透明细胞癌,称为透明细胞变型。

4.3. 鉴别诊断

1) 恶性淋巴瘤:恶性淋巴瘤无腺泡状结构,且表达淋巴瘤相关标CD79a、CD3等,不表达肌源性标志物desmin、Myoglobin、MyoD1等。2) 透明细胞肉瘤(也称为软组织的恶性黑色素瘤):肿瘤由透明细胞构成,可显示不同水平的黑素细胞分化,免疫组化S-100蛋白和HMB-45呈强阳性。另外,透明细胞肉瘤的染色体移位t (12; 22) (q13; q12)产生融合蛋白EWSR1/ATF1可与ARMS鉴别。3) 尤因氏肉瘤:以小圆细胞为主要结构与ARMS相似,但尤因氏肉瘤无散在横纹肌母细胞分化,免疫组化染色vimentin、NSE阳性,不表达desmin、Myogenin和MyoD1。4) 滑膜肉瘤:好发于青少年,包括上皮细胞和梭形肉瘤细胞两种,分化差的单相滑膜肉瘤可以模拟小圆形细胞恶性肿瘤。大多数病例对上皮膜抗原(EMA)和角蛋白呈阳性可以与ARMS鉴别。

4.4. 遗传学改变

研究发现大约85%的ARMS有特征性t (2; 13) (q35; q14)或t (1; 13) (p36; q14)易位,导致PAX3-FOXO1 [8] 和PAX7-FOXO1融合蛋白的表达 [1] , PAX3-FOXO1是最常见的,通过编码转录激活子,通过异常驱动多种基因的表达促进肿瘤的发生,小部分ARMS为融合阴性。ARMS中2、12、13号染色体易发生基因扩增。约55%的RMS患者N-Myc过表达。另外,p53是一个重要的抗癌基因,涉及细胞周期调控、凋亡、衰老以及具有帮助细胞基因修复缺陷的功能。p53突变型会提高癌变可能性,而ARMS中p53通路的突变率为7%,突变型提示ARMS预后较差。

4.5. 治疗及预后

ARMS是一种高度恶性的横纹肌肉瘤,宜采用手术、化疗和放疗相结合的综合性治疗,具体根据肿瘤大小、组织学分型、远处转移以及患者自身情况制定个性化治疗方案。临床数据分析显示环磷酰胺 + 蒽环类或环磷酰胺 + 异环磷酰胺 + 蒽环类组合治疗的患者在5y-PFS方面表现明显更好 [7] 。研究表明G9a表达的丧失可导致AKT和RAC1活性降低并减弱肿瘤细胞的增殖和迁移的能力,因此选择性G9a抑制剂为ARMS新的治疗方法 [1] 。另外,将NRF2 [10] 作为新的潜在分子靶标,并在放射治疗中维持氧化剂/抗氧化剂平衡也是种有效的治疗手段。

ARMS预后差 [11] , Elsebaie [7] 等分析了553名成人ARMS患者的临床数据,发现成人患者的5y-OS率较低:20%~40%。另外,对78例ARMS病例的预后数据分析发现ARMS中与PAX3-FKHR阳性相比,PAX7-FKHR阳性的总生存期更好 [12] 。

文章引用

彭 洁,王 卫,张仁亚,崔 文. 成人实体型腺泡状横纹肌肉瘤1例并文献复习
Adult Solid Alveolar Rhabdomyosarcoma: A Case Report and Literature Review[J]. 亚洲肿瘤科病例研究, 2019, 08(02): 15-21. https://doi.org/10.12677/ACRPO.2019.82003

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  13. NOTES

    *通讯作者。

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