Microscopic thyroid cancer is an old topic in the endocrine system. In recent years, the detection rate of microscopic thyroid cancer has increased significantly due to the rapid update of screening methods and the increased frequency of health checkups, resulting in a certain degree of “cancer-phobic” epidemic; American scholars have even compared the increase of microscopic thyroid cancer to a “tsunami”. The epidemiology, clinical characteristics and treatment of microscopic thyroid cancer are described below. The prevalence of microscopic thyroid cancer refers to malignant tumors of the thyroid gland with a diameter of ≤1.0 cm; since most thyroid cancers are papillary thyroid cancers, microscopic thyroid cancer refers to papillary microscopic cancer. In a meta-analysis published by Lee et al. in 2014, the detection rate of thyroid cancer in autopsies was also mentioned as 11.5%, and most of them were microscopic cancers of 1 to 3 mm. These studies indicate on the one hand that microscopic thyroid cancer is a relatively low malignancy tumor and a typical example of human cancer coexistence; on the other hand, they also reveal the high prevalence of microscopic thyroid cancer. Analysis of the SEER database in recent years has shown a significant increase in the prevalence of thyroid cancer, dominated by an increase in microscopic thyroid cancer, but not in its mortality. Combined with the reports of Harach et al. and Lee et al. we believe that the inherent prevalence of microscopic thyroid cancer in the population is high, but it has not been revealed in the past due to health awareness, screening methods and frequency of screening. Clinical characteristics of microscopic thyroid cancer In 2008, Roti et al. included 17 articles with more than 9300 cases of microscopic thyroid cancer and obtained the following clinical characteristics: (1) the proportion of female patients was 82.9%, which was much higher than that of male patients (17.1%); (2) the proportion of papillary thyroid cancer was 65% to 99%; the proportion of highly malignant pathological types (including high cell subtypes) was 0.8%; (3) 15.0% of patients had lymph node metastases at diagnosis and 0.37% had distant metastases. in 2012, Pacini reviewed six studies of microscopic thyroid cancer and confirmed that more than 20% of microscopic thyroid cancers were multifocal, with an average of 11% presenting with extraglandular invasion and 28% with lymph node metastases at diagnosis. in 2014, Mehanna et al.’s In 2014, a meta-analysis by Mehanna et al. compared the clinical differences between accidentally detected microscopic cancers and non-accidentally detected microscopic cancers, showing that accidentally detected microscopic thyroid cancers were smaller and had a lower risk of lymph node metastasis. In the same year, another review found that more than half of patients with microscopic thyroid cancer had mutations in the BRAF gene, one of the mutations associated with the development and progression of papillary thyroid cancer. However, although some microscopic thyroid cancers exhibit clinical features such as high-risk pathological subtypes (e.g., high-cell type), extraglandular invasion, and lymph node metastasis and distant metastasis, the overall long-term prognosis of microscopic thyroid cancers is good. Hay et al. followed up 900 patients with microscopic thyroid cancer with an average diameter of 7 mm at Mayo Clinic for an average of 17.2 years after thyroid surgery, and showed recurrence rates of 6% and 8% at 20 and 40 years, respectively, with only 3 patients eventually dying of thyroid cancer. In a retrospective study done in Hong Kong, China, 185 patients with microscopic thyroid cancer and 443 patients with non-microscopic cancer between 1964 and 2003 were included, with a mean follow-up time of 8.2 years, and the survival curve suggested that the postoperative survival rate of microscopic thyroid cancer was significantly higher than that of non-microscopic cancer patients. In view of the high incidence of microscopic thyroid cancer and the above clinical features, we should see that a considerable proportion of microscopic thyroid cancer has inert progression and poses almost no threat to survival. Therefore, how to provide “reasonable” treatment for microscopic thyroid cancer has attracted the attention and debates of the academia and the public. Surgery: For a long time, total/near-total thyroidectomy has been the mainstay of thyroid cancer surgery. However, more and more studies suggest that for low-risk thyroid cancers (most microscopic thyroid cancers are classified as low-risk thyroid cancers), a single extended thyroidectomy does not bring significant clinical prognostic benefit. In an analysis by Bilimoria et al. of 52 173 thyroid cancer patients from 1985-1998 in the US National Cancer Database, total thyroidectomy was found to mildly improve recurrence and mortality of thyroid cancer compared with lobectomy, but the study did not exclude certain confounding factors (e.g., extraglandular invasion) that affect prognosis. Subsequently, Adam et al. analyzed 61 775 patients who underwent surgical treatment for thyroid cancer from 1998-2006 in the same database and found no statistically significant difference in the effect of total thyroidectomy versus lobectomy on the prognosis of <4 cm thyroid cancer after correction for clinicopathologic features of thyroid cancer. In addition, several analyses based on information from the SEER database also showed that the extent of thyroid surgery per se had no effect on patient survival after correcting for several prognostic influences such as age, duration of diagnosis, tumor pathological characteristics, gender, and radioiodine treatment. In addition, two single-center studies have confirmed that long-term survival rates for patients with stage T1 and T2 thyroid cancer who undergo lobectomy alone are more than 98% if the indication is chosen appropriately. Based on these data, the 2009 American Thyroid Association (ATA) Guidelines for the Management of Thyroid Nodules and Differentiated Thyroid Cancer (hereinafter referred to as "the Guidelines") recommended lobectomy for patients with low-risk, solitary lesions, confined to the thyroid gland, no previous history of head and neck radiation, and no clinical judgment of lymph node metastasis for differentiated thyroid microcarcinoma. In 2012, a multidisciplinary guideline also pointed out that single differentiated thyroid cancer confined to one lobe, with a primary tumor ≤1 cm, low risk of recurrence, no history of head and neck radiation exposure during childhood, no cervical lymph node