Multifocal follicular adenomas of thyroid discovers PTEN-hamartoma tumor syndrome in children

IF 1.9 3区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Oral Surgery Oral Medicine Oral Pathology Oral Radiology Pub Date : 2025-07-21 DOI:10.1016/j.oooo.2025.04.011

John Hicks , Catherine Flaitz

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引用次数: 0

Abstract

Introduction

PTEN-hamartoma tumor syndrome (PHTS) is due to phosphatase and tensin homolog gene (PTEN, located on 10q23.3) deletion or mutation. This results in the loss of function of PTEN tumor suppressor inhibitory effects and regulation of cell proliferation, leading to the development of hamartomas and benign and malignant tumors.

Methods and Materials

Two preadolescent females presented with markedly enlarged thyroids, which upon ultrasound examination demonstrated multiple nodules of variable sizes. Thyroid function tests were not abnormal. Fine needle aspirations of the thyroid nodules demonstrated benign follicular lesions. Total thyroidectomies identified numerous multifocal follicular adenomas ranging from macroscopic to microscopic in size, with no malignant features.

Results

Molecular testing identified PTEN mutation with thyroid tissue, and subsequently identified germline PTEN mutation in both patients. Upon follow-up screening examination, a benign lipoma and hamartomatous ductal hyperplasia with PASH (pseudoangiomatous stromal hyperplasia) were identified in one patient; while the other patient had a breast intraductal papilloma and PTEN hamartoma of soft tissue (PHOST) involving an extremity. Both patients will be followed long-term for the development of other lesions.

Conclusion

PTEN-hamartoma tumor syndrome (PHTS) is primarily comprised of Cowden Syndrome and Bannayan–Riley–Ruvalcaba syndrome, and less often by Proteus-like syndrome, autism with macrocephaly, and other syndromes. A variety of thyroid diseases occurs in at least 75% of children with PHTS, with multiple adenomatous nodules being the hallmark, as in the present cases. Other thyroid diseases include lymphocytic thyroiditis, multinodular hyperplasia, and C-cell hyperplasia. The major long-term concern is the development of malignant tumors. Lifetime risk of cancer in individuals with PTEN mutations is significant and involves many organ systems (85% breast, 35% thyroid, 30% endometrium, 30% kidney, 12% colorectum, 5% melanoma). Multiple adenomatous nodules in a child may lead to the discovery of PHTS and reinforce the need for tumoral genetic testing in such instances.

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儿童甲状腺多灶滤泡腺瘤发现pten错构瘤综合征

PTEN-错构瘤肿瘤综合征（PHTS）是由于磷酸酶和紧张素同源基因（PTEN，位于10q23.3）缺失或突变引起的。这导致PTEN肿瘤抑制因子的抑制作用和调节细胞增殖的功能丧失，导致错构瘤和良恶性肿瘤的发生发展。方法与材料2例青春期前女性甲状腺肿大，超声检查显示多个大小不等的结节。甲状腺功能检查未见异常。细针穿刺甲状腺结节显示良性滤泡病变。全甲状腺切除术发现许多多灶性滤泡腺瘤，从肉眼到显微镜下大小不等，无恶性特征。结果分子检测在甲状腺组织中发现PTEN突变，随后在两例患者中发现种系PTEN突变。在随访筛查检查中，在一名患者中发现了良性脂肪瘤和错构瘤性导管增生伴PASH（假性血管瘤间质增生）；而另一位患者患有乳腺导管内乳头状瘤和软组织PTEN错构瘤（PHOST），累及四肢。两名患者将被长期随访以观察其他病变的发展。结论pten -错构瘤肿瘤综合征（PHTS）以coden综合征和Bannayan-Riley-Ruvalcaba综合征为主，较少由proteus样综合征、孤独症伴大头畸形等综合征组成。至少75%的PHTS患儿出现多种甲状腺疾病，以多发腺瘤结节为标志，如本病例。其他甲状腺疾病包括淋巴细胞性甲状腺炎、多结节增生和c细胞增生。主要的长期担忧是恶性肿瘤的发展。携带PTEN突变的个体一生中患癌症的风险很大，涉及许多器官系统（85%的乳房，35%的甲状腺，30%的子宫内膜，30%的肾脏，12%的结肠直肠，5%的黑色素瘤）。儿童多发腺瘤结节可能导致PHTS的发现，并加强了在这种情况下进行肿瘤基因检测的必要性。

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来源期刊

Oral Surgery Oral Medicine Oral Pathology Oral Radiology DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

3.80

自引率

6.90%

发文量

1217

审稿时长

2-4 weeks

期刊介绍： Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology is required reading for anyone in the fields of oral surgery, oral medicine, oral pathology, oral radiology or advanced general practice dentistry. It is the only major dental journal that provides a practical and complete overview of the medical and surgical techniques of dental practice in four areas. Topics covered include such current issues as dental implants, treatment of HIV-infected patients, and evaluation and treatment of TMJ disorders. The official publication for nine societies, the Journal is recommended for initial purchase in the Brandon Hill study, Selected List of Books and Journals for the Small Medical Library.