颌骨多原发性牙源性角化囊性瘤影像学特征研究
|
摘要
一、研究背景
颌骨牙源性角化囊性瘤(keratocystic odontogenic tumor, KCOT)是一种良性、单囊或多囊的牙源性肿瘤,好发于下颌骨磨牙区和下颌升支,但是任何与牙列发育相关的区域都有可能发生。其具有较高的增殖潜能,生长方式特殊,内衬不全角化的复层鳞状上皮可发生癌变还可与基底细胞痣综合征(Basal cell nevus syndrome, BCNS)并发,保守性手术后易复发。其传统的命名为牙源性角化囊肿(odontogenic keratocyst, OKC)。Ahlfors等的研究结果表明,角化囊肿的有丝分裂指数增加与成釉细胞瘤相似,认为角化囊肿是一种良性肿瘤。Stenmen等通过细胞培养,将角化囊肿与成釉细胞瘤比较,角化囊肿上皮细胞在培养基上继续保持代谢功能,与成釉细胞瘤相似。因此,认为角化囊肿也具有肿瘤特征。
王恩博等研究表明,角化囊肿具有较高的上皮增殖活性,表现为增殖细胞核抗原(proliferating cell nuclear antigen, PCNA)阳性细胞较多。应用PCNA阳性细胞及DNA含量测定等细胞增殖动力学研究方法进行综合分析,结果表明,角化囊肿上皮细胞增殖活跃,与成釉细胞瘤相似。上皮增殖是上皮性肿瘤的基本特征,而牙源性角化囊肿也具备这一基本特点,因此角化囊肿可视为一种良性肿瘤,具有侵袭性生长的特点,其性质类似壁性成釉细胞瘤。建议把牙源性角化囊肿命名为“牙源性角化囊性瘤”。2005年WHO对头颈部肿瘤的新分类中,已将其归为牙源性良性肿瘤,并提出牙源性角化囊性瘤的命名。
牙源性角化囊性瘤好发年龄为10-29岁,Browne:报道40-50岁为其第二发病高峰。男性较女性多见。牙源性角化囊性瘤临床上主要表现为颌骨膨大,继发感染时可出现疼痛。由于其生长的隐匿性,除非增大到导致颌骨膨隆或引起症状,否则极难早期发现。牙源性角化囊性瘤生长缺乏自限性,可导致严重的颌骨破坏,术后具有较高的复发倾向。可能与其衬里上皮的生物学行为有关。研究认为其上皮层有丝分裂活性增加和细胞增殖标志物高表达,具有肿瘤细胞增殖活性。
多原发性牙源性角化囊性瘤(Multiple primary keratocystic odontogenic tumor, MPKCOT)是指宿主同时或先后发生两个或两个以上的原发角化囊性瘤。按照两个囊性肿瘤发现的时间间隔可分为同时性和异时性两种,间隔不超过6个月者归为同时性,超过6个月者归为异时性。多原发性牙源性角化囊性瘤文献报导较多,如含有多发性牙源性角化囊性瘤的基底细胞痣综合征患者,目前对牙源性角化囊性瘤基础研究较多,尤其基因方面的研究；对牙源性角化囊性瘤治疗手段的研究也取得了较好的效果；但对此类疾病的影像学特征剖析得不够充分,尤其对多原发性牙源性角化囊性瘤早期病灶的诊断尚未见文献总结报道,对异时性原发性牙源性角化囊性瘤病灶极易误诊为复发,基底细胞痣综合征牙源性角化囊性瘤复发率各文献统计差异极大,约22%-60%。其复发率较高的原因：一是囊壁薄而脆,在有骨破坏时难于完整摘除；二是衬里上皮具有较高的分裂活性；三是囊壁内外的上皮岛和子囊可能遗留；四是多原发异时性牙源性角化囊性瘤的发生,把原发灶当成复发统计；五是检查手段的落后,对同时性牙源性角化囊性瘤早期微小病灶漏诊,复查时当成复发灶；六是由于有“异位复发”这一概念的存在,易被临床滥用,这可能与临床医师和患者易接受复发这一事实,而对漏诊、误诊原发灶极为反感；上述六点是造成复发率偏高的主要原因。
本文首次提出多原发性牙源性角化囊性瘤(MPKCOT)这一命名,主要是为了方便统计和对其影像学特征更好地总结,尤其对多原发性牙源性角化囊性瘤早期微小病灶的诊断、治疗及预后提供理论指导。如果使用“多中心性牙源性角化囊性瘤”这一命名,对同时性病灶的表述不会存在问题,但对异时性病灶的描述将有较大的局限性,对异时性原发囊性瘤病灶必须要用原发性来描述,以明确区分是否为复发,因此,综合考虑使用“多原发性”这一命名较“多中心性”更加合适,更能体现MPKCOT的特征。
基底细胞痣综合征,即颌骨囊性瘤-基底细胞痣-肋骨分叉综合征(jawcysts-naevoid basal cell epithelioma-bifid rib asyndrome)或称Gorlin综合征(Gorlin's syndrome)。是一种常染色体显性遗传性疾病,具有遗传倾向,可有家族史,亦可散发。BCNS发病率为1/57000,男/女约3：1；该综合征主要体征有皮肤多发性基底细胞痣、颌骨多发性KCOT和骨骼异常、中枢神经异常、颅内钙化、掌足凹陷、特殊面征等多种疾病。与该综合征有关的疾病超过100多种,如某些内分泌疾病、智力迟钝、卵巢纤维瘤、唇腭裂等。颌骨多发性囊性瘤为该综合征常见表现之一,见于65%-90%的患者。一般认为,只要有三项主要体征符合即可诊断本征。
本作者长期追踪1例基底细胞痣综合征患者发现,其多原发性囊性肿瘤具有异时对称的影像学特点,说明多原发性牙源性角化囊性瘤在影像学表现上可能是有规律可循的,本文对本院确诊的15例牙源性角化囊性瘤的囊肿数目、发病部位、发病时间、影像学特点及MPKCOT与基底细胞痣综合征的关系等方面进行系统总结,旨在发现多原发性牙源性角化囊性瘤共同的影像学规律,为该疾病的早期微小病变的诊断提供理论支持。
二、研究目的
1、本研究利用颌骨全景片并结合锥形束CT对本院15例颌骨多原发性牙源性角化囊性瘤影像学特征进行分类统计和总结分析,旨在揭示其多原发灶的发生规律,为早期微小原发灶的诊断提供理论支持。
2、探讨锥形束CT对早期微小原发性角化囊性瘤病灶的诊断价值。
三、研究方法
1、病例选取
选取1997年7月—2010年2月在广东省口腔医院住院治疗的多原发性牙源性角化囊性瘤患者20例为研究对象,其中5例因为影像资料不完整没有纳入研究,其它15例均有完整的影像学(全景片、头颅正位、头颅侧位或锥形束CT、胸片等)、详细住院病历和病理等资料。
2、影像资料分析
对我院9例多原发性牙源性角化囊性瘤原始的和各个时间段回访的影像学资料进行系统复查,对其影像学特点分类统计和总结分析,如发病部位是否恒定、病灶与牙位的关系、原发灶出现规律、与基底细胞痣综合征的关系等。利用分析所得影像学规律对随后6例多原发性牙源性角化囊性瘤的患者进行系统诊断。可疑微小病灶利用锥形束CT筛查。
四、结果
1、多原发性牙源性角化囊性瘤新影像学特点：
①.多原发灶具有对称性：多原发性牙源性角化囊性瘤的发病是由基因控制,人体的上、下颌骨在发育过程中是由左右两块骨融合而成,双侧上、下颌骨同时发病就会呈现对称性,由于人体受多种调节系统的控制,部分区域会延时发作或到死亡时仍未表现,本组样本虽然有少部分病例个别病灶暂未出现对称灶,但纵观整个样本不难看出,多原发性牙源性角化囊性瘤对称性趋势非常明显；
②.原发灶位置恒定：原发灶恒定出现在87 78、543 345、543345这4个区域,其中87 78：12例,87 78：12例,543 345：10例,543345：7例,可以看出543 345区较其它区域出现频率少；
③.部分病例具有异时性的影像学特点：虽然多原发性牙源性角化囊性瘤受基因控制,但同时其也受多种调控系统的调节,部分区域会延时发病。异时的影像学特征符合Knudson的二次突变(双重受击)学说(two-hit model),即第一击为显性基因的存在,第二击因素可能是多方面的,包括放射因素,如X线或光化性等。双重受击学说可以解释同时或异时对称多原发病灶,第一击显性基因激活特定部位的全部(同时性)或部分(异时性)靶器官,第二击刺激未激活的靶器官导致后期多个病灶陆续出现。
④.高含牙率：本样本15例患者共发现囊性病灶77个,平均5.1个/人,其中含牙囊性病灶41个,含牙率为53.2%。
2、基底细胞痣综合征与多原发性牙源性角化囊性瘤的关联性
本组样本15例多原发性牙源性角化囊性瘤均有3项以上体征支持基底细胞痣综合征,说明多原发性牙源性角化囊性瘤与基底细胞痣综合征高度相关,可能所有多原发性牙源性角化囊性瘤均为基底细胞痣综合征,反之是则不成立的,多原发性牙源性角化囊性瘤与基底细胞痣综合征是否一一对应尚需大量样本验证,即只须颌骨多原发性角化囊性瘤病灶就可诊断基底细胞痣综合征,而不是目前公认的诊断标准——具备三项或三项以上基底细胞痣综合征体征。
3、锥形束CT在诊断多原发性牙源性角化囊性瘤早期微小病灶的价值
锥形束CT可以发现2mm左右的早期微小病灶,可以弥补全景片对早期微小病灶易漏诊的局限性：①全景片断层阈[即成像厚度约2 mm(前牙区)-4mm(磨牙区)]以外的所有骨质均可以完全模糊掉,当早期病灶位于断层阈外可完全不显影；②全景片为厚约2-4mm颌骨的重叠二维影像,直径小于2-4mm的早期病灶仅表现骨质密度轻微不均匀降低；③稍大一些的早期病灶如果全景片的断层阈不通过病灶中心也同样表现为骨质密度降低。上述三点将会造成早期囊性病灶在全景片上缺乏囊性病灶内部密度均匀、边缘有清晰致密线状硬化边等影像学特征,从而导致大量早期病灶漏诊。
早期微小囊性病灶因完全局限于颌骨松质骨内,生长阻力较均匀,表现为圆形或椭圆形均匀低密度灶,高分辨锥形束CT重建层厚可达100μm以下,完全可以克服病灶因重叠太多掩盖其显示,早期KCOT在锥形束CT上表现为圆形或椭圆形均匀低密度灶,边缘见清晰致密线状硬化边,沿颌骨长轴生长趋势不明显。
利用上述总结的多原发性牙源性角化囊性瘤影像学特征及其发病规律,对在全景片上特定区域可疑影像,结合锥形束CT进行筛查,6例多原发性牙源性角化囊性瘤患者新发现13处早期微小原发病灶。
五、结论
1、多原发性牙源性角化囊性瘤具有对称、位置恒定且大部分病例具有异时性的影像学特点。利用对称、恒定和异时的观点可早期诊断颌骨其它不同部位的早期微小原发性角化囊性瘤病灶；
2、基底细胞痣综合征伴发多原发性牙源性角化囊性瘤病灶同样具有上述影像学特点；今后尚需证明的一个观点是多原发性牙源性角化囊性瘤与基底细胞痣综合征可能是一一对应的关系。
3、高分辩率锥形束CT在诊断颌骨微小病变方面有极高的应用价值,极大地提高了颌骨早期微小原发性角化囊性瘤病灶的发现。
Background
Keratocystic odontogenic tumor(KCOT) is a benign uniloculus or multiloculus odontogenic tumor. It frequently occurs in manidbular molar region and mandiular ramus, and it possibly happens in any region which is associated with the development of tooh. KCOT presents relatively higher reproduction potentiality and special growth pattern. Its characteristic lining with parakeratinized stratified squamous epithelium maybe cancerization. It also associated with nevoid basal cell nevus syndrome and easily recurs after conservative operations. KCOT's original name is odontogenic keratocyst (OKC). AHLFORS et al research results show that increases of Mitogenic index of keratocyst looks similar to that of ameloblastoma, and then they think Keratocyst is a benign tumor. STENMEN et al compared keratorcyst and ameloblastoma through cell culture, and found that epithelial cell of keratocyst remains metabolism in the nutrient medium and this is very resemble to ameloblastoma. In result, they think keratocyst also has the characteristic of tumors.
