Basaloid Follicular Hamartoma: An Additional Criterion of Nevoid Basal Cell Carcinoma Syndrome.

ABSTRACT: Basaloid follicular hamartoma (BFH) is a rare, benign follicular neoplasm which typically presents as brown to skin-colored papules on the face, scalp, and trunk. Histologically, BFH consists of cords and strands of basaloid cells forming cystic structures with scant stroma and should be distinguished from infundibulocystic basal cell carcinoma to avoid overly aggressive treatment. Although BFH has been found to be associated with distinct syndromes, including alopecia, myasthenia gravis, and cystic fibrosis, there is often clinical, histopathologic, and genetic overlap with nevoid basal cell carcinoma syndrome (NBCCS). In this article, we describe a case of a 13-year-old patient with NBCCS who presented with multiple BFHs and propose that it its inclusion into the diagnostic criteria for NBCCS be considered.

Keratinocytes from Gorlin Syndrome-induced pluripotent stem cells are resistant against UV radiation.

Gorlin syndrome (GS) is an autosomal dominant genetic disorder involving Patched 1 (PTCH1) mutations. The PTCH1 is a receptor as well as an inhibitor of hedgehog (Hh) to sequester downstream Hh pathway molecules called Smoothened (SMO). PTCH1 mutations causes a variety of GS conditions including falx calcification, odontogenic keratocytes and basal cell carcinomas (BCC). Because PTCH1 is a major driver gene of sporadic BCC, GS patients are characteristically prone to BCC. In order to elucidate the pathological mechanism of BCC-prone GS patients, we investigated keratinocytes derived from GS patient specific iPS cells (G-OFiPSCs) which were generated and reported previously. We found that keratinocytes derived from G-OFiPSCs (GKCs) have increased expression of Hh target molecules. GKCs were irradiated and those cells showed high resistance to UV induced apoptosis. BCL2, known as anti-apoptotic molecule as well as Hh target, significantly increased in GKCs. Several molecules involved in DNA repair, cell cycle control, senescence, and genotoxic stress such as TP53, BRCA1 and GADD45A increased only in GKCs. GKCs are indicated to be resistant to UV irradiation by upregulating molecules which control DNA repair and genotoxic even under DNA damage caused by UV. The anti-apoptotic properties of GKCs may contribute BCC.

Dental, dermatological and radiographic findings in a case of Gorlin-Goltz Syndrome: report and review.

Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder. The disease shows multiple organ involvement with variable clinical presentation. Thus a multidisciplinary approach is required for its prompt clinical diagnosis and management of this condition. This paper highlights a case of GGS presenting in a young male patient with cranial, facial, dermatological, dental and skeletal involvement. The diagnosis of the syndrome was based on its clinical presentation, radiological features and histopathological findings. A review of the diagnostic criteria is also presented.

Gorlin-Goltz syndrome: case report and review of literature

Description of a case report of Gorlin-Goltz Syndrome diagnosed in a male newborn who presented increased head circumference and bifid ribs. Mother and grandmother presented typical physical findings of the syndrome, including palmar pits, odontogenic cysts, and history of multiple skin cancer resections. The diagnosis was based on clinical findings of three relatives. A literature review is also presented.

The impact of inoperable advanced basal cell carcinoma: the economic, physical, and psychological burden of the disease.

The development of vismodegib and its recent approval by the United States Food and Drug Administration for use in patients with locally advanced or metastatic basal cell carcinoma (BCC) carries with it a renewed sense of optimism. Once BCC has progressed to an advanced, or so-called inoperable stage, there has been a paucity of effective therapies, making the new small molecule inhibitors targeting the hedgehog pathway particularly hopeful prospects. In order to better understand the utility of these new treatments, it is important to assess the existing economic, physical, and psychological burden of advanced BCC. This review aims to recognize the impact of inoperable and metastatic BCC, as well as to better characterize the various types of advanced BCC. The use of vismodegib as a prophylactic treatment in patients with basal cell nevus syndrome is also addressed, including possible adverse events, tumor resistance, and new onset malignancies.

