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Nevoid basal cell carcinoma syndrome is a rare autosomal dominant disorder characterized by a diverse clinical presentation, which includes developmental abnormalities and tumorigenesis that can impact multiple organ systems. Basal cell carcinoma is the most common and characteristic clinical presentation in patients with NBCCS. There are three identified causative genes for this disease, the PTCH1 gene located at 9q22-31, the PTCH2 gene at 1p32-34, and the SUFU gene at 10q24.32. In this paper, we report a case of multiple nevoid basal cell carcinoma. The mutated gene in this patient was determined to be the ELP1 gene located on chromosome 9. This patient's ELP1 gene mutation may contribute to the development of multiple nevoid basal cell carcinomas on the face. [ABSTRACT FROM AUTHOR]

Abstract 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.

Simple Summary: Gorlin syndrome (GS) is a genetic disorder characterized by multiple basal cell carcinomas (BCCs) due to mutations in the hedgehog signaling pathway. Patients with GS may need dozens or even hundreds of surgical procedures in their lifetime, which can leave them severely scarred, deformed, and disfigured. In 16 patients with GS, we examined the effectiveness, safety, and length of response to oral hedgehog inhibitors. According to our retrospective study, sonidegib inhibited the growth of both newly diagnosed and pre-existing basal cell carcinomas more successfully and safely than vismodegib. Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors—vismodegib and sonidegib—has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Gorlin-Goltz syndrome also known as Nevoid Basal Cell Carcinoma Syndrome is a rare phakomatoses inherited as an autosomal dominant disorder characterized by mutations of PTCH-1 gene along with microdeletion of chromosome 9q. It is manifested by multiple tumours and abnormalities most importantly featured with multiple basal cell carcinoma, Odontogenic Keratocyst (OKC) and other skeletal disorders. Case Report: A 11- year-old girl having facial asymmetry and pain on the right side of the jaw reported to the department. Radiographic examination revealed multiple radiolucencies in the mandible. The biopsy and histopathological examination confirmed the presence of multiple OKC. Further investigations led to the case fulfilling 3 major criteria of multiple OKC, falx and tentorium cerebelli calcifications, palmar and plantar pits which established the diagnosis of Gorlin-Goltz syndrome. Conclusion: Being a condition requiring a multidisciplinary approach, early diagnosis and appropriate prophylactic measures along with proper treatment is essential for a better prognosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gorlin-Goltz syndrome, also known as Gorlin syndrome, basal cell nevus syndrome, and nevoid basal cell carcinoma syndrome, is an autosomal dominant genetic disorder. Its hallmark is an early onset of basal cell carcinoma. Additionally, the syndrome is characterized by a spectrum of distinct clinical attributes encompassing oral, skeletal, ophthalmic, neurological, and developmental aberrations. This condition arises due to anomalies in the Hedgehog signaling pathway, leading to constant pathway activity and uncontrolled growth of tumor cells. Early identification of the disorder through available diagnostic methods and clinical and radiological findings is crucial for accurate diagnosis, which subsequently leads to the formulation of an effective treatment regimen. The purpose of this case report is to discuss the role of a dentist in early detection based on various author-prescribed criteria and the need for a multidisciplinary approach to the treatment of patients with this syndrome. [ABSTRACT FROM AUTHOR]

A patient presenting with several basal cell carcinomas, pigmented nevi, and developmental defects was diagnosed with nevoid basal cell carcinoma syndrome. Gene panel sequencing and Sanger sequencing were used to identify a novel heterozygous frameshift mutation, c.1312dupA:p.Ser438Lysfs, in exon 9 of PTCH1. I-Tasser and PyMol analyses indicated that the mutated protein patched homolog 1 (PTCH1) lacked 12 transmembrane domains and the intracellular and extracellular rings of ECD2 compared with the wild-type protein, resulting in a remarkably different structure from that of the wild-type protein. This case extends our knowledge of the mutation spectrum of NBCCS.

