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.     

Nevoid-basal cell carcinoma syndrome: a case report and overview on diagnosis and management

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is a rare condition characterized by varied clinical manifestations like multiple Basal Cell Carcinomas (BCC), multiple Keratocystic Odontogenic Tumours (KCOT), palmar and/or plantar pits and ectopic calcification of the falx cerebri, which are considered as the major criteria for diagnosis. The occurrence of jaw manifestations makes it an important diagnostic problem for oral and maxillofacial surgeons and often clinicians encounter this aspect which finally leads to the diagnosis of this syndrome. This paper reports a case of NBCCS and provides an overview on the diagnosis and management of this enigmatic entity.     

Early diagnosis of nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome, or NBCCS, is a hereditary condition characterized by basal cell carcinomas, or BCCs; odontogenic keratocysts, or OKCs; and skeletal abnormalities. The authors conducted this study to determine the early signs of NBCCS. METHODS: The authors reviewed files from two Italian dental schools from January 1980 to January 1995 to determine the early signs of NBCCS and the age at which patients were first examined. They re-examined all of the patients, using the diagnostic criteria for NBCCS. RESULTS: The authors found 14 patients who fulfilled the criteria for diagnosis of NBCCS in five families. All of the patients were 16 years of age or younger. In 11 cases (78 percent), the first sign of NBCCS in the patients was an OKC. The OKCs diagnosed in patients older than 13 years of age were large and characterized by widespread bone resorption. One 11-year-old patient had six large OKCs. The authors also found a case of multiple OKCs in an 8-year-old patient. Only one patient showed BCCs. CONCLUSIONS: OKCs are often the first signs of NBCCS and can be detected in patients younger than 10 years of age. Our data suggest that OKCs arise earlier in patients who have NBCCS than in patients who do not have NBCCS. The patients' young ages explain the low incidence of BCCs in this study. CLINICAL IMPLICATIONS: The presence of multiple OKCs in a child or onset of BCC in a patient younger than 20 years of age should alert dentists to the possibility of the patient's having NBCCS.     

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.     

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.     

Changes in Elongation of Falx Cerebri During Craniosacral Therapy Techniques Applied on the Skull of an Embalmed Cadaver

CranioSacral therapy supports that light forces applied to the skull may be transmitted to the dura membrane having a therapeutic effect to the cranial system. This study examines the changes in elongation of falx cerebri during the application of some of the craniosacral therapy techniques to the skull of an embalmed cadaver. The study demonstrates that the relative elongation of the falx cerebri changes as follows: for the frontal lift, 1.44 mm; for the parietal lift, 1.08 mm; for the sphenobasilar compression, -0.33 mm; for the sphenobasilar decompression, 0.28 mm; and for the ear pull, inconclusive results. The present study offers validation for the scientific basis of craniosacral therapy and the contention for cranial suture mobility.     

痣样基底细胞癌综合征伴先天性左眼缺失1例

痣样基底细胞癌综合征（NBCCS）又称基底细胞痣综合征或Goltz-Gorlin综合征，是一种复杂且罕见的常染色体显性遗传疾病，大量研究文献证实PTCH1基因与NBCCS有关。本文报道1例NBCCS伴先天性左眼缺失的病例，并结合相关文献探讨以进一步了解该综合征。     

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.     

