RESUMO
Superficial fibromas are a group of mesenchymal spindle cell lesions with pathomorphological heterogeneity and diverse molecular backgrounds. In part, they may be indicators of an underlying syndrome. Among the best-known entities of superficial fibromas is Gardner fibroma, a plaque-like benign tumor, which is associated with APC germline mutations and occurs in patients with familial adenomatosis polyposis (Gardner syndrome). Affected patients also have an increased risk to develop desmoid fibromatosis (DTF), a locally aggressive neoplasm of the deep soft tissue highly prone to local recurrences. Although a minority of DTFs occur in the syndromic context and harbor APC germline mutations, most frequently their underlying molecular aberration is a sporadic mutation in Exon 3 of the CTNNB1 gene. Up to date, a non-syndromic equivalent to Gardner fibroma carrying a CTNNB1 mutation has not been defined. Here, we present two cases of (sub-)cutaneous tumors with a hypocellular and collagen-rich Gardner fibroma-like appearance and pathogenic, somatic CTNNB1 mutations. We aim to differentiate these tumors from other fibromas according to their histological appearance, immunohistochemical staining profile and underlying somatic CTNNB1 mutations. Furthermore, we distinguish them from locally aggressive desmoid fibromatosis regarding their biological behavior, prognosis and indicated therapeutic strategies. Consequently, we call them CTNNB1-mutated superficial fibromas as a sporadic counterpart lesion to syndromic Gardner fibromas.
Assuntos
Fibroma , beta Catenina , Humanos , beta Catenina/genética , Fibroma/genética , Fibroma/patologia , Masculino , Feminino , Mutação , Pessoa de Meia-Idade , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Adulto , Síndrome de Gardner/genética , Síndrome de Gardner/patologia , Mutação em Linhagem GerminativaRESUMO
Background: Gardner syndrome is a rare genetic cancer predisposition disorder characterized by intestinal polyposis, multiple osteomas, and soft and hard tissue tumors. Dental anomalies are present in approximately 30%-70% of patients with Gardner syndrome and can be discovered during routine dental examinations. However, sometimes the diagnosis is challenging due to the high clinical variability and incomplete clinical picture. Herein, we report a family with various dental and bone anomalies, in which the definitive diagnosis was established with the help of a comprehensive genetic analysis based on state-of-the-art next-generation sequencing technology. Case presentation: A 17-year-old female index patient presented with dental (caries, impacted, retained and anteriorly located teeth) and atypical bone anomalies not resembling Gardner syndrome. She was first referred to our Genetic Counselling Unit at the age of 11 due to an atypical bone abnormality identified by a panoramic X-ray. Tooth 3.6 was surgically removed and the histopathology report revealed a Paget's disease-like bone metabolic disorder with mixed osteoblastic and osteoclastic activity of the mandible. A small lumbar subcutaneous tumor was discovered by physical examination. Ultrasound examination of the tumor raised the possibility of a soft tissue propagation of chondromatosis. Her sister, 2 years younger at the age of 14, had some benign tumors (multiple exostoses, odontomas, epidermoid cysts) and impacted teeth. Their mother had also skeletal symptoms. Her lower teeth did not develop, the 9th-10th ribs were fused, and she complained of intermittent jaw pain. A cranial CT scan showed fibrous dysplasia on the cranial bones. Whole exome sequencing identified a heterozygous pathogenic nonsense mutation (c.4700C>G; p.Ser1567*) in the APC gene in the index patient's DNA. Targeted sequencing revealed the same variant in the DNA of the other affected family members (the sister and the mother). Conclusion: Early diagnosis of this rare, genetically determined syndrome is very important, because of the potentially high malignant transformation of intestinal polyps. Dentists should be familiar with the typical maxillofacial features of this disorder, to be able to refer patients to genetic counseling. Dental anomalies often precede the intestinal polyposis and facilitate the early diagnosis, thereby increasing the patients' chances of survival. Genetic analysis may be necessary in patients with atypical phenotypic signs.
Assuntos
Síndrome de Gardner , Testes Genéticos , Humanos , Síndrome de Gardner/genética , Síndrome de Gardner/diagnóstico , Síndrome de Gardner/patologia , Feminino , Adolescente , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologia , Anormalidades Dentárias/diagnóstico , Diagnóstico Precoce , LinhagemRESUMO
Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.
