Search Results (13)

Background: Gorlin–Goltz syndrome (GGS), also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare genetic disorder caused by mutations in the PTCH1, PTCH2, or SUFU genes, leading to an increased risk of neoplasms. Craniofacial anomalies are among the most common features of GGS. This paper aimed to highlight the similarities and differences in clinical presentation across different ages and to emphasize the importance of including all family members in the diagnostic process. The diagnosis can often be initiated by a dentist through routine radiographic imaging. Case Presentation: We present a 17-year longitudinal follow-up of a male patient with recurrent multiple odontogenic keratocysts and other manifestations consistent with GGS. Nearly 20 years later, the patient’s mother presented with similar clinical features suggestive of GGS. Diagnostic imaging, including contrast-enhanced computed tomography (CT), cone-beam CT, magnetic resonance imaging, and orthopantomography, was performed, and the diagnosis was confirmed through genetic testing. Interdisciplinary management included age-appropriate surgical and dermatological treatments tailored to lesion severity. Conclusions: Given the frequent involvement of the stomatognathic system in GGS, dentists play a critical role in early detection and referral. Comprehensive family-based screening is essential for timely diagnosis, improved monitoring, and effective management of this multisystem disorder. Full article

Gorlin-Goltz syndrome (GGS) is also known as Nevoid basal cell carcinoma syndrome (NBCCS). In the most common manifestation, GGS is diagnosed based on multiple cysts in the jaw bones, namely OKCs (odontogenic keratocysts). Other features might include major and minor clinical and radiological criteria to confirm this syndrome. Quite commonly, BCCs (basal cell carcinomas), bifid ribs, palmar and plantar pits, and ectopic calcification of the falx cerebri can be found in the majority of patients. Currently, the mutation of the PTCH1 gene seems to be responsible for GGS occurrence, while the male-to-female ratio is 1:1. The following radiological study based on OPGs and CBCT confirmed multiple cystic lesions in jaw bones, confirmed to be OKCs in the histopathological evaluation with an occurrence of numerous skin BCC lesions. In cases of most oral OKC cystic lesions, either surgical removal, curettage, or enucleation with or without any bone grafting can be used with a good amount of success. Rarely, some stable bone osteosynthesis procedures have to be carried out to avoid pathological bone fractures after cyst removal. A special consideration should include the temporomandibular joint. TMJ surgery and the replacement of the joint with an alloplastic material can be performed to improve biting, chewing, proper mouth opening, and maintain good patient occlusion. The authors want to present how effective and simple a standard dental panoramic radiograph combined with CBCT is and how it is suitable for GGS detection. They also want to underline how a standard TMJ prosthesis can be used as an alternative to a custom-made prosthesis. Full article

Gorlin–Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare, inherited autosomal dominant disorder primarily caused by mutations in the PTCH1 gene, which regulates the Hedgehog signaling pathway. This genetic defect leads to the uncontrolled proliferation of basal cells, resulting in the formation of multiple basal cell carcinomas (BCCs) and odontogenic keratocysts (OKCs). This study aims to present a complex clinical case of a patient with Gorlin–Goltz syndrome who developed multiple recurrent metastatic basal cell carcinomas on the facial region, detailing the multidisciplinary treatment strategies employed and the challenges encountered during the management of the disease. The patient, diagnosed with a pathogenic PTCH1 gene mutation, underwent a series of treatment interventions over several years. These included multiple surgical excisions aimed at tumor removal, diverse radiotherapy approaches for residual or inoperable lesions, and systemic targeted therapy with Hedgehog pathway inhibitors to control tumor progression. The recurrent and aggressive nature of the basal cell carcinomas resulted in extensive facial tissue loss, posing significant challenges for radical tumor excision and subsequent reconstructive procedures. Multimodal therapeutic strategies, including Mohs micrographic surgery for precise tumor clearance and targeted systemic therapy with vismodegib, were implemented. However, the aggressive progression of lesions required ongoing surgical interventions, highlighting the limitations of current treatment modalities in achieving long-term disease control. This case underscores the critical need for a comprehensive, multidisciplinary approach to managing Gorlin–Goltz syndrome. Successful management requires close collaboration between dermatologists, oncologists, maxillofacial surgeons, and plastic surgeons to balance effective tumor control with optimal functional and aesthetic outcomes. The integration of advanced surgical techniques and targeted molecular therapies shows promise in improving patient outcomes. Nonetheless, early diagnosis, rigorous follow-up, and patient education remain essential components in minimizing disease progression and enhancing the quality of life for affected individuals. Full article

