甲狀腺癌

Thyroid Cancers

甲狀腺癌

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.

甲狀腺癌一般有4種類型：乳頭狀(包括乳頭－濾泡混合型癌)、濾泡狀、髓樣(實體，伴淀粉樣甲狀腺腫)和未分化及間變細胞癌（罕見)。多數(shù)甲狀腺結(jié)節(jié)為良性。甲狀腺癌一般也非極度惡性，如果治療得當，患者可以達到正常壽命。

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，病人或醫(yī)生會注意到頸部有一個并無其他癥狀的腫塊。小甲狀腺癌轉(zhuǎn)移可能導(dǎo)致一些因淋巴結(jié)增大、肺部癥狀或破壞性骨損所致的癥狀，但這種情況較罕見。

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)年齡(年輕病人更易患癌)；(2)性別,如果病人為男性(女性與男性的甲狀腺癌比為2：1，但女性更多的是得甲狀腺病，約為8:1，因此，男性有甲狀腺結(jié)節(jié)時應(yīng)考慮癌的可能性更大)；(3)孤立小結(jié)(多結(jié)節(jié)病變一般為良性，除非甲狀腺掃描時呈明顯的冷結(jié)節(jié))；(4)甲狀腺同位素掃描時發(fā)現(xiàn)冷結(jié)節(jié)(熱結(jié)節(jié)很少表現(xiàn)為癌)；(5)有過頭、頸、胸放射接觸史,尤其是嬰兒和兒童期(例如，因胸腺增大或扁桃體腫大、痤瘡或淋巴瘤等)；(6)X線片見細、斑點狀、沙粒樣鈣化(乳頭狀癌)或致密、勻質(zhì)鈣化(髓樣癌)；(7)最近增大或快速增大；(8)質(zhì)地石頭樣堅硬。如擁有技術(shù)熟練的活檢技術(shù)員和細胞學(xué)家，針吸活檢便是區(qū)別淋巴瘤良性與惡性的最佳診斷方法。

PAPILLARY CARCINOMA

乳頭狀癌

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.

乳頭狀癌是最常見的甲狀腺癌(占全部甲狀腺癌的60%~70%)。女性病人是男性病人的2-3倍。年輕人較常見，但老年人惡性率更高。有照射史病人較常見，癌細胞可經(jīng)淋巴系統(tǒng)擴散。可以發(fā)現(xiàn)一側(cè)迷走性甲狀腺殘余，實際上這是帶有良性組織表觀的癌的隱性轉(zhuǎn)移。.這些高分化癌屬TSH（促甲狀腺激素)依賴型，可以在繼發(fā)于橋本甲狀腺炎的甲狀腺腫中發(fā)展。許多乳頭狀癌含有濾泡成分，但這并不改變腫瘤的基本生物學(xué)特征。

Treatment

治療

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.

對局限于一葉的包裹性小腫瘤（< 1.5 cm),通常作葉切除和峽部切除，但有些專家建議進行更廣泛的甲狀腺外科治療。TSH抑制劑量甲狀腺激素用于減少癌的再生或使顯微鏡鏡檢下的乳頭狀癌殘余出現(xiàn)萎縮；外科治療幾乎總是可以治愈它。大的(＞1.5cm)或彌漫擴散性腫瘤常需行甲狀腺全切或次全切伴術(shù)后放射性碘掃描和后續(xù)甲狀腺殘余組織切除伴適當?shù)拇髣┝?31I（放射性碘)（如果病人甲狀腺功能減退)。還有一種方法是在射碘前先予2天重組TSH(目前無貨)，為診斷掃描作準備，以探查殘余的甲狀腺組織或癌，這樣就可避免在診斷性掃描前病人出現(xiàn)甲狀腺功能減退。每6－12個月進行一次重復(fù)治療，以確保殘余甲狀腺組織的清除。治療后應(yīng)服用TSH抑制劑量的L－T4。血清甲狀腺球蛋白測定有助于發(fā)現(xiàn)疾病的復(fù)發(fā)或持續(xù)。

FOLLICULAR CARCINOMA

濾泡狀癌

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.