Assuntos
Polipose Adenomatosa do Colo , Síndrome de Gardner , Odontoma , Osteoma , Humanos , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Proteína da Polipose Adenomatosa do Colo/genética , China , Síndrome de Gardner/genética , Síndrome de Gardner/complicações , Síndrome de Gardner/patologia , Genes APC , Mutação em Linhagem Germinativa , Mutação , Odontoma/complicações , Odontoma/genética , Osteoma/complicações , Osteoma/genéticaAssuntos
Neoplasias da Mama , Fibromatose Agressiva , Síndrome de Gardner , Mama/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Fibromatose Agressiva/complicações , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/patologia , Síndrome de Gardner/complicações , Síndrome de Gardner/diagnóstico , Síndrome de Gardner/patologia , HumanosRESUMO
Fibromatoses encompass a broad group of histopathologically similar fibroblastic/myofibroblastic proliferations with divergent clinical manifestations and behavior. Deep (desmoid-type) fibromatoses are typically large, rapidly growing, and locally aggressive tumors that occur in the abdominal wall, mesentery, and extra-abdominal soft tissue, principally the musculature of the trunk and extremities. Most sporadic cases of desmoid fibromatosis harbor inactivating mutations in CTNNB1, the gene encoding beta-catenin. Tumors occurring in the context of familial adenomatous polyposis and Gardner syndrome bear inactivating mutations in APC. By contrast, mutations in CTNNB1 or APC have not been identified in cases of superficial fibromatosis. Cutaneous involvement by desmoid fibromatosis is exceedingly rare. Here we present a 78-year-old male with desmoid-type fibromatosis arising in the dermis of the right medial calf with a pathogenic mutation in CTNNB1 and a variant of unknown significance in APC.
Assuntos
Polipose Adenomatosa do Colo/patologia , Derme/patologia , Fibromatose Agressiva/diagnóstico , Síndrome de Gardner/patologia , Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo , Idoso , Diagnóstico Diferencial , Fibromatose Agressiva/genética , Fibromatose Agressiva/cirurgia , Síndrome de Gardner/genética , Humanos , Masculino , Mutação , Resultado do Tratamento , beta Catenina/metabolismoRESUMO
Gardner fibroma (GF) is a benign soft-tissue tumor that is associated with Gardner syndrome and can progress to, or co-occur with, desmoid fibromatosis (DF). Herein, we report a unique case of an 11-year-old boy who presented with a rapidly growing soft-tissue mass after biopsy of a stable fat-rich lesion present in the calf muscles since infancy, with Magnetic resonance imaging findings suggesting an intramuscular adipocytic tumor. The resection showed GF and DF. DF arising from a preexisting GF (the so-called "GF-DF sequence") is a well-documented phenomenon. Although immunohistochemistry was negative for nuclear ß-catenin expression, a CTTNB1 S45F mutation, which has been associated with aggressive behavior in DF, was identified in both components using a next-generation sequencing-based molecular assay. This is the first time a mutation in CTNNB1 has been identified in GF and the GF-DF sequence, thus expanding our knowledge of the molecular pathogenesis of the GF-DF sequence and highlighting the role of molecular testing in pediatric soft-tissue tumors. The histologic findings of an adipocyte-rich intramuscular GF also are unique, expanding the morphological spectrum of GF and adding GF to the differential diagnosis of intramuscular lesions with an adipocytic component.
