Nevoid basal cell carcinoma (Gorlin-Goltz) syndrome: an incidental finding.

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome, is a rare condition characterised by skeletal abnormalities, odontogenic keratocysts and basal cell nevi. Diagnosis of this condition is based on major and minor clinical and radiological criteria. Oral medicine and radiology specialists are crucial in diagnosing this condition due to the oral and maxillofacial symptoms. However, conventional radiographs may not provide enough information for an accurate diagnosis, including the two-dimensional imaging modalities. Therefore, the importance of advanced digital imaging for diagnosis is highlighted in this case report of a male patient in his late 20s. The patient had missing teeth and asymptomatic multiple swelling in the orofacial region for 2 months. Routine clinical examination, radiographic investigations and histopathological evaluation led to incidental finding of multiple cystic lesions in the maxillary and mandibular region which on further evaluation led to the final diagnosis of Gorlin-Goltz syndrome.

18F-FDG PET/CT findings in nevoid basal cell carcinoma syndrome: a systematic review and a new case report.

BACKGROUND: To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). CASE PRESENTATION: A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. CONCLUSIONS: It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.

ABSTRACT: Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 ( Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.

Gorlin-Goltz Syndrome - A Rare Case Entity in Young Child.

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, which depicted presence of numerous basal cell carcinoma in conjunction with multiorgan abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the keratocystic odontogenic tumour are usually one of the first manifestations of the syndrome. This article includes a case report of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumour and treatment modalities.

Novel PTCH1 Mutation Causes Gorlin-Goltz Syndrome.

OBJECTIVE: To analyse the aetiology and pathogenesis of Gorlin-Goltz syndrome (GS; also known as nevoid basal cell carcinoma syndrome [NBCCS] or basal cell nevus syndrome [BCNS]) in a Chinese family. METHODS: Whole-exome sequencing (WES) was performed on genomic DNA samples from the subjects in a family, followed by the investigation of pathogenesis via bioinformatic approaches and conformational analysis. RESULTS: A novel heterozygous non-frameshift deletion patched 1 (PTCH1) [NM_000264: c.3512_3526del (p.1171_1176del)] was identified by WES and further validated by Sanger sequencing. Bioinformatic and conformational analysis showed that the mutation caused altered PTCH1 protein structure, which may be related to functional abnormalities. CONCLUSION: This study expands the mutation spectrum of PTCH1 in GS and facilitates the early diagnosis and screening of GS. PTCH1 [c.3512_3526del (p.1171_1176del)] may cause structural abnormalities and functional disabilities, leading to GS in families.

Recurrent central odontogenic fibroma in a patient with nevoid basal cell carcinoma syndrome: case report and in vitro analysis.

OBJECTIVE: Central odontogenic fibromas (COF) are rare, benign tumors derived from dental mesenchymal tissue that may occur in the maxilla or mandible. This report describes primary and recurrent COF in the mandible of a patient with nevoid basal cell carcinoma syndrome (NBCCS). STUDY DESIGN: A 36-year-old African American male presented with a COF and its recurrence 17 months later. Tissue pieces were obtained from both occurrences with IRB-approved signed consent. Collected tissue pieces were dissected; one portion was formalin-fixed and paraffin-embedded, and the other was cultured for the isolation of cell populations from the primary (COdF-1) and recurrent (COdF-1a) tumors. Quantification real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and DNA sequencing were used for gene and protein analysis of the primary tumor and cell populations. RESULTS: Histopathologic analysis of the tumor showed sparse odontogenic epithelial cords in fibrous connective tissue, and qRT-PCR analysis of tumor and cell populations (COdF-1 and COdF-1a) detected VIM, CK14, CD34, CD99 and ALPL mRNA expression. Protein expression was confirmed by immunohistochemistry. CD34 expression in primary tissues was higher than in tumor cells due to tumor vascularization. DNA sequencing indicated the patient had PTCH1 mutations. CONCLUSIONS: Histopathology, mRNA, and protein expression indicate the rare occurrence of COF in a patient with mutated PTCH1 gene and NBCCS.

Gorlin-Like Phenotype in a Young Girl With a De Novo PTCH2 Variant Mutation of Uncertain Significance.

