Cowden Syndrome Research Articles

7925 Cowden Disease Occurring in Association with Common Variable Hypogammaglobulinemia: A Case Report

Abstract Disclosure: M.K. Shakir: None. I.C. Ebrahim: None. D.B. Maxwell: None. N.O. Vietor: None. T.D. Hoang: None. Carriers of a pathogenic germline mutations in the PTEN gene, a tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, including thyroid, breast, endometrial and colon cancer, termed as PTEN Hamartoma Tumor Syndrome (PHTS). Recent studies have shown that PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. We are reporting a 47-year-old female with Cowden disease (CD) and common variable hypogammaglobulinemia (CVH). Our patient was diagnosed with CVH at the age of 25 after several episodes of pneumonia as well as poor wound healing. Since then, she is being treated with monthly intravenous immunoglobulin therapy. At the age of 24 years, she had a fainting episode and a diagnosis of gangliocytoma of cerebellum was made and she underwent resection of the tumor. At this time, she was also diagnosed with CD. She has a personal history of multiple other tumors including phyllodes tumor of breast, s/p bilateral mastectomy at the age of 32, status post hysterectomy for endometrial hyperplasia at the age 35. Hurthle cell adenomas of thyroid s/p total thyroidectomy at the age of 38. Her family history was significant for sister and father with CD. Physical examination was remarkable for only acral keratosis without mucocutaneous neuromas, oral papillomas and trichilemmomas. Cowden syndrome is the best-described phenotype of PHTS; it is characterized by mucocutaneous lesions and an elevated risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as various benign manifestations such as macrocephaly and dysplastic gangliocytoma of the cerebellum. Our patient was diagnosed with CD when she presented with gangliocytoma of the cerebellum. Immunodeficiency has been reported previously in patients with CD, and these patients often present with recurrent cellulitis and abscesses, and reduced T cell numbers and in vitro T cell proliferative function. Thus, PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. Additionally, a decreased ability of dendritic cells to prime CD8+ T cells may occur, leading to impaired tumor eradication. Immune dysfunction in PHTS patients might be a potentially manageable contributing factor to the increased cancer risk in PHTS. In conclusion, patients presenting with CD should also be screened for disorders of immunological dysregulation. Presentation: 6/2/2024

Classification of PTEN germline non-truncating variants: a new approach to interpretation

BackgroundPTEN hamartoma tumour syndrome (PHTS) encompasses distinct syndromes, including Cowden syndrome resulting from PTEN pathogenic variants. Missense variants account for 30% of PHTS cases, but their classification remains challenging. To...

S2869 The Importance of Early Diagnosis in a Patient With Macrocephaly and Iron Deficiency Anemia: A Case of Cowden Syndrome

S2869 The Importance of Early Diagnosis in a Patient With Macrocephaly and Iron Deficiency Anemia: A Case of Cowden Syndrome

Pathologists’ integration of prior biopsies of women with germline PTEN mutations may expedite the identification of this rare cancer predisposition syndrome

PTEN hamartoma tumour syndrome (PHTS) is a rare cancer predisposition syndrome, caused chiefly by pathogenic and likely pathogenic (P/LP) variants in in the PTEN gene. Carriers have substantially elevated risks of various malignancies and develop benign lesions in multiple organ systems. The rarity of this disease, the decades long unfolding of its clinical features, involvement of multiple sites and the absence of distinguishing features of each lesion, hamper the identification of this condition, limiting opportunities for screening of affected individuals and their families.Given laboratory information systems are the repositories of patients’ biopsies, we are interested in whether PHTS patients’ prior biopsies may serve as clues to the possibility of this syndrome. With ethics committee approval, through a collaboration among our state-wide Adult Genetics Unit and all pathology laboratories in our state, we have undertaken a 28-year longitudinal survey (1990-2018) of the biopsy histories of 12 women known to have P/LP PTEN variants.Only one woman had a family history of Cowden syndrome, the remaining 11 patients’ mutations becoming discovered later. The earliest biopsy was at age 19. The most common finding was the development of multiple benign mucocutaneous lesions,10 women presenting with these. These included a range of benign vascular lesions: eight patients, various fibromatous lesions of skin and mucosal sites: six patients, a ganglioneuroma and a juvenile polyp. Ten women developed breast cancer, only four before the age of 40. Seven women developed a second breast cancer, two synchronously and five at intervals of 3-11 years. Other neoplasms included endometrial carcinoma (two patients) and dysplastic cerebellar gangliocytoma (three patients).Integrating the biopsy histories of PTEN P/LP variant carriers over time may assist in raising the possibility of an underlying cancer susceptibility syndrome, so appropriate clinical and genetic counselling and evaluation may be considered.