Síndrome de Gorlin-Goltz: manejo del carcinoma basocelular facial / Gorlin-Goltz syndrome: management of facial basal cell carcinoma

Introducción/objetivo. El síndrome de Gorlin-Goltz (SGG) es un trastorno hereditario autosómico dominante que predispone principalmente a la proliferación de tumores como los carcinomas basocelulares y queratoquistes maxilares. Está causado por la mutación del gen Patched localizado en el cromosoma 9. Los carcinomas basocelulares que aparecen en pacientes con el SGG suelen ser múltiples, de aspecto clínico polimórfico y sin predilección por el sexo, detectándose a veces a edades precoces de la vida y afectando incluso a zonas no expuestas a la luz solar. Muestran un comportamiento clínico variable, si bien en ocasiones pueden ser muy agresivos, sobre todo a nivel facial. Con el fin de estudiar el comportamiento de los carcinomas basocelulares en los pacientes con SGG se ha realizado un estudio de los pacientes tratados en nuestro hospital durante el periodo comprendido entre 2001 y 2011 y que cumplían criterios de la enfermedad. Material y métodos. Se incluyeron 11 pacientes con diagnóstico clínico y/o genético de SGG. Se estudió la distribución según edad y sexo, manifestaciones clínicas, características histológicas, técnica quirúrgica empleada, presencia de recidiva y evolución de los pacientes. Resultados. Un 36% de los pacientes presentaron carcinomas basocelulares en la cara. El número de tumores por paciente osciló entre 9 y 21. El tratamiento preferido fue la exéresis quirúrgica, si bien todos los pacientes desarrollaron nuevas lesiones y recidivas que requirieron varios procedimientos. El estudio histológico reveló un contacto o proximidad del tumor con los márgenes quirúrgicos en el 28% de las lesiones. Conclusiones. En la literatura no hay evidencia suficiente para determinar el tratamiento de elección entre los distintos métodos disponibles para el manejo del carcinoma basocelular en el SGG. Es necesario un enfoque preventivo evitando la exposición al sol(AU)

Introduction/objective. Gorlin Goltz syndrome (GGS) is an autosomal dominant inherited disorder that mainly predisposes to the proliferation of tumors, such as basal cell carcinomas and jaw keratocysts. GGS is caused by the Patched gene mutation on chromosome 9. Basal cell carcinomas in patients with GGS usually present as multiple tumors, with polymorphic clinical features, a non-gender predilection, sometimes occurring in the early stages of life, and even affecting areas not exposed to sunlight. The clinical behavior may vary, and sometimes can be very aggressive, especially in the face. In order to study the behavior of basal cell carcinomas in GGS patients, a study was performed on the patients who met criteria for the disease and were treated in our hospital in the period between 2001 and 2011. Material and methods. The study included 11 patients with clinical and/or genetic diagnosis of GGS. The patients were studied according sex and age, clinical aspects, histological features, surgical treatment provided, presence of recurrence, and follow-up. Results. Basal cell carcinomas were seen on the face in 36% of the patients. The number of tumors per patient ranged between 9 and 21. The preferred treatment was surgical excision, although all patients developed new lesions and recurrences which required several procedures. The histological study revealed a contact or proximity of the tumor to surgical margins in 28% of lesions. Conclusions. There is insufficient evidence in the literature to determine the treatment of choice among the different methods available for the management of the basal cell carcinoma in GGS. A preventive approach is necessary to avoid sunlight exposure(AU)

Neurooncology of familial cancer syndromes.

The majority of tumors of the nervous system are sporadic. However, a subset of patients with tumors and their families are predisposed to developing cancers of the central nervous system and other organs because of a germline mutation. In the last decade, many of the genes responsible for these typically autosomal dominant familial tumor syndromes have been identified. Additionally, our understanding of the mechanisms of carcinogenesis in these syndromes has increased, allowing for more targeted therapies for these patients as well as those with sporadic cancers. Because these patients present a unique set of issues regarding diagnosis and neurooncological management, the most common familial cancer syndromes involving the nervous system are reviewed: neurofibromatosis type 1 and 2; tuberous sclerosis complex; von Hippel Lindau, Li-Fraumeni, Gorlin, and Turcot syndrome.

Basal cell carcinomas: attack of the hedgehog.

Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.

Update on the management of familial central nervous system tumor syndromes.

Hereditary central nervous tumor syndromes are a varied group of conditions that include neurofibromatosis type 1 and 2, tuberous sclerosis, Von Hippel-Lindau disease, and Cowden, Turcot, and Gorlin syndromes. The responsible genes have been identified in most of these disorders. These genes typically act as tumor suppressor genes, maintain normal cellular function and homeostasis, and regulate cell growth and differentiation. Familial central nervous system tumors are mostly inherited as autosomal dominant traits and involve germline mutations. Neoplastic development occurs when a somatic mutation inactivates the second allele. These patients also present unique challenges for their management. This review highlights the clinical manifestations, molecular genetics, pathophysiology, and current treatment options of these disorders with a focus on neuro-oncologic manifestations of the diseases.

Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome: implications for treatment and surveillance.

INTRODUCTION: We report two cases of radiation-induced intracranial tumours after treatment for medulloblastoma presenting in children with nevoid basal cell carcinoma syndrome. DISCUSSION: These cases illustrate the need for judicious use of post-operative radiotherapy as secondary tumors are commonly reported. This is particularly important as the initial tumour in this cohort is of the 'less aggressive' desmoplastic subtype.

Cancer-associated genodermatoses: a personal history.

Cancer-associated genodermatoses are a group of genetic disorders inherited in an autosomal-dominant fashion in which unique cutaneous findings are a reliable marker for the risk of developing internal malignancies. The historical, clinical and dermatopathological aspects of basal cell nevus syndrome, Muir-Torre syndrome, Cowden syndrome, Carney complex and Birt-Hogg-Dubé syndrome are reviewed in a personal and informal fashion. The latest advances in the molecular genetics of the disorders are also summarized.

Mutation in exon 7 of PTCH deregulates SHH/PTCH/SMO signaling: possible linkage to WNT.

The novel PTCH mutation and clinical manifestations within Gorlin syndrome family links PTCH haploinsufficiency and aberrant activation of the Wnt pathway. We report a family case with Gorlin syndrome, characterized by the usual phenotype features such as widespread basocellular tumors and craniofacial and bone malformations, but also including a less common appearance of craniopharyngioma. These clinical manifestations might be associated with a novel constitutional mutation of the PTCH gene, 1047insAGAA, which we found in exon 7. It changes the normal amino acid sequence leading to termination of the PTCH protein at exon 9. The analyzed tumors of the family show extensive loss of heterozygosity in the PTCH region, both basocellular and in particular craniopharyngioma, and in the latter a high expression of beta-catenin was detected. Our findings suggest involvement of the SHH/PTCH/SMO pathway in pathogenesis of the analyzed disorders, including its possible contribution to aberrant activation of the Wnt pathway in craniopharyngioma.

Síndrome de Gorlin (síndrome de carcinoma basocelular nevoide). Presentación de dos casos y revisión de la literatura / Gorlin's symdrome (nevoid basal cell carcinoma syndrome). Presentation of two cases and review of the literature

El síndrome de carcinoma basocelular nevoide fue descrito hace cuatro décadas por Gorlin y Goltz; ha sido caracterizado por múltiples carcinoma basocelulares en áreas expuestas o no al sol. Además, los pacientes con este síndrome cursan con quistes mandibulares, alteraciones esqueléticas (costilla bífida), puntilleo palmoplantar y calcificaciones ectópicas. Este síndrome está asociado con otras alteraciones de cara, de piel y de los sistemas musculoesquelético, genitourinario, neurológico y oftalmológico, así como algunas neoplasias, incluyendo, linfoma de Hodgkin, no-Hodgkin, meduloblastoma, fibromas de ovario y fibrosarcomas, melanoma y rabdomioma fetal. Se ha establecido que para el diagnóstico de síndrome de Gorlin, se requiere de dos características principales, consideradas como criterios mayores, o bien de una alteración mayor y dos menores. Algunos estudios han demostrado que este síndrome es una alteración autosómica dominante en el cromosoma 9, lo cual es relevante como un evento temprano en la carcinogénesis. Esta serie presenta dos casos de síndrome basocelular nevoide. En uno de ellos se efectuó estudio completo familiar y se detecto que había ocho miembros más de la familia que padecían esta enfermedad

Effects of Photofrin on in vivo skin reflectivity.

Skin reflection spectra were measured before and 24 h after administration of Photofrin to nevoid basal-cell carcinoma syndrome patients. The presence of the drug reduced the reflectivity of uninvolved skin and increased the reflectivity of erythematous basal cell cancers. Data analysis with diffusion approximation and Monte Carlo simulation were employed to estimate the optical constant changes and localized drug concentration.

Unusual presentation of a third ventricular cyst in a patient with basal cell nevus syndrome.

Patients with basil cell nevus syndrome often have neurologic manifestations that occasionally cause complications. I report a case of a third ventricular cyst causing unusual symptoms in a 16-year-old boy. The discussion includes a review of the various neurologic signs and symptoms in this syndrome.