Plantar Pits Research Articles

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.

18F-FDG PET/CT and Whole-Body Bone Scan Findings in Gorlin-Goltz Syndrome.

Gorlin-Goltz syndrome (basal cell nevus syndromes) is an uncommon, autosomal dominant inherited disorder characterized by developing basal cell carcinomas from a young age. Other distinct clinical features include keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, and skeletal abnormalities. Clinicopathological findings of the syndrome are very diverse, and many symptoms manifest during a certain period of life. We present the compelling whole-body bone scan and 18F-FDG PET/CT findings in a 32-year-old man with odontogenic keratocyst, early-onset basal cell carcinoma, multiple ectopic calcifications in extremities, calcified falx cerebri, spinal scoliosis, macrocephaly, and ocular hypertelorism.

Whole-Exome Sequencing Identified Two Novel Pathogenic Mutations in the PTCH1 Gene in BCNS.

Basal cell nevus syndrome (BCNS, OMIM 109400) is a familial cancer syndrome characterized by the development of numerous basal cell cancers and various other developmental abnormalities, including epidermal cysts of the skin, calcified dural folds, keratocysts of the jaw, palmar and plantar pits, ovarian fibromas, medulloblastomas, lymphomesenteric cysts, and fetal rhabdomyomas. BCNS shows autosomal dominant inheritance and is caused by mutations in the patched 1 (PTCH1) gene and the suppressor of the fused homolog (SUFU) gene. In a few cases, variants of patched 2 (PTCH2) have been found in patients who met the criteria for BCNS. In an investigation of 11 Hungarian families who fulfilled the diagnostic criteria for BCNS, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) identified two novel pathogenic variants (c.2994C>A; p.Cys998Ter and c.814_818del; p.Asn272SerfsTer11), one recently identified variant (c.1737_1745del p.Val580_Val582del), and three recurrent disease-causing variants of the PTCH1 gene with a diagnosis rate of 63.6%. Disease-causing variants were not found for the SUFU and PTCH2 genes. These applied methods could not fully elucidate the genetic background of all the BCNS cases that we investigated. To uncover the missing heritability of BCNS, whole-genome sequencing or an epigenetic approach might be considered in the future.

Noninvasive real‐time imaging of palmar pits in basal cell nevus syndrome with line‐field confocal optical coherence tomography

Palmar and plantar pits are, besides childhood onset of multiple basal cell carcinomas (BCCs), odontogenic jaw cysts, intracranial calcification, and affected first-degree relatives, one of the major criteria for diagnosis of basal cell nevus syndrome (BCNS). These defective areas of keratinization are present in up to 90% of affected individuals. Lesions may be subtle and easily missed clinically. Dermoscopy or histopathological examination may be useful to diagnose them.1 Palmar pits in a 49-year-old woman with BCNS (deletion exon 2 and 3 PTCH1 gene) are shown using a new diagnostic imaging device: line-field confocal optical coherence tomography (LC-OCT). The device provides real-time and bedside visualization of the features that are typically observed in histopathology (hypokeratosis with inconstant hypogranulosis and palisading proliferation of basal keratinocytes). LC-OCT provides effective, noninvasive, and quick diagnosis of palmar pits and BCCs,2 two of the major diagnostic criteria of BCNS (Figure 1). Sergio del Río-Sancho: Visualization; writing—original draft; writing—review and editing. Caroline Gallay: Investigation; writing—review and editing. Sarah Ventéjou: Investigation; writing—review and editing. Stephanie Christen-Zaech: Conceptualization; resources; supervision; writing—review and editing. All authors read and approved the final manuscript. This study was funded by the Accentus foundation via the CHUV foundation. The authors declare have no conflict of interest. The study was approved by the Local Ethics Committee (Protocol Number: 2021_00683_2104). All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. The data that support the findings of this study are available on request from the corresponding author.

Presentation and management of syndromic and non-syndromic patients with multiple odontogenic keratocysts

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

Conservative management of odontogenic keratocyst by marsupialization

Odontogenic keratocyst (OKC) is a locally aggressive intraosseous tumor of odontogenic origin, associated with syndromes such as nevoid basal cell carcinoma syndrome. Also known as Gorlin syndrome, it is an autosomal dominant inherited condition. The disease is characterized by multiple basal cell carcinomas of the skin, multiple keratocystic odontogenic tumors, rib anomalies, and palmar and plantar pits. This article reviews a 3-year follow-up case that we have reported in the Dental University Hospital OMFS clinic at King Saud University, Riyadh, Saudi Arabia. The patient was a 13-year-old female that has been diagnosed with Gorlin–Goltz syndrome in 2018. She had multiple radiolucent lesions, two mandibular OKC, and maxillary dentigerous cyst. The extensive left OKC was treated with marsupialization followed by enucleation. Optimal results with low recurrence rate have been shown after using the marsupialization followed by enucleation and curettage, which agree with the present case results. Unfortunately, there is no gold standard or concrete recommendations that emphasize particular treatment modality. Nevertheless, this approach is considered effective and less invasive in treating OKCs, reducing the lesion size by drainage and decompression up to 47% of the initial size, allowing the preservation of critical anatomical structures. Furthermore, marsupialization prior to enucleation is an appropriate approach in young patients because it is the least treatment modality that interferes with the developmental process of jaws.

