The immunohistochemical profile of basal cell nevus syndrome–associated and sporadic odontogenic keratocysts: a systematic review and meta-analysis

Clinical Oral Investigations - To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)–associated and sporadic...     

Nevoid Basal Cell Carcinoma Syndrome: A Case Report and Review

Nevoid basal cell carcinoma syndrome, a rare autosomal dominant disorder, comprises of a number of abnormalities such as multiple nevoid basal cell carcinomas, skeletal abnormalities and multiple keratocystic odontogenic tumors. Diagnosis may be difficult because of the variability of expressivity and different ages of onset for different traits of this disorder. The dental clinician may be the first to encounter and identify this syndrome, when the multiple cysts like radiolucencies are discovered on panoramic view. This article reports a case of Nevoid basal cell carcinoma syndrome and provides an overview on diagnosis and management.     

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.     

Expression of the T‐cell‐specific adapter protein in oral epithelium

Kolltveit KM, Schreurs O, Østrem J, Søland TM, Khuu C, Berge T, Messelt E, Hayashi K, Granum S, Spurkland A, Schenck K. Expression of the T‐cell‐specific adapter protein in oral epithelium. Eur J Oral Sci 2010; 118: 159–167. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci The multifunctional T‐cell‐specific adapter protein (TSAd) was originally described in T cells but is also expressed in epithelial cells from the respiratory tract and in endothelium. In this study, we found expression of TSAd messenger RNA (mRNA) and protein in both human and murine oral mucosal epithelium as well as in human primary oral keratinocyte cell cultures. In TSAd^?/? mice, the mucosa and skin appeared macroscopically normal, but severe disturbances were observed in the fine structures of the basal membrane and intercellular epithelial spaces upon analysis using transmission electron microscopy. Oral epithelial cells from TSAd^?/? mice displayed decreased migration compared with cells from wild‐type mice, whereas overexpression of TSAd in a human epithelial cell line resulted in impaired proliferation. This study is the first to show that TSAd is expressed in normal oral mucosa, that it is important for the normal ultrastructural morphology of the epithelium and the basal membrane, and that it is involved in the migration and proliferation of oral keratinocytes.     

痣样基底细胞癌综合征家系1例

痣样基底细胞癌综合征是一种罕见的常染色体显性遗传病,以发育异常和肿瘤发生为主要临床特征。本文报告1例痣样基底细胞癌综合征家系,并结合相关文献对该病的发病率、发病机制、临床表现、治疗方法等进行讨论。     

Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias

BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers. METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index. RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia. CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.     

痣样基底细胞癌综合征1例报告

痣样基底细胞癌综合征是一种罕见的常染色体显性遗传疾病，以颌骨多发性角化囊肿、皮肤痣样基底细胞癌及多种骨骼异常为主要临床表现。作者报告1例典型病例．并对其临床、病理和治疗进行了讨论．     

Nuclear β‐catenin expression in basal cell adenomas of salivary gland

J Oral Pathol Med (2010) 40 : 460–466 Background: Nuclear localization of β‐catenin is known in a wide variety of human neoplasms; however, there are few reports in basal cell adenoma of the salivary gland. Our objective was to confirm the nuclear localization of β‐catenin in basal cell adenoma and to examine whether nuclear β‐catenin expression could be a useful marker in the diagnosis of basal cell adenoma. Methods: To evaluate the nuclear localization of β‐catenin in basal cell adenomas, immunohistochemistry (IHC) and mutation analysis of CTNNB1 were performed in 22 and 21 cases, respectively. Mutation analysis of CTNNB1 in exon 3 was performed by DNA direct sequencing. In a comparative study, IHC for β‐catenin was also performed in 157 other salivary gland tumors. Results: Nuclear β‐catenin expression was examined in 22 basal cell adenomas; scores were 2+ in 18 cases (81.8%), 1+ in three cases (13.6%), and 0 in one case (4.5%). Expression was localized in the basaloid myoepithelial cells. CTNNB1 mutation analysis was performed in 21 basal cell adenomas; mutations, including I35T and T41P, were detected in 11/21 (52%) cases. In comparison with other salivary gland tumors, one of three basal cell adenocarcinomas showed nuclear β‐catenin expression, whereas there was no nuclear β‐catenin expression in 154 other salivary gland tumors. Conclusions: We demonstrated nuclear β‐catenin expression and activation of the CTNNB1 gene in basal cell adenoma. Although nuclear β‐catenin expression may be unable to distinguish basal cell adenoma from basal cell adenocarcinoma, it should be a helpful marker in the diagnosis of basal cell adenoma.     

