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< Brief History
>
A 66-year-old woman was seen
because of progressive enlargement of the neck in recent 3
months. She had a palpable nodule of the thyroid for 4 years,
which was about 2 cm in diameter and benign by cytology exam.
However, she noted that the nodule enlarged progressively
about 3 months earlier prior to this admission. Besides, she
felt pain over the nodule and developed hoarseness, cough,
dyspnea, swallowing difficulty and weight loss of 2 kg per
month. There was no fever, sore throat, resting tremor of the
hands, palpitation, heat intolerance, or polyphagia. She
visited OPD where cytology of the nodule by aspiration
reported necrotic tissue. Because of compressing symptoms,
operative excision was suggested and she was admitted for
further management.
She had no any systemic disease
except multinodular goiter. She did not consume alcohol, or
tobacco, and had no history of animal contact or travel
recently.
On examination, she had clear
consciousness but was ill-looking. Her height was 154.6 cm and
weight was 58 kg. The temperature was 37.1°C, the pulse rate
90 beats per minute and the respiratory rate 20 breaths per
minute. Blood pressure while in supine position was 124/70
mmHg. Her conjunctivae were pink, the sclerae were anicteric
and the pupils were isocoric with prompt light reflexes. The
neck was supple without lymphadenopathy, engorged jugular
veins, or carotid bruits. A nodule, which was unmovable, hard
and tender, was about 1.0 cm in diameter and located at the
right thyroid gland. The skin over the nodule was slightly
red. The chest wall expansion was symmetric and breath sounds
were bilaterally clear. The heart beats were regular without
audible murmur. The abdomen was soft and bowel sounds were
normoactive. The liver and spleen were impalpable. The liver
span was estimated 10 cm at the right mid-clavicular line. The
extremities were freely movable without edema.
< Laboratory data
>
1. CBC/DC
|
WBC |
RBC |
HB |
HCT |
MCV |
MCHC |
PLT |
|
K/μL |
M/μL |
g/dL |
％ |
fL |
g/dL |
K/μL |
|
16.79 |
3.83 |
11.5 |
37.1 |
95.9 |
31 |
465 |
2. Biochemistry and electrolytes
|
ALB |
T-Bil |
AST |
ALT |
UN |
CRE |
|
g/dL |
mg/dL |
U/L |
U/L |
mg/dL |
mg/dL |
|
3.7 |
0.4 |
17 |
22 |
11.4 |
0.7 |
|
Na |
K |
Cl |
CRP |
hsTSH |
free T4
|
|
mmol/L |
mmol/L |
mmol/L |
mg/dL |
0.1-4.5
μU/mL |
0.60-1.75
ng/dL |
|
137 |
4.3 |
103 |
2 |
1.76 |
1.09 | *high sensitivity thyroid-stimulating hormone＝hsTSH; free
thyroxine＝free
T4
3. Urine analysis
|
Appearance |
Sp. Gr |
pH |
Protein |
Glucose |
Ketone |
Bacteria |
|
|
|
|
g/dL |
mg/dL |
|
|
|
Y;C |
1.028 |
6.0 |
- |
- |
- |
- |
|
Urobilirubin |
Bilirubin |
Nitrate |
WBC |
RBC |
Epi |
Cast |
|
|
|
|
/HPF |
/HPF |
HPF |
|
|
1.0 |
- |
- |
1-2 |
1-2 |
3-5 |
- |
< Course and
treatment
>
A chest
radiograph revealed a soft tissue mass at the right neck,
deviation of the upper airway to the left, and a nodule at the
right upper lung field (fig 1 ). Computerized tomography of
the neck showed a mass with necrotic part in the right
anterior paramedian region; the trachea and adjacent major
vessels were deviated to the left (fig 2
and 3). There
was no obvious lymphadenopathy. She underwent right
thyroidectomy with resection of a large mass. There was no
enlargement of the paratracheal lymph nodes. The pathology of
the tumor reported anaplastic carcinoma of the thyroid (fig 4
). Follow-up chest radiograph showed progressive
enlargement of the nodule at the right upper lobe. Under the
impression of anaplastic carcinoma of the thyroid with lung
metastasis, palliative chemotherapy with bleomycin (15 mg) and
doxorubicin (40 mg) were given, but the response was poor.
