PTEN hamartoma tumour syndrome: case report based on data from the Iranian hereditary colorectal cancer registry and literature review

Abstract

Background PTEN hamartoma tumour syndrome (PHTS) is a rare hereditary disorder caused by germline pathogenic mutations in the PTEN gene. This study presents a case of PHTS referred for genetic evaluation due to multiple polyps in the rectosigmoid area, and provides a literature review of PHTS case reports published between March 2010 and March 2022. Case presentation A 39-year-old Iranian female with a family history of gastric cancer in a first-degree relative presented with minimal bright red blood per rectum and resistant dyspepsia. Colonoscopy revealed the presence of over 20 polyps in the rectosigmoid area, while the rest of the colon appeared normal. Further upper endoscopy showed multiple small polyps in the stomach and duodenum, leading to a referral for genetic evaluation of hereditary colorectal polyposis. Whole-exome sequencing led to a PHTS diagnosis, even though the patient displayed no clinical or skin symptoms of the condition. Further screenings identified early-stage breast cancer and benign thyroid nodules through mammography and thyroid ultrasound. Method and results of literature review A search of PubMed using the search terms “Hamartoma syndrome, Multiple” [Mesh] AND “case report” OR “case series” yielded 43 case reports, predominantly in women with a median age of 39 years. The literature suggests that patients with PHTS often have a family history of breast, thyroid and endometrial neoplasms along with pathogenic variants in the PTEN/MMAC1 gene. Gastrointestinal polyps are one of the most common signs reported in the literature, and the presence of acral keratosis, trichilemmomas and mucocutaneous papillomas are pathognomonic characteristics of PHTS. Conclusion When a patient presents with more than 20 rectosigmoid polyps, PHTS should be considered. In such cases, it is recommended to conduct further investigations to identify other potential manifestations and the phenotype of PHTS. Women with PHTS should undergo annual mammography and magnetic resonance testing for breast cancer screening from the age of 30, in addition to annual transvaginal ultrasounds and blind suction endometrial biopsies.

Insights into Clinical Disorders in Cowden Syndrome: A Comprehensive Review

“…Intriguingly, a significant proportion of individuals who present at least one mutant PTEN allele, ranging from 90% to 95%, display colorectal polyps upon undergoing colonoscopy [2,23,24,33]. These polyps encompass diverse histologies, including hamartomas (present in 65.8% of cases), juvenile polyps, ganglioneuromas (hamartomatous tumours that originate in enteric nervous system cells [34]), adenomatous polyps, inflammatory polyps, leiomyomas, lipomas, lymphoid polyps, and hyperplastic polyps, even though the last ones are common in the general population [2,23,24,29,35]. Synchronous histologies can be observed within the gastrointestinal polyps of individuals with CS [24].…”

The complexity of phosphatase and tensin homolog hamartoma tumor syndrome: A case report

“… 2 , 3 Frequently described clinical findings are developmental delay (DD), macrocephaly, skin lesions, thyroid pathologies, gastrointestinal hamartomas, and breast cancer (BC). 4 All of the above-mentioned syndromes are linked to pathogenic variants in the phosphatase and tensin homolog ( PTEN ) tumor suppressor gene on chromosome 10q23 (OMIM 601728). The PTEN gene is an important tumor suppressor gene that plays a critical role in the molecular mechanisms regulating cell migration, proliferation, and apoptosis.…”

“… 6 Individuals with PHTS are at significant risk for malignancies and the most commonly involved organs are the breast, endometrium, and thyroid. 4 , 7 …”

“… 3 Recent literature review by Rahmatinejad et al demonstrated that PHTS cases involving individuals under 18 are rare. 4 Hence, it is important to report cases of PHTS in this age group to better characterize clinical findings and prognosis. Here, we describe a case of PHTS in a 12-year-old boy.…”