Nevoid Basal Cell Carcinoma Syndrome Research Articles

Acquisition of Drug Resistance in Basal Cell Nevus Syndrome Tumors through Basal to Squamous Cell Carcinoma Transition

Although basal cell carcinomas arise from ectopic Hedgehog pathway activation and can be treated with pathway inhibitors, sporadic basal cell carcinomas display high resistance rates, whereas tumors arising in patients with Gorlin syndrome with germline Patched (PTCH1) alterations are uniformly suppressed by inhibitor therapy. In rare cases, patients with Gorlin syndrome on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. In this study, we report a case of an SMO inhibitor-resistant tumor arising in a patient with Gorlin syndrome on suppressive SMO inhibitor for nearly a decade. Using a combination of multiomics and spatial transcriptomics, we define the tumor populations at the cellular and tissue level to conclude that Gorlin tumors can develop resistance to SMO inhibitors through the previously described basal to squamous cell carcinoma transition. Intriguingly, through spatial whole-exome genomic analysis, we nominate PCYT2, ETNK1, and the phosphatidylethanolamine biosynthetic pathway as genetic suppressors of basal to squamous cell carcinoma transition resistance. These observations provide a general framework for studying tumor evolution and provide important clinical insight into mechanisms of resistance to SMO inhibitors for not only Gorlin syndrome but also sporadic basal cell carcinomas.

Hedgehog Inhibitors Beyond Clinical Complete Response in Basal Cell Carcinoma: Should I Stop or Should I Go?

In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need. We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS). Reasons to stop vismodegib were (R1) toxicity and (R2) disease recurrence. The relationship between DTCR, DTS, TTD, and DFS in the whole population and in R1 subgroup was assessed by Pearson's correlation coefficient (P < .05) and Bayesian statistics (BF10). Sixty-eight BCC patients with a median (m) age of 75.5 years (39-100) were included. Most patients were male (N = 43, 63%), without Gorlin syndrome (N = 56, 82%) and with head and neck area as primary site (N = 51, 75%). After cCR, out of 68 patients, 90% (N = 61/68) discontinued vismodegib: 82% (N = 50/61) due to toxicity (R1), and 18% (N = 11/61) due to recurrence (R2). Conversely, 10% (N = 7/68) continued vismodegib until last follow-up. In the whole population (N = 68), cCR was achieved with a mDTCR of 180.50 days. DFS showed a significant correlation with DTS (P < .01, BF10 = 39.2) and TTD (P < .01, BF10 = 35566), while it was not correlated to DTCR (BF10 < 0.1). The analysis of R1 subgroup (N = 50) confirmed these results. DFS correlated with DTS in all recurrent patients (N = 38, r = 0.44, P < .01) and in the recurrent patients who stopped vismodegib for toxicity (N = 26, r = 0.665, P < .01). DFS was longer when vismodegib was maintained for >2 months after cCR (mDFS > 2 months, N = 54 vs. ≤ 2 months, N = 14: 470 vs. 175 d, P < .01). Our retrospective results suggest that HHIs should be continued after cCR to improve DFS in BCC.

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.

A novel pathogenic splice-site variant in the PTCH1 gene c.3549+1G>T, associated with Gorlin syndrome: a case report

BackgroundGorlin syndrome (GS) is a rare genetic disorder inherited in an autosomal dominant manner caused by genetic variants in PTCH1, SUFU, or PTCH2 genes. It is characterized by multiple basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities, and predisposition to neoplasms.Case presentationA novel splice-site variant in the PTCH1 gene, c.3549+1G>T classified as pathogenic, was identified in a patient with a phenotype compatible with GS (multiple basal cell carcinomas and skeletal malformations).ConclusionsThis case contributes to expand the spectrum of identified variants in Gorlin syndrome increasing knowledge about molecular bases and the diagnosis approach of this syndrome.

Photodynamic Therapy in Treating a Subset of Basal Cell Carcinoma: Strengths, Shortcomings, Comparisons with Surgical Modalities, and Potential Role as Adjunctive Therapy.

Basal cell carcinoma (BCC) is the most common skin cancer, for which there are multiple treatment options, including the gold standard Mohs micrographic surgery (MMS), surgical excision, electrodesiccation and curettage, radiation therapy, cryosurgery, and photodynamic therapy (PDT). While PDT is currently approved for treating actinic keratosis, it has been used off-label to treat BCC patients who may not tolerate surgery or other treatment modalities. We present a review of the efficacy of these modalities and describe important considerations that affect the usage of PDT and MMS. ALA-PDT and MAL-PDT are both efficacious treatment options for lower-risk BCC that can serve as non-invasive alternatives to surgical excision with favorable cosmetic outcomes in patients unsuitable to undergo surgery. In particular, PDT may be considered an adjuvant for the prevention and treatment of BCC lesions in patients with some genetic syndromes such as Gorlin syndrome, and in combination with surgical excision in lesions presenting in certain locations. Limitations to PDT include lack of margin control to prevent recurrence, pain, and cost of certain photosensitizers. Future studies should investigate the role of PDT as adjunctive therapy, standardization of protocols, and causes and ways to address recurrence following PDT treatment.

