Multiple Basal Cell Carcinomas Research Articles

Genetic profiling of basal cell carcinomas detects postzygotic mosaicism in basal cell naevus syndrome

Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene. Postzygotic mosaicism can also cause BCNS. Here we describe two patients, one with multiple basal cell carcinomas (BCCs) and one with clinical BCNS, who had no PTCH1 mutation in DNA extracted from blood. In both patients, we performed genetic analysis on different BCCs, revealing the presence of a shared PTCH1 mutation in all tumours. Our findings show that in patients with symptoms of BCNS and initial absence of a PTCH1 mutation in blood, genetic profiling of BCCs can detect postzygotic mosaicism. What's already known about this topic? Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene, but it can also be caused by low-grade postzygotic mosaicism in PTCH1. What does this study add? In patients suspected of having BCNS or patients with multiple basal cell carcinomas (BCCs) with a special distribution on the body and no mutation detected in blood, it is worthwhile to search for a shared PTCH1 mutation in their BCCs as this can detect postzygotic mosaicism. This information is important to ensure proper surveillance programmes, choose the right therapy and provide adequate genetic counselling.

Multiple basal cell carcinomas after bone marrow transplantation

Multiple basal cell carcinomas after bone marrow transplantation

Risk Factors for Basal Cell Carcinoma in Men Younger Than 40 Years: A Case-Control Study.

Basal cell carcinoma (BCC) is the most common malignancy in the United States and is more prevalent in older populations. The aim of this study was to investigate BCC risk factors in male patients younger than 40 years. A consecutive series of male patients with pathology-proven BCC and younger than 40 years at time of diagnosis were retrospectively identified along with matched controls. Phone interviews were conducted using a structured questionnaire, and differences between patients with and without BCC were investigated. A total of 50 patients with BCC and 27 controls were included in this study. Compared with controls, patients with BCC worked outdoor jobs for longer lengths of time (43.2 vs 15.6 months; p = .04), were more likely to have a family history of skin cancer (66% vs 44%; p = .02), and were more likely to use sunscreen heavily after biopsy (p = .02). Patients with multiple BCCs (n = 20) were more likely to have a history of substantial recreational sun exposure (p = .01) than patients with solitary lesions (n = 30). The authors conclude that outdoor sun exposure in patients with underlying genetic susceptibility is the most likely mechanism of BCC formation in young male patients.

Experience With Vismodegib in the Treatment of Advanced Basal Cell Carcinoma at a Cancer Center

Introduction and objectivesVismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years. Material and methodsWe analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences. ResultsWe treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment. ConclusionsWith a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency.

Multiple basal cell carcinoma combined with giant epidermal cyst and vascular malformation: a case report

Multiple basal cell carcinoma combined with giant epidermal cyst and vascular malformation: a case report

Three Different Types of Skin Neoplasms on The Face

Skin cancers are mainly subclasified into two types: melanoma and non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There are some reported cases of multiple BCC and SCC of the skin in the literature. However, to our knowledge there is no case report about melanoma and NMSC in the same patient at the same time. Here, the authors report a female patient who had simultaneouslly BCC, SCC and lentigo maligna on her face.

Programmed death-1 blockade for multiple basal cell carcinomas: clearing the field systemically?

Programmed death-1 blockade for multiple basal cell carcinomas: clearing the field systemically?

Experiencia con vismodegib en carcinoma basocelular avanzado en un centro oncológico

Introduction and objectivesVismodegib is the first selective Hedgehog inhibitor approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). In this article, we describe our experience with the use of this drug to treat advanced and/or multiple BCCs at a cancer center over 5 years. Material and methodsWe analyzed the following variables: patient age and sex; tumor location, size, type, and characteristics; time since onset; primary or recurrent status; duration of treatment; response to treatment (complete, partial, stabilization, or absence of response); adverse effects; and recurrences. ResultsWe treated 22 patients, of whom 20 had locally advanced BCCs and 2 had metastatic BCCs with lymph node involvement. The treatment was administered over a mean of 11.8 months. Nine patients (41%) achieved complete response and 10 (45%) partial response. The disease was stabilized in 3 (14%). Two patients relapsed after a median of 21 months. The main adverse effects were dysgeusia, alopecia, and muscle cramps, all of which were mild. None of the patients developed squamous cell carcinoma in an area treated with vismodegib, although metatypical changes were observed after treatment. ConclusionsWith a response rate of 96%, vismodegib is a safe and effective treatment for locally advanced BCC. Adverse effects are generally mild but they need to be taken into account owing to their high frequency.