Assuntos
Adipócitos/patologia , Fibroma/genética , Fibromatose Agressiva/genética , Síndrome de Gardner/genética , Neoplasias Musculares/genética , Mutação , beta Catenina/genética , Pré-Escolar , Progressão da Doença , Fibroma/patologia , Fibroma/cirurgia , Fibromatose Agressiva/patologia , Fibromatose Agressiva/cirurgia , Síndrome de Gardner/patologia , Síndrome de Gardner/cirurgia , Predisposição Genética para Doença , Humanos , Masculino , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , FenótipoRESUMO
Desmoid-type fibromatosis (DTF, aggressive fibromatosis) is a non-metastasizing mesenchymal neoplasm of deep soft tissue with a tendency towards local recurrence. Genetic alterations affecting canonical Wnt/ß-catenin signaling are reported in the majority of DTF. While most sporadic DTF harbor somatic mutations in CTNNB1, germline mutations in adenomatous polyposis coli (APC) are known to occur in hereditary DTF types (FAP, Gardner-Syndrome). Additional single nucleotide variants (SNVs) in AKT1 (E17K) and BRAF (V600E) were reported in pediatric DTF with potential clinical implications. We performed targeted next-generation sequencing (NGS) in a large cohort of 204 formalin-fixed DTF samples, comprising 22 pediatric cases (patients age ≤18 years). The mutational status was correlated with clinicopathological characteristics. Overall, deleterious CTNNB1 mutations were detected in 89% of DTF, most frequently affecting the serine/threonine phosphorylation sites T41 and S45 of ß-catenin. While the T41A CTNNB1 mutation was significantly more often identified in the mesenterial localization, DTF originating from extra-intestinal sites more frequently harbored the S45P CTNNB1 alteration. Beyond common mutations in CTNNB1, additional SNVs were demonstrated in 7% of the DTF cohort and in 18% of the pediatric DTF subgroup. The mutational spectrum included deleterious mutations in AKT1 (G311S/D and T312I), ALK (R806H and G924S), AR (A159T), EGFR (P848L), ERBB2 (H174Y), IDH2 (H354Y), KIT (V559D), RET (T1038A), SDHA (R325M), and SDHD (R115W), as characterized by in silico prediction tools. In conclusion, our study indicates that DTF may harbor a broader mutational spectrum beyond CTNNB1 mutations, comprising targetable alterations including the herewith first reported imatinib-sensitive KIT V559D mutation in DTF.
Assuntos
Fibromatose Agressiva/genética , Síndrome de Gardner/genética , Recidiva Local de Neoplasia/genética , beta Catenina/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Fibromatose Agressiva/epidemiologia , Fibromatose Agressiva/patologia , Síndrome de Gardner/epidemiologia , Síndrome de Gardner/patologia , Mutação em Linhagem Germinativa/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-akt/genética , Via de Sinalização Wnt/genética , Adulto JovemRESUMO
Superior vena cava (SVC) syndrome refers to the clinical manifestation due to an obstruction in the SVC; resulting in decreased venous return from the head, neck and upper extremities. The obstruction can occur either due to tumour invasion of the vessel wall with associated thrombus or due to vessel wall compression by the tumour mass. The patient being reported is a young male who presented with recurrent episodes of syncope and was found to have mediastinal Gardner fibroma causing SVC syndrome. Gardner fibroma is a benign soft tissue lesion; and its occurrence in the mediastinum resulting in SVC syndrome has not been reported yet.
Assuntos
Síndrome de Gardner/complicações , Neoplasias do Mediastino/complicações , Síndrome da Veia Cava Superior/etiologia , Síncope/etiologia , Adulto , Síndrome de Gardner/diagnóstico por imagem , Síndrome de Gardner/patologia , Síndrome de Gardner/cirurgia , Humanos , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/cirurgia , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Gardner's syndrome is a variant of familial adenomatous polyposis, characterized by gastrointestinal polyps, multiple osteomas, and skin and soft tissue lesions. Diagnosis by means of an understanding of its various symptoms is of great importance. CASE REPOSRT: This report presents the case of a 32-year-old man with obvious asymmetry and disfigurement on his face, due to multiple osteomas and soft tissue lesions. These clinical signs prompted us to further investigation, leading to the diagnosis of a case of Gardner's syndrome, with asymptomatic polyposis of the colon. Polyps have virtually an almost 100% risk of undergoing malignant transformation. CONCLUSION: Early diagnosis and treatment of this pathological entity are crucial, while the presence of osteomas should alert us to this diagnosis.
Assuntos
Neoplasias Ósseas/complicações , Ossos Faciais , Síndrome de Gardner/patologia , Osteoma/complicações , Neoplasias de Tecidos Moles/complicações , Adulto , Neoplasias Ósseas/patologia , Transformação Celular Neoplásica/patologia , Diagnóstico Precoce , Síndrome de Gardner/complicações , Humanos , Masculino , Osteoma/patologia , Neoplasias de Tecidos Moles/patologiaRESUMO
Introduction: Gardner's syndrome is a clinical subgroup of Familial Adenomatosus Polyposis, arare, autosomal disease. It is characterized by gastrointestinal polyps and extra-intestinal manifestations including multiple osteomas, skin and tissue tumours. The authors describe a case of a male patient, and discuss the diagnosis, treatment and follow-up of patients with Gardner's syndrome. We conclude that the knowledge of rare syndromes is very important for the correct treatment.
