甲状腺癌

Thyroid Cancers

甲状腺癌

There are four general types of thyroid cancer: papillary (including mixed papillary-follicular), follicular, medullary (solid, with amyloid struma), and undifferentiated and anaplastic (rare). Most thyroid nodules are benign, and thyroid cancers generally are not highly malignant and are compatible with normal life expectancy if treated properly.

甲状腺癌一般有4种类型：乳头状(包括乳头－滤泡混合型癌)、滤泡状、髓样(实体，伴淀粉样甲状腺肿)和未分化及间变细胞癌（罕见)。多数甲状腺结节为良性。甲状腺癌一般也非极度恶性，如果治疗得当，患者可以达到正常寿命。

Usually, either the patient or the physician notices an otherwise symptomless lump in the neck. Rarely, metastases from a small thyroid cancer may lead to presenting complaints due to lymph node enlargement, pulmonary symptoms, or a destructive bone lesion.

通常，病人或医生会注意到颈部有一个并无其他症状的肿块。小甲状腺癌转移可能导致一些因淋巴结增大、肺部症状或破坏性骨损所致的症状，但这种情况较罕见。

The suspicion of cancer is increased by the following factors: (1) age (young patients are more susceptible); (2) sex, if the patient is a man (more women have thyroid cancer by a ratio of 2:1, but women have more thyroid disease by a ratio of about 8:1; thus, a man with a nodule should be regarded with greater suspicion); (3) a solitary nodule (multinodular lesions are usually benign unless there is a dominant cold nodule by thyroid scan); (4) a cold nodule on thyroid isotopic scanning (hot nodules are seldom cancerous); (5) a history of radiation exposure to the head, neck, or chest, especially in infancy and childhood (eg, for an enlarged thymus or enlarged tonsils, acne, or lymphoma); (6) radiographic evidence of fine, stippled psammomatous calcification (papillary carcinoma) or dense, homogeneous calcification (medullary carcinoma); (7) recent or rapid enlargement; and (8) stony-hard consistency. Needle aspiration biopsy is the best diagnostic approach to distinguish benign from malignant nodules providing that a skilled biopsier and cytologist are available.

下列因素可增加癌的可疑性：(1)年龄(年轻病人更易患癌)；(2)性别,如果病人为男性(女性与男性的甲状腺癌比为2：1，但女性更多的是得甲状腺病，约为8:1，因此，男性有甲状腺结节时应考虑癌的可能性更大)；(3)孤立小结(多结节病变一般为良性，除非甲状腺扫描时呈明显的冷结节)；(4)甲状腺同位素扫描时发现冷结节(热结节很少表现为癌)；(5)有过头、颈、胸放射接触史,尤其是婴儿和儿童期(例如，因胸腺增大或扁桃体肿大、痤疮或淋巴瘤等)；(6)X线片见细、斑点状、沙粒样钙化(乳头状癌)或致密、匀质钙化(髓样癌)；(7)最近增大或快速增大；(8)质地石头样坚硬。如拥有技术熟练的活检技术员和细胞学家，针吸活检便是区别淋巴瘤良性与恶性的最佳诊断方法。

PAPILLARY CARCINOMA

乳头状癌

Papillary carcinoma is the most common thyroid cancer (60 to 70% of all thyroid cancers). Females are affected two to three times more often than males. It is more frequent in the young, but is more malignant in the elderly. It is more common in patients with a history of radiation exposure and spreads via the lymphatic system. Lateral aberrant thyroid rests may be found that are actually occult metastases with a benign histologic appearance. These well-differentiated cancers may be TSH-dependent and may develop in goiters secondary to Hashimoto's thyroiditis. Many papillary carcinomas contain follicular elements, but this does not alter the basic biology of the tumor.

