This web site is conducted by Kennichi Kakudo, MD, PhD, professor emeritus of Wakayama Medical University and visiting professor of Kindai University, Faculty of Medicine, Japan. I am also a visiting professor of Shandon University and Taishan Medical University, China. It is designed for a personal communication with you to discuss one of the followings; 1) (to pathologists) about pathology and its future directions and case consultation, 2) (to patients) about your diagnosis and advises for your decision making, as a second opinion consultation and 3) (to physicians in the other fields), as consultation and quality control for your patients’pathology reports.
Although the most parts of this home page are written in Japanese, you may enjoy my English pages and my scientific publications written in English. Please send your comments and discussion to me at E-mail:

Second Opinion Consultation on Thyroid Diseases from Patients.
It is a well-known fact that there are severe observer disagreements in benign and malignant diagnosis of thyroid tumors (Hirokawa M, et al.: Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol, 26:1508-1514, 2002 & Lloyd RV, et al.: Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma. Am J Surg Pathol, 28(10):1336-1340, 2004). Although an accurate diagnosis is essential to ensure the most effective treatments, over-diagnoses and over-treatments are serious problems in some areas including thyroid tumors (Esserman LJ et al: Addressing overdiagnosis and overtreatment in cancer: a prescription for change. Lancet Oncol, 15:234-242, 2014.). Second opinion consultation will solve some of the problems and lead you to most proper treatments with confidence.

How to get a second opinion from Dr Kakudo.
Ask your doctor to obtain a second opinion from Dr Kakudo showing this HP ( ), and then your physician or hospital send me your histological slides and a case summary to the following address. As no official request form prepared in this HP, please includes followings in your request letter; 1) contact address, E-mail address and names where my second opinion diagnosis should be sent, 2) patient name, date of birth, and PDFs (copies) of pathology reports (first opinion) together with histological slides, 3) a case summary including clinical diagnosis and medical history of the patient, 4) questions and points where you (patient) most concern and 5) address the histological samples should be returned.
(Gross photos of resected specimens and image files such as ultrasound, CT or MRI are desirable but not must.)
Address where samples and request should be sent.
K. Kakudo, MD, PhD
Nishitomigaoka 3-11-2,
Nara-city, Nara, 631-0006 Japan.
Consultation Fee: $200.00(Two hundred US dollars).
Please transfer above sum to
The Bank of Tokyo-Mitsubishi UFJ, Ltd, Japan (bank code: 0005).
Account holder: Kakudo Kenichi
Account number: 5054926 and branch number: 458 (Kintetsu-Gakuenmae branch).
After confirmation of receipt, the samples will be returned to the address you indicated.

Risk stratification of thyroid nodules with fine-needle aspiration cytology presented at the 2020 KTA Virtual Annual Meeting in Daegu, Korea.

Thyroid nodules: Are they malignant or indolent tumors?” presented in The 1stInternational Symposium on Overdiagnosis of Juvenile Thyroid Cancer held in Nara Japan.

Thyroid cancer in young people often shows metastasis and recurrence. However, the prognosis is excellent, which puzzled researchers for a long time. A part of this mystery has been understood from the recent accumulation of clinical evidence. Papillary thyroid microcarcinomas (PTMs) are found frequently in adults after their thirties. They hardly grow after middle age, and a considerable number of them decrease in size. In addition, during the observation trails, no patient died from thyroid cancer, and no patient experienced anaplastic transformation. The results of large-scale screening for thyroid cancer in young people in Fukushima Prefecture show that the frequency of thyroid cancer, which can be found only by ultrasound, increases rapidly after teens, and that the growth of these cancers slows down as they grow. Therefore, its growth is speculated to stop in the future. >From this evidences, the natural history of thyroid cancer may be as follows. Most thyroid cancers occur in childhood and rapidly grow in their 10s to 20s, causing metastasis and invasion. A small proportion of these grow to a size that requires treatment in early life, but the rest cease to grow, remaining as a PTM throughout the lifetime. Thyroid cancer, which leads to cancer death in middle-aged and older people, is fundamentally different from thyroid cancer in the young or PTM. We distinguish this type of cancer that occurs in young people from conventional thyroid cancer and call it juvenile thyroid cancer. It is also designated as self-limiting cancer (SLC). SLC metastasizes and invades like thyroid cancer that is seen in the middle-aged and older patients. However, due to its limited growth ability, it rarely kills patients. Early diagnosis of SLC is prone to cause the harm of overdiagnosis, while it does not improve prognosis or quality of life. Besides, in young patients, because a small cancer is likely to be at its rapidly proliferating and spreading phase, a small surgery for small cancer can result in an increase in the recurrence rate. It has been said that early diagnosis and early treatment are the golden standards for cancer. However, SLC’s existence, the details of which have been clarified for the first time in thyroid cancer, overturned this common sense. We should be fully aware of the fact that in some cancers, early diagnosis can harm patients.