Testicular Lipomatosis Incidentally Detected by F-18 FDG PET/CT in a Cowden Syndrome Patient.

Testicular Lipomatosis Incidentally Detected by F-18 FDG PET/CT in a Cowden Syndrome Patient.

Cowden Syndrome: A Case Series Highlighting Cutaneous and Systemic Diversity

Cowden Syndrome: A Case Series Highlighting Cutaneous and Systemic Diversity

Genetic analysis of a Chinese pedigree affected with Cowden syndrome due to variant of PTEN gene

To explore the clinical features and genetic etiology of a Chinese pedigree affected with Cowden syndrome (CS). A CS pedigree diagnosed in November 2022 at the Ningde Municipal Hospital Affiliated to Ningde Normal University was selected as the study subject. Clinical data were collected, and genetic testing was carried out for available members. Pathogenicity analysis was carried out for the candidate variant. The proband, a 7-year-old male, was found to have autism and intellectual disability. Whole exome sequencing revealed that he has harbored a c.462_463del (p.F154Lfs25) variant of the PTEN gene. The proband's 35-year-old mother, who was diagnosed with pulmonary hamartomas at our hospital, has manifested with lipomas, nodular goiter, and adenomas. Sanger sequencing confirmed that she was also heterozygous for the c.462_463del (p.F154Lfs25) variant of the PTEN gene. No other family members has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2_Supporting+PM6). The newly discovered c.462_463del (p.F154Lfs*25) variant of the PTEN gene probably underlay the CS in this pedigree. CS patients have higher risk for developing malignant tumors. Clinicians should be aware of this condition and emphasize follow-up of the patients.

Analysis of the loss of phosphatase and tensin homolog expression in thyroid tissue for the diagnosis of Cowden syndrome

BackgroundCowden syndrome is an autosomal-dominant disorder caused by a germline phosphatase and tensin homolog mutation, giving rise to several tumors with an aggressive clinical course. In the thyroid, there are certain histologic criteria that could be related to this syndrome that could be useful for its early detection. We sought to analyze the loss of phosphatase and tensin homolog in thyroid histologic pieces with certain histologic criteria and to determine the percentage of patients diagnosed with Cowden syndrome with this methodology. MethodsFive hundred thirty-five thyroid specimens collected were retrospectively analyzed (2017–2020). Those samples that presented certain histologic criteria were studied for loss of phosphatase and tensin homolog expression. Patients with loss of expression underwent a clinical study to rule out dermatologic or other lesions compatible with Cowden syndrome. Patients with positive clinical study were referred for genetic study. ResultsThe phosphatase and tensin homolog study was performed in 6.7% (n = 36) of the thyroidectomy samples, showing loss of expression in 22% (n = 8); the most frequent histologic finding was the presence of multiple monomorphous adenomatous nodules. The samples with loss of expression showed more diffuse oncocytic changes. Of the 8 patients with loss of expression, 5 showed dermatologic lesions that could be associated with Cowden syndrome and 1 had a history of macrocephaly. These patients were referred for genetic study, being positive for Cowden syndromein in one quarter of the cases (n = 2). ConclusionThe immunohistochemical study of phosphatase and tensin homolog in pieces of thyroidectomies with histologic criteria suggestive of Cowden syndrome can help in its early diagnosis.

