Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research.
Department of Anatomical Pathology, NSW Health Pathology.
Am J Surg Pathol. 2020 Oct;44(10):1419-1428. doi: 10.1097/PAS.0000000000001505.
We investigated the prognostic value of a range of histologic parameters in medullary thyroid carcinoma (MTC) to design a grading system to predict overall survival. We assessed 76 patients with MTCs undergoing primary tumor resection for age, sex, tumor size, vascular space invasion, lymph node metastasis, multiple endocrine neoplasia type 2 (MEN2) status, mitotic count, Ki-67 proliferative index, spindled morphology, sheet-like growth pattern, coagulative necrosis, incipient necrosis, nuclear grade, multinucleation, prominent nucleoli, fibrosis, and amyloid deposition. In addition to the clinical features of age and the diagnosis of MEN2, the only histologic features that significantly predicted reduced overall survival were Ki-67 proliferative index, mitotic count, and the presence of coagulative necrosis. Using a combination of these 3 variables, we propose a 3-tiered grading system based solely on proliferative activity (Ki-67 proliferative index and mitotic count) and necrosis. There were 62 (82%) low-grade MTCs (low proliferative activity, no necrosis), 9 (12%) intermediate grade (low proliferative activity and necrosis present, or intermediate proliferative activity and no necrosis), and 5 (7%) high grade (intermediate proliferative activity and necrosis present, or high proliferative activity with or without necrosis). The mean overall survival was 193, 146, and 45 months, respectively (P=0.0001) for the 3 grades. The grading system remained prognostic when controlled for other factors associated with survival including age and known MEN2 syndrome. We conclude that this proposed grading system, which uses only a combination of proliferative activity (Ki-67 index, mitotic count) and coagulative necrosis, is a strong predictor of overall survival in MTC.
我们研究了一系列组织学参数在髓样甲状腺癌（MTC）中的预后价值，以设计一种分级系统来预测总生存。我们评估了 76 例接受原发性肿瘤切除术的 MTC 患者的年龄、性别、肿瘤大小、血管空间侵犯、淋巴结转移、多发性内分泌肿瘤 2 型（MEN2）状态、有丝分裂计数、Ki-67 增殖指数、梭形形态、片状生长模式、凝固性坏死、起始性坏死、核级、多核、明显核仁、纤维化和淀粉样物质沉积。除了年龄和 MEN2 诊断的临床特征外，唯一显著预测总生存降低的组织学特征是 Ki-67 增殖指数、有丝分裂计数和凝固性坏死的存在。使用这 3 个变量的组合，我们提出了一种仅基于增殖活性（Ki-67 增殖指数和有丝分裂计数）和坏死的 3 级分级系统。有 62 例（82%）低级别 MTC（增殖活性低，无坏死），9 例（12%）中级（增殖活性低且存在坏死，或增殖活性中等且无坏死），5 例（7%）高级（增殖活性中等且存在坏死，或增殖活性高且有或无坏死）。在 3 个级别中，总生存的平均值分别为 193、146 和 45 个月（P=0.0001）。当控制与生存相关的其他因素，包括年龄和已知的 MEN2 综合征时，分级系统仍然具有预后意义。我们得出结论，这种仅使用增殖活性（Ki-67 指数、有丝分裂计数）和凝固性坏死的组合的分级系统是 MTC 总生存的强有力预测指标。