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.     

Pathogenesis of oral lichen planus – a review

J Oral Pathol Med (2010) 39 : 729–734 Oral lichen planus (OLP) is a T‐cell‐mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen‐specific and non‐specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen‐specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen‐specific keratinocyte killing by CD8⁺ cytotoxic T cells. Non‐specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra‐epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.     

Altered CD40 and E-cadherin expression – putative role in oral lichen planus

BACKGROUND: Oral lichen planus (OLP) is characterized among other features by apoptosis of basal keratinocytes. To identify potential regulatory mechanisms associated with basal cell apoptosis in OLP, we investigated the expression of CD40, CD40 ligand (CD40L), CD44 and epithelial (E)-cadherin. METHODS: Biopsies from 22 patients with OLP were investigated by immunohistochemistry for detection of CD40, CD40L, E-cadherin, CD44, Laminin-5 and Collagen IV, double-labelling for CD40 and CD3, and in situ mRNA hybridization for CD40 and CD40L. RESULTS: In actively diseased areas of OLP lesions, basal keratinocytes did not express CD40 and were focally E-cadherin-negative, in contrast to non-diseased areas and normal oral mucosa. Demonstration of intraepithelial T cells expressing CD40 and CD40L, indicates a potential role in inflammatory cell responses involved in the disease process of OLP. CONCLUSION: T cells may orchestrate inflammatory cell responses in OLP via CD40-CD40L interactions. As basal keratinocytes downregulate CD40, they may escape CD40-CD40L-induced apoptosis in OLP. On the other hand, loss of E-cadherin expression may contribute to epithelial basal cell destruction and T-cell migration into the epithelial compartment in OLP.     

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.     

Alstrom syndrome: a case report.

Alstrom syndrome is a rare disorder characterized by early obesity, loss of central vision, diabetes mellitus, hearing loss and short stature. Previous studies, have reported no information regarding oral findings. This article describes oral findings in two cases of Alstrom syndrome. In both cases, gingivitis was present and also light yellow-brown discolored enamel bands were observed on the anterior teeth. This staining may have resulted from discoloration of the preexisting slight band-like enamel hypoplasia. The gingiva was examined histologically by light and transmission electron microscopy. Irregular thickness of the basal lamina and delamination of the myelin sheath were detected by transmission electron microscopy. There is no information about pathological odontogenesis in Alstrom syndrome in previous reports. Oral present findings may contribute further information about the clinical manifestations of Alstrom syndrome.     

Implications of giant cell arteritis in older adults

Giant cell arteritis, a vascular inflammatory disorder of unknown etiology, is most often observed in Caucasian females over age 50. The vascular changes, involving the cranial arteries, result in oral and perioral symptoms as well as headache and scalp tenderness. Since involvement of the ophthalmic artery can result in visual disturbances and sudden blindness, dentists must be familiar with the signs and symptoms of this condition and refer patients for immediate medical assessment and care. Oral corticosteroid therapy is the treatment of choice.     

Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus

Keratins form intermediate filaments of the cytoskeleton in keratinocytes and have roles in cell structure, signaling, intracellular transport, and cell death. Oral lichen planus (OLP) is an oral inflammatory disease with derangements in basal keratinocytes and disruption of the basal membrane. Here, we focused on epithelial expression of keratins 8, 18, and 19 because these proteins are known to modulate cell death. Biopsies were taken from buccal oral mucosa of persons with normal oral mucosa (n = 10) or atrophic OLP (n = 10). Cultured normal oral keratinocytes (n = 4) showed expression of mRNA and protein for keratins 8, 18, and 19. Immunohistochemistry showed consistent staining for keratins 8 and 18 in basal keratinocytes of normal oral mucosa. In OLP, staining for keratin (K)8 was mostly negative and staining for K18 was weak. Keratin 19 was expressed irregularly in most biopsies of normal oral mucosa and not at all in OLP. Several mononuclear leukocytes in the cellular infiltrate showed membrane staining for K8 and K18. Positive staining for K16 confirmed partial collapse of the basal cell layer in OLP. The basal cell niche in OLP therefore appeared to be partly populated with keratinocytes demonstrating a higher degree of differentiation (K8⁻ K18⁻ K19⁻ K16⁺); consequently, such areas may be more susceptible to the action of cell death factors released from the cell infiltrate as a result of lacking the protective, normal keratin present in the basal epithelial cell layer of normal oral mucosa.     