Assuntos
Síndrome de Gardner/diagnóstico , Síndrome de Gardner/terapia , Polipose Adenomatosa do Colo/patologia , Adulto , Fibromatose Agressiva/patologia , Síndrome de Gardner/patologia , Humanos , Masculino , Doenças RarasRESUMO
RESUMEN El sindrome de Gardner- Diamond conocido también como púrpura psicógena o síndrome de autosensibilización eritrocitaria es muy poco frecuente. Se presenta el caso de un hombre de 50 años, blanco, ingresado en el Servicio de Medicina Interna del Hospital Clínico Quirúrgico Docente "Faustino Pérez Hernández" por síndrome febril agudo, cefalea holocraneana, epistaxis y hemolacria. En el examen físico realizado se notó la salida de lágrimas con sangre, por el ángulo interno de ambos ojos y epistaxis. La inyección intradérmica en la cara dorsal del muslo izquierdo de 0,1 mL de sangre autóloga, no indujo reacción equimótica. La inyección de 0,1 mL de solución salina al 0,9 % como control en el muslo contralateral resultó negativa. Sobre la base del examen clínico y otras pruebas, se concluyó como un Síndrome de Gardner-Diamond. Esta infrecuente enfermedad debe ser considerada en el diagnóstico diferencial de un síndrome purpúrico de etiología no bien precisada, fundamentalmente en pacientes con problemas psiquiátricos.
ABSTRACT The Gardner-Diamond syndrome, also known as psychogenetic purpura or erythrocyte autosensitization syndrome is very few frequent. The case of a white patient aged 50 years is presented. He entered the Service of Internal Medicine of the Teaching Clinic-surgical Hospital "Faustino Pérez Hernández" because of an acute fever syndrome, holocraneal headache, epistaxis and haemolacria. At the physical examination it was stated the flow of tears with blood, through the internal angle of both eyes and epistaxis. The intradermal injection of 0.1 ml of autologous blood in the left thigh dorsal side did not induce an ecchymotic reaction. The injection of 0.1 ml of 0.9 % saline solution as control in the contralateral side was negative. On the basis of the clinical examination and other tests, the authors arrived to the conclusion it is a Gardner-Diamond syndrome. This infrequent disease should be considered in the differential diagnosis of a purpuric syndrome of non-good précised etiology, mainly in patients with psychiatric problems.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Gardner/etiologia , Síndrome de Gardner/história , Síndrome de Gardner/patologia , Síndrome de Gardner/epidemiologia , Síndrome de Gardner/diagnóstico por imagem , Epistaxe/diagnóstico , Febre/diagnóstico , Cefaleia/diagnósticoRESUMO
Gardner syndrome describes a variant phenotype of familial adenomatous polyposis (FAP), primarily characterized by extracolonic lesions including osteomas, dental abnormalities, epidermal cysts, and soft tissue tumors. We describe a 2-yr-old boy presenting with a 2-cm soft tissue mass of the forehead. Pathologic evaluation revealed a nuchal-type/Gardner-associated fibroma. Sequencing of the APC gene revealed a pathologic variant c.4666dupA. Parental sequencing of both blood and buccal tissue supported the de novo occurrence of this pathologic variant. Further imaging revealed a number of additional lesions including a large lumbar paraspinal desmoid, a 1-cm palpable lesion posterior to the left knee, firm lesions on bilateral heels, and multiple subdermal lesions. Colonoscopy was negative. This case illustrates a genetic variant of Gardner syndrome resulting in an aggressive early childhood phenotype and highlights the need for an individualized approach to treatment.
Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Testa/patologia , Síndrome de Gardner/patologia , Calcanhar/patologia , Joelho/patologia , Pré-Escolar , Testa/diagnóstico por imagem , Síndrome de Gardner/genética , Variação Genética , Calcanhar/diagnóstico por imagem , Humanos , Joelho/diagnóstico por imagem , Masculino , Linhagem , Fenótipo , Análise de Sequência de DNA , Carga TumoralRESUMO
Gardner syndrome is an autosomal dominant disease. It is characterized by a combination of familial adenomatous polyposis (FAP) of the intestine with extraintestinal changes as multiple osteomas and fibromas. Odontogenic Myxoma is a benign, aggressive intraosseous neoplasm. We report a rare case of a 14-year-old male patient with Gardner's syndrome and odontogenic myxoma, which involved the entire left half of the mandible, resulting in a gross facial deformity, within a span of one year.