A rare case report of the Cowden syndrome

Cowden syndrome (CS) is a rare autosomal dominant genodermatosis caused by a heterozygous germline mutation in the PTEN gene, found in nearly 80% of cases. It is characterized by multiple benign hamartomas which manifest across various organs. This condition is further distinguished by its association with macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and a heightened susceptibility to certain malignant neoplasms, particularly affecting the thyroid, endometrium, and the breast (OMIM no. 58350).In this report, we detail the case of an Indian patient presenting with macrocephaly and multiple blackish pigmented areas on the face, alongside several small papules on the dorsum of the hands, and the presence of gastric and duodenal polyps, among other symptoms. Genetic analysis through Sanger sequencing of the PTEN gene revealed a heterozygous nonsense pathogenic variant (ENST00000371953.8: c.388C > T, p.Arg130Ter), thereby confirming a CS diagnosis. The report encompasses a comprehensive review of the existing literature, emphasizing the significance of genetic evaluation and discussing the intricacies of managing patients diagnosed with CS.

Mexican physicians' knowledge and attitudes towards hereditary colorectal cancer risk management.

e22552 Background: Genetic cancer risk assessment (GCRA) has become an integral component of the management of patients with colorectal cancer (CRC). Understanding clinical criteria and interpreting screening tests to identify patients who should be prioritized for genetic testing is especially critical in resource-constrained settings such as Mexico, where access to genetic testing is limited. Methods: We designed a self-applicable survey consisting of 18 items, divided into three sections: 7 on knowledge, 5 on clinical approaches, and 6 on access to genetic testing. The aim was to assess the practice patterns of Mexican physicians in contact with patients at risk for hereditary CRC. Initially, the survey was piloted among oncology fellows to refine and improve its relevance and applicability. Following adjustments, it was disseminated using a QR code at the annual meeting of the Mexican Society of Oncology (SMeO) in September 2023. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. Results: A total of 78 physicians completed the survey, with a median age of 37 years (range, 27-70). Among them, 47.2% were female, 82% were medical oncologists, with a median practice duration of 6 years (range, 1- 40). 52.6% practice in cancer community centers, 83.4% were employed in public primary care settings, and 60% were affiliated to academic centers. Referral criteria for GCRA was identified correctly in 66.7% who recognized age at CRC diagnosis < 50 years, 57.7% synchronous or metachronous CRC, 50% deficient mismatch repair CRC, and 37.2% PREMM5 score of ≥2.5%. Lynch syndrome, Familial Adenomatous Polyposis (FAP), and Cowden syndrome were identified as syndromes with an increased CRC risk by 76.9%, 71.8% and 56.7% of respondents, respectively. Decision-making based on likely pathogenic and pathogenic variants was indicated by 26.9% and 69.2%, while 12.8% reported making decisions based on variants of uncertain significance (VUS). Regarding clinical approach, 74.4% inquired about a family history of cancer at the initial consultation, and 66.7% referred patients for genetic counseling. The primary obstacles to accessing GCRA were the cost of genetic testing (43.6%) and the absence of medical genetics services at their centers (39.7%). Only 23% reported the availability of cascade testing within their practice. Conclusions: The identification of patients at risk of hereditary CRC was suboptimal among Mexican physicians. A high proportion of respondents were not fully qualified to interpret correctly genetic testing results. These indicate a need for awareness and educational programs to improve providers’ knowledge on predisposition cancer syndromes.

Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review

PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.

Hepatic failure as a rare cause of death in Cowden syndrome: A case report and literature review

Hepatic failure as a rare cause of death in Cowden syndrome: A case report and literature review

Abstract 6102: Clinicopathological and genetics features of endometrial cancer in Algerian women: The first nation-wide study

