Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome

Tischkowitz, Marc; Colas, Chrystelle; Bisseling, Tanya M.; Gotthardt, Martin; Kets, Marleen; Kool, Leo J. Schultze; Mann, Ritse M.; Ligtenberg, M.J.L.; Pouwels, Sjaak; Hoogerbrugge, Nicoline

doi:10.1038/s41431-020-0651-7

Cited by 82 publications

(59 citation statements)

References 16 publications

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“…Based on these observations, we agree with the proposed recommendation of Jonker and colleagues that children with a pathogenic PTEN variant begin thyroid US monitoring no earlier than 10 years of age [16] and at the latest by 18 years of age, in keeping with the recent recommendation by the European PHTS Guideline Development Group [30]. This approach would provide the potential benefit of early detection of PHTS-associated DTC while reducing the risk for invasive procedures (FNA and/or thyroidectomy) that do not appear to have a clinical advantage.…”

Section: Discussion/conclusionsupporting

confidence: 90%

The Clinical Spectrum of PTEN Hamartoma Tumor Syndrome: Exploring the Value of Thyroid Surveillance

et al. 2020

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Introduction: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) comprises a collection of clinical features characterized by constitutional variants in PTEN. Several guidelines recommend thyroid screening, beginning at the pediatric age at the time of PHTS diagnosis; however, the benefits of early surveillance has not been well defined. Methods: We conducted a retrospective investigation of patients followed up at the Children’s Hospital of Philadelphia with a diagnosis of PHTS between January 2003 and June 2019. In total, 81 patients younger than 19 years were identified. Results: The most common clinical feature at presentation was macrocephaly (85.1%), followed by impaired development (42.0%), skin/oral lesions (30.9%), and autism spectrum disorder (27.2%). A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (51.7%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 7.4% (6/81) diagnosed with thyroid cancer. All thyroid cancer patients were older than 10 years at diagnosis, and all displayed low-invasive behavior. Of the patients younger than 10 years at the time of thyroid ultrasound (US) surveillance, 71.4% (15/21) had a normal US. The remaining 6 patients had thyroid nodules, including 4 undergoing thyroid surgery with benign histology. Discussion/Conclusion: Patients with macrocephaly, impaired cognitive development and thyroid nodules, and/or early-onset gastrointestinal polyps should undergo constitutional testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance before 10 years of age. In PHTS patients with a normal physical examination, thyroid US surveillance can be delayed until 10 years of age.

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Section: Discussion/conclusionsupporting

confidence: 90%

The Clinical Spectrum of PTEN Hamartoma Tumor Syndrome: Exploring the Value of Thyroid Surveillance

et al. 2020

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“…The most frequent phenotype is called Cowden Syndrome, characterized by multiple hamartomas that can occur in any organ, macrocephaly, mucocutaneous lesions, and an increased risk of several tumors, including CRC. The estimated lifetime risk of cancer in individuals with PHTS range from 85% to 89% for any cancer, 67–85% for female breast cancer, 6–38% for thyroid cancer, 2–28% for endometrial cancer, 2–34% for renal cancer, 9–20% for colorectal cancer, and 0–6% for melanoma [ 77 ]. Patients usually present with colorectal polyps (typically hamartomas, but other types such as ganglioneuromas, hyperplastic, adenomatous and inflammatory polyps often occur), and CRC (age at diagnosis: 44–60 years) [ 78 ].…”

Section: Inherited Syndromes That Predispose To Eocrcmentioning

confidence: 99%

The Inherited and Familial Component of Early-Onset Colorectal Cancer

Daca‐Alvarez

Quintana

Terradas

et al. 2021

Cells

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Early-onset colorectal cancer (EOCRC), defined as that diagnosed before the age of 50, accounts for 10–12% of all new colorectal cancer (CRC) diagnoses. Epidemiological data indicate that EOCRC incidence is increasing, despite the observed heterogeneity among countries. Although the cause for such increase remains obscure, ≈13% (range: 9–26%) of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% of patients with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. Approximately 28% of EOCRC patients have family history of the disease. This article recapitulates current evidence on the inherited syndromes that predispose to EOCRC and its familial component. The evidence gathered support that all patients diagnosed with an EOCRC should be referred to a specialized genetic counseling service and offered somatic and germline pancancer multigene panel testing. The identification of a germline pathogenic variant in a known hereditary cancer gene has relevant implications for the clinical management of the patient and his/her relatives, and it may guide surgical and therapeutic decisions. The relative high prevalence of hereditary cancer syndromes and familial component among EOCRC patients supports further research that helps understand the genetic background, either monogenic or polygenic, behind this increasingly common disease.

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“…The European guidelines for CS follow-up suggest an systematic surveillance for thyroid cancer by cervical spine ultrasound ( Figure 4 ) ( 195 ). An annual investigation starting at 18 years of age is proposed, although the levels of evidence supporting those modalities are moderate and some authors suggest beginning surveillance at 10 years of age ( 196 ).…”

Section: Thyroid Tumorsmentioning

confidence: 99%

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

Chevalier

Dupuis²,

Jannin

et al. 2021

Front. Endocrinol.

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Phakomatoses encompass a group of rare genetic diseases, such as von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC) and Cowden syndrome (CS). These disorders are due to molecular abnormalities on the RAS-PI3K-Akt-mTOR pathway for NF1, TSC and CS, and to hypoxia sensing for VHL. Phakomatoses share some phenotypic traits such as neurological, ophthalmological and cutaneous features. Patients with these diseases are also predisposed to developing multiple endocrine tissue tumors, e.g., pheochromocytomas/paragangliomas are frequent in VHL and NF1. All forms of phakomatoses except CS may be associated with digestive neuroendocrine tumors. More rarely, thyroid cancer and pituitary or parathyroid adenomas have been reported. These susceptibilities are noteworthy, because their occurrence rate, prognosis and management differ slightly from the sporadic forms. The aim of this review is to summarize current knowledge on endocrine glands tumors associated with VHL, NF1, TSC, and CS, especially neuroendocrine tumors and pheochromocytomas/paragangliomas. We particularly detail recent advances concerning prognosis and management, especially parenchyma-sparing surgery and medical targeted therapies such as mTOR, MEK and HIF-2 α inhibitors, which have shown truly encouraging results.

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Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome

Cited by 82 publications

References 16 publications

The Clinical Spectrum of PTEN Hamartoma Tumor Syndrome: Exploring the Value of Thyroid Surveillance

The Clinical Spectrum of PTEN Hamartoma Tumor Syndrome: Exploring the Value of Thyroid Surveillance

The Inherited and Familial Component of Early-Onset Colorectal Cancer

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

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