Differentiated thyroid cancer (DTC) is the most common thyroid malignancy, including papillary and follicular carcinomas, accounting for approximately 90% of all thyroid tumors. The incidence of thyroid cancer has steadily increased in recent years, with a 240% increase in 30 years, of which approximately 75% occurs in women [1]. There are still controversies in the diagnosis and treatment of DTC, such as the surgical approach and extent of resection of the primary cancer site, whether to perform lymph node dissection and the extent of dissection, the indications and efficacy of postoperative radioiodine therapy, the necessity of endocrine therapy, and the treatment after recurrence or metastasis, etc. The latest updated guidelines for the standardized treatment of differentiated thyroid cancer published by the American Thyroid Association (ATA) (2009) and The new NCCN guideline (2010) is a guideline for clinical diagnosis and treatment, and the relevant studies are still emerging, putting forward new requirements and protocols. 1. Diagnosis of differentiated thyroid cancer History, symptoms and signs Most of the differentiated thyroid cancer has no obvious symptoms in early stage. Patients may find thyroid nodules in the neck unintentionally or during screening, or a fixed enlarged cervical lymph node without an obvious thyroid mass, or they may visit the doctor because of newly developed hoarseness or difficulty in breathing and swallowing. On physical examination, a painless mass in the gland with poorly defined borders, an uneven surface, a hard texture, little mobility or complete fixation may be palpable, often accompanied by an enlarged ipsilateral cervical lymph node [2]. Some patients with DTC have certain risk factors, such as family history of thyroid cancer, autoimmune diseases, and previous high-dose X-ray or radiotherapy to the neck. However, thyroid cancer lacks specific symptoms and its clinical manifestations are not easily distinguished from benign diseases such as nodular goiter and thyroid adenoma. It is sometimes difficult to confirm the diagnosis based on medical history and physical examination alone, and its benignity and malignancy cannot be inferred based on the size and growth rate of the tumor. Ultrasonography Ultrasonography has the advantages of being economical, non-invasive and reproducible, and has become one of the preferred methods for thyroid cancer. Ultrasonography shows hypoechoic nodules, rich blood supply in the nodules, irregular margins, microcalcifications in the nodules, absence of halo or nodules with height exceeding the width, etc., which suggest possible malignancy, but the above ultrasound features alone are not ideal for determining benign and malignant nodules. Factors such as whether the nodule is solitary, nodule size, and gender are not significantly correlated with benignity or malignancy [3]. In addition, neck ultrasonography is also important in the preoperative evaluation of cervical lymph nodes in differentiated thyroid cancer to determine whether cervical lymph node metastasis has occurred and to be able to accurately localize it. Lateral cervical lymph nodes ≥ O.8 cm and paratracheal lymph nodes ≥ O.5 cm are diagnosed as metastases if they are round or oval; have abundant pericortical blood flow, poorly defined corticomedullary demarcation and loss of medullary structures; have poorly defined borders, irregular morphology and strong internal echogenicity; have abundant blood supply in the lymph nodes with small sand-like calcifications and have significantly increased peak arterial flow velocity and resistance index [4]. Other imaging includes CT, magnetic resonance imaging, and nuclide scanning.CT is significantly more sensitive than ultrasound at every level in the neck, magnetic resonance imaging shows small cystic changes and hemorrhage in thyroid cancer significantly better than CT, and nuclide imaging is mainly used to determine the nature of the node.Lymph nodes found on CT with central necrosis or cystic changes, greater cortical enhancement than muscle density, or calcification are considered to be Metastatic lymph nodes, size? criteria were used only for region VI, i.e. metastatic lymph nodes with a maximum axial diameter of ≥5?? mm. For detailed analysis of the results of CT scans at all levels, sensitivity is slightly higher than specificity, and the accuracy of the diagnosis of lymph nodes in the lateral zone tends to be higher than in the central zone, with statistically significant specificity [5]. MRI can image in multiple directions, facilitating the detection of lymph node metastases in the neck, and can also perform enhanced scans in hyperthyroidism. Differentiated thyroid cancer has certain ability to absorb iodine, and warm nodules seen on nuclear scan cannot absolutely exclude cancer, while cold nodules can help in the diagnosis of thyroid cancer. Various imaging tests have limited ability to differentiate benign from malignant thyroid nodules and must be combined with clinical aspects. Fine needle aspiration cytology (FNAB-cytology) and fine needle aspiration combined with thyroglobulin (FNAB-Tg) are the most accurate and cost effective methods to evaluate thyroid nodules. FNAB-Tg has a higher accuracy and sensitivity than fine-needle aspiration cytology in the diagnosis of cervical lymph node metastasis in thyroid cancer [6], especially in the diagnosis of cystic metastatic lymph nodes. the threshold value for the diagnosis of FNAB-Tg is 1.1 µg/mL [7], which is of great value in the diagnosis of benign and malignant nodes and in the qualitative diagnosis of the pathological types of malignant nodes . For cystic nodules, follicular or eosinophilic tumors that cannot be