乳头状癌是最常见的甲状腺癌(占全部甲状腺癌的60%~70%)。女性病人是男性病人的2-3倍。年轻人较常见，但老年人恶性率更高。有照射史病人较常见，癌细胞可经淋巴系统扩散。可以发现一侧迷走性甲状腺残余，实际上这是带有良性组织表观的癌的隐性转移。.这些高分化癌属TSH（促甲状腺激素)依赖型，可以在继发于桥本甲状腺炎的甲状腺肿中发展。许多乳头状癌含有滤泡成分，但这并不改变肿瘤的基本生物学特征。

Treatment

治疗

Treatment for small (< 1.5 cm) encapsulated tumors localized to one lobe is usually lobectomy and isthmectomy, although some experts recommend more extensive thyroid surgical treatment. Thyroid hormone in TSH suppressive doses is given to minimize chances of regrowth or to regress any microscopic remnants of papillary carcinoma; surgical treatment is almost always curative. Large (> 1.5 cm) or diffusely spreading tumors often require total or near-total thyroidectomy with postoperative radioiodine scans and subsequent ablation of residual thyroid tissue with appropriately large doses of 131I administered when the patient is hypothyroid. Alternatively, recombinant TSH (not yet available) can be administered for 2 days prior to 131I for the diagnostic scan to detect residual thyroid tissue or cancer, thus avoiding the need to let the patient become hypothyroid prior to the diagnostic scan. Repeat treatment may be required every 6 to 12 mo to achieve ablation of the remaining thyroid tissue. TSH suppressive doses of L-thyroxine are given after treatment, and measurement of serum thyroglobulin is useful in detecting recurrent or persistent disease.

对局限于一叶的包裹性小肿瘤（< 1.5 cm),通常作叶切除和峡部切除，但有些专家建议进行更广泛的甲状腺外科治疗。TSH抑制剂量甲状腺激素用于减少癌的再生或使显微镜镜检下的乳头状癌残余出现萎缩；外科治疗几乎总是可以治愈它。大的(＞1.5cm)或弥漫扩散性肿瘤常需行甲状腺全切或次全切伴术后放射性碘扫描和后续甲状腺残余组织切除伴适当的大剂量131I（放射性碘)（如果病人甲状腺功能减退)。还有一种方法是在射碘前先予2天重组TSH(目前无货)，为诊断扫描作准备，以探查残余的甲状腺组织或癌，这样就可避免在诊断性扫描前病人出现甲状腺功能减退。每6－12个月进行一次重复治疗，以确保残余甲状腺组织的清除。治疗后应服用TSH抑制剂量的L－T4。血清甲状腺球蛋白测定有助于发现疾病的复发或持续。

FOLLICULAR CARCINOMA

滤泡状癌

Follicular carcinoma accounts for about 15% of thyroid cancers and is more common in the elderly. It is more malignant than papillary carcinoma, spreading hematogenously with distant metastases. It also is occasionally associated with a history of radiation exposure and occurs more frequently in females than in males.

滤泡状癌约占甲状腺癌的15%，老年人较常见。其恶性率高于乳头状癌，可沿血道向远处转移。偶尔也与放射线接触有关，女性得病率高于男性。

Treatment

治疗

Treatment for follicular carcinoma of any size requires near-total thyroidectomy with postoperative radioiodine ablation of residual thyroid tissue as in treatment for papillary carcinoma. Metastases appear to be more amenable to radioiodine therapy than those of papillary carcinoma. TSH suppressive doses of L-thyroxine and serum thyroglobulin measurements should be followed.医学.全在.线www.med126.com

滤泡状癌的治疗，不论大小，均需行次全切伴术后残余甲状腺组织射碘清除，这一点与乳头状癌治疗相同，射碘治疗转移效果较乳头状癌更佳。术后应使用TSH抑制剂量L－T4，并进行血清甲状腺球蛋白测定。

ANAPLASTIC CARCINOMA

未分化癌

Anaplastic carcinoma accounts for 10% or less of thyroid cancers and occurs mostly in elderly patients and in women slightly more than in men. The tumor is characterized by rapid and painful enlargement, and about 80% of patients die within 1 yr of diagnosis. Rapid enlargement of the thyroid gland may also suggest thyroid lymphoma, particularly if found in association with high levels of thyroid peroxidase antibodies and Hashimoto's thyroiditis.

