Seguchi Kyosuke, Enokida Tomohiro, Oba Toshiki, Yoshikawa Akira L, Nakatake Nobuhiro, Yu Oyama
Medical Oncology, Kameda Medical Center, Kamogawa, JPN.
Head and Neck Cancer Oncology, National Cancer Center Hospital East, Kashiwa, JPN.
Cureus. 2025 Jul 1;17(7):e87085. doi: 10.7759/cureus.87085. eCollection 2025 Jul.
Cancer of unknown primary (CUP) with neuroendocrine features is classified as a favorable subset, and treatment is recommended based on the grade of the neuroendocrine tumor (NET). Although rare, medullary thyroid carcinoma (MTC) can present as CUP with neuroendocrine features and should be carefully considered as a crucial differential diagnosis in such cases. A 65-year-old man with no relevant medical history presented with a gradually enlarging left cervical mass. Laboratory evaluation revealed hypokalemia due to adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome. Contrast-enhanced computed tomography (CT) demonstrated multiple lymphadenopathies, hepatic masses, and bilateral pulmonary ground-glass opacities. A biopsy of a cervical lymph node revealed a neuroendocrine tumor grade 2 (NET G2), but the primary tumor was undetectable on imaging. Elevated serum calcitonin and thyroid ultrasound identified a small left thyroid nodule, fine-needle aspiration, and calcitonin immunostaining on the lesion pathologically revealed MTC. Given the rapidly progressive disease, vandetanib was initiated while awaiting molecular testing for rearranged during transfection (RET)-alteration. Following the detection of the RET M918T mutation, treatment was switched to selpercatinib, and rapid tumor response and endocrine symptom resolution were observed. This case highlights the importance of evaluating serum calcitonin, specifically in patients with neuroendocrine carcinoma of unknown primary, where MTC should be considered as a critical differential diagnosis. Thyroid ultrasound should be performed to identify even small lesions of medullary thyroid carcinoma (micro-MTC). Identification of MTC not only leads to targeted therapies that may improve prognosis, but also allows for genetic risk assessment and early intervention in family members when multiple endocrine neoplasia type 2 (MEN2) is suspected.
具有神经内分泌特征的原发灶不明癌（CUP）被归类为预后较好的亚组，建议根据神经内分泌肿瘤（NET）的分级进行治疗。虽然罕见，但甲状腺髓样癌（MTC）可表现为具有神经内分泌特征的CUP，在这类病例中应仔细考虑将其作为重要的鉴别诊断。一名65岁无相关病史的男性因左侧颈部肿块逐渐增大就诊。实验室检查发现因促肾上腺皮质激素（ACTH）依赖性库欣综合征导致低钾血症。增强计算机断层扫描（CT）显示多发淋巴结病、肝脏肿块和双侧肺部磨玻璃影。颈部淋巴结活检显示为2级神经内分泌肿瘤（NET G2），但影像学检查未发现原发肿瘤。血清降钙素升高及甲状腺超声检查发现左侧甲状腺有一个小结节，对该病变进行细针穿刺及降钙素免疫染色病理检查显示为MTC。鉴于疾病进展迅速，在等待转染重排（RET）改变的分子检测期间开始使用凡德他尼治疗。检测到RET M918T突变后，治疗改为使用塞尔帕替尼，观察到肿瘤迅速缓解且内分泌症状消失。该病例强调了评估血清降钙素的重要性，特别是在原发灶不明的神经内分泌癌患者中，其中MTC应被视为关键的鉴别诊断。应进行甲状腺超声检查以发现即使是微小的甲状腺髓样癌（微MTC）病变。识别MTC不仅能带来可能改善预后的靶向治疗，还能在怀疑有多发性内分泌肿瘤2型（MEN2）时对家庭成员进行遗传风险评估和早期干预。