ABSTRACT: Gorlin syndrome, also known as basal cell nevus syndrome, is an autosomal dominant genetic disorder that predisposes humans to tumors. In most cases, this syndrome results from inactivating mutations in the patched homologue 1 gene. Basal cell carcinomas are one of the main characteristics of this syndrome and serve as a major diagnostic criterion. Gorlin syndrome shows a variable phenotype, and recently, other less common mutations in the suppressor of fused homologue or patched homologue 2 genes have been documented in individuals with this syndrome. We present the case of a patient with early-onset basal cell carcinomas and a mild Gorlin syndrome phenotype, attributed to a de novo patched homologue 2 variant of uncertain significance, which has not been previously reported in the literature.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts.

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898-0.973) and prognosis (AUC = 0.840, 95%CI: 0.751-0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Medulloblastoma and other neoplasms in patients with heterozygous germline SUFU variants: A scoping review.

In 2002, heterozygous suppressor of fused variants (SUFU+/-) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline SUFU+/- variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin-Goltz syndrome; OMIM 109400), an autosomal-dominant cancer predisposition syndrome. The phenotype of patients with germline SUFU+/- variants is very poorly characterized due to a paucity of large studies with long-term follow-up. As such, there is a clinical need to better characterize the spectrum of neoplasms among patients with germline SUFU+/- variants so that clinicians can provide accurate counseling and optimize tumor surveillance strategies. The objective of this study is to perform a scoping review to map the evidence on the rate of medulloblastoma and to describe the spectrum of other neoplasms among patients with germline SUFU+/- variants. A review of all published literature in PubMed (MEDLINE), EMBASE, Cochrane, and Web of Science were searched from the beginning of each respective database until October 9, 2021. Studies of pediatric and adult patients with a confirmed germline SUFU+/- variant who were evaluated for the presence of any neoplasm (benign or malignant) were included. There were 176 patients (N = 30 studies) identified with a confirmed germline SUFU+/- variant who met inclusion criteria. Data were extracted from two cohort studies, two case-control studies, 18 case series, and eight case reports. The median age at diagnosis of a germline SUFU+/- variant was 4.5 years where 44.4% identified as female and 13.4% of variants were de novo. There were 34 different neoplasms (benign and malignant) documented among patients with confirmed germline SUFU+/- variants, and the most common were medulloblastoma (N = 59 patients), BCC (N = 21 patients), and meningioma (N = 19 patients). The median age at medulloblastoma diagnosis was 1.42 years (range 0.083-3; interquartile range 1.2). When data were available for these three most frequent neoplasms (N = 95 patients), 31 patients (32.6%) had neither MB, BCC nor meningioma; 51 patients (53.7%) had one of medulloblastoma or BCC or meningioma; eight patients (8.4%) had two of medulloblastoma or BCC or meningioma, and five patients (5.3%) had medulloblastoma and BCC and meningioma. This is the first study to synthesize the data on the frequency and spectrum of neoplasms specifically among patients with a confirmed germline SUFU+/- variant. This scoping review is a necessary step forward in optimizing evidence-based tumor surveillance strategies for medulloblastoma and estimating the risk of other neoplasms that could impact patient outcomes.

Acquisition of Drug Resistance in Basal Cell Nevus Syndrome Tumors through Basal to Squamous Cell Carcinoma Transition.

Although basal cell carcinomas arise from ectopic Hedgehog pathway activation and can be treated with pathway inhibitors, sporadic basal cell carcinomas display high resistance rates, whereas tumors arising in patients with Gorlin syndrome with germline Patched (PTCH1) alterations are uniformly suppressed by inhibitor therapy. In rare cases, patients with Gorlin syndrome on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. In this study, we report a case of an SMO inhibitor-resistant tumor arising in a patient with Gorlin syndrome on suppressive SMO inhibitor for nearly a decade. Using a combination of multiomics and spatial transcriptomics, we define the tumor populations at the cellular and tissue level to conclude that Gorlin tumors can develop resistance to SMO inhibitors through the previously described basal to squamous cell carcinoma transition. Intriguingly, through spatial whole-exome genomic analysis, we nominate PCYT2, ETNK1, and the phosphatidylethanolamine biosynthetic pathway as genetic suppressors of basal to squamous cell carcinoma transition resistance. These observations provide a general framework for studying tumor evolution and provide important clinical insight into mechanisms of resistance to SMO inhibitors for not only Gorlin syndrome but also sporadic basal cell carcinomas.