濾泡狀癌約占甲狀腺癌的15%，老年人較常見。其惡性率高于乳頭狀癌，可沿血道向遠處轉(zhuǎn)移。偶爾也與放射線接觸有關(guān)，女性得病率高于男性。

Treatment

治療

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.醫(yī)學(xué).全在.線www.med126.com

濾泡狀癌的治療，不論大小，均需行次全切伴術(shù)后殘余甲狀腺組織射碘清除，這一點與乳頭狀癌治療相同，射碘治療轉(zhuǎn)移效果較乳頭狀癌更佳。術(shù)后應(yīng)使用TSH抑制劑量L－T4，并進行血清甲狀腺球蛋白測定。

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.

未分化癌在甲狀腺癌中所占比例為≤10%，大多發(fā)生在老年人，女性略多于男性。其特征為腫瘤的快速、疼痛性增大，約80%病人在確診后1年內(nèi)死亡。甲狀腺迅速增大亦可提示甲狀腺淋巴瘤，特別是在伴有高水平甲狀腺過氧化酶抗體和橋本甲狀腺炎時。

MEDULLARY CARCINOMA

髓樣癌

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.

髓樣（實體)癌可以是散發(fā)性（通常單側(cè))也可以是家族性（常為雙側(cè))，常染色體顯性遺傳。病理學(xué)顯示有濾泡旁細胞（C細胞)的增生，產(chǎn)生過量降鈣素。該激素可降低血清鈣和磷酸鹽（PO4)，但該激素很少能達到可以改變血清鈣和磷酸鹽（PO4)水平的濃度。同時有特征性剛果紅染色的淀粉樣沉著物。

Symptoms and Signs

癥狀體征

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.醫(yī)學(xué)全.在線網(wǎng).站.提供

通常表現(xiàn)為無癥狀甲狀腺結(jié)節(jié)，雖然很多病例在腫瘤捫及前就可通過多內(nèi)分泌腫瘤IIA或IIB血緣關(guān)系的常規(guī)檢查得到確診。

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.

當伴有其他激素或肽異位分泌時，如促腎上腺皮質(zhì)激素（ACTH)、血管活性腸多肽、前列腺素、血管舒緩素、血清素等，髓樣癌就可能出現(xiàn)戲劇性生化改變。該腫瘤是賽普爾綜合癥組成之一，其特征是甲狀腺髓樣癌、嗜鉻細胞瘤和甲狀旁腺功能亢進。這三種病癥不會出現(xiàn)于同一病人，嗜鉻細胞瘤的出現(xiàn)率為50－75%，甲狀旁腺功能亢進為50%。該綜合癥的其他非常見伴發(fā)癥包括神經(jīng)外胚層疾病，如神經(jīng)粘膜瘤；巨結(jié)腸；漏斗胸；肌肉組織發(fā)育不全；馬方樣外表伴長臂長指。當出現(xiàn)這些伴發(fā)癥時，該綜合癥就被歸類為多內(nèi)分泌腫瘤IIB。在該分組中不存在甲狀旁腺功能亢進。

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

病灶通過淋巴系統(tǒng)轉(zhuǎn)移到頸和縱隔淋巴結(jié)，有時也可能轉(zhuǎn)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.

髓樣癌及多發(fā)性內(nèi)分泌瘤IIA病人長期存活是常見的，2/3以上病人可存活10年。散發(fā)性髓樣癌預(yù)后較差。

Diagnosis

診斷

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.

同位素掃描顯示無功能（冷)節(jié)，它不能濃集射碘。X線可顯示致密、勻質(zhì)、團塊狀鈣化。髓樣癌檢實的最佳結(jié)果是發(fā)現(xiàn)血清降鈣素水平增高，因為該值很少正常。鈣（15 mg/kg IV滴注4 h)或五肽胃泌素（0.5µg/kg IV 5秒鐘內(nèi)推注)激發(fā)可刺激降鈣素的過度分泌。降鈣素確度因?qū)嶒炇叶�異�?/P>

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.

