Diagnosis Of Nevoid Basal Cell Carcinoma Syndrome Research Articles

SYNCHRONOUS ODONTOGENIC MYXOMA AND ODONTOGENIC KERATOCYSTS IN NEVOID BASAL CELL CARCINOMA SYNDROME: A CASE REPORT

Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. An 11-year-old girl was referred for evaluation due to a lack of eruption of teeth 14 and 15. Her past medical history and physical examination were unremarkable. Imaging exams showed well-defined pericoronal radiolucencies associated with teeth 14 and 37, as well as an additional radiolucent lesion affecting the right mandibular body. Microscopic analyses of both pericoronal lesions proved to be odontogenic keratocysts (OKC). The additional mandibular lesion showed a proliferation of spindle and stellate cells in a predominantly myxoid stroma and numerous concentric basophilic calcifications, consistent with odontogenic myxoma (OM). The patient was referred for genetic counseling and the diagnosis of NBCCS was made. To the best of our knowledge, this represents the second case of synchronous OKC and OM in a patient with NBCCS. Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. An 11-year-old girl was referred for evaluation due to a lack of eruption of teeth 14 and 15. Her past medical history and physical examination were unremarkable. Imaging exams showed well-defined pericoronal radiolucencies associated with teeth 14 and 37, as well as an additional radiolucent lesion affecting the right mandibular body. Microscopic analyses of both pericoronal lesions proved to be odontogenic keratocysts (OKC). The additional mandibular lesion showed a proliferation of spindle and stellate cells in a predominantly myxoid stroma and numerous concentric basophilic calcifications, consistent with odontogenic myxoma (OM). The patient was referred for genetic counseling and the diagnosis of NBCCS was made. To the best of our knowledge, this represents the second case of synchronous OKC and OM in a patient with NBCCS.

MULTIPLE ODONTOGENIC CYSTS ASSOCIATED WITH NEVOID BASAL CELL CARCINOMA SYNDROME

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by wide variety of developmental abnormalities. Common symptoms include multiple basal cell carcinomas, recurrent keratocystic odontogenic tumors (KCOT), pits of the palms and soles, and skeletal malformations. Herein we report a case of NBCCS in a 22-year-old male patient with multiple cysts, 2 of them were diagnosed as odontogenic cysts and the others as KCOT. Clinical examination revealed ocular hypertelorism and facial asymmetry. Imaging tests showed calcifications in the falx cerebri, 3 osteolytic lesions in the anterior mandible region, and 1 in maxillar sinus. Treatment of choice was enucleation and the patient is being monitored. Based on clinical, radiologic, and histopathologic findings, the diagnosis of NBCCS was confirmed. Recurrence of KCOT associated with NBCCS is frequently encountered. This case leads us to believe in the possible association between NBCCS and other cystic lesions, in addition to KCOT.

Abstract 2722: Next generation targeted sequencing reveals four unknown mutations in the Mexican population with Gorlin syndrome

Abstract Aim: Nevoid Basal Cell Carcinoma Syndrome (NBCCS), an autosomal dominant disorder, is characterized by the presence of a variety of developmental anomalies, and predisposition to multiple basal cell carcinomas (BCCs), and other neoplasias. NBCCS mainly results from germinal mutations in the PTCH1 gene, that encodes a transmembrane glycoprotein, component of the hedgehog signalling pathway. The incidence of NBCCS in general population is estimated at 1 in 150000. Data related to NBCCS in Mexican patients is reduced to clinical case reports, without molecular testing. Therefore, we conducted next-generation sequencing (NGS) of PTCH1, in 9 Mexican patients with diagnosis of NBCCS. Material and methods: NGS of PTCH1 was performed, in the context of a hereditary cancer gene panel. The PTCH1 regions with insufficient coverage (<30× read depth), were complemented by Sanger sequencing, to ensure 100% coverage of the gene. In-silico analysis was perfomed for missenses mutations. The identified pathogenic mutations were verified by capillary sequencing. Results: Targeted analysis of PTCH1 gene, looking for deletions, insertions, splice-site alterations, nonsense and missense mutations, was done. Four PTCH1 mutations (4/9) were identified: a deletion (c.1044delG); one insertion (c.631dupA); a non-sense mutation (c.3406G>T), and a missense mutation (c.1488C>A). None of the mutations had been previously reported. Conclusions : NGS of PTCH1 gene in 9 Mexican patients with clinical criteria for NBCCS allowed the identification of four novel pathogenic mutations (44% frequency). This is the first molecular overview of PTCH1 in NBCCS patients of our population. The perspectives of the current study lie in the molecular testing of other genes involved in NBCCS (PTCH2, SUFU), and other mechanisms (whole gene deletion), as well as the review of possible phenotype-genotype correlations. Citation Format: Fragoso Veronica, Natalia Espinosa, Julieta Dominguez, Felipe Vaca-Paniagua, Luis A. Herrera, Rosa M. Alvarez. Next generation targeted sequencing reveals four unknown mutations in the Mexican population with Gorlin syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2722. doi:10.1158/1538-7445.AM2017-2722