A Variant of Gorlin-Goltz Syndrome with Synchronous Malignant and Multiple Benign Lesions of the Jaws - A Case Report.

INTRODUCTION: Although numerous syndromic and non-syndromic odontogenic lesions of the jaws have been documented in the literature, there are very few cases of simultaneous benign and malignant jaw lesions. PATIENT CONCERNS: We present a case of right maxillary squamous cell carcinoma along with several benign odontogenic cystic lesions of the jaws and skeletal abnormalities that meet the criteria for Gorlin-Goltz syndrome. TAKEAWAY LESSONS: With a review of the literature, the specifics of management and follow-up are discussed.

Trombose séptica do seio cavernoso associada à infecção odontogênica: relato de caso / Septic Cavernous Sinus Thrombosis Associated to Odontogenic Infection: Case Report / Trombosis séptica del seno cavernoso asociada a infección odontogénica: reporte de un caso

Introdução: A Trombose Séptica do Seio Cavernoso é uma condição rara, de difícil diagnóstico e seu tratamento deve ser incisivo e assertivo. Mais frequentemente a etiologia da trombose é a extensão de processos infecciosos no terço médio da face, como sinusites dos seios paranasais. Objetivo: Esse trabalho tem como objetivo apresentar um relato de caso clínico de um paciente de 26 anos acometido por trombose séptica do seio cavernoso odontogênica. Relato de caso: O paciente foi submetido a duas drenagens cirúrgicas dos sítios infectados, assim como remoção das causas (dois molares superiores), seguidas de antibioticoretapia endovenosa e controles imaginológico e laboratorial. Conclusão: O diagnóstico precoce e etiologicamente correto seguido de um tratamento clínico e cirúrgico emergente e incisivo são fundamentais na resolução favorável da trombose séptica do seio cavernoso e na diminuição de suas sequelas... (AU)

Introduction: Septic Cavernous Sinus Thrombosis is a rare condition, hard to diagnose and its treatment must be incisive and assertive. More often the etiology of thrombosis is the extension of infectious processes in the middle third of the face, such as sinusitis of the paranasal sinuses. Objectives: This paper aims to present a case report of a 26-year-old patient with odontogenic Cavernous Sinus Septic Thrombosis. Case Report: The patient underwent two surgical drainage of the infected sites, as well as removal of the causes (two maxillary molars), followed by intravenous antibiotic therapy and imaging and laboratory controls. Conclusion: Early and etiologically correct diagnosis followed by an emergent and incisive clinical and surgical treatment are fundamental in the favorable resolution of septic cavernous sinus thrombosis and in the reduction of its sequelae... (AU)

Introducción: La Trombosis del Seno Cavernoso Séptico es una condición rara, difícil de diagnosticar y su tratamiento debe ser incisivo y asertivo. Más a menudo, la etiología de la trombosis es la extensión de procesos infecciosos en el tercio medio de la cara, como la sinusitis de los senos paranasales. Objetivos: El presente trabajo tiene como objetivo presentar el reporte de un caso de un paciente de 26 años con Trombosis Séptica del Seno Cavernoso odontogénica. Reporte de caso: El paciente fue sometido a dos drenajes quirúrgicos de los sitios infectados, así como a la extirpación de las causas (dos molares maxilares), seguido de antibioticoterapia endovenosa y controles de imagen y laboratorio. Conclusión: El diagnóstico precoz y etiologicamente correcto seguido de un tratamiento clínico y quirúrgico emergente e incisivo son fundamentales en la resolución favorable de la trombosis del seno cavernoso séptico y en la reducción de sus secuelas... (AU)

Tratamento de ceratocistos na síndrome de Gorlin Goltz / Diagnosis and treatment of oral keratocysts in Gorlin Goltz Syndrome / Tratamento de ceratocistos na Síndrome de Gorlin Goltz