未分化癌在甲状腺癌中所占比例为≤10%，大多发生在老年人，女性略多于男性。其特征为肿瘤的快速、疼痛性增大，约80%病人在确诊后1年内死亡。甲状腺迅速增大亦可提示甲状腺淋巴瘤，特别是在伴有高水平甲状腺过氧化酶抗体和桥本甲状腺炎时。

MEDULLARY CARCINOMA

髓样癌

Medullary (solid) carcinoma may occur as sporadic (usually unilateral) or as familial (frequently bilateral), transmitted as an autosomal dominant trait. Pathologically there is a proliferation of parafollicular cells (C cells) that produce excessive amounts of calcitonin, a hormone that can lower serum Ca and phosphate (PO4), but that is rarely present in sufficiently high concentrations to alter serum Ca and PO4 levels. There are also characteristic amyloid deposits that stain with Congo red.

髓样（实体)癌可以是散发性（通常单侧)也可以是家族性（常为双侧)，常染色体显性遗传。病理学显示有滤泡旁细胞（C细胞)的增生，产生过量降钙素。该激素可降低血清钙和磷酸盐（PO4)，但该激素很少能达到可以改变血清钙和磷酸盐（PO4)水平的浓度。同时有特征性刚果红染色的淀粉样沉着物。

Symptoms and Signs

症状体征

The usual presentation is that of an asymptomatic thyroid nodule, although many cases are now diagnosed during routine screening of affected kindreds with multiple endocrine neoplasia type IIA or IIB before a palpable tumor develops.医学全.在线网.站.提供

通常表现为无症状甲状腺结节，虽然很多病例在肿瘤扪及前就可通过多内分泌肿瘤IIA或IIB血缘关系的常规检查得到确诊。

Medullary carcinoma may have a dramatic biochemical presentation when associated with ectopic production of other hormones or peptides, such as ACTH, vasoactive intestinal polypeptide, prostaglandins, kallikreins, and serotonin. This tumor is a component of Sipple's syndrome, which is characterized by medullary carcinoma of the thyroid, pheochromocytoma, and hyperparathyroidism. All three disorders are not always found in the same patient. Pheochromocytoma is present in 50 to 75%; hyperparathyroidism, in 50%. Additional findings not regularly associated with this syndrome include disorders of the neural ectoderm, including mucosal neuromas; megacolon; pectus excavatum; poorly developed musculature; and marfanoid appearance, with long arms and fingers. When these associated conditions occur, the syndrome is classified as multiple endocrine neoplasia, type IIB; hyperparathyroidism is not present in this subset.

当伴有其他激素或肽异位分泌时，如促肾上腺皮质激素（ACTH)、血管活性肠多肽、前列腺素、血管舒缓素、血清素等，髓样癌就可能出现戏剧性生化改变。该肿瘤是赛普尔综合症组成之一，其特征是甲状腺髓样癌、嗜铬细胞瘤和甲状旁腺功能亢进。这三种病症不会出现于同一病人，嗜铬细胞瘤的出现率为50－75%，甲状旁腺功能亢进为50%。该综合症的其他非常见伴发症包括神经外胚层疾病，如神经粘膜瘤；巨结肠；漏斗胸；肌肉组织发育不全；马方样外表伴长臂长指。当出现这些伴发症时，该综合症就被归类为多内分泌肿瘤IIB。在该分组中不存在甲状旁腺功能亢进。

Metastases spread via the lymphatic system to cervical and mediastinal nodes, but sometimes to liver, lungs, and bone as well.