International Thyroid Cancer Symposium was held at the IRCAD in Taiwan on October 4, 2015.

Please find the following link for my presentation, and my title is “Classification of the thyroid follicular cell tumors – identification of borderline lesions-”.
Things usually move very slowly but sometimes the change may occur dramatically. Pathology is a very old science and usually stable and immutable, however we are facing to an epoch making drastic change in diagnosis of thyroid tumors. This is my history of diagnostic criteria for encapsulated follicular variant papillary carcinoma. The pathology diagnosis is no longer a gold standard for cancer diagnosis in thyroid tumors. You will find it in my lecture.

The 55th Annual Meeting of the Japan Thyroid Association

Centennial of Hashimoto Disease International Symposium I ”Future Perspective of Thyroid Autoimmunity”

2012.12.1 ACROS Fukuoka B2F Event Hall

[Session 5]

Yuji Nagayama (Nagasaki University Graduate School of Biomedical Sciences, Japan)
Wilmar M.Wiersinga (University of Amsterdam, The Netherlands)

3)IgG4 Thyroiditis and Fibrotic Variant of Hashimoto’s Disease
Kenich Kakudo, Yaqion Li
(Department of Medical Technology, Kobe Tokiwa University, Japan
Department of Human Pathology, Wakayama Medical University, Japan)


Recent Posts

Focused Issue published in the Gland Surgery


The Gland Surgery published a focused issue, “Asian and Western practice in thyroid pathology: similarities and differences.”  It is open access and available at a link: Your comments are welcome.

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Lecture by Professor Grace Yang


My old friend Professor Grace Yang,  Weill Cornell Medicine, Papanicolaou Cytology Laboratory, sent me the link ( ) of her retirement memorial lecture. I believe it is useful for your cytology practice and contains the rich experience of her thyroid practice. She is famous in this field and published a famous textbook, “Thyroid Fine Needle Aspiration.”    

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A doctor becomes a patient, thyroid cancer.


Dr Kitayama and I wrote an essay for patients to understand thyroid cancer.

I hope it helps patients to understand it before surgery.

A doctor becomes a patient, thyroid cancer

Available at a link:

Naomi Kitayama Graduate Student, Department of Dermatology, Kyoto University Graduate School of Medicine Kennichi Kakudo Izumi City General Hospital, Department of Pathology and Thyroid Disease Center

Dermatologist Kitayama herself noticed a lump in her thyroid gland, underwent a medical examination, and was diagnosed with thyroid cancer. She was notified of cancer by an endocrinologist and referred to a hospital for a surgical treatment. She asked a surgeon for a second opinion in order to examine and decide the treatment modality and surgery. In the process, a doctor who was not an expert in thyroid cancer worked hard to understand thyroid cancer and select better treatments. This process is described here and we hope it will be useful for those receiving treatment as a patient. The peculiarities of thyroid cancer, such as its differences and characteristics from other cancers, are also discussed. For the sake of brevity/clarity, the author focused on Stage I papillary thyroid cancer found in a 32-year-old Japanese woman. See Table 1 for cancer types in the human thyroid gland (References 1 and 2). Papillary thyroid cancer is the most common thyroid cancer, accounting for 80-90% of all thyroid malignancies and has the best prognosis of all human cancers. For cancer staging, refer to References 3 and 4. In brief, if the patient is 55 years of age or younger, all cases with no distant metastases are classified as Stage I regardless of lymph node metastases or extrathyroid extensions. As a result, over 85% of papillary cancers are Stage I cancers; therefore, the topics discussed apply to most thyroid cancer patients.

