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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Antal, Zsigmond, Till, Orsi, Szanto, Büki, Kereskai, Herbert, Hadzsiev and Bene.)

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., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 β-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.

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/β-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 β-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.

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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (Copyright © 2019 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

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., (© 2019 Kiessling et al.; Published by Cold Spring Harbor Laboratory Press.)

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., (© 2018 médecine/sciences – Inserm.)

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 whole‑exome sequencing of two affected individuals from a family with GS to identify a candidate mutation in mutL‑homolog (MLH)1. The two patients with GS were diagnosed based on a combination of clinical features, family history, physical examinations and cone‑beam computed tomographic imaging. Through whole‑genome 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:​p.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 whole‑exome sequencing in identifying disease mutations in a family.

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.

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/β-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 β-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 (+), β-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.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ameloblastic carcinoma and ghost cell odontogenic carcinoma are rare malignancies arising in odontogenic epithelium within the jaws. Gardner syndrome is a multifaceted autosomal dominant condition, which results in multiple dentofacial anomalies along with premalignant colon polyp formation and tumor formation in the skin and other organs. We report a case of ameloblastic carcinoma with features of ghost cell odontogenic carcinoma and extensive clear cell change and melanin pigmentation in a patient with clinical features of Gardner syndrome. To the best of our knowledge, odontogenic carcinoma arising in a patient with features of Gardner syndrome has not been reported previously. The clinical, radiographic, and histologic features of the case are discussed along with a review of the relevant literature., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Familial adenomatous polyposis (FAP) or Gardner's syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner's syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option.

Desmoid tumours are benign, myofibroblastic stromal neoplasms common in Gardner's syndrome, which is a subtype of familial adenomatous polyposis characterized by colonic polyps, osteomas, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The primary treatment is surgery, followed by adjuvant radiotherapy, but the local recurrence rate is high, and wide resection can result in debilitating loss of function. We report the case of a 39-year-old man with Gardner's syndrome who had already undergone a total prophylactic colectomy. He developed desmoid tumours localized in the mesenteric root, abdominal wall and dorsal region, which were treated from 2003 through 2013 with several surgical procedures and percutaneous radiofrequency ablation. In 2008 and 2013, RFA was applied under ultrasonographic guidance to two desmoid tumours localized in the dorsal thoracic wall. The outcomes were low-grade pain and one case of superficial skin necrosis, but so far there has been no recurrence of desmoid tumours in these locations. Surgical resection remains the first-line therapy for patients with desmoid tumours, but wide resection may lead to a poor quality of life. Radiofrequency ablation is less invasive and expensive and is a possible therapeutic option for desmoid tumours in patients with Gardner's syndrome.

Gardner's syndrome is an autosomal dominant disease characterised by the presence of colonic polyposis, osteomas and a multitude of soft tissue tumours. Pathological features such as osteomas of the mandible, skull and facial skeleton are unaesthetic as well as incapacitating. We present the case of a 22-year-old man with pain and discharge from the left eye and a firm swelling in the left infraorbital region leading to proptosis of the left eye. A detailed examination of the patient led to the presence of a large osteoma in the left orbital region, multiple cystic lesion, corneal opacity and parapapillary atrophy in the left eye. Radiography revealed the presence of multiple unerupted supernumerary teeth and osteomas. Colonoscopic findings showed the presence of multiple polyps. Thus, external manifestations of the patient's facial region led to the establishment of the diagnosis of Gardner's syndrome. The importance of our case highlights the necessity of maintaining a high vigilance with regard to the occurrence of such an entity., (2014 BMJ Publishing Group Ltd.)

