INTRODUCTION

Ectomesenchymal chondromyxoid tumor(ECT)is a very rare lesion almost exclusively occurring in the tongue.At present 74 lingual cases have been reported in the English and German literatures,nearly equally affecting males and females with a mean age of 39.3 years.1–31The term “ectomesenchymal chondromyxoid tumor,”given in the first relevant publication,is descriptive,based on the presumption of tumor origin from migrated ectomesenchymal cells of the neural crest,and on histological and immunohistological features.1

Interestingly,unequivocal extralingual ECTs have been reported hitherto only twice,on the hard palate of a 13-year-old boy32and in the left tonsillar bed of a 71-year-old woman.33In addition,we report for the first time a palatal case in a 54-year-old woman,which extends the knowledge on the epidemiology of extralingual ECTs.

To update and check all reports on ECTs in detail and to compare lingual and extralingual cases,we carried out an exhaustive review of the relevant literature.

The literature was reviewed using PubMed for publications related to ECT in English and German languages.The following search strings were applied:ectomesenchymal chondromyxoid tumor,ectomesenchymal chondromyxoid tumor and tongue,ectomesenchymal chondromyxoid tumor and hard palate,ectomesenchymalchondromyxoid liketumor,ectomesenchymal chondromyxoid like tumor and tongue,ectomesenchymal chondromyxoid like tumor and hard palate,Ektomesenchymaler chondromyxoider Tumor,Ektomesenchymaler chondromyxoider Tumor und Zunge,Ektomesenchymaler chondromyxoider Tumor und harter Gaumen.Additionally,the references of all publications were checked for reports on ECT not found by Pubmed using the above-mentioned strings.The search was limited by the end of 2016.

CASE REPORT

A 54-year-old woman presented at the Department of Oral Surgery and Orthodontics of the Medical University of Graz with a nodular lesion of the palatal gingiva.The lesion was located between the first and second incisor on the right upper jaw(Fig.1).The patient reported that she had the lesion for a long time;it had grown larger within recent months but was painless.A pre-operative X-ray showed no tumor involvement of the neighboring maxillary bone(Fig.2).Clinical differential diagnoses comprised epuliform lesions,most likely a fibroma or peripheral ossifying fibroma.The lesion was totally excised down to the periosteum under local anesthesia(Ultracain dental®4%,Sano fi-Aventis,Frankfurt am Main,Germany)and examined histopathologically by one of us(A.B.).A follow-up after 41 months showed no recurrence.

Pathological examination

The operative specimen measured 7:5:3 mm and was covered by an otherwise inconspicuous mucous membrane;the cut surface showed gelatinous tissue.Microscopically,the specimen was covered superficially by reactive hyperplastic squamous epithelium.A multinodular lesion was found in the underlying stroma(Fig.3).The nodules varied in size and consisted of myxoid/chondroid stroma,in which many cells,mostly spindle-shaped,were embedded(Figs.4 and 5).In general,the nodules were rich in cells,often showing eosinophilic cytoplasm.The nuclei were enlarged and hyperchromatic in some places,exceptionally with nucleoli.Perinuclear cytoplasmic vacuolization was seen in many cells.With the exception of tiny nodules,each nodule was surrounded by dense,capsule-like tissue.There were no ductal structures.Immunohistochemically the lesional cells showed variable expression of S-100 protein and smooth muscle actin(SMA).The Kiel 67 protein(Ki67)-associated cellular proliferation rate was＜5%.Interestingly,there were few nodules without any S-100 protein and SMA-positive cells(Fig.6a and b).No cells were immunoreactive for pancytokeratin,glial fibrillary acidic protein(GFAP),and cytokeratin(CK14).