Hence chemotherapy regimen was switched to Phyxol and CDDP
(Phyxol 120 mg and cisplatin 90 mg). She received a total of 4
courses of Phyxol and CDDP afterwards. She was followed up
regularly at OPD.
< Discussion
>
甲狀腺出現塊狀突起時，稱為甲狀腺結節(nodule)，常見原因包括：結節性甲狀腺腫、良性甲狀腺瘤、甲狀腺囊腫、亞急性甲狀腺炎、功能自主性甲狀腺結節腺瘤、慢性甲狀腺炎、分化良好的甲狀腺癌；罕見的原因如：淋巴瘤、髓質癌(medullary
cancer)、未分化甲狀腺癌、急性化膿性甲狀腺炎、轉移性癌、先天性甲狀腺發育缺陷或僅有單葉甲狀腺等。
甲狀腺惡性腫瘤約占所有惡性腫瘤的1%，原因仍不清，可能與下列因素有關：兒童或青少年時期頭頸部或胸部上方曾接受Ｘ光或放射線治療、某些橋本氏甲狀腺炎(Hashimoto's
thyroiditis)患者可能與甲狀腺淋巴瘤(lymphoma)有關，及家族遺傳性甲狀腺髓質癌。根據組織型態可以將原發性甲狀腺癌，分為乳突癌(papillary
cancer)、濾泡癌(follicular cancer)、未分化癌(anaplastic
cancer)、髓質癌、及甲狀腺淋巴癌。
初期並無自覺症狀，直到腫瘤長到一定大小，病人自己可以摸到結節，於檢查之後才知道。症狀包括：局部頸部腫大或摸到硬塊，通常較硬、易與周圍組織沾黏、活動性較差；當腫瘤壓迫到返喉神經時會出現聲音沙啞；侵犯食道時出現吞嚥困難、體重減輕；侵犯或壓迫到氣管時則出現咳血、呼吸困難及胸部不適；其他局部及遠端轉移症狀，如頸部淋巴結腫大、頭痛、嘔吐、咳嗽、咳血、胸部不適、病理性骨折及疼痛，與脊髓轉移引起之手腳酸麻或無力等。
甲狀腺乳突癌由濾泡上皮細胞衍生而來，占甲狀腺癌的50-70%，生長很緩慢，10年存活率約90%。癌瘤為多發性、缺少包膜、易局部淋巴轉移，而不易經血流轉移遠端。發病年齡40歲以下者約占一半，女性為男性的三倍。癌細胞生長受到促甲狀腺素(thyroid
stimulating hormone，TSH)的影響，故服用甲狀腺素抑制TSH
時，乳突癌的轉移常會退化。年齡是乳突癌預後最重要的影響因子；大於50歲、腫瘤直徑大於4公分、男性、癌細胞直接侵犯出甲狀腺包膜外、有頸部以外的遠處轉移、癌細胞周邊的甲狀腺組織缺乏橋本氏甲狀腺炎的病理變化，都是預後較差的危險因子。癌細胞積聚碘的能力不及正常細胞，所以核醫檢查呈現cold
nodule，有時頸部X光可以看到砂樣體(psamoma bodies)的點狀鈣化。
濾泡癌由濾泡上皮細胞衍生而來，佔甲狀腺癌15%，生長緩慢、單發性、有包膜、大小不一、缺碘地區的發生率較高，10年存活率約為80%。通常40歲後發生，較少轉移到局部淋巴結，而常經血流轉移至遠端，轉移也受血中TSH濃度影響。年齡是重要的預後因子，雖有積聚碘的能力，但不如正常細胞，所以掃描也呈cold
nodule。
未分化癌也是由濾泡上皮細胞衍生而來，約佔甲狀腺癌的l0%，病患以50歲以上及女性居多。癌細胞極為惡性且迅速侵犯周邊組織及轉移到全身，沒有良好包覆且常使整個甲狀腺變形，病灶處有些部分柔軟，有些部分堅硬如石。通常在頸部出現一個硬塊或結節，固定不易移動，且造成局部淋巴結腫大及疼痛、聲音沙啞、呼吸喘鳴及吞嚥困難等。患者常在診斷確定後數月內死亡，預後很差。組織形態常見局部壞死或多型核白血球(polymorphonuclear
leukocytes)浸潤，有些部位有類似乳突癌或濾泡癌的細胞型態，因此懷疑此二者可能是未分化癌的前驅。癌細胞沒有積聚碘的能力。