Nevoid basal-cell carcinoma syndrome (Gorlin syndrome) is characterized by numerous cutaneous basal cell carcinomas mediated by mutations in the hedgehog pathway. Vismodegib or sonidegib represent promising treatment options. We identified 10 Gorlin patients who were treated with sonidegib (n = 6) or vismodegib (n = 4) between March 2012 and March 2022. We analyzed the activity, toxicity, and duration of the response to oral hedgehog inhibitors. The number of new tumors that developed prior to treatment or after treatment as well as the time of response and durability of responses were assessed. All patients achieved a complete remission. With a 30.7 ± 48.4-month median follow-up, the drug treatment significantly reduced the number of new basal cell cancers from a mean of 28.3 ± 24.6 prior to treatment to a mean of 1.4 ± 2.0 during treatment (p = 0.0048). The median time to develop a new basal cell cancer was 47.3 months. Three patients eventually developed localized recurrences. After resection, ongoing treatment suppressed the development of additional lesions. One patient developed numerous new drug-resistant basal cell cancers and died of acute leukemia. Six patients required treatment modifications for toxicity. Sustained hedgehog inhibitor treatment can suppress the progression of both new and existing basal cell carcinomas for an extended period. Drug administration schedule adjustments improved tolerance without altering efficacy, potentially contributing to a prolonged response duration.

Nevoid basal-cell carcinoma syndrome (Gorlin syndrome) is characterized by numerous cutaneous basal cell carcinomas mediated by mutations in the hedgehog pathway. Vismodegib or sonidegib represent promising treatment options. We identified 10 Gorlin patients who were treated with sonidegib (n = 6) or vismodegib (n = 4) between March 2012 and March 2022. We analyzed the activity, toxicity, and duration of the response to oral hedgehog inhibitors. The number of new tumors that developed prior to treatment or after treatment as well as the time of response and durability of responses were assessed. All patients achieved a complete remission. With a 30.7 ± 48.4-month median follow-up, the drug treatment significantly reduced the number of new basal cell cancers from a mean of 28.3 ± 24.6 prior to treatment to a mean of 1.4 ± 2.0 during treatment (p = 0.0048). The median time to develop a new basal cell cancer was 47.3 months. Three patients eventually developed localized recurrences. After resection, ongoing treatment suppressed the development of additional lesions. One patient developed numerous new drug-resistant basal cell cancers and died of acute leukemia. Six patients required treatment modifications for toxicity. Sustained hedgehog inhibitor treatment can suppress the progression of both new and existing basal cell carcinomas for an extended period. Drug administration schedule adjustments improved tolerance without altering efficacy, potentially contributing to a prolonged response duration. [ABSTRACT FROM AUTHOR]

Introduction: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition characterized by the development of odontogenic keratocyst (OKC), basal cell carcinomas and palmar–plantar pits among other conditions. Reports about Latin American population are scarce. Objective: To analyze the clinical, radiographic, histopathologic and inherited features of odontogenic keratocyst and palmar pits in three Chilean families with nevoid basal cell carcinoma syndrome. Material and methods: After histopathologic diagnosis of OKC, notified consent was requested and evaluation of the affected patients and their families was done. Results: Two families appeared to have only one affected adolescent, and both of them were considered de novo cases. In the third family, three affected members participated in this study, with an autosomal dominant presentation. All affected patients had OKC and palmar pits. Basal cell carcinomas were present only among adult patients. All examined patients were from Latin American ethnic groups. Conclusions: Patients with NBCCS had single or multiple OKCs that were located more frequently in the mandibular area. One family had autosomal dominant inheritance and the other two families were de novo cases. None of the three teenage patients had basal cell carcinomas. [ABSTRACT FROM AUTHOR]

Introduction: Gorlin- Goltz syndrome is an inherited autosomal dominant disorder. This shows a high level of penetrance and variable expressiveness. Early diagnosis of this syndrome is important for counseling of patients to prevent harmful exposure to Ultra-Violet and ionizing radiations that increase the risk of developing Basal Cell Carcinoma. Presentation of Case: A 18 years old male patient came with chief complaint of swelling in lower front region of jaw. Clinical examination done. Orthopantomograph revealed multiple multi-locular, well-defined radiolucency with sclerotic border located in maxilla and mandible. Relevant investigations were done including chest X-ray, Computed Tomography scan and Histopathological examination revealed presence of Gorlin- goltz syndrome. Discussion: The Gorlin-Goltz syndrome is manifested by multiple defects involving the skin, nervous system, eyes, endocrine system, and bones. The presence of two major and one minor or one major and three minor criteria are necessary to establish diagnosis. The present reported case of Gorlin-Goltz syndrome fulfilled 3 major and 1 minor criteria. Conclusion: In the treatment of recurrent Odontogenic Keratocyst, associated with Gorlin- goltz syndrome, the overlying surface epithelium should be excised along with the cystic lining to prevent recurrence. This paper focus on the importance of oral and maxillofacial health professionals in the early diagnosis of Gorlin-Goltz syndrome and in a multidisciplinary approach to provide a better prognosis to the patient. [ABSTRACT FROM AUTHOR]

