Mutations of PTCH1 gene in two pedigrees with bifid rib-basal cell nevus-jaw cyst syndrome / 浙江大学学报·医学版

Two male patients with bifid rib-basal cell nevus-jaw cyst syndrome (BCNS) were admitted to Department of Stomatology, the First Affiliated Hospital of Bengbu Medical College due to radiological findings of multiple low density shadows in the jaw. Clinical and imaging findings showed thoracic malformation, calcification of the tentorium cerebellum and falx cerebrum as well as widening of the orbital distance. Whole exon high-throughput sequencing was performed in two patients and their family members. The heterozygous mutations of c.C2541C>A(p.Y847X) and c.C1501C>T(p.Q501X) in PTCH1 gene were detected in both patients. Diagnosis of BCNS was confirmed. The heterozygous mutations of PTCH1 gene locus were also found in the mothers of the two probands. Proband 1 showed clinical manifestations of low intelligence, and heterozygous mutations of c.C2141T(p.P714L) and c.G3343A(p.V1115I) were detected in FANCD2 gene. Proband 2 had normal intelligence and no FANCD2 mutation. The fenestration decompression and curettage of jaw cyst were performed in both patients. Regular follow-up showed good bone growth at the original lesion, and no recurrence has been observed so far.

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)

Detection of SMO gene mutations in odontogenic keratocyst / 中华口腔医学杂志

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247_1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.

A case of nevoid basal cell carcinoma syndrome dominated by facial basal cell carcinoma / 中南大学学报(医学版)

Nevus-like basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the occurrence of multiple maxillofacial keratocysts, basal cell carcinoma, child medulloblastoma, and various skeletal and soft tissue dysplasia. In 2020, a patient with NBCCS dominated by facial basal cell carcinoma was admitted to Xiangya Hospital of Central South University. The patient was an elderly woman. Ten years ago, the systemic mass appeared, especially on the face, but it was not treated. Later, these masses gradually increased in volume and number, and showed invasive properties. The nasal mass was broken and suppurated, seriously affecting the patient's life quality. The patient came to the hospital to improve the symptoms. Staphylococcus aureus and Providencia rettgeri were cultured in the patient's nasal secretions. Nasal sinus enhanced MRI showed that the subcutaneous soft tissue of the right cheek and the anterolateral mucosa of the left nasal cavity were invaded, indicating multiple malignant skin lesions. After admission, local anesthesia was performed and some masses were removed. Pathological examination of the mass showed basal cell carcinoma. After general anesthesia, multiple masses were resected. The postoperative pathological examination showed that multiple basal cell carcinoma invaded the deep dermis near subcutaneous fat layer. Combined with the results of clinical and immunohistochemical examination, the patient was diagnosed as NBCCS. There were no clear tumor thrombus in the vessel and no nerve invasion. No recurrence or new tumor was found after 1 year follow-up. The incidence rate of NBCCS is low and clinical symptoms are different. The patient's life quality is poor and the patient needs long-term individualized treatment.

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.

Basal cell nevus syndrome with Duchenne muscular dystrophy: a case report / 华西口腔医学杂志

Basal cell nevus syndrome (BCNS), also known as Gorlin-Goltz syndrome, is a rare autosomal dominant genetic disease. It is thought to be caused by a mutation in the PTCH1 gene, and its incidence is 1/57 000 to 1/256 000. The case of a 7-year-old patient with BCNS and Duchenne muscular dystrophy was reported in this paper.

