Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome

Jonker, Leon; Lebbink, Chantal A; Jongmans, Marjolijn C.J.; Nievelstein, Rutger A.J.; Merks, Johannes H. M.; Dijkum, E. J. M. Nieveen van; Links, Thera P.; Hoogerbrugge, Nicoline; Trotsenburg, A S Paul van; Santen, Hanneke M van

doi:10.1159/000508872

Cited by 24 publications

(30 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately 50% of patients (30/58) that had a US were found to have a nodule; however, only 6 noninvasive DOI: 10.1159/000515731 DTCs were ultimately diagnosed (6/81, 7.4%), including 2 FTCs and 4 PTCs with no distant metastasis. These results are consistent with previously published data reporting that 5% of individuals with PHTS younger than 20 years develop DTC [7,16]. There were no patients in our cohort diagnosed with DTC prior to 10 years of age, with the youngest diagnosed at 12 years old (shown in Table 3).…”

Section: Discussion/conclusionsupporting

confidence: 93%

“…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%

“…Previous studies exploring the clinical spectrum of PHTS in pediatrics have confirmed a diagnosis of thyroid cancer in 9 patients younger than 10 years, with the youngest presenting DTC at 4 years old [13,16]. Smith and colleague's report of one patient diagnosed with DTC at 7 years of age [13].…”

Section: Discussion/conclusionmentioning

confidence: 92%

“…The lifetime risk of developing DTC for individuals with PHTS is between 35 and 38%, with previous recommendations to initiate thyroid ultrasound (US) surveillance after 18 years of age [7][8][9][10][11]. After several reports documenting the diagnosis of thyroid nodules and DTC in patients younger than 18 years, with the youngest reported case of PHTS-related DTC in a 4-year-old patient, multiple groups suggested that US surveillance should be initiated earlier -at the time of diagnosis, by 10 years of age, by 7 years of age, or even as early as 2-3 years depending on the age of diagnosis and the patient's ability to cooperate with the examination [8,[12][13][14][15][16]. Despite these recommendations, the benefit of early thyroid surveillance in pediatrics with PHTS has not been well defined.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Discussion/conclusionsupporting

confidence: 93%

Section: Discussion/conclusionsupporting

confidence: 90%

Section: Discussion/conclusionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…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 ). Indeed, systematic annual ultrasound monitoring could lead to overdiagnosis and excessive thyroidectomy, therefore follow up frequency could be modified based on the first cervical screening results.…”

Section: Thyroid Tumorsmentioning

confidence: 99%

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

Chevalier

Dupuis²,

Jannin

et al. 2021

Front. Endocrinol.

View full text Add to dashboard Cite

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.

show abstract

The PTEN hamartoma tumor syndrome: how oral clinicians may save lives

Fardal

Nevland

Johannessen

et al. 2022

Clin Adv Periodontics

View full text Add to dashboard Cite

Introduction: Patients with the PTEN hamartoma tumor syndrome (PHTS) have an 81%-90% cumulative lifetime risk of developing cancer. Around 90% of these patients have recognizable oral features. Receiving a diagnosis may save these patients' lives. This is the first presentation of a family with the PHTS diagnosis with focus on the oral and periodontal findings and treatments. Case Presentation: All three children (one son and two daughters) inherited the same heterozygous variant in the PTEN gene from their father. Gingival overgrowth was observed in all patients in addition to macrocephaly. Other findings included fissured tongue, high arched palate, papules, and trichilemmomas. The father had experienced severe tooth loss. Surgery was performed to treat the gingival overgrowth and periodontal pockets; however, the treatment was characterized by multiple recurrences of the overgrowth. Conclusions: Oral changes, macrocephaly, tumors, and/or a family history of benign or malignant lesions are important features that oral clinicians should be aware of for a possible PHTS diagnosis. Patients suspected of having PHTS should be referred to a medical practitioner, specifically a geneticist, for further diagnostic investigations. The periodontal problems seemed to be difficult to control for these patients. They will likely need an active and frequent maintenance therapy to control the persistent inflammation and gingival overgrowth. In addition, they need a thorough monitoring for benign or malignant changes in the orofacial regions.

show abstract

Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome

Cited by 24 publications

References 30 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

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

The PTEN hamartoma tumor syndrome: how oral clinicians may save lives

Contact Info

Product

Resources

About