A Síndrome de Gorlin Goltz apresenta características com comprometimento craniofaciais que incluem carcinomas basocelulares, ceratocístos odontogênicos e fenda labial e/ou palatina. Ceratocísticos odontogênico aparecem durante as primeiras décadas de vida, mais comumente na mandíbula, associados a dentes impactados. O diagnóstico precoce possibilita a cura da lesão, minimiza as deformidades ósseas e pode ser concluído com exames como radiográfico e histopatológico. Relato de caso: Com o objetivo descrever o diagnóstico e analisar as possibilidades de tratamento das manifestações faciais da Síndrome de Gorlin Goltz será relatado um caso clínico de uma paciente infantil. A paciente tem um acompanhamento clínico multidisciplinar com geneticista, oncologista e cirurgião-dentista de 6 anos. Apresentou 5 ceratocisticos odontogênicos, carcinomas basocelulares na região do pescoço, calcificação da foice cerebral, ceratose palmo-plantar e macrocefalia. O tratamento para as lesões císticas foi a enucleação, seguida de osteotomia periférica. O defeito ósseo produzido pela enucleação de cisto mandibular foi enxertado com bloco de osso alógeno do banco de tecidos do INTO-RJ. Conclusão: Constata-se que o Cirurgião-dentista é capacitado para fazer o diagnóstico desta síndrome e encaminhar para o tratamento multidisciplinar. O enxerto alógeno é uma opção adequada de reconstrução de cavidades císticas, beneficiando pacientes do Sistema Único de Saúde... (AU)

Gorlin Goltz Syndrome has features with craniofacial involvement that include basal cell carcinomas, odontogenic keratocysts, and cleft lip and/or palate. Odontogenic keratocysts appear during the first decades of life, most commonly in the mandible, associated with impacted teeth. Early diagnosis enables healing of the lesion, minimizes bone deformities and can be completed with exams such as radiographic and histopathological exams. Case report: In order to describe the diagnosis and analyze the treatment possibilities of the facial manifestations of Gorlin Goltz Syndrome, a clinical case of a child patient will be reported.The patient has a multidisciplinary clinical follow-up with a 6-year geneticist, oncologist and dental surgeon. She had 5 odontogenic keratocystic keratocysts, basal cell carcinomas in the neck region, sickle cerebral calcification, palmoplantar keratosis and macrocephaly. The treatment for cystic lesions was enucleation, followed by peripheral osteotomy. The bone defect produced by the enucleation of a mandibular cyst was grafted with an allogeneic bone block from the tissue bank of INTO-RJ. Conclusion: It is concluded that the dentist is trained to make the diagnosis of this syndrome and refer to multidisciplinary treatment. Allogeneic graft is an appropriate option for the reconstruction of cystic cavities, benefiting patients from the Unified Health System... (AU)

El Síndrome de Gorlin Goltz tiene características con compromiso craneofacial que incluyen carcinomas de células basales, queratoquistes odontogénicos y labio leporino o paladar hendido. Los queratoquistes odontogénicos aparecen durante las primeras décadas de vida, más comúnmente en la mandíbula, asociados con dientes retenidos. El diagnóstico precoz permite la curación de la lesión, minimiza las deformidades óseas y se puede concluir con exámenes como exámenes radiográficos e histopatológicos. Reporte de caso: Con el fin de describir el diagnóstico y analizar las posibilidades de tratamiento de las manifestaciones faciales del Síndrome de Gorlin Goltz, se reportará un caso clínico de un paciente infantil. El paciente tiene un seguimiento clínico multidisciplinario con un genetista, oncólogo y cirujano dentista de 6 años. Presentó 5 queratocísticos odontogénicos, carcinomas basocelulares en la región del cuello, calcificación de la hoz cerebral, queratosis palmoplantar y macrocefalia. El tratamiento de las lesiones quísticas fue la enucleación, seguida de una osteotomía periférica. El defecto óseo producido por la enucleación de un quiste mandibular se injertó con un bloque óseo alogénico del banco de tejidos de INTO-RJ. Conclusión: Parece que el odontólogo está capacitado para realizar el diagnóstico de este síndrome y derivar al tratamiento multidisciplinario. El injerto alogénico es una opción adecuada para la reconstrucción de cavidades quísticas, beneficiando a los pacientes del Sistema Único de Salud... (AU)