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)

Gorlin-Goltz Syndrome: Multiple Basal Cell Carcinoma, Bifid Rib, Palmar and Plantar Pits in a 50-Year-Old Woman

@#<p>A 50-year-old single Filipino woman was referred to our clinic by the Dermatology Department due to multiple large nevi on the face. Her history started 29 years prior to consult when a 0.5 cm by 0.5 cm nevus appeared on her right lower eyelid. Excision of the mass and histopathology revealed basal cell carcinoma of the skin and she ceased followup visits. Meanwhile, progressively enlarging nevi appeared over multiple sites of her face. Some of the lesions developed ulceration and occasionally bled. Finally, she consulted again at our institution due to disfiguring multiple large nevi, and was seen by Dermatology and Ophthalmology services and underwent excision biopsy revealing basal cell carcinoma. She was then referred to us for definitive surgical management</p><p>The patient was a non-smoker, non-alcoholic beverage drinker and work did not undergo any prolonged sun exposure. She recalled that her mother had a similar condition and expired due to complications of the disease</p><p>Physical examination revealed many large nevi over multiple sites of the face, the largest over the left nasolabial area. (Figure 1A) There were hyperpigmented nevi over the central forehead and left infraorbital area, and the patient's left eye was closed due to scarring from the previous excision in the left medial canthal area. (Figure 1B) An ulcerating lesion that occasionally bled, involved multiple subsites of the nose. (Figure 1C)</p><p>Due to the recurrent multiple basal cell carcinoma on the face, we suspected a possible syndromic disease. Complete systemic physical examination revealed multiple nevi over the chest and back as well as plantar and palmar pits. (Figure 2A, B) Chest radiography revealed an incidental finding of a bifid third rib on the left. (Figure 3) With these findings, we diagnosed her condition as Gorlin-Goltz syndrome with multiple basal cell carcinoma on the face.</p><p>Our goal of treatment was complete excision of tumors with preservation of function and cosmesis. Following the National Comprehensive Cancer Network (NCCN) Guidelines1 surgical excision with frozen section for adequate margins was performed. (Figure 4) Reconstruction with multiple skin grafts was performed to cover the defects. However, graft failures were noted over multiple sites two weeks post-operatively. (Figure 5) </p><p>Our patient continued to follow-up for a year but declined any offers of reconstructive surgery. She maintained a good disposition and was satisfied with her appearance despite a less than ideal aesthetic postoperative outcome. (Figure 6)</p><p>DISCUSSION Nevoid Basal Cell Carcinoma or Gorlin-Goltz Syndrome is a rare autosomal dominant syndrome with near complete penetrance and extreme variable expressivity.2,3 This was first described in depth by Doctors Robert Gorlin and Robert Goltz in 1960. Genetic mutation in PTCH1 and SUFU that are related with the Hedgehog signalling pathway were identified in the pathogenesis of this disease.2 GorlinGoltz syndrome commonly presents with dermatologic, odontogenic and neurologic findings and affected patients have developmental anomalies and predisposition to cancer, specifically basal cell carcinoma (BCC). The incidence of Gorlin-Goltz syndrome ranges from 1 in 50,000 to 1 in 560,0004 with only one published case reported in the Philippines.5</p><p>To establish the diagnosis of Gorlin-Goltz syndrome, either one major and two minor criteria or two major criteria must be fulfilled.6,7 Our patient presented with multiple BCC, bifid third left rib and palmar and plantar pits, fulfilling three major criteria.</p><p>Only 67% of patients diagnosed with Gorlin-Goltz syndrome present with basal cell carcinoma with an equal male to female ratio.8 The mean age of BCC presentation in Gorlin-Goltz syndrome is roughly 25 years old and the probability of developing increases with age.9 There are racial differences in the occurrence of BCC; higher in Caucasians than in African-Americans and Asians.6,8 However, BCC in patients diagnosed with Gorlin-Goltz syndrome have the same histology and presentation as sporadic cases.</p><p>Palmar and plantar pits are among the common dermatologic findings in Gorlin-Goltz syndrome. These lesions are found in 45% to 87% of Gorlin-Goltz syndrome and the percentage rises with age.6 The presence of palmar and plantar pits in a child should prompt a complete physical evaluation due to its association with other diseases.</p><p>A bifid or forked rib is a developmental abnormality in which the sternal end is cleaved in two. This may be asymptomatic and is oftentimes an incidental finding, and can be observed as an isolated defect or may be associated with other multisystem malformations. In the general population, it was reported to occur at 3 to 6.3 per 1,000.10 Among the rib anomalies, bifid rib occurs in 28% of cases.11 In GorlinGoltz syndrome, it occurs in 36.4% of cases.12</p><p>Gorlin-Goltz Syndrome has a wide spectrum of presentations varying from livable symptoms until adulthood to detrimental complications even during childhood. Since this is a genetic mutation, there is no cure for disease and treatment is symptomatic. In our case, there is higher chance of recurrence or new lesions that may require multiple surgical procedures in the future. Other lesions associated with this syndrome may still appear and immediate consultation is advised to prevent complications. Genetic counselling is highly advised since it has high inheritance.</p><p>In summary, our experience taught us that a high index of suspicion for syndromic disease and a complete physical examination are especially important in such cases. The diagnosis and management are challenging, and should consider the biopsychosocial context of the patient. As long as full disclosure of the condition is made and all options are clearly communicated, the patient's wishes should be respected.</p><p> </p>