Mohs excision of multiple basal cell carcinomas in a child with xeroderma pigmentosum: The first case of its kind in the UK

Mohs excision of multiple basal cell carcinomas in a child with xeroderma pigmentosum: The first case of its kind in the UK

Clinical Utility of Bedside Multibeam Optical Coherence Tomography Imaging in a Patient With Multiple Basal Cell Carcinomas

Clinical Utility of Bedside Multibeam Optical Coherence Tomography Imaging in a Patient With Multiple Basal Cell Carcinomas

New mutations and an updated database for the patched-1 (PTCH1) gene.

BackgroundBasal cell nevus syndrome (BCNS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), maxillary keratocysts, and cerebral calcifications. BCNS most commonly is caused by a germline mutation in the patched‐1 (PTCH1) gene. PTCH1 mutations are also described in patients with holoprosencephaly.MethodsWe have established a locus‐specific database for the PTCH1 gene using the Leiden Open Variation Database (LOVD). We included 117 new PTCH1 variations, in addition to 331 previously published unique PTCH1 mutations. These new mutations were found in 141 patients who had a positive PTCH1 mutation analysis in either the VU University Medical Centre (VUMC) or Maastricht University Medical Centre (MUMC) between 1995 and 2015.ResultsThe database contains 331 previously published unique PTCH1 mutations and 117 new PTCH1 variations.ConclusionWe have established a locus‐specific database for the PTCH1 gene using the Leiden Open Variation Database (LOVD). The database provides an open collection for both clinicians and researchers and is accessible online at http://www.lovd.nl/PTCH1.

Gorlin Syndrome

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The disease is characterized by the development of multiple basal cell carcinomas at young ages. These tumors may present with other skin manifestations such as palmoplantar pits and with extracutaneous manifestations such as odontogenic keratocysts and medulloblastoma. Although the dermatologist may be key for recognizing clinical suspicion of the syndrome, a multidisciplinary team is usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be complicated due to the large number of basal cell carcinomas and the extent of involvement. In recent years, new drugs that inhibit targets in the sonic hedgehog pathway have been developed. Although these agents appear promising options for patients with Gorlin syndrome, their efficacy is limited by adverse effects and the development of resistance.

Síndrome de Gorlin

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The disease is characterized by the development of multiple basal cell carcinomas at young ages. These tumors may present with other skin manifestations such as palmoplantar pits and with extracutaneous manifestations such as odontogenic keratocysts and medulloblastoma. Although the dermatologist may be key for recognizing clinical suspicion of the syndrome, a multidisciplinary team is usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be complicated due to the large number of basal cell carcinomas and the extent of involvement. In recent years, new drugs that inhibit targets in the sonic hedgehog pathway have been developed. Although these agents appear promising options for patients with Gorlin syndrome, their efficacy is limited by adverse effects and the development of resistance.

Multicystic Lesion in Jaws: A Rare Case Report on Gorlin-Goltz Syndrome

Background and Objectives: Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder, which is characterized by multiple odontogenickeratocysts (OKC) and basal cell carcinomas, skeletal, dental, ophthalmic and neurological abnormalities.Material and Methods: Thirteen years old male patient came with swelling of left maxilla obliterating buccal vestibule with pus discharge for 1 month. The orthopantomograph and computed tomography scan demonstrated multiple lytic lesions in maxilla and mandible. Incisional biopsy was suggestive of odontogenickeratocyst (OKC). Besides multiple OKCs; bifid ribs, palmer pits and hypertelorism were present supporting for the diagnosis as Gorlin-Goltz Syndrome.Results: The classical treatment of KCOT with enucleation with curettage or resection would have resulted in significant morbidity. Therefore we first decompressed and then enucleated the cysts.Conclusion: Gorlin-Goltz syndrome is a rare entity and the multiple KCOT can be managed with decompression followed by enucleation.Janaki Medical College Journal of Medical Sciences (2017) Vol. 5(2): 46-50

PTCH1 Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS).

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities. The aim of our single-institution study was the analysis of a cohort of PTCH1-mutated patients in order to define clinical and biomolecular relationship between NBCCS and BFHs. In our study we evaluated PTCH1 gene-carrier probands affected by NBCCS to detect the incidence of BFHs and their correlation with this rare syndrome. Among probands we recognized 4 patients with BFHs. We found 15 germline PTCH1 mutations, uniformly distributed across the PTCH1 gene. Six of them had familial history of NBCCS, two of them were novel and have not been described previously. NBCCS and BFHS may be the same genetic entity and not two distinctive syndromes. The inclusion of BFH in the NBCCS cutaneous tumor spectrum might be useful for the recognition of misdiagnosed NBCCS cases that could benefit from tailored surveillance strategies.