Like the lingual lesions,the extralingual ones have to be discriminated clinically from a range of different lesions frequently occuring in the oral cavity32,33,36,whereas pathohistologically mainly pleomorphic adenomas and myoepitheliomas have to be considered in the differential diagnosis.In general,in classical histopathology pleomorphic adenomas are characterized by ductal structures,whereas these features have never been reported for ECT or should not appear in proper myoepitheliomas.35,39On the other hand,chondroid changes of the stroma may be seen in pleomorphic adenomas and ECTs,which is in contrast to typical myoepitheliomas.39

REVIEW OF THE LITERATURE

Lingual cases

Thirty-one publications were identified in the English and German literatures dealing with 36 female and 38 male patients with an age range of 7–78 years(Table 1,Fig.7).

Histogenesis.In their seminal paper on ECT,Smith et al.1favored the histogenesis of these tumors from ectomesenchymal cells that had migrated from the neural crest.They backed up this theory with embryonic considerations and immunohistochemical examinations demonstrating GFAP in 73%of the cases tested with a monoclonal antibody,and in 100%with a polyclonal antibody.Yoshioka et al.24were able to confirm the origin of ECT in ectomesenchymal cells derived from neural crest by demonstrating the expression of homeobox protein-transcription factor(Nanog),GFAP and microtubule associated protein 2(MAP2)in cell cultures and positivity for octamer binding protein 3/4(OCT3/4),transcription factor Sox2,Nanog,MAP2 and CD 105mRNAs in real-time polymerase chain reaction(RT-PCR)analysis.Moreover,withimmunohistochemicalmethods,Lacoetal.30showed expression of transcription factor Sox10 in one of their two cases,so supporting the proposed neural crest theory.

Of the cases tested with the pan-cytokeratin antibody AE1/AE3,55.3%stained positive1,8,9,11,13,20,27,28,31,while cytokeratin antibodies directed against a single subclass of cytokeratins almost always were negative.Using an antibody to SMA,51.1%of 47 cases exhibited positive immunostaining.1,11,12,15,17,20,23,24,27,28,30,which was exceeded by the muscle-specific actin marker HHF-35,which stained 3 of 3 cases2An immunoreaction for desmin could be detected in 30%of the cases evaluated.2,5,11,15,25,27,31Since transformation-related protein 63(p63)is thought to be one of several myoepithelial markers,it is remarkable that 31.8%of the cases examined were at least immunoreactive for this marker.8,12,15,24,27

Imaging:Imaging studies of the tumors were available for four cases.Sonograms of two cases revealed one hyperechoic and one hypovascular lesion.17,18Computed tomography(CT)scan without contrast in a further case showed a partially cystic mass25and magnetic resonance imaging(MRI)in the fourth case featured low-level signals and contrast enhancement.24

However,stimulated by previous genetic examinations on soft tissue myoepithelial tumors35Argyris et al.29successfully demonstrated rearrangement or gain of Ewing sarcoma breakpoint region 1(EWSR1)in 3 of 11 and 8 of 9 ECTs,respectively,whereas Laco et al.30failed to find an EWSR1 rearrangement in two such tumors.

Clinical features

Age and sex:The seven-case series of Aldojain et al.27does not provide data on age and sex of the individual patients,so that detailed relevant data were only available for the remaining 67 cases(90.5%)of the tumors of the tongue.The age range was between 7 and 78 years with a mean age of 39.3 years.For male patients,the age range was 7–78,for a mean age of 38.7 years,while the age range of female patients was 7–68 years,for a mean age of 40 years.The majority of the male cases(n=20,52.6%)appeared in the fourth,fifth,and sixth decades,which is in some contrast to female cases,which most often occurred in the third and sixth decades(in total 20 cases,55.5%).Interestingly,no female was older than 68,though the oldest male was 10 years older.The 67 cases involved 34 males and 33 females,for a nearly equal sex distribution of 1.03:1.