metastasis or distant metastasis, and no nodules in the contralateral lobe are indications for thyroid lobectomy + isthmus. In the latest 2015 edition of the ATA guidelines, the indications for thyroid lobectomy have actually been further relaxed to include only thyroid lobectomy for differentiated thyroid cancer of low risk (all of the following: no significant extraglandular invasion, no cervical lymph node involvement or distant metastasis, no family history of thyroid cancer, no history of head and neck radiation therapy, and age ≤45 years), provided that the cancer is <4 cm in diameter. The lobe of the thyroid gland can be resected. Therefore, for microscopic thyroid cancer, careful preoperative evaluation should be performed, and most patients may only require thyroid lobectomy. Postoperative radioactive iodine and thyroid hormone therapy: Whether to perform radioactive iodine to remove residual normal thyroid tissue (nail clearance) after microscopic thyroid cancer depends on the risk of recurrence based on clinical and postoperative pathological findings. In both single and multiple lesions, if the tumor is confined to the thyroid gland without lymph node metastases or distant metastases, radioactive iodine treatment is not required. This view is recommended in the ATA 2009 and 2015 editions of the guidelines and in the 2012 edition of the Chinese guidelines. This recommendation was made based on a series of studies and meta-analyses suggesting that postoperative nail scavenging with radioactive iodine does not further reduce disease-specific recurrence or death in this type of low-risk microscopic thyroid cancer. Postoperative oral thyroid hormone for thyroid stimulating hormone (TSH) suppression is an important component of thyroid cancer treatment. Early targets for TSH suppression therapy were often set at levels consistently below 0.1 mU/L, or even undetectable; in recent years, it has been proposed that the goals of TSH suppression therapy should balance the risk of tumor recurrence with the risk of side effects from levothyroxine therapy. For thyroid cancer with a low risk of death and recurrence, a growing number of studies have shown that excessive TSH suppression does not significantly increase the benefit. In a recent US study, for example, which included 4,941 patients with differentiated thyroid cancer at 11 study centers in the US and Canada, with follow-up ranging from 0 to 25 years (median follow-up 6 years), moderate TSH suppression (0.1 mU/L to the lower limit of normal) was found to provide a significant survival benefit for patients with differentiated thyroid cancer at TNM stage I/II (low risk of death). There is no further benefit from further TSH suppression to <0.1 mU/L. On the other hand, if TSH is oversuppressed in low-risk patients, it may lead to increased side effects such as osteoporosis. Therefore, in the latest version of ATA guidelines, TSH suppression therapy for low-risk thyroid cancer is significantly more relaxed than before: if thyroglobulin (Tg) and thyroglobulin antibody (TgAb) are not measurable in postoperative serum, TSH control at 0.5-2.0 mU/L is sufficient in the primary treatment period (usually 1 year after surgery); if serum Tg is still measurable after surgery, the TSH target in the primary treatment period is 0.1 to 0.5 mU/L, after which the TSH target was changed to 0.5 to 2.0 mU/L if the patient responded well to treatment and showed no signs of recurrence[. This is not significantly different from the recommendation of our 2012 edition guidelines, which do not recommend too low TSH suppression in patients with differentiated thyroid cancer with low risk of recurrence (suppression targets: lower limit of normal range within 1 year after surgery; <2.0 mU/L after 1 year to 10 years; within normal range after 10 years). In view of the fact that most microscopic thyroid cancers belong to the low-risk grade, it is important to consider appropriately relaxing the target of TSH suppression therapy for this group of patients when performing postoperative thyroid hormone therapy. In recent years, Japanese scholars have conducted several non-surgical follow-up studies on microscopic thyroid cancer. They have not operated on selected patients with microscopic thyroid cancer [no regional lymph nodes or distant metastases; no involvement of the recurrent laryngeal nerve or trachea; fine needle aspiration cytology (FNAB) of the thyroid showed a non-malignant subtype; tumor was far from the recurrent laryngeal nerve or trachea or trachea] were not treated with immediate surgery, and instead of close follow-up, valuable information on the natural course of microscopic cancer was obtained. The results showed that only 5% to 10% of patients had an enlarged primary focus and 2% to 4% had clinical lymph node metastases during the 5-10 year observation period. Importantly, patients who had surgery when the primary foci appeared and lymph nodes progressed during the observation period still had a good clinical prognosis, suggesting that this "delayed treatment" is not clinically harmful; elderly, low-risk microscopic cancer patients are most suitable for the observation strategy. However, in the context of China's current situation, this non-surgical observation strategy for microscopic cancer needs to be promoted cautiously because: first, there is no clear basis to distinguish those who benefit more from follow-up and observation than from surgery; second, it is difficult to predict the acceptance level of both doctors and patients regarding the possible deterioration of the disease during the observation process, which affects physicians' decision making and patients' informed consent to a certain extent. However, there is no doubt that non-surgical follow-up of microscopic thyroid cancer deserves further exploration and is promising to become the preferred management of some "inert" microscopic thyroid cancers. In conclusion, microscopic thyroid cancer is a common endocrine malignancy. A significant proportion of microscopic thyroid cancers have inert progression and pose little threat to survival. Therefore, its treatment and management should be rationalized and individualized. A large number of well-designed and rigorously executed clinical studies are needed in the future. It is expected that molecular markers of tumors and other indicators can provide valuable information for the rational treatment of microscopic thyroid cancer. There is a lack of information on prospective studies of microscopic thyroid cancer in China, and most of the current views are based on foreign studies, and this status quo needs to be changed urgently.