9q22.3 Microdeletion Syndrome with Multiple Basal Cell Carcinomas Treated with Vismodegib: Three Key Messages in One Patient

9q22.3 Microdeletion Syndrome with Multiple Basal Cell Carcinomas Treated with Vismodegib: Three Key Messages in One Patient

Nevoid basal cell carcinoma syndrome: A case report with literature review

Nevoid basal cell carcinoma or Gorlin–Goltz syndrome is an autosomal dominant inherited disorder that results in numerous basal cell carcinomas (BCC) as well as a number of other facial and skeletal findings. The estimated prevalence varies from 1/57000 to 1/256000 with a male-to-female ratio of 1:1. Main clinical manifestations include multiple BCCs, odontogenic keratocysts of jaws, intracranial ectopic calcifications, and skeletal abnormalities affecting the ribs, vertebra, and skull. Management requires a multidisciplinary approach, with surgical removal of odontogenic keratocysts; surgery for BCCs should be indicated when the number of such lesions is limited. We report a case that was managed surgically, with a follow-up of more than 2 years having no signs of recurrence and relevant literature review.

Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome

Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental alterations and multiple basal cell carcinomas. Mutations in PTCH1, which encodes a membrane receptor for Sonic Hedgehog, are associated with the development of the disease. Most of them produce a truncated protein, which is unable to suppress Smoothened protein and continuously activates the downstream pathway. We aimed to characterize 22 unrelated Spanish patients with NBCCS, the largest cohort with Gorlin syndrome reported to date in Spain. Genomic analysis of PTCH1 was performed in patients with NBCCS and controls, and mutations were analysed using bioinformatics tools. We report for the first time two young patients, one each with uterus didelphys and ganglioneuroma, within the context of NBCCS. One patient showing a severe phenotype of the disease had developed basal cell carcinomas since childhood. Sanger sequencing of PTCH1 in this cohort identified 17 novel truncating mutations (11 frameshift, five nonsense and one mutation affecting an exon-intron splice site) and two novel missense mutations that were predicted to be pathogenic. The patients showed great clinical variability and inconsistent genotype-phenotype correlation, as seen in relatives carrying similar mutations. This study contributes to increase the pool of clinical manifestations of NBCCS, as well as increasing the number of pathogenic mutations identified in PTCH1 predisposing to the condition. The inconsistencies found between phenotype and genotype suggest the involvement of other modifying factors, genetic, epigenetic or environmental.

Exploring the Link between Radiation Exposure and Multifocal Basal Cell Carcinomas in a Former Chernobyl Clean-up Worker by Combining Different Molecular Biological Techniques.

Thirty years after the Chernobyl nuclear power plant accident we report on a patient who was a clean-up worker, who subsequently developed multiple cutaneous basal cell carcinomas (BCCs). We used several methods to assess the biological long-term effects related to low-dose external and internal radiation exposure. Specifically, because BCC risk may be increased with ionizing radiation exposure, we endeavored to determine whether the multifocal BCCs were related to the patient's past clean-up work. We assessed cytogenetic changes using peripheral blood, and internal incorporation was measured with a whole-body counter. Gene expression alterations were determined and array-based comparative genomic hybridization was performed for copy number aberration analysis of available BCC samples. In 1,053 metaphase cells, the dicentric yield of 0.005 dicentrics, with acentrics/cell, was significantly increased compared to the established calibration curve (P < 0.001). A 2.5-fold increase in total translocations was observed compared to the expected translocation rate. No internal contamination was detected with the whole-body counter. At the RNA level, two of seven genes (HNRNPA1, AGAP4/6/8) indicated internal plutonium exposure associated with the lowest dose category found in Mayak workers (>0-0.055 Gy). Relevant DNA copy number changes were only detected within the most aggressive BCC focus. Our results suggest that the examined worker had low and more recent radiation exposure with presumably internalized radionuclides that were below the detection level of a whole-body counter. The multifocal BCC could not be related to past occupational radiation exposure. The findings from our study suggest that integrating different methodologies potentially provides an improved overall assessment of individual health risks associated with or excluding occupational radiation exposure.

Nonsyndromic Multiple Basal Cell Carcinomas.

Basal cell carcinoma (BCC) comprising several lesions is not uncommon, but nonsyndromic multiple BCCs with parotid invasion are rare entities. We present two cases of multiple sporadic, nonsyndromic BCCs, and one of these cases is a unique case of parotid invasion associated purely with actinic keratosis. In Case 1, a 79-year-old female presented with multiple skin lesions on the face and left hand. All lesions were completely removed by surgery. The pathologic results showed lesions consistent with BCC and some lesions consistent with actinic keratosis. After 8 months, the patient presented with skin lesions in bilateral temporal areas and left cheek area. Surgical excision of the lesions was performed, and the biopsy results were squamous cell carcinoma in situ and actinic keratosis. In Case 2, a 43-year-old woman presented with multiple skin lesions on the face, scalp, right chest, abdomen and right leg. All lesions were completely removed by surgery. Pathologic evaluation confirmed the diagnosis of BCC. BCC is rarely metastatic, but it can lead to severe disfiguration or destruction. It is important to diagnose and treat BCC at an early stage.