WANG En-bo et al research results show Keratocyst has relative higher epitheliosis ability and present more positive cells of proliferating cell nuclear antigen (PCNA). Through study cell proliferation dynamics by measuring the quantity of PCNA positive cells and DNA content, they found that the Proliferative activity of epithelial cell of Keratocyst looks similar to that of ameloblastoma. Epitheliosis is the basic characteristic of Epithelial tumor and odontogenic keratocyst also has this basic characteristic. So, odontogenic keratocyst is regarded as a benign tumor with invasive growth. Its invasive growth resemble to that of mural ameloblastoma. Based on this, odontogenic keratocyst (OKC) is suggested to be changed to keratocystic odontogenic tumor. In the WHO new classification of head and neck tumor in 2005, odontogenic keratocyst (OKC) is classified in odontogenic benign tumor and named it as keratocystic odontogenic tumor (KCOT).
The most frequent occurrence age range of keratocystic odontogenic tumor (KCOT) is 10-29 years old and BROWNE reported that 40-50 years old is the second. Male is more than female. KCOT's clinical features is enlargement of jaw and ache after secondary infection. Due to its concealed growth, it is difficult to be diagnosed earlier except it caused enlargement of jaw or other symptom. The growth of KCOT has no self-limitation and this leads to serious destruction of jaw. The chances of recurrence are relatively higher after operations and it is maybe associated with the biological behavior of the lining with epithelial cell stratum. Study shows the ability of mitochysis of epithelial cell stratum of KCOT and its marker of cell proliferation increased, and this proves that KCOT has the proliferative ability of tumor cell.
Multiple primary keratocystic odontogenic tumor(MPKCOT) means the host has two or more primary keratocystic odontogenic tumor at the same time or in line. Cystic tumors can be classified synchronous cystic tumor and asynchronous tcystic tumore by the appearance interval. The interval for the former is less than 6 six months and the latter is more than that. For example, MPKCOT, is reported in many pape, is Nevoid basal cell carcinoma syndrome containing multiple primary cystic tumor. Many basic researches are being done for keratocystic odontogenic tumor, specially in the Gene field. Therapy methods of KOCT have been improved but analysis of radiological features is incomprehensive. Diagnosis of early primary lesions of MPKCOT is never seen in any literature. Primary lesions of Asynchronous Multiple primary keratocystic is easily be diagnosed as recurrence by mistake. The statistical odds of the recurrence rate about Keratocystic odontogenic tumor is 22%-60%. There are five main factors leads to high recurrence:first of all, Cyst wall is very thin and crisp, and this makes it very hard to completely remove KCOT by surgery when bones are destructed. Secondly, epithelial cell with lining has higher dissociative ability. Thirdly, Inner or outside epithelial islands t of cyst wall and ascus may remnant. Fourth, Primary lesions of Asynchronous multiple primary keratocystic was easily regarded as recurrence lesions. Fifth, less advanced examining facilities made KCOT earlier minor primary lesions missed diagnosis, however return checkup regard it as recurrence lesions.
To better collect statistic and better summarize its radiological features, this paper name it as MPKCOT the first time, and it is helpful to diagnose the earlier minor primary lesions of MPKCOT, threrapy it and provide theoretical instructions for prognosis.
Basal cell nevus syndrome(BCNS), also known as jaw cysts-naevoid basal cell epithelioma-bifid rib asyndrome or Gorlin's syndrome. It is an inherited autosomal dominant disorder with complete penetrance and extreme variable expressivity. In a population, the prevalence is 1 per 57,000 people, with a 3:1 male/female gender predilection. It is characterized by main features, including multiple basal cell nevoid, jaw cysts, congenital skeletal anomalies, central nervous system abnormalities, intracranial ectopic calcification, palmar and plantar pits and specifical physiognomy etc. Moreover, this syndrome is characterized by up to 100 less common features, including associated endocrinopathies, potential for mental retardation, medulloblastoma, ovarian fibromas, and an increased incidence of cleft lip and/or palate. Multiple cystic tumor of jaw is one of the characters of BCNS, and 65%-90 % of BCNS have multiple cystic tumor of jaw. Generally speaking, patient with three or more aboved main features can be diagnosed as BCNS.
I studied one BCNS patient for a long term and found that its multiple cystic tumor showed some special images features such as asynchronism and symmetry. It means MPKCOT Radiologic features maybe have regularity. To investigate the common radiologic features of multiple primary cystic lesions and provide supportive theory for diagnosis of earlier minor primary lesions, it summed up the no. of cysts, location of lesion, sick time, radiologic features, connection between MPKCOT and BCNS in 15 diagnosed cases in this paper.
Objective
1. To reveal the occurrence regularity of multi primary keratocystic odontogenic tumor by investiging and analyzing the radilogic features on panormagram and Cone bean-CT images, and will be made to theory support to diagonose earlier minor primary cystic tumor lesions.
2. To explore the diagnostic value of Cone-bean CT in diagnosis of earlier minor primary keratocystic odontogenic tumor.
Materials and Methods
1. Study cases selects
20 cases were collected from July,1997 to Feb.2010 by Guangdong Provincial Stamatological Hospital. Among them,5 cases are not included into study due to imcomplete radiologic data. The remaining 15 cases were analyzed and investigated respectively as all these cases have a complete set of radiologic data including panoramagram, posteroanterior radiograph of skull, lateral radiograph of skull or Cone-bean CT, Chest radiograph, detailed hospital medical records and histopathology etc.
2. Radiologic analysis
Classified and analyzed the radiologic features of all the original radiologic data and return-visit exam of 9 cases. All these radiologic features includes position constancy of lesion, relation between lesion and the location of the tooth, appearce regularity of original lesion, connection between MPKCOT and BCNS etc.6 subsequent MPKCOT cases are given comprehensive diagnosis with radiologic regularity revealed by above study and doubtful minor lesions are screened Cone-bean CT.
Results
1、New radiologic features of MPKCOT:
①.Lesions Symmetry:Occurance of MPKCOT is dominated by Gene. Maxillary and mandibular develope from amalgamation of two bones. Lesions are usually detected in both Bilateral maxillary and bilateral mandibular at the same time and it shows symmetry feature. Human body is controlled by many regulatory systems and this made some of lesion are suspended and did not show. Although few cases did show symmetry, it is very obvious that MPKCOT are symmetric.
②. Lesions Position Constancy:the position of primary lesions are found in 87 (?)78、87(?)78、543(?)345、543(?)345 area.
③. Asynchronism feature:although MPKCOT is dominated by Gene, it is regulated by many regulatory systems at the same time and this makes occurrance of lesions deferred. Radiologic feature of Asynchronism accord with Knudson's two-hit model, namely the first hit is the existence of dominant gene and the seond hit is diverse influence aspects including radiation such as X-rays or actinicity etc. Two-hit model could explain symmetrical and constant multi primary lesion very well. Dominant gene activating all target organs (synchronism) or partial target organs (aynchronism) in a particular location. Stimulating inactive target organs and lead to the late multi lesionsoccurrance in succession are the second hit.
④.High rate of containg teeth:77 cystic lesion were found in 15 cases, average 5.1 per person.41 lesions containing teeth occupy 53.2% of all these lesions.
2 Correlation between basal cell nevoid syndrome (BCNS) and MPKCOT
Each MPKCOT in 15 cases has three or more than three main features of BCNS and this means MPKCOT had a high correlation with BCNS-most possibly all the MPKCOT are BCNS, however, not all BCNS have multiple primary cystic lesions of jaws. So, whether all BCNS are MPKCOT, this needs to be proved by a mass of cases, that's having disease of MPKCOT can be diagonised as BCNS needs to be proved by a mass of cases insteading of having three or more than three above radiologic features can be diagonosed as BCNS.