遺傳性髓樣癌目前可通過10號染色體上”RET”原癌基因體點突變檢查得以確診，幾乎所有此類病人都有這種情況。

Treatment

治療

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.

即使雙側(cè)累及不明顯，也需行甲狀腺全切。并行淋巴結(jié)清除。如存在甲狀旁腺功能亢進，就需行甲狀旁腺增生或腺瘤切除。如有嗜鉻細胞瘤，通常為雙側(cè)性，最好行前腹腔開腹法。因術(shù)中有促發(fā)高血壓危象可能，在施行甲狀腺切除前應(yīng)先確診嗜鉻細胞瘤。

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.

髓樣癌呈家族性，因此，對親屬進行染色體分析篩選，探測其RET原癌基因突變情況，定期測定其基礎(chǔ)和激發(fā)的降鈣素水平，這一點很重要。對于降鈣素水平升高，但未捫及甲狀腺異常的親屬，應(yīng)行甲狀腺切除，因為該階段的治愈機率更高。有些專家建議，對基礎(chǔ)和激發(fā)降鈣素正常，但有RET原癌基因突變的親屬應(yīng)行外科治療。

UNDIFFERENTIATED THYROID CANCER

未分化甲狀腺癌

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.

本病為最惡性的甲狀腺癌，見于老年人，病理各異，包括紡錘狀、鱗狀和未分化細胞。雖然預(yù)后差，但最近有人主張在甲狀腺切除前先做化療和放療，術(shù)后再做一個療程。這種方法可使緩解期延長。

RADIATION-INDUCED THYROID CANCER

放射誘導(dǎo)的甲狀腺癌

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.

嬰兒和兒童期相對小劑量照射增加良性和惡性甲狀腺瘤危險。照射后5年可能出現(xiàn)甲狀腺異常，至少在接觸放射線后30~40年間，病人仍處于腫瘤多危期。大概不到1/3的放射病人會得甲狀腺瘤，大多為良性。不過，約7%病人會得甲狀腺癌，多數(shù)為乳頭狀癌或濾泡－乳頭混合型癌，一般生長緩慢，相對無侵犯性。腫瘤呈多中心，甲狀腺掃描并不總能顯示病變部位。顯微鏡所顯示的癌灶通常見于臨床認為正常的區(qū)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.

所有接受甲狀腺外、內(nèi)照射病人的最初評估包括123I甲狀腺掃描，或甲狀腺超聲，和甲狀腺異常觸診檢查。在無任何異常情況下，許多醫(yī)生主張用TSH抑制劑量的甲狀腺激素，以抑制甲狀腺功能和促甲狀腺系分泌，減少甲狀腺腫瘤的發(fā)生機率。未捫及異常但有掃描或超聲異常的病人可根據(jù)臨床判斷決定是否需作針吸活檢，是否需要進行一個時期的甲狀腺激素抑制治療，或是否應(yīng)行外科治療。此外，在初期評估時也應(yīng)作甲狀腺自身抗體測定，既然彌散性或不規(guī)則性甲狀腺增大可能是由橋本(淋巴細胞性)甲狀腺炎引起的。每年應(yīng)作頸部檢查，按常規(guī)不需要進行同位素重復(fù)掃描。

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.

若需手術(shù)，應(yīng)首選甲狀腺次全切或全切。如發(fā)現(xiàn)甲狀腺癌，可根據(jù)其大小、組織學(xué)和侵犯性情況，隨后施行甲狀腺殘余組織射碘切除。手術(shù)應(yīng)在甲狀腺外科由有經(jīng)驗的外科醫(yī)生進行，因為手術(shù)本身具有一定的危險性，如甲狀旁腺功能減退和喉返神經(jīng)損傷。