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.

Depicting dermoscopic and confocal findings in patients with Gorlin-Goltz Syndrome.

Depicting dermoscopic and confocal findings in patients with Gorlin-Goltz Syndrome.

Bilateral ovarian fibromas as the sole manifestation of Gorlin syndrome in a 22-year-old woman: a case report and literature review

BackgroundNevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare autosomal dominantly inherited disorder that is characterized by multisystem disorder such as basal cell carcinomas, keratocystic odontogenic tumors and skeletal abnormalities. Bilateral and/or unilateral ovarian fibromas have been reported in individuals diagnosed with NBCCS.Case presentationA 22-year-old female, presented with low back pain, and was found to have bilateral giant adnexal masses on pelvic ultrasonography, which had been suspected to be malignant ovarian tumors. Positron emission tomography/computed tomography showed multiple intracranial calcification and skeletal abnormalities. The left adnexa and right ovarian tumor were resected with laparotomy, and pathology revealed bilateral ovarian fibromas with marked calcification. We recommended the patient to receive genetic testing and dermatological examination. No skin lesion was detected. Germline testing identified pathogenic heterozygous mutation in PTCH1 (Patched1).ConclusionsThe possibility of NBCCS needs to be considered in patients with ovarian fibromas diagnosed in an early age. Skin lesions are not necessary for the diagnosis of NBCCS. Ovarian fibromas are managed with surgical excision with an attempt at preserving ovarian function. Follow-up regime and counseling on options for future fertility should be offered to patients.

Comparison of the Recurrence Rate in Marsupialization with and Without Peripheral Sectomy in the Treatment of Odontogenic Keratocyte Tumor in Patients Referred to Bahoner Hospital, Kerman

Aim: Odontogenic keratocyte tumor is a developmental cyst with proliferative and invasive nature. which is often observed in the posterior region of the mandible and is commonly seen in the third decade of life. The highest age of prevalence is in the 3rd to 6th decades and the male to female ratio is 2 to 1. Normally, if there is no infection, it is not manifested and it is discovered accidentally in rayograph, but if the size increases, it manifests as an extension in the form of pain, swelling and infection in the dental and bone area if the tooth is hidden. In radiographs, it appears as a radiolucent lesion with distinct ionic or multilocular boundaries and sometimes with a scallop border in the dental area or even extending to the ascending ramus and condylar area. Research shows that the origin of this cyst is the remaining odontogenic epithelium of Ceres in the alveolar region. And it can be syndromic (Gorlin syndrome) or non-syndromic. This cyst has a thin epithelium and has multiple daughter cysts, which causes the risk of recurrence due to incomplete removal of the lesion. Enucleation, marsupialization, Carney’s solution and resection are treatment methods. What is investigated in this project is the comparison of the prevalence of the two therapeutic methods of marsupialization alone and the combination of marsupialization and peripheral sect my in patients with odontogenic keratocytes regardless of whether they are syndromic or sporadic. Method and Materials: In this study, which is conducted on 10 patients referred to Behoney Hospital in Kerman. First, the patient is selected with clinical examinations and then with the preparation of panoramic radiographs. If there is visible swelling, aspiration is performed with a 10-cc syringe, and then the patient is operated on for a biopsy to definitively diagnose the odontogenic keratocyte of the tumor. In this study, there is no difference between the age and sex of the patient, and whether KOT is syndromic or sporadic; Both are included in the review. The patient is subjected to marsupialization, then the patient undergoes follow-up and periodic x-rays are used to ensure that the lesion shrinks. In the lesions where there is involvement of the surrounding bone in the form of a saucerization, after the lesion is reduced, the patients are treated with peripheral sect my or removal of the bone around the lesion in the form of a curt shape, and in small lesions, the treatment is completed with marsupialization. arrives. Then the patients are followed up and the recovery process and the rate of recurrence are checked by preparing periodical x-rays. Results: In this study, out of ten patients, 4 patients (40%) had recurrence, and among these 4 patients, 3 patients (75%) were in the first group who were treated with marsupialization. The follow-up of the patients was one year, and after the preparation of OPG, the reduction of cyst dimensions was compared to the size before the operation. The criterion for the recurrence of keratocyte odontogenic lesion is the increase in the size of the lesion according to the qualitative scale and the comparison of the graph prepared before and after marsupialization. Out of 4 patients with recurrence, one case in the second group (25%) is treated with marsupialization and peripheral sitcom, a ten-year-old boy has multiple jaw cysts in the front of the mandible, behind the maxilla on both sides, and behind the mandible on both sides. The maxillary sinus is left. According to the obtained results, the treatment of marsupialization with peripheral sect my has more effectiveness and the results had a significant difference. p value=0.043 Conclusion: According to the obtained results, the treatment of marsupialization with peripheral sitcom has more effectiveness and less recurrence.