3. The value of Cone-bean CT in diagonosis of earlier minor primary cystic tumor lesion.
Cone-bean CT can detect even 2mm earlier minor primary lesion and this offsets the defects of panoramagram:①. The width of focal trough of Panoramagram machine is about 2 mm (front teeth region)-4 mm (molar region). If the position of lesions does not fall in the width of focal trough, then early lesions will become very blurred or will not be detected.②. Panoramagram radiography is a 2 dimension image of 2-4mm overlapped jaw bones, early lesions with diameters less than 2-4mm only be showed as the slightly uneven decreased bone density on 2 dimension image.③. When diameter of early lesions is more than 2-4mm and the pafocal trough of panoramagram machine does not pass the lesion center, the images also shows decreased bone density. Above mentioned three points caused missing diagnosis of many early lesions.
Early minor Cystic lesion is completely located the cancellous jaw bones and the growth resistance is even. It presents a smooth round or oval shape uniform radiolucency lesion in high resolution Cone-bean CT images. The section of high resolution Cone-bean CT images can reach 100μm, it can completely overcome the defects of no presence of being overlapped images. Early KCOT lesions demonstrate a smooth round or oval shape uniform radiolucency lesion with well-defined border in Cone-bean CT.
With above mentioned MPKCOT's radiologic features and its lesions occurrence regularity, screening exams to the specific doubtful images in panoramagram are done by Cone-bean CT and found 13 earlier minor primary lesions in 6 cases of MPKCOT.
Conclusions
1. MPKCOT presented special image features of asynchronism, symmetry and position constancy. Basing on the features mentioned above, the minor primary lesion of MPKCOT in other regions can be diagnosed earlier.
2. BCNS with MPKCOT also have aboved mentioned radiological features. One view point will be proved in future that all the NPKCOT probably are BCNS.
3. High resolution Cone-bean CT has a great value in diagonosis of the minor primary cystic tumor lesion and the minor primary lesion can be diagnosed earlier.
颌骨牙源性角化囊性瘤(keratocystic odontogenic tumor, KCOT)是一种良性、单囊或多囊的牙源性肿瘤,好发于下颌骨磨牙区和下颌升支,但是任何与牙列发育相关的区域都有可能发生。其具有较高的增殖潜能,生长方式特殊,内衬不全角化的复层鳞状上皮可发生癌变还可与基底细胞痣综合征(Basal cell nevus syndrome, BCNS)并发,保守性手术后易复发。其传统的命名为牙源性角化囊肿(odontogenic keratocyst, OKC)。Ahlfors等的研究结果表明,角化囊肿的有丝分裂指数增加与成釉细胞瘤相似,认为角化囊肿是一种良性肿瘤。Stenmen等通过细胞培养,将角化囊肿与成釉细胞瘤比较,角化囊肿上皮细胞在培养基上继续保持代谢功能,与成釉细胞瘤相似。因此,认为角化囊肿也具有肿瘤特征。
王恩博等研究表明,角化囊肿具有较高的上皮增殖活性,表现为增殖细胞核抗原(proliferating cell nuclear antigen, PCNA)阳性细胞较多。应用PCNA阳性细胞及DNA含量测定等细胞增殖动力学研究方法进行综合分析,结果表明,角化囊肿上皮细胞增殖活跃,与成釉细胞瘤相似。上皮增殖是上皮性肿瘤的基本特征,而牙源性角化囊肿也具备这一基本特点,因此角化囊肿可视为一种良性肿瘤,具有侵袭性生长的特点,其性质类似壁性成釉细胞瘤。建议把牙源性角化囊肿命名为“牙源性角化囊性瘤”。2005年WHO对头颈部肿瘤的新分类中,已将其归为牙源性良性肿瘤,并提出牙源性角化囊性瘤的命名。
牙源性角化囊性瘤好发年龄为10-29岁,Browne:报道40-50岁为其第二发病高峰。男性较女性多见。牙源性角化囊性瘤临床上主要表现为颌骨膨大,继发感染时可出现疼痛。由于其生长的隐匿性,除非增大到导致颌骨膨隆或引起症状,否则极难早期发现。牙源性角化囊性瘤生长缺乏自限性,可导致严重的颌骨破坏,术后具有较高的复发倾向。可能与其衬里上皮的生物学行为有关。研究认为其上皮层有丝分裂活性增加和细胞增殖标志物高表达,具有肿瘤细胞增殖活性。
多原发性牙源性角化囊性瘤(Multiple primary keratocystic odontogenic tumor, MPKCOT)是指宿主同时或先后发生两个或两个以上的原发角化囊性瘤。按照两个囊性肿瘤发现的时间间隔可分为同时性和异时性两种,间隔不超过6个月者归为同时性,超过6个月者归为异时性。多原发性牙源性角化囊性瘤文献报导较多,如含有多发性牙源性角化囊性瘤的基底细胞痣综合征患者,目前对牙源性角化囊性瘤基础研究较多,尤其基因方面的研究；对牙源性角化囊性瘤治疗手段的研究也取得了较好的效果；但对此类疾病的影像学特征剖析得不够充分,尤其对多原发性牙源性角化囊性瘤早期病灶的诊断尚未见文献总结报道,对异时性原发性牙源性角化囊性瘤病灶极易误诊为复发,基底细胞痣综合征牙源性角化囊性瘤复发率各文献统计差异极大,约22%-60%。其复发率较高的原因：一是囊壁薄而脆,在有骨破坏时难于完整摘除；二是衬里上皮具有较高的分裂活性；三是囊壁内外的上皮岛和子囊可能遗留；四是多原发异时性牙源性角化囊性瘤的发生,把原发灶当成复发统计；五是检查手段的落后,对同时性牙源性角化囊性瘤早期微小病灶漏诊,复查时当成复发灶；六是由于有“异位复发”这一概念的存在,易被临床滥用,这可能与临床医师和患者易接受复发这一事实,而对漏诊、误诊原发灶极为反感；上述六点是造成复发率偏高的主要原因。
本文首次提出多原发性牙源性角化囊性瘤(MPKCOT)这一命名,主要是为了方便统计和对其影像学特征更好地总结,尤其对多原发性牙源性角化囊性瘤早期微小病灶的诊断、治疗及预后提供理论指导。如果使用“多中心性牙源性角化囊性瘤”这一命名,对同时性病灶的表述不会存在问题,但对异时性病灶的描述将有较大的局限性,对异时性原发囊性瘤病灶必须要用原发性来描述,以明确区分是否为复发,因此,综合考虑使用“多原发性”这一命名较“多中心性”更加合适,更能体现MPKCOT的特征。
基底细胞痣综合征,即颌骨囊性瘤-基底细胞痣-肋骨分叉综合征(jawcysts-naevoid basal cell epithelioma-bifid rib asyndrome)或称Gorlin综合征(Gorlin's syndrome)。是一种常染色体显性遗传性疾病,具有遗传倾向,可有家族史,亦可散发。BCNS发病率为1/57000,男/女约3：1；该综合征主要体征有皮肤多发性基底细胞痣、颌骨多发性KCOT和骨骼异常、中枢神经异常、颅内钙化、掌足凹陷、特殊面征等多种疾病。与该综合征有关的疾病超过100多种,如某些内分泌疾病、智力迟钝、卵巢纤维瘤、唇腭裂等。颌骨多发性囊性瘤为该综合征常见表现之一,见于65%-90%的患者。一般认为,只要有三项主要体征符合即可诊断本征。
本作者长期追踪1例基底细胞痣综合征患者发现,其多原发性囊性肿瘤具有异时对称的影像学特点,说明多原发性牙源性角化囊性瘤在影像学表现上可能是有规律可循的,本文对本院确诊的15例牙源性角化囊性瘤的囊肿数目、发病部位、发病时间、影像学特点及MPKCOT与基底细胞痣综合征的关系等方面进行系统总结,旨在发现多原发性牙源性角化囊性瘤共同的影像学规律,为该疾病的早期微小病变的诊断提供理论支持。
二、研究目的
1、本研究利用颌骨全景片并结合锥形束CT对本院15例颌骨多原发性牙源性角化囊性瘤影像学特征进行分类统计和总结分析,旨在揭示其多原发灶的发生规律,为早期微小原发灶的诊断提供理论支持。
2、探讨锥形束CT对早期微小原发性角化囊性瘤病灶的诊断价值。
三、研究方法
1、病例选取
选取1997年7月—2010年2月在广东省口腔医院住院治疗的多原发性牙源性角化囊性瘤患者20例为研究对象,其中5例因为影像资料不完整没有纳入研究,其它15例均有完整的影像学(全景片、头颅正位、头颅侧位或锥形束CT、胸片等)、详细住院病历和病理等资料。
2、影像资料分析
对我院9例多原发性牙源性角化囊性瘤原始的和各个时间段回访的影像学资料进行系统复查,对其影像学特点分类统计和总结分析,如发病部位是否恒定、病灶与牙位的关系、原发灶出现规律、与基底细胞痣综合征的关系等。利用分析所得影像学规律对随后6例多原发性牙源性角化囊性瘤的患者进行系统诊断。可疑微小病灶利用锥形束CT筛查。
四、结果
1、多原发性牙源性角化囊性瘤新影像学特点：
①.多原发灶具有对称性：多原发性牙源性角化囊性瘤的发病是由基因控制,人体的上、下颌骨在发育过程中是由左右两块骨融合而成,双侧上、下颌骨同时发病就会呈现对称性,由于人体受多种调节系统的控制,部分区域会延时发作或到死亡时仍未表现,本组样本虽然有少部分病例个别病灶暂未出现对称灶,但纵观整个样本不难看出,多原发性牙源性角化囊性瘤对称性趋势非常明显；
②.原发灶位置恒定：原发灶恒定出现在87 78、543 345、543345这4个区域,其中87 78：12例,87 78：12例,543 345：10例,543345：7例,可以看出543 345区较其它区域出现频率少；
③.部分病例具有异时性的影像学特点：虽然多原发性牙源性角化囊性瘤受基因控制,但同时其也受多种调控系统的调节,部分区域会延时发病。异时的影像学特征符合Knudson的二次突变(双重受击)学说(two-hit model),即第一击为显性基因的存在,第二击因素可能是多方面的,包括放射因素,如X线或光化性等。双重受击学说可以解释同时或异时对称多原发病灶,第一击显性基因激活特定部位的全部(同时性)或部分(异时性)靶器官,第二击刺激未激活的靶器官导致后期多个病灶陆续出现。
④.高含牙率：本样本15例患者共发现囊性病灶77个,平均5.1个/人,其中含牙囊性病灶41个,含牙率为53.2%。
2、基底细胞痣综合征与多原发性牙源性角化囊性瘤的关联性
本组样本15例多原发性牙源性角化囊性瘤均有3项以上体征支持基底细胞痣综合征,说明多原发性牙源性角化囊性瘤与基底细胞痣综合征高度相关,可能所有多原发性牙源性角化囊性瘤均为基底细胞痣综合征,反之是则不成立的,多原发性牙源性角化囊性瘤与基底细胞痣综合征是否一一对应尚需大量样本验证,即只须颌骨多原发性角化囊性瘤病灶就可诊断基底细胞痣综合征,而不是目前公认的诊断标准——具备三项或三项以上基底细胞痣综合征体征。
3、锥形束CT在诊断多原发性牙源性角化囊性瘤早期微小病灶的价值
锥形束CT可以发现2mm左右的早期微小病灶,可以弥补全景片对早期微小病灶易漏诊的局限性：①全景片断层阈[即成像厚度约2 mm(前牙区)-4mm(磨牙区)]以外的所有骨质均可以完全模糊掉,当早期病灶位于断层阈外可完全不显影；②全景片为厚约2-4mm颌骨的重叠二维影像,直径小于2-4mm的早期病灶仅表现骨质密度轻微不均匀降低；③稍大一些的早期病灶如果全景片的断层阈不通过病灶中心也同样表现为骨质密度降低。上述三点将会造成早期囊性病灶在全景片上缺乏囊性病灶内部密度均匀、边缘有清晰致密线状硬化边等影像学特征,从而导致大量早期病灶漏诊。
早期微小囊性病灶因完全局限于颌骨松质骨内,生长阻力较均匀,表现为圆形或椭圆形均匀低密度灶,高分辨锥形束CT重建层厚可达100μm以下,完全可以克服病灶因重叠太多掩盖其显示,早期KCOT在锥形束CT上表现为圆形或椭圆形均匀低密度灶,边缘见清晰致密线状硬化边,沿颌骨长轴生长趋势不明显。
利用上述总结的多原发性牙源性角化囊性瘤影像学特征及其发病规律,对在全景片上特定区域可疑影像,结合锥形束CT进行筛查,6例多原发性牙源性角化囊性瘤患者新发现13处早期微小原发病灶。
五、结论
1、多原发性牙源性角化囊性瘤具有对称、位置恒定且大部分病例具有异时性的影像学特点。利用对称、恒定和异时的观点可早期诊断颌骨其它不同部位的早期微小原发性角化囊性瘤病灶；
2、基底细胞痣综合征伴发多原发性牙源性角化囊性瘤病灶同样具有上述影像学特点；今后尚需证明的一个观点是多原发性牙源性角化囊性瘤与基底细胞痣综合征可能是一一对应的关系。
3、高分辩率锥形束CT在诊断颌骨微小病变方面有极高的应用价值,极大地提高了颌骨早期微小原发性角化囊性瘤病灶的发现。
Background