Queratoquistes odontogénicos maxilares en paciente con síndrome de Gorlin. Descripción de un caso y revisión de la literatura / Maxillary odontogenic keratocysts in a Gorlin síndrome patient: Case report and literatura review

Los queratoquistes maxilares son frecuentes en pacientes con síndrome de Gorlin. Su tratamiento es debatido por su alta tendencia a la recidiva. En los últimos años la cirugía endoscópica nasosinusal ha adquirido importancia en el manejo de esta patología. Exponemos en caso de un varón de 16 años afecto de este síndrome con queratoquistes maxilares donde se realiza un abordaje combinado, endonasal y transoral.

Maxillary keratocysts are frequent in Gorlin Syndrome patients. Its treatment is discussed due to the high tendency to recurrence. In the last years the sinonasal endoscopic surgery has become an important tool in the management of this pathology. We report a 16 years old boy with Gorlin Syndrome and maxillary keratocysts treated with a trans-nasal endoscopic and intra-oral combined approach.

Síndrome de Gorlin-Goltz. Diagnóstico molecular, nuevos tratamientos / Gorlin-Goltz syndrome. Molecular diagnosis, new treatments

Introducción: El síndrome de Gorlin-Goltz o síndrome de carcinoma de nevo basocelular es un desorden hereditario autosómico dominante que predispone principalmente a la proliferación de múltiples carcinomas basocelulares, queratoquistes odontogénicos y defectos del desarrollo, causados por la mutación del gen Patched localizado en el cromosoma 9. Presentación del caso: Se reporta un paciente con características de este síndrome, en la clínica de COMF de la UNAM. El diagnóstico fue basado en los estudios clínicos, imagenológicos y moleculares. Conclusiones: El conocimiento de esta enfermedad puede orientarnos a la sospecha diagnóstica de lesión quística o premaligna en forma oportuna, lo que permite prevenir complicaciones y brindar un tratamiento integral para así mejorar la calidad de vida de este tipo de pacientes (AU)

Introduction: Gorlin-Goltz syndrome or cell-based nevus carcinoma syndrome is an autosomal dominant inherited disorder that predisposes mainly to the proliferation of multiple basal cell carcinomas, maxillary keratocysts and developmental defects, caused by the mutation of the Patched gene located on chromosome 9. Case presentation: A patient with specific characteristics compatible with this syndrome was reported in the COMF Department of the UNAM. The diagnosis was based on clinical studies, radiology and genetic studies. Conclusions: Knowledge of this problem can guide us to the diagnostic suspicion in a timely manner, thus preventing complications, and to provide an improved integral treatment of the quality of life of this type of patients (AU)

Diagnóstico precoce e tratamento da síndrome de Gorlin-Goltz: acompanhamento de oito anos / Diagnóstico precoz y tratamiento del síndrome de Gorlin-Goltz: seguimiento de ocho años / Early diagnosis and treatment of Gorlin-Goltz syndrome: eight-year follow-up