Gorlin-Goltz Syndrome: Multiple Basal Cell Carcinoma, Bifid Rib, Palmar and Plantar Pits in a 50-Year-Old Woman

Gorlin-Goltz Syndrome: Multiple Basal Cell Carcinoma, Bifid Rib, Palmar and Plantar Pits in a 50-Year-Old Woman

Nevoid basal cell carcinoma – A case report with familial manifestation

Nevoid basal cell carcinoma – A case report with familial manifestation - IJOHD- Print ISSN No: - 2395-4914 Online ISSN No:- 2395-499X Article DOI No:- 10.18231/j.ijohd.2019.051, International Journal of Oral Health Dentistry-Int J Oral Health Dent

Happle-Tinschert Syndrome: A Case Report of Unilateral Segmentally Arranged Basaloid Follicular Hamartoma with Scoliosis and Review of Literature

Happle-Tinschert syndrome is a rare disease characterized by unilateral, segmentally arranged basaloid follicular hamartoma (BFH) with osseous, dental, and cerebral anomalies. Although BFH has been demonstrated to be associated with mutations in the patched gene, the genetic basis for Happle-Tinschert syndrome is still unknown. We describe a case of Happle-Tinschert syndrome in a 26-year-old female. The patient presented with unilateral skin color change to brownish papules and atrophoderma following the development of Blaschko's lines, plantar pitting, and nail dystrophy on the right side of the body. She also had scoliosis, hemihypotrophy, and dental anomalies. The skin lesions were histologically confirmed as BFHs. Next-generation sequencing of the patient's genomic DNA obtained from a peripheral blood sample identified no pathogenic mutation. This case illustrates the characteristic clinical features of Happle-Tinschert syndrome. Thus far, 14 cases of Happle-Tinschert syndrome have been reported, and we report another case of this syndrome.

In Situ Melanoma in Collision With a Basal Cell Carcinoma in a Patient With Basal Cell Nevus Syndrome: Clinical and Dermoscopic Features.

Basal cell nevus syndrome (BCNS), also known as Gorlin-Goltz syndrome, is a rare autosomal dominantly inherited disorder characterized by the development of basal cell carcinomas (BCCs) from a young age, multiple keratocysts, palmar and/or plantar pits, calcification of falx cerebri, and family aggregations. Other criteria are skeletal anomalies, frontal bossing, cardiac and ovarian fibromas, medulloblastoma, glaucoma, and cleft lip/palate. The disorder is caused by an alteration of the sonic hedgehog signaling pathway, which results in constitutive activity and tumor cell proliferation. Some germline pathogenic variants of these genes, including PTCH1 and SUFU, have been found and are responsible for clinical heterogeneity. Only 2 case reports have described the occurrence of melanoma in patients with BCNS, but neither reported the occurrence of collision lesions [1,2]. Here we present clinical, dermoscopic, and histological features of a collision tumor of BCC and in situ melanoma in a patient with multiple BCCs and BCNS.

Gorlin syndrome in a patient with skin type VI

Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare autosomal dominant disorder that is characterized by multiple basal cell carcinomas developing at a young age, keratocystic odontogenic tumors of the jaw, palmar or plantar pits, calcification of the falx cerebri, and skeletal abnormalities. Nevoid basal cell carcinoma syndrome is caused by mutations in the PTCH1 or SUFU genes. Our patient with Fitzpatrick skin type VI was diagnosed with Gorlin syndrome based on the presentation of multiple major diagnostic characteristics. Although he is 33 years old, he has not developed any multiple basal cell carcinomas to date.

Darier-White disease: A rare genetic disorder

Background: The clinical manifestation of Darier-White disease, an autosomal dominant genodermatosis, are greasy hyperkeratotic papules in seborrheic regions with nail abnormalities and mucous membrane changes due to a defective sarcoendoplasmic calcium pump. The clinical appearance and unpleasant odor in some sites of the lesions may cause psychosocial disturbances and pose a major morbidity. Case Illustration: We report a case of a 20-year old female with clinical manifestations of multiple erythematous to hyperpigmented hyperkeratotic papules, multiple flesh-colored keratotic papules with red and white longitudinal bands on dystrophic fingernails, as well as plantar pits. Skin punch biopsy was performed to support the diagnosis. Urea-containing emollients and acitretin at a dose of 0.3 mg/kg/day were prescribed for the patient. Discussion: Our case showed the classic clinical manifestations of Darier’s Disease. The skin punch biopsy result is also consistent with Darier’s disease. We provided the patient with emollients and acitretin, a systemic retinoid, which are found to be the most effective treatment for DD. While no relationship is established between Darier’s disease and other medical problems, the patient developed anxiety and social isolation due to the clinical appearance and odor, creating a negative impact on her quality of life. Conclusion: Comprehensive and holistic management should be the goals for the management of this rare genetic disorder Keywords: acantholytic disease, Darier-White Disease, genodermatosis