Abstract Background: Endometrial cancer represents the fourth common cancer in women in Algeria and the fifth cause of cancer mortality. In the present study, we aimed to determine, clinical, tumor and genetics characteristics associated with endometrial cancer in Algerian women. In addition, we screened for germline pathogenic variants in MMR genes in endometrial cancer patients with strong family history of Lynch syndrome (LS). Materials and Methods: Our study population included 273 patients diagnosed with endometrial cancer between 2010 and 2021. Data were collected from three public hospitals that covered 29 provinces among 48 in Algeria. Patient and tumor information included: age at diagnosis, menopausal status, histological type, histological grade, TNM stage, FIGO stage, tumor markers CA125, ACE, CA19-9, family history with cancer and age at menarche . MLH1 (exons 1, 9, 10, 13, 16), MSH2 (exons 5, 6, 7, 12), MSH6 (exons 4 and 8) and PMS 2(exons 6 and 10) were screened by PCR-Sanger direct sequencing in 14 LS families . Results: The mean age at diagnosis was 58.88 years. The mean age at menarche was 13.5 years. The proportion of endometrial cancer patients with premenopausal status was 21.62%. The commonest histological type was endometrioid adenocarcinoma (66.79%) followed by clear cell carcinoma (8.10%), carcinosarcomas (3.86%), serous carcinoma (3.47%) and mucinous carcinoma (2.7%). We found that the proportion of tumors with histological grade I (34.74%), grade II (27.41%) and grade IV (21.40%) was commonest in 83.55% of the patients. Our results showed that 73.74% of the patients were diagnosed at stage I (50.19%), stage II (12.74%) and stage III (10.81%), respectively. For the FIGO staging, our results showed that 74.12% of the patients were diagnosed at stage I (52.89%), stage III (10.81%) and stage I (10.42%), respectively. 16.21%, 3.08%, 6.94% of the patients were positive for CA125, ACE and CA19-9, respectively. We noticed that 56 patients (20.43%) had a positive family history with HBOC syndrome (17), Lynch syndrome (26) and Cowden syndrome (13), respectively. We identified two distinct germline pathogenic variants in MLH1 gene in two LS families. We detected the new germline pathogenic variant MLH1 c.53_63delinsT in young patient diagnosed with endometrial cancer and colorectal cancer (CRC) at age 43y and 44 y, respectively. The rare pathogenic germline variant MLH1 c.1546C>T has been detected in young woman diagnosed with CRC at age 41y and endometrial and ovarian cancers at age 52y, respectively. Conclusions : In this first study, we reported some clinical, biological, tumor and genetics features of endometrial cancer in Algerian women. Interestingly, we noticed that the median age of diagnosis was younger that the average age in Europe and America. Genetic counseling and testing is recommended for endometrial cancer patients diagnosed before age 50 with a family history of Lynch syndrome. Citation Format: Farid Cherbal, Chiraz Mehemmai, Mouchira Saidi, Yasmine Santoudji, Djamel-Eddine Seddik, Asma-Lamia Boumehdi, Fatiha Gouaref, Kamel Bentabak, Hassen Mahfouf, Mohammed Oukkal. Clinicopathological and genetics features of endometrial cancer in Algerian women: The first nation-wide study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6102.

A case of Cowden syndrome diagnosed after multiple tumors of the oral cavity

A case of Cowden syndrome diagnosed after multiple tumors of the oral cavity

Differential Diagnoses and Management Approaches for Gastric Polyposis

Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis.

Familial DICER1 syndrome with thyroid pathology. A series of clinical cases

Thyroid diseases in childhood occupy the second place after obesity in the structure of the general pathology of the endocrine system, eating disorders and metabolic disorders in children in the Russian Federation. Thyroid cancer in children makes up from 1.5 to 3 % of all malignant tumors, and from 8 to 22 % of malignant solid tumors of the head and neck, and the younger the child’s age, the more aggressive the disease proceeds.Familial forms of thyroid diseases may be associated with geographical features (living in iodine-deficient regions), but may also be part of hereditary syndromes, such as: multiple endocrine neoplasia syndromes (Sipple syndrome, Gorner syndrome, familial medullary thyroid cancer), DICER1 syndrome, Gardner syndrome, Cowden syndrome, McCune–Albright–Braitsev syndrome et al.This article describes several cases of thyroid pathology associated with DICER1 syndrome.