Keratocystic odontogenic tumor(KCOT) is a benign uniloculus or multiloculus odontogenic tumor. It frequently occurs in manidbular molar region and mandiular ramus, and it possibly happens in any region which is associated with the development of tooh. KCOT presents relatively higher reproduction potentiality and special growth pattern. Its characteristic lining with parakeratinized stratified squamous epithelium maybe cancerization. It also associated with nevoid basal cell nevus syndrome and easily recurs after conservative operations. KCOT's original name is odontogenic keratocyst (OKC). AHLFORS et al research results show that increases of Mitogenic index of keratocyst looks similar to that of ameloblastoma, and then they think Keratocyst is a benign tumor. STENMEN et al compared keratorcyst and ameloblastoma through cell culture, and found that epithelial cell of keratocyst remains metabolism in the nutrient medium and this is very resemble to ameloblastoma. In result, they think keratocyst also has the characteristic of tumors.
WANG En-bo et al research results show Keratocyst has relative higher epitheliosis ability and present more positive cells of proliferating cell nuclear antigen (PCNA). Through study cell proliferation dynamics by measuring the quantity of PCNA positive cells and DNA content, they found that the Proliferative activity of epithelial cell of Keratocyst looks similar to that of ameloblastoma. Epitheliosis is the basic characteristic of Epithelial tumor and odontogenic keratocyst also has this basic characteristic. So, odontogenic keratocyst is regarded as a benign tumor with invasive growth. Its invasive growth resemble to that of mural ameloblastoma. Based on this, odontogenic keratocyst (OKC) is suggested to be changed to keratocystic odontogenic tumor. In the WHO new classification of head and neck tumor in 2005, odontogenic keratocyst (OKC) is classified in odontogenic benign tumor and named it as keratocystic odontogenic tumor (KCOT).
The most frequent occurrence age range of keratocystic odontogenic tumor (KCOT) is 10-29 years old and BROWNE reported that 40-50 years old is the second. Male is more than female. KCOT's clinical features is enlargement of jaw and ache after secondary infection. Due to its concealed growth, it is difficult to be diagnosed earlier except it caused enlargement of jaw or other symptom. The growth of KCOT has no self-limitation and this leads to serious destruction of jaw. The chances of recurrence are relatively higher after operations and it is maybe associated with the biological behavior of the lining with epithelial cell stratum. Study shows the ability of mitochysis of epithelial cell stratum of KCOT and its marker of cell proliferation increased, and this proves that KCOT has the proliferative ability of tumor cell.
Multiple primary keratocystic odontogenic tumor(MPKCOT) means the host has two or more primary keratocystic odontogenic tumor at the same time or in line. Cystic tumors can be classified synchronous cystic tumor and asynchronous tcystic tumore by the appearance interval. The interval for the former is less than 6 six months and the latter is more than that. For example, MPKCOT, is reported in many pape, is Nevoid basal cell carcinoma syndrome containing multiple primary cystic tumor. Many basic researches are being done for keratocystic odontogenic tumor, specially in the Gene field. Therapy methods of KOCT have been improved but analysis of radiological features is incomprehensive. Diagnosis of early primary lesions of MPKCOT is never seen in any literature. Primary lesions of Asynchronous Multiple primary keratocystic is easily be diagnosed as recurrence by mistake. The statistical odds of the recurrence rate about Keratocystic odontogenic tumor is 22%-60%. There are five main factors leads to high recurrence:first of all, Cyst wall is very thin and crisp, and this makes it very hard to completely remove KCOT by surgery when bones are destructed. Secondly, epithelial cell with lining has higher dissociative ability. Thirdly, Inner or outside epithelial islands t of cyst wall and ascus may remnant. Fourth, Primary lesions of Asynchronous multiple primary keratocystic was easily regarded as recurrence lesions. Fifth, less advanced examining facilities made KCOT earlier minor primary lesions missed diagnosis, however return checkup regard it as recurrence lesions.
To better collect statistic and better summarize its radiological features, this paper name it as MPKCOT the first time, and it is helpful to diagnose the earlier minor primary lesions of MPKCOT, threrapy it and provide theoretical instructions for prognosis.
Basal cell nevus syndrome(BCNS), also known as jaw cysts-naevoid basal cell epithelioma-bifid rib asyndrome or Gorlin's syndrome. It is an inherited autosomal dominant disorder with complete penetrance and extreme variable expressivity. In a population, the prevalence is 1 per 57,000 people, with a 3:1 male/female gender predilection. It is characterized by main features, including multiple basal cell nevoid, jaw cysts, congenital skeletal anomalies, central nervous system abnormalities, intracranial ectopic calcification, palmar and plantar pits and specifical physiognomy etc. Moreover, this syndrome is characterized by up to 100 less common features, including associated endocrinopathies, potential for mental retardation, medulloblastoma, ovarian fibromas, and an increased incidence of cleft lip and/or palate. Multiple cystic tumor of jaw is one of the characters of BCNS, and 65%-90 % of BCNS have multiple cystic tumor of jaw. Generally speaking, patient with three or more aboved main features can be diagnosed as BCNS.
I studied one BCNS patient for a long term and found that its multiple cystic tumor showed some special images features such as asynchronism and symmetry. It means MPKCOT Radiologic features maybe have regularity. To investigate the common radiologic features of multiple primary cystic lesions and provide supportive theory for diagnosis of earlier minor primary lesions, it summed up the no. of cysts, location of lesion, sick time, radiologic features, connection between MPKCOT and BCNS in 15 diagnosed cases in this paper.
Objective
1. To reveal the occurrence regularity of multi primary keratocystic odontogenic tumor by investiging and analyzing the radilogic features on panormagram and Cone bean-CT images, and will be made to theory support to diagonose earlier minor primary cystic tumor lesions.
2. To explore the diagnostic value of Cone-bean CT in diagnosis of earlier minor primary keratocystic odontogenic tumor.
Materials and Methods
1. Study cases selects
20 cases were collected from July,1997 to Feb.2010 by Guangdong Provincial Stamatological Hospital. Among them,5 cases are not included into study due to imcomplete radiologic data. The remaining 15 cases were analyzed and investigated respectively as all these cases have a complete set of radiologic data including panoramagram, posteroanterior radiograph of skull, lateral radiograph of skull or Cone-bean CT, Chest radiograph, detailed hospital medical records and histopathology etc.
