Nevoid basal cell carcinoma syndrome: a retrospective analysis of 33 affected Korean individuals

This article describes a pooled analysis of Korean individuals with nevoid basal cell carcinoma syndrome (NBCCS). The data upon which this review is based has been retrieved from published case reports in Korean dental and medical literature between the years 1981 to 2002. We found 33 subjects who met the diagnostic criteria for NBCCS. Relative frequencies of associated complications are presented and compared with those of the English literature. Odontogenic keratocyst (OKC) and palmar and/or plantar pits, and hypertelorism were the most frequently observed anomalies. OKCs are often the first signs of NBCCS and can be detected in patients younger than 20 years of age. However, the incidence and clinical manifestations of NBCCS in Korean individuals were found to be rather different from those of other countries. The relatively low frequency of basal cell carcinomas and falx calcification among the major criteria were two major differences. The frequencies of the minor criteria concur in general with the ranges given by some others. It is concluded that these differences may be attributed to genetic and geographic differences.     

Nevoid basal cell carcinoma syndrome: a review of the literature and a report of a case

The purpose of this paper is to report the development of multiple odontogenic keratocysts (OKCs) in a 15-year-old female with nevoid basal cell carcinoma syndrome (NBCCS) and review the literature pertinent to NBCCS. Although more than 100 abnormalities have been reported in NBCCS, the development of OKCs is one of its principle features. In view of this, the patient was subjected to further medical, dermatological and radiographic investigation. Multiple basal cell naevi and skeletal anomalies associated with NBCCS were found. Because of the autosomal dominant inheritance of this syndrome, the patient's family was then investigated. The patient's father was found to have multiple OKCs. The report highlights the need for vigilance in considering the diagnosis of NBCCS in all cases of OKCs, particularly those affecting young patients.     

Nevoid basal cell carcinoma syndrome: a 17‐year study of 19 cases in Iranian population (1991–2008)

J Oral Pathol Med (2010) 39 : 677–680 Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary autosomal dominant disorder with a wide range of clinical signs and symptoms. The major criteria are more than two basal cell carcinoma, keratocystic odontogenic tumor, three or more palmar pits, and calcification of the falx cerebri, spine and rib anomalies, and a family history of the syndrome. Methods: This study reports 19 cases in an Iranian population and presents this rare syndrome as a differential diagnosis of skeletal anomalies. Between 1991 and 2008, the demographic, clinical, radiologic and histologic data of 19 patients with NBCCS were analyzed. Results: The average age at the time of diagnosis of NBCCS was 35.12 years. All patients had a minimum of two major criteria. The major criteria with the most frequency were the keratocysts odontogenic tumor (19 patients), and the average number was 6.2. Basal cell carcinoma (8 patients), and the average number was 14.7 calcification of the falx cerebri (17 patients), palmo‐plantar pits (14 patients), mild hypertelorism (10 patients), and bilateral cleft lip and palate (1 patient). Only one patient was affected with an unusual case of NBCCS in a 30‐year‐old man with an associated squamous cell carcinoma of the maxillary sinus. Only two cases of this unusual association have been reported. This case is one of a large family including 14 NBCCS‐affected patients.     

Ameloblastoma associated with the nevoid basal cell carcinoma (Gorlin) syndrome

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a wide range of clinical signs and symptoms. The major criteria for the diagnosis are multiple cutaneous basal cell carcinomas, multiple odontogenic keratocysts of the jaw, palmar and plantar pits, and skeletal abnormalities. Here, we report an unusual case of NBCCS in a 68-year-old woman with late onset of clinical signs and symptoms and with an associated ameloblastoma. Only 4 other cases of this unusual association have been reported.     

A case of central odontogenic fibroma of the mandible in a nevoid basal cell carcinoma syndrome patient

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis and physical deformities. Although more than 50 clinical manifestations have been described, only two major criteria or one major and two minor criteria are necessary for diagnosis. The most frequently observed manifestation in the oral and the maxillofacial region is an odontogenic keratocyst. In this study, we describe a 14-year-old boy with a diagnosis of NBCCS who presented with a central odontogenic fibroma (COF) in the mandible. This report highlights the importance of precise diagnosis and the choice of surgical method for COF.     

