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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...
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Birt-Hogg-Dubè (BHD) is an autosomal dominant syndrome characterised by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal cancer. The association of benign cutaneous lesions and increased cancer risk is also a feature of Cowden Syndrome (CS), an autosomal dominant disease caused by PTEN mutations. BHD and CS patients may develo...
A 5-month-old female Great Dane puppy was treated for hematochezia, tenesmus, and rectal prolapse by resection of a 10-cm-long segment of colon and rectum. Grossly, the colorectal segment had diffuse mucosal and submucosal thickening with multiple polypoid nodules. The histologic diagnosis was colorectal hamartomatous polyps with ganglioneuromatosi...
We present the case of a female patient with facial cutaneous lesions, a
cobblestone-like pattern of the oral mucosa, and verruciform lesions on the hand
since her youth. She reported a history of breast cancer, endometrial cancer,
melanoma and multiple benign tumors and cysts. PTEN gene analysis was performed and
confirmed Cowden Syndrome, a rare...
Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C-terminal function is less defined. Here, we describe a knockin mouse model of a nonsense mutation that results in the deletion of the entire Pten C-terminal region, referred to as Pten(ΔC...
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Citations
... The most common oral manifestation includes papillomatous lesions that affect various parts of the oral mucosa, including the tongue, the gingiva, the palate, and the buccal and labial mucosa (Chaudhry, et al., 2000). Other manifestations may include maxillary and mandibular hypoplasia, an enlarged and fissured tongue, hypodontia, severe dental caries, and periodontitis (Swart, et al., 1985, Chaudhry, et al., 2000, Blanco and Keochgerian, 2006. Dental practitioners may play an essential role in screening for CS, since the skin and mucosal lesions are common around the oral area (Swart, et al., 1985, Mignogna, et al., 1995. ...
Aim
In this review, several gastrointestinal diseases that dentists may encounter in practice are highlighted and discussed.
Materials and methods
Using MEDLINE (PubMed), a comprehensive review of gastrointestinal diseases and their oral cavity manifestations was performed.
Results
Many gastrointestinal diseases present with oral symptoms that are detectable by dentists and dental hygienists. Often, oral manifestations of the disease may appear before systemic signs and symptoms. Managing patients with these conditions requires dentists to adjust their treatment and/or involve other health professionals.
Conclusion
Care must be taken when providing periodontal therapy or dental implants to patients suffering gastrointestinal diseases who are at high risk of bleeding, infection, or malnutrition, for example. Also, pharmacological therapy for these patients may need to be customized.
... All extracted data were tabulated in Micro- . The articles were from Argentina [8], Brazil [6,7,39], Germany [31,32,34], Italy [40], Japan [22, 24-26, 28, 29, 47, 49], Yugoslavia [18], Portugal [45], Spain [37,48], South Korea [42], The Netherlands [19,20,38], Turkey [35], United Kingdom [21,23,27,30,41], United States [5, 13-17, 36, 43, 44, 46], and Uruguay [33] (Fig. 4A). A total of 56 cases of CS subjects (≥ 50 years) with orofacial manifestations were analyzed. ...
... Family history is another aspect used to support the diagnosis of CS. These data were reported in 21.4% of cases of individuals aged ≥ 50 years [6,13,15,18,20,26,29,33,34,40,41]. These features are in line with our case of a woman without a family background of CS, but unfortunately without further genetic information. ...
... Acral keratosis was reported in six cases [6,28,29,34,35,45] and was observed in the present patient, with this manifestation being helpful in confirming the diagnosis of CS based on the criteria of Pilarski [1]. Macrocephaly and adenoid facies (or "narrow bird-like" face), also described in our case, were observed in 26.8% [6, 19, 20, 23, 24, 33, 34, 37-39, 41, 43, 45, 47, 49] and 3.6% [21,33] literature cases, respectively. The etiology of oral papillomatous lesions remains uncertain [7]. ...
Middle-aged and old adults (≥ 50 years) diagnosed with Cowden syndrome (CS) with orofacial manifestations are uncommon. We describe a case of CS in a 53-year-old female showing “narrow bird-like” face, macrocephaly, acral keratoses, oral candidiasis, burning in the mouth, and multiple asymptomatic papillomatous lesions with a cobblestone pattern distributed on the alveolar ridge, tongue, buccal mucosa, and commissure. The histopathological features of lesions of the oral mucosa were those of papillary fibroepithelial hyperplasia. Immunohistochemistry revealed strong positivity for PTEN and p53 in most epithelial cells, while the expression of Bcl-2, S-100, and Ki-67 was weak/negative. According to a review conducted in PubMed, Web of Science, Embase, and Scopus for the analysis of reports of CS individuals ≥ 50 years with orofacial manifestations, 56 cases have been described in literature. Predilection for women was observed, with a female:male ratio of 2.3:1. Thirty-five (62.5%) individuals developed some malignant neoplasms. Oral health providers should be aware of the orofacial aspects of CS, including multiple papillomatosis, which can be an important criterion for diagnosis. Since malignancies may occur in older adults with CS, the need for strict surveillance is necessary. The present case has been under follow-up for 7 years without evidence of other manifestations.