Assuntos
Síndrome de Gardner/diagnóstico por imagem , Tumores Odontogênicos/diagnóstico por imagem , Radiografia Dentária/métodos , Adolescente , Tomografia Computadorizada de Feixe Cônico , Fibroma/diagnóstico por imagem , Síndrome de Gardner/patologia , Síndrome de Gardner/cirurgia , Síndrome de Gardner/terapia , Humanos , Imageamento Tridimensional , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Tumores Odontogênicos/patologia , Tumores Odontogênicos/cirurgia , Tumores Odontogênicos/terapia , Odontoma/diagnóstico por imagem , Osteoma/diagnóstico por imagemRESUMO
Gardner's syndrome (GS) is an autosomal dominant disease characterized by the presence of familial adenomatous polyposis (FAP) as well as extraintestinal manifestations such as osteomas, dental anomalies, epidermoid cysts and ocular abnormalities. These intestinal polyps carry a 100% risk of malignant change, so early diagnosis is crucial. As craniofacial osteomas and dental anomalies of GS usually precede gastrointestinal symptoms, otolaryngologists, oral surgeons and dentists play an important role in the diagnosis of GS. GS is extensively reported in literature in the Caucasian race but not in the Mongoloid race. We report a case of a 22-year-old patient with a manifestation of three features of GS - multiple osteomas, soft tissue tumors and dental anomalies in the craniofacial region, with no intestinal polyps at the time of reporting. A family pedigree with our patient as the proband was constructed and revealed 3 consecutive generations in his lineage with GS.
Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Síndrome de Gardner/diagnóstico , Osteoma/diagnóstico , Neoplasias Cranianas/diagnóstico , Anormalidades Dentárias/diagnóstico , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/patologia , Adulto , Povo Asiático , Diagnóstico Diferencial , Família , Síndrome de Gardner/complicações , Síndrome de Gardner/patologia , Humanos , Masculino , Osteoma/etiologia , Linhagem , Neoplasias Cranianas/etiologia , Tomografia Computadorizada por Raios X , Anormalidades Dentárias/complicações , Adulto JovemRESUMO
Gardner syndrome (GS), a variant of familial adenomatous polyposis, is a rare genetic disorder with autosomal dominant inheritance, characterized by the presence of multiple intestinal polyps, multiple osteomas, dental abnormalities and soft tissue tumors. To date, only a few gene mutations have been demonstrated to be responsible for GS. To explore potential unknown mutations responsible for GS, the present study used wholeexome sequencing of two affected individuals from a family with GS to identify a candidate mutation in mutLhomolog (MLH)1. The two patients with GS were diagnosed based on a combination of clinical features, family history, physical examinations and conebeam computed tomographic imaging. Through wholegenome sequencing, the present study subsequently identified a missense mutation in MLH1 (NM_000249.3:p.Tyr379Ser/c.1136A>C), which was further confirmed by Sanger sequencing. Furthermore, the amino acid residue p.Tyr379 was identified to be highly conserved among different species through sequence alignment with ClustalW2. In conclusion, the results identified for the first time a MLH1 missense mutation (NM_000249.3:âp.Tyr379Ser/c.1136A>C) in a Chinese family with GS, thus broadening the range of mutated genes associated with GS. This highlights the value of wholeexome sequencing in identifying disease mutations in a family.