2. Radiologic analysis
Classified and analyzed the radiologic features of all the original radiologic data and return-visit exam of 9 cases. All these radiologic features includes position constancy of lesion, relation between lesion and the location of the tooth, appearce regularity of original lesion, connection between MPKCOT and BCNS etc.6 subsequent MPKCOT cases are given comprehensive diagnosis with radiologic regularity revealed by above study and doubtful minor lesions are screened Cone-bean CT.
Results
1、New radiologic features of MPKCOT:
①.Lesions Symmetry:Occurance of MPKCOT is dominated by Gene. Maxillary and mandibular develope from amalgamation of two bones. Lesions are usually detected in both Bilateral maxillary and bilateral mandibular at the same time and it shows symmetry feature. Human body is controlled by many regulatory systems and this made some of lesion are suspended and did not show. Although few cases did show symmetry, it is very obvious that MPKCOT are symmetric.
②. Lesions Position Constancy:the position of primary lesions are found in 87 (?)78、87(?)78、543(?)345、543(?)345 area.
③. Asynchronism feature:although MPKCOT is dominated by Gene, it is regulated by many regulatory systems at the same time and this makes occurrance of lesions deferred. Radiologic feature of Asynchronism accord with Knudson's two-hit model, namely the first hit is the existence of dominant gene and the seond hit is diverse influence aspects including radiation such as X-rays or actinicity etc. Two-hit model could explain symmetrical and constant multi primary lesion very well. Dominant gene activating all target organs (synchronism) or partial target organs (aynchronism) in a particular location. Stimulating inactive target organs and lead to the late multi lesionsoccurrance in succession are the second hit.
④.High rate of containg teeth:77 cystic lesion were found in 15 cases, average 5.1 per person.41 lesions containing teeth occupy 53.2% of all these lesions.
2 Correlation between basal cell nevoid syndrome (BCNS) and MPKCOT
Each MPKCOT in 15 cases has three or more than three main features of BCNS and this means MPKCOT had a high correlation with BCNS-most possibly all the MPKCOT are BCNS, however, not all BCNS have multiple primary cystic lesions of jaws. So, whether all BCNS are MPKCOT, this needs to be proved by a mass of cases, that's having disease of MPKCOT can be diagonised as BCNS needs to be proved by a mass of cases insteading of having three or more than three above radiologic features can be diagonosed as BCNS.
3. The value of Cone-bean CT in diagonosis of earlier minor primary cystic tumor lesion.
Cone-bean CT can detect even 2mm earlier minor primary lesion and this offsets the defects of panoramagram:①. The width of focal trough of Panoramagram machine is about 2 mm (front teeth region)-4 mm (molar region). If the position of lesions does not fall in the width of focal trough, then early lesions will become very blurred or will not be detected.②. Panoramagram radiography is a 2 dimension image of 2-4mm overlapped jaw bones, early lesions with diameters less than 2-4mm only be showed as the slightly uneven decreased bone density on 2 dimension image.③. When diameter of early lesions is more than 2-4mm and the pafocal trough of panoramagram machine does not pass the lesion center, the images also shows decreased bone density. Above mentioned three points caused missing diagnosis of many early lesions.
Early minor Cystic lesion is completely located the cancellous jaw bones and the growth resistance is even. It presents a smooth round or oval shape uniform radiolucency lesion in high resolution Cone-bean CT images. The section of high resolution Cone-bean CT images can reach 100μm, it can completely overcome the defects of no presence of being overlapped images. Early KCOT lesions demonstrate a smooth round or oval shape uniform radiolucency lesion with well-defined border in Cone-bean CT.
With above mentioned MPKCOT's radiologic features and its lesions occurrence regularity, screening exams to the specific doubtful images in panoramagram are done by Cone-bean CT and found 13 earlier minor primary lesions in 6 cases of MPKCOT.
Conclusions
1. MPKCOT presented special image features of asynchronism, symmetry and position constancy. Basing on the features mentioned above, the minor primary lesion of MPKCOT in other regions can be diagnosed earlier.
2. BCNS with MPKCOT also have aboved mentioned radiological features. One view point will be proved in future that all the NPKCOT probably are BCNS.
3. High resolution Cone-bean CT has a great value in diagonosis of the minor primary cystic tumor lesion and the minor primary lesion can be diagnosed earlier.
引文
[1]Barnes L, Eveson JW, Reichart PA, et al. World Health Organization classification of tumours:pathology and genetics of tumours of the head and neck[M]. Lyon:IARC,2005:306-307.
[2]Browne RM.Per[cyst]ent growth:the odontogenic keratocyst 40 years on[J].Ann R Coll Surg Engl,1994,76:426-433.
[3]Kramer IRH, Pindborg JJ, Shear M. Typing of odontogenic tumours[M],2nd edn. Berlin, Heidelberg:Springer-Verlag,1992.34-42.
[4]Myoung H, Hong SP, Hong SD, et al. Odontogenic keratocyst:Review of 256 cases for recurrence and clinicopathologic[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2001,91(3):328-333.
[5]周永青,李晓明,高春梅,等.71例头颈部鳞状细胞癌的多原发癌临床资料分析.中华耳鼻喉科杂志,2004,39(4)：232-236.、
[6]郭小玲,魏奉才,孙善珍.多原发恶性肿瘤合并口腔病变的临床研究.华西口腔医学杂志,2006,24(1)：42-44.
[7]Melo ES, Kawamura JY, Alves CA, et al. Imaging modality correlations of an odontogenic keratocyst in the nevoid basal cell carcinoma syndrome:a family case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2004, 98(2):232-236.
[8]白振西,顾晓明,彭品祥.基底细胞痣综合征(附24例报告).实用口腔医学杂志,2002,18(1)：51-53.
[9]周晌辉,李力力,翦新春,等.痣样基底细胞癌综合征家系1例.华西口腔医学杂志,2008,26(1)：109-111.
[10]钟凡,彭国光,赵继刚,等.基底细胞痣综合征1例报告及文献复习.中国口腔颌面外科杂志,2007,5(4)：309-312.
[11]王茜,潘朝斌,李海刚.痣样基底细胞癌综合征1例报告.中国口腔颌面外科杂志,2007,5(3)：235-236.
[12]Hahn H, Wicking C, Zaphiropoulos P, et al. Mutations of the human homolog of Drosophila PTCHed in the nevoid basal call carcinoma syndrome[J]. Cell, 1996,85:841-851.
[13]Lench NJ, Telford EA, High AS, et al. Characterization of human patched germ line mutations in naevoid basal cell carcinoma syndrome. Hum Genet, 1997,100(5-6):497.
[14]Barreto DC, Gomez RS, Bale AE, et al. PTCH gene mutation in odontogenic keratocysts[J].J Dent Res,2000,79(6):1418-1422.
[15]Xiaomei G, Hongshan Z, Lisha S, et al. PTCH mutations in nonsyndromic and Gorlin syndrome related odontogenic keratocysts[J]. J Dent Res,2006, 85:859-863.
[16]徐丽莉,李铁军.伴基底细胞痣综合征的牙源性角化囊性瘤中PTCH2基因的突变检测[J].北京大学学报(医学版),2008,40(1)：15-18.
[17]Wine WM, Welch JT, Graves RW. Marsup ialization of a dentigerous cyst of the mandible:report of case. J Oral Surg,1971,29(10):742-745.
[18]Gorlin RJ. Syndrome of the head and neck.3rd ed. New York:Oxford University Press,1990.392.
[19]刘冰,赵怡芳,张文峰,等.负压吸引术治疗下颌骨牙源性角化囊肿[J].武汉大学学报：医学版,2006,27(5)：620-623.
[20]王卫红,范红渠,周卫兵,等.保守治疗牙源性角化囊肿的初步探讨[J].临床口腔医学杂志,2005,21(7)：415-417.
[21]Thosaporn W, lamaroom A, Pongsiriwet S, et al. A comparative study of epithelial cell proliferation between the odontogenic keratocysts orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma[J].Oral Diseases,2004,10 (1):22-26.
[22]卫晋雄,赵怡芳,李宏礼.Carnoy液和三氯醋酸与对牙源性角化囊肿作用的实验研究[J].湖北医科大学学报,2000,21,248.
[23]Zhao YF, Wei JX, Wang XP. Treatment of odontogenic keratocysts:A follow-up of 255 Chinese patients[J].Oral Surg Oral Pathol Oral Radiol Endod,2002,94 (2):151-156.
[24]赵怡芳,刘冰.颌骨囊肿的手术治疗[J].继续医学教育,2006,20(22)：83-85.
[25]杜小铭,孙树平,韩荣红,等.腔内热灌注治疗颌骨巨大角化囊性瘤的临床研究.武警医学院学报,2009,18(12)：1039-1042.
[26]张治勇,邝喆,李晓敏,等.异时对称多原发性牙源性角化囊性瘤——特殊基底细胞痣综合征1例.广东牙病防治,2009,17(2)：56-59.
[27]李铁军.牙源性角化囊肿的生长与行为[J].中华口腔医学杂志,2000,35：306-308.
[28]王恩博,俞光岩,高岩,等.牙源性角化囊肿上皮细胞增殖动力学初步研究.中华口腔医学杂志,1998,33(4)：210-212.
[29]Scharffetter K, Balz-Herrmann C, Lagrange W. Proliferation kinetics study of the growth of keratocysts. Morpho-functional explanation for recurences. J Cranio Maxillofac Surg,1989,17:226-233.
[30]Mathhews LB, Mason G, Browne RM. Epithelial cell markers and proliferating cells in odontogenic jaw cysts. J Pathol,1988,156:283-287.
[31]Ahlfors E, Larsson A, Sjogren S. The odontogenic keratocyst:a benign cystic tumor? J Oral Maxillofac Surg,1984,42:10-19.
[32]Stenmen G, Magnusson B, Lennartsson B, et al. In vitro growth characteristics of human odontogenic keratocysts and dentigerous cysts. J Oral Pathol,1986, 15:143-145.
[33]Rapidis AD, Angelopoulos AP, Skouteris CA. Mural(intracystic) ameloblastoma. Int J Oral Surg,1982,11:162-164.