Turcot's syndrome is a rare clinical syndrome, characterized by the association between familial adenomatous polyposis (FAP) and a primary central nervous system tumour. Gardner's syndrome is characterized by the association between FAP and several tumour types such as multiple osteomas, fibromas, epidermoid cysts and desmoid tumours. We report here the case of a twenty-six year-old woman with a history of both Turcot's and Gardner syndromes. She had a family history of adenomatous polyposis with a mutation in the APC (Adenomatous Polyposis Coli) gene. At the age of 26, she presented a mucoepidermoid carcinoma of the right parotid gland in which the MECT1-MAML2 fusion was showed. We discuss the possible addition of this latter cancer type in the definition of Gardner's syndrome., (Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Gardner's syndrome (GS) is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon together with osseous tumors and soft-tissue tumors, such as epidermoid cysts and lipomas. An osteoma is a benign, osteogenic tumor and may be sporadic or related to GS. Here, we present a patient with a giant sino-orbital osteoma and blepharoptosis as the only symptom of incomplete GS. A 74-year-old woman, with no previous history of trauma or ophthalmic surgery, presented with a 2 years history of right blepharoptosis without diplopia. The results of slit-lamp and fundoscopic examination were normal. Computed tomography showed a giant sino-orbital osteoma. With suspicion for GS, we thoroughly examined the patient and found no soft-tissue tumors. Fifteen years ago, the patient, who had a family history of colonic polyposis, underwent right colectomy and chemotherapy for adenocarcinoma. We report a case of incomplete GS with blepharoptosis as the first symptom.

Gardner's syndrome is a variant of Familial Adenomatous Polyposis (FAP), a condition that manifests as hundreds of colorectal polyps likely to undergo malignant change by the fourth decade. Early diagnosis of this condition has the potential to be life saving for individuals and due to its inherited nature other family members can often also be affected. Additional features of Gardner's Syndrome include multiple jaw osteomas with missing teeth that can make prosthodontic treatment a challenge. This case report highlights the presenting features and the prosthodontic problems faced when treating a patient with Gardner's syndrome.

The authors describe a patient with an adamantinomatous craniopharyngioma (CPG) arising in the cerebellopontine angle (CPA), who also had probable Gardner's syndrome. This 31-year-old man presented with headache and dizziness. Brain CT and MRI showed a 5 × 4-cm lesion with multiple small calcifications in the left CPA. The patient underwent suboccipital craniotomy with tumor removal. Histopathological findings indicated an adamantinomatous CPG. This patient also showed characteristics of Gardner's syndrome. Although this syndrome is associated with intracranial neoplasms, it is unclear whether patients with both Gardner's syndrome and CPG are part of the heterogeneity of Gardner's syndrome.

Gardner's syndrome occurs when mutation of the adenomatous polyposis coli gene is associated with extra-intestinal manifestations in addition to colorectal adenomas. Only eleven cases of gallbladder adenoma in Gardner's syndrome have been previously reported in the literature. We report a case of Gardner's syndrome in which multiple adenomas are associated with unicryptal adenomas. The lesion showed cytoplasmic and nuclear expression of β-catenin. The identification of multiple fully formed and unicryptal adenomas in the gallbladder are suggestive of Gardner's syndrome, and these patients require further investigation and follow up., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Background: This study was designed to investigate the clinical features and the growth rate of craniofacial osteomas., Methods: Retrospective chart review was performed of 200 cases of craniofacial osteomas diagnosed from January 2001 to September 2011. Data pertinent to patient and osteoma lesion characteristics were collected. Histology of operated cases was reviewed. Computer tomography (CT) charts were reviewed and those with multiple images were analyzed for growth characteristics., Results: One hundred forty-nine patients met our inclusion criteria. Eighty-nine percent of these osteomas were found incidentally. Forty-three percent were in the frontal sinus. Fifteen percent of the patients complained of headaches and only 6.71% of patients with osteoma had headaches congruent with osteoma location. Thirty-one percent of CT scans had sinus mucosal disease; only 8% had mucosal disease adjacent to the osteoma. Ten of the 149 patients underwent surgery for cosmetic and/or rapidly growing osteomas. Thirteen patients had intestinal tubular adenoma, and one was genetically positive for Gardner's syndrome. Fifty-two patients had multiple CT scans that were included in growth rate analysis. The mean linear growth rate of osteomas was estimated to be 0.117 mm/yr (95% CI, 0.004, 0.230) in maximal dimension, assuming linear growth. A descriptive analysis of osteoma growth divided the osteomas into several intervals and studied the growth rate separately in each interval. The median change in maximum dimension was different in each interval in a nonsystematic manner, ranging from -0.066 mm, over 3- to 9-month interval (interquartile range [IQR] = -0.404-1.069), to 0.369 mm over 9- to 15-month interval (IQR = -0.032-0.855), and 0.082 mm over 45- to 51-month interval (IQR = -0.000-0.197). There was no significant association between tumor size, location, or complications., Conclusion: Craniofacial osteomas are slow-growing lesions with no specific growth pattern and rare complications. Their clinical behavior is ill defined and justifies a conservative approach toward asymptomatic lesions with close radiological follow-up.