基底细胞痣综合征1例报告及文献复习

基底细胞痣综合征属常染色体显性遗传性疾病,系由多发性颌骨角化囊肿、皮肤基底细胞痣(癌)、骨骼系统异常以及各种其他缺陷所组成的一种复杂罕见的综合征,本文报告1例典型病例,对其主要发病机制、临床特点、诊断和治疗等进行回顾分析。     

Gorlin's syndrome. Case report

The authors present a case of Gorlin's Syndrome, more satisfactorily defined as nevoid basal cell carcinoma syndrome (NBCS), a rare genetic disorder characterized mainly by multiple basal cell carcinomas and odontogenic keratocysts and other less frequent skeletal, sexual and neurological manifestations. Patient 75 years old, male. Previously treated surgically for multiple cutaneous basal cell carcinomas, comes to our Department to remove a suspected asymptomatic keratocyst. Clinical examination reveals cutaneous alterations of hands and feet (webbed hands and feet), a little progenism and multiple nevi and basal cell carcinomas on the body and the head. The oral cavity is free of alterations or clinical signs. NBCS is probably caused by chromosomal abnormalities of chromosome 5 and 9. The abnormalities seen in the latter are similar to those seen in people exposed for long periods to UV radiation. These abnormalities could determine malignant cutaneous tumors removing anti neoplastic protection. The association with odontogenic keratocysts, however not clearly understood, appears in more than 90% of cases. All the other disorders are less frequent. Juvenile basal cell carcinomas, especially if associated with odontogenic keratocysts suggest, the hypothesis of NBCS; if confirmed, this diagnosis makes further familial investigations necessary, to diagnose other cases, at the time unknown.     

Langerhans cell histiocytosis: impact on the permanent dentition after an 8-year follow-up

Langerhans cell histiocytosis (LCH) is a rare disorder which mainly affects children. Oral changes, such as gingival ulceration, halitosis, osseous lesions associated with tooth mobility, and early loss of primary teeth, comprise the disease's first manifestations for most patients. In the long term, dental changes may occur as a result of dental and systemic treatment. Therefore, this study's purpose is to report Langerhans cell histiocytosis' effects on the permanent dentition 8 years after diagnosis, which had been established by performing a biopsy of gingival tissue on a 3-year-old patient.     

Oral dysesthesia associated with autistic traits: a retrospective chart review

Oral dysesthesia denotes a condition characterized by abnormal sensations in oral regions without a somatic basis, and is often seen in people with autistic traits, including those with autism spectrum disorder. This study aimed to examine the association between the symptoms of oral dysesthesia and the degree of autistic traits. A retrospective chart review was performed on 44 patients with oral dysesthesia, and associations among the subscales of the Oral Dysesthesia Rating Scale (Oral DRS), Autism Spectrum Quotient (AQ), and Glasgow Sensory Questionnaire (GSQ) were investigated. A Pearson correlation analysis revealed a significant, positive correlation between AQ scores and the A3 (squeezing or pulling) subscale of the Oral DRS (r = 0.37), but there were no significant correlations between the AQ and other subscale scores. There was a significant correlation between the AQ and GSQ score, but no correlation was detected between the GSQ and A3 scores or any other Oral DRS subscale scores. In conclusion, an abnormal squeezing or pulling sensation in oral regions without a somatic basis was associated with autistic traits and could be highlighted as a specific abnormality in sensory processing in autism spectrum disorder.     

Radiological features of familial Gorlin-Goltz syndrome

Gorlin-Goltz syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocystic odontogenic tumors, and skeletal anomalies. This syndrome may be diagnosed early by dentist because keratocystic odontogenic tumors are usually one of the first manifestations of the syndrome. Early diagnosis and treatment are of utmost importance in reducing the severity of long term sequelae of this syndrome. This report presents a rare event of Gorlin-Goltz syndrome occurring in a 39-year-old male and his 8-year-old daughter. The clinical and investigative features of this familial disorder has been described in detail.