[34]Leider AS, Eversole HR, Barkin ME. Cystic ameloblastoma——a clinicopathologic analysis. Oral Surg Oral Med Oral Pathol,1985,60:624-630.
[35]吴运堂,于世凤,张祖燕,等.56例壁性造釉细胞瘤临床和X线分析.中华口腔医学杂志,1995,30：263-265.
[36]Main DMG. The enlargement of epithelial jaw cysts[J].Odont Revy,1970,21: 29-49.
[37]Toller PA. Autoradiography of explants from odontogenic cysts[J]. Br Dent J, 1970,131:57-61.
[38]High AS, Quirke P, Hume WJ. DNA-ploidy studies in a keratocyst undergoing subsequent tmalignant transformation[J].J Oral Pathol,1987,16:135-138.
[39]张志良,徐冶敏.下颌骨牙源性角化囊肿X线影像分析.放射学实践,2002,17(4)：335-337.
[40]谭伟昌,张海荣,何平华.造釉细胞瘤与角化囊肿侵犯下颌骨升支部的X线诊断比较.江西医学院学报,40：32.
[41]White SC, Pharoah MJ. Oral Radiology principles and interpretation.4th ed. Missouri:Mosby Publication,2000,9:185.
[42]Gorlin RJ, Golts RW. Multiple naevoid basal cell epithelioma, jaw cysts and bifid rib:asyndrome[J].New Eng J Med,1960,262:908-912.
[43]Lovin JD, Talarico CL, Wegert SL, Gaynor LF, Sutley SS. Gorlin's syndrome with associated odontogenic cysts. Pediatr Radiol 1991;21:584-587.
[44]Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin 1995;13:113-125.
[45]Lambrecht JT, Kreusch T. Examine your orofacial cleft patients for Gorlin-Goltz syndrome. Cleft Palate Craniofac J 1997;34:342-350.
[46]Amlashi SF, Riffaud L, Brassier G, Morandi X. Nevoid basal cell carcinoma syndrome:relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Cancer 2003;98:618-624.
[47]卜鸣华,潘效志.口腔颌面部多原发癌(附2例报告).徐州医学院学报,1994,14(3)：259-260.
[1]Barnes L, Eveson JW, Reichart PA, et al. World Health Organization classification of tumours:pathology and genetics of tumours of the head and neck[M]. Lyon:IARC,2005:306-307.
[2]Browne RM. Per[cyst]ent growth:the odontogenic keratocyst 40 years on[J].Ann R Coll Surg Engl,1994,76:426-433.
[3]Kramer IRH, Pindborg JJ, Shear M. Typing of odontogenic tumours [M],2nd edn. Berlin, Heidelberg:Springer-Verlag,1992.34-42.
[4]Myoung H, Hong SP, Hong SD, et al. Odontogenic keratocyst:Review of 256 cases for recurrence and clinicopathologic[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2001,91(3):328-333.
[5]Shear M, Speight P. Cysts of the oral and maxillofacial regions[M].4thed.Oxford:Blackwell,2007.6-58.
[6]李铁军.牙源性角化囊肿是真性肿瘤吗?[J].北京大学学报(医学版),2007,39(1)：6-9.
[7]李铁军.牙源性角化囊肿的生长与行为[J].中华口腔医学杂志,2000,35：306-308.
[8]Gorlin RJ, Golts RW. Multiple naevoid basal cell epithelioma, jaw cysts and bifid rib:asyndrome[J].New Eng J Med,1960,262:908-912.
[9]Ide F, Saito I. Many faces of odontogenic keratocysts [J]. Oral Oncol,2003, 39:204-205.
[10]Vered M, Buchner A, Dayan D, et al. Solid variant of odontogenic keratocyst [J]. J Oral Pathol Med,2004,33:125-128.
[11]Li Tiejun, Kitano M, Chen Xinming, et al. Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study of 15cases [J]. Histopathology,1998,32:242-251.
[12]Tawfik MA. Odontogenic tumors in Dakahlia, Egypt:analysis of 82 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2010,109(2):67-73
[13]Main DMG. The enlargement of epithelial jaw cysts[J].Odont Revy,1970,21: 29-49.
[14]Toller PA. Autoradiography of explants from odontogenic cysts[J]. Br Dent J, 1970,131:57-61.
[15]High AS, Quirke P, Hume WJ.DNA-ploidy studies in a keratocyst undergoing subsequent tmalignant transformation[J]. J Oral Pathol,1987,16:135-138.
[16]Tiejun L, Kitano M, Xinming C, et al. Squamous cell carcinoma arising in recurrent odontogenic cyst:a clinicopat hological and immunocytochemical study of 15 cases[J]. Histopathology,1998,32:242-251.
[17]李铁军.几种牙源性肿瘤及其相关病损的临床与病理研究现状[J].上海口腔医学,2005,14(5)：441-448.
[18]李铁军,罗海燕,于世凤.正角化牙源性囊肿的临床病理及免疫组化研究[J].中华口腔医学杂志,2003,38(1)：49-511.
[19]Li TJ, Browne RM, Prime SS, et al. p53 protein in odontogenic cysts: increased expression in some odontogenic keratocysts[J]. J Clin Pathol,1992, 45:1007-1010.
[20]Vedofte P, Holmstrup P, Dabelsteen E. Human odontogenic keratocyst transplants in nude mice[J].J Dent Res,1982,90:306-314.
[21]Stenman G, Magnusson B, Lennart sson B, et al. In vitro growth characteristics of human odontogenic keratocysts and dentigerous cysts [J]. Oral Pathol,1986, 15:143-145.
[22]Pogrel MA. The use of liquid nitrogen cryotheraphy in the management of locally aggressive bone lesions[J]. J Oral Maxillofac Surg,1993,51:269-273.
[23]Lovin JD, Talarico CL, Wegert SL, Gaynor LF, Sutley SS. Gorlin's syndrome with associated odontogenic cysts. Pediatr Radiol,1991, 21:584-7.
[24]Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin,1995,13: 113-125.
[25]Lambrecht JT, Kreusch T. Examine your orofacial cleft patients for Gorlin-Goltz syndrome. Cleft Palate Craniofac J,1997,34:342-50.
[26]Amlashi SF, Riffaud L, Brassier G, et al. Nevoid basal cell carcinoma syndrome:relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Cancer,2003, 98:618-24.
[27]白振西,顾晓明,彭品祥.基底细胞痣综合征(附24例报告).实用口腔医学杂志,2002,18(1)：51-53.
[28]周晌辉,李力力,翦新春,等.痣样基底细胞癌综合征家系1例.华西口腔医学杂志,2008,26(1)：109-111.
[29]钟凡,彭国光,赵继刚,等.基底细胞痣综合征1例报告及文献复习.中国口腔颌面外科杂志,2007,5(4)：309-312.
[30]王茜,潘朝斌,李海刚.痣样基底细胞癌综合征1例报告.中国口腔颌面外科杂志,2007,5(3)：235-236.
[31]Lench NJ, Telford EA, High AS, et al. Characterization of human patched germ line mutations in naevoid basal cell carcinoma syndrome. Hum Genet, 1997,100(5-6):497.
[32]Barreto DC, Gomez RS, Bale AE, et al. PTCH gene mutation in odontogenic keratocysts[J]. J Dent Res,2000,79(6):1418-1422.
[33]Hahn H, Wicking C, Zaphiropoulos P, et al. Mutations of the human homolog of Drosophila PTCHed in the nevoid basal call carcinoma syndrome [J]. Cell, 1996,85:841-851.
[34]Xiaomei G, Hongshan Z, Lisha S, et al. PTCH mutations in nonsyndromic and Gorlin syndrome related odontogenic keratocysts[J]. J Dent Res,2006,85: 859-863.
[35]Gorlin RJ. Syndrome of the head and neck[M].3rd ed. New York:Oxford University Press,1990:392.
[36]徐丽莉,李铁军.伴基底细胞痣综合征的牙源性角化囊性瘤中PTCH2基因的突变检测[J].北京大学学报(医学版),2008,40(1)：15-18.
[37]Shanley S, Ratcliffe J, Hockey A, et al. Nevoid basal cell carcinoma syndrome: Review of 118 affected individuals. Am J Med Genet,1994,50(3):282.
[38]王永海,毛天球,石子英.关于基底细胞痣综合征的临床病理讨论.实用口腔医学杂志,1987,3(3)：151.
[39]Dowling PA, Fleming P, Saunders ID, et al. Odontogenic keratocysts in a 5-year-old:Initial manifestations of nevoid basal cell carcinoma syndrome. Pediatr Dent,2000,22(1):53.
[40]张志良,徐冶敏.下颌骨牙源性角化囊肿X线影像分析.放射学实践,2002,17(4)：335-337.
[41]谭伟昌,张海荣,何平华.造釉细胞瘤与角化囊肿侵犯下颌骨升支部的X线诊断比较.江西医学院学报,2000,40：32.
[42]张治勇,汪森明,李晓敏等.多原发性牙源性角化囊性瘤新影像学特征—附11例基底细胞痣综合征病例报告.实用口腔医学杂志,2009,25(4)： 491-496.
[43]张治勇,邝喆,李晓敏,等.异时对称多原发性牙源性角化囊性瘤——特殊基底细胞痣综合征1例.广东牙病防治,2009,17(2)：56-59.
[44]刘冰,赵怡芳,张文峰,等.负压吸引术治疗下颌骨牙源性角化囊肿[J].武汉大学学报：医学版,2006,27(5)：620-623.
[45]王卫红,范红渠,周卫兵,等.保守治疗牙源性角化囊肿的初步探讨[J].临床口腔医学杂志,2005,21(7)：415-417.
[46]Browne RM. The odontogenic keratocysts. Histological features and their correlation with behavior[J]. Br Dent J,1971,131:249.
[47]Wine WM, Welch JT, Graves RW. Marsup ialization of a dentigerous cyst of the mandible:report of case. J Oral Surg,1971,29(10):742-745.