Osteomas are benign slow-growing tumors. These lesions are essentially restricted to the craniofacial skeleton and rarely diagnosed in other bones. The etiology is often multifactorial. It could be genetic or congenital, (Gardner syndrome) or related to endocrine disorders, chronic inflammatory processes, or traumas. In this work, the authors wanted to illustrate the correlation between the presence of multiple osteomas in the craniofacial skeleton and Gardner syndrome to underscore the importance of the role of the oral surgeon in the early identification of this pathology. Malignant evolution of intestinal lesions arising from Gardner syndrome can be avoided if diagnosed in an early stage. Two significant clinical cases are described and discussed. In the first one, a diagnosis of Gardner syndrome was made after colonoscopy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Attenuated familial adenomatous polyposis (AFAP) is characterized by the presence of 10-99 colorectal adenomas. The disease may be associated with mutations in either APC or MUTYH genes. We purposed to evaluate the contribution of adenomatous polyposis coli (APC) and MutY homologue (MUTYH) germline alterations to the AFAP phenotype and to identify genotype/phenotype correlations., Methods: During counselling for familial adenomatous polyposis (FAP), 91 probands (and 107 affected individuals) who met the criteria of AFAP were identified. Eighty-two families were screened for constitutional mutations of the APC and MUTYH genes., Results: MUTYH mutations were detected in 21 families (25.6 % of the 82 tested), and APC mutations in 7 (8.5 %). Overall, constitutional alterations were found in 34.1 % of the probands. Patients with APC mutations were younger at cancer onset and had a higher mean number of polyps (48.5 ± 33.0 in APC+ individuals vs. 35.7 ± 24.9 in MUTYH+ individuals, and 33.2 ± 18.4 in the "no mutation" group). Clinical features rendered the "no mutation" group closer to MUTYH+ than to the APC+ group. Colorectal cancer at diagnosis was detected in 40 % of AFAP individuals., Conclusions: AFAP is a new clinical entity with its frequency in the general population still undefined. The number of adenomas varies greatly, with an average of 30-40 lesions. The molecular basis of AFAP can be established in approximately 1/3 of the patients. Both MUTYH and APC genes are implicated in AFAP, though the role of MUTYH is of considerably greater relevance.

Aims and Methods:   Desmoid-type fibromatosis (desmoid) is a fibroblastic tumour that shows locally aggressive growth. Mesenteric desmoid is a rare lesion that shares morphological and biological features with fibromatoses occurring in the abdominal wall or in extraabdominal sites, but differs in terms of gross appearance and clinical presentation. We report on a series of 56 cases of mesenteric desmoids from our consultation files and compare them with cases of non-mesenteric desmoids and retroperitoneal fibrosis., Results:   Primary diagnosis of desmoid-type fibromatosis was correct in 42%, and gastrointestinal stromal tumour was a common misdiagnosis. Nuclear expression of β-catenin was detected in 91.6% of all desmoids. Mutational analysis of exon 3 of the β-catenin gene (CTNNB1) revealed that mesenteric desmoids carried mutations significantly more often (51/56, 91.1%) than non-mesenteric tumours (20/28; 71.4%; P = 0.027). p.T41A occurred significantly more frequently in mesenteric fibromatoses (80.4%) than in abdominal wall and extra-abdominal fibromatoses (46.4%; P = 0.002). Two novel mutations (p.S45C and p.D32G) were found. In retroperitoneal fibrosis, mutations and nuclear β-catenin expression were absent. β-Catenin-negative desmoids either carried a CTNNB1 mutation or were associated with Gardner syndrome., Conclusions: Our study provides evidence that some clinical and genetic features of mesenteric desmoids differ from those of non-mesenteric fibromatosis, and corroborates the usefulness of mutational analysis, especially in diagnosing β-catenin-negative mesenteric desmoids., (© 2012 Blackwell Publishing Limited.)