Odontogenic keratocysts (OKC) has a high potential for recurrence. Resection is currently the only fool-proof method to ensure that recurrence does not occur; however, it drastically affects the patient's function and aesthetics. Application of modified Carnoy's solution (MCS) as an adjunct to reduce the recurrence rate is currently in vogue. 5- Flurouracil (5-FU) is an anti-metabolite that has been used in the treatment of basal cell carcinoma and is relatively safer than MCS. The present study aims to compare the effectiveness of 5-UC and MCS in reducing the recurrence rate in OKC.. A total of 42 OKCs were enucleated followed by application of MCS (control group, n = 21) or 5-FU dressing (study group, n = 21) following enucleation. Pain, swelling, temporary and permanent paresthesia paresthesia, bone sequestrum formation, osteomyelitis and recurrence in both groups were evaluated at periodic intervals up to 12 months post-surgery. There was no significant difference in terms of pain, or swelling in both groups. Permanent paresthesia and recurrence rates were higher in patients treated with MC but the difference was not statistically significant. 5-FU is an easy-to-use, feasible, biocompatible and cost-effective alternative for MCS in the management of OKCs. Treatment with 5-FU, therefore, reduces the risk of recurrence and also the post-surgical morbidity associated with other treatment procedures. [Display omitted] [ABSTRACT FROM AUTHOR]

Basaloid follicular hamartoma is a rare benign malformation of hair follicles, characterised clinically as generalised or localised multiple brown papules mostly on face, scalp and trunk. It may be congenital or acquired with or without any associated disease. Histologically it is composed of epithelial proliferation of basaloid cells with radial disposition enclosed in a fibrous stroma. It is of important consideration because it can be mistaken for basal cell carcinoma both clinically and histologically. Here we report the case of a 51-year-old female with acquired, generalised basaloid follicular hamartomas associated with alopecia, hypothyroidism and hypohidrosis which is an extremely rare disease. Key Words: Basaloid follicular hamartoma, benign neoplasm, basal cell carcinoma, rare disease, nevoid basal cell carcinoma syndrome.

Abstract Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder with an increased incidence of tumors, such as basal cell carcinomas and medulloblastomas. The PTCH1 gene, responsible for NBCCS, suppresses the hedgehog signaling pathway, which is recognized as one of the important pathways in tumorigenesis and, thus, is a therapeutic target in cancer. In the present study, we generated PTCH1 −/− induced pluripotent stem cells (iPSCs) from NBCCS patient-derived iPSCs (PTCH1 +/−) by gene editing. The proliferation of PTCH1 −/− iPSCs was accelerated due to the activation of the hedgehog signaling pathway. When PTCH1 −/− iPSCs were subcutaneously injected into immunodeficient mice, the resulting teratomas almost exclusively contained immature ectodermal lineage cells expressing medulloblastoma markers, and the percentages of the area occupied by medulloblastoma-like tissue were larger in PTCH1 −/− teratomas than in PTCH1 +/− teratomas. In contrast, in PTCH1 +/+ teratomas, medulloblastoma-like tissue positive for all of these medulloblastoma markers was not observed. The present results indicate the importance of PTCH1 in medulloblastoma formation and the suitability of these gene-edited iPSCs and PTCH1 −/− teratomas as models for the formation of tumors, such as medulloblastomas and Hh-related tumors.

Odontogenic keratocysts (OKCs) are developmental odontogenic cyst of epithelial origin. Multiple OKCs are often associated with a syndrome, especially nevoid basal cell carcinoma syndrome. The present article presents a series of two nonsyndromic cases of multiple OKCs. The presence of multiple OKCs and their recurrence can be attributed to factors such as the friable cystic lining, and daughter cysts. However, a comprehensive evaluation of any patients reporting multiple cysts/OKCs always has to be undertaken and the syndromic association should be ruled out.