p53 expression in odontogenic keratocyst epithelium

The expression of p53 protein was studied in odontogenic keratocysts (OKC, 11 solitary, 5 recurrent and 6 NBCCS cysts), radicular (RC, n=5) and dentigerous (DC, n=5) cysts, using a panel of antibodies to p53 (clone BP53-12, clone 1801 and polyclonal CM1) and a sensitive biotin-streptavidin method on paraffin embedded sections. Of the three antibodies tested, clone BP53-12 gave the most intense and consistent nuclear staining pattern. Clone 1801 and polyclonal CM1 stained only 38% and 71% OKC linings, respectively, but not RC and DC linings. However, BP53-12⁺ cells were detected in the epithelial linings of all cyst types. Quantification of BP53-12⁺ cells was performed by manual counting and by relating cell number to unit length of basement membrane as determined by TV image analysis. BP53-12⁺ cell counts in solitary OKC linings (25.5 ± 11.0 cells/mmBM) were significantly greater than those in DC (9.3 ± 4.9 cells/mmBM, P<0.01) and RC (6.7 ±2.6 cells/mmmBM. P<0.01) linings. The epithelial distribution of positive cells in OKC was predominantly suprabasal, which also varied from that of DC and RC linings (P<0.005). There were no detectable differences in BP53-12 reactivity between the different subtypes of OKC (i.e., solitary, recurrent and NBCCS-associated OKC: P>0.1). When data for the NBCCS-related OKC group were excluded, there was a significant correlation (r=0.55. P<0.01) between p53 and Ki67 labelling. To detect the presence of p53 gene mutations, genomic DNA, extracted from paraffin sections of OKC (4 solitary, 2 recurrent and 4 NBCCS cysts). RC (n=3) and normal oral mucosa (n=1), was subjected to a combination of polymerase chain reaction and single-stranded conformation polymorphism (PCR-SSCP) analysis for exons 5-10 of the p53 gene. Exon 4 was not analysed because of compromised DNA quality. No abnormality in banding patterns was found and all samples save results similar to DNA from known, sequenced, normal p53 gene controls. Absence of p53 mutations within exons 5–9 was confirmed by the direct sequencing of 2 fresh frozen OKC samples (1 solitary and 1 NBCCS cyst). These results suggest that over expression of p53 protein in OKC epithelium, detected by immunocytochemistry, is not reflected by alteration of the p53 gene and presumably reflects overproduction and/or stabilisation of normal p53 protein.     

痣样基底细胞癌综合征1例报道

痣样基底细胞癌综合征(nevoid basal cell carcinoma syndrome,NBCCS)是一种少见的常染色体显性遗传病,临床表现多达一百多种,主要临床表现为皮肤基底细胞癌,颌骨牙源角化囊性瘤（odontogenic keratocystic tumor, OKC）,手掌及脚底的过度角化、点状凹陷,颅骨异常,小脑镰钙化,眶距增宽,面部畸形,巨头巨脑畸形,唇腭裂等。本文报告1例痣样基底细胞癌综合征,并结合相关文献对该病的发病机制、发病率、临床表现、诊断、治疗方法等进行讨论。     

Craniofacial and dental findings in cystinosis

Oral Diseases (2010) 16 , 488–495 Objectives: Cystinosis is a rare autosomal recessive lysosomal storage disorder with developmental and mineralization anomalies as part of its clinical presentation. The objective of this study was to provide the first systematic assessment of the craniofacial and dental characteristics associated with cystinosis. Study Design: Oral and radiographic evaluations were performed on 73 patients with cystinosis. Analyses of cephalometry (n = 20), taurodontism (n = 47), caries (n = 47), enamel defects (n = 48), soft tissue anomalies (n = 48), and dental age (n = 41) were performed on the cystinosis group, and compared with age‐ and sex‐comparable controls or standards. Results: Cystinosis patients manifested relative mandibular deficiency, an increased facial height, and a reduced airway space. Taurodontism and enamel defects were significantly more prevalent in cystinosis patients compared with controls (P < 0.0001 and P = 0.027, respectively). Children (aged <15 years) with cystinosis also demonstrated a significant delay, of almost 9 months, of their dental development (P < 0.001). Conclusion: Novel craniofacial and dental features are associated with cystinosis. Craniofacial deficiencies may influence the swallowing and respiratory complications seen in cystinosis. Renal pathology and associated mineral imbalance may explain the dental root and enamel anomalies found in cystinosis patients; the developmental delays in cystinosis include delayed dental formation.     

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.     

MMP‐13 expression in keratocyst odontogenic tumour associated with NBCCS and sporadic keratocysts

Oral Diseases (2010) 16 , 795–800 Objective: To investigate the matrix metalloproteinase (MMP)‐13 expression in associated and non‐nevoid basal cell carcinoma syndrome (NBCCS) Odontogenic Keratocysts (OCKs) in order to contribute to a better understanding of the differences in the growth pattern between them. Materials and methods: Thirty‐nine paraffin‐embedded blocks of OCKs, 26 sporadic OCKs and 11 NBCCS‐associated KCOTs were studied by immunohistochemistry to evaluate MMP‐13 expression both in epithelial and stromal layers. A semi‐quantitative scale was used to evaluate immunostaining. Obtained data were compared between the two groups, using Fischer’s exact test and the chi‐square test. Results: Only 13 of 26 sporadic OCKs showed a positive immunostaining, whilst 11 KCOTs resulted in positive labelling for MMP‐13 expression. Moreover, syndromic cysts displayed a more intense and diffuse MMP‐13 labelling of the stromal tissue. Instead, in non‐syndromic forms, the staining pattern of MMP‐13 in stromal tissue was completely absent. Fisher's exact test showed a statistically significant greater prevalence of KCOTs‐immunolabelled cysts with respect to sporadic OCKs. Conclusions: Results from this study point out that the biological behaviour of these cysts could be related not only to the epithelial layer but also to stromal tissue in that... MMP‐13 overexpression in stromal tissue of NBCCS‐associated KCOTs could clarify the higher aggressiveness of these cysts.     