Assuntos
Síndrome de Gardner/genética , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Proteína 1 Homóloga a MutL/genética , Mutação de Sentido Incorreto , Adulto , Substituição de Aminoácidos , Povo Asiático , Família , Síndrome de Gardner/patologia , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Fibroma/patologia , Fibroma/cirurgia , Síndrome de Gardner/patologia , Neoplasias Cutâneas/patologia , Biópsia por Agulha , Bulgária , Criança , Fibroma/diagnóstico , Seguimentos , Síndrome de Gardner/diagnóstico , Síndrome de Gardner/cirurgia , Cabeça/patologia , Humanos , Imuno-Histoquímica , Masculino , Doenças Raras , Couro Cabeludo/patologia , Índice de Gravidade de Doença , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Resultado do TratamentoRESUMO
Gardner syndrome (GS) is caused by mutations in the APC and besides adenomatous colorectal polyps includes such manifestations as osteomas, epidermoid cysts (ECs) and occasionally multiple pilomatricomas. More than 50 % of ECs in patients with GS exhibit pilomatricoma-like ghost cell keratinization. The latter may be explained by the fact that the development of both GS and pilomatricoma is driven by activation of the Wnt/ß-catenin signaling pathway. A 62-year-old, Caucasian male with history of GS presented with a unilocular, mixed radiopaque/radiolucent mandibular lesion causing divergence and external root resorption of involved teeth. Histopathologically, the lesion was composed of two cystic components, an orthokeratinized odontogenic cyst (OOC) and a smaller one with characteristics of keratocystic odontogenic tumor (KCOT) featuring, focally, ghost cells and an epithelial morule-like structure. Dystrophic calcifications essentially similar to those seen in pilomatricomas were observed in the fibrous connective tissue wall. The KCOT and OOC epithelia revealed strong and diffuse cytokeratin (AE1/AE3) and ß-catenin immunoreactivity. CD10 positive immunostaining was seen in the keratin and superficial spinous cell layers in both OOC and KCOT. The intraepithelial and mural ghost cells showed a cytokeratin (+), ß-catenin and CD10 (-) immunophenotype. The diagnosis of OOC with ghost cell calcifications in association with KCOT was rendered. The patient was lost to follow-up. Although a coincidental co-existence cannot be excluded, ghost cell calcifications mimicking pilomatricoma-like changes in an unusual odontogenic cyst combining OOC and KCOT features as seen in this patient with GS may be explained by the common molecular mechanisms underlying the pathogenesis of cutaneous pilomatricomas and GS.
Assuntos
Síndrome de Gardner/patologia , Neoplasias Maxilomandibulares/patologia , Cisto Odontogênico Calcificante/patologia , Tumores Odontogênicos/patologia , Síndrome de Gardner/complicações , Humanos , Neoplasias Maxilomandibulares/etiologia , Masculino , Pessoa de Meia-Idade , Cisto Odontogênico Calcificante/etiologia , Tumores Odontogênicos/etiologiaRESUMO
The skin is often the herald of an underlying systemic illness, and gastrointestinal malignancies can present in numerous ways in the skin. Paraneoplastic phenomenon, such as acanthosis nigricans and tripe palm, may be the first indicator of a gastrointestinal malignancy. In addition, gastrointestinal cancers can metastasize to the skin, as described in the well-known Sister Mary Joseph's nodule. Inflammatory systemic conditions such as dermatomyositis and multicentric reticulohistiocytosis can be associated with underlying malignancy. Finally, in numerous genetic syndromes with underlying malignancies, such as Muir-Torre, recognition of the skin signs leads to early diagnosis and screening.
Assuntos
Neoplasias Gastrointestinais/patologia , Síndromes Paraneoplásicas/etiologia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/patologia , Dermatomiosite/etiologia , Dermatomiosite/patologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Síndrome de Gardner/etiologia , Síndrome de Gardner/patologia , Humanos , Hipertricose/etiologia , Hipotricose/etiologia , Hipotricose/patologia , Ceratodermia Palmar e Plantar/etiologia , Ceratodermia Palmar e Plantar/patologia , Síndrome de Muir-Torre/etiologia , Síndrome de Muir-Torre/patologia , Síndromes Paraneoplásicas/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/secundárioRESUMO
Numerous familial tumor syndromes are associated with distinctive oral mucosal findings, which may make possible an early diagnosis as an efficacious marker for the risk of developing visceral malignancies. In detail, Familial Adenomatous Polyposis (FAP), Gardner syndrome, Peutz-Jeghers syndrome, Cowden Syndrome, Gorlin Syndrome, Lynch/Muir-Torre Syndrome and Multiple Endocrine Neoplasia show specific lesions of the oral mucosa and other distinct clinical and molecular features. The common genetic background of the above mentioned syndromes involve germline mutations in tumor suppressor genes, such as APC, PTEN, PTCH1, STK11, RET, clearly implied in both ectodermal and mesodermal differentiation, being the oral mucosal and dental stigmata frequently associated in the specific clinical phenotypes. The oral and maxillofacial manifestations of these syndromes may become visible several years before the intestinal lesions, constituting a clinical marker that is predictive for the development of intestinal polyps and/or other visceral malignancies. A multidisciplinary approach is therefore necessary for both clinical diagnosis and management of the gene-carriers probands and their family members who have to be referred for genetic testing or have to be investigated for the presence of visceral cancers.