Oral manifestations of Cowden's disease. Presentation of a clinical case

Cowden's disease, or multiple hamartoma syndrome, is an autosomal dominant genodermatosis, characterized by the presence of multiple cutaneous hamartomas, oral fibromas and benign acral keratosis. It affects multiple organs (breast, thyroids, stomach, colon), with the strong possibility of malignant neoplasia developing in these organs. We present a case of this rare syndrome, highlighting the presentation of some clinical characteristics that, in suspected cases, can help to establish an early diagnosis of this disease, this being of great importance given the high frequency of tumors in people with this clinical picture.     

Cowden's syndrome. Case report, with reference to an affected family

Cowden's syndrome is a rare genodermatosis characterized by multiple hamartomas in several tissues and organs derived from all three embryonic layers. Clinical features of Cowden's disease are explained by the mutation of the PTEN tumour suppressor gene, whose modification leads to an uncoordinated growth of tissues. The importance of this disease lies in the increased susceptibility to malignization of some lesions, specially breast, thyroid and genito-urinary tract lesions. As a result, the disease has been considered a preneoplasic condition. Despite its varied phenotypic expression, this disease is generally unknown. Consequently, many cases are undiagnosed or diagnosis comes at a late stage, what points out the importance of an early diagnosis of the disease so the patient can have periodic check-ups to prevent malignant diseases. A family case is presented here, whose diagnosis was based upon oral clinical findings and which most distinct systemic alteration is the presence of hamartomatous polyps in the digestive tract in several family members.     

Gingival fibrous nodule.

Five patients with small, exophytic, asymptomatic fibrous nodules, single or multiple, of the mandibular mucogingival zone of the anterior labial gingiva are presented. Such nodules are benign and resemble small fibromas. The clinical and histologic appearance distinguishes them from entities such as retrocuspid papilla, reticular mandibular gingival ridges, oral hamartomas associated with Cowden's syndrome, tuberous sclerosis oral lesions, and oral nodules secondary to epidermolysis bullosa. Gingival fibrous nodule, or gingival nodule, is the proposed name for this lesion, which is essentially a variation of normal oral structures that may be mistaken for disease.     

Cowden's syndrome affecting the mouth, gastrointestinal, and central nervous system: a case report and review of the literature

Cowden's syndrome (CS) is a rare genodermatosis, of autosomal dominant inheritance and variable phenotype, principally characterized by the formation of hamartomas in various organs, including skin, thyroid, breast, brain, and gastrointestinal tract and by the increased risk for the development of malignancy. The present report details the features of a very rare presentation of Cowden's syndrome affecting not only the mouth and gastrointestinal mucosa but also the central nervous system.     

Multiple oral fibropapillomatosis as an initial manifestation of Cowden Syndrome. Case report

Cowden syndrome is a rare hereditary disease included within hamartoma-type gastrointestinal polyposis. It is characterised by associated mucocutaneous anomalies and by the extraordinary tendency to develop malignant neoplasia, mainly in the breast and thyroid. Early diagnosis of the syndrome and adequate tumoral screening in patients with mucocutaneous papillomatosis make it possible to make an earlier diagnosis of associated pathologies which have great morbidity when detected late. We present the case of a patient diagnosed with Cowden syndrome after consultation for labial papillomatous lesions of long evolution who was subsequently treated for breast and kidney cancer in initial stages. The correct diagnosis of a banal pathology of oral mucosa made it possible for us to take early action against the neoplastic pathology associated with this disease.     

Cowden syndrome: mucocutaneous lesions as precursors of internal malignancy

Background

Cowden syndrome is an autosomal-dominant hereditary cancer syndrome with high variability and susceptibility. It is characterized by multiple hamartomas and neoplasms of ectodermal, endodermal and mesodermal origin affecting many organs and also by the increased risk of development of internal malignancies.

Case report

A 62-year-old woman was referred to our Maxillofacial Unit with a hamartomatous mass of the left lateral tongue which had slowly grown and was obstructing normal speech and restricting oral intake. The patient had a known history of Cowden syndrome and underwent excision of the lesion under general anaesthetic.

Discussion

Orofacial mucocutaneous features are very common in multiple hamartoma and neoplasia syndrome with almost up to 90 % of the patients being affected. These cutaneous and mucosal lesions, which are predominantly benign, often manifest prior to the development of the internal malignant tumours associated with the syndrome.

Conclusions

The prompt identification of Cowden syndrome’s plethoric signs and symptoms can lead to appropriate surveillance and multidisciplinary management. Oral manifestations are frequent, prominent and usually precede the establishment of malignant tumours of visceral organs; hence, the maxillofacial surgeon or general dentist may have a significant role in the recognition of the disease. Overall prognosis is dependent on prevention or early treatment of internal malignancies; consequently, early diagnosis together with frequent follow-up forms the cornerstone of management.     