Desmoplastic fibroblastoma (DF) is a benign fibroblastic/myofibroblastic tumor. Cytogenetic analyses have revealed consistent rearrangement of chromosome band 11q12, strongly suggesting that this region harbors a gene of pathogenetic importance. To identify the target gene of the 11q12 rearrangements, we analyzed six cases diagnosed as DF using chromosome banding, fluorescence in situ hybridization (FISH), single-nucleotide polymorphism array and gene expression approaches. Different structural rearrangements involving 11q12 were found in five of the six cases. Metaphase FISH analyses in two of them mapped the 11q12 breakpoints to an ~20-kb region, harboring FOSL1. Global gene expression profiling followed by quantitative real-time PCR showed that FOSL1 was expressed at higher levels in DF with 11q12 rearrangements than in desmoid-type fibromatoses. Furthermore, FOSL1 was not upregulated in the single case of DF that did not show cytogenetic involvement of 11q12; instead this tumor was found to display a hemizygous loss on 5q, including the APC (adenomatous polyposis coli) locus, raising the possibility that it actually was a misdiagnosed Gardner fibroma. 5'RACE-PCR in two 11q12-positive DF did not identify any fusion transcripts. Thus, in agreement with the finding at chromosome banding analysis that varying translocation partners are involved in the 11q12 rearrangement, the molecular data suggest that the functional outcome of the 11q12 rearrangements is deregulated expression of FOSL1.

Approximately 5% of differentiated thyroid carcinomas with follicular cell differentiation, papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) and 25-30% of medullary thyroid carcinoma (MTC) are hereditary. They occur either as part of a defined syndrome or are confined to the thyroid gland. Compared to their sporadic non-hereditary counterparts hereditary thyroid carcinomas generally develop earlier and regularly show multifocal tumour growth. With the exception of familial MTC, which is preceded by neoplastic C cell hyperplasia, no precursor lesions of hereditary thyroid carcinoma are known. In strong correlation with the localisation of the germline mutation of the RET protooncogene, familial MTC shows a distinct clinical course which allows precise clinical decision-making for prophylactic thyroidectomy to prevent invasive MTC. According to current knowledge prophylactic thyroidectomy of all other types of hereditary thyroid carcinoma is not justified.

Adnexal tumours of the skin are benign, more rarely malignant, primary skin tumours that originate from, or differentiate towards, hair follicles, sebaceous and sweat glands. Although they are usually encountered as single, sporadic tumours, they may occasionally be multiple, hereditary; in that case, they may herald complex genetic syndromes that comprise visceral cancers. Dermatologists should be aware of these adnexal skin tumours, the diagnosis of which may contribute to an early detection of a cancer-prone syndrome with a potentially lethal outcome. The main tumours falling into this category and their associated syndromes are reviewed here.

Gardner fibroma represents a rare and recently described soft tissue tumor entity in children and young adults. It consists of haphazardly arranged coarse and hyalinized collagen fibers combined with loosely arranged bland spindle and fibroblastic cells. The case of a 13-year-old male patient with Gardner fibroma and osteoma and multicentric desmoid type fibromatosis in his mother is presented with detection of a (heterozygotic) germline mutation of the APC gene leading to a de novo stop codon (deletion of base pairs 5033-5036). FISH analysis revealed a structural loss of heterozygosity (LOH) in the APC gene on chromosomal locus 5q21 in one out of five analysed desmoids of the mother, no LOH of APC gene in the Gardner fibroma. Gardner fibroma in children and young adults may serve as an indicator lesion for familial adenomatous polyposis (FAP), Gardner syndrome, a familial desmoid type fibromatosis without other manifestations of APC or a new APC gene mutation. For the clinician, this diagnosis should be commented upon accordingly by the surgical pathologist. As the result of a detected APC gene mutation, continuous follow-up for the development of colorectal tumors and desmoid type fibromatosis as well as a familial screening for FAP is recommended.