Background and Clinical Significance: Basal cell nevoid carcinoma syndrome, or Gorlin–Goltz Syndrome (GGS), is a genetic disease caused by germline mutations in genes involved in the Sonic HedgeHog (SHH) signaling pathway, mainly in the PTCH1 gene. PTCH1 is a receptor for SHH, and the activation of SHH signaling exerts a direct effect on the proliferation and maintenance of stem cells; alteration of its signaling could promote a favorable microenvironment for the maintenance of tumor viability. The main clinical manifestations of patients with GGS include multiple basal cell carcinomas, odontogenic keratocysts, calcification of the falx cerebri, palmoplantar fossae, hypertelorism, prognathism, fused or bifid ribs, and macrocephaly, which occur at different stages of life. Case Presentation: Here, the case of a 48-year-old woman is described, for whom a clinical and histopathological diagnosis of GGS was made due to the presence of two major criteria (multiple odontogenic keratocysts and calcification of the falx cerebri) and one minor criterion (congenital anomalies), according to Kimonis. Additionally, an end-point RT-PCR assay showed a decrease in PTCH1 gene expression. A conservative therapy was established, and satisfactory results were obtained in a follow-up period of 18 months. Conclusions: Kimonis' clinical criteria are important for establishing the diagnosis of Gorlin syndrome. Full article

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. Full article

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. Full article

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. Full article

(1) Background: The aim of this study was to compare the histopathological features of syndromic and non-syndromic odontogenic keratocysts (OKs) using conventional and Confocal Laser Scanning Microscopy (CLSM) with their biological behaviour. (2) Methods: Data from the medical records of 113 patients with histological diagnosis of (single and/or multiple) OKs were collected. Globally, 213 OKs (120 syndromic and 93 sporadic) were retrieved, and their histological slides were re-evaluated with conventional H&E staining and with autofluorescence on the same slides using CLSM (Nikon Eclipse E600 microscope). (3) Results: Syndromic OKs showed more satellite cysts than sporadic cases, as well as a basophilic layer in the basement membrane, which was absent in sporadic OKs; both were highlighted with CLSM. The basement membrane in syndromic OKs appeared amorphous and fragile, thus possibly being responsible for the epithelial detachment and collapse, with scalloped features. Furthermore, the basal epithelial layers in such cases also showed increased cellularity and proliferative activity. All these histological features may possibly justify their higher tendency to recur. (4) Conclusions: CLSM is useful advanced technology that could help to quickly and easily discriminate between syndromic and non-syndromic OKs and to more accurately predict their biological behaviour in order to set fitter clinico-radiological follow-ups for individual patients. Full article

Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior. Full article

Activating mutations in the Hh pathway underlies the development of sporadic and familial skin BCC. For these oncogenic proliferations displaying ligand-independent activation of the intracellular pathway, two molecules have been approved for therapeutic purposes: vismodegib and sonidegib. Improper Hh signalling occurs in many human tumours also via a paracrine mechanism (ligand-dependent) in which the secretion of Hh ligands by stromal cells support tumour growth. On the other hand, the mobilization of neoplastic stroma by cancer cells is sustained by the activation of Hh signalling in surrounding fibroblasts suggesting a central role of this bidirectional crosstalk in carcinogenesis. Additionally, loss-of-function mutations in the PTCH1 gene in the context of NBCCS, an autosomal dominant disorder predisposing to multiple BCCs, determine tumour permissive phenotypes in dermal fibroblasts. Here, profiling syndromic and BCC-associated fibroblasts unveiled an extraordinary similarity characterized by overexpression of several Hh target genes and a marked pro-inflammatory outline. Both cell types exposed to Hh inhibitors displayed reversion of the tumour-prone phenotype. Under vismodegib and sonidegib treatment, the Wnt/β-catenin pathway, frequently over-active in tumour stroma, resulted down-regulated by pAKT-GSK3β axis and consequent increase of β-catenin turnover. Overall, this study demonstrated that vismodegib and sonidegib impacting on fibroblast tumour supportive functions might be considered in therapy for BCC independently to the mutation status of Hh components in neoplastic cells. Full article

