Minuto Michele, Varaldo Emanuela, Marcocci Gianluca, de Santanna Amleto, Ciccone Ermanno, Cortese Katia
DISC, Department of Surgical Sciences, University of Genoa, Largo R. Benzi, 8, 16132 Genoa, Italy.
DIMES, Department of Experimental Medicine, University of Genoa, Via Antonio de Toni 14, 16132 Genoa, Italy.
Diseases. 2018 Apr 10;6(2):25. doi: 10.3390/diseases6020025.
Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both sporadic and hereditary forms, whose pathogenesis is related to RET proto-oncogene alterations. MTCs originate from parafollicular cells, which produce calcitonin that represents the biochemical activity of MTC. Total thyroidectomy is the main treatment for MTC and often cures patients with confined diseases. In the presence of metastasis, the therapeutic approach depends on the rate of disease progression. We report a case of a 54-year-old female with a single, incidentally discovered, thyroid nodule of 1 cm, classified as suspicious MTC after a stimulation test with intravenous (iv) calcium. After surgery, we examined the nodule using immunohistochemistry, immunofluorescence, and electron microscopy. In addition to calcitonin, we found that it expressed intracellular positivity for the tyrosine kinase RTK receptors ERBB1 and ERBB2. Consistently with MTC features, the ultrastructural examination of the tumor displayed heterogeneous spindle-shaped cells containing two groups of secretory granules. Because of the significant correlation found between high ERBB1/ERBB2 levels in MTCs and extrathyroidal growth, the detection of ERBB1 and ERBB2 expression suggests that the two oncoproteins may be involved in the tumor proliferative responses and/or in the differentiation of parafollicular C-cells. The biological, prognostic, and therapeutic significance of these patterns would merit further investigations.
甲状腺髓样癌（MTC）是一种罕见的甲状腺肿瘤，有散发性和遗传性两种形式，其发病机制与RET原癌基因改变有关。MTC起源于滤泡旁细胞，这些细胞产生降钙素，而降钙素代表了MTC的生化活性。甲状腺全切术是MTC的主要治疗方法，通常能治愈局限性疾病的患者。出现转移时，治疗方法取决于疾病进展速度。我们报告一例54岁女性病例，其偶然发现一个1厘米的甲状腺结节，经静脉注射钙剂刺激试验后分类为可疑MTC。手术后，我们通过免疫组织化学、免疫荧光和电子显微镜检查该结节。除降钙素外，我们发现它对酪氨酸激酶RTK受体ERBB1和ERBB2呈细胞内阳性表达。与MTC特征一致，肿瘤的超微结构检查显示有含两组分泌颗粒的异质性梭形细胞。由于在MTC中发现ERBB1/ERBB2高表达水平与甲状腺外生长之间存在显著相关性，ERBB1和ERBB2表达的检测表明这两种癌蛋白可能参与肿瘤增殖反应和/或滤泡旁C细胞的分化。这些模式的生物学、预后和治疗意义值得进一步研究。
