Atypical Manifestations of Cowden Syndrome in Pediatric Patients
<b>Background/Objectives:</b> Cowden syndrome (or <i>PTEN</i> hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, ma...
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2025-06-01
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| author | Ekaterina Zelenova Tatiana Belysheva Elena Sharapova Irina Barinova Alexandra Fedorova Vera Semenova Yana Vishnevskaya Irina Kletskaya Anna Mitrofanova Denis Sofronov Ivan Karasev Denis Romanov Timur Valiev Tatiana Nasedkina |
| author_facet | Ekaterina Zelenova Tatiana Belysheva Elena Sharapova Irina Barinova Alexandra Fedorova Vera Semenova Yana Vishnevskaya Irina Kletskaya Anna Mitrofanova Denis Sofronov Ivan Karasev Denis Romanov Timur Valiev Tatiana Nasedkina |
| author_sort | Ekaterina Zelenova |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Cowden syndrome (or <i>PTEN</i> hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. <b>Methods:</b> Next-generation sequencing and Sanger sequencing were used to search for <i>PTEN</i> genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. <b>Results:</b> A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the <i>PTEN</i> pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the <i>PTEN</i> gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. <b>Conclusions:</b> Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. |
| format | Article |
| id | doaj-art-42ca5df07e0040ac8bd2a0c209009ed4 |
| institution | OA Journals |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Diagnostics |
| spelling | doaj-art-42ca5df07e0040ac8bd2a0c209009ed42025-08-20T02:24:38ZengMDPI AGDiagnostics2075-44182025-06-011512145610.3390/diagnostics15121456Atypical Manifestations of Cowden Syndrome in Pediatric PatientsEkaterina Zelenova0Tatiana Belysheva1Elena Sharapova2Irina Barinova3Alexandra Fedorova4Vera Semenova5Yana Vishnevskaya6Irina Kletskaya7Anna Mitrofanova8Denis Sofronov9Ivan Karasev10Denis Romanov11Timur Valiev12Tatiana Nasedkina13N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaRussian Children’s Clinical Hospital, Pirogov Russian National Research Medical University, 117997 Moscow, RussiaDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117198 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaLimited Liability Company, Center of Innovative Medical Technologies, 115191 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia<b>Background/Objectives:</b> Cowden syndrome (or <i>PTEN</i> hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. <b>Methods:</b> Next-generation sequencing and Sanger sequencing were used to search for <i>PTEN</i> genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. <b>Results:</b> A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the <i>PTEN</i> pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the <i>PTEN</i> gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. <b>Conclusions:</b> Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS.https://www.mdpi.com/2075-4418/15/12/1456Cowden syndromefamilial case<i>PTEN</i>epidermal nevusdiffuse B-cell lymphomagerm cell tumors |
| spellingShingle | Ekaterina Zelenova Tatiana Belysheva Elena Sharapova Irina Barinova Alexandra Fedorova Vera Semenova Yana Vishnevskaya Irina Kletskaya Anna Mitrofanova Denis Sofronov Ivan Karasev Denis Romanov Timur Valiev Tatiana Nasedkina Atypical Manifestations of Cowden Syndrome in Pediatric Patients Diagnostics Cowden syndrome familial case <i>PTEN</i> epidermal nevus diffuse B-cell lymphoma germ cell tumors |
| title | Atypical Manifestations of Cowden Syndrome in Pediatric Patients |
| title_full | Atypical Manifestations of Cowden Syndrome in Pediatric Patients |
| title_fullStr | Atypical Manifestations of Cowden Syndrome in Pediatric Patients |
| title_full_unstemmed | Atypical Manifestations of Cowden Syndrome in Pediatric Patients |
| title_short | Atypical Manifestations of Cowden Syndrome in Pediatric Patients |
| title_sort | atypical manifestations of cowden syndrome in pediatric patients |
| topic | Cowden syndrome familial case <i>PTEN</i> epidermal nevus diffuse B-cell lymphoma germ cell tumors |
| url | https://www.mdpi.com/2075-4418/15/12/1456 |
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