Nevoid Basal Cell Carcinoma Research Articles

Nevoid basal cell carcinoma syndrome: a rare case report

Nevoid basal cell carcinoma syndrome: a rare case report

Re-evaluation of the concept of basaloid follicular hamartoma associated with naevoid basal cell carcinoma syndrome: a morphological, immunohistochemical and molecular study

Naevoid basal cell carcinoma syndrome (NBCCS) is a rare genodermatosis caused by germline mutations in genes of the Sonic Hedgehog pathway (SHH) and is characterised by early onset of multiple basal cell carcinomas (BCCs). Although skin tumours with follicular differentiation, notably basaloid follicular hamartoma (BFH), have been reported in NBCCS, their relations with BCC are poorly defined. In this context, the aim of this study was to clarify morphological, immunohistochemical ​and molecular features of BFH arising in a context of NBCCS.A total of 140 skin tumours from NBCCS and 140 control BCC tumours were reviewed, blinded to clinical data and classified as BCC or BFH. The morphological characteristics of these two groups were then compared. Twenty cases were submitted for immunohistochemical and molecular analysis. Thirty-three tumours among the exploratory cohort were classified as BFH and were exclusively detected in NBCCS patients. Histopathological criteria that were significantly different from BCC were as follows: a small size (<1.5 mm), connection to a hair follicle, arborescent organoid architecture, lack of cytologic atypia and infundibulocystic differentiation. Immunohistochemical analysis confirmed activation of the SHH pathway in these lesions. Targeted next-generation sequencing suggested that MYCN and GLI2/3 amplifications and TP53 mutations might be involved in progression of these follicular tumours to BCC.Our study confirms the high prevalence of BFH representing up to 24% of skin tumours in NBCCS and potentially being BCC precursors.

Reticulate acropigmentation of Kitamura in a case of Gorlin-Goltz syndrome − coincidence or association?

Gorlin-Goltz syndrome also known as nevoid basal cell carcinoma syndrome (NBCCS) is a rare, complex hereditary disorder characterized by phenotypic developmental anomalies and postnatal tumors especially basal cell carcinomas (BCCs) and medulloblastomas. It is inherited as autosomal dominant disorder with inactivating mutation in PTCH 1 gene. Reticulate acropigmentation of Kitamura, a rare pigmented genodermatosis has not been described in the literature in association with NBCCS and may be a new finding. Considering the rarity of the disease and its wide clinical spectrum and complications, it is of paramount importance to identity these atypical presentations of the syndrome at an early stage for holistic approach, early intervention, monitoring of basal cell carcinoma, and genetic counselling.

Navigating the maze: A comprehensive journey in the management of odontogenic Keratocyst

This case report describes the intricate management of an odontogenic keratocyst (OKC) associated with a mandibular tooth. Formerly known as keratocystic odontogenic tumor, OKC is a benign intraosseous lesion with diverse manifestations that occurs either as a solitary entity or as multiple lesions within the same individual. Often linked to nevoid basal cell carcinoma syndrome (NBCCS), OKC presents a unique challenge requiring meticulous diagnosis and treatment. In this case, a 71-year-old male with significant mandibular swelling sought treatment after a failed endodontic procedure. Detailed clinical and radiographic evaluations revealed an extensive radiolucent lesion affecting teeth 45 to 36. The treatment involved a multidisciplinary approach, including endodontic therapy and surgical enucleation with bone curettage. The patient exhibited successful healing and bone formation during a one-year follow-up, emphasizing the significance of comprehensive management strategies for OKCs. This case underscores the importance of early diagnosis, collaboration between specialties, and long-term follow-up in ensuring optimal outcomes for patients with OKCs associated with mandibular teeth.

Gorlin Syndrome-Associated Basal Cell Carcinomas Treated with Vismodegib or Sonidegib: A Retrospective Study.

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.

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

BackgroundTo demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS).Case presentationA 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.ConclusionsIt is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

Update on Cancer Predisposition Syndromes and Surveillance Guidelines for Childhood Brain Tumors.

Tumors of the central nervous system (CNS) comprise the second most common group of neoplasms in childhood. The incidence of germline predisposition among children with brain tumors continues to grow as our knowledge on disease etiology increases. Some children with brain tumors may present with nonmalignant phenotypic features of specific syndromes (e.g., nevoid basal cell carcinoma syndrome, neurofibromatosis type 1 and type 2, DICER1 syndrome, and constitutional mismatch-repair deficiency), while others may present with a strong family history of cancer (e.g., Li-Fraumeni syndrome) or with a rare tumor commonly found in the context of germline predisposition (e.g., rhabdoid tumor predisposition syndrome). Approximately 50% of patients with a brain tumor may be the first in a family identified to have a predisposition. The past decade has witnessed a rapid expansion in our molecular understanding of CNS tumors. A significant proportion of CNS tumors are now well characterized and known to harbor specific genetic changes that can be found in the germline. Additional novel predisposition syndromes are also being described. Identification of these germline syndromes in individual patients has not only enabled cascade testing of family members and early tumor surveillance but also increasingly affected cancer management in those patients. Therefore, the AACR Cancer Predisposition Working Group chose to highlight these advances in CNS tumor predisposition and summarize and/or generate surveillance recommendations for established and more recently emerging pediatric brain tumor predisposition syndromes.