Sarcoidosis with oral involvement

A case of sarcoidosis with bilateral hilar lymphadenopathy and multiple submucosal papular oral mucosa lesions is presented. The clinical signs and symptoms described in this case are not uncommon, and their distinguishing features may expedite accurate diagnosis. Early incisional biopsy of the oral mucosa appears useful for histopathologic proof of the diagnosis.     

Gingival and cutaneous angiosarcoma

Multiple oral and cutaneous nodular and papular reddish-blue lesions are described in the case of a 60-year-old woman. The duration of the lesions was more than 1 year, with the oral lesion preceding the skin lesions. Histopathological examination revealed malignant vascular tumour with changes consistent with angiosarcoma. Angiosarcoma is an extremely rare malignant tumour of the oral cavity, and the present case describes oral and skin lesions with a unique clinical behaviour.     

Cowden's syndrome: a case report.

Cowden's syndrome, a rare genodermatosis of autosomal-dominant inheritance with variable expressivity, is characterized by a combination of ectodermal, mesodermal, and endodermal hamartomas that may involve the skin, mucous membranes, breasts, gastrointestinal tract, and thyroid. A 26-year-old woman who presented for replacement of her teeth, all of which had been extracted because of rapidly progressive periodontitis. She was diagnosed with Cowden's syndrome based on mucocutaneous abnormalities, thyroid involvement, and abnormalities of the skeletal and genitourinary systems. The clinical significance and differential diagnosis of this disease are highlighted.     

Viruses and chronic disorders involving the human oral mucosa.

Viruses have been implicated in the etiology of several chronic disorders of the oral mucosa. Most of these associations have been with DNA viruses, particularly certain herpesviruses, which are associated, for example, with some cases of erythema multiforme and with hairy leukoplakia. Papillomaviruses are associated with various papillomatous lesions, focal epithelial hyperplasia, and possibly with some carcinomas. Viruses may possibly be associated with recurrent aphthae, Beh?et's syndrome, and some dermatoses. The literature concerning these possible associations is reviewed. However, much more research needs to be done before the full story of viral associations with oral mucosal disorders can be written.     

Oral lichen planus: a review

Oral lichen planus is a disease that can persist in some patients for a long time. The buccal mucosa, tongue and gingiva are the most common sites, whereas palatal lesions are uncommon. Oral lichen planus affects women more often than men in a ratio of 2:3. It can present in a number of forms: reticular, papular, plaque-like, erosive, atrophic and bullous. The question of malignant transformation of oral lichen planus remains controversial. The management can be non-surgical or surgical and the choice of treatment may vary from patient to patient and depends on the choice of the clinician.     

Neoplastic transformation of oral lichen planus. II: association with risk co-factors

The possible malignant transformation of oral lichen planus is still controversial. It is not clear if this is in fact due to the premalignant nature of oral lichen planus or to the presence of some risk-factors in patients with this pathology. The risk co-factors that may he involved in this malignant transformation are numerous. Some authors suggested a correlation between oral lichen planus and HCV or HGV, or with the presence of some oncogenic viruses (EBV, HSV, HPV). Cases of this malignant transformation on oral and genital mucosa with lichen are reported, hut none on the skin lesions. The aim of this study is to investigate, through the literature, these correlations that may have a role in the malignant transformation of oral lichen planus.     

Soft-tissue lesions in children

This article reviews some of the benign and malignant oral soft-tissue swellings that occur in children, with an emphasis on their clinical presentation, etiology, histopathology, and treatment. These lesions include single and multiple nodules, reactive lesions, and benign and malignant neoplasms. Diseases discussed include reactive gingival swelling, generalized gingival fibromatosis, melanotic neuroectodermal tumor of infancy, fibromas, vascular lesions, salivary gland lesions, and infantile rhabdomyomas. Also covered are lesions that may present in multiples, such as neuromas, multiple endocrine neoplasia type 2b, neurofibromatosis, and human papilloma virus-related benign epithelial lesions. Benign but locally aggressive and malignant neoplasms are discussed, such as aggressive fibromatosis, myofibromatosis, fibrosarcoma, and rhabdomyosarcoma.     