O-11 A rare cause of thyroid cancer - Li Fraumeni 2 syndrome

Abstract Introduction Thyroid cancer often originates from follicular cells, and papillary thyroid cancer (PTC) is the most common type. There is a familial predisposition in some cases of thyroid cancer. However, a minority of cases have thyroid cancer syndrome (e.g., familial polyposis, MEN 2, or Cowden syndrome). Many known genetic susceptibility genes are RET/PTC, BRAF, RAS, TERT, and TP53. We want to present a case of Li Fraumeni type 2 syndrome as a rare cause of thyroid cancer. Clinical Case A 69-year-old female patient with a history of PTC is admitted to the endocrinology department for follow-up. In 1976, this patient had a thyroid lobectomy, but the pathology result is unknown, and she takes 75 mcg of levothyroxine daily. In 1999, she was diagnosed with rectal cancer. The patient had a completion thyroidectomy in 2002, and the pathology was compatible with PTC. In 2014, she was diagnosed with right breast noninvasive ductal cancer. Cases of cancer were also quite common in her family history. The results of laboratory tests revealed normal TSH levels with negative thyroglobulin and anti-thyroglobulin levels. Neck ultrasonography showed no rest gland and pathological LAP. We requested genetic analysis (55 genes) for familial cancer syndromes. As a result of the analysis, 2 genes were found to be heterozygous. The c.599T>c heterozygous variant in the CHEK 2 gene was found (Figure 1). It was evaluated as pathogenic in the database review. Another heterozygous mutation in the BRIP1 gene, which was evaluated as a VUS also detected. Conclusion The CHEK 2 gene is a DNA-repairing protein kinase at position 22.q12.1. It is responsible for TP53 stabilization, genome maintenance, and apoptosis. CHEK2 phosphorylates p53 in response to DNA damage, leading to cell cycle arrest and stabilization (Figure 2). The mutation(CHEK 2 c.599T>c) we detected in this case has been considered possibly pathogenic in the academic databases. There are reported CHEK 2 c.599T>c cases on the CLINVAR site; the first report is from 2013. Classic Li-Fraumeni syndrome is a rare autosomal dominant syndrome caused by TP53 gene mutation. The chromosome location on classical Li fraumeni is 17p13.1. Li-Fraumeni type 2 develops due to the CHEK 2 gene mutation on chromosome 22q12.1. The results of a mutation of the CHEK2 gene are breast cancer, prostate cancer, PTC, colon cancer, kidney cancer, adrenocortical cancer, lung cancer, and rare cases of myelodysplastic syndromes. There are no data on thyroid-specific mortality in carriers of the CHEK2 mutations, and it is not yet known whether thyroid cancer in this population is more aggressive or has a better outcome.The familial syndromes should also be considered if PTC is detected in breast, colon, and prostate cancer patients. Studies on Li-Fraumeni type 2 syndrome are scarce, and considering the prevalence in European countries, further investigations of this syndrome and screening in patients with multiple cancers in the family should be warranted.Figure 1.Genetic sequencing image of the case

Utilizing PTEN immunohistochemistry as a screening test for Cowden syndrome.

Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors. We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases. Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively. PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS.

Clinical description of two cases of Cowden syndrome and the implication regarding thyroid cancer.

Thyroid cancer is one of the most common manifestations of Cowden syndrome, yet the syndrome is rare. The incidence of Cowden syndrome is 1 in 200,000. The diagnosis can be made clinically when patients present with a combination of symptoms such as mucocutaneous lesions with a strong personal or family history of thyroid, breast, endometrial, and colorectal cancer. A high index of suspicion is required to provide a clinical diagnosis utilizing major and minor criteria. Once a clinical diagnosis is made, genetic testing for a PTEN mutation, a tumor suppressor gene, is recommended. Cancer surveillance should be performed for those with positive genetic testing as well as those with negative genetic testing who still meet clinical diagnostic criteria. We present two cases of Cowden syndrome: one case involving an increasing number of thyroid nodules in a patient with known Cowden syndrome and another patient with a strong family history of cancer, personal history of follicular thyroid cancer, and numerous colonic polyps on screening colonoscopy. These cases demonstrate how early diagnosis of Cowden syndrome can help detect early cancer in both the patient and affected relatives. Diagnosing Cowden syndrome helps pre-risk stratification for early cancer screening. The diagnosis of Cowden syndrome can be made with a combination of major and minor criteria: any two major criteria with or without a minor criterion; one major and one minor criterion; or three minor criteria. Patients who meet the diagnostic criteria for Cowden syndrome should undergo genetic screening.

Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.