Diagnosis of thyroid cancer

One day in 2019 >> Kitayama I consulted about my illness. Yesterday, I noticed a lump in my thyroid and visited the clinic of a thyroid specialist. Ultrasonography revealed two large nodules with microcalcification in the left and right thyroid lobes, and swollen lymph nodes in the neck. Fine-needle aspiration (FNA) cytology was performed on the two suspicious nodules. Although I have yet to receive the results, the probability of thyroid cancer is high. (Note 1) My endocrinologist advised me that the larger nodule on the left lobe was approximately 3 cm and total thyroidectomy may be necessary. (Note 2) [See Table 2 for the flow of thyroid cancer diagnosis and treatment.] >> Kakudo That is a little worrisome. The increased incidence of thyroid cancer is a hot topic worldwide. (References 5 and 6) At present, over-diagnosis/over-treatment of low-risk thyroid cancer has become a hot topic, and non-surgical follow-up of papillary cancers of 1 cm or less was added to global guidelines (References 7-10). It was also recommended to stop the screening of asymptomatic adults for thyroid cancer (Reference 11). That means “Many thyroid cancers do not need require surgery.” As it is such a low-grade cancer, do not be afraid. On average, over 70% of patients with small papillary cancers (papillary cancers smaller than 1 cm are called papillary microcarcinomas) do not need surgical treatment. According to a national survey by Sugitani et al., less than half of patients with low-risk papillary microcancer chose surgery immediately. More than 50% of patients chose follow-up in Japan (Reference 12). To date, non-surgical follow-up has been selected by more than 2000 patients with microcarcinomas, and no patients died due to thyroid cancer even after treatment by conversion surgery. There are many cases in which the size increases at a young age, as in your case, and immediate surgery is an option even if it is less than 1 cm (Reference 9). In cases with lymph node metastasis/extrathyroid invasion, surgical treatment is recommended. If there is invasion into the muscle or other surrounding tissues by the tumor, removal of these involved organs is recommended for curative intent. If the 3-cm left lobe tumor is papillary cancer and lymph node metastasis is confirmed, surgical treatment will be unavoidable, but the extent of surgery is controversial. Please consult with your surgeon about the best and standard procedure. Clinical guidelines, including the selection of surgical procedures, are published by the American Thyroid Association, the Japanese Thyroid Association, and the Japanese Society of Thyroid Surgery (References 10, 13, and 14). (Note 3) >> Kitayama Contrast-enhanced CT examination revealed a nodule with a rich blood flow of 25 mm on the left and 12 mm on the right. There was a 1-cm lymph node suspected of metastasis near the right common carotid bifurcation. No distant metastases were found. When I contacted the XX hospital, the schedule was full. They said that the operation would be three to four months later. What would happen while waiting for surgery for three months? I was worried about significant cancer progression during the waiting time because my endocrinologist recommended undergoing surgical removal as soon as possible. >> Kakudo Thyroid cancer is a malignant tumor, but treatments should not be rushed until you have sufficient knowledge of the best treatments. Doing things quickly leads to poor results. Please understand how harmless papillary thyroid cancer in patients younger than 55 years is. Cancer is Stage I until distant metastasis appears and Stage II even if there is distant metastasis (Reference 3). As we have not confirmed cancer yet, it will be checked (Table 2) by imaging diagnosis and FNA cytology. If necessary, both the large nodule in the left lobe and the smaller nodule and swollen lymph nodes on the right side will be evaluated. From CT, there is a slight chance they are benign adenomatous nodules with calcification. The left and right nodules are encapsulated or well-demarcated. Even if they are papillary cancer by FNA cytology, they are of low-grade cancer and cannot be high-risk. >> Kitayama It seems rare having two types of tumors in the thyroid, one papillary cancer and another benign or borderline malignant. Is this a common observation? I am concerned about primary cancer in one lobe and metastatic lesion in the other lobe. >> Kakudo According to Shimura, thyroid echo analysis for cancer screening revealed that 20-30% of the general adult population has thyroid nodules, but only 0.79% were thyroid cancer (Reference 15). As there are 30-times as many benign nodules, I think it is a relatively common finding. There are many benign nodules coexisting in patients with thyroid cancer (being in 20-30%).

