Rossi S, Fugazzola L, De Pasquale L, Braidotti P, Cirello V, Beck-Peccoz P, Bosari S, Bastagli A
Pathology Unit, Department of Medicine, Surgery and Dentistry, Ospedale S Paolo and Ospedale Maggiore IRCCS, University of Milan School of Medicine, Milan, Italy.
Endocr Relat Cancer. 2005 Jun;12(2):281-9. doi: 10.1677/erc.1.00901.
We report the simultaneous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC), presenting as spatially distinct and well-defined tumour components, in three cases. In the first patient, histology, immunohistochemistry and electron microscopy demonstrated an MTC in the one nodule and PTC in two additional lesions. Non-neoplastic thyroid parenchyma separated the three nodules. Metastasis from PTC was diagnosed in a regional lymph node. Genetic analysis of both tumour components showed a distinctive mutational pattern: in the MTC a Cys634Arg substitution in exon 11 of the RET gene and in the two PTC foci a Val600Glu substitution in exon 15 of the BRAF gene. The other two patients are members of a large multigenerational family affected with familial MTC due to a germline mutation of the RET gene (Ala891Ser). Both patients harboured, besides medullary cancer and C-cell hyperplasia, distinct foci of papillary thyroid cancer, which was positive for Val600Glu BRAF mutation. Review of the literature disclosed 18 similar lesions reported and allowed the identification of different patterns of clinical presentation and biological behaviour. So far, the pathogenesis of these peculiar cases of thyroid malignancy has been completely unknown, but an underlying common genetic drive has been hypothesised. This is the first report in which two mutations, in the RET and BRAF genes, have been identified in three cases of MTC/PTC collision tumour, thus documenting the different genetic origin of these two coexisting carcinomas.
我们报告了3例同时发生髓样甲状腺癌（MTC）和乳头状甲状腺癌（PTC）的病例，表现为空间上不同且界限清晰的肿瘤成分。在首例患者中，组织学、免疫组化及电子显微镜检查显示一个结节为MTC，另外两个病灶为PTC。非肿瘤性甲状腺实质将这三个结节分隔开。在一个区域淋巴结中诊断出PTC转移。对两种肿瘤成分进行基因分析显示出独特的突变模式：MTC中RET基因第11外显子存在Cys634Arg替换，两个PTC病灶中BRAF基因第15外显子存在Val600Glu替换。另外两名患者是一个因RET基因（Ala891Ser）种系突变而患家族性MTC的大型多代家族的成员。两名患者除了患有髓样癌和C细胞增生外，还存在不同的乳头状甲状腺癌病灶，该病灶Val600Glu BRAF突变呈阳性。文献回顾发现了18例类似病变的报道，并确定了不同的临床表现和生物学行为模式。到目前为止，这些特殊甲状腺恶性肿瘤病例的发病机制完全未知，但已推测存在潜在的共同遗传驱动因素。这是首次在3例MTC/PTC碰撞瘤病例中鉴定出RET和BRAF基因的两种突变，从而证明了这两种共存癌的不同遗传起源。