Location:In 63 cases(85.1%)data concerning the location were given.1–28,30,31Fifty-six lesions occurred on the anterior part of the tongue,and four lesions on the posterior part;the remaining three lesions were only reported to be on the dorsum of the tongue but without further positional information.Of the “anterior cases”26 could be found in males and 24 in females.The remaining six cases were listed by location only without gender.27Three of the four“posterior cases”occurred in males.The fourth case was given only by location but without gender.27

Clinical aspect:In 47 cases the size of the lesions could be determined by clinical inspection;they ranged in size from 3 to 50 mm(mean 13.6 mm).Of them,45 were located on the anterior aspect of the tongue and ranged in size from 3 to 50mm(mean 13.3mm)1–3,5–7,9–24,26,28,30,31;the two lesions on the posterior tongue each had a diameter of 20 mm.4,16In the 31 cases(exclusively anterior lesions)that described the impression of palpation, 19 cases were described as firm1,2,5,7,9,10,12–14,16,17,20,23,26,31,1 as soft1,1 cystic,11 firm-cystic1,4 elastic,3,18,19,22 2 non-tender24,28,1 tender20,1 firm-cystic1,1 soft-cystic.6

Clinical differential diagnoses:The reported differential diagnoses included various mainly mesenchymal lesions36,whose spectrum expanded when histopathology was taken into consideration.27However,judging the macroscopic illustrations in all the publications on the basis of our own clinical experience,we suggestfibroma,neurofibroma,myoepithelioma,and pleomorphic adenoma as the most likely clinical diagnoses.

恩施州内8县市旅游业发展不均衡，从历史发展状况来看，恩施市、利川市等各个方面发展较其他县市就处于领先地位，资金、基础设施、接待水平等较好、投入较大，且作为恩施州首府所在，有较好的发展基础和资源；从旅游资源来看，恩施州大多数景区的同质性较高，较早开发的景区通过加大广告投入等措施有较大的知名度，后来发展的景区对游客的吸引力减弱；州内旅游业整体上还是较为粗放的模式，而这些问题与资金投入相关性很大，资金充足、投入大的恩施市、利川市在旅游业发展中遥遥领先，其他县市都偏弱，从而造成了恩施州旅游业的发展不均衡。

Preoperative procedures

Looking for classical light microscopic features pointing topleomorphic adenomas,Ide et al.,6Chopra et al.,14and Closmann et al.23were unable to find ductal structures in ECTs.In addition,Argyris et al.29could not find molecular genetic rearrangement of pleomorphic adenoma gene 1(PLAG1)in seven cases.

As in the overwhelming majority of the cases in the tongue,two of the three extralingual cases were initially excised completely.In the third such case,by contrast,the lesion was first biopsied and then excised32,to establish a firm diagnosis prior to surgery,identically to the therapeutic procedure by Closmann et al.23in a lingual case.The extralingual tumors showed no recurrences within a short period of 6 months’follow-up32,33,and a long period of 41 months(present case).This is in contrast to the tumors of the tongue,which recurred in three cases1,12,which may be due to incomplete initial excision.

The location of ECTs in the tongue may be explained by their embryological development,in which migrating ectomesenchymal cells of the neural crest of branchial arches play an important role.24In this context,the nearly exclusively lingual occurrence of ECTs can be elucidated by the development of the anterior 2/3 of the tongue from the first branchial arch.38The same considerations are applicable to the cases involving the hard palate.By contrast,the posterior third of the tongue,where ECTs have been found very rarely,originates from the second,third,and fourth branchial arches.38This is in accordance with a recently published ECT of the left tonsillar bed/parapharyngeal space33,which are known to originate from the second branchial arch.38

20世纪初，为了严格地定义的数学基础，康托尔(Cantor)发明了集合论[17].在康托尔的成果基础下，对有理数进行如下定义：S是由任意整数m、n构成的有序数对(m,n)的集合,其中n非零.对于有序数对(a,b)和(c,d)，按如下法则将S划分为子集，当a/b=c/d，或者当且仅当ad=bc时，就将有序数对(a,b)和(c,d)视作相同的子集，二者也被看作相同分数.随着数学的发展，这种(m，n)形式的分数表达方式逐渐得以淡化，以通常在教科书上所见的形态展现出来：{m/n|m、n∈Z,n≠0}.因为形如(m,n)或m/n的数本身被集合所定义，所以集合论视域下的这些分数形式是毋庸置疑的数.

