目的:PTEN错构瘤综合征(PRTS)是由PTEN基因的种系失活突变引起的遗传性疾病。PHTS包括Cowden综合征和Bannayan-Riley-Ruvalcaba综合征。我们描述了特殊的病理和免疫组织化学甲状腺特征如何引导病理学家建议PHTS。
方法:一名28岁的西班牙白人女性患有多结节性甲状腺肿。细针穿刺活检后进行甲状腺全切除术。微观,免疫组织化学,并实现了甲状腺病变的分子分析。
结果:甲状腺呈多结节,显示一个乳头状微小癌,五个滤泡性腺瘤,三个腺脂肪瘤,46个微小腺瘤结节(微腺瘤),脂肪组织的分散病灶,和淋巴细胞性甲状腺炎.肿瘤甲状腺球蛋白呈阳性,甲状腺过氧化物酶,Pendrin,细胞周期蛋白D1和p27,但降钙素和PTEN阴性。证实了PTEN基因外显子8中核苷酸827处的一个腺嘌呤的种系杂合缺失。没有BRAF,NRAS,或在乳头状微癌中检测到KRAS体细胞突变,滤泡性腺瘤,腺脂肪瘤,或微腺瘤。在结肠肾小管绒毛状腺瘤和上皮样胶原瘤中也发现了PTEN的阴性。
结论:病理学家在识别与PHTS相关的病理性甲状腺表现以选择患者进行基因检测方面发挥着至关重要的作用。
OBJECTIVE: PTEN hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations of the PTEN gene. PHTS includes Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. We describe how the peculiar pathologic and immunohistochemical thyroid features lead pathologists to suggest PHTS.
METHODS: A 28-year-old white Spanish woman had a multinodular goiter. Total thyroidectomy was performed after fine-needle aspiration biopsy. Microscopic, immunohistochemical, and molecular analyses of the thyroid lesions were realized.
RESULTS: The thyroid was multinodular, showing one papillary microcarcinoma, five follicular adenomas, three adenolipomas, 46 tiny adenomatous nodules (microadenomas), scattered foci of adipose tissue, and lymphocytic thyroiditis. Tumors were positive for thyroglobulin, thyroperoxidase, pendrin, cyclin D1, and p27 but negative for calcitonin and PTEN. A germline heterozygous deletion of one adenine at nucleotide 827 in exon 8 of the PTEN gene was confirmed. No BRAF, NRAS, or KRAS somatic mutations were detected in the papillary microcarcinoma, follicular adenoma, adenolipomas, or microadenomas. Negativity for PTEN was also found in the colonic tubulovillous adenoma and the storiform collagenoma.
CONCLUSIONS: Pathologists play a crucial role in recognizing pathologic thyroid findings associated with PHTS for selecting patients for genetic testing.