病灶通过淋巴系统转移到颈和纵隔淋巴结，有时也可能转移到肝、肺和骨。

Long-term survival is common in patients with medullary carcinoma and multiple endocrine neoplasia, type IIA, with > 2/3 of affected patients alive at 10 yr. Medullary carcinoma of the sporadic type carries a worse prognosis.

髓样癌及多发性内分泌瘤IIA病人长期存活是常见的，2/3以上病人可存活10年。散发性髓样癌预后较差。

Diagnosis

诊断

Isotopic scans demonstrate a nonfunctioning (cold) nodule that does not concentrate radioiodine. X-rays may show a dense, homogenous, conglomerate calcification. The best test for medullary carcinoma is the presence of an elevated serum calcitonin level, since only rarely is the level normal. A challenge with calcium (15 mg/kg IV over 4 h) or pentagastrin (0.5 µg/kg IV in 5 sec) provokes excessive secretion of calcitonin. Precise figures for calcitonin levels vary among laboratories.

同位素扫描显示无功能（冷)节，它不能浓集射碘。X线可显示致密、匀质、团块状钙化。髓样癌检实的最佳结果是发现血清降钙素水平增高，因为该值很少正常。钙（15 mg/kg IV滴注4 h)或五肽胃泌素（0.5µg/kg IV 5秒钟内推注)激发可刺激降钙素的过度分泌。降钙素确度因实验室而异。

Hereditary medullary carcinoma can now be diagnosed by detecting somatic point mutations in the ret proto-oncogene on chromosome 10, which are present in almost all of these patients.

遗传性髓样癌目前可通过10号染色体上”RET”原癌基因体点突变检查得以确诊，几乎所有此类病人都有这种情况。

Treatment

治疗

Total thyroidectomy is indicated, even if bilateral involvement is not obvious. Lymph nodes are also dissected. If hyperparathyroidism is present, removal of hyperplastic or adenomatous parathyroids is required. If pheochromocytoma occurs, it is usually bilateral; therefore, an anterior abdominal approach is preferred for the operation. Pheochromocytomas should be identified and removed before thyroidectomy because of the danger of provoking hypertensive crisis during the operation.

即使双侧累及不明显，也需行甲状腺全切。并行淋巴结清除。如存在甲状旁腺功能亢进，就需行甲状旁腺增生或腺瘤切除。如有嗜铬细胞瘤，通常为双侧性，最好行前腹腔开腹法。因术中有促发高血压危象可能，在施行甲状腺切除前应先确诊嗜铬细胞瘤。

Because of the familial incidence of medullary carcinoma, it is important to screen relatives by chromosomal analysis to detect mutations in the ret proto-oncogene and to periodically determine the basal and stimulated levels of serum calcitonin. Relatives in whom an elevated calcitonin level without a palpable thyroid abnormality is detected should undergo thyroidectomy, since there is a greater chance of cure at this stage. Some experts recommend surgical treatment in relatives who have normal basal and stimulated serum calcitonin but who have the ret proto-oncogene mutation.

髓样癌呈家族性，因此，对亲属进行染色体分析筛选，探测其RET原癌基因突变情况，定期测定其基础和激发的降钙素水平，这一点很重要。对于降钙素水平升高，但未扪及甲状腺异常的亲属，应行甲状腺切除，因为该阶段的治愈机率更高。有些专家建议，对基础和激发降钙素正常，但有RET原癌基因突变的亲属应行外科治疗。

UNDIFFERENTIATED THYROID CANCER

未分化甲状腺癌

This is a particularly virulent form of thyroid carcinoma. It occurs in the elderly and has a variable pathology, including spindle, squamous, and anaplastic cells. Although the prognosis is poor, a recent approach has been advocated consisting of chemotherapy and radiation before thyroidectomy and another course after surgical treatment. This approach has resulted in some prolonged remissions.