diagnosed by FNA results, and follicular lesions whose nature cannot be determined, pathological confirmation is required in conjunction with surgery. Treatment of differentiated thyroid cancer The goals of treatment for differentiated thyroid cancer are to remove the primary tumor, the diseased tissue that has spread beyond the thyroid envelope, and the involved cervical lymph nodes; to minimize treatment- and disease-related disability; to stage the tumor accurately; to treat the tumor with 131I at the appropriate time after surgery; to accurately monitor the disease recurrence in the long term after surgery; and to minimize the risk of tumor recurrence and metastasis. Surgery is recognized as the best option for the treatment of thyroid cancer, but the extent of thyroid excision, whether cervical lymph node dissection is routinely performed, and the extent of lymphatic dissection have been debated. Treatment of the primary site The surgical approach includes lobectomy, total bilateral excision and secondary bilateral excision. Total or subtotal thyroidectomy is the more common treatment in Western countries. Indications for total thyroidectomy (subtotal thyroidectomy): tumor diameter >1 cm; presence of thyroid nodules on the opposite side of the tumor; history of head and neck radiation therapy; family history of thyroid cancer; age >45 years; preoperative or intraoperative diagnosis of malignant lesions. The extent of thyroidectomy can affect the local recurrence rate. Even for tumors of 1 to 2 cm, there is still a 24% risk of recurrence and a 49% risk of death after lobectomy; total thyroidectomy significantly improves the postoperative recurrence rate and survival in patients with tumors >1 cm. For patients who can safely undergo total thyroidectomy, it is important that the first operation is complete to increase the patient’s chance of cure, unless the cancer is small and occult (<1 cm), confined to the perineum and without local and distant lymph node metastases [8]. It has also been shown that the recurrence rate in patients undergoing total thyroidectomy (2.8%) is similar to that in patients treated with subtotal surgery (2.5%) [9]. After partial thyroidectomy, the rate of residual cancer is high, but with the better understanding of the biological characteristics of thyroid cancer and thyroid function and from the results of long-term clinical follow-up, many scholars still advocate glandular lobectomy plus isthmus for patients with no history of neck radiation, no distant metastasis, no extra-thyroidal invasion, and tumor diameter <4 cm. In addition, for patients aged <15 years, subtotal resection is recommended, and total lobectomy should be performed with caution. In conclusion, the choice of procedure needs to be evaluated based on the patient's condition, postoperative complications, prognosis and recurrence rate. Lymph node dissection Differentiated thyroid cancer has a high rate of cervical lymph node metastasis, and the most frequently involved areas are zones II, III , IV , V and VI. Currently, there is a clinical consensus on whether to perform lymph node dissection on one or both sides of the neck in patients with positive cervical lymph nodes; there are different opinions on whether to perform prophylactic cervical lymph node dissection in negative patients and which procedure to choose. The ideal surgical approach is to perform different cervical lymph node dissection according to each patient's specific condition, i.e. the principle of individualized surgery. The guidelines for the management of differentiated thyroid cancer in China (preliminary draft) require: if the lymph nodes are negative, at least central lymph node dissection (Zone VI) should be considered; if there are positive lymph nodes in Zone VI, lateral cervical lymph node dissection (Zones II-IV) should be added; if there are positive lymph nodes in Zones II-IV, Zone V dissection should be added. Central cervical lymphatic dissection is the most common cervical lymphatic dissection in patients with papillary thyroid cancer and plays an important role in the treatment of primary and recurrent papillary thyroid cancer. Central cervical lymphatic dissection can be used as a routine treatment option for patients with a clear clinical diagnosis; prophylactic central cervical lymphatic dissection can be used to clarify the accurate staging of high-risk patients [10]. Routine central lymph node dissection is not mandatory in patients with DTC who have tumors less than 1 cm in diameter, are non-invasive, and in whom ultrasound and imaging exclude the possibility of lymph node metastasis [11]. In cervical lymph node dissection for thyroid cancer, functional cervical lymph node dissection, i.e., preserving the greater auricular nerve, lesser occipital nerve, superior clavicular nerve, external jugular vein, and transverse cervical artery and vein on the basis of preserving the sternocleidomastoid muscle, internal jugular vein, and collateral nerve, is reasonable and feasible for the purpose of eradicating the tumor while effectively preserving the sensation in the auricular region, neck, and superior clavicular region [12]. For DTC, especially for unresectable primary foci, residual foci, recurrent or distant metastases, RAI therapy can be used. 131I removal of residual thyroid tissue after total or subtotal thyroidectomy for DTC is an indispensable part of the treatment plan for DTC, and the more complete the surgical resection of DTC and the less residual thyroid tissue after surgery, the better the effect of the first RAI therapy. Indications for RAI treatment: distant metastasis, peripheral invasion visible to the naked eye, regardless of tumor size; primary tumor > 4 