Sato Yo, Watanabe Yusuke, Morisaki Takafumi, Hayashi Saori, Otsubo Yoshiki, Ochiai Yurina, Mizoguchi Kimihisa, Takao Yuka, Yamada Mai, Mizuuchi Yusuke, Nakamura Masafumi, Kubo Makoto
Departments of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Department of Breast Surgical Oncology, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Surg Case Rep. 2024 Mar 22;10(1):69. doi: 10.1186/s40792-024-01865-2.
Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors. Notably however, reports of patients with BWS and breast tumors are rare, and the association between these conditions is still unclear. Insulin-like growth factor-2 (IGF2) expression is known to be associated with the development of various cancers, including breast cancer, and patients with BWS with specific subtypes of molecular defects are known to show characteristic clinical features and IGF2 overexpression.
A 17-year-old girl who had been diagnosed with BWS based on an umbilical hernia, hyperinsulinemia, and left hemihypertrophy at birth, visited our department with a gradually swelling left breast. Her left breast was markedly larger than her right breast on visual examination. Imaging examinations showed two tumors measuring about 10 cm each in the left breast, and she was diagnosed with juvenile fibroadenoma following core needle biopsy. The two breast tumors were removed surgically and the patient remained alive with no recurrence. The final diagnosis was juvenile fibroadenoma without malignant findings. Immunohistochemical staining using IGF2 antibody revealed overexpression of IGF2 in the cytoplasm of ductal epithelial cells. Because of her clinical features and IGF2 overexpression, molecular defects of 11p15.5 including a possible genetic background of paternal uniparental disomy of chromosome 11 or hypermethylation of imprinting center 1 was suspected.
In this case, overexpression of IGF2 suggested a possible relationship between BWS and breast tumors. Moreover, the characteristic clinical features and IGF2 staining predicted the subtype of 11p15.5 molecular defects in this patient.
贝克威思-维德曼综合征（BWS）是一种基因组印记紊乱疾病，由11号染色体p15.5区域的多种遗传和/或表观遗传紊乱引起。BWS具有多种临床特征，包括过度生长和胚胎性肿瘤风险增加。然而，值得注意的是，BWS患者合并乳腺肿瘤的报道很少，两者之间的关联仍不清楚。已知胰岛素样生长因子2（IGF2）表达与包括乳腺癌在内的多种癌症的发生有关，已知具有特定分子缺陷亚型的BWS患者表现出特征性临床特征和IGF2过表达。
一名17岁女孩，出生时因脐疝、高胰岛素血症和左侧半身肥大被诊断为BWS，因左侧乳房逐渐肿胀前来我院就诊。肉眼检查发现她的左侧乳房明显大于右侧乳房。影像学检查显示左侧乳房有两个肿瘤，每个约10厘米，经粗针活检后诊断为青少年纤维腺瘤。手术切除了两个乳腺肿瘤，患者存活且无复发。最终诊断为无恶性表现的青少年纤维腺瘤。使用IGF2抗体进行免疫组织化学染色显示导管上皮细胞胞质中IGF2过表达。由于她的临床特征和IGF2过表达，怀疑11p15.5存在分子缺陷，包括可能的11号染色体父源单亲二倍体遗传背景或印记中心1的高甲基化。
在本病例中，IGF2过表达提示BWS与乳腺肿瘤之间可能存在关联。此外，特征性临床特征和IGF2染色预测了该患者11p15.5分子缺陷的亚型。