Pathology

Histopathology:For 74 lesions,only partial information was available for the following parameters:61 lesions were described as circumscribed1–3,5–8,10,11,13–23,26,28–31and 37 as lobular/nodular1,2,7,8,12–14,17,19,22–24,26,28,30;44 lesions revealed a growth pattern forming cords,strands,and net-like structures.1,3,5,6,8,14,16,17,20–27,31All lesions showed a mixture of varying numbers of round,spindled,ovoid,and fusiform cells.1–3,5–31Among them four lesions also exhibited epithelioid cells.29Every single lesion was characterized by a chondromyxoid stroma.1–3,5–31Entrapment of the adjacent skeletal muscle was found in 44 lesions.1,2,5,8,12–19,21,26–29 Immunohistopathology:A great many antibodies were applied in the examination of ECTs,among which neurogenic markers,cytokeratins and myogenic markers play an outstanding role.Most ECTs were immunoreactive for GFAP(85.7%),S-100 protein(80.4%),and CD57(77.4%).1,2,6,7,15,18,20,27,30

Nature.ECT is currently classified as an entity by the World Health Organization(WHO),34but has morphological and immunohistochemical properties in common with myoepithelioma,and to a lesser extent with pleomorphic adenoma.

Electron microscopy:Ultrastructural studies were performed in only three exclusively anterior cases.The lesions of a 27-year-old female and a 58-year-old male exhibited tumor cells with lobulated/concave nuclei,homogeneous chromatin distribution and one to two small nucleoli,dilated endoplasmic reticulum,intermediate filaments,and a partial basal lamina;desmosomes or condensed thin filaments could not,however,be demonstrated.1,30Tumor cells in the case of a 51-year-old woman probably were poorly sampled and so showed no intracytoplasmic matrix production,but pinocytotic vesicles,a well-developed rough endoplasmic reticulum and tight junctions.2

Differential diagnosis:Histopathologically, myoepithelioma1,2,8,14,25,29,and pleomorphic adenoma1,8,14,29were the most relevant differential diagnosis because of their pronounced histological similarities.

Follow-up.In 33(44.6%)of 74 lingual cases unequivocal data were available for follow-up.The follow-up period was between 2 and 240 months.1,6Three of the 33 cases(9.1%)revealed recurrences appearing after 3 months,19 months1,60 months.12 Metastatic deposits were never reported.

Extralingual cases

At present only three extralingual cases including the present one and concerning two female patients and one male patient aged between 13 and 71 years have been reported.Detailed data are given in Table 1.

In all three cases tumor cells were immunoreactive for S-100 protein,in two cases for GFAP32,33,and in only one case for cytokeratin33and SMA(present case).

A further case reported in the hard palate was not acceptable due to lack of immunohistochemical data.37

DISCUSSION

The authors of the first publication on the tumors under discussion suggested the descriptive name“ectomesenchymal chondromyxoidtumor”(ECT)based on morphologicaland immunohistochemical parameters and,more importantly,on histogenetic and embryologic considerations.1In 2005,ECT was adopted by the World Health Organization as a diagnostic term,which is still in use.34

Therapy.In 54 of 74 cases the lesions were removed in toto by excision1–3,5–22,24–26,28,30,31,whereas in the remaining cases there was no information on the nature of the surgical procedure.2,4,13,27

据不完全统计，全国约有23.4%的乡镇水利站作为县(市)水利局的派出机构，或实行县（市）乡“双重管理，以条为主”管理，纳入财政预算；约36.69%的乡镇水利站由乡镇管理；约24.81%的乡镇水利站机构被撤销并入到乡镇农业综合服务中心（站）。全额拨款型比重最高（58.62%），差额拨款型、自收自支型与企业型分别占总量的24.40%、16.78%及0.20%。经费来源上，自筹经费占总经费的90.81%，以办公费用为主（占自筹经费总额的87.18%）；而财政拨款仅占总经费的9.19%，其中56.08%为前期费用。

Although thenumberofextralingualECTsisextremely small32,33,the clinical data mirror those of the lingual cases;i.e.the former also occurred in both sexes(one male and two female patients),with an age distribution of 13–71 years and a mean age of 46 years.