Yan Jing Chen,* Qin Yi,* Yi Ming Li, Li Li Department of Dermatology and Venereology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li LiDepartment of Dermatology and Venereology, West China Hospital, Sichuan University, Guoxue Alley No. 37, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel +86 18980601692Email lilihx_scu@scu.edu.cnAbstract: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant-inherited disease characterized by multiple basal cell carcinomas, multiple keratocystic odontogenic tumors, palmar and/or plantar pits. A 50-year-old male patient presented to our hospital with multiple plaques and maculopapular lesions on his face and trunk for more than 20 years. A skin biopsy revealed a number of discrete nests of basaloid cells in the dermis where the peripheral cells are arrayed like a palisade. Multiple odontogenic keratocysts and falx cerebri calcification were found. The diagnosis of NBCCS was made. We treated this patient with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with red light activation, 5% imiquimod cream and surgical excision for the basal cell carcinomas. All the skin lesions on his face improved substantially after eight sessions of red-light ALA-PDT from clinical observation. Red-light ALA-PDT proved to be a good therapeutic method for NBCCS in this case.Keywords: nevoid basal cell carcinoma syndrome, basal cell carcinomas, ALA-PDT, renal cysts

Background: Ovarian sex cord‐stromal tumors (OSCTs) are rare ovarian tumors that can develop from sex cord, stromal cells, or both. OSCTs can be benign or malignant. Bilateral and/or unilateral ovarian fibromas, a type of OSCT of the stromal cells, have been reported in individuals diagnosed with nevoid basal cell carcinoma syndrome (NBCCS). Calcified ovarian fibromas have been reported in 15–25% of individuals diagnosed with NBCCS while 75% of those cases occur bilaterally. The average age at diagnosis of OSCT/ovarian fibromas in patients with NBCSS is in the second to third decade compared with age 50 in the general population. Ovarian tumors are rare in pediatric populations. Methods: The patient is a 5‐year‐old female diagnosed with bilateral ovarian fibromas at age 4. Multigene panel for the patient and subsequent targeted molecular evaluation of parents were completed. Histological evaluations on the surgically resected ovaries were performed for microscopic characterization of fibromas. Results: Germline testing identified de novo heterozygous novel likely pathogenic variants in PTCH1 gene, exon 12 deletion, and an SMARCA4 splicing variant c.2002‐1G > A. Microscopic examination of bilateral tumors was consistent with an ovarian fibroma. Conclusions: To our knowledge, this is the first report of bilateral benign ovarian fibroma in a child with a diagnosis of nevoid basal cell carcinoma syndrome (NBCCS) with a potential predisposition to Rhabdoid Tumor Predisposition Syndrome (RTPS). [ABSTRACT FROM AUTHOR]

Gorlin-Goltz syndrome (GGS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant condition characterized by a predisposition to multiple basal cell carcinomas (BCCs) and other neoplasms and is commonly associated with pathogenic variants in the PTCH1 or SUFU tumor suppressor genes. However, the absence of these genetic markers does not preclude the diagnosis due to the variable genetic expression of the syndrome. Diagnosis relies on a set of established major and minor criteria, particularly when genetic testing fails to identify the typical pathogenic variants. The primary clinical manifestation of GGS is the development of multiple BCCs. While these typically exhibit slow growth and remain localized, they can manifest more aggressive behavior in individuals with GGS, including local invasiveness and metastatic potential. Moreover, patients with GGS display heightened sensitivity to ionizing radiation, leading to general contraindications for radiation therapy (RT) due to the risk of inducing additional BCCs. Despite these concerns, we report a case where RT was the only feasible treatment for an inoperable BCC that had metastasized to the parotid gland in a GGS patient. The successful use of RT, which resulted in a cure without adverse effects, illustrates that RT may be a viable option for some GGS patients, reflecting individual variability in radiation sensitivity. This case underscores the importance of personalized treatment plans in managing the complex presentations of GGS, challenging the traditional constraints regarding the use of RT in these patients and suggesting the potential for its reconsideration under specific circumstances., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Neaga et al.)

