Procedimento terapia fotodinâmica para tratamento de carcinoma basocelular superficial e nodular / Photodynamic therapy procedure for treating superficial and nodular basal cell carcinoma

INTRODUÇÃO: O carcinoma basocelular (CB) compreende de 80% a 90% dos casos de câncer de pele não melanoma e o mais frequente entre todas as neoplasias malignas diagnosticadas. A primeira linha de tratamento do carcinoma basocelular é a excisão cirúrgica. Para pacientes inoperáveis ou com tumores de baixo risco, a terapia fotodinâmica é um tratamento em duas etapas que consiste na aplicação de um fotossensibilizador seguida por um período de incubação por irradiação. Entre os fotossensibilizadores utilizados na terapia estão o ácido 5-aminolevulínico (ALA) e seu éster, o aminolevulinato de metila (metil-ALA). Apenas o metil-ALA possui registro sanitário válido no Brasil. PERGUNTA: A terapia fotodinâmica com metil-ALA é eficaz, segura e custo-efetiva para o tratamento de carcinoma basocelular quando comparada à excisão cirúrgica? EVIDÊNCIAS CLÍNICAS: Foi realizada um overview de revisões sistemáticas para identificar uma revisão que contemplasse a pergunta de pesquisa e atendesse aos critérios de elegibilidade. Para eleger a de melhor qualidade metodológica foi realizada a avali

Basal cell nevus syndrome: From DNA to therapeutics.

Basal cell nevus syndrome, also known as Gorlin syndrome, is a hereditary cancer syndrome associated with multiple basal cell carcinomas, congenital defects, and nondermatologic tumors. This disease is autosomal dominant with variable expressivity and is caused by abnormalities in the sonic hedgehog signaling pathway. Management requires a multidisciplinary approach and should include the biopsychosocial needs of patients and their families. Genetic testing is necessary to confirm an unclear diagnosis, evaluate at-risk relatives, and assist with family planning.

A pediatric approach to management of skin growths in basal cell nevus syndrome.

Little guidance on management of basal cell nevus syndrome in children exists. We report a case series of four patients diagnosed with BCNS in early childhood, in whom several highly suspicious lesions were biopsied, but several smaller and questionably concerning lesions were treated with therapies that are more tolerable for children, including topical imiquimod, 5-fluorouracil, cryotherapy, or touch electrodessication following topical anesthetic cream. These therapies were well tolerated, and all residual or persistent lesions were subsequently biopsied and found to be benign. This approach is often preferable for pediatric BCNS patients, in whom concerning lesions can be identified clinically and managed compassionately. However, any lesion that exhibits growth, bleeding, or symptoms should be biopsied for definitive diagnosis.

[The complex dental and oral surgical management with 8-year follow up of a Gorlin‒Goltz syndrome patient]. / Gorlin­Goltz-szindrómás beteg komplex fogorvosi, szájsebészeti kezelése és 8 éves követése.

Gorlin-Goltz syndrome is an autosomal dominant hereditary disease. Its leading symptoms include keratocysts of the jaws, multiple basal cell carcinomas, skeletal abnormalities, intracranial calcifications and dyskeratosis of the soles and palms. One of the most common and often firstly discovered symptoms is the single or multiplex keratocysts of the jaws. The authors present a case of a child, diagnosed in their orthodontic department. Despite the rare occurrence of the disease, an early detection is important, especially in young patients. Regular follow-up and timely care for patients may avoid life-threatening malformations and radical surgical treatments. Orv Hetil. 2020; 161(2): 67-74.

What's New in Genetic Skin Diseases.

The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved understanding of disease mechanisms at a molecular level and identified new therapeutic options based on molecular targets. This article highlights just a few of these recent discoveries for a diverse group of skin diseases, including tuberous sclerosis complex, ichthyoses, overgrowth syndromes, interferonopathies, and basal cell nevus syndrome, and how this has translated into novel targeted therapies and improved patient care.

Gorlin Syndrome. / 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.

[Gorlin-Goltz Syndrome: Diagnosis and Treatment Options]. / Síndrome de Gorlin-Goltz: Diagnóstico e Hipóteses de Tratamento.

The Gorlin-Goltz syndrome is a rare autosomal dominant hereditary condition, with complete penetrance and variable expressivity. Characterized by the appearance of multiple basaliomas, and often the development of keratocyst, it can also express itself by the presence of palmar/plantar depressions, calcification of brain sickle, and skeletal birth defects, although less frequently. This article presents two cases involving direct relatives, referred after the identification of several basaliomas and jaw cysts. After establishing the diagnosis, given the identification of three major criteria, the treatment consisted in the excision of the lesions followed, in one case, with vismodegib treatment resulting in complete remission. Gorlin-Goltz syndrome is therefore a multidisciplinary challenge, whose variable morbidity and high risk of recurrence make treatment and surveillance critical. However, new molecular targeted therapies have brought a new hope in treating these patients.