Gardner syndrome is a variant of familial adenomatous polyposis (FAP) and results in the manifestation of numerous external and internal symptoms including gastrointestinal polyps, osteomas, tumors, and epidermoid cysts. As such, it is highly recommended that physicians conduct full body examinations to catch the key clinical features of the disease when it is suspected. Stemming from a mutation in the adenomatous polyposis coli (APC) gene, Gardner syndrome shares genetic correlations with the FAP phenotype; as a result, it becomes all the more crucial for physicians to be able to discern Gardner syndrome from other differential diagnoses such as Turcot syndrome, FAP, and other attenuated forms of familial polyposis. Fortunately, Gardner syndrome has characteristic polyps in the colon, osteomas, and also exhibits abnormalities in the retinal epithelium that discern it from others. Surgery is the most effective method of management for Gardner syndrome; restorative proctocolectomy with ileal pouch anal anastomosis with mucosectomy is the top choice for colonic malignancies, and skin manifestations can be treated through a variety of excisions and therapy depending on location, size, and number of malignancies. Currently, there are no specific screening recommendations for Gardner syndrome, but testing following general screening recommendations for extra-colonic malignancies, genetic counseling, and endoscopy are encouraged.

Gardner's syndrome is a clinical subgroup of familial adenomatous polyposis, an autosomal dominant disease. It is characterized by gastrointestinal polyps and extra-intestinal manifestations including multiple osteomas, skin and soft tissue tumours. Aggressive desmoid tumours can be very difficult to manage in patients with Gardner's syndrome. We present a case of a 17-year-old female who presented with an aggressive desmoid tumor arising of the lumbar area as part of her Gardner's syndrome. She was treated with surgery, nonsteroidal anti-inflammatory drugs, tamoxifen and radiotherapy, and was followed up for 80 months. We conclude that desmoid tumors can precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome. Such patients should be evaluated with genetic testing followed by colonoscopy. Desmoid tumours should be managed in a multidisciplinary setting, as well.

Deep fibromatosis is a rare locally aggressive but not metastasizing proliferation. Intra-abdominal fibromatosis (IAF) occurs either in association with Gardner's syndrome or as a sporadic event and presents in most cases differential diagnostic problems with myofibroblastic or fibroblastic tumors, characterized by a more aggressive biological behaviour such as gastrointestinal stromal tumors (GISTs). In absence of loco-regional and/or distant metastasis differential diagnosis may be difficult and represents a topical issue, since it influences treatment choice. We describe the case of a patient with sporadic IAF in which the tumor locally involved the mesentery and presented no loco-regional and distant spread. On histology, some morphological features of the neoplasm were in common with a GIST. Definitive diagnosis was made, postoperatively, on the basis of immunohistochemical findings.

