Recently, the incidence of thyroid cancer, especially differentiated nail cancer, is increasing year by year and is getting younger. It is gratifying that differentiated nail cancer is an inert tumor with excellent prognosis, but there are differences and controversies in the treatment of thyroid cancer in different hospitals, or medical disputes related to it are increasing due to high surgical risks and lack of skillful surgical techniques. With the development of pathology and molecular immunology techniques, certain papillary carcinoma subtypes (high cell type, columnar cell type and diffuse sclerosing type), follicular carcinoma subtypes (Schottel cell carcinoma) and other low-differentiated thyroid carcinomas (trabecular structure, island and solid carcinoma) are highly invasive and have poor prognosis. Therefore, standardized treatment of thyroid cancer is based on comprehensive evaluation of patient’s age, gender, history of neck radiation exposure, tumor histological type, tumor size, degree of local invasion and presence of distant metastasis.
1.Differentiated thyroid cancer Differentiated thyroid cancer (DTC) includes papillary carcinoma and follicular carcinoma, with the incidence rate of 85% and 10% respectively. Surgery is still one of the important treatment methods for differentiated thyroid cancer, which includes two parts.
resection of the primary tumor and clearance of regional lymph nodes. The risk of postoperative recurrence is stratified to help guide treatment and prognosis. The current internationally adopted methods (CAEORTC, AGES, AMES, MACIS and OSU, etc.) classify the risk of postoperative recurrence into three levels based on age, tumor size, presence of distant metastases, degree of local invasion and completeness of surgical resection.
(1) Low risk group
①No local and distant metastasis.
② All tumors under the naked eye were removed.
(3) No tumor invasion of local structures.
④No invasive histological features of the tumor.
⑤ No 131I uptake foci outside the thyroid bed.
(2) Intermediate risk group
(1) Microscopic tumor invasion to soft tissues outside the envelope.
(2) Lymph node metastasis in the neck.
(3) 131I uptake foci outside the thyroid bed.
(3) High-risk group
①Tumor invasion to the outer envelope by the naked eye.
(ii) residual tumor.
③Distant metastasis. There are differences in the indications for thyroidectomy and lymph node dissection, but the most commonly accepted ranges of thyroidectomy are total thyroidectomy (no thyroid tissue remains under the naked eye), subtotal excision (only less than 1g of tissue at the laryngeal entry point of the recurrent laryngeal nerve), and total excision of the affected lobe and isthmus. Total or near-total resection is preferable for those with the following conditions.
① the maximum diameter of the tumor is greater than 1M.
② multiple cancer foci or contralateral nodules.
(iii) local or distant metastasis.
④History of radiation exposure to the head and neck.
⑤ First-degree relatives with a history of nail cancer.
⑥45 years old. If the tumor diameter is less than 1M, single lesion, low risk and confined to one lobe of the gland, total excision of the lobe and isthmus can be chosen. Most scholars believe that subtotal excision (preserved tissue >1g) is inappropriate for nail cancer. If the preoperative physical examination, imaging and cytological examination (FNA) suspect malignancy, frozen section should be performed intraoperatively, but sometimes there are inconsistencies between frozen section and paraffin section results, which is extremely difficult to handle. If the postoperative paraffin section is reported as malignant tumor, total or near-total excision of the contralateral gland can be performed in the second stage. Lymph node metastases are present in 20-90% of papillary carcinomas at the time of diagnosis, but are mostly limited to lymph nodes in regions II-VII.
Some prospective analyses have shown that regional lymph node metastasis in differentiated nail cancer does not affect survival, but regional lymph node status can be used as an indicator of prognosis. Therefore, neck clearance is also an important part of radical thyroid cancer treatment to improve local control, reduce recurrence and mortality. Neck clearing is divided into prophylactic and curative according to its therapeutic purpose. Most experts and scholars recommend intraoperative simultaneous bilateral or unilateral central group (region VI) neck clearing, although this increases the chance of parathyroid gland and laryngeal recurrent nerve injury. If imaging suggests cervical lymph node enlargement, cN1 or central group lymph node metastasis (determined by FNA or intraoperative frozen section), unilateral or bilateral lymph node dissection of the lateral cervical region (regions II-V) can be performed, preserving as many important structures as possible and performing functional or regional cervical clearance. The thyroidectomy and lymph node dissection must be performed in such a way that the laryngeal nerve is exposed throughout and the parathyroid glands and their blood supply are preserved. In vitro trials have demonstrated that stimulation of TSH receptors can lead to DTC progression and that postoperative TSH suppression can reduce recurrence and mortality. Most experts recommend lifelong TSH suppression of 0.1 mU/L (complete TSH suppression) for intermediate and high risk groups and 0.1-0.5 mU/L (partial TSH suppression) for 5-10 years for low risk groups. Long-term users should be aware of ischemic heart disease, atrial fibrillation and osteoporosis due to subclinical hyperthyroidism. 131I clearance of residual cancerous and normal thyroid tissue after total thyroidectomy may reduce local recurrence and mortality and improve the chance of early detection of recurrent cancer foci on TG or 131I whole-body scans. 131I treatment is recommended for anyone who has one of the following conditions.