RESUMO Introdução: A síndrome de Gorlin-Goltz, conhecida também como síndrome do Carcinoma Basocelular Nevóide, é um transtorno hereditário autossômico dominante de alta penetrância e expressividade variável. Foi primeiramente descrita por Jarisch em 1894 e, em 1960 Gorlin e Goltz relacionaram o conjunto de doença de casos anteriormente relatados na literatura, concluindo que se tratava de uma síndrome caracterizada por uma tríade (carcinomas basocelulares, queratocistos odontogênicos múltiplos e anomalias esqueléticas). Atualmente, sabe-se que um amplo espectro de outras manifestações sistêmicas pode estar presente como neurológicas, oftálmicas, genitais, cardiovasculares e endócrinas. Objetivo: O presente artigo tem como objetivo relatar um caso clínico de síndrome de Gorlin-Goltz com proservação de oito anos, bem como destacar a importância do Cirurgião-Dentista no diagnóstico precoce e tratamento da síndrome. Caso clínico: Paciente 10 anos, sexo masculino, compareceu em fevereiro de 2004 ao Serviço de Estomatologia e Cirurgia Bucomaxilofacial da Santa Casa de Misericórdia de São Felix, Bahia, Brasil, acompanhado de sua avó, que relatava a seguinte queixa: "Os dentes do meu neto estão tortos". Ao exame físico foi observado aumento do volume do lado direito da face, hipertelorismo, base nasal larga, bossa frontal, leve prognatismo mandibular e dedos dos pés encurtados. Ao exame físico intrabucal foram identificados dentes fora de posição e desvio de linha média. O paciente foi acompanhado por 8 anos e, durante este tempo, foram realizados exames imaginológicos observando grandes áreas de lesões radiolúcidas com recidiva. O diagnóstico conclusivo de Queratocisto Odontogênico foi então comprovado no exame histopatológico, a hipótese diagnóstica de síndrome de Gorlin-Goltz foi então confirmada. O paciente foi encaminhado para avaliação genética e atualmente encontra-se em proservação na Universidade Estadual de Feira de Santana, Bahia. Conclusão: É essencial o acompanhamento multidisciplinar e a longo prazo nos casos dessa síndrome, oferecendo melhor qualidade de vida a esses pacientes(AU)

RESUMEN Introducción: El síndrome de Gorlin-Goltz, conocido también como síndrome del carcinoma basocelular nevoide, es un trastorno hereditario autosómico dominante de alta penetración y expresividad variable. En 1960, Gorlin y Goltz relacionaron el conjunto de enfermedades de casos con anterioridad informados en la literatura, y concluyeron que se trataba de un síndrome caracterizado por una tríada (carcinomas basocelulares, queratocistos odontogénicos múltiples y anomalías esqueléticas). Actualmente, se conoce que un amplio espectro de otras manifestaciones sistémicas puede estar presente, como neurológicas, oftálmicas, genitales, cardiovasculares y endocrinas. Objetivo: describir un caso clínico de síndrome de Gorlin-Goltz con seguimiento de ocho años, así como destacar la importancia del dentista en el diagnóstico precoz y tratamiento del síndrome. Caso clínico: Paciente de 10 años, de sexo masculino, acudió en febrero de 2004 al Servicio de Estomatología y Cirugía Maxilofacial de la Santa Casa de Misericordia de São Félix, Bahia, Brasil, acompañado de su abuela, que refería: "Los dientes de mi nieto están torcidos". En el examen físico se observó aumento del volumen del lado derecho de la cara, hipertelorismo, base nasal ancha, bóveda frontal, leve prognatismo mandibular y dedos de los pies acortados. En el examen físico intrabucal se identificaron dientes fuera de posición y desviación de línea media. El paciente tuvo seguimiento por ocho años y durante este tiempo se realizaron exámenes imaginológicos en los que se observaron grandes áreas de lesiones radiolúcidas con recidiva. El diagnóstico conclusivo de queratocisto odontogénico fue comprobado en el examen histopatológico; la hipótesis diagnóstica del síndrome de Gorlin-Goltz fue entonces confirmada. El paciente fue dirigido para evaluación genética y actualmente se encuentra en seguimiento en la Universidad Estadual de Feira de Santana, Bahia. Conclusiones: Es esencial el seguimiento multidisciplinario y a largo plazo en los casos de este síndrome, a fin de ofrecer mejor calidad de vida a esos pacientes(AU)

ABSTRACT Introduction: Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant inherited disorder of high level penetrance and variable expressiveness. In 1960 Gorlin and Goltz listed the disease cases previously reported in the literature, concluding that it was a triad syndrome (basal cell carcinomas, multiple odontogenic keratocysts and skeletal anomalies). It is now known that a broad spectrum of other systemic manifestations may be present, such as neurological, ophthalmic, genital, cardiovascular and endocrine. Objective: Describe a clinical case of Gorlin-Goltz syndrome and its eight-year follow-up, and highlight the importance of the dentist in the early diagnosis and treatment of the syndrome. Case report: A 10-year-old male patient attended the Oral and Maxillofacial Surgery Service of Santa Casa de Misericordia Hospital in Sao Felix, Bahia, Brazil, in February 2004, accompanied by his grandmother, who reported that her grandson's teeth "were crooked". Physical examination revealed an increase in the volume of the right side of the face, hypertelorism, broad nasal base, frontal bossing, mild mandibular prognathism and shortened toes, whereas oral examination found ill-positioned teeth and midline deviation. The patient was followed up for eight years, and during this time imaging tests were performed which showed large areas of recurrent radiolucent lesions. Diagnosis of odontogenic keratocyst was verified by histopathological examination, confirming the diagnostic hypothesis of Gorlin-Goltz syndrome. The patient was referred for genetic evaluation and is currently being followed up at the State University of Feira de Santana, Bahia. Conclusions: Multidisciplinary long-term follow-up is essential in cases of this syndrome to improve the quality of life of patients(AU)

