Thyroid cancer is generally divided into differentiated thyroid cancer including papillary thyroid cancer and follicular thyroid cancer, low differentiated thyroid cancer such as medullary thyroid cancer and undifferentiated thyroid cancer, and some rare malignant tumors such as thyroid lymphoma, metastatic thyroid cancer and squamous thyroid cancer. Among them, the proportion of papillary thyroid cancer is about 90%, follicular thyroid cancer is about 5%, medullary thyroid cancer is about 4%, and the rest are other malignant tumors such as undifferentiated thyroid cancer.
I. Symptoms.
Usually, differentiated thyroid cancer is more common in women, the ratio of female:male is about 3:1, and the incidence of differentiated thyroid cancer increases with age, commonly aged 30-60. Symptoms: Differentiated thyroid cancer develops slowly. Patients may find a gradually increasing painless lump in the neck, which is discovered unintentionally by themselves or during physical examination, or during ultrasound and other examinations. In the advanced stage of the disease, different degrees of hoarseness, dysphonia, dysphagia, dyspnea, cough and coughing up blood may occur. On physical examination, cancer tumors are mostly hard, and the surface may be smooth and the boundary may be clear. If the cancer is confined to the thyroid gland, it can move up and down with swallowing; if it has invaded the trachea or adjacent tissues, it will be more fixed.
II. Diagnosis.
Needle aspiration cytology examination. This method is one of the most reliable diagnostic methods for thyroid cancer, with a correct rate of more than 80%; intraoperative rapid frozen section examination is the key diagnostic tool for thyroid cancer, with a correct rate of nearly 90%; and paraffin section pathological examination is the most ideal diagnostic measure for thyroid cancer, with a correct rate of 100%.
Differential diagnosis.
Thyroid adenoma: Most benign thyroid tumors are isolated thyroid nodules, except for functional autonomic thyroid adenoma, and a few are multiple nodules. Most of them are found in a few months to several years or even longer due to slight discomfort or a lump of 25px or more, or they are found in the neck without any symptoms during routine physical examination by ultrasound. Most of them are single, round or oval, with smooth surface, clear border, firm texture, no adhesion with surrounding tissues, no pressure pain, and can move up and down with swallowing. Tumors are usually several centimeters in size, and huge ones are rare. Huge tumors can produce pressure on adjacent organs, but do not invade these organs, such as compression of the trachea and displacement of organs. In a few cases, the tumor may suddenly increase in size due to intra-tumor hemorrhage with localized swelling and pain. In principle, thyroid adenomas should be removed at an early stage because they may cause hyperthyroidism (about 20% of cases) and malignancy (about 10% of cases).
The following points can be used as reference when differentiating from thyroid cancer.
①Thyroid cancer should be considered as a possibility in children or male patients over 60 years old, while thyroid adenoma mostly occurs in female patients under 40 years old.
②Thyroid cancer nodules have uneven surface, hard texture, little mobility when swallowing, and grow faster in a short period of time. Sometimes, although the nodules in the thyroid gland are small, enlarged lymph nodes can be found in the ipsilateral neck. Thyroid adenoma has a smooth surface, soft texture, high mobility up and down during swallowing, slow growth, and mostly no enlarged lymph nodes in the neck.
③131 iodine scan or nuclear imaging of thyroid cancer mostly shows cold nodules, while thyroid adenoma may show warm nodules, cool nodules or cold nodules. Cold nodules are mostly cystic on ultrasound.
The thyroid adenoma has an intact envelope and normal surrounding thyroid tissue.
2. Nodular goiter: Nodular goiter (NG) may be caused by iodine deficiency in the diet or enzyme deficiency in thyroid hormone synthesis. Most of the nodules are multinodular, while a few are single nodules. Most of the nodules are gelatinous, with some forming cysts due to hemorrhage and necrosis; some areas may be more fibrotic or calcified, or even ossified, in long-standing cases. Thyroid bleeding often has a history of sudden pain and cyst-like masses within the gland; those with gelatinous nodules have a hard texture; those with calcification or ossification have a hard texture. Generally, conservative treatment is available, but nodules should be treated surgically if they produce symptoms of compression (difficulty in breathing, swallowing or hoarseness) due to their size, have a tendency to become malignant, or are combined with symptoms of hyperthyroidism.
3. Thyroiditis: subacute thyroiditis: the size of the nodule depends on the extent of the lesion, and the texture is often hard. There is a typical medical history, including rapid onset, fever, sore throat, and significant thyroid pain and tenderness. In the acute phase, the thyroid uptake rate decreases and the image is mostly “cold nodules” with elevated serum T3 and T4, which are “separated” and help in the diagnosis. In mild cases, non-steroidal anti-inflammatory drugs such as aspirin can be used, while more severe cases are treated with prednisone and dry thyroid preparations.
Chronic lymphocytic thyroiditis: a symmetrical diffuse goiter without nodules; sometimes due to asymmetric enlargement and surface lobing, it can resemble nodules, hard as rubber, without pressure pain. The disease starts slowly and develops chronically, but it can occur simultaneously with thyroid cancer, so it is not easy to distinguish clinically. Anti-thyroglobulin and anti-thyroid peroxidase antibody titers are often elevated.