Odontogenic keratocyst and uterus bicornis in nevoid basal cell carcinoma syndrome: case report and literature review

Nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder with a high degree of penetrance and variable expressivity, is characterized by basal cell carcinomas, odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. More than 100 minor criteria have been described, but 2 major and 1 minor criteria or 1 major and 3 minor criteria are necessary for the diagnosis. In this report we present an 8-year-old girl affected by NBCCS showing a uterus bicornis, a hitherto unreported association. However, further research is needed to confirm the association between NBCCS and mullerian fusion defects and to assess the hypothesis that focuses on chromosome 9 the mutant gene for NBCCS and fusion defects of female genital tract.     

Familial multiple odontogenic keratocysts

Multiple odontogenic keratocysts (OKCs) are principle features of nevoid basal cell carcinoma syndrome (NBCCS; Gorlin-Goltz syndrome). NBCCS is a genetic disorder transmitted by an autosomal dominant gene with variable expressivity, which is important to recognize when a patient has multiple OKCs. The cysts of the jaws are among the most common findings. Another feature is a certain appearance of the face, such as: large calvaria, high-arched eyebrows, broad nasal root, and mild hypertelorism. Before-therapy diagnosis is, therefore, as important as after-therapy diagnosis. Genetic counseling and examination may also be indicated. The purpose of this paper was to present a family case report of nevoid basal cell carcinoma syndrome with multiple odontogenic keratocysts. The features identified by these combined clinical, imaging, and histologic findings are described, along with a brief mention of the family history and a review of the literature.     

Odontogenic Keratocyst: To Decompress or Not to Decompress? A Comparative Study of Decompression and Enucleation Versus Resection/Peripheral Ostectomy

PURPOSE: We discuss the outcome of 2 well-established and widely accepted methods used for the treatment of odontogenic keratocyst (OKC), enucleation with peripheral ostectomy or resection and decompression followed by enucleation and peripheral ostectomy. PATIENTS AND METHODS: A retrospective chart review of all cases of OKC treated in the University of Maryland's Department of Oral and Maxillofacial Surgery between 1994 and 2004 was undertaken. A total of 31 patients with OKCs was identified. Three of these patients diagnosed with basal cell nevus syndrome and multiple OKCs and 6 patients who did not have adequate follow-up were excluded from this study; thus, 22 patients were evaluated. Of these 22 patients, 11 were treated with resection or enucleation with peripheral ostectomy (group I) and 11 were treated with decompression followed by enucleation when indicated (group II). RESULTS: A total of 22 patients with biopsy-proven OKC ranging in age from 18 to 90 years were separated into 2 treatment arms. Group I comprised 6 females and 5 males, age 18 to 71 years, with 6 OKCs located in the mandible and 5 in the maxilla. Group II comprised 6 females and 5 males, age 24 to 90 years, with 10 OKCs in the mandible and 1 in the maxilla. The choice of treatment approach was based on the size of the cyst, recurrence status, and radiographic evidence of cortical perforation. The last follow-up revealed no recurrences in group I and 2 recurrences in group II. Both patients with recurrence in group II had undergone enucleation of the same lesion in the past, and both cysts recurred within 2 years after initial treatment. CONCLUSIONS: Our study results concur with the literature regarding recurrence rates of OKC. The aggressive nature of some OKCs necessitates equally aggressive treatment, whereas long-term follow up even for nonsyndromic patients with single lesions is of paramount importance. Age of the patient and the site and histological characteristics of the treated lesions were not significantly associated with the incidence of recurrence.     

PCR-SSCP和DNA测序检测牙源性角化囊肿中PTCH基因的突变

目的 检测牙源性角化囊肿（OKC）中PTCH基因突变的特点。方法 采用PCR-SSCP筛查与DNA直接测序的方法对12例OKC进行PTCH基因突变的检测, 其中2例为痣样基底细胞癌综合征（NBCCS）相关OKC,10例为散发OKC。 结果 在4例OKC中发现了4处突变,其中2处生殖细胞突变发生在2例NBCCS相关OKC,2处体细胞突变发生在2例散发OKC。另外,还在10例OKC中检测到了8处PTCH基因多态性。结论 NBCCS相关OKC和散发OKC均可发生PTCH基因突变,但突变水平不同,PTCH基因的突变在二者的发病中可能均起重要作用。     