Oral health status and reasons for not attending dental care among 12- to 16-year-old children with Down syndrome in special needs centres in Jordan

To cite this article:
Int J Dent Hygiene 10 , 2012; 259–264
DOI: 10.1111/j.1601‐5037.2012.00545.x Al Habashneh R, Al‐Jundi S, Khader Y, Nofel N. Oral health status and reasons for not attending dental care among 12‐ to 16‐year‐old children with Down syndrome in special needs centres in Jordan. Abstract: Objectives: The objective of this study was to assess oral health status, treatment needs, soft and hard tissue findings, as well as reasons for not attending dental care among children with Down syndrome (DS) registered in special needs centres in Jordan. Methods: The sample consisted of a total of 206 participants with a mean age of 13.66 ± 1.47 comprising 103 with DS and 103 age‐ and gender‐matched non‐DS/public school children. Clinical levels of oral hygiene were assessed using Simplified Oral hygiene index, and caries detection was carried out according to WHO caries recording criteria. Results: Children who had DS had a significantly higher percentage of surfaces with severe gingival index (39.9 ± 9.1 versus 15.9 ± 8.0, P < 0.001) and a higher mean of probing pocket depth than children without DS (2.27 ± 0.2 versus 1.81 ± 0.32, P < 0.000). Significantly more peg‐shaped maxillary lateral incisors and retained primary teeth (P < 0.001) were observed in subjects with DS, compared with non‐DS children. Average decayed, missing and filled teeth (DMFT) was significantly lower in male children with DS compared with male non‐DS children only (P = 0.034). The most common reason cited for not taking children to the dentist for DS group was ‘Not aware of the dental problems of their children’ and for non‐DS groups ‘No awareness of the importance of dental visit’ (61.2% and 53%, respectively). Conclusions: While having similar caries level, Jordanian teenagers with DS had more dental anomalies, poorer periodontal health and less dental attendance than age‐ and gender‐matched non‐DS/public school children.     

3D histology-guided surgery for basal cell carcinoma and squamous cell carcinoma: recurrence rates and clinical outcome

In a prospective study, a large number of patients with basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) underwent surgery using three dimensional (3D) histology and were evaluated with respect to local recurrence. The excised tumours were treated using 3D-histology with a routine paraffin procedure until the surgical margins were clear of tumour. Prospective evaluation of recurrence-free survival and overall survival of 5227 primary BCCs in 3320 patients and 615 invasive primary SCCs in 600 patients was conducted in the form of a letter-based follow-up with feedback from the patients and the referring physicians. The mean follow-up period was 5 years. In the BCC collective, 36 out of 3320 patients developed local recurrence (1%, calculated as a percentage of treated BCCs: 0.7%). In the SCC collective, 20 local recurrences appeared (3%). The recurrence rate for SCCs with desmoplasia was 24%, whilst the recurrence rate for common types of SCC without desmoplasia was 1%. Surgery followed by 3D histology results in very low recurrence rates for BCC and SCC with no additional effort compared with the normal histopathological procedure.     

Nevoid basal cell carcinoma syndrome: a review of the literature

The nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin-Goltz Syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The present report reviews current knowledge of this disorder that has profound relevance to specialists in Oral and Maxillo-Facial Surgery, Oral Medicine and Radiology.     

Cheilitis glandularis: clinico-histopathological diagnostic criteria

Oral Diseases (2011) 17 , 335–339 Objectives: To present a combination of clinical and histopathological criteria for diagnosing cheilitis glandularis (CG), and to evaluate the association between CG and squamous cell carcinoma (SCC). Materials and Methods: The medical literature in English was searched from 1950 to 2010 and selected demographic data, and clinical and histopathological features of CG were retrieved and analysed. Results: A total of 77 cases have been published and four new cases were added to the collective data. The clinical criteria applied included the coexistence of multiple lesions and mucoid/purulent discharge, while the histopathological criteria included two or more of the following findings: sialectasia, chronic inflammation, mucous/oncocytic metaplasia and mucin in ducts. Only 47 (58.0%) cases involving patients with a mean age of 48.5 ± 20.3 years and a male‐to‐female ratio of 2.9:1 fulfilled the criteria. The lower lip alone was most commonly affected (70.2%). CG was associated with SCC in only three cases (3.5%) for which there was a clear aetiological factor for the malignancy. Conclusions: The proposed diagnostic criteria can assist in delineating true CG from a variety of lesions with a comparable clinical/histopathological presentation. CG in association with premalignant/malignant epithelial changes of the lower lip may represent secondary, reactive changes of the salivary glands.     