A síndrome de Gorlin-Goltz é uma patologia hereditária, rara, autossómica dominante de penetrância completa, com expressividade variável. Caracterizada pelo aparecimento de múltiplos basaliomas, cursa, frequentemente, com o desenvolvimento de queratoquistos. Depressões palmares/plantares, calcificações da foice cerebral, anomalias esqueléticas congénitas, constituem, igualmente, critérios de diagnóstico, embora menos frequentes. Este artigo expõe dois casos clínicos, envolvendo familiares diretos, referenciados após identificação de vários basaliomas e quistos maxilares. Estabelecido o diagnóstico, perante a identificação de três critérios major, o tratamento consistiu na excisão das lesões, seguida, num dos casos, da terapêutica com vismodegib, com remissão completa. A síndrome de Gorlin-Goltz é, assim, um desafio multidisciplinar, cuja morbilidade variável e o elevado risco de recorrência tornam fundamental o tratamento e vigilância. Contudo, o aparecimento de novas terapêuticas moleculares dirigidas trazem uma nova esperança no tratamento destes doentes.

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.

Clinical Finding and Management of 12 Orofacial Clefts Cases With Nevoid Basal Cell Carcinoma Syndrome.

Objective To study the phenotype and overview the clinical management on Cleft Lip and/or Palate (CL/P) with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) patients in Peking University School and Hospital of Stomatology. Design Case series study. Main Outcome Measures To describe the clinical phenotype of 12 CL/P with NBCCS patients who fulfilled the diagnostic criteria as well as to explore clinical management. Results Seven cases (7/12, 58.33%) were classified as bilateral complete cleft lip and palate (BCCLP). Two cases (2/12, 16.67%) were classified as unilateral complete cleft lip and palate (UCCLP). Three cases (1/12, 8.33%) were classified as unilateral complete cleft lip (UCCL), submucosa cleft uvula (SCU), and bifid uvula (BU), respectively. The ratio of male/female was 9/:3. Keratocystic odontogenic tumors (KCOTs) were presented in all 12 cases. The most common site was the mandible region (12/12, 100%) followed by the maxilla region (7/12, 58.33%). The diagnostic age of 12 NBCCS with CL/P ranged from 11 to 42 years old (usually postponed to the occurring of KCOTs). The delayed diagnosis of NBCCS can be attributed to its complicated clinical manifestations. In some cases, the mutual effect between the surgical therapy of removing KCOTs and alveolar bone grafting made the team approach (TA) of CL/P more complicated. Conclusion CL/P may become important clinical phenotype in NBCCS. The type of cleft varied, with bilateral cleft lip and palate comprising above 50%. Larger sample sizes are needed to study and confirm this result. KCOTs, as one of the most common clinical feature of NBCCS, make the diagnosis delayed and the TA more difficult because of the occurring time and site. This compels us to improve the diagnostic criteria to make an early diagnosis and explore a better therapeutic protocol for CL/P.

Myelodysplastic Syndrome Occurring in a Patient with Gorlin Syndrome.

We report a case of myelodysplastic syndrome (MDS) occurring in an African American boy with Gorlin syndrome with a novel PTCH1 mutation. Before developing MDS, the patient had been treated with chemotherapy and radiation for a medulloblastoma. He received a bone marrow transplant for the MDS and eventually died of treatment complications. Secondary hematologic malignancies are a known complication of certain chemotherapeutics, although whether a patient with Gorlin syndrome has a greater propensity for the development of such malignancies is unclear.

Basal cell naevus syndrome: an update on genetics and treatment.

Basal cell naevus syndrome is an autosomal dominant disorder that stems from mutations in multiple genes, most commonly patched 1 (PTCH1). The classic triad of symptoms consists of basal cell carcinomas, jaw keratocysts and cerebral calcifications, although there are many other systemic manifestations. Because of the broad range of symptoms and development of several types of tumours, early diagnosis and close monitoring are essential to preserve quality of life. Targeting treatment is often difficult because of tumour prevalence. Newer inhibitors of the hedgehog signalling pathway and proteins involved in proliferative growth have shown therapeutic promise. In addition, preventive medications are being devised. We propose a method for determining appropriate treatment for cutaneous tumours.

The Gorlin-Goltz Syndrome: diagnosis of a case associated with heart disease and type 2 diabetes mellitus / Síndrome de Gorlin-Goltz: diagnóstico de um caso associado à cardiopatia e diabetes mellitus 2

The Gorlin-Goltz syndrome (GGS) is a hereditary, autosomal dominant condition, with high penetrance and variable expressivity, resulting from mutations in the genes PTCH1, PTCH2, or SUFU. The diagnosis is based on the presence of 2 major criteria or a major criterion associated with 2 minor criteria, including multiple basal cell carcinomas, keratocystic odontogenic tumor (KOT), and bifid rib. Other endocrine, neurological, ophthalmologic, genital, respiratory, and cardiovascular alterations are found in the literature, but with variable manifestations. This study reports the case of a patient diagnosed with GGS associated with diastolic congestive heart failure and type 2 diabetes mellitus, who underwent multiple treatments for components of the syndrome. More recently, the patient underwent decompression followed by cystic enucleation of two KOTs in the jaw, oral rehabilitation with removable prosthodontics, cardiological evaluation, and attempted clinical control of endocrine and cardiac problems.