Abstract Background Ovarian sex cord‐stromal tumors (OSCTs) are rare ovarian tumors that can develop from sex cord, stromal cells, or both. OSCTs can be benign or malignant. Bilateral and/or unilateral ovarian fibromas, a type of OSCT of the stromal cells, have been reported in individuals diagnosed with nevoid basal cell carcinoma syndrome (NBCCS). Calcified ovarian fibromas have been reported in 15–25% of individuals diagnosed with NBCCS while 75% of those cases occur bilaterally. The average age at diagnosis of OSCT/ovarian fibromas in patients with NBCSS is in the second to third decade compared with age 50 in the general population. Ovarian tumors are rare in pediatric populations. Methods The patient is a 5‐year‐old female diagnosed with bilateral ovarian fibromas at age 4. Multigene panel for the patient and subsequent targeted molecular evaluation of parents were completed. Histological evaluations on the surgically resected ovaries were performed for microscopic characterization of fibromas. Results Germline testing identified de novo heterozygous novel likely pathogenic variants in PTCH1 gene, exon 12 deletion, and an SMARCA4 splicing variant c.2002‐1G > A. Microscopic examination of bilateral tumors was consistent with an ovarian fibroma. Conclusions To our knowledge, this is the first report of bilateral benign ovarian fibroma in a child with a diagnosis of nevoid basal cell carcinoma syndrome (NBCCS) with a potential predisposition to Rhabdoid Tumor Predisposition Syndrome (RTPS).

Objective: This case series reports the clinical presentation and management of multiple odontogenic keratocysts (OKCs) in patients with Gorlin Goltz syndrome and in non-syndromic patients. Material and methods: Eight patients presented with features of multiple odontogenic keratocyst at department of Oral and Maxillofacial Surgery. The diagnosis was confirmed following clinical, radiographic and histopathological examination. Initially the diagnosis of OKC was confirmed on an incisional biopsy. Major and minor criteria were followed for the diagnosis of Gorlin Goltz syndrome. Smaller cysts in all patients were enucleated and for larger cysts marsupialization was planned either alone or followed by enucleation. Patients were followed at 1 month, 3 months, 6 months and yearly interval to check for bone healing and recurrences. Results: Association of Gorlin Goltz syndrome was identified in four patients all of whom were males with age range of 12–37 years. Among four patients that had non-syndromic OKCs, three were female and one was male with age range of 09–50 years; two patients had familial non-syndromic multiple OKCs. In syndromic patients, multiple OKCs, recognized manifestations of Gorlin Goltz syndrome were identified with variable frequency: calcification of falx cerebri and chest deformity (100%); macrocephaly with frontal bossing (100%); hypertelorism (75%); basal cell carcinoma (25%); pectus deformity with flame shaped hands and feet (25%) and syndactyly (50%). Palmar or plantar pits, cleft lip or palate, ovarian fibroma and medulloblastoma was not identified in any patient. In patients with non-syndromic multiple OKCs mandible was more commonly involved than maxilla. Conclusion: Patients with multiple OKCs, should be evaluated thoroughly and basal cell carcinomatous lesions should be ruled out. Meticulous follow up is vital as Gorlin Goltz syndrome is associated with malignancies and OKCs may be the first manifestation of this syndrome. Given the fact that OKCs associated with this syndrome have higher rate of recurrence than the isolated OKCs, long term follow up is warranted.