本病为最恶性的甲状腺癌，见于老年人，病理各异，包括纺锤状、鳞状和未分化细胞。虽然预后差，但最近有人主张在甲状腺切除前先做化疗和放疗，术后再做一个疗程。这种方法可使缓解期延长。

RADIATION-INDUCED THYROID CANCER

放射诱导的甲状腺癌

Relatively small doses of radiation during infancy and childhood increase the risk of developing benign and malignant thyroid neoplasms. A thyroid abnormality may develop about 5 yr after exposure, but the patient remains at increased risk for at least 30 to 40 yr after exposure. Probably no more than 1/3 of those irradiated develop a thyroid neoplasm; most are benign. However, about 7% of the irradiated group develop thyroid carcinoma; most are papillary or mixed follicular-papillary and are generally slow-growing and relatively nonaggressive. The tumors are frequently multicentric, and a thyroid scan does not always reflect areas of involvement. Microscopic foci of cancer often have been observed in areas considered clinically normal.

婴儿和儿童期相对小剂量照射增加良性和恶性甲状腺瘤危险。照射后5年可能出现甲状腺异常，至少在接触放射线后30~40年间，病人仍处于肿瘤多危期。大概不到1/3的放射病人会得甲状腺瘤，大多为良性。不过，约7%病人会得甲状腺癌，多数为乳头状癌或滤泡－乳头混合型癌，一般生长缓慢，相对无侵犯性。肿瘤呈多中心，甲状腺扫描并不总能显示病变部位。显微镜所显示的癌灶通常见于临床认为正常的区域。

Initial evaluation of all patients who received external and internal irradiation to the thyroid gland should include an 123I thyroid scan, perhaps a thyroid ultrasound, and examination of the thyroid gland for any palpable abnormality. In the absence of any abnormality, many physicians recommend TSH-lowering doses of thyroid hormone, with the aim of suppressing thyroid function and thyrotropin secretion to decrease the chance of developing a thyroid neoplasm. A scan or ultrasound abnormality in the absence of a palpable abnormality requires clinical judgment as to whether a needle aspiration biopsy should be performed, whether a period of suppressive therapy with thyroid hormone is required, or whether surgical treatment should be performed. Additionally, thyroid autoantibodies should be measured during the initial evaluation, since diffuse or irregular enlargement of the thyroid gland may be due to Hashimoto's (lymphocytic) thyroiditis. The neck should be examined yearly. Isotopic scanning is not repeated routinely.

所有接受甲状腺外、内照射病人的最初评估包括123I甲状腺扫描，或甲状腺超声，和甲状腺异常触诊检查。在无任何异常情况下，许多医生主张用TSH抑制剂量的甲状腺激素，以抑制甲状腺功能和促甲状腺系分泌，减少甲状腺肿瘤的发生机率。未扪及异常但有扫描或超声异常的病人可根据临床判断决定是否需作针吸活检，是否需要进行一个时期的甲状腺激素抑制治疗，或是否应行外科治疗。此外，在初期评估时也应作甲状腺自身抗体测定，既然弥散性或不规则性甲状腺增大可能是由桥本(淋巴细胞性)甲状腺炎引起的。每年应作颈部检查，按常规不需要进行同位素重复扫描。

When operative intervention is required, near-total or total thyroidectomy is the treatment of choice, to be followed by ablation of residual thyroid tissue with radioiodine if a cancer is found depending on the size, histology, and invasiveness. The operation must be performed by a surgeon with proven expertise in thyroid surgical treatment because of the risks inherent in such a procedure, including hypoparathyroidism and injury to the recurrent laryngeal nerve.

若需手术，应首选甲状腺次全切或全切。如发现甲状腺癌，可根据其大小、组织学和侵犯性情况，随后施行甲状腺残余组织射碘切除。手术应在甲状腺外科由有经验的外科医生进行，因为手术本身具有一定的危险性，如甲状旁腺功能减退和喉返神经损伤。