The odontogenic keratocyst and its occurrence in the nevoid basal cell carcinoma syndrome

There are histologic differences between odontogenic keratocysts occurring in the basal cell carcinoma syndrome (NBCCS) and as single lesions in otherwise healthy persons. This study identifies certain differences in age, gender, and site between the two groups. The age at removal of the first keratocyst is significantly lower in the syndrome group. On more thorough examination, patients with multiple keratocysts (excluding recurrences) are found to have other features of NBCCS. The term multiple cysts refers to the lifetime history of the patient and does not necessarily imply that more than one cyst is present at any one time.     

PTCH1 and SMO gene alterations in keratocystic odontogenic tumors

Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 (PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. Abbreviations: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.     

A mandibular swelling

Nevoid basal cell carcinoma syndrome (NBCCS) is characterised by skeletal anomalies, cutaneous basal cell carcinomas and multiple keratocysts. NBCCS is an autosomal dominant disorder, but can have a variable phenotypic penetration. NBCCS can also arise spontaneously. The prevalence is 1:60.000 and 50-65% of patients with NBCCS have affected family members. A recently diagnosed patient is presented and the manifestations of the syndrome are discussed.     

牙源性角化囊肿中PTCH基因的突变检测

目的检测牙源性角化囊肿（OKC）中PTCH基因突变的发生频率、类型及分布特点，分析散发OKC与伴发痣样基底细胞癌综合征（NBCCS）OKC之间的分子病理联系。方法收集8例OKC新鲜病变组织（4例散发，4例伴发NBCCS），提取DNA，采用PCR直接测序法检测OKC病变组织中的PTCH基因突变。结果分别于4例NBCCS—OKC和2例散发OKC中检测到6处PTCH基因突变，2例为错义突变，引起1个氨基酸的改变；其余4例突变分别为1～7个碱基插入或缺失，其中3例引起读码框的改变（移码突变），并导致蛋白质的提前截断，1例导致了2个氨基酸的插入。结论PTCH基因突变不仅常见于NBCCS—OKC，部分散发OKC病变也可以发生该基因的异常。     

Marsupialization as a definitive treatment for the odontogenic keratocyst.

PURPOSE: We sought to show that marsupialization can be a definitive treatment for the odontogenic keratocyst (OKC). MATERIALS AND METHODS: Ten patients (10 males and 4 females) between the ages of 11 and 64 with biopsy-proven OKC (8 mandibular and 2 maxillary) measuring between 2 and 8 cm were treated by marsupialization consisting of excision of the overlying mucosa and the opening of a 1-cm window into the cystic cavity and, where possible, suturing of the cyst lining to the oral mucosa. Immunohistologic determination of bcl-2 was done for all samples of cyst lining. The cavities were kept open either by vigorous use of a home syringe by the patient or by suturing into place the flange and short length of a nasopharyngeal airway. Once the cyst had largely filled in, histologic material was taken from the base of the residual depression and studied by light microscopy and bcl-2 expression. RESULTS: In the 10 patients, the OKCs completely resolved both clinically and radiographically. The time taken for resolution varied from 7 to 19 months. In all cases, the histologic material obtained after marsupialization showed normal epithelium only, with no signs of cystic remnants, daughter cysts, or budding of the basal layer of the epithelium. At initial biopsy, bcl-2 was expressed in the keratocyst lining, but not in the histologic material obtained after marsupialization. Follow-up time ranged from a minimum of 1.8 years to a maximum of 4.8 years. Teeth at the periphery of the cysts were observed to upright and erupt. CONCLUSIONS: All 10 OKCs resolved completely after marsupialization. Teeth within the cyst were found to be upright and erupt. Marsupialization requires a cooperative patient who will irrigate the cavity and keep it open. It appears that the cyst lining is replaced by normal epithelium during this treatment.     