In the two palatal cases,x-rays showed no pathology in the underlying bone.32Since the lingual cases were set in purely soft tissue,these locations did not lend themselves to radiographic studies.Probably because of its location,only the peritonsillar/parapharyngeal lesion was investigated by CT scan,showing a central calcification and no enhancement of contrast medium.33 This is paralleled by an MRI analysis of a lesion of the tongue,also without contrast medium enhancement.24

Fine needle aspiration biopsy(FNAB):In six cases a preoperative FNAB was performed,which,however,was always inconclusive with the final diagnosis.5,14,17,18,25,26

The extralingual specimens ranged in size from 7 to 30.5 mm(mean 20.7 mm),and so were larger than the lingual ones(3–50 mm;mean 13.9mm).

Whether localized in the hard palate or in the tonsillar bed/parapharyngealspace,the lesions were histopathologically characterized by circumscribed unencapsulated proliferation with lobular architecture and by monomorphic rounded,spindled,stellate,or polygonal cells set in a chondromyxoid stroma.Since their features are identical to tongue lesions,it can be said that the morphologicalpattern ofECT is independentoftumor localization.

从浙江经验走向全国，“最多跑一次”改革书写了深化放管服改革的新篇章，迈入“互联网+政务服务”发展的新阶段。

腐败危及和破坏法律的权威性和有效实施，又破坏我国社会主义的经济基础。它不仅仅是官员滥用职权的问题，还包括各个层面为谋取私利而滥用职权的行为。反腐倡廉，即反对腐败，倡导廉政。要廉政就必须反腐，而反腐才能廉政，古今中外概莫能外。中国共产党历来坚持“反腐倡廉”，尤其在经济体制转换的改革开放的时期，更是把“反腐倡廉”作为党风廉政建设的重要内容。

司法部提出的以政治改造为统领，统筹推进监管改造、教育改造、文化改造、劳动改造的工作要求，抓住了监狱改造罪犯工作的根本问题，拓展和深化了监狱改造罪犯工作体系，是新时代党的方针政策在监狱工作中的具体体现，是监狱工作的指导原则和努力方向，体现了监狱的本质属性和重要功能。在世情、国情、党情、社情、狱情均发生深刻变化的新形势下，构建以政治改造为统领的五大改造新格局，具有很强的必然性。笔者认为，这种必然性主要体现在以下几个方面：

Immunohistochemically,all three extralingual cases expressed S-100 protein,which could also be detected in more than threequarters of the lingual cases.The same can be said with regard to the reactivity for GFAP in two cases.32,33The negativity for GFAP in our case may be explained by the use of a monoclonal antibody,which is a finding also seen in lingual cases8,16,17,27and in contrast to examinations with polyclonal antibodies.The impossibility of demonstrating pancytokeratins in the two palatal cases32mirrors the variability of pancytokeratin expression in tongue lesions.

2型糖尿病患者的主要死亡原因为大血管病变，而非酒精性脂肪性肝病(non-alcoholic fatty liver disease，NAFLD)可以预测心脑血管疾病的发生[1]，提示2型糖尿病合并NAFLD患者患心脑血管风险更高。在2型糖尿病患者中，有约2/3的人合并NAFLD，NAFLD患病率是一般人群的5～9倍[2-3]。然而，有关2型糖尿病患者发生NAFLD危险因素的研究较少。

Both palatal cases differ in the immunoreaction for SMA.This discrepancy may be explained by the use of different antibodies to SMA,the source of which is not given in the SMA-negative case by Gouvêa et al.32or by the tumors themselves because only 51.1%of lingual cases are also SMA positive.Since pleomorphic adenomas and myoepitheliomas are known to express the antigens mentioned above35,39,immunohistochemistry alone does not allow a strict differentiation of these lesions from ECT.