Antonietta Moramarco,1,* Ludovico Alisi,1,* Alessandro Lambiase,1 Sandra Giustini,2 Luca Lucchino,1 Emanuele Miraglia,2 Vincenzo Roberti,2 Marcella Nebbioso1 1Department of Sense Organs, Faculty of Medicine and Odontology, Sapienza University of Rome, Rome, 00161, Italy; 2Department of Dermatology, Sapienza University of Rome, Rome, 00185, Italy*These authors contributed equally to this workCorrespondence: Alessandro LambiaseDepartment of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161, ItalyTel +39 06 49975357Fax +39 06 49975425Email alessandro.lambiase@uniroma1.itIntroduction: Gorlin-Goltz syndrome (GGS) also known as nevoid basal cell carcinoma syndrome (NBCCS) is a complex rare genetic disorder characterized by a wide range of clinical and radiological manifestations. Ophthalmological alterations have always been reported, but no study on the eventual pattern visual evoked potentials (pVEPs) abnormalities has yet been published.Purpose: The purpose of the study was to evaluate the functionality of the optic pathways in a group of NBCCS patients through pattern reversal VEPs, after a thorough exclusion of subjects with preexisting ocular and optic pathways pathologies.Methods: Nineteen NBCCS patients (31 eyes) and 20 healthy controls (40 eyes) have been recruited for this study. All subjects underwent an evaluation of the functionality of the optic pathways through pVEPs with small (120ʹ), medium (60ʹ), and large (15ʹ) check size stimulation.Results: NBCCS patients showed a statistically significant alteration in the transmission of the macular pathway function when compared to controls. PVEPs analysis confirmed a reduced amplitude and an increased latency of the P100 component, suggesting an involvement of the visual pathway even in the absence of ocular clinical manifestations.Conclusion: Visual pathways may have been affected both by a subclinical myelination deficit, determined directly by the genetic alteration, as well as by neurological abnormalities typical of this syndrome. Further studies are warranted.Keywords: Gorlin-Goltz syndrome, nevoid basal cell carcinoma syndrome, pattern visual evoked potentials, rare diseases, electrophysiology, visual pathway, genodermatosis, PATCH1

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Goltz-Gorlin syndrome, also known as focal dermal hypoplasia or nevoid basal cell carcinoma syndrome, is a rare multisystemic disease caused by autosomal dominant mutations in the PORCN gene. The characterizing features are keratocystic odontogenic tumors in the jaw, multiple basal cell carcinomas, calcification of the falx cerebri, palmar or plantar pits, and skeletal abnormalities. This paper reports the case of a 3-yearold girl with Goltz-Gorlin syndrome, showing progressively increasing tonsillar hypertrophy with obstructive effect on the oropharynx. The lymphatic tissue was remarkably papillomatous in aspect. Pathologic examination after tonsillectomy showed hyperplastic, morphologically normal tonsillar tissue, without arguments for papilloma, active inflammation, or malignancy. This paper highlights the rare manifestations of ENT pathologies in GGS which demand attention early on and long-term follow-up. [ABSTRACT FROM AUTHOR]

John T Lear,1 Axel Hauschild,2 Eggert Stockfleth,3 Nicholas Squittieri,4 Nicole Basset-Seguin,5 Reinhard Dummer6 1Manchester Royal Infirmary, Manchester, UK; 2Klinik Für Dermatologie, Venerologie Und Allergologie Universitätsklinikum Schleswig-Holstein, Kiel, Germany; 3Universitätshautklinik Bochum, Bochum, Germany; 4Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA; 5Department of Dermatology, Hôpital Saint Louis, Paris, France; 6Skin Cancer Center University Hospital, Zürich, SwitzerlandCorrespondence: John T LearUniversity of Manchester, 46 Grafton Street, Manchester M13 9NT, UKTel +44 161 276 4173Fax +44 161 276 8881Email john.lear@srft.nhs.ukNevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome, is a rare hereditary disease characterized by the development of multiple cutaneous basal cell carcinomas (BCCs) from a young age.1 Loss-of-function germline mutations in the hedgehog-related patched 1 (PTCH1) tumor suppressor gene are the most common cause of NBCCS.1 The hedgehog signaling pathway plays a major role in embryonic development, and in adulthood, is involved in the renewal and maintenance of distinct tissues, including hair follicles, muscle stem cells, and gastric epithelium.2 Its abnormal activation is thought to drive the formation of both sporadic BCCs and those resulting from NBCCS.1 Patients with NBCCS inherit one inactive copy of PTCH1 and then acquire a “second-hit” mutation, resulting in hedgehog pathway activation and BCC formation.1 Mutations in Suppressor of fused (SUFU) or the PTCH1 homolog PTCH2 have also been found in a subset of patients meeting criteria for NBCCS.1,3