Novel PTCH1 Mutation Causes Gorlin-Goltz Syndrome.

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. 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. 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. 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.

Imaging approaches for the diagnosis of genetic diseases affecting the female reproductive organs and beyond.

This review aims to provide an overview of neoplastic lesions associated with genetic diseases affecting the female reproductive organs. It seeks to enhance our understanding of the radiological aspects in diagnosing genetic diseases including hereditary breast and ovarian cancer syndromes, Lynch syndrome, Peutz-Jeghers syndrome, nevoid basal cell carcinoma syndrome, and Swyer syndrome, and explores the patterns and mechanisms of inheritance that require elucidation. Additionally, we discuss the imaging characteristics of lesions occurring in other regions due to the same genetic diseases.

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

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

Surgical Treatment of Multiple Bone Cysts Using a Platelet-Rich Fibrin and BoneAlbumin Composite Graft: A Case Report

Promising research results have been obtained on the tissue-regeneration properties of PRF (platelet-rich fibrin) in dentistry and maxillofacial surgery. PRF presumably promotes healing and accelerates ossification. In this case report, the patient had a history of Gorlin–Goltz syndrome, also called nevoid basal cell carcinoma syndrome, an autosomal dominant neurocutaneous disease that was known for many years. As a consequence, cysts were detected in both the mandible and maxilla. We performed decompression on this 37-year-old patient, followed by a cystectomy on an extensive lesion in the right angle of the mandible. One cyst from each side of the body mandible and one from the maxilla were completely enucleated, as determined using an intraoral exploration. The resulting bone defect was filled with a composite graft composed of a mixture of A-PRF and a serum albumin-coated bone allograft (BoneAlbumin). The wound was then covered with a PRF membrane. The surgical sites were closed per primam. The postoperative period was uneventful. Biopsies were performed after three and six months of healing for histological micromorphometry analyses. Dental implants were placed at the sampling site. Three months after the implantation, the ossified implants were fitted with superstructures. To date, no complications have appeared with the bone augmentation. The authors interpret from the findings that the combination of A-PRF and BoneAlbumin can be validated as a prosperous bone substitute. It can be safely implanted after a 3-month ossification period.

Further Expanding the Mutational Spectrum of Gorlin Syndrome in Three Unrelated Families

Introduction: Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in PTCH1 are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in PTCH1 cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis. Methods: Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families. Results: In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift PTCH1 variant in family 1, a nonsense previously reported PTCH1 variant in family 2, and a novel heterozygous splice-site PTCH1 variant in family 3 were detected. Conclusion: Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.

Odontogenic keratocysts: A retrospective histopathological study.

Odontogenic keratocyst (OKC) is an aggressive recurrent cyst with intriguing features. Various factors such as the surgical procedure are involved, and certain histological features contribute to its recurrence. We assessed the clinical, radiographic, and histopathological data of OKCs to better comprehend the true nature of this cyst. A total of 58 lesions including four cases in association with nevoid basal cell carcinoma syndrome (NBCCS) were assessed. Radiographic features and histopathological features within the epithelium and capsule were assessed. 72% of cases were seen in males and 28% in females. 43% of cases were seen in the mandibular ramus, and 65% exhibited unilocular radiolucency. 95% showed true parakeratinization. Cuboidal basal cell morphology was seen in 41.3% of cases and reversal of polarity in 60%. Basal budding, rete pegs, and mitosis were also observed within the epithelium. The epithelium showed separation at the subbasal level and suprabasal levels in 55 (94.9%) cases. Features such as basal cell budding, suprabasal mitotic activity, suprabasal split, localized inflammation, subepithelial hyalinization, and satellite cysts were commonly associated with recurrent cysts. Many newer genetic and molecular hypotheses have generated path-breaking contributions to the understanding of the biology of OKC. With the guidance and help of such factors, improved post-surgery results can be anticipated.