Odontogenic keratocyst

@#A 37-year-old woman consulted for a slow-growing mass of one-year duration on the left side of the mandible with associated tooth mobility. Clinical examination showed buccal expansion along the left hemi-mandible from the mid-body to the molar-ramus region with associated mobility and displacement of the pre-molar and molar teeth. Radiographs showed a well-defined unilocular radiolucency with root resorption of the overlying teeth. Decompression and unroofing of the cystic lesion was performed. Received in the surgical pathology laboratory were several gray-white rubbery to focally gritty tissue fragments with an aggregate diameter of 1 cm. Histopathologic examination shows a fibrocollagenous cyst wall lined by a fairly thin and flat stratified squamous epithelium without rete ridges. (Figure 1) The epithelium is parakeratinized with a wavy, corrugated surface while the basal layer is cuboidal and quite distinct with hyperchromatic nuclei. (Figure 2) Based on these features, we signed the case out as odontogenic keratocyst (OKC). Odontogenic keratocysts are the third most common cysts of the gnathic bones, comprising up to 11% of all odontogenic cysts, and most frequently occurring in the second to third decades of life.1,2 The vast majority of cases occur in the mandible particularly in the posterior segments of the body and the ramus. They typically present as fairly large unilocular radiolucencies with displacement of adjacent or overlying teeth.1 If associated with an impacted tooth the radiograph may mimic that of a dentigerous cyst.2 Microscopically, the parakeratinized epithelium without rete ridges, and with a corrugated luminal surface and a prominent cuboidal basal layer are distinctive features that enable recognition and diagnosis.1,2,3 Occasionally, smaller “satellite” or “daughter” cysts may be seen within the underlying supporting stroma, sometimes budding off from the basal layer. Most are unilocular although multilocular examples are encountered occasionally.1 Secondary inflammation may render these diagnostic features unrecognizable and non-specific.2 Morphologic differential diagnoses include other odontogenic cysts and unicystic ameloblastoma. The corrugated and parakeratinized epithelial surface is sufficiently consistent to allow recognition of an OKC over other odontogenic cysts, while the absence of a stellate reticulum and reverse nuclear polarization will not favor the latter diagnosis.2,3 Odontogenic keratocysts are developmental in origin arising from remnants of the dental lamina. Mutations in the PTCH1 gene have been identified in cases associated with the naevoid basal cell carcinoma syndrome as well as in non-syndromic or sporadic cases.1,3 These genetic alterations were once the basis for proposing a neoplastic nature for OKCs and thus the nomenclature “keratocystic odontogenic tumor” was for a time adopted as the preferred name for the lesion.3,4 Presently, it is felt there is not yet enough evidence to support a neoplastic origin and hence the latest WHO classification reverts back to OKC as the appropriate term.1 Sekhar et al. gives a good review of the evolution of the nomenclature for this lesion.3 Treatments range from conservative enucleation to surgical resection via peripheral osteotomy.5 Reported recurrences vary in the literature ranging from less than 2% of resected cases up to 28% for conservatively managed cases.1,5 These are either ascribed to incomplete removal or to the previously mentioned satellite cysts - the latter being a feature associated with OKCs that are in the setting of the naevoid basal cell carcinoma syndrome.1,2,3 Thus, long term follow-up is recommended.5 Malignant transformation, though reported, is distinctly rare.

