Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Histopathology. 2023 Oct;83(4):657-663. doi: 10.1111/his.15013. Epub 2023 Jul 28.
Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in-vivo changes in patients who underwent thyroidectomy after lenvatinib therapy.
We screened 167 patients with thyroid cancer [papillary thyroid cancer (PTC), n = 102; follicular thyroid cancer (FTC), n = 26; anaplastic thyroid cancer (ATC), n = 39] who underwent lenvatinib therapy. Among these patients, six underwent thyroidectomy (lenvatinib-treated group: PTC, n = 3; FTC, n = 1; ATC, n = 2), and the specimens were examined. Five patients with PTC who did not receive lenvatinib therapy were included for comparison (untreated group). Microvessel density (MVD) was evaluated in both groups. The PTC and FTC specimens showed relatively more ischaemic changes than ATC specimens. Coagulative necrosis and ischaemic changes in cancer cells were frequently observed. ATC specimens showed fibrosis and mild cell damage. As hypothyroidism is a common side effect of lenvatinib therapy, non-cancerous thyroid tissues were also examined. Histological findings included mild lymphocytic infiltration, lymphoid follicular formation, histiocytic reaction and follicular epithelial destruction. The MVD in lenvatinib-treated tissues was significantly lower than that in untreated tissues.
Lenvatinib therapy probably induces relatively specific ischaemic changes in thyroid cancer cells. Moreover, inflammatory cell infiltration and decreased MVD occur to varying degrees in non-cancerous thyroid tissue and may be related to hypothyroidism, a side effect of lenvatinib.
仑伐替尼是一种多激酶抑制剂,用于治疗不可切除或转移性癌症,包括甲状腺癌。由于甲状腺全切除术联合放射性碘治疗是甲状腺癌的常用初始治疗方法,因此仑伐替尼治疗后甲状腺的组织学发现尚不清楚。因此,本研究旨在分析接受仑伐替尼治疗后行甲状腺切除术患者的体内变化。
我们筛选了 167 例接受仑伐替尼治疗的甲状腺癌患者[甲状腺乳头状癌(PTC),n=102;滤泡性甲状腺癌(FTC),n=26;间变性甲状腺癌(ATC),n=39]。其中 6 例行甲状腺切除术(仑伐替尼治疗组:PTC,n=3;FTC,n=1;ATC,n=2),并对标本进行了检查。纳入了 5 例未接受仑伐替尼治疗的 PTC 患者作为对照(未治疗组)。对两组的微血管密度(MVD)进行了评估。PTC 和 FTC 标本比 ATC 标本表现出更多的缺血性改变。经常观察到癌细胞的凝固性坏死和缺血性改变。ATC 标本表现为纤维化和轻度细胞损伤。由于甲状腺功能减退是仑伐替尼治疗的常见副作用,因此还检查了非癌性甲状腺组织。组织学发现包括轻度淋巴细胞浸润、淋巴滤泡形成、组织细胞反应和滤泡上皮破坏。仑伐替尼治疗组织的 MVD 明显低于未治疗组织。
仑伐替尼治疗可能会导致甲状腺癌细胞出现相对特异的缺血性改变。此外,非癌性甲状腺组织中不同程度地出现炎症细胞浸润和 MVD 降低,这可能与甲状腺功能减退有关,这是仑伐替尼的副作用。