Análise da imunoexpressão de proteínas de reparo do DNA envolvidas nas vias BER e NER em lesões odontogênicas epiteliais benignas / Immunoexpression analysis of DNA repair proteins involved in BER and NER pathways in benign epithelial odontogenic lesions

As lesões odontogênicas epiteliais benignas apresentam comportamento biológico heterogêneo e patogênese ainda não totalmente esclarecida. As vias de reparo do ácido desoxirribonucleico (DNA) atuam em tipos específicos de danos ao material genético, realizando o reparo e regulando diversos processos celulares. Dentre as principais vias de reparo do DNA, destacamse o reparo por excisão de bases (BER) e o reparo por excisão de nucleotídeos (NER). Investigações têm demonstrado que as proteínas envolvidas nessas vias se encontram desreguladas e, por vezes, altamente expressas em algumas neoplasias malignas, contribuindo para a progressão tumoral. Levando em consideração a heterogeneidade do comportamento biológico das lesões odontogênicas epiteliais benignas e a escassez de estudos que tenham avaliado a expressão de proteínas de reparo do DNA nestas lesões, este trabalho avaliou a imunoexpressão de proteínas da via BER (APE-1 e XRCC-1) e NER (XPF) em ameloblastomas (AMEs) sólidos (n = 30), ceratocistos odontogênicos não sindrômicos (CONS) (n = 30), ceratocistos odontogênicos sindrômicos (COS) (associados à Síndrome de Gorlin) (n = 29), cistos dentígeros (CDs) (n = 30) e folículos dentários (FDs) (n = 20). A análise da expressão imunoistoquímica de APE-1, XRCC-1 e XPF foi realizada de forma quantitativa por um avaliador previamente calibrado e sem acesso aos dados clínicos dos casos. Em cinco campos de maior imunorreatividade, foram quantificadas as células positivas e negativas para as proteínas no componente epitelial de todos os casos, sendo estabelecido o percentual de células positivas em relação ao número total de células contadas para cada anticorpo. As marcações nucleares e citoplasmáticas foram analisadas separadamente para APE-1 e XPF, enquanto apenas a imunoexpressão nuclear foi considerada para XRCC-1. As comparações das medianas dos percentuais de imunorreatividade em relação aos grupos estudados foram realizadas por meio dos testes não paramétricos de Kruskal-Wallis e Mann-Whitney. Possíveis correlações entre a expressão de APE-1, XRCC-1 e XPF foram avaliadas por meio do teste de correlação de Spearman. O nível de significância foi estabelecido em 5% (p < 0,05). Foi verificada uma maior imunoexpressão nuclear de APE-1 nos CONSs, COSs e AMEs sólidos, em comparação com os CDs (p < 0,001). Dentre todos os grupos avaliados, a expressão citoplasmática de APE1 só foi encontrada em 4 CONSs e 6 COSs. A expressão nuclear de XRCC-1 foi estatisticamente maior nos CONSs e COSs em relação aos CDs (p < 0,05). Em nível nuclear, a expressão de XPF foi significativamente maior nos CONSs e COSs em relação aos CDs e AMEs (p < 0,05) e, embora sem significância estatística, foi observada uma maior expressão nuclear dessa proteína nos AMEs quando comparado aos CDs. Em relação à expressão citoplasmática de XPF, foi observada uma maior expressão nos COSs em relação aos CDs (p = 0,04). Nenhuma diferença estatisticamente significativa foi encontrada entre as expressões nucleares de APE-1, XRCC-1 e XPF entre CONSs e COSs (p > 0,05). Além disso, todas as lesões odontogênicas estudadas revelaram uma maior expressão estatisticamente significativa de APE-1 (nuclear), XRCC-1 (nuclear) e XPF (nuclear e citoplasmática) quando comparados aos FDs (p < 0,05). Para todas as lesões, o teste de correlação de Spearman mostrou uma correlação positiva entre a expressão nuclear de APE-1 e XRCC-1 ou XPF, em nível nuclear (p < 0,05). Os resultados deste estudo sugerem um potencial envolvimento das proteínas APE-1, XRCC-1 e XPF na patogênese das lesões odontogênicas epiteliais benignas, com destaque para aquelas com comportamento biológico mais agressivo (AU).