[48]Nakamura N, Mitsuyasu T, Mitsuyasu Y, et al. Marsup ialization for odontogenic keratocysts:long-term follow-up analysis of the effectsand changes in growth characteristics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2002,94 (5):543-553.
[49]Anthony PM, Jordan RR. Marsupialization as a definitive treatment for the odontogenic keratocyst. Oral Maxillofac Surg,2004,62 (6):651-655.
[50]Chow HT. Odontogenic keratocyst:a clinical experience in Singapore. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,1998,86(5):573-577.
[51]Thosaporn W, lamaroom A, Pongsiriwet S, et al. A comparative study of epithelial cell proliferation between the odontogenic keratocysts, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma[J].Oral Diseases,2004,10(1):22-26.
[52]卫晋雄,赵怡芳,李宏礼.Carnoy液和三氯醋酸与对牙源性角化囊肿作用的实验研究[J].湖北医科大学学报,2000,21,248.
[53]Zhao YF, Wei JX, Wang XP. Treatment of odontogenic keratocysts:A follow-up of 255 Chinese patients[J].Oral Surg Oral Pathol Oral Radiol Endod, 2002,94(2):151-156.
[54]赵怡芳,刘冰.颌骨囊肿的手术治疗[J].继续医学教育,2006,20(22)：83-85.
[55]Chiapasco M, Rossi A, Motta JJ, et al. Spontaneous bone regeneration after enucleation of large mandibular cysts:a radiographic computed analysis of 27 consecutive cases. J Oral Maxillofac Surg,2000,58(9):942-948.
[56]Bataineh AB, al Qudah M. Treatment of mandibular odontogenic keratocysts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,1998,86(1):42-47.
[57]Dammer R. Niederdellmann H, Dammer P, et al. Conservative or radical treatment of keratocysts:a retrospective review. Br J Oral Maxillofac Surg, 1997,35 (1):46-48.
[58]Salmassy DA, Pogrel MA. Liquid nitrogen cryosurgery and immediate bone grafting in the management of aggressive primary jaw lesions. J Oral Maxillofac Surg,1995,53(7):784-790.
[59]杜小铭,孙树平,韩荣红,等.腔内热灌注治疗颌骨巨大角化囊性瘤的临床研究.武警医学院学报,2009,18(12)：1039-1042.
[2]Browne RM.Per[cyst]ent growth:the odontogenic keratocyst 40 years on[J].Ann R Coll Surg Engl,1994,76:426-433.
[3]Kramer IRH, Pindborg JJ, Shear M. Typing of odontogenic tumours[M],2nd edn. Berlin, Heidelberg:Springer-Verlag,1992.34-42.
[4]Myoung H, Hong SP, Hong SD, et al. Odontogenic keratocyst:Review of 256 cases for recurrence and clinicopathologic[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2001,91(3):328-333.
[5]周永青,李晓明,高春梅,等.71例头颈部鳞状细胞癌的多原发癌临床资料分析.中华耳鼻喉科杂志,2004,39(4)：232-236.、
[6]郭小玲,魏奉才,孙善珍.多原发恶性肿瘤合并口腔病变的临床研究.华西口腔医学杂志,2006,24(1)：42-44.
[7]Melo ES, Kawamura JY, Alves CA, et al. Imaging modality correlations of an odontogenic keratocyst in the nevoid basal cell carcinoma syndrome:a family case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2004, 98(2):232-236.
[8]白振西,顾晓明,彭品祥.基底细胞痣综合征(附24例报告).实用口腔医学杂志,2002,18(1)：51-53.
[9]周晌辉,李力力,翦新春,等.痣样基底细胞癌综合征家系1例.华西口腔医学杂志,2008,26(1)：109-111.
[10]钟凡,彭国光,赵继刚,等.基底细胞痣综合征1例报告及文献复习.中国口腔颌面外科杂志,2007,5(4)：309-312.
[11]王茜,潘朝斌,李海刚.痣样基底细胞癌综合征1例报告.中国口腔颌面外科杂志,2007,5(3)：235-236.
[12]Hahn H, Wicking C, Zaphiropoulos P, et al. Mutations of the human homolog of Drosophila PTCHed in the nevoid basal call carcinoma syndrome[J]. Cell, 1996,85:841-851.
[13]Lench NJ, Telford EA, High AS, et al. Characterization of human patched germ line mutations in naevoid basal cell carcinoma syndrome. Hum Genet, 1997,100(5-6):497.
[14]Barreto DC, Gomez RS, Bale AE, et al. PTCH gene mutation in odontogenic keratocysts[J].J Dent Res,2000,79(6):1418-1422.
[15]Xiaomei G, Hongshan Z, Lisha S, et al. PTCH mutations in nonsyndromic and Gorlin syndrome related odontogenic keratocysts[J]. J Dent Res,2006, 85:859-863.
[16]徐丽莉,李铁军.伴基底细胞痣综合征的牙源性角化囊性瘤中PTCH2基因的突变检测[J].北京大学学报(医学版),2008,40(1)：15-18.
[17]Wine WM, Welch JT, Graves RW. Marsup ialization of a dentigerous cyst of the mandible:report of case. J Oral Surg,1971,29(10):742-745.
[18]Gorlin RJ. Syndrome of the head and neck.3rd ed. New York:Oxford University Press,1990.392.
[19]刘冰,赵怡芳,张文峰,等.负压吸引术治疗下颌骨牙源性角化囊肿[J].武汉大学学报：医学版,2006,27(5)：620-623.
[20]王卫红,范红渠,周卫兵,等.保守治疗牙源性角化囊肿的初步探讨[J].临床口腔医学杂志,2005,21(7)：415-417.
[21]Thosaporn W, lamaroom A, Pongsiriwet S, et al. A comparative study of epithelial cell proliferation between the odontogenic keratocysts orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma[J].Oral Diseases,2004,10 (1):22-26.
[22]卫晋雄,赵怡芳,李宏礼.Carnoy液和三氯醋酸与对牙源性角化囊肿作用的实验研究[J].湖北医科大学学报,2000,21,248.
[23]Zhao YF, Wei JX, Wang XP. Treatment of odontogenic keratocysts:A follow-up of 255 Chinese patients[J].Oral Surg Oral Pathol Oral Radiol Endod,2002,94 (2):151-156.
[24]赵怡芳,刘冰.颌骨囊肿的手术治疗[J].继续医学教育,2006,20(22)：83-85.
[25]杜小铭,孙树平,韩荣红,等.腔内热灌注治疗颌骨巨大角化囊性瘤的临床研究.武警医学院学报,2009,18(12)：1039-1042.
[26]张治勇,邝喆,李晓敏,等.异时对称多原发性牙源性角化囊性瘤——特殊基底细胞痣综合征1例.广东牙病防治,2009,17(2)：56-59.
[27]李铁军.牙源性角化囊肿的生长与行为[J].中华口腔医学杂志,2000,35：306-308.
[28]王恩博,俞光岩,高岩,等.牙源性角化囊肿上皮细胞增殖动力学初步研究.中华口腔医学杂志,1998,33(4)：210-212.
[29]Scharffetter K, Balz-Herrmann C, Lagrange W. Proliferation kinetics study of the growth of keratocysts. Morpho-functional explanation for recurences. J Cranio Maxillofac Surg,1989,17:226-233.
[30]Mathhews LB, Mason G, Browne RM. Epithelial cell markers and proliferating cells in odontogenic jaw cysts. J Pathol,1988,156:283-287.
[31]Ahlfors E, Larsson A, Sjogren S. The odontogenic keratocyst:a benign cystic tumor? J Oral Maxillofac Surg,1984,42:10-19.
[32]Stenmen G, Magnusson B, Lennartsson B, et al. In vitro growth characteristics of human odontogenic keratocysts and dentigerous cysts. J Oral Pathol,1986, 15:143-145.
[33]Rapidis AD, Angelopoulos AP, Skouteris CA. Mural(intracystic) ameloblastoma. Int J Oral Surg,1982,11:162-164.
[34]Leider AS, Eversole HR, Barkin ME. Cystic ameloblastoma——a clinicopathologic analysis. Oral Surg Oral Med Oral Pathol,1985,60:624-630.
[35]吴运堂,于世凤,张祖燕,等.56例壁性造釉细胞瘤临床和X线分析.中华口腔医学杂志,1995,30：263-265.
[36]Main DMG. The enlargement of epithelial jaw cysts[J].Odont Revy,1970,21: 29-49.
[37]Toller PA. Autoradiography of explants from odontogenic cysts[J]. Br Dent J, 1970,131:57-61.
[38]High AS, Quirke P, Hume WJ. DNA-ploidy studies in a keratocyst undergoing subsequent tmalignant transformation[J].J Oral Pathol,1987,16:135-138.
[39]张志良,徐冶敏.下颌骨牙源性角化囊肿X线影像分析.放射学实践,2002,17(4)：335-337.
[40]谭伟昌,张海荣,何平华.造釉细胞瘤与角化囊肿侵犯下颌骨升支部的X线诊断比较.江西医学院学报,40：32.
[41]White SC, Pharoah MJ. Oral Radiology principles and interpretation.4th ed. Missouri:Mosby Publication,2000,9:185.
[42]Gorlin RJ, Golts RW. Multiple naevoid basal cell epithelioma, jaw cysts and bifid rib:asyndrome[J].New Eng J Med,1960,262:908-912.
[43]Lovin JD, Talarico CL, Wegert SL, Gaynor LF, Sutley SS. Gorlin's syndrome with associated odontogenic cysts. Pediatr Radiol 1991;21:584-587.
[44]Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin 1995;13:113-125.
[45]Lambrecht JT, Kreusch T. Examine your orofacial cleft patients for Gorlin-Goltz syndrome. Cleft Palate Craniofac J 1997;34:342-350.
[46]Amlashi SF, Riffaud L, Brassier G, Morandi X. Nevoid basal cell carcinoma syndrome:relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Cancer 2003;98:618-624.
[47]卜鸣华,潘效志.口腔颌面部多原发癌(附2例报告).徐州医学院学报,1994,14(3)：259-260.
