无症状的甲状腺结节最容易在30岁到40岁之间的女性中检测出来。
头颈部放射史是甲状腺癌的危险因素之一,是较强的但不是常见的因素。 甲状腺癌多发于女性,但男性甲状腺结节癌变的患病率更高。[16]Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016;22(Suppl 1):1-60.http://journals.aace.com/doi/pdf/10.4158/EP161208.GLhttp://www.ncbi.nlm.nih.gov/pubmed/27167915?tool=bestpractice.com 甲状腺癌作为家族性综合征,如多发性内分泌肿瘤(MEN)综合征的情况是少见的。
检查和检测
甲状腺结节可能在体格检查时被发现,或者在颈部超声和 CT 检查时意外发现。无意间发现的 PET 阳性甲状腺结节可能具有较高的恶性风险,有必要进一步行相应的检查。一项研究显示,采用18 F 氟代脱氧葡萄糖正电子发射计算机断层显像 (F-18-FDG-PET)/CT 来检测甲状腺偶发肿瘤,可发现近 1/3 的局灶性甲状腺摄取为恶性的,其中大多数为甲状腺乳头状癌。[4]Bertagna F, Treglia G, Piccardo A, et al. Diagnostic and clinical significance of F-18-FDG-PET/CT thyroid incidentalomas. J Clin Endocrinol Metab. 2012 Nov;97(11):3866-75.http://www.ncbi.nlm.nih.gov/pubmed/22904176?tool=bestpractice.com 临床查体可能作用有限,有时或可触及颈部淋巴病变。 肿瘤局部进展可能导致同侧声带麻痹,从而出现声音嘶哑症状,也可伴有呼吸困难或吞咽困难。 气管可因受压而向对侧偏移。结节本身可为实质性,质地中等或偏硬。 短期内颈部快速肿大较少见,如出现则提示淋巴瘤(多有桥本甲状腺炎基础)、结节内出血或未分化癌。
检查
首先需检测TSH水平。 如果TSH水平下降,下一步需检测甲状腺激素水平,并做放射性碘扫描。 放射性碘扫描可能提示高功能结节(热结节),大多数为良性。
如果THS水平正常,则下一步需对甲状腺结节进行诊断性细针穿刺。 无法触及的结节需在超声引导下进行穿刺。 美国甲状腺协会(ATA)和美国临床内分泌协会(AACE)均提出,对于临床可触及的结节,细针穿刺之前需要先做超声检查,以确定结节的大小、位置和囊性成分。[2]Haugen BR, Alexander EK, Bible KC, et al; American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016 Jan;26(1):1-133.http://online.liebertpub.com/doi/pdf/10.1089/thy.2015.0020http://www.ncbi.nlm.nih.gov/pubmed/26462967?tool=bestpractice.com[16]Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016;22(Suppl 1):1-60.http://journals.aace.com/doi/pdf/10.4158/EP161208.GLhttp://www.ncbi.nlm.nih.gov/pubmed/27167915?tool=bestpractice.com[18]American College of Radiology. ACR-AIUM-SPR-SRU practice parameter for the performance of a thyroid and parathyroid ultrasound examination. 2014. [internet publication].http://www.acr.org/~/media/ACR/Documents/PGTS/guidelines/US_Thyroid_Parathyroid.pdf 大部分囊性结节其实是囊实性的,其恶性风险与实性结节相似。 因而,超声引导有助于对结节的实性成分进行穿刺。 对于多发性结节性甲状腺肿,细针穿刺的依据应该是可疑的超声特征而不是结节的大小。[16]Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016;22(Suppl 1):1-60.http://journals.aace.com/doi/pdf/10.4158/EP161208.GLhttp://www.ncbi.nlm.nih.gov/pubmed/27167915?tool=bestpractice.com AACE不推荐对<1cm的结节进行细针穿刺,除非该结节具有可疑的超声特征,或该患者具有高危因素。[16]Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016;22(Suppl 1):1-60.http://journals.aace.com/doi/pdf/10.4158/EP161208.GLhttp://www.ncbi.nlm.nih.gov/pubmed/27167915?tool=bestpractice.com
细胞学检查可提示甲状腺癌的类型。 然而,组织学检查虽然能识别出滤泡性肿瘤,但不能区分滤泡腺瘤和滤泡癌。 此时,必须将结节切除,才能对包膜情况和血管侵犯做进一步的检查。 不能明确的细胞学检查结果,被认为是存在恶性可疑的。[16]Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules - 2016 update. Endocr Pract. 2016;22(Suppl 1):1-60.http://journals.aace.com/doi/pdf/10.4158/EP161208.GLhttp://www.ncbi.nlm.nih.gov/pubmed/27167915?tool=bestpractice.com
[Figure caption and citation for the preceding image starts]: 甲状腺滤泡癌的组织病理CDC Image Library/Dr Edwin P. Ewing, Jr [Citation ends].
[Figure caption and citation for the preceding image starts]: 甲状腺乳头状癌的组织病理:可见沙砾体(箭头)CDC Image Library/Dr Edwin P. Ewing, Jr [Citation ends].