髓質癌由甲狀腺旁細胞（C-cells）衍生而來，約占甲狀腺癌1-2%。40歲以上及女性較易發生，惡性程度介於濾泡癌及未分化癌之間，10年存活率約60-70%。可以藉由腺內淋巴轉移到腺內其他部位或局部淋巴結，也可藉由血流轉移至遠處，預後由診斷年齡及是否轉移決定。因為會分泌抑鈣素(calcitonin)，因而提供了早期診斷及治療的契機。髓質癌可能是家族遺傳性或偶發性的，前者約占20%，多侵犯兩側甲狀腺，且常合併其他多發性內分泌腺體的異常增生，發病年齡較輕、診斷時少有轉移，預後較佳。
甲狀腺淋巴癌極為罕見，約占甲狀腺癌的1%。有人懷疑長期橋本氏甲狀腺炎會發展成甲狀腺淋巴癌。甲狀腺掃描也是coId
nodule。
診斷方法有：甲狀腺觸診、頸部淋巴結檢視、血液生化檢查(抑鈣素)、超音波、核子醫學、X光、及細針抽吸腫瘤細胞學檢查。細針抽吸腫瘤細胞學檢查對乳突癌、髓質癌及未分化癌的診斷率都很高，而濾泡癌的診斷則較為困難。
甲狀腺癌的治療方法包括：外科手術、放射性同位素碘、體外放射線、化學及藥物治療。然而，一旦診斷為甲狀腺癌，開刀切除是最佳的治療方法，切除範圍可以是全甲狀腺切除、近全甲狀腺切除、次全甲狀腺切除、小部分甲狀腺切除及合併廣泛性頸部淋巴結切除。開刀併發症包括：暫時或永久性副甲狀腺功能低下症及聲帶麻痺等。即使是分化不良性甲狀腺癌細胞對碘的親和力也較身體其他部位細胞高400-600倍，所以建議於完全切除甲狀腺約4至6週且患者血中TSH濃度大於30
μU/ml(或術後給予合成的TSH)後，再給予100
mCi放射性碘治療效果較佳。放射性碘治療的副作用少，如厭食、噁心、頭暈、皮膚搔癢、前頸部疼痛(放射性甲狀腺炎)、唾液腺腫脹、及骨髓抑制等，通常於1至2星期後消失。目前學者建議一生的累積劑量不要超過500
mCi，且二次的治療間隔最好至少間隔一年以上，可以減少白血病及肺部纖維化的發生率。放射性碘治療對乳突癌及濾泡癌較有效，但對骨骼轉移或肺部大結節性轉移的治療效果較差，至於未分化癌、髓質癌及淋巴癌則對放射性碘治療無反應。使用鈷六十直線加速器所產生的放射線能量來破壞極惡性未分化癌或併骨轉移導致的劇痛。化學療法的效果有限。分化良好型甲狀腺癌細胞生長受到TSH的刺激，因此手術及放射性碘治療後，均應給予較高劑量的甲狀腺素治療。
手術及放射性碘治療後的第一年，應每3個月檢查一次血中甲狀腺素、TSH及甲狀腺球蛋白(thyroglobulin)濃度。第二年每6個月檢查一次，如一切正常，之後可以一年檢查一次。甲狀腺球蛋白濃度可以作為分化良好型甲狀腺癌是否復發的指標，髓質癌患者則可追蹤抑鈣素濃度。此外，所有患者每年都應作一次胸部Ｘ光檢查是否有肺部轉移，過量補充甲狀腺素會造成骨質疏鬆症，因此女性患者每年應檢查一次骨質密度。
< References
>
- Weiss RE, Lado-Abeal J: Thyroid
nodules: diagnosis and therapy. Curr Opin Oncol 2002;14:46.
- Basaria M et al: The use of
recombinant thyrotropin in the follow-up of patients with
differentiated thyroid cancer. Am J Med 2002;112:721.
- Giuffrida D, Gharib H: Anaplastic thyroid carcinoma:
current diagnosis and treatment. Ann Oncol 2000;11;1083.
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Case Discussion
繼續教育考題