GORLIN GOLTZ SYNDROME: A CASE REPORT

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, being due to a genetic alteration which produced by mutation in the “Patched” tumor suppressor gene, and it is inherited in an autosomal dominant way. This syndrome is about multisystemic process that is characterized by the presence of multiple pigmented basocellular carcinomas, odontogenic keratocysts in the jaws, palmar and/or plantar pits and calcification of falx cerebri. Together with these major features a great number of processes considered as minor features have also been described which include numerous skeletal, dermatological and neurological anomalies among others. Due to the importance of oral and maxillofacial manifestations of this syndrome, it is fundamental to know its characteristic in order to make a diagnosis, an early preventive treatment and establish right genetic advice.

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

Clinical and dermatoscopic features of porokeratosis palmaris et plantaris

A dermatoscope is an important tool in a dermatologist's armamentarium as it can eliminate the need for a biopsy in a wide array of conditions. Porokeratosis was described by Mibelli and Respighi in 1893, as a disorder of keratinization which on the basis of distribution patterns was described as five clinical variants that portrayed a coronoid lamella on histopathology. We describe a case of asymptomatic, long-standing palmar and plantar pits, which on dermatoscopy showed features suggestive of porokeratosis, which was later reconfirmed by histopathologic sections. This report depicts diagnostic features of porokeratosis and obviates the need for invasive procedures for its diagnosis.

同一家系に発現した母斑基底細胞癌症候群の3例

The main stigmata of the nevoid basal cell carcinoma syndrome (NBCCS) are developmental abnormalities, including palmar or plantar pits, bifid ribs, calcification of the falx cerebri, and a high susceptibility to several neoplasms, such as basal cell carcinomas of the skin, keratocystic odontogenic tumors (KCOTs) of the jaw, and medulloblastomas. NBCCS is a hereditary disorder caused by mutations in human patched-1 gene (PTCH1) and transmitted in an autosomal dominant manner. Three cases of NBCCS in a maternal relationship are reported. We analyzed the PTCH1 gene in 2 patients (siblings) and detected identical deletion mutations (germline mutations). In patients with NBCCS, the KCOT-causing mutation is usually inherited through the germline. Thus the susceptibility to KCOT is present in every cell of the body. Consequently, KCOT associated with NBCCS shows a trend toward multiplicity. The early detection of KCOT during follow-up using computed tomography and other diagnostic imaging techniques allowed minimally invasive surgical treatment and good outcomes.

Gorlin-Goltz Syndrome - A Rare Cause of Recurrent Jaw Pain in a Young Child

Gorlin-Goltz syndrome is an infrequent multisystem disease. At least two major criteria or one major and two minor criteria must be present to make the diagnosis. However, the most important criteria are the presence of basal cell carcinomas, odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcification of falx cerebri. It is necessary to identify the syndrome early due to its predisposition to cancer. An early diagnosis can be made using a multi-disciplinary approach. We report a rare case of an 11-year-old boy with this syndrome with an additional unusual finding of gynaecomastia.

A systematic review of the literature of nevoid basal cell carcinoma syndrome affecting East Asians and North Europeans

To compare, by systematic review, North European and East Asian consecutive case series of nevoid basal cell carcinoma syndrome (NBCCS). A systematic review of the literature was performed for all consecutive case series of NBCCS, which included keratocystic odontgenic tumors (KCOTs) arising in North European and East Asian communities. The clinical and radiologically apparent features were identified and synthesized, and a meta-analysis was performed. East Asian reports were significantly more "proband only" compared with North European reports. Significant differences between these 2 communities were observed for 5 of the 6 major features and 11 of the 27 minor features. With regard to the major NBCCS features, the North Europeans displayed significantly more frequent basal cell carcinomas, calcified falx cerebri, palmar and plantar pits, and a family history, whereas the East Asians displayed KCOTs significantly more frequently. With regard to minor features, East Asians displayed significantly more frequent cleft lips and palates and hypertelorism. East Asians displayed multiple KCOTs and cleft lips and palates more frequently compared with North Europeans.

Gorlin Goltz syndrome: A case report

Not many cases have been reported in India, and hence we report here a rare case of Gorlin Goltz syndrome (GGS) especially in young patients without any skin lesions. A 21 year old male reported to our department, with swelling in the lower posterior region of the right side of jaw since last 2 years. Thorough extraoral and intraoral examinations along with orthopantomogram (OPG), CT scan (skull) and chest radiograph helped in proper diagnosis of the condition. No skin lesion in the form of basal cell nevus, palmar or plantar pits, or keratosis were present. All the cystic lesions of the jaws were enucleated surgically and chemical cauterization done by Carnoy's solution. No sign of recurrence observed still date. Our case highlights the importance of the awareness of this rare syndrome, especially in young patients without any skin lesions because early verification of the disease prevent recurrence and better survival rates from the existent disease.