对于疑似为淋巴瘤者,可通过粗针活检来定性。 尽管不推荐使用粗针活检对病变进行鉴别和评估,仍有许多中心开展这一操作。[19]Novoa E, Gürtler N, Arnoux A, et al. Role of ultrasound-guided core-needle biopsy in the assessment of head and neck lesions: a meta-analysis and systematic review of the literature. Head Neck. 2012 Oct;34(10):1497-503.http://www.ncbi.nlm.nih.gov/pubmed/22127851?tool=bestpractice.com
如怀疑髓样癌,应检查血清降钙素水平;例如,当有提示家族性髓样癌或多发性内分泌瘤形成 (MEN) 综合征的家族史时。 对于有 MEN 综合征家族史的个体,还需要进行基因检测。 对于这些患者,术前需充分评估颈部淋巴结情况(通过超声和CT检查)。
所有患者均需进行喉镜检查,可发现声嘶患者的声带麻痹情况。
血清甲状腺球蛋白(Tg)水平可作为乳头状癌或滤泡癌治疗后的监测手段,但不能用于诊断甲状腺恶性肿瘤。 在利用放射性碘消除残灶之前,血清Tg可用来预测远期无病生存状况。 在分化性甲状腺癌患者中,低水平Tg被认为是预后良好的因素。[20]Webb RC, Howard RS, Stojadinovic A, et al. The utility of serum thyroglobulin measurement at the time of remnant ablation for predicting disease-free status in patients with differentiated thyroid cancer: a meta-analysis involving 3947 patients. J Clin Endocrinol Metab. 2012 Aug;97(8):2754-63.http://www.ncbi.nlm.nih.gov/pubmed/22639291?tool=bestpractice.com
新兴检查
初步的研究数据显示,对于细胞学无法明确诊断的患者,超声弹性评分可作为是否需要手术的一个依据。[21]Sebag F, Vaillant-Lombard J, Berbis J, et al. Shear wave elastography: a new ultrasound imaging mode for the differential diagnosis of benign and malignant thyroid nodules. J Clin Endocrinol Metab. 2010 Dec;95(12):5281-8.http://www.ncbi.nlm.nih.gov/pubmed/20881263?tool=bestpractice.com[22]Rago T, Scutari M, Santini F, et al. Real-time elastosonography: useful tool for refining the presurgical diagnosis in thyroid nodules with indeterminate or nondiagnostic cytology. J Clin Endocrinol Metab. 2010 Dec;95(12):5274-80.http://www.ncbi.nlm.nih.gov/pubmed/20810572?tool=bestpractice.com
术前超声检查是术前评估甲状腺乳头状癌淋巴结分期的有价值的手段。[23]Wu LM, Gu HY, Qu XH, et al. The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma: a meta-analysis. Eur J Radiol. 2012 Aug;81(8):1798-805.http://www.ncbi.nlm.nih.gov/pubmed/21536396?tool=bestpractice.com 然而,超声检查对于颈部淋巴结评估的准确性,尚需要更多高质量的前瞻性研究。
当细胞学无法明确时,对样本进行分子水平的分析,如检测BRAF、RET/PTC、RAS等基因突变,可作为进一步的阐述。[11]Kim TH, Park YJ, Lim JA. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012 Apr 1;118(7):1764-73.http://onlinelibrary.wiley.com/doi/10.1002/cncr.26500/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21882184?tool=bestpractice.com 然而,一部分乳头状癌或滤泡癌可能不含有基因突变。[24]Mekel M, Nucera C, Hodin RA, et al. Surgical implications of B-RafV600E mutation in fine-needle aspiration of thyroid nodules. Am J Surg. 2010 Jul;200(1):136-43.http://www.ncbi.nlm.nih.gov/pubmed/20637346?tool=bestpractice.com[25]Hegedus L. Can elastography stretch our understanding of thyroid histomorphology? J Clin Endocrinol Metab. 2010 Dec;95(12):5213-5.http://www.ncbi.nlm.nih.gov/pubmed/21131544?tool=bestpractice.com[26]Hershman JM, Cheng S, Gianoukakis, et al. Update in thyroidology. 2010. J Clin Endocrinol Metab. 2011 Jan;96(1):9-14.http://www.ncbi.nlm.nih.gov/pubmed/21209040?tool=bestpractice.com[27]Nikiforov YE. Molecular diagnostics of thyroid tumors. Arch Pathol Lab Med. 2011 May;135(5):569-77.http://www.archivesofpathology.org/doi/full/10.1043/2010-0664-RAIR.1http://www.ncbi.nlm.nih.gov/pubmed/21526955?tool=bestpractice.com
利用蓝色染料、放射性核素、或两者联合的手段进行前哨淋巴结活检,可避免对临床评估淋巴结阴性的患者进行不必要的预防性淋巴结清扫。 在可检出前哨淋巴结的甲状腺乳头状癌患者中,其阳性率约为40%,如采用免疫组织化学方法来评估,则阳性率将更高。[28]Balasubramanian SP, Harrison BJ. Systematic review and meta-analysis of sentinel node biopsy in thyroid cancer. Br J Surg. 2011 Mar;98(3):334-44.http://www.ncbi.nlm.nih.gov/pubmed/21246517?tool=bestpractice.com