Major Manifestations of Gorlin Syndrome in a Patient With Hemophilia A

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominantly inherited condition in which constitutive pathway activity and tumor cell proliferation are disturbed due to defects in hedgehog signaling. This study reports an adult case of hemophilia A suspected of having Gorlin syndrome. There is no similar evidence in the literature to describe the association between these disorders. NBCCS is characterized by the development of multiple basal cell carcinomas (BCCs). The case presented in this study had two major manifestations of NBCCS, including the calcification of the falx cerebri and the presence of keratocystic odontogenic tumors (KOTs); however, no minor manifestations of NBCCS were found in this case. On the other hand, given the financial restrictions, it was impossible to perform a genetic examination to confirm the presence of NBCCS.

Multiple-lesion, non-familial basal cell carcinoma-An interesting oddity

Basal cell carcinoma (BCC) is the most common primary carcinoma of skin, which accounts for three-fourth of all primary skin tumours. Basal carcinoma occurs commonly as a single lesion, though occasionally it can occur as Multiple lesions, which may occur in close association with heredofamilial conditions such as nevoid basal cell carcinoma syndrome (Gorlin’s syndrome), Bazex syndrome, Rombo syndrome, and unilateral basal cell nevus syndrome. The case of multiple basal cell carcinomas being presented here is unique in its occurrence inasmuch as it is not associated with heredofamilial conditions, and despite not being associated with heredofamilial conditions there is occurrence of multiple basal carcinomas in a patient in a tertiary care hospital in a dominantly tribal region. The patient has no family history of genodermatosis that could increase the incidence of multiple basal cell carcinomas such as xeroderma pigmentosum, and no history of other predisposing conditions including actinic keratosis, Bowen’s Disease, leukoplakia, Erythroplasia of Queyrat, keratoacanthoma, radiation dermatitis and exposure to arsenicals, psoralen and other photosensitizing medications. However, the patient had history of having raised macules over the face which were diagnosed as seborrheic keratosis.

Nevoid Basal Cell Carcinoma Syndrome on Scalp: A Rare Case Report

Nevoid basal cell carcinoma syndrome is a rare disease that can be accompanied by various clinical symptoms in addition to basal cell carcinoma. Cancers usually occur at an earlier age or later in multiple areas. According to a recent study, genetic mutations are highly suspected as the cause of the syndrome. Since this gene mutation is inherited as an autosomal dominant, it must be accompanied by a screening test for the patient's family along with the patient's treatment. In this study, we was experienced a patient diagnosed with nevoid basal cell carcinoma syndrome after genetic mutation was confirmed, so it is reported along with a review of the literature.

Exploring the Changing Diagnostic Criteria of Gorlin-Goltz Syndrome: A Case Report

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.

Gorlin-Goltz syndrome: an uncommon case

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin-Goltz syndrome), is a rare autosomal dominant inherited disorder which is characterized by multiple basal cell carcinomas from a young age. Other distinguishing clinical features that are seen in a majority of patients, includes keratocystic odontogenic tumors (formerly odontogenic keratocysts) and dyskeratotic palmar and plantar pitting. Estimated prevalence is 1 in 57,000 to 1 in 164,000. We report a case of this syndrome seen in a 43-year-old female patient with multiple black pigmented papules and plaques on face and trunk that first appeared when she was teenager. Her clinical features of were fitting within the criteria for the diagnosis of BCNS. Early diagnosis and treatment of this syndrome is important to reduce severity of complications including cutaneous and cerebral malignancy and oromaxillofacial deformation and destruction due to jaw cysts.

Sustained Suppression of Gorlin Syndrome-Associated Basal Cell Carcinomas with Vismodegib or Sonidegib: A Case Series.

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.

Gorlin-Goltz Syndrome: A Comprehensive Analysis of the Clinical, Genetic and Therapeutic Manifestations of a Rare and Complex Disease

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare and heterogeneous genetic disease with a varied clinical presentation involving multiple systems and organs. This comprehensive review aims to provide an in-depth understanding of this syndrome from a medical and scientific perspective. Gorlin-Goltz syndrome is characterized by an inherited predisposition to the formation of skin and skeletal tumors, as well as the development of jaw cysts, cleft palates, facial deformities, ocular malformations and other anomalies. At the genetic level, this syndrome is linked to mutations in the PTCH1 gene, which regulates the hedgehog signaling pathway, playing a crucial role in the regulation of cell growth and differentiation. Early and accurate diagnosis of Gorlin-Goltz syndrome is essential to prevent serious complications, such as advanced basal cell carcinomas and facial disfigurement. Molecular diagnostic strategies and therapeutic options, including reconstructive surgery, hedgehog pathway inhibitor therapy, and multidisciplinary patient management will be addressed. This review will also explore the psychological and social impact on patients and their families, as well as advances in genetic and therapeutic research that may open new perspectives for the management and prevention of this complex disease. Ultimately, detailed knowledge of Gorlin-Goltz syndrome is essential to improve the quality of life of those affected and to promote future research in this evolving field.