①Distant metastasis is present.
② extra-peripheral invasion under the naked eye.
③Tumor diameter of 4cm.
④1cm in diameter with lymph node metastasis in the neck or other high-risk factors. 131I therapy is not recommended for single or multiple cancer foci of 1 cm in diameter without risk factors. 131I therapy must be preceded by discontinuation of thyroxine preparations (eugenol) for 2-3 weeks and restriction of iodine intake (50 μg/d), with best results at TSH 30 mU/L. The efficacy of 131I can be improved with genetically recombinant TSH for those who cannot tolerate hypothyroidism. External irradiation can be considered for recurrent or incomplete resection of the cancer, and may be effective in some cases. Postoperative follow up should be done every 6-12 months with TG, anti-TG antibody, neck ultrasound or CT, 131I whole body scan for early detection of lesions.
2.Medullary carcinoma
Medullary carcinoma (MTC) is a moderate malignant tumor originated from C cells, mostly accompanied by lymph node metastasis in the neck. The incidence rate is 3%-10%. FNA has an accuracy rate of 82% for MTC, and FNA, Ct and CEA should be performed routinely for clinical suspicion of MTC. If there is no evidence of lymph node and distant metastasis in the neck, total thyroidectomy with prophylactic central neck clearance is recommended. If the tumor is 1 cm in diameter, with limited lesions and no distant metastases, total thyroidectomy with prophylactic central neck clearance is recommended, with one or both necks cleared (IIA, III, IV, V) depending on the situation. For those with distant metastases, a less invasive palliative surgery is recommended to preserve pronunciation, swallowing and parathyroid function as much as possible to improve the quality of life. Since MTC lacks TSH receptors, TSH suppressive therapy is not required and only eugenol replacement therapy is given. 131I therapy is ineffective in MTC without iodine uptake. External irradiation can be tried for those whose local invasion cannot be completely removed, but the efficacy is not sure. post-MTC follow-up should be reviewed every 3-6 months for Ct, CEA and neck ultrasound to detect recurrence at an early stage.
3.Undifferentiated carcinoma
Undifferentiated carcinoma (ATC) is a tumor with extremely high malignancy. All ATCs are stage IV (2002 AJCC 6th edition), and the average survival time is 4-12 months. Tumor invasion of trachea and recurrent laryngeal nerve leading to asphyxia or extensive distant metastasis is the main cause of death. FNA has an accuracy rate of 90% in diagnosing ATC, but the diagnosis can only be confirmed after routine postoperative examination, which is easily confused with lymphoma and poorly differentiated myeloid carcinoma. Typical ATC has symptoms such as rapid mass growth with pain, mass fixation, and compression, etc. The age of onset is older, and 75% of patients have distant metastases after diagnosis, mostly involving lung, bone and brain, and 50% are transformed from DTC, mostly with P53 mutation. Although the extent of surgical resection and whether complete resection is not beneficial to improve their prognosis, total thyroidectomy and neck clearance for T stage, postoperative external irradiation (hyper-segmentation irradiation method), chemotherapy, and targeted therapy can still prolong the survival time of some patients, and intraoperative or postoperative prophylactic tracheostomy can be used to avoid resection of important structures and palliative surgery to improve the quality of life. Current cytotoxic drugs effective for ATC include anthracyclines, platinum and paclitaxel, which can be tried in combination with chemotherapy (ADM+DDP regimen) or as single agents. CA4P targeting the tumor vasculature has shown good efficacy with minimal toxic side effects.