Immunocytochemical detection of ornithine decarboxylase (ODC) in paraffin-embedded tissues as a possible prognostic indicator for oral lesions

Intracellular levels of ornithine decarboxylase (ODC) are raised following mitogenic stimulus and in neoplasia. Because lesions of the oral cavity are often difficult to assess histologically, we have determined the value of immunocytochemical detection of ODC as a prognostic indicator in 74 routinely fixed and paraffin-embedded oral biopsies using peroxidase-antiperoxidase and immunogold-silver staining. The latter proved more sensitive, yielding positive reactions in 32 of 43 oral carcinomas (11/14 well differentiated, 16/21 moderately differentiated and 3/5 poorly differentiated) and 7/11 potentially malignant lesions, compared with 19/45 carcinomas and 1/15 potentially malignant lesions, by peroxidase anti-peroxidase. Hyperplastic lesions ( n = 7) and normal non-keratinized buccal mucosa ( n = 7) were all negative. Follow-up was possible in 13 of the carcinoma patients. Of 7 positive ODC reactions but clinically node-free at biopsy, 2 died and 2 had recurrences within 3 years, whereas all of 6 with no immunoreactivity were symptom-free after 3–5 years. Immunostaining for ODC may be helpful for the prognostic assessment of routinely processed oral lesions and in choosing treatment.     

Cowden's syndrome (multiple hamartoma and neoplasia syndrome): diagnostic dilemmas in three cases

Cowden's syndrome is a multisystem disease inherited as an autosomal dominant trait with incomplete penetrance and variable expression. The disease has typical oral manifestations which often precede more systemic involvement, and the dental professional is therefore well placed to institute a regime of regular checks to ensure early treatment of any neoplasms which may occur. However, since not all of the classical signs are present in all patients, diagnosis may be difficult. The case report of a patient with most of the features of Cowden's syndrome is presented and features compared with two other possible cases.     

Some effects of N-methylnitrosourea on the oral and odontogenic tissues of the Syrian golden hamster.

The carcinogen NMU produces oral carcinoma and malformation of the incisor teeth in hamsters, but it is not clear whether neoplasia occurs in odontogenic tissues. Ten weanling hamsters received 1 mg NMU intragastrically, twice a week for 4 weeks. Eight survived for up to 3 to 15 months after dosing. All but one of these had premalignant papillomatosis of the forestomach, and premalignant lesions of oral epithelium which developed into carcinoma in two instances. Half the animals had visceral neoplasms. Between 4 and 18 weeks after dosing, the lower incisors became stunted, often permanently. Three hamsters developed odontogenic cysts in incisor enamel organs that had undergone squamous metaplasia. Other microscopic changes were dentinal dysplasia and the growth of islands of odontogenic epithelium in the periodontal ligament. The enduring dental malformation appeared to result from repetitive cytotoxic injury and resultant hamartoplasia, complicated by secondary metabolic deficiency of systemic origin, and by permanent disturbance of induction in odontogenesis. The proliferation of epithelium in the periodontium resembled early neoplastic change suggesting ameloblastoma. Although indisputable odontogenic tumours were not induced, this procedure may be developed as a model for production of odontogenic hamartomas and neoplasms.     

Papillomaviruses: the current status in relation to oral disease

Human papillomaviruses of different types are associated with a variety of benign oral lesions and may be associated with some premalignant and malignant oral lesions. However, since it is now clear that a variant of human papillomavirus 16 is harbored by normal oral mucosa, as well as by premalignant and malignant lesions, such associations may not necessarily always be causal. The rapid progress of recent research in this field is reviewed, with particular reference to oral disease, and the current status is discussed.     

Neoplastic transformation of oral lichen planus. I: Review of the literature

Lichen planus is described like a well-characterized dermatological condition affecting the skin and the oral and genital mucosa. Over the years, different authors have expressed the possible oral lichen planus premalignant nature, but this is still controversial. This criticism is due to the insufficiency of the clinical and histopathological data to support the initial diagnosis of oral lichen planus, the occurrence of some wrong diagnostic criteria for this pathology, the contemporary presence in the same region of the oral lichen planus lesions and of neoplasia. The malignant transformation of oral lichen planus rate varies, according to authors, from 0.4 to 3.7%. The aim of this study is to review the literature from 1910 to 1999, focusing on the suggested possible premalignant nature of oral lichen planus.     

Mucosal ganglioneuromatosis, medullary thyroid carcinoma, and pheochromocytoma: multiple endocrine neoplasia, type 2b.

Multiple endocrine neoplasia, type 2b, is a designation that has been proposed for the combination of medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and somatic abnormalities. The neural lesions produce a characteristic diffuse or nodular enlargement of lips, tongue, and buccal mucosa. Microscopically, the lesions are composed of unencapsulated masses of hypertrophied and elongated nerves in which are found rare ganglion cells. The histologic similarity between the oral mucosal lesions and the alimentary tract ganglioneuromatosis in the syndrome suggests that the term ganglioneuromatosis is the most appropriate designation for the oral lesions. The oral lesions signal high risk for two potentially lethal neoplasms--medullary thyroid carcinoma and pheochromocytoma. Thus, patients having the characteristic findings are in urgent need of repeated evaluation of thyroidal C-cell and adrenal medullary function.