Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023, Lisboa, Portugal.
Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 , Lisboa, Portugal.
J Endocrinol Invest. 2021 Sep;44(9):1837-1846. doi: 10.1007/s40618-020-01456-6. Epub 2021 Feb 11.
Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC.
The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics.
Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome.
Our results support the idea that a genotype-phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.
髓样甲状腺癌（MTC）表现出多种组织病理学特征，已经描述了几种组织学变体。在滤泡细胞来源的甲状腺癌中，基因型与表型之间存在良好的相关性。在这项研究中，我们研究了这种相关性是否也存在于 MTC 中。
在一系列 66 个分子特征明确的肿瘤中评估了组织病理学特征，并将其与临床特征相关联。
大多数 MTC 表现为经典变体（83.3%）。其他变体包括梭形细胞（6.1%）、假乳头（4.5%）、副神经节瘤样（3.0%）、血管肉瘤样（1.5%）和嗜酸细胞滤泡（1.5%）。肿瘤分为四组：组 1，体细胞 p.Met918Thr 和 p.Ala883Phe RET 突变；组 2，其他 RET 突变；组 3，RAS 突变；组 4，无 RET 或 RAS 突变。组 1 和 4 的肿瘤通常与经典变体相关，具有丰富的纤维化、血管淋巴管侵犯、甲状腺外延伸和更晚期的疾病阶段，而组 2 包括除经典变体以外的组织学变体（即假乳头和副神经节瘤样），肿瘤细胞丰富，侵袭性低，整体预后较好。在组 4 的肿瘤中，淀粉样物质沉积特征性地缺失或低。梭形细胞变体仅出现在组 3 的肿瘤中，其细胞性高，侵袭性和预后介于组 1 和 2 之间，但优于组 4。纤维化程度与临床结果直接相关。
我们的结果支持 MTC 中确实存在基因型-表型相关性的观点。然而，需要进一步的研究来在更大的样本量中证实这些发现。
