Medulloblastoma with Extensive Nodularity in a Child with Gorlin Syndrome – Case Report from Regional Cancer Centre

Nevoid Basal Cell Carcinoma Syndrome, also called as Gorlin Gotz syndrome is an autosomal dominant disorder characterized by the presence of multiple odontogenic keratocysts (OKCs) of the jaw, basal cell carcinomas and skeletal anomalies. Presence of multiple OKCs is the first clinical manifestation in majority of the cases. Early diagnosis and treatment are of utmost importance in reducing the severity of this syndrome. We hereby report a rare case of Gorlin Goltz syndrome in a 28 years old female patient who presented with multiple cystic lesions in the jaws. Present case also highlights the clinical, radiographic and histopathologic features of this uncommon syndrome.

Background Nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disorder associated with basal cell carcinomas (BCC), skeletal anomalies, and jaw cysts, and a number of ocular abnormalities. We describe a case of a 12-year-old boy diagnosed with NBCCS found to have several ophthalmic manifestations including a myelinated retinal nerve fiber. We conducted a literature review targeting the ocular and systemic manifestations of NBCCS, with a focus on the ophthalmic findings that have not been well characterized. Materials and Methods We conducted a literature search from 1960 to 2021 utilizing specific keywords and criteria and excluded non-clinical articles. A total of 46 articles were ultimately used for the literature review. Results In NBCCS, BCCs typically present before the age of 30 and gradually become numerous. Certain ocular features, less common in the general population, are much more common with NBCCS. Depending on the study, prevalence of these features in patients with NBCCS ranges from 26–80% for hypertelorism and 7–36% for myelinated retinal nerve fiber layer. Prevalence of nystagmus in patients with NBCCS was found to be approximately 6%. Systemic findings such as bilamellar calcification of the falx cerebri, palmar pits, and odontogenic keratocysts (OKCs) are also prevalent. Conclusion NBCCS may affect numerous organ systems, and thus requires a multidisciplinary team to manage. BCCs and jaw cysts are commonly occurring clinical features that have various surgical excisional options. The ocular anomalies of NBCCS are individually rare, and certain anomalies may present in the amblyogenic period of development and contribute to visual impairment.

We report that patients with nevoid basal cell carcinoma syndrome (Gorlin syndrome) are at risk for developing neoplasms, especially basal cell carcinomas and rarely medulloblastoma. A case report is presented of a 5-year-old child with medulloblastoma and multiple basal cell carcinomas who was diagnosed with nevoid basal cell carcinoma syndrome. Genetic analyses were performed on tumor DNA from the patient's medulloblastoma and basal cell carcinoma as well as germline DNA from the patient and unaffected family members. After radiation therapy for medulloblastoma, the patient developed thousands of additional basal cell carcinomas. Analysis of tumor DNA revealed the characteristic defect of nevoid basal cell carcinoma syndrome, loss of heterozygosity at 9q22. Photodynamic therapy was successfully used to control the majority of her cutaneous tumors. DNA analysis confirmed the presence of the distinctive genetic lesion of nevoid basal cell carcinoma syndrome in both medulloblastoma and basal cell carcinoma. Omitting or limiting radiation therapy for children with nevoid basal cell carcinoma syndrome and medulloblastoma should be considered.

Medical and Pediatric OncologyVolume 40, Issue 4 p. 266-267 Medulloblastoma with extensive nodularity in nevoid basal cell carcinoma syndrome Schahin Aliani MD, Corresponding Author Schahin Aliani MD kisali@med-rz.uni-saarland.de Department of Pediatrics, Faculty of Medicine, Homburg, GermanyUniversitätsklinik für Kinder-und, Jugendmedizin, Kirrbergerstr., 66421 Homburg, Germany.Search for more papers by this authorJuergen Brunner MD, Juergen Brunner MD Department of Pediatrics, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorNorbert Graf MD, Norbert Graf MD Department of Pediatrics, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorKatrin Altmeyer MD, Katrin Altmeyer MD Department of Radiology, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorIsolde Niedermayer MD, Isolde Niedermayer MD Department of Neuropathology, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorMartin Strowitzki MD, Martin Strowitzki MD Department of Neurosurgery, Faculty of Medicine, Homburg, GermanySearch for more papers by this author Schahin Aliani MD, Corresponding Author Schahin Aliani MD kisali@med-rz.uni-saarland.de Department of Pediatrics, Faculty of Medicine, Homburg, GermanyUniversitätsklinik für Kinder-und, Jugendmedizin, Kirrbergerstr., 66421 Homburg, Germany.Search for more papers by this authorJuergen Brunner MD, Juergen Brunner MD Department of Pediatrics, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorNorbert Graf MD, Norbert Graf MD Department of Pediatrics, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorKatrin Altmeyer MD, Katrin Altmeyer MD Department of Radiology, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorIsolde Niedermayer MD, Isolde Niedermayer MD Department of Neuropathology, Faculty of Medicine, Homburg, GermanySearch for more papers by this authorMartin Strowitzki MD, Martin Strowitzki MD Department of Neurosurgery, Faculty of Medicine, Homburg, GermanySearch for more papers by this author First published: 10 February 2003 https://doi.org/10.1002/mpo.10163Citations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume40, Issue4April 2003Pages 266-267 RelatedInformation