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).

Basal cell nevus syndrome in a 56-year old Filipino female: A case report

Introduction@#Basal cell nevus syndrome (BCNS) (Gorlin-Goltz syndrome or Nevoid basal cell carcinoma syndrome) is a rare inherited multisystem and tumor-predisposing disorder caused by the patched tumor suppressor gene mutations and suppressor of fused gene. Its diagnosis follows a set of criteria based on specific cutaneous features and radiologic findings. Although an autosomal dominant disorder with a high degree of penetrance, BCNS has variable expression making its diagnosis difficult. The limited epidemiologic data among Asians especially in the Philippines hamper early detection or cause frequent misdiagnosis of the condition.@*Case report@#A 56-year-old Filipino female with Fitzpatrick skin type V presented with early onset multiple basal cell carcinomas and bilateral palmoplantar pits. Radiologic investigation reveals odontogenic keratocyst, calcification of the falx cerebri, bridging of the sella turcica, bifid/splayed ribs and vertebral anomalies. The patient exhibits coarse facial features and bilateral cataracts. Cranial computed tomography scan shows cerebrocerebellar atrophy with ventricular dilatation. Management included wide excision of the nodular basal cell carcinomas (BCC), application of 5-flourouracil cream on the superficial BCC and electrodessication and curettage of the smaller lesions. Oral acitretin was also prescribed.@*Conclusion@#This is a case that highlights the approach to diagnosis, clinical features and management of BCNS in a Filipino patient. Since various phenotypic presentations may exist among dark-skinned individuals, early diagnosis poses a challenge among physicians. Epidemiologic and prevalence studies among Filipinos may be done to aid in the diagnosis and early management of this rare genodermatosis.

Effect of the sonic hedgehog inhibitor GDC-0449 on an in vitro isogenic cellular model simulating odontogenic keratocysts / 国际口腔科学杂志·英文版

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.

Síndrome de Gorlin Goltz. A propósito de un caso / Gorlin-Goltz Syndrome. Case presentation

RESUMEN Fundamento: El síndrome de Gorlin-Goltz un trastorno hereditario autosómico dominante poco frecuente que se caracteriza por tres anomalías distintivas: predisposición al desarrollo de múltiples neoplasias como el meduloblastoma o el carcinoma basocelular, las depresiones palmoplantares y los quistes odontogénicos de la mandíbula. Objetivo: Describir el caso de una paciente con síndrome de Gorlin-Goltz que representa una situación clínica poco común por su incidencia. Presentación de caso: Paciente femenina de 47 años con síndrome de Gorlin-Goltz que la operaron en varias ocasiones y recibió tratamiento con HeberFERON obteniéndose respuestas completas y parciales al reducir o eliminar el tumor. Conclusiones: El síndrome de Gorlin-Goltz es una enfermedad infrecuente en la práctica médica y no se ha encontrado evidencia suficiente que determine el tratamiento de elección para el manejo del carcinoma basocelular en esta enfermedad, por lo que el HeberFERON puede ser una opción terapéutica en el manejo de estos casos.

ABSTRACT Background: Gorlin-Goltz Syndrome (SGG) is a rare autosomal dominant hereditary disorder characterized by three distinctive abnormalities: predisposition to the development of multiple neoplasms such as medulloblastoma or basal cell carcinoma, palmoplantar depressions and odontogenic jaw drops. Objective: To describe a case with the Gorlin-Goltz syndrome that represents a strange clinical situation for its incidence. Case report: A 47 year-old female patient with a Gorlin syndrome who has been operated on several occasions and received treatment with HeberFeron, obtaining complete and partial responses by reducing or eliminating the tumor. Conclusions: Gorlin-Goltz syndrome is an infrequent disease in medical practice and there is not sufficient evidence to determine the choice treatment for the management of basal cell carcinoma in this disease, so that HeberFERON may be a therapeutic option in the management of these cases.

