Late diagnosis and oral rehabilitation in a patient with Cowden syndrome: case report

Gabriel Miranda de Oliveira Abdalla; Letícia Maria Cotta; Caroline Miranda Pernambuco; Alexandra Goulart Silvério; Carine Ervolino de Oliveira; Marcela Filié Haddad; Leonardo Amaral dos Reis

doi:10.5327/2525-5711.416

Authors

Gabriel Miranda de Oliveira Abdalla Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0009-0002-7990-3888
Letícia Maria Cotta Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0009-0009-6344-3507
Caroline Miranda Pernambuco Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0009-0005-7090-5432
Alexandra Goulart Silvério Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0009-0001-0762-0726
Carine Ervolino de Oliveira Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0000-0003-3103-090X
Marcela Filié Haddad Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0000-0003-3455-6624
Leonardo Amaral dos Reis Federal University of Alfenas, School of Dentistry – Alfenas (MG), Brazil. https://orcid.org/0000-0003-0701-1565

DOI:

https://doi.org/10.5327/2525-5711.416

Keywords:

Cowden Syndrome, PTEN Tumor Suppressor Gene, Oral Manifestations, Case Report, Oral Rehabilitation

Abstract

Cowden syndrome is a rare autosomal dominant disorder associated with germline mutations in the PTEN gene and characterized by multiple hamartomas and an increased risk of malignancy. A 64-year-old woman was referred for evaluation of papillomatous lesions in the oral cavity. Clinical examination revealed verrucous lesions, macrocephaly, acral keratoses, and facial trichilemmomas. Complementary examinations showed benign breast nodules and gastrointestinal polyposis without malignant transformation. Based on clinical, histopathological, and imaging findings, a diagnosis of Cowden syndrome was established according to the criteria of the International Cowden Syndrome Consortium. The patient underwent surgical excision of the oral papillomatous lesions followed by prosthetic rehabilitation with complete removable dentures, which restored function and aesthetics. This report emphasizes the essential role of dentists in the recognition of Cowden syndrome and in the multidisciplinary management required for affected patients.

References

Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Couns. 2009;18(1):13-27. https://doi.org/10.1007/s10897-008-9187-7

Nelen MR, Kremer H, Konings IB, Schoute F, van Essen AJ, Koch R, et al. Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet. 1999;7(3):267-73. https://doi.org/10.1038/sj.ejhg.5200289

Pilarski R. PTEN hamartoma tumor syndrome: a clinical overview. Cancers (Basel). 2019;11(6):844. https://doi.org/10.3390/cancers1106084

Marshall M, Otero D, Niklander S, Martínez-Flores R. Cowden’s syndrome diagnosed through oral lesions: a case report. J Clin Exp Dent. 2021;13(11):e1162-6. https://doi.org/10.4317/jced.58890

Webber LP, Martins MD, Carrard VC, Martins MAT, Munerato MC. Cowden syndrome--case report emphasizing the role of the dental surgeon in diagnosis. Spec Care Dentist. 2015;35(1):51-4. https://doi.org/10.1111/scd.12081

Hammerschmidt M, Lourenço SV, Simonsen Nico MM. A clinicopathological study of the oral lesions of Cowden disease. Oral Pathol Med. 2017;46(8):637-43. https://doi.org/10.1111/jop.12519

Flores IL, Romo SA, Nava FJT, Santos-Silva AR, Vargas PA, Almeida OP, et al. Oral presentation of 10 patients with Cowden syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(4):e301-10. https://doi.org/10.1016/j.oooo.2014.01.015

Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607-16. https://doi.org/10.1093/jnci/djt277

Gammon A, Jasperson K, Champine M. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. Appl Clin Genet. 2016;9:83-92. https://doi.org/10.2147/TACG.S41947

Takayama T, Muguruma N, Igarashi M, Ohsumi S, Oka S, Kakuta F, et al. Clinical guidelines for diagnosis and management of Cowden Syndrome/PTEN hamartoma tumor syndrome in children and adults-secondary publication. J Anus Rectum Colon. 2023;7(4):284-300. https://doi.org/10.23922/jarc.2023-028

Tan MH, Mester JL, Peterson C, Yang Y, Chen JL, Rybicki LA, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet. 2011;88(1):42-56. https://doi.org/10.1016/j.ajhg.2010.11.013

Yehia L, Eng C. PTEN hamartoma tumor syndrome. In: Adam MP, Bick S, Mirzaa GM, et al. GeneReviews®. Seattle: University of Washington; 2025.

