Yamamoto Hiroyuki, Ishii Jun, Chiba Tomohiro, Nakazato Yoko, Hirano Kouichi, Kamma Hiroshi
Department of Pathology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-8611.
Division of Nephrology and Endocrinology, The University of Tokyo, School of Medicine, 7-3-1, Hongo, Bunkyo, Tokyo, 113-8655.
Pathol Int. 2017 Nov;67(11):580-584. doi: 10.1111/pin.12588. Epub 2017 Sep 27.
We describe a 74-year-old man with a nodular goiter accompanied by an incidental sporadic minute medullary thyroid carcinoma (MTC). Histopathologically, the MTC was a well-defined 1.7 mm tumor in the upper one-third right lobe, with solid cell nests (SCNs) adjacent to the MTC. C-cells were scattered mainly around the SCNs, but C-cell hyperplasia was not evident in the background thyroid. The MTC cell phenotype was immunohistochemically identical to background C-cells, but was completely different from the SCN main cells. Direct DNA analyses of isolated MTC paraffin-embedded specimens revealed two RET proto-oncogene missense point mutations in exon 11 (i.e., C630R and C634W). The non-tumor thyroid tissue did not reveal any mutations. This study reports the smallest case of sporadic MTC with a double RET somatic mutation, substantiating that RET mutations can occur during a very early stage of carcinogenesis. The combined presence of C630R and C634W represent a novel somatic mutation in sporadic MTC. The present case indicates that the sporadic MTC originated from the surrounding C-cells of the SCNs without C-cell hyperplasia and that the SCN main cells may not be able to develop into an MTC.
我们描述了一名74岁男性，患有结节性甲状腺肿，并伴有偶然发现的散发性微小甲状腺髓样癌（MTC）。组织病理学检查显示，MTC是位于右叶上三分之一处一个边界清晰的1.7毫米肿瘤，在MTC附近有实性细胞巢（SCNs）。C细胞主要散在于SCNs周围，但背景甲状腺组织中未见C细胞增生。MTC细胞表型在免疫组化上与背景C细胞相同，但与SCNs的主要细胞完全不同。对分离的MTC石蜡包埋标本进行直接DNA分析，发现第11外显子有两个RET原癌基因错义点突变（即C630R和C634W）。非肿瘤性甲状腺组织未发现任何突变。本研究报告了散发性MTC伴双RET体细胞突变的最小病例，证实RET突变可发生在癌变的非常早期阶段。C630R和C634W的联合存在代表了散发性MTC中的一种新的体细胞突变。本病例表明，散发性MTC起源于SCNs周围无C细胞增生的C细胞，且SCNs的主要细胞可能无法发展为MTC。