... Most of the polyps of the gastrointestinal system in Cowden syndrome patients are hyperplastic, inflammatory, hamartomatous or neoplastic [52]. Many authors agree that the potential of these lesions for malignant transformation is low [5,19,34,50,52]. ...
... Most of the polyps of the gastrointestinal system in Cowden syndrome patients are hyperplastic, inflammatory, hamartomatous or neoplastic [52]. Many authors agree that the potential of these lesions for malignant transformation is low [5,19,34,50,52]. However, a literature review which included 93 Cowden syndrome patients from Japan revealed that there were 9 cases with colorectal carcinoma involvement [38]. ...
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.
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.
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.
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.
... 3,6 Nevertheless, even with advances in the molecular field, CS is still little known in the medical and dental fields. 5,12,14 The present case series confirms this status, because these 10 patients had systemic and head and neck involvement in which no association with this genodermatosis was made by other health care professionals before our evaluation and subsequent diagnosis of CS. 3,5,14 The clinical manifestations of CS reported in the recent literature are summarized in the following subsections, along with a discussion of our findings in this case series. ...
... 3,6 Nevertheless, even with advances in the molecular field, CS is still little known in the medical and dental fields. 5,12,14 The present case series confirms this status, because these 10 patients had systemic and head and neck involvement in which no association with this genodermatosis was made by other health care professionals before our evaluation and subsequent diagnosis of CS. 3,5,14 The clinical manifestations of CS reported in the recent literature are summarized in the following subsections, along with a discussion of our findings in this case series. ...
... Acral keratosis, another common finding, presents as flesh-colored hyperkeratotic papules with a central depression resembling flat warts on the dorsal surfaces of the hands and feet. 5,14 Palmoplantar keratoses punctata are translucent keratoses that occur on the palms, soles, and lateral surfaces of the hands and feet in patients with CS. 5 Both cutaneous lesions were also found in 60% of our patients (see Table II). Café au lait pigmentation is an uncommon manifestation in CS, 15 and only 1 patient had this lesion. ...
... There are several case reports of vaginal cysts in the patients with Cowden's disease, which is associated with Pten mutation. 2,3 In addition, there is one reported description of a vaginal squamous cell carcinoma in Pten mutant mice. 4 However, little is known about the usual function of Pten/PI3K/Akt signaling or its relationship with estrogen signaling in the vagina. ...
Numerous studies support a role of phosphatase and tensin homolog deleted from chromosome 10 (Pten) as a tumor suppressor gene that controls epithelial cell homeostasis to prevent tumor formation. Mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing homeostasis of stratified squamous epithelia. We analyzed vaginal epithelium-specific Pten conditional knockout (CKO) mice to provide new insights into Pten/phosphoinositide-3-kinase (PI3K)/Akt function. The vaginal epithelium of ovariectomized (OVX) mice (control) was composed of 1-2 layers of cuboidal cells, whereas OVX CKO mice exhibited epithelial hyperplasia in the suprabasal cells with increased cell mass and mucin production. This is possibly due to misactivation of mammalian target of rapamycin and mitogen-activated protein kinase. Intriguingly, estrogen administration to OVX Pten CKO mice induced stratification and keratinized differentiation in the vaginal epithelium, as in estrogen-treated controls. We found that Pten is exclusively expressed in the suprabasal cells in the absence of estrogens, whereas estrogen administration induced Pten expression in the basal cells. This suggests that Pten acts to prevent excessive cell proliferation as in the case of other squamous tissues. Thus, Pten exhibits a dual role on the control of vaginal homeostasis, depending on whether estrogens are present or absent. Our results provide new insights into how Pten functions in tissue homeostasis.Oncogene advance online publication, 17 March 2014; doi:10.1038/onc.2014.62.
... [5] Some of these lesions are prone to malignization, hence the disease belongs to "paraneoplastic hereditary syndrome". [6] Until now approximately 300 cases have been reported in the English literature, [3] the number of reports increasing owing to the greater awareness of this disorder. [5] Case Report A 19-year-old female patient reported to our Department with the chief complaint of swollen lower lip since 1 year. ...