Invasive fibrous thyroiditis: the nodules are hard and adherent to adjacent tissues outside the gland. The onset and progression of the disease are slow, and there may be local vague pain and pressure, accompanied by obvious pressure symptoms. The clinical manifestations resemble thyroid cancer, but the local lymph nodes are not large, and the uptake I rate is normal or low.
4.Thyroid cyst: The cyst contains blood or clear liquid, clearly demarcated from the surrounding thyroid tissue, and can be quite hard.
Auxiliary tests.
1, thyroid function tests: mainly thyroid stimulating hormone (TSH) measurement. highly functional hot nodules with reduced TSH are less likely to be malignant, so it is more important to treat their hyperthyroidism. thyroid nodules with normal or elevated TSH, as well as cold or warm nodules with reduced TSH, should be further evaluated (e.g., puncture biopsy).
2. Nuclear scan: Isotope scan examination (ECT) with radioactive iodine or technetium is an important tool to determine the functional size of thyroid nodules. According to the American Thyroid Association, “The results of ECT include highly functional (higher uptake than the surrounding normal thyroid tissue), equifunctional or warm nodules (same uptake as the surrounding tissue) or nonfunctional nodules (lower uptake than the surrounding thyroid tissue). High-functioning nodules have a low rate of malignancy, and nodules need to be evaluated if the patient has significant or subclinical hyperthyroidism. If serum TSH levels are high, nodules should be evaluated even if they are only at the highest limit of the reference value, as this is when nodules have a higher rate of malignancy”. However, ECT often cannot show nodules smaller than 25px or microscopic cancer, so ECT should not be used for such nodules.
Ultrasound: Ultrasound is an important tool to detect thyroid nodules and determine their benignity and malignancy, and is the standard for determining the possibility of performing fine needle aspiration biopsy (FNA). The European and American guidelines mention the following indications for suspicion of malignancy on ultrasound: hypoechoic nodules, microcalcifications, abundant blood flow signals, poorly defined borders, nodule height greater than width, solid nodules, and halo absence. Most thyroid cancers are substantial masses, papillary thyroid cancers are hypo- or very hypoechoic, and follicular thyroid cancers are very homogeneous hyperechoic masses.
4.CT/Magnetic Resonance Imaging (MRI): examination to understand lymph node metastasis and tumor invasion of surrounding organs and tissues to determine whether surgery is possible.
V. Treatment
Differentiated thyroid cancer: total thyroidectomy is the standard treatment. For those with lymph node metastasis, postoperative iodine 131 therapy is recommended to consolidate the efficacy and prevent recurrence. However, for those with more residual thyroid gland, since iodine 131 cannot kill metastases directly, and at the same time, thyroxine preparation has to be stopped during iodine therapy, which increases the risk of tumor recurrence and dedifferentiation.
Surgical treatment of thyroid cancer includes surgery of the thyroid gland itself, as well as cervical lymph node dissection. The extent of thyroid removal is still a matter of disagreement, but complete removal of the tumor is important, and there is evidence of a low recurrence rate after subtotal or total thyroidectomy. The main disadvantage is the increase in recent or long-term complications after surgery, whereas lobectomy rarely results in damage to the recurrent laryngeal nerve and little or no severe hypoparathyroidism occurs.
The extent of cervical lymph node dissection is also debated, whether it should be performed routinely in the central region or with modified lymph node dissection, or whether only the palpable enlarged lymph nodes should be removed, is still inconclusive.
After surgery, thyroxine suppressive therapy (eugenol) is recommended to prevent recurrence of thyroid cancer.
High-risk group with differentiated type: take thyroxine preparation to make TSH <0.1mU/L;
Differentiated low-risk group: take thyroxine preparations to achieve 0.1 mU/L
Multi-year low-risk group: 0.3 mU/L with thyroxine preparations
Since TSH suppression can cause certain toxic effects on the organism, such as tachyarrhythmias (especially in the elderly), bone decalcification (especially in postmenopausal women), and thyrotoxicosis-related manifestations. Therefore, for each patient, the pros and cons of TSH suppression therapy need to be considered. In patients with long-term TSH suppression, a daily intake of calcium (1.2 mg/d) and vitamin D (1.0 U/d) should be ensured.
Radionuclide therapy (131 iodine therapy): For papillary and follicular carcinoma, postoperative application of iodine is suitable for patients over 45 years old, multiple cancer foci, locally invasive tumors and those with distant metastases. It mainly destroys the residual thyroid tissue after thyroidectomy and is beneficial to reduce recurrence and mortality in high-risk cases. The purpose of applying iodine treatment is: ① to destroy the hidden microscopic cancer in the residual thyroid gland;? easy to detect recurring or metastatic lesions using nuclear hormone; ③ increase the value of using thyroglobulin as a tumor marker during postoperative follow-up.
Medullary thyroid cancer: surgery is the preferred and only possible cure for medullary carcinoma because of the lack of effect on thyroxine agent suppression and iodine 131 treatment.