Baran JA, Tsai SD, Isaza A, Brodeur GM, MacFarland SP, Zelley K, et al. The clinical spectrum of PTEN hamartoma tumor syndrome: exploring the value of thyroid surveillance. Horm Res Paediatr. 2020;93(11-12):634-42. https://doi.org/10.1159/000515731

Dragoo DD, Taher A, Wong VK, Elsaiey A, Consul N, Mahmoud HS, et al. PTEN hamartoma tumor syndrome/Cowden syndrome: genomics, oncogenesis, and imaging review for Associated Lesions and Malignancy. Cancers (Basel). 2021;13(13):3120. https://doi.org/10.3390/cancers13133120

Sousa-Neto SS, Arruda JAA, Martins AFL, Abreu LG, Mesquita RA, Mendonça EF. Orofacial manifestations assisting the diagnosis of Cowden syndrome in a middle-aged patient: case report and literature overview. Head Neck Pathol. 2022;16(1):304-13. https://doi.org/10.1007/s12105-021-01345-1

Starink TM, van der Veen JP, Arwert F, de Waal LP, de Lange GG, Gille JJP, et al. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet. 1986;29(3):222-33. https://doi.org/10.1111/j.1399-0004.1986.tb00816.x

Schei-Andersen AJ, van Oirschot B, Drissen MMCM, Schieving J, Schuurs-Hoeijmakers JHM, Vos JR, et al. Exploring the prevalence of oral features for early detection of PTEN hamartoma tumour syndrome. Int Dent J. 2024;74(6):1424-31. https://doi.org/10.1016/j.identj.2024.04.014

Fardal Ø, Nevland K, Johannessen AC, Vetti HH. The PTEN hamartoma tumor syndrome: how oral clinicians may save lives. Clin Adv Periodontics. 2023;13(1):21-6. https://doi.org/10.1002/cap.10196

Perić M, Toma S, Lasserre JF, Brecx M. Cowden Syndrome Associated with severe periodontal disease: a short literature review and a case report. Oral Health Prev Dent. 2018;16(3):225-32. https://doi.org/10.3290/j.ohpd.a40673

Barrón-Márquez MC, González-González R, Bobadilla-Morales L, Rodriguez-Machuca VU, Bologna-Molina R, Molina-Frechero N, et al. Cowden Syndrome and Oral Lesions: A Case Report Using MLPA. Am J Case Rep. 2025:26:e945876. https://doi.org/10.12659/AJCR.945876

Yuan W, Liu X, Sun Y, Su Y, Qin Y, Huang H. Case report: Rare oral manifestations in Cowden syndrome with PTEN mutation. Front Oncol. 2024;14:1323225. https://doi.org/10.3389/fonc.2024.1323225

Hendricks LAJ, Hoogerbrugge N, Schuurs-Hoeijmakers JHM, Vos JR. A review on age-related cancer risks in PTEN hamartoma tumor syndrome. Clin Genet. 2021;99(2):219-25. https://doi.org/10.1111/cge.13875

Dhawan A, Baitamouni S, Liu D, Eng C. Clinical neurologic features and evaluation of PTEN hamartoma tumor syndrome: a systematic review. Neurology. 2024;103(7):e209844. https://doi.org/10.1212/WNL.0000000000209844

Stanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM. Colonic manifestations of PTEN hamartoma tumor syndrome: case series and systematic review. World J Gastroenterol. 2014;20(7):1833-8. https://doi.org/10.3748/wjg.v20.i7.1833

Pîrlog L, Pătrășcanu A, Militaru MS, Cătană A. Insights into clinical disorders in Cowden syndrome: a comprehendice review. Medicina (Kaunas). 2024;60(5):767. https://doi.org/10.3390/medicina60050767

Sutera S, Giachino DF, Pelle A, Zuntini R, Pentero M. Gingival overgrowths revealing PTEN hamartoma tumor syndrome: report of novel PTEN pathogenic variants. Biomedicines. 2022;11(1):81. https://doi.org/10.3390/biomedicines11010081

Botsali A, Caliskan E, Eşme P, Dündar Ö. Oral hamartomatous lesion of Cowden’s disease treated with the combination of erbium: YAG laser and topical sirolimus. Dermatol Ther. 2019;32(5):e13002. https://doi.org/10.1111/dth.13002

Patini R, Staderini E, Gallenzi P. Multidisciplinary surgical management of Cowden syndrome: report of a case. J Clin Exp Dent. 2016;8(4):e472-4. https://doi.org/10.4317/jced.52919