（1）通过对11类食品8种致病菌检验结果表明，婴幼儿食品、乳品及乳制品中蜡样芽胞杆菌污染较为严重，乳品及乳制品检出率最高；在城市流动早餐、节令食品（棕子）中分别检出了3株和1株，表明蜡样芽胞杆菌是当前我市高危病源菌。尽管我国未曾大规模爆发蜡样芽胞杆菌引起的食源性疾病，但由于其广泛存在于自然界中，属于条件致病菌，也是本地区经常发生食物中毒的病源菌之一，其潜在危害性需引起足够重视。

随着我国乡村振兴战略的部署，我国农村现代化发展水平在不断提高，农村金融所要服务的对象也在不断变化，更多的农村经营组织需要金融服务，需要建立动态性农村金融服务体系，满足不同对象的差异化和个性化服务需求，紧跟市场最新动态，提供不同类别的金融服务，适时地对金融服务进行调整和优化。

Despite close histological and immunohistological similarities,for several reasons it is unlikely that ECT is a subtype of pleomorphic adenoma.ECTs are mainly located in the anterior part of the tongue,an area that is devoid of salivary glands,which are considered to be the origin of pleomorphic adenomas.Moreover,ductal structures have never been found in ECT.6,14,23In any case,genetic examinations showed no rearrangement of PLAG1 in 7 cases.29

傍晚时分，杨宗祥站在云南祥丰集团温泉商贸中心酒店楼顶的露台上眺望，冬日暖阳撒在他的身上，形成一圈淡淡的光晕，这样的瞬间似乎很久都没有过了。

Very recent genetic studies,however,have demonstrated rearrangementorgain ofEWSR129,implying thatECTis genetically somehow similar to myoepithelioma.

Summarizing,based on histopathological,immunohistpathological,and common genetic features,some degree of relationship between ECT,myoepithelioma,and pleomorphic adenoma may be supposed.

In the setting discussed above in detail,our unique extralingual case in the hard palate of a woman differs substantially in its location from the vast majority of ECTs reported,but is similar in terms of histopathology,immunohistopathology,and biological behavior.

Addendum

随时抹掉核桃砧木上萌发的全部芽眼，以集中养分供给接芽萌发和新梢生长。当新梢长到30 cm以上时，及时摘心，促发二次枝，适时解除接口包扎物。

After finishing our study by the end of 2016 in 2017 the further relevant paper on ectomesenchymal chondromyxoid tumors was published:“Kato MG,Erkul E,Brewer KS,Harruff EE,Nguyen SA,Day TA.Clinical features of ectomesenchymal chondromyxoid tumors.A systematic review of the literature.Oral Oncol 2017;67:192–197”.

ADDITIONAL INFORMATION

有了适合的文章，做好课本剧的准备工作，是保障课本剧能够顺利进行的重点工作。课本剧的准备工作，包括剧本改写、动作排练、场景设置等环节。首先，我们教师要带领学生深入理解文章内容，如文章发生的背景、主人公的心理和行为。其次，教师要根据学生的特点进行角色分配、道具准备，指导学生进行剧情的排练。

Conflict of interest:The authors declare that they have no conflict of interest.

通过技术措施提高混凝土的耐久性，使其更具有抗碱-集料反应、抗裂、抗碳化、抗渗的能力，以保证混凝土隧洞的正常使用，以及延长混凝土隧洞的使用寿命。本文通过对提高混凝土耐久性技术措施的简要阐述，可以为类似工程提供参考。

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