Conservative management of gynecomastia in Peutz-Jeghers syndrome: Case series and review of the literature.

Peutz-Jeghers syndrome (PJS) is a childhood-onset cancer predisposition syndrome that is associated with oral freckling and gastrointestinal polyposis. Male patients with PJS are at risk for large-cell calcifying Sertoli cell tumors in childhood. These tumors are estrogen-producing and can cause symptoms of precocious puberty, gynecomastia, and growth acceleration. Here we discuss our experience with spontaneous resolution or stabilization of breast enlargement without medical intervention in three patients with PJS and gynecomastia. These cases indicate that a watchful waiting approach can be considered in the management of gynecomastia in male children with PJS.

A Bi-Institutional Study of Gastrointestinal and Hepatic Manifestations in Children With PTEN Hamartoma Tumor Syndrome.

Background and Aims: PTEN hamartoma tumor syndrome (PHTS) confers a high risk of specific cancers and is the most common genetic cause of autism spectrum disorder (ASD). Gastrointestinal (GI) phenotypes in PHTS are poorly characterized in children. Thus, we aimed to characterize the GI and hepatic manifestations in children with PHTS and to investigate genotype-phenotype associations. Methods: We performed a retrospective chart review of prospectively accrued children with PHTS at 2 tertiary-care centers. Wilcoxon rank-sum, Chi-squared, and Fisher's exact tests and Firth's logistic regression were utilized to explore associations between variables. Results: This series included 80 children with disease-causing PTEN variants. Common GI manifestations included constipation in 41 (51%), feeding issues in 31 (39%), and polyps in 22 (28%) children. The polyps were of mixed histologic types. Eosinophilic gastrointestinal disorders were observed in 5 (6%) children. Crohn's disease, celiac disease, and protein-losing enteropathy were observed once each. Eosinophilic gastrointestinal disorders were observed exclusively in patients without ASD (P = .052). Nonsense PTEN variants were enriched in those with polyps (P = .029). Missense PTEN variants (OR 2.9, P = .034) and upper GI polyps (OR 4.4, P = .018) were associated with increased odds of constipation. Conclusion: Constipation and feeding issues are common in children with PHTS. Polyps are more prevalent in children with PHTS than previously described and associated with nonsense PTEN variants. Children without ASD represent a distinct patient subset with a predisposition to eosinophilic gastrointestinal disorders and possibly upper GI polyps. Endoscopic evaluation should continue to be performed in symptomatic children with PHTS, with consideration of closer follow-up in those without ASD.

Rates of Intervention and Cancer Detection on Initial versus Subsequent Whole-body MRI Screening in Li-Fraumeni Syndrome.

Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on initial screening. Intervention and cancer detection rates on subsequent screenings are unknown. Clinical data for pediatric and adult patients with LFS (n = 182) were reviewed, including instances of WB-MRI screening and interventions based on screening results. For each WB-MRI screening, interventions including biopsy and secondary imaging, as well as rate of cancer diagnosis, were analyzed comparing initial versus subsequent WB-MRI. Of the total cohort (n = 182), we identified 68 adult patients and 50 pediatric patients who had undergone at least two WB-MRI screenings, with a mean of 3.8 ± 1.9 (adults) and 4.0 ± 2.1 (pediatric) screenings. Findings on initial screening led to an imaging or invasive intervention in 38% of adults and 20% of children. On follow up, overall intervention rates were lower for adults (19%, P = 0.0026) and stable for children (19%, P = NS). Thirteen cancers were detected overall (7% of adult and 14% of pediatric scans), on both initial (pediatric: 4%, adult: 3%) and subsequent (pediatric: 10%, adult: 6%) screenings. Rates of intervention after WB-MRI screening decreased significantly in adults between first and subsequent exams and remained stable in pediatric patients. Cancer detection rates were similar on screening (3%-4% initial, 6%-10% subsequent) for both children and adults. These findings provide important data for counseling patients with LFS about screening outcomes. PREVENTION RELEVANCE: The cancer detection rate, burden of recommended interventions, and rate of false-positive findings found on subsequent WB-MRI screenings in patients with LFS are not well understood. Our findings suggest that annual WB-MRI screening has clinical utility and likely does not result in an unnecessary invasive intervention burden for patients.