Basal cell carcinoma is the most commonly occurring cancer worldwide but it is rarely seen in non-sun-exposed areas of the body such as the scrotum.1 Basal cell carcinomas account for 5–10% of all scrotal tumours.2,3 Scrotal basal cell carcinoma is considered more aggressive with higher rates of metastasis versus non-scrotal basal cell carcinoma.1 Gorlin syndrome or nevoid basal cell carcinoma syndrome is an autosomal dominant condition characterised by the development of multiple basal cell carcinomas at a young age.4,5 Prevalence of nevoid basal cell carcinoma syndrome is reported to range from 1 in 57,000 to 1 in 164,000.5 We present the case of a 58-year-old gentleman with a 3-month history of bleeding scrotal and penile lesions. These lesions were excised with 2 cm margins and without complication. Histology showed surface ulceration with basaloid infiltrating tumour extending into the dermis. Given the potential for a very high rate of tumour occurrence within individuals, surgical management of basal cell carcinomas can result in significant, lifestyle-limiting disfigurement.5 As understanding of the pathogenesis of nevoid basal cell carcinoma syndrome has advanced, a number of targeted therapies have been developed.5 Vismodegib targets the Hedgehog signalling pathway and is used in the treatment of locally advanced and metastatic basal cell carcinomas. This represents a rare case of basal cell carcinoma of the scrotum associated with nevoid basal cell carcinoma syndrome caused by a de novo mutation. It is not clear from the literature whether incidence of scrotal tumours is increased in Gorlin syndrome but given the increased risk of basal cell carcinoma elsewhere, it may be prudent for those with known Gorlin syndrome to regularly examine the scrotal skin along with recommended frequent dermatologic surveillance. Level of evidence: 5. [ABSTRACT FROM AUTHOR]

We present the first and rare case report of syndromic multiple odontogenic keratocysts (OKCs) associated with extensive lymphoid proliferation. A 22-year-old male patient presented with radiolucent lesions in bilateral mandible and maxilla. Histopathology of the lesions showed features of multiple odontogenic keratocysts with reactive lymphoid proliferation. Additionally, presence of calcification of falx cerebri, palmar plantar pits and cervical scoliosis in the patient favored the diagnosis of nevoid basal cell carcinoma syndrome or Gorlin Goltz syndrome. Follow up after 2 years did not show any recurrence. Knowledge of this finding is important so that such entities are not confused with associated lymphoid neoplasms. Presence of lymphoid aggregates may be attributed to associated infection or remnants of cystic lining or breakdown products triggering cell mediated immunity leading to lymphoid hyperplasia. [ABSTRACT FROM AUTHOR]

Objectives: To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)–associated and sporadic odontogenic keratocysts (OKCs), in order to identify markers that could accurately distinguish the two OKC subtypes. Materials and methods: We searched MEDLINE/Pubmed, Web of Science, EMBASE via OVID, and grey literature for publications until December 28th, 2019, that compared the immunohistochemical expression of the two OKC subtypes. The studies were qualitatively assessed using the Critical Appraisal Tool for Case Series (Joana Briggs Institute). Sensitivity and specificity, positive and negative likelihood ratio, diagnostic odds ratio and area under the curve, and pooled estimates were calculated, using a random-effects model. Results: Seventy-one studies were qualitatively analyzed; 61 markers were evaluated in one study and 32 in ≥ 2 studies. Twenty-five studies reported differential expression of 29 markers in the form of higher number of positive cells or greater staining intensity usually in BCNS-associated OKCs. Meta-analysis for bcl-2, Cyclin D1, CD56, CK18, p53, and PCNA showed that none of those markers is distinguishable between BCNS-associated and sporadic OKCs, in a 95% confidence interval. The risk of bias was high in 34 studies, moderate in 22, and low in 15. Conclusions: The present systematic review and meta-analysis uncovered that, although several immunohistochemical markers might characterize the OKC phenotype, they cannot discriminate between the BCNS-associated and sporadic OKCs. Clinical relevance: This study highlighted the requirement for additional screening for markers by immunohistochemistry, preferentially coupled to alternative diagnostic applications such as genomics technologies. [ABSTRACT FROM AUTHOR]

Gorlin–Goltz syndrome, is an uncommon genetic condition characterized by the presence of multiple odontogenic keratocysts of jaws along with several other abnormal, cutaneous, ophthalmic, and osseous displays. This syndrome is also acknowledged by various names, such as nevoid basal cell carcinoma syndrome, jaw cyst, and bifid rib syndrome. This article illustrates about the clinical, radiological, and histological diagnostic findings and the multidisciplinary approach of treatment given to one such rare case of Gorlin–Goltz syndrome.

Abstract Background Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients. Results Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients. Conclusions The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients.