cm; tumors of 1-4 cm with lymph node metastasis, or other high-risk factors (age, tumor size, lymph node status, histologic type) RAI treatment not only significantly reduces the recurrence rate of thyroid cancer, but also allows the serum Tg level to be used as a very sensitive follow-up after RAI treatment. level can be used as a very sensitive follow-up indicator after RAI treatment [14]. In addition scans during RAI ablation of remnants can be used to determine previously undetermined staging and to kill possible residual cancer cells. According to the 7th edition of the AJC??C/Union Internationale Cancer Control Staging System (stages I, II, III or IV) and the American Thyroid Association (ATA) risk of recurrence stratification system (low, intermediate or high risk of recurrence) to properly assess risk, patients with differentiated thyroid cancer with low to intermediate risk of recurrence undergoing lobectomy or total thyroidectomy without radioactive iodine removal of residuals have a 5-year recurrence rate was reduced to very low. For patients with thyroid cancer with significantly elevated serum Tg, additional therapy and RAI treatment may be required [15]. RAI therapy is not recommended for single lesion tumors <1 cm with no high-risk factors, and for multiple lesions but all lesions <1 cm with no high-risk factors. Thyrotropin (TSH) inhibition therapy The cell membrane of TSHR is expressed, and TSH stimulation can increase the expression of Tg and NIS and accelerate tumor growth. By feedback inhibition and reduction of thyrotropin levels, an environment unfavorable to the recurrence or metastasis of residual thyroid cancer cells is established, and the application of greater than physiological doses of LT4 can suppress TSH levels thereby reducing the recurrence rate of DTC. Because of the potential cardiac and bone metabolic side effects of TSH suppression therapy, the dose of eugenol should be determined on a case-by-case basis. In addition, for patients with metastatic cancer requiring high doses of eugenol, routine supplementation with adequate amounts of calcium (1200mg/day) and vitamin D (1000u/day) is recommended. 2. Follow-up Long-term follow-up is required for patients with persistent disease or recurrence, those at high risk of recurrence, patients with total or near-total thyroidectomy (or +RAI treatment), and those with disease-free status (no clinical or imaging evidence of tumor presence, no detectable Tg with TSH suppression or stimulation in the absence of antibody presence). Detection After total thyroidectomy, or after near-total excision + RAI treatment, TSH stimulation is given without the presence of antibodies to Tg, and the detection of Tg is highly sensitive and specific for determining DTC recurrence or residual. If Tg is <0.5ng/L after TSH stimulation, it suggests that the patient has 98-99.5% possibility of being in tumor-free survival. If Tg is >2ng/L, especially >10ng/L or persistently elevated, it is a highly sensitive indicator to suggest the persistence of tumor. Imaging examination After thyroid cancer surgery, if a low or moderate echogenic mass with rich blood flow signal inside the lesion is found locally in the surgical bed or contralaterally by neck ultrasound, it must be noted whether it is a recurrence or reoccurrence of cancer. If necessary, ultrasound-guided aspiration histopathology should be performed to confirm the diagnosis. Ultrasound can clearly and visually show the sonographic manifestations of residual glands and suture scar tissues after thyroid cancer surgery, and can detect lymph node metastasis in the neck and local and contralateral recurrent lesions in the surgical bed at an early stage, which is one of the preferred methods for postoperative follow-up observation of thyroid cancer and timely detection of recurrence and reoccurrence of thyroid cancer and the presence of metastatic lymph nodes, providing reliable clinical diagnosis and determination of treatment plan [16]. It provides a reliable guarantee for accurate clinical diagnosis and treatment plan [16]. In addition, for patients with Tg>10ng/L and negative RAI scan, PET-CT is feasible for the search and localization of recurrent metastatic lesions. 3. Treatment of recurrence and metastasis For those who have residual primary cancer foci due to irregular surgical treatment, or tumor recurrence and cervical lymph node metastasis after radical thyroid cancer surgery, re-surgical treatment is necessary. The surgical method should be analyzed according to the first surgical method, patient’s examination and pathological type. The surgery should pay attention to the anatomical exposure of the recurrent laryngeal nerve to avoid damage and complete removal of the lesion. By choosing the correct and reasonable reoperation modality, it is the key to successful reoperation for thyroid cancer [17]. There is a significant positive correlation between the number of malignant lymph nodes removed by reoperation and the decreasing level of serum Tg. If the sTg level is elevated, there is a high probability of recurrence. Surgery is an effective treatment for locally recurrent or persistent PTC, and serum Tg can be used as a marker to assess the efficacy of reoperation for locally recurrent PTC and to predict second recurrence [18]. Thyroid tissue is rich in blood vessels and lymphatic vessels, and cancer cells can metastasize via bloodstream or lymphatic metastasis. Follicular adenocarcinoma is more prone to distant metastasis than papillary adenocarcinoma, mainly in the lung, bone and liver. Metastatic foci are sensitive to 131I radiotherapy, so radiotherapy is feasible. If there is no significant change, local lesion resection can be considered.