[1]Barnes L, Eveson JW, Reichart PA, et al. World Health Organization classification of tumours:pathology and genetics of tumours of the head and neck[M]. Lyon:IARC,2005:306-307.
[2]Browne RM. Per[cyst]ent growth:the odontogenic keratocyst 40 years on[J].Ann R Coll Surg Engl,1994,76:426-433.
[3]Kramer IRH, Pindborg JJ, Shear M. Typing of odontogenic tumours [M],2nd edn. Berlin, Heidelberg:Springer-Verlag,1992.34-42.
[4]Myoung H, Hong SP, Hong SD, et al. Odontogenic keratocyst:Review of 256 cases for recurrence and clinicopathologic[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2001,91(3):328-333.
[5]Shear M, Speight P. Cysts of the oral and maxillofacial regions[M].4thed.Oxford:Blackwell,2007.6-58.
[6]李铁军.牙源性角化囊肿是真性肿瘤吗?[J].北京大学学报(医学版),2007,39(1)：6-9.
[7]李铁军.牙源性角化囊肿的生长与行为[J].中华口腔医学杂志,2000,35：306-308.
[8]Gorlin RJ, Golts RW. Multiple naevoid basal cell epithelioma, jaw cysts and bifid rib:asyndrome[J].New Eng J Med,1960,262:908-912.
[9]Ide F, Saito I. Many faces of odontogenic keratocysts [J]. Oral Oncol,2003, 39:204-205.
[10]Vered M, Buchner A, Dayan D, et al. Solid variant of odontogenic keratocyst [J]. J Oral Pathol Med,2004,33:125-128.
[11]Li Tiejun, Kitano M, Chen Xinming, et al. Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study of 15cases [J]. Histopathology,1998,32:242-251.
[12]Tawfik MA. Odontogenic tumors in Dakahlia, Egypt:analysis of 82 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2010,109(2):67-73
[13]Main DMG. The enlargement of epithelial jaw cysts[J].Odont Revy,1970,21: 29-49.
[14]Toller PA. Autoradiography of explants from odontogenic cysts[J]. Br Dent J, 1970,131:57-61.
[15]High AS, Quirke P, Hume WJ.DNA-ploidy studies in a keratocyst undergoing subsequent tmalignant transformation[J]. J Oral Pathol,1987,16:135-138.
[16]Tiejun L, Kitano M, Xinming C, et al. Squamous cell carcinoma arising in recurrent odontogenic cyst:a clinicopat hological and immunocytochemical study of 15 cases[J]. Histopathology,1998,32:242-251.
[17]李铁军.几种牙源性肿瘤及其相关病损的临床与病理研究现状[J].上海口腔医学,2005,14(5)：441-448.
[18]李铁军,罗海燕,于世凤.正角化牙源性囊肿的临床病理及免疫组化研究[J].中华口腔医学杂志,2003,38(1)：49-511.
[19]Li TJ, Browne RM, Prime SS, et al. p53 protein in odontogenic cysts: increased expression in some odontogenic keratocysts[J]. J Clin Pathol,1992, 45:1007-1010.
[20]Vedofte P, Holmstrup P, Dabelsteen E. Human odontogenic keratocyst transplants in nude mice[J].J Dent Res,1982,90:306-314.
[21]Stenman G, Magnusson B, Lennart sson B, et al. In vitro growth characteristics of human odontogenic keratocysts and dentigerous cysts [J]. Oral Pathol,1986, 15:143-145.
[22]Pogrel MA. The use of liquid nitrogen cryotheraphy in the management of locally aggressive bone lesions[J]. J Oral Maxillofac Surg,1993,51:269-273.
[23]Lovin JD, Talarico CL, Wegert SL, Gaynor LF, Sutley SS. Gorlin's syndrome with associated odontogenic cysts. Pediatr Radiol,1991, 21:584-7.
[24]Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin,1995,13: 113-125.
[25]Lambrecht JT, Kreusch T. Examine your orofacial cleft patients for Gorlin-Goltz syndrome. Cleft Palate Craniofac J,1997,34:342-50.
[26]Amlashi SF, Riffaud L, Brassier G, et al. Nevoid basal cell carcinoma syndrome:relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Cancer,2003, 98:618-24.
[27]白振西,顾晓明,彭品祥.基底细胞痣综合征(附24例报告).实用口腔医学杂志,2002,18(1)：51-53.
[28]周晌辉,李力力,翦新春,等.痣样基底细胞癌综合征家系1例.华西口腔医学杂志,2008,26(1)：109-111.
[29]钟凡,彭国光,赵继刚,等.基底细胞痣综合征1例报告及文献复习.中国口腔颌面外科杂志,2007,5(4)：309-312.
[30]王茜,潘朝斌,李海刚.痣样基底细胞癌综合征1例报告.中国口腔颌面外科杂志,2007,5(3)：235-236.
[31]Lench NJ, Telford EA, High AS, et al. Characterization of human patched germ line mutations in naevoid basal cell carcinoma syndrome. Hum Genet, 1997,100(5-6):497.
[32]Barreto DC, Gomez RS, Bale AE, et al. PTCH gene mutation in odontogenic keratocysts[J]. J Dent Res,2000,79(6):1418-1422.
[33]Hahn H, Wicking C, Zaphiropoulos P, et al. Mutations of the human homolog of Drosophila PTCHed in the nevoid basal call carcinoma syndrome [J]. Cell, 1996,85:841-851.
[34]Xiaomei G, Hongshan Z, Lisha S, et al. PTCH mutations in nonsyndromic and Gorlin syndrome related odontogenic keratocysts[J]. J Dent Res,2006,85: 859-863.
[35]Gorlin RJ. Syndrome of the head and neck[M].3rd ed. New York:Oxford University Press,1990:392.
[36]徐丽莉,李铁军.伴基底细胞痣综合征的牙源性角化囊性瘤中PTCH2基因的突变检测[J].北京大学学报(医学版),2008,40(1)：15-18.
[37]Shanley S, Ratcliffe J, Hockey A, et al. Nevoid basal cell carcinoma syndrome: Review of 118 affected individuals. Am J Med Genet,1994,50(3):282.
[38]王永海,毛天球,石子英.关于基底细胞痣综合征的临床病理讨论.实用口腔医学杂志,1987,3(3)：151.
[39]Dowling PA, Fleming P, Saunders ID, et al. Odontogenic keratocysts in a 5-year-old:Initial manifestations of nevoid basal cell carcinoma syndrome. Pediatr Dent,2000,22(1):53.
[40]张志良,徐冶敏.下颌骨牙源性角化囊肿X线影像分析.放射学实践,2002,17(4)：335-337.
[41]谭伟昌,张海荣,何平华.造釉细胞瘤与角化囊肿侵犯下颌骨升支部的X线诊断比较.江西医学院学报,2000,40：32.
[42]张治勇,汪森明,李晓敏等.多原发性牙源性角化囊性瘤新影像学特征—附11例基底细胞痣综合征病例报告.实用口腔医学杂志,2009,25(4)： 491-496.
[43]张治勇,邝喆,李晓敏,等.异时对称多原发性牙源性角化囊性瘤——特殊基底细胞痣综合征1例.广东牙病防治,2009,17(2)：56-59.
[44]刘冰,赵怡芳,张文峰,等.负压吸引术治疗下颌骨牙源性角化囊肿[J].武汉大学学报：医学版,2006,27(5)：620-623.
[45]王卫红,范红渠,周卫兵,等.保守治疗牙源性角化囊肿的初步探讨[J].临床口腔医学杂志,2005,21(7)：415-417.
[46]Browne RM. The odontogenic keratocysts. Histological features and their correlation with behavior[J]. Br Dent J,1971,131:249.
[47]Wine WM, Welch JT, Graves RW. Marsup ialization of a dentigerous cyst of the mandible:report of case. J Oral Surg,1971,29(10):742-745.
[48]Nakamura N, Mitsuyasu T, Mitsuyasu Y, et al. Marsup ialization for odontogenic keratocysts:long-term follow-up analysis of the effectsand changes in growth characteristics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2002,94 (5):543-553.
[49]Anthony PM, Jordan RR. Marsupialization as a definitive treatment for the odontogenic keratocyst. Oral Maxillofac Surg,2004,62 (6):651-655.
[50]Chow HT. Odontogenic keratocyst:a clinical experience in Singapore. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,1998,86(5):573-577.
[51]Thosaporn W, lamaroom A, Pongsiriwet S, et al. A comparative study of epithelial cell proliferation between the odontogenic keratocysts, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma[J].Oral Diseases,2004,10(1):22-26.
[52]卫晋雄,赵怡芳,李宏礼.Carnoy液和三氯醋酸与对牙源性角化囊肿作用的实验研究[J].湖北医科大学学报,2000,21,248.
[53]Zhao YF, Wei JX, Wang XP. Treatment of odontogenic keratocysts:A follow-up of 255 Chinese patients[J].Oral Surg Oral Pathol Oral Radiol Endod, 2002,94(2):151-156.
[54]赵怡芳,刘冰.颌骨囊肿的手术治疗[J].继续医学教育,2006,20(22)：83-85.
[55]Chiapasco M, Rossi A, Motta JJ, et al. Spontaneous bone regeneration after enucleation of large mandibular cysts:a radiographic computed analysis of 27 consecutive cases. J Oral Maxillofac Surg,2000,58(9):942-948.
[56]Bataineh AB, al Qudah M. Treatment of mandibular odontogenic keratocysts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,1998,86(1):42-47.
[57]Dammer R. Niederdellmann H, Dammer P, et al. Conservative or radical treatment of keratocysts:a retrospective review. Br J Oral Maxillofac Surg, 1997,35 (1):46-48.
[58]Salmassy DA, Pogrel MA. Liquid nitrogen cryosurgery and immediate bone grafting in the management of aggressive primary jaw lesions. J Oral Maxillofac Surg,1995,53(7):784-790.
[59]杜小铭,孙树平,韩荣红,等.腔内热灌注治疗颌骨巨大角化囊性瘤的临床研究.武警医学院学报,2009,18(12)：1039-1042.