Undifferentiated thyroid cancer: Because of its high malignancy and very rapid progression, it easily invades the surrounding organs and tissues such as trachea, esophagus, nerves and blood vessels in the neck, therefore, it is often diagnosed at an advanced stage and cannot be removed surgically, only external radiation therapy and chemotherapy can be administered.
Standardized treatment
1. For benign thyroid nodules, local excision or enucleation is advocated to preserve the normal gland and avoid total thyroidectomy, especially for adolescent patients.
At least lobectomy and isthmus resection should be performed. Many other scholars advocate total thyroidectomy, which is believed to reduce the local recurrence rate but increase the probability of damage to the laryngeal nerve and parathyroid function.
3. Advocating routine dissection of the recurrent laryngeal nerve intraoperatively can reduce the injury of the recurrent laryngeal nerve and reduce medical disputes. If the tumor is diagnosed, the lymph nodes in the central region (paratracheoesophageal) should be routinely explored or removed.
4.Chemotherapy, radiotherapy and radioactive particle implantation are not effective for differentiated carcinoma and medullary carcinoma, and are only applicable to trace residual tumor at important organs and blood vessels.
For low-risk patients, if the enlarged lymph nodes are not touched during clinical examination and operation, only the central region can be cleared. For high-risk patients, if the enlarged lymph nodes are touched during clinical examination and operation, biopsy can be excised and those with positive results can be cleared functionally.
For differentiated thyroid carcinoma with localized invasion, we should still strive to preserve important organs, such as larynx and trachea, and not to sacrifice the function of organs by forcing complete surgery.
Ultrasound examination is of great value in determining the nature of thyroid nodules and in the follow-up after treatment. Experienced ultrasound diagnosis can more accurately identify the benignity and malignancy of thyroid nodules and cervical lymph nodes, and should be strongly advocated to replace the traditional method based on palpation and reduce unnecessary superfluous surgery.
8. For malignant thyroid tumors, postoperative hormone replacement is necessary to suppress the level of thyrotropin and prevent recurrence. It is recommended to take thyroxine after thyroid cancer surgery to keep TSH below the normal low boundary and above zero value, and to monitor TSH level for life.
9. For the high-risk age group, if the local lesion is late, the neck metastasis is extensive, or the tumor is poorly differentiated, aggressive surgery (including total thyroidectomy) and postoperative isotope therapy should be adopted.
Prognosis
The overall 10-year survival rate of differentiated thyroid cancer is up to 85%. According to the aforementioned high- and low-risk staging, its 20-year survival rate is about 90% for low-risk and 61% for high-risk. Even with metastases from other parts of the body, the 10-year survival rate of differentiated thyroid cancer can be 25%-40%.
Diet and precautions: Postoperative iodine diet should be avoided for differentiated thyroid cancer, which includes consuming non-iodized salt and avoiding seafood. In addition, postoperative thyroid cancer patients should avoid fatigue and heavy physical work, and can take appropriate Chinese herbal medication.
Medullary thyroid carcinoma can develop lymphatic metastasis at an early stage and distant metastasis can occur through bloodstream, so the prognosis is worse than that of differentiated thyroid carcinoma. The malignancy of medullary thyroid cancer varies greatly from case to case, some of them can be stable for many years or even insidious, while others are highly aggressive and have a high death rate. Overall, the 10-year survival rate associated with medullary thyroid cancer is 75%. Major prognostic factors include age at diagnosis, size of the primary lesion, presence of lymph node metastases and distant metastases. Survival rates according to TMN staging were 100%, 93%, 71%, and 21% for stages I, II, III, and IV, respectively.
The morbidity and mortality rate of undifferentiated thyroid cancer is about 50%, and only very few patients can survive long-term, and many die within a short period of time. Generally, the median survival period from diagnosis to death is only 4~8 months.
VII. Review and recurrence
Differentiated thyroid cancer: If total thyroidectomy is performed, the TG (thyroglobulin) is significantly elevated, indicating the possibility of tumor recurrence;
Medullary thyroid cancer: a significant increase in serum calcitonin level also indicates tumor recurrence or metastasis.
If local recurrence or lymph node metastasis in the neck or upper mediastinum is detected, most patients can still achieve radical treatment through reoperation. For differentiated thyroid cancer, if lung metastasis occurs, all residual thyroid glands can be removed and all metastatic lymph nodes can be cleared, and then 131 iodine isotope therapy can be performed, which can also achieve better results. For distant metastases in bone and brain, the metastases can sometimes be removed first and then treated with isotope therapy. If surgical resection is not possible, the treatment is the same as pulmonary metastases.
Special reminder: for differentiated thyroid cancer and medullary carcinoma that can be excised by surgery, radiotherapy and chemotherapy are not recommended after surgery. Because radiotherapy and chemotherapy cannot bring higher cure rate and control rate, on the contrary, they will bring more side effects and complications. Only for patients who only have a small amount of tumor left after surgery, postoperative radiotherapy can improve the control rate and prognosis.