The benign epithelial odontogenic lesions present a heterogeneous biological behavior and their pathogenesis are not fully understood. The deoxyribonucleic acid (DNA) repair pathways act on specific types of damage to the genetic material, performing the repair and regulating several cellular processes. Among the main DNA repair pathways, the most notable are the base excision repair (BER) and the nucleotide excision repair (NER). Investigations have shown that the proteins involved in these pathways are deregulated and sometimes highly expressed in some malignancies, contributing to tumor progression. Taking into account the heterogeneity of the biological behavior of benign epithelial odontogenic lesions and the scarcity of studies that have evaluated the expression of DNA repair proteins in these lesions, this study evaluated the immunoexpression of BER (APE-1 and XRCC-1) proteins and NER (XPF) in solid ameloblastomas (AMEs) (n = 30), non-syndromic odontogenic keratocysts (NSOKCs) (n = 30), syndromic odontogenic keratocysts (SKOCs) (associated with Gorlin's Syndrome) (n = 29), dentigerous cysts (DCs) (n = 30) and dental follicles (DFs) (n = 20). The immunohistochemical analysis of APE-1, XRCC-1 and XPF was performed quantitatively by a previously calibrated evaluator and without access to the clinical data of the cases. In five fields of higher immunoreactivity, positive and negative cells were quantified for the proteins in the epithelial component of all cases, and the percentage of positive cells was established in relation to the total number of cells counted for each antibody. Nuclear and cytoplasmic markers were analyzed separately for APE-1 and XPF, while only nuclear immunoexpression was considered for XRCC-1. The comparisons of the median percentages of immunoreactivity in relation to the studied groups were performed using the non-parametric Kruskal-Wallis and MannWhitney tests. Possible correlations between the expression of APE-1, XRCC-1 and XPF were assessed by Spearman's correlation test. The level of significance was set at 5% (p < 0.05). A higher nuclear immunoexpression of APE-1 in the NSOKCs, SOKCs and solid AMEs was verified in comparison with the DCs (p < 0.001). Among all the evaluated groups, the cytoplasmic expression of APE-1 was only found in 4 NSOKCs and 6 SOKCs. Nuclear expression of XRCC-1 was statistically higher in NSOKCs and SOKCs than in DCs (p < 0.05). At the nuclear level, XPF expression was significantly higher in NSOKCs and SOKCs than in DCs and AMEs (p < 0.05) and, although without statistical significance, a higher nuclear expression of this protein was observed in AMEs when compared to CDs. Regarding the cytoplasmic expression of XPF, a greater expression was observed in the SOKCs in relation to the DCs (p = 0.04). No statistically significant difference was found between the nuclear expressions of APE-1, XRCC-1 and XPF between NSOKCs and SOKCs (p > 0.05). In addition, all the odontogenic lesions studied revealed a statistically significant expression of APE-1 (nuclear), XRCC-1 (nuclear) and XPF (nuclear and cytoplasmic) when compared to DFs (p < 0.05). For all lesions, Spearman's correlation test showed a positive correlation between nuclear expression of APE-1 and XRCC-1 or XPF at the nuclear level (p < 0.05). The results of this study suggest a potential involvement of APE-1, XRCC-1 and XPF proteins in the pathogenesis of benign epithelial odontogenic lesions. The role played by these proteins may be more important in odontogenic lesions with more aggressive biological behavior (AU).