A síndrome de Gorlin-Goltz (SGG) é uma condição hereditária, autossômica dominante, com alta penetrância e expressividade variável, decorrente de mutações nos genes PTCH1, PTCH2 ou SUFU. O diagnóstico é baseado na presença de dois critérios maiores ou um critério maior associado a dois critérios menores, dentre eles múltiplos carcinomas basocelulares, tumor odontogênico ceratocístico (TOC) e costela bífida. Outras alterações endócrinas, neurológicas, oftalmológicas, genitais, respiratórias e cardiovasculares são encontradas na literatura, porém com manifestações variáveis. O objetivo deste trabalho é relatar um caso clínico de uma paciente sistematicamente diagnosticada com SGG associada à insuficiência cardíaca congestiva diastólica e diabetes mellitus 2 submetida a tratamentos seriados das respectivas manifestações sindrômicas. Mais recentemente, à descompressão cística seguida da enucleação de dois TOC em mandíbula, reabilitação oral com prótese total removível, avaliação cardiológica e tentativa de controle clínico das alterações endócrinas e cardíacas.

Utilidad de la microscopia confocal en el diagnóstico diferencial de epiteliomas basocelulares y nevus melanocíticos intradérmicos de localización facial / Usefulness of Confocal Microscopy in Distinguishing Between Basal Cell Carcinoma and Intradermal Melanocytic Nevus on the Face

El diagnóstico clínico diferencial entre el epitelioma basocelular y el nevus melanocítico intradérmico facial puede ser a veces complicado, sobre todo en pacientes jóvenes o con múltiples nevus. La dermatoscopia es una herramienta útil que permite observar signos dermatoscópicos asociados a epitelioma como las ruedas de carro, las hojas de arce, los nidos y puntos azul grisáceos y la ulceración, además permite distinguir los vasos telangiéctasicos arboriformes y los vasos cortos curvados bien enfocados característicos de los epiteliomas basocelulares de los vasos en coma presentes en los nevus melanocíticos intradérmicos. Sin embargo, el diagnóstico diferencial clínico y dermatoscópico entre estas 2 afecciones dermatológicas puede ser complejo. Presentamos 2 lesiones faciales en 2 pacientes de 38 años de difícil diagnóstico clínico y dermatoscópico en los que la microscopia confocal mostró nidos celulares con separación entre los nidos y el estroma, y polarización de los núcleos de las células tumorales, que son signos confocales asociados a epitelioma basocelular

The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf–like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma

[Patients with basal cell naevus syndrome should be offered an early multidisciplinary follow-up and treatment]. / Patienter med basalcellenævussyndrom bør tilbydes tidlig interdisciplinær opfølgning og behandling.

Basal cell naevus syndrome (Gorlin-Goltz syndrome) is a rare, autosomal dominantly inherited condition with a wide range of developmental and multiple organ-related anomalies. Cardinal features include multiple basal cell carcinomas, jaw cysts, palmoplantar pits and calcification of the falx cerebri. Other important clinical features are skeletal abnormalities and facial dysmorphism including macrocephaly. Germ-line mutations are found in PTCH1. Management of the syndrome requires a multidisciplinary approach, and in this article management guidelines are reviewed and discussed.

Gorlin syndrome and desmoplastic medulloblastoma: Report of 3 cases with unfavorable clinical course and novel mutations.

We present three cases of genetically confirmed Gorlin syndrome with desmoplastic medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One patient was found to have a novel germline missense PTCH1 mutation. Molecular analysis of recurrent tumor using fluorescent in situ hybridization (FISH) revealed PTEN and/ or PTCH1 loss in 2 patients. Whole exome sequencing (WES) of tumor in one patient revealed loss of heterozygosity of PTCH1 and a mutation of GNAS gene in its non-coding 3' -untranslated region (UTR) with corresponding decreased protein expression. While one patient died despite high-dose chemotherapy (HDC) plus stem cell rescue (ASCR) and palliative radiotherapy, two patients are currently alive for 18+ and 120+ months respectively following retrieval therapy that did not include irradiation. Infants with DMB and GS should be treated aggressively with chemotherapy at diagnosis to prevent relapse but radiotherapy should be avoided. The use of molecular prognostic markers for DMB should be routinely used to identify the subset of tumors that might have an aggressive course.