Hipermelanosis nevoide lineal y espiral: comunicación de un caso en Ecuador / Nevoid linear and spiral hypermelanosis, communication of a case in Ecuador

La hipermelanosis nevoide lineal o espiralada es un trastorno esporádico poco frecuente que es caracterizado por máculas hiperpigmentadas, reticuladas o lineales que siguen las líneas de Blaschko.En este artículo se presenta el caso de una infante de 1 año 6 meses con hipermelanosis nevoide. No hubo antecedentes familiares.Esta entidad no ha sido reportada en Ecuador. Se expone un caso clásico en relación a la literatura y sustentado en el examen histopatológico.

Linear or spiral nevus hypermelanosis is a rare sporadic disorder that is characterized by hyperpigmented, reticulated or linear macules that follow the Blaschko lines.This article presents the case of a 1 year old infant 6 months with nevoid hypermelanosis. There was no family history. This entity has not been reported in Ecuador. A classic case is presented in relation to the literature and supported by histopathological examination.

Novel Patched 1 Mutations in Patients with Gorlin-Goltz Syndrome Strategic Treated by Smoothened Inhibitor

We studied a family with Gorlin-Goltz syndrome. The novel mutations of our cases were located on the 21st exon of the PTCH1 gene (c.3450C>G). The father, who received a strategic 56-day vismodegib treatment for disease control, was the first patient with Gorlin syndrome treated with the hedgehog inhibitor in Taiwan. The lesions regressed gradually, with scar formation, and were subsequently removed via a wide excision. Further details are provided below.

Retrospective clinical study of multiple keratocystic odontogenic tumors in non-syndromic patients

OBJECTIVES: A keratocystic odontogenic tumor (KOT) is a type of odontogenic tumor that mainly occurs in the posterior mandible. Most KOTs appear as solitary lesions; however, they sometimes occur as multiple cysts. This study analyzed the clinical features of multiple KOTs. MATERIALS AND METHODS: The participants were diagnosed with KOT by biopsy with multiple surgical sites, and were patients at the Pusan National University Hospital and the Pusan National University Dental Hospital from January 1, 2005 to March 31, 2016. Charts, records, images and other findings were reviewed. RESULTS: A total of 31 operations were conducted in 17 patients. The mean patient age was 28.4±20.1 years. Multiple KOTs were found to occur at a young age (P<0.01). The predominant sites were in the posterior mandible (28.6%). Most cases of multiple lesions appeared in both the upper and lower jaw, and 40.3% of lesions were associated with unerupted and impacted teeth. The overall recurrence rate measured by operation site was 10.4% (8/77 sites). No patients were associated with nevoid basal cell carcinoma syndrome. CONCLUSION: The pure recurrence rate was lower than estimated, but there was a higher possibility of secondary lesions regardless of the previous operation site; therefore, long-term follow-up is necessary.

Síndrome de carcinoma de células basales nevoides (Síndrome Gorlin): reporte de dos casos y revisión de la literatura / Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature

RESUMEN El síndrome Gorlin (SG) es una condición genética, con patrón de herencia autosómico dominante, con penetrancia completa y expresividad variable, debida a mutaciones germinales en los genes PTCH1 o SUFU, los cuales son componentes de la vía molecular Sonic hedgehog. El SG se caracteriza por la presencia de múltiples carcinomas de células basales nevoides, quistes odontogénicos, calcificación de la hoz del cerebro y lesiones en sacabocado en palmas y plantas. Este es el primer reporte de casos en el Perú sobre pacientes con SG, que cuentan con evaluación y asesoría genética. Presentamos dos casos de SG que cumplen criterios clínicos del síndrome y una revisión de la literatura.

ABSTRACT Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature