P2.229: Case Report: Follicular Thyroid Carcinoma Due to a Pathogenic Variant c.164+1G>A in the PTEN Gene and Its Diverse Presentations Within a Family

Introduction: PTEN hamartoma tumor syndrome (PHTS) is a rare autosomal dominant disorder affecting multiple organ systems and predisposing patients to various neoplasms, including thyroid cancer. We describe a case of follicular thyroid carcinoma due to a pathogenic variant of c.164+1G>A in the PTEN gene and its diverse presentations within the same family.

Case Description: A 15-year-old female of Moroccan descent was evaluated due to an enlarged thyroid with dysphagia and shortness of breath. She met developmental milestones without intellectual disability. The initial physical examination identified a large goiter, macrocephaly, and facial papules. A thyroid ultrasound showed an enlarged gland with large nodules throughout. The largest nodule was in the right thyroid lobe, with surrounding/internal vascularity and questionable small internal calcifications. The patient underwent total thyroidectomy, with pathology confirmed follicular thyroid carcinoma arising in a background of numerous follicular adenomas in the right lobe with the largest dimension of 4.1 cm. PTEN immunohistochemistry showed aberrant loss of staining in both the carcinoma and adenomas. Sequencing of the PTEN gene revealed a pathogenic variant of c.164+1G>A. Her younger sister was evaluated due to an enlarged thyroid at 10 years of age. She had developmental delays and was diagnosed with autism. She had macrocephaly, facial papules, scoliosis, and nevus of Ota. She had a total thyroidectomy at the age of 11 years. Pathology showed atypical follicular adenoma in a background of diffuse multinodular hyperplasia. She showed a recurrent multinodular goiter 5 years after the thyroidectomy. The patient’s mother had thyroid surgeries at age 17, 31, and 39 years. The pathology showed benign multinodular thyroid hyperplasia. She also had a history of macrocephaly, facial papules, and uterine fibroid. Genetic analysis confirmed that the younger sister and the mother were heterozygous for the same pathogenic variant.

Discussion: In our case report, patients had diverse clinical presentations and variable penetrance from the same pathogenic variant of c.164+1G>A in the PTEN gene, following an autosomal dominant pattern. A thorough medical and family history was essential to raise a high index of suspicion for PHTS. According to the literature, thyroid diseases are relatively common in PHTS patients, and all patients in our case report had thyroid involvement. The diagnosis of thyroid malignancy in our case report facilitated the identification of the c.164+1G>A mutation in the PTEN gene.

Conclusion: This case serves as a reminder of the importance of clinician awareness of PHTS. Despite the challenges in recognizing this rare disease, the presence of thyroid malignancy with a strong family history of thyroid disease should prompt medical professionals to consider PHTS and pursue genetic testing. As patients with PHTS are at risk of developing multi-cancers, early recognition, appropriate surveillance, and proactive management are crucial to minimizing the disease burden.