Skin Cancer

ABSTRACT Basal cell nevus syndrome is a genetically linked multisystem disorder with a hallmark tendency for development of multiple basal cell carcinomas at a young age. It is associated with a multitude of other anomalies including keratocytes of the jaw, palmar or plantar pits, and ectopic intracranial calcifications. This disease is most commonly caused by loss of function in tumor suppressor gene PTCH1 resulting in overactivation of the Hedgehog pathway and basal cell carcinoma formation. Diagnosis is largely clinical; patients must meet criteria of both major and minor categories. Genetic testing is warranted in specific situations where clinical diagnosis is unclear or for genetic counseling purposes. Given that basal cell carcinoma is a very common dermatologic disorder, it is important to recognize when it arises in the setting of genetically associated diseases. Early detection allows for proper management and surveillance of not only basal cell carcinomas but also the other multisystem effects of basal cell nevus syndrome. This review gives an in-depth overview of the etiology, pathogenesis, diagnosis, and management of basal cell nevus 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 case report

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.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. 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. 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.

Gorlin-Goltz Syndrome: An Incidental Finding of a Rare Entity.

Gorlin-Goltz syndrome (GGS) is a rare hereditary disease characterized by multiple basal cell carcinomas, odontogenic keratocyst (OKCs) and musculoskeletal malformations. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and mutations in the human patched gene (PTCH1 gene). Here, we report a rare case of an incidental finding of GGS in an 18-year-old male patient presenting multiple OKCs, calcification of the falx cerebri, and bifid rib.

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.

A novel de novo canonical splice site mutation in the PTCH1 gene in a male patient with mild psychomotor retardation and autistic traits: a case report

Basal cell nevus syndrome (BCNS), or Gorlin syndrome, is a rare autosomal dominant disorder caused by mutations in the tumor suppressor gene PTCH1 with complete penetrance and variable expressivity characterized by a broad spectrum of developmental anomalies and a predisposition to neoplasms. Herein, we report a novel de novo splice site mutation in the PTCH1 gene related to mild developmental delay and autistic traits in a 4-year-old male patient.

Odontogenic keratocyst in the mandible of a 7‐year‐old child: A case report and literature review

AbstractOdontogenic keratocysts (OKCs) are one of the most frequently encountered cystic diseases of the jaw in clinical practice. Although OKC has been reported as a manifestation of nevoid basal cell carcinoma syndrome (Gorlin syndrome) in many pediatric patients, there have been few reports of OKC occurring in isolation. Herein, we report the case of a relatively large OKC in the mandibular body of a 7‐year‐old girl who was treated conservatively using cystectomy and open wound surgery, and the permanent teeth were unaffected. Regular check‐ups, including radiographic examinations, starting in childhood may contribute to the early detection of lesions in the maxillofacial region.

Incidence and Prevalence of 73 Different Genodermatoses: A Nationwide Study in Sweden.

This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated healthcare usage. Patients diagnosed with genodermatoses were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) between 2016 and 2020. Clinical data from medical records were used to verify diagnoses recorded in the National Patient Registry (NPR). The NPR was then searched for International Classification of Diseases, Tenth Revision (ICD-10) codes Q80-82 and Q84 from 2001 to 2020. The local cohort included 298 patients with 36 unique genodermatosis diagnoses. Verification of these diagnoses in the NPR showed positive predictive values of over 90%. The NPR search yielded 13,318 patients with 73 unique diagnoses, including ichthyoses (n = 3,341; 25%), porokeratosis (n = 2,277; 17%), palmoplantar keratodermas (n = 1,754; 13%), the epidermolysis bullosa group (n = 1011; 7%); Darier disease (n = 770; 6%), Hailey-Hailey disease (n = 477; 4%) and Gorlin syndrome (n = 402; 3%). The incidence and prevalence of each diagnosis were calculated based on the nationwide cohort and are reported. A total of 149,538 outpatient visits were registered, a mean of 4.6 visits per patient. This study provides a valuable resource for the epidemiology of genodermatoses by reporting on the incidence and prevalence of 73 different genodermatoses.

LB1763 Combinatorial BRD9 and SMO targeting synergistically suppress UV-induced BCC tumor burden in a murine model of Gorlin syndrome (GS)

LB1763 Combinatorial BRD9 and SMO targeting synergistically suppress UV-induced BCC tumor burden in a murine model of Gorlin syndrome (GS)