Nevoid basal cell carcinoma syndrome with a unilateral giant ovarian fibroma in a Japanese 6-year-old girl

Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by basal cell carcinoma, skeletal abnormalities, benign tumors including ovarian fibroma, and various other phenotypic expressions. Ovarian fibromas in NBCCS before puberty are very rare. We report a 6-year-old prepubescent girl with NBCCS showing skeletal abnormalities, medulloblastoma, and ovarian fibromas. The patient was referred to our hospital owing to abdominal distension. On admission, a huge elastic hard tumor was palpable and computed tomography showed a huge tumor of the left ovary. We performed a left salpingo-oophorectomy and diagnosed the tumor as a benign fibroma. Further examination of the computed tomography images showed skeletal abnormalities. In addition, the patient had a history of medulloblastoma at the age of 4years. Therefore, we diagnosed NBCCS. A genetic examination indicated a novel 1bp deletion in exon 18 (c.3055delG). Sequence analysis of exon 18 using DNA from the ovarian tumor revealed a mutant allele (c.3055delG) dominant to the wild-type allele, thus suggesting loss of heterozygosity in the PTCH1 gene, which is known to be associated with NBCCS. Conclusion On the basis of our experience, physicians treating pediatric ovarian tumors should be aware that such huge benign ovarian tumors may be a phenotype of NBCCS, as shown in our patient. In addition, genetic examination focusing on the PTCH1 gene might be important for diagnosis of NBCCS in pediatric patients.

Nevoid Basal Cell Carcinoma Syndrome

Craniofacial morphology of patients with nevoid basal cell carcinoma syndrome (NBCCS) has sometimes been reported at clinical examination, but any investigation has described it on the basis of cephalometric measurements.The purpose of this study was to conduct a cephalometric analysis of patients with NBCCS and to compare measurements with non-NBCCS subjects of similar ages, to elucidate if there is any relationship between NBCCS and craniofacial morphology.The study population consisted of 14 adult patients (9 men and 5 women), ranging in age from 18.2 to 56.8 years, with the diagnosis of NBCCS, with good-quality lateral cephalometric radiographs, and 14 adult healthy patients matched for age and sex to the NBCCS group. Cephalometric measurements were carried out on radiographs, and measurements of angles and distances were performed.Statistical differences between NBCCS subjects and controls were observed. Data analysis displayed that the measurements of the anterior cranial base (P <or= 0.0043), mandibular length (P <or= 0.0168), and maxillary length (P <or= 0.0284), posterior facial height (P <or= 0.0406), and of mandibular angle (P <or= 0.0026), facial axis angle (P <or= 0.0402), lower facial height angles (P <or= 0.0135), and of interincisal angulation (P <or= 0.0148) were higher in NBCCS subjects in respect to controls. On the contrary, the facial convexity (P <or= 0.0189) and the mandibular arc angle (P <or= 0.0378) were reduced in NBCCS subjects.According to these findings, NBCCS patients presented a sagittal lengthening of the anterior cranial base and maxilla and a vertically and horizontally overdeveloped mandible, together with the features of a long-face syndrome with a large gonial angle.

Multifocal desmoplastic medulloblastoma in an African-American child with nevoid basal cell carcinoma (Gorlin) syndrome

The authors present the case of a 2.5-year-old African-American boy with desmoplastic medulloblastoma (MB) and nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, an autosomal dominant disorder resulting from mutations in the patched (PTCH) gene that predisposes to neoplasias (including basal cell carcinomas [BCCs] and MB) and to widespread congenital malformations. The diagnosis of NBCCS was suspected based on the clinical examination, patient and family medical histories, and histopathological characteristics of the tumor. Radiotherapy was withheld. The diagnosis of NBCCS was confirmed by DNA testing, which revealed a novel mutation in the PTCH gene. This is the first report of an African-American child with MB diagnosed with NBCCS prior to radiotherapy. Although only a small number of patients with MB have NBCCS, the diagnosis must be considered because radiotherapy in such patients can lead to the formation of BCCs and other intracranial neoplasms within the irradiated field. This case emphasizes the importance of obtaining thorough family and patient medical histories and of carefully examining the patient and close relatives for signs of NBCCS to avoid the potentially devastating consequences of missing this diagnosis.

Nevoid Basal Cell Carcinoma Syndrome in infants: improving diagnosis

Diagnosis of Nevoid Basal Cell Carcinoma Syndrome (NBCCS) in infants may pose significant challenges to clinicians owing to its variable expressivity and age-related manifestations. We report two paediatric cases of NBCCS who presented initially with a non-specific phenotype. In case 1, a diagnosis of NBCCS was possible only after the father was interviewed and found to present with two major criteria for the disease. Subsequent molecular testing confirmed the diagnosis. In case 2, molecular testing of the infant and his father had diagnostic value as neither satisfied fully the current diagnostic criteria for NBCCS. Presence of the few clinical manifestations of NBCCS that appear in infants, typically congenital malformations and skeletal abnormalities, should prompt clinicians to conduct in-person interviews with both parents. In general, paediatricians should refer both parents of infants who are suspected of having an inherited condition to clinical geneticists for expert examination, given the potential unreliability of reported medical history.