Immunohistochemical analysis of cell-cycle- and apoptosis-related factors in lining epithelium of odontogenic keratocysts

We examined the immunohistochemical expressions of cell-cycle- and apoptosis-related factors to investigate the possible role of these factors in odontogenic keratocyst (OKC). Expression of cyclin D1 and p16 protein was detected in the basal and parabasal cells in lining epithelium of OKCs and was found more frequently in basal cell nevus syndrome (BCNS)-associated OKCs than in primary or recurrent OKCs. Positivity for p21 protein was detected in basal to superficial cells, whereas that for p27 protein was detected in parabasal to superficial cells in lining epithelium of OKCs. DNA topoisomerase IIalpha reacted with nuclei in basal and parabasal cells of the lining epithelium of OKCs, and positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. Expression of Fas in suprabasal to superficial cells and expression of Fas-L in basal and parabasal cells were detected in lining epithelium of OKCs. Immunoreactivity for caspase-3 was detected in basal to suprabasal or superficial cells in lining epithelium of OKCs. Single stranded (ss)DNA-positive nuclei were detected in superficial cells in lining epithelium of OKCs. Fas was more broadly distributed in BCNS-associated OKCs than in primary OKCs, and ssDNA-positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. These results suggest that BCNS-associated OKCs might be a distinguishable entity from solitary OKCs.     

Maxillary odontogenic keratocyst: a common and serious clinical misdiagnosis

BACKGROUND: The authors conducted this study to determine the most common location of odontogenic keratocysts, or OKCs, in the maxilla and the implication of this for dental practice. METHODS: The authors reviewed all cases diagnosed as an OKC by the Oral and Maxillofacial Pathology Diagnostic Laboratory at University of Florida College of Dentistry from July 1, 1993, to June 30, 2001. They determined the location for each cyst and recorded relevant clinical information such as age and sex. In addition, the authors noted the practitioners' clinical diagnoses for the cases in the most common location in the maxilla and compared them with the final diagnosis. RESULTS: A total of 398 OKCs occurred in 393 patients. Of the 398 cysts, 266 (66.8 percent) were in the mandible, and 132 (33.2 percent) were in the maxilla. The most common location for OKCs was the third molar and ramus area of the mandible, with 137 cysts. The canine region of the maxilla, with 54 cysts, was the second most common location. Submitting clinicians mentioned OKC as a diagnostic possibility in only 31.5 percent of the maxillary canine region cases. CONCLUSION: The most common maxillary location for OKCs is the canine region where they commonly are mistaken for an apical inflammatory lesion or lateral periodontal cyst. Accurate diagnosis is essential for proper patient therapy and follow-up. CLINICAL IMPLICATION: A diagnosis based solely on clinical information can be problematic. In many cases, histologic examination of surgically removed tissue is necessary to establish a definitive diagnosis. That is particularly true for cases that do not resolve when treated by conservative endodontic therapy.     

Odontogenic keratocyst: Review of 256 cases for recurrence and clinicopathologic parameters

Odontogenic keratocyst (OKC) is of particular interest because of its high recurrence rate and aggressive behavior. Two hundred fifty-six cases of OKC were reviewed for the age of the patient at diagnosis, sex of the patient, OKC location, and radiographic findings, and 132 patients with OKC were observed to estimate recurrence, which was analyzed for age, sex, location, and several histopathologic findings. OKCs occurred more frequently in men (58.6%) than in women (41.4%), and they occurred in patients within a wide age range, most commonly in patients in the third decade of life (28.9%), followed by those in the second decade (25.0%); the mean age of patients with OKC was 30.8 years. One hundred ninety-six of the 256 cases (76.5%) occurred in the mandible, and the other 60 cases (23.5%) occurred in the maxilla. The mandibular molar and the premolar areas (51.2%) were the most common sites, and the most frequent clinical manifestations at first admission were swelling, pain, or both (82.4% of total cases). Radiographic impressions included dentigerous cyst (27.3%), OKC (25.4%), primordial cyst (14.8%), ameloblastoma (11.7%), residual cyst (9.8%), and radicular cyst (3.1%). The frequency of recurrence at the follow-up examination was 58.3%. There was no significant difference in the recurrence rate on the basis of the sex of the patient. However, OKCs had a significantly higher recurrence rate in patients in the fifth decade of life than in patients in the other age groups (P = .005).Recurrence rates were significantly dependent on the sites of involvement, and OKCs in the mandibular molar region had significantly higher recurrence rates than those in other sites (P = .001). The histopathologic presence of one or more daughter cysts was significantly related to recurrence (P = .03).     

The multifocal nature of odontogenic keratocysts

The odontogenic keratocyst, OKC, is a very aggressive intraosseos lesion with a recurrence rate of approximately 25 percent to 60 percent.' The tendency for this lesion to "return" after surgical treatment has prompted studies to obtain more information concerning the inherent nature of the lesion. The OKC lesions are usually treated with enucleation of the soft tissue lining, curettage and ostectomy of the bony margins, or with more aggressive block resection. The purpose of this study was to characterize the multifocal aspect of the OKC and to demonstrate the presence of cystic lesions remote from the margins of the primarily diagnosed cyst itself. A retrospective chart review was conducted of seven patients who had sustained a long history of recurrent OKCs. Three types of documentation were reviewed for each patient: Orthopantomograms, cephalograms, and CT scans, which had been taken over the long-term course of the disease, Detailed operation reports of surgical procedures to treat the OKC lesions, and; Large histologic specimens from the six patients who received total resection of the involved mandibular bodies. These hemimandibulectomy slides offered a unique opportunity to observe OKC activity throughout a wide osseous area. All patients hod been operated multiple times over a period of 10 to 21 years, coming eventually to mandibular resection. The operating surgeon in all of the cases was one of the authors, Philip J. Boyne, DMD, MS, DSc. All patients exhibited the multifocal nature of OKCs with demonstrable cyst formation at distant sites in the mandible. Two patients had local recurrences at the margins of the primary lesion in addition to cyst formation at distant sites. The authors concluded that clinicians should respect the multifocal nature of OKCs. The "recurrences" observed in OKCs may not necessarily be due to the degree of skill of the surgeon or the technique used to eradicate the primary cyst, but instead are probably a reflection of the multifocal nature of the pathologic lesion itself. The OKC is a very aggressive intraosseos lesion of the jaws, which not infrequently clinicians detect in the process of routine oral examination.     

72例腭隐裂修复方式的回顾分析

目的：通过回顾性分析8年的腭隐裂修复治疗，寻求较合适的修复方法及修复时机。方法：1999年9月至2007年1月行腭隐裂修复的患者72例，男37例，女35例，年龄1-35岁，平均11．2岁。术后1个月复诊，检查伤口愈合情况，并进行语音评估。同时将72例患者按所接受的手术方法分为三组：Ⅰ组（腭成形术），Ⅱ组（改良咽后壁组织瓣转移术），Ⅲ组（腭咽成形术）；按手术年龄将其分为：〈4周岁；t〉4周岁、〈8周岁；≥8周岁三组，统计各组的构成比，及比较各组术后的腭咽闭合及语音情况。结果：术后穿孔的患者为3例（4．2％），69例患者术后接受了语音评估，1例（兰氏术后）仍遗留VPI。10例患者语音检测为正常（96．15％±2．11％），余58例患者腭咽闭合功能改善，但仍伴代偿性发音，需语音治疗。手术方式分组：Ⅰ组13例（18．1％），Ⅱ组46例（63．89％），Ⅲ组13例（18．1％）；年龄分组：〈4周岁7例（9．72％），t≥4周岁、但〈8周岁25例（34．72％），≥8周岁40例（55．56％）。〈4周岁的患者采用腭成形术最多，占57．1％，≥4周岁、但〈8周岁及≥8周岁的患者采用改良咽后壁组织瓣转移术的最多，各占68％，和70％。语音评估发现〈4周岁组的患者术后正常语音的比例最高，占71．4％，其次是t〉4周岁、但〈8周岁组，正常语音的比例为该年龄组的19．2％，VP完全，有代偿性发音的占76．9％，而大年龄组（≥8周岁），均伴有代偿性发音而需语音治疗。结论：小年龄组（〈4周岁）的腭隐裂修复术后语音效果较好，大年龄组（≥8周岁）的腭隐裂修复可首选咽成形术或腭咽成形术，术后须辅以语音训练，t≥4周岁、但〈8周岁的患者修复方式的选择可根据具体情况选用。