... [5] Because the development of associated malignancy may take several years, these mucocutaneous lesions may serve as an important clinical markers in identifying patients at high-risk of malignancy of the breast and thyroid. [5,6] The syndrome is usually diagnosed between ages of 13 and 64 with average being 22 years with a slight female predilection. [3] Mutation of the Phosphatase and tensin homolog/Mutated in multiple advanced cancer gene, a tumor suppressor gene located in the chromosome 10q 22-23 has been documented to be responsible for the malignancy of the breast and thyroid in these patients. ...
... Cutaneous lesions are present in the form of trichilemmomas, acral keratosis and palmoplantar keratosis. [3,4,6] The present case also showed a thick keratotic plaque involving the left thumb. Less frequently noted lesions include lipomas, neuromas and hemangiomas. ...
Cowden syndrome (CS) or multiple hamartoma syndrome is an infrequent genodermatoses, which is inherited as an autosomal dominant trait resulting from the mutation in the Phosphatase and Tensin homolog gene on the arm 10q and is principally characterized by multiple hamartomas with an increased risk of development of malignancies. Facial and oral signs are remarkable in the form of multiple papules and trichilemmomas on the face. We report one such rare case of CS in a 19-year-old patient who was diagnosed on the basis of her oral mucosal lesions and was further investigated and diagnosed with other hamartomas. The present case report signifies the responsibility of the oral physician in the early diagnosis of this progressive pathological syndrome as it leaves its footmark in the oral cavity in the form of oral mucosal lesions.
... Microscopic examination of facial biopsies in our cases revealed trichilemmomas in most biopsies. Trichilemmomas constitute one of the most important systematic manifestations of the disease, 16 but in our cases facial lesions displayed features intermediate between trichilemmoma and inverted follicular keratosis. Moreover, one facial biopsy showed features of trichoepithelioma. ...
Cowden's syndrome is a rare, autosomal dominant condition characterized by hamartomas of the gastrointestinal tract and cancer of the breast and thyroid. This study describes the clinical, immunological, and histopathological status of four Cowden's syndrome cases from two different families.
Biopsies were taken from different skin, mucous membrane, and intestinal lesions in all patients. Blood samples from patients and their parents were also examined.
Two brothers in the first family had more flexural distribution of papular and warty skin lesions as well as other manifestations of the syndrome, including recurrent pyogenic and fungal infections. Flow cytometric study revealed decreased total T and B-cell percentages and abnormal helper: suppressor ratios in these patients. The other two patients from the second family showed the classical picture of the syndrome and normal immunological parameters. Histopathologically, most skin lesions of the face showed trichilemmomas, and all oral and some of the other skin lesions showed benign fibromas with giant cells (Cowden's fibroma). Examination of intestinal biopsies revealed hamartomatous and hyperplastic polyps.
Some cases of Cowden's syndrome may be associated with prominent flexural skin lesions, recurrent pyogenic and fungal skin infections, decreased total T and B-cell counts, and an abnormal helper:suppressor ratio.
... In the maxillofacial territory, they are concentrated around the mouth, ears, periorbita and glabellar zone (23). Histopathologically these lesions, identified as trichilemmomas, are hamartomatous in nature, derive from pilose follicles and constitute one of the most important systematic manifestations of the disease (24,25). ...
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.
... En el territorio maxilofacial se concentran alrededor de la boca, orejas, periórbita y zona glabelar (23). Histopatológicamente estas lesiones, identificadas como triquilemomas, son de naturaleza hamartomatosa, derivan de las folículos pilosos y constituyen una de las manifestaciones sistémicas más significativas de la enfermedad (24,25). La queratosis acral es la segunda manifestación dermatológica más frecuente (3), con la presencia de pápulas de superficie lisa o rugosa en el dorso de manos y pies. ...
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. El síndrome de Cowden es una infrecuente enfermedad hereditaria englobada dentro de las poliposis gastrointestinales de tipo hamartomatoso. Se caracteriza por asociar anomalías cutaneomucosas y por la extraordinaria tendencia a desarrollar neoplasias malignas, principalmente de mama y tiroides. La importancia de un diagnóstico precoz del síndrome y de un adecuado screening tumoral en pacientes con lesiones papilomatosas cutaneomucosas, nos va a permitir adelantarnos en el diagnóstico de patologías con enorme morbimortalidad asociada en caso de una detección tardía. Presentamos el caso de una paciente diagnosticada de síndrome de Cowden tras consultar por lesiones papilomatosas labiales de largo tiempo de evolución y tratada posteriormente de cáncer de mama y riñón en estadios iniciales. El correcto diagnóstico de una patología banal de mucosa oral, nos ha permitido actuar de manera muy precoz frente a la patología neoplásica asociada a dicha enfermedad.