Nevoid basal cell carcinoma syndrome (NBCCS), also named Gorlin syndrome, is a rare multisystem genetic disorder characterized by marked predisposition to basal cell carcinomas (BCCs), childhood medulloblastomas, maxillary keratocysts, celebral calcifications, in addition to various skeletal and soft tissue developmental abnormalities. Mutations in the tumor suppressor gene PATCHED1 (PTCH1) have been found to be associated in the majority of NBCCS cases. PATCH1 somatic mutations and loss of heterozygosity are also very frequent in sporadic BCCs. Unlike non-syndromic patients, NBCCS patients develop multiple BCCs in sun-protected skin area starting from early adulthood. Recent studies suggest that dermo/epidermal interaction could be implicated in BCC predisposition. According to this idea, NBCCS fibroblasts, sharing with keratinocytes the same PTCH1 germline mutation and consequent constitutive activation of the Hh pathway, display features of carcinoma-associated fibroblasts (CAF). This phenotypic traits include the overexpression of growth factors, specific microRNAs profile, modification of extracellular matrix and basement membrane composition, increased cytokines and pro-angiogenic factors secretion, and a complex alteration of the Wnt/β-catenin pathway. Here, we review studies about the involvement of dermal fibroblasts in BCC predisposition of Gorlin syndrome patients. Further, we matched the emerged NBCCS fibroblast profile to those of CAF to compare the impact of cell autonomous “pre-activated state” due to PTCH1 mutations to those of skin tumor stroma. Full article

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCC), mainly caused by PTCH1 gene mutations. Our current study aimed to establish (1) PTCH1 germinal and somatic mutational status, (2) component and Hedgehog (HH) pathway targets gene expression patterns, and (3) profile variations according to the genetic background in BCC and normal surrounding skin (NSS). We collected 23 blood and 20 BCC patient samples and analyzed the PTCH1 gene using bidirectional sequencing and multiplex ligation-dependent probe amplification. Quantitative PCR was used to determine the mRNA expression levels of PTCH1, SMO, GLI3, and CCND1 in paired samples of BCC and NSS from 20 patients and four non-NBCCS skin controls (C). Our analyses identified 12 germline and five somatic sequence variants in PTCH1. mRNA levels of PTCH1, SMO, and GLI3 were higher in NSS compared to C samples, reaching maximum values in BCC samples (p < 0.05). NSS with PTCH1 germline mutations had modified SMO, PTCH1, and GLI3 mRNA levels compared to samples without mutation (p < 0.01). Two PTCH1 mutations in BCC led to an increase in PTCH1, SMO, and GLI3, and a decrease in CCND1 mRNA levels (p < 0.01 vs. BCC with germline mutation only). These results indicate that besides PTCH1, other genes are responsible for NBCCS and BCC development in a population exposed to high UV radiation. Additionally, the mutational events caused increased expression of HH-related genes, even in phenotypically normal skin. Full article

We present a family case series with 10 individuals having nevoid basal cell carcinoma syndrome (NBCCS) with a 10-year follow-up. All articles published in the literature between 1967 and 2011 on familial Gorlin-Goltz syndrome in any language were surveyed to determine the mapping of cases per country of occurrence of this disease. All patients in the present series were presented with calcification of the falx cerebri, mild hypertelorism, and frontal bossing. Odontogenic keratocystic tumors, palmar and plantar pits, and multiple basal cell carcinomas occurred in 90, 40, and 20%, respectively, of the patients. One of the patients died of skin cancer. Diagnosis of odontogenic keratocyst tumors was confirmed by histopathological examination. NBCCS is a rare autosomal dominant cancer predisposition syndrome; it is important to recognize it when a patient has multiple odontogenic keratocyst tumors because life-long monitoring is essential for patient management. Full article