Colorectal polyposis as a clue to the diagnosis of Cowden syndrome: Report of two cases and literature review

Innella, Giovanni; Miccoli, Sara; Colussi, Dora; Pradella, Laura Maria; Amato, Laura Benedetta; Zuntini, Roberta; Salfi, Nunzio; Collina, Guido; Ferrara, Francesco; Ricciardiello, Luigi; Turchetti, Daniela

doi:10.1016/j.prp.2020.153339

Cited by 9 publications

(10 citation statements)

References 26 publications

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“…Additional molecular studies were performed in some of our patients, as described here and in previous reports, in the attempt of gaining insights into mechanisms involved in clinical manifestations of PHTS. First, we have found that in the majority of lesions analyzed the wild-type PTEN allele is retained (findings summarized in Supplementary Table 1 ): thyroid papillary and oxyphilic cell carcinomas from patient II ( 25 , 36 ), breast carcinoma from patient IV ( 24 ), colon polyps from patients Ia and IXa ( 31 ), labial verruca from patient Ia and melanoma from patient VII (present study). The follicular thyroid carcinoma of patient VII is the only exception: in the DNA extracted from the tumor, in fact, LOH clearly emerges, suggesting that the wild-type allele is at least partially deleted; consistently, the IHC analyses demonstrates absent expression of the PTEN protein associated with overexpression of phosphorylated-AKT.…”

Section: Discussionmentioning

confidence: 51%

“…Indeed, although PHTS features often present early in life, a proportion of patients remain undiagnosed until adulthood, after they have already developed malignancies. Yet, in some cases, referral for genetic assessment is motivated by the suspicion of another disease, such as Familial Adenomatous Polyposis (31) or dysplastic nevi/melanoma syndrome (patient VII in this report). Therefore, recognizing typical mucocutaneous manifestations is crucial to allow patients be properly diagnosed and managed: the presence of three or more of trichilemmomas, acral keratoses, mucocutaneous, neuromas, and oral papillomas, which generally occur by the second or third decade of life, corresponds to one major criteria (32).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis

et al. 2021

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Germline PTEN pathogenic variants cause a spectrum of disorders collectively labeled PTEN Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that PTEN is a “haploinsufficient” tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of PTEN-associated manifestations, with special focus on mucocutaneous manifestations. Typical mucocutaneous features were present in all patients assessed, confirming that these are the most important clue to the diagnosis. The most frequent were papules located in the trunk or extremities (73.7%), oral mucosa papules (68.4%), acral/palmoplantar keratosis and facial papules (both 57.9%), according with literature data. Molecular analyses on one trichilemmoma suggested that the wild-type PTEN allele was retained and expressed, reinforcing the evidence that PTEN does not require a second somatic hit to initiate pathogenic processes. Unexpectedly, one patient also displayed a cutaneous phenotype consistent with atypical mole/melanoma syndrome; no variants were detected in known melanoma genes, but Whole Exome Sequencing showed the rare truncating variant c.495G>A in the CDH13 gene that might have cooperated with PTEN-haploinsufficiency to generate such phenotype. Our findings confirm the reproducibility of known PHTS manifestations in real-world practice, highlighting the role of mucocutaneous manifestations in facilitating prompt diagnosis of the syndrome, and provide some insights into the pathogenic process induced by PTEN alterations, which may contribute to its understanding.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis

et al. 2021

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“…The authors suggested that the presence of these features should prompt physicians and dentists to consider a further assessment for PHTS in adults [74]. These findings were supported by an Italian study of 20 patients with PTHS (16 adults and 4 children) wherein all patients had the typical mucocutaneous features of papules on the trunk or extremities (74%), papules in the oral mucosa (68%), facial papules (58%), and acral/palmoplantar keratosis (58%) [75,76].…”

Section: Pten Hamartoma Tumor Syndromementioning

confidence: 79%

Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

Haimov

Lieberman

Castellví–Bel

et al. 2022

Cancers

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Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-β, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation.

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“…Cowden syndrome (CS) is considered a component of the “PTEN hamartoma tumor syndrome” (PHTS) because the mutation in the PTEN gene was carried by most patients (80%) with CS ( 16 , 17 ). Because PTEN as the gene responsible for CS had been identified, the estimated incidence rises from 1/1,000,000 to 1/200,000.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Duodenal Carcinoma in a 40-Year-Old Asian Man With Cowden Syndrome

et al. 2022

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IntroductionCowden syndrome is a rare autosomal dominant genetic disease associated with PTEN mutation and is mainly shown as systemic multisystem lesions. The incidence of adenocarcinoma of the duodenum with Cowden syndrome in Asian males is rare. We hereby describe the diagnosis, treatment, and prognosis of a patient with duodenal carcinoma and Cowden syndrome.Case DescriptionA 40-year-old Chinese man was hospitalized because of gastrointestinal hemorrhage and anemia due to infiltrating adenocarcinoma of the descending part of the duodenum. He also had typical signs of Cowden syndrome, such as multiple polyps of the gastrointestinal tract, macrocephaly, papilloma of the tongue, soles hyperkeratosis, and melanosis spots. After the pancreaticoduodenectomy (classic Whipple), the lesions revealed the presence of hamartomatoid polyps, and some of them mutated into non-mucinous adenocarcinoma (80%) and mucinous adenocarcinoma (20%). Further investigation showed a lack of PTEN protein expression in the duodenal neoplasm, and genetic analysis showed the mutation of p.E242fs in PTEN. The patient was followed up for 1 year. There was no appearance of recurrence or distant metastasis.ConclusionIt is suggested that we should pay more attention to the differential diagnosis of duodenal carcinoma combined with gastrointestinal polyps. If multiple gastrointestinal polyps with gastrointestinal bleeding are encountered, Cowden syndrome should be considered, and timely diagnosis and treatment should be implemented.

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Colorectal polyposis as a clue to the diagnosis of Cowden syndrome: Report of two cases and literature review

Cited by 9 publications

References 26 publications

PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis

PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis

Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

Case Report: Duodenal Carcinoma in a 40-Year-Old Asian Man With Cowden Syndrome

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