Gardner fibroma (GAF) is a benign soft tissue lesion with a predilection for childhood and adolescence and an association with familial adenomatous polyposis (FAP) and desmoid type fibromatosis (desmoid). We report 45 patients with GAF with clinicopathologic correlation and immunohistochemical analysis for beta-catenin and related proteins. Forty-five patients with 57 GAFs were identified from surgical pathology and consultation files. Immunohistochemistry for beta-catenin, cyclin-D1, and C-myc was performed on formalin-fixed, paraffin-embedded tissues using standard techniques in 25 GAFs from 24 patients. Information about family history, intestinal polyps, colon cancer, and soft tissue tumors was available in 23 patients. Sixty-nine percent had known FAP or adenomatous polyposis coli (APC), 22% had no history of familial polyps or soft tissue tumors, and 13% had an individual or family history of soft tissue masses and/or desmoids, with follow-up periods of 6 months to 26 years (median 3 y, mean 5 y). The age range at initial diagnosis was 2 months to 36 years. Seventy-eight percent were diagnosed in the first decade, 15% in the second decade, and 7% in the third decade. Eight patients (18%) had documented desmoids concurrently or later; 4 of these had FAP and 1 had familial desmoids. Sites of GAF included the back and paraspinal region in 61%, the head and neck in 14%, the extremities in 14%, and the chest and abdomen in 11%. All displayed a bland hypocellular proliferation of haphazardly arranged coarse collagen fibers with a bland hypocellular proliferation of inconspicuous spindle cells, small blood vessels, and a sparse mast cell infiltrate. Immunohistochemically, 64% showed nuclear reactivity for beta-catenin (9 patients with known APC, 5 without definite information about FAP). One hundred percent showed nuclear reactivity for both cyclin-D1 and C-myc. beta-catenin reactivity had no correlation with age, site, or recurrence. Two beta-catenin-negative GAFs were from FAP patients. In conclusion, GAF has a predilection for childhood and early adulthood, a strong association with FAP/APC, an association with concurrent or subsequent development of desmoids, and overexpression of beta-catenin and other proteins in the APC and Wnt pathways. The proportion of sporadic GAFs that have APC mutation remains to be determined.

The authors report on the case of a craniopharyngioma arising in the cerebellopontine angle (CPA) in a patient with Gardner syndrome. Although familial adenomatous polyposis (FAP) is associated with intracranial neoplasms, the current case is only the third reported craniopharyngioma in a patient with Gardner syndrome. Two of these tumors, including that of the current case, originated in the CPA, an unusual location for craniopharyngiomas. The literature concerning FAP and its associations with intracranial neoplasia, as well as the pathogenesis of craniopharyngiomas in the posterior fossa, is discussed.

Gardner's syndrome is an autosomal dominant disease characterized by the presence of colonic polyposis, osteomas and a multitude of soft tissue tumors. The syndrome may present at any age from 2 mo to 70 years with a variety of symptoms, either colonic or extracolonic. We present a case of a 11-year-old female patient with Gardner's syndrome who presented with a lumbar area desmoid tumor and treated with resection of the desmoid, restorative proctocolectomy and ileal pouch anal anastomosis, A review of the current literature has been performed.

Patients suffering from familial adenomatosis polyposis develop multiple pre-malignant gastrointestinal polyps and are at high risk of developing colon cancer. In addition extra-intestinal manifestations are observed frequently. The combination of extra-intestinal manifestations and familial adenomatosis polyposis is named Gardner's syndrome. An early diagnosis of this disease is important because it could mean a better prognosis for the patient. This review describes the oral and maxillofacial symptoms of FAP, and its potential implications for dental treatment.

Familial adenomatous polyposis (FAP) is a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colonic polyp become evident at a mean age of 16 years (range, 7-36 years). By age 35 years, 95% of patients have polyps. Gardner syndrome is the eponym given to a subgroup of FAP with extracolonic manifestations, such as pigmented ocular fundus lesions that resemble congenital hypertrophy of the retinal pigment epithelium, among others.

Three patients with Gardner's syndrome having benign fibrous proliferations in the soft tissues and the oral cavity are presented. Lesions in all three patients were morphologically different. Two excised lesions in Case 1 were histologically identical to nuchal-type fibroma (NTF) and one lesion in this patient was an epidermal cyst. Case 2 had a lesion located in the soft tissues of the shoulder, which was morphologically similar to NTF and, in addition, contained mildly atypical and multinucleated fibroblastic cells. The oral lesion in Case 3 looked like a fibroma and was morphologically different from all fibrous lesions that have ever been described in Gardner's syndrome. The cases in the present report show that the term Gardner's fibroma is just a descriptive name encompassing a spectrum of morphologically different benign fibrous proliferations associated with this syndrome. Therefore, the term Gardner's fibroma should not be used as a specific name for NTF arising in patients with Gardner's syndrome as suggested in the most recent WHO classification of soft tissue and bone tumors.