Situs inversus in a patient with nevoid basal cell carcinoma syndrome: a histogenetic relationship?

Nevoid basal cell carcinoma syndrome (NBCCS) is an uncommon autosomal dominant inherited disorder with high penetrance and variable expressivity. It affects multiple organ systems, including the stomatological, skeletal, skin, eye, reproductive, and central nervous systems. It is caused by mutations in the patched tumor suppressor gene, PTCHI, located in the 9q22.3-q31 chromosome. To our knowledge, this is the first report of a patient with unusual radiological features, i. e. dextrocardia and situs inversus totalis, in conjunction with common features including multiple keratocystic odontogenic tumors, bifid ribs, palmar and plantar pits, bridging of the sella turcica and calcification of the falx cerebri. We examined whether these genetic conditions were associated, as both involve ciliary dysfunction.     

An audit of oral diseases at a Nairobi centre, 2000-2004

OBJECTIVES: To describe oral diseases diagnosed in an urban referral centre in Kenya in terms of age, gender and anatomical distribution and to compare this with reports in the literature. METHODOLOGY: A retrospective histopathological audit. SETTING: Oral Pathology Laboratory at the University of Nairobi Dental Hospital, a tertiary referral centre in Kenya. RESULTS: 548 (53.83%) patients were diagnosed with oral and maxillofacial tumours. Benign tumours (mean age +/- SD = 29.93 +/- 18.27 years) peaked in the third decade and tended to affect men at a younger age (p = 0.001). The most common benign tumour was the ameloblastoma (50.23%: n = 109), which predominantly affected the mandible, and also occurred in male patients at a younger age (p = 0.023). Peak incidences for malignant disease were observed in the sixth decade (mean age +/- SD = 46.94 +/- 18.99 years). Oral squamous cell carcinoma (OSCC) was the most common malignant tumour (59.55%; n = 187); occurring in the tongue, floor of the mouth, buccal mucosa and palate. 10.30% of OSCC occurred in patients under 40 years of age. 147 patients presented with cysts, which were mainly (68.10%) of odontogenic origin. Reactive lesions, infections, salivary gland diseases and autoimmune conditions constituted 26.60% of the case load. CONCLUSION: The tendency of oral squamous cell carcinoma to occur in younger age groups may be an indication of carcinogenic factors that could be peculiar to this population. There is an urgent need for the expansion of reporting systems for oral diseases as an integral part of development of appropriate strategies in the improvement of general health in Kenya.     

Clinicopathological and immunohistochemical features of oral spindle cell carcinoma

J Oral Pathol Med (2010) 39 : 335–341 Background: Oral spindle cell carcinoma (SpCC) is a rare variant of oral squamous cell carcinoma (SCC). The aims of this study were to compare the clinicopathologic and immunohistochemical features of oral SpCC with conventional oral SCC. Methods: Five cases of oral SpCC and 10 cases of oral SCC (five well‐differentiated and five poorly differentiated) were evaluated through conventional hematoxylin and eosin staining and immunohistochemical reactions to cytokeratins (CK), vimentin, desmin, smooth muscle actin, muscle‐specific actin, S‐100 protein, epithelial membrane antigen (EMA), p53, and ki‐67. Results: Oral SpCC showed predilection for males on their sixth decade of life, presenting clinically as painful infiltrative ulcers or ulcerated exophytic polypoid masses, preferably located on the alveolar mucosa. Mesenchymal markers were expressed in the spindle cell but not in the carcinomatous component of SpCC, and it was negative in all SCC. CKs AE1/AE3, 6, 14, and EMA were positive on both carcinomatous and spindle cell components of most SpCCs. These tumors also presented higher p53 and ki‐67 expression and no CK 1 expression in contrast to well‐differentiated SCC. Conclusion: Oral SpCC presented a different clinical profile than conventional SCC and histopathologic features and p53 and ki‐67 expression closer to poorly differentiated SCC. Besides mesenchymal markers, CK AE1/AE3, 6, 14, and EMA expression on spindle cells may be useful as an adjunct on microscopical differential diagnosis of SpCC.