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by multisystem anomalies. Although cleft lip and palate (CLP) have been reported in 5% to 8.5% of cases in patients with NBCCS, their pathogenesis and clinical significance remain unclear. The study reports a case of NBCCS with CLP and elucidates its clinical associations and molecular mechanisms through literature reviews. Cases of NBCCS with CLP were searched in PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science databases. Clinical features, genetic data, and phenotypic patterns were retrospectively analyzed. A total of 14 cases were included in this study combined with a 16-year-old female patient we treated, who presented with unilateral CLP and multiple odontogenic keratocysts (OKCs). Among the 15 cases, the male-to-female ratio approaches 1:1. Skeletal anomalies were observed in 86.7% cases, hypertelorism in 53.3%, and nasal deformities in 46.7%. In contrast, classic NBCCS features such as OKCs (53.3%), basal cell carcinomas (BCCs) (20.0%), and palmar/plantar pits (13.3%) were less prevalent compared to classic NBCCS cohorts. All cases met the minor diagnostic criteria for NBCCS, while PTCH1 mutations were detected in 13.3% of patients. This study confirms CLP as an associated symptom of NBCCS and summarizes its molecular mechanisms. The comprehensive analysis of cases suggests that clinicians should consider NBCCS screening in patients with CLP with concomitant skeletal/craniofacial anomalies, even in the absence of typical OKC/BCC phenotypes.

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

The purpose of this report is to document the clinical, radiographic, pathological and molecular findings of the first case of multiple orthokeratinized odontogenic cysts (OOCs). Multiple odontogenic keratocysts are one of the major features of nevoid basal cell carcinoma syndrome (NBCCS), and loss of heterozygosity in the PTCH gene, the culprit gene for NBCCS, has recently been found in sporadic OOC cases. Therefore, in this presenting case, we also investigated the possibility that this patient might also have NBCCS, by comparing the available clinical information and the molecular findings of this case to the diagnostic criteria for NBCCS (as proposed by the First International Colloquium on NBCCS in 2011). However, this patient with multiple OOCs showed no evidence of having NBCCS. This conclusion supports the findings from previous case series based on sporadic cases that OOC does not appear to be associated with NBCCS.

Introduction: Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by developmental malformations and carcinogenic activity. Multi-systemic anomalies may occur in this syndrome, such as odentogenic keratocysts of the mandible and postnatal tumors, especially multiple basal cell carcinoma. Case presentation: A 60 year old man presented with systemic plaques and nodules for more than 30 years. Cutaneous examination revealed that invasive erythema and black papules scattered on the face, trunk and limbs. He underwent extended surgical excision of lesions at multiple sites. No new lesions were found in the treated areas during a 3-year follow-up. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) was given as a palliative treatment for ulcerated tumors on the right lower eyelid and bleeding of the right temporal lesion. After application of ALA-PDT, the ulcers almost healed and the recurring hemorrhage ceased. Discussion: The management of multiple tumors in patients with nevoid basal cell carcinoma syndrome is extremely difficult, especially in the face. Surgical excision is the standard method, but the procedure can be applied in limited sites and may result in significant disfigurement and the difficulty of wound recovery. PDT can play a significant role in combination therapy for tumors that are extremely difficult to remove completely by surgical excision. Conclusion: We present a rare case manifested as multiple basal cell carcinoma and palmar pits who treated by surgery combined with topical 5-aminolevulinic acid-mediated photodynamic therapy. The combined therapy plays a complementary role in the treatment of nevoid basal cell carcinoma syndrome.

We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004. Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages <or=3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages <or=3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001). Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages <or=3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.

Multiple keratocystic odontogenic tumors associated with nevoid basal cell carcinoma syndrome having distinct PTCH1 mutations: a case report

Nevoid basal cell carcinoma syndrome: report of an aggressive case with ethmoid sinus invasion

The relevance of a suppressor of fused (SUFU) mutation in the diagnosis and treatment of Gorlin syndrome

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

IntroductionNevoid basal cell carcinoma syndrome, or Gorlin syndrome, is an inherited disorder characterized by malignancies of the skin and other organs, skeletal abnormalities, and congenital malformations. The syndrome follows an autosomal dominant inheritance pattern with a gene mutation localized to 9q22.3.Case presentationWe present the case of a 22-year-old Caucasian woman with a unilateral ovarian fibroma, falx cerebri calcification and odontogenic keratocysts, but without any skin manifestations. The diagnosis of nevoid basal cell carcinoma syndrome was made after a right salpingo-oophorectomy for a calcified ovarian fibroma with cystic degeneration. Pathologic examination of the 10 cm right ovarian mass revealed a well-circumscribed spindle cell lesion. Immunohistochemical staining of the lesion demonstrated positivity for vimentin and smooth muscle actin.ConclusionIt is important to recognize that nevoid basal cell carcinoma syndrome may present in the absence of skin lesions. Additionally, ovarian fibromas are typically bilateral in nevoid basal cell carcinoma syndrome, but can uncommonly be unilateral, which may alter clinical management. Ovarian fibromas are managed with surgical excision with an attempt at ovarian functional preservation.

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