Background: Basal cell carcinoma (BCC) is a common malignancy among light-skin races. Chronic solar exposure is the most important precipitating factor. In India, BCC is the second in order among the nonmelanoma skin cancers, the first being squamous cell carcinoma. Actual incidence and prevalence of this tumor in various geographical regions of India remain undefined. Aim: The aim is to study the demographic, clinical, and histopathological parameters of the patients suffering from BCC residing in a rural area of northern Karnataka. Materials and Methods: Retrospective data analysis of the patients suffering from BCC was performed from the records of dermatology outpatients' department of a tertiary healthcare center in north Karnataka. Results: A total of 41 cases of BCC were examined during 12 years. The duration of the lesions varied from 6 months to 20 years. Female patients outnumbered males in a ratio of 3.36:1. Majority of the patients were homemakers and agricultural workers. Nodular, noduloulcerative, and pigmented BCC were the most common clinical pattern and 9 (28.1%) cases of morpheaform BCC were recorded. Four patients had genodermatoses; three were xeroderma pigmentosum and one case of nevoid BCC syndrome. These patients had multiple lesions of BCC. Classical histopathological features were recorded in all cases. One specimen showed evidence of metatypical epithelioma. Conclusion: Most of the patients in this series belonged to the rural part of North Karnataka, predominantly homemakers and agricultural workers. Females were more commonly affected, attributable to the intermittent type of solar exposure. Morpheaform BCC accounted for less than a quarter of cases, and multiple BCCs associated with genodermatoses were seen in four cases.

Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a neurocutaneous disease, characterized by tumorigenesis and developmental anomalies due to aberrant sonic hedgehog (Shh) signaling. Patients with NBCCS typically appear calm and carefree, suggesting that a specific personality in these patients may be associated with an enhanced hedgehog pathway. Our study aimed to determine the personality type in these patients. Methods: We enrolled 14 mentally normal patients with genetically confirmed NBCCS (seven males and seven females; mean age = 25.2 years) and 20 controls (10 males and 10 females; mean age = 27.9 years). The patients were assessed with the Japanese version of the Temperament and Character Inventory, based on the seven‐dimensional model of temperament and character, and their clinical symptoms were evaluated. The amygdala volumes of six patients with NBCCS were measured using magnetic resonance imaging with image‐processing software. Results: Patients with NBCCS scored significantly lower on harm avoidance (0.89) than controls (1.00; P = 0.0084). Moreover, patients with NBCCS and developmental malformations such as rib anomalies, who may have experienced Shh signaling enhancement from the prenatal period, scored significantly lower on harm avoidance (0.80 [P = 0.0031]). The left amygdala volume was also significantly reduced in patients with NBCCS (P = 0.0426). Conclusions: Patients with NBCCS who experienced increased Shh signaling from the prenatal period showed significantly lower harm avoidance related to serotonin. The left amygdala volume was significantly reduced in these patients. Our results indicate that Shh signaling may influence the human personality. [ABSTRACT FROM AUTHOR]

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.2

PurposeNevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, spine and rib anomalies, and falx cerebri calcification. Current diagnostic criteria are suboptimal when applied to pediatric populations, as most common symptoms often do not begin to appear until teenage years.MethodsWe studied minor and major clinical features in 30 children/teenagers and compared the findings with 75 adults from 26 families with nevoid basal cell carcinoma syndrome.ResultsFifty percent of children/teenagers and 82% of adults had at least one basal cell carcinoma. Jaw cysts occurred in 60% of children/teenagers and 81% of adults. Palmar/plantar pits were the most frequent feature seen in affected individuals at all ages. Macrocephaly was seen in 50% of affected and 8% of unaffected children/teenagers. Frontal bossing, hypertelorism, Sprengel deformity, pectus deformity, and cleft lip/palate were seen among affected children/teenagers but not among their unaffected siblings. Falx calcification, the most frequent radiological feature, was present in 37% of individuals 20 years.ConclusionWe report clinical and radiological manifestations of nevoid basal cell carcinoma syndrome in children/teenagers, many of whom lacked major features such as basal cell carcinomas, jaw cysts, and falx calcification. Evaluations for palmar/plantar pits, craniofacial features, and radiological manifestations permit early diagnosis and optimum surveillance.