Surgery and postoperative pathological diagnosis

FNA cytology revealed that both nodules were papillary cancer. Following the second opinion consultation, both thyroid surgeons recommended total thyroidectomy and right cervical lymph node dissection as standard procedures. Total thyroidectomy and right side cervical lymph node dissection were performed by an experienced thyroid surgeon at XX hospital, a high-volume thyroid hospital. The histopathological diagnosis of the surgical specimen was multiple papillary carcinomas, common (classic) type, with lymph node metastases and Stage I (pT2(m), ex0, pN1b[9/15], M0). The risk classification by the Japanese Society of Thyroid Surgery was an intermediate risk (Reference 16). The Ki-67 labeling index (growth fraction) was less than 2% and prognostic classification by Kakudo (Table 4) (Reference 17) was low-risk.

Is it fatal cancer?

Thyroid cancer is abnormal in that has a low growth rate different from other cancers. It grows slowly like a uterine fibroid. However, benign uterine fibroids differ from thyroid cancer in that they do not metastasize. If you look at the definition of cancer in a textbook, it is defined as a lesion that meets the following two requirements. 1) Invasion and metastatic potential to nearby tissues. 2) Abnormal cell proliferation without control. Thyroid cancers that meet these two requirements are high-grade cancers, such as anaplastic cancers and poorly differentiated cancers, C-cell (medullary) cancers, and a small portion of papillary cancers (aggressive variants) and follicular cancers (angio-invasive and widely invasive) (Table 1). Many thyroid cancers lack the second requirement (abnormal cell proliferation without control), being common (classic) types of papillary cancer and capsular invasion-only follicular cancers. Cancers can be classified into two groups based on the growth speed according to Welch, one in which the patient dies of thyroid cancer if left untreated (red and green arrows) and the other in which the patient does not die of cancer even if left untreated (blue arrow) (Fig.1) (Reference 5). Among the papillary cancers, most of the classic type is slow-growing tumors (Welch named it very slow growing cancer), indicated by the blue arrow (Fig.1). It grows slowly and remains small and not large enough to kill the patient. Welch included a fourth type of cancer that disappears spontaneously (spontaneous regression) in his original illustration, which was excluded from Fig.1 to make it an original illustration. In this fourth group, patients die of other diseases (death from other illnesses) without symptoms of thyroid tumors. Thyroid cancer that is incidentally found by pathological examination at autopsy (latent cancer) belongs to this group. Many symptomatic cancers and cancers with lymph node metastases have a Ki-67 labeling index of less than 5%. They can be of this type (very slow growing shown by the blue arrow in Fig.1). Thyroid cancer is not always the cause of death of the patient in such cases. Du et al. analyzed the Surveillance, Epidemiology and End Results (SEER) thyroid cancer database, and reported that if a patient with papillary cancer survives for more than 10 years (cases confirmed to be slow growing cancer), 90% of all deaths are not due to thyroid cancer such as second cancer in other organs and cardiovascular disease (Reference 18). Please refer to the prognostic data from Kuma Hospital by Ito et al. (Reference 4). The disease-specific survival rate of patients with Stage I papillary cancer at 20 years after surgery was 99.3%. The 0.7% risk of death from thyroid cancer is significantly lower than the 2-3% total risk of death in people in their 30s by the time they are in their 50s after 20 years. Thyroid cancer is a mysterious cancer in which patients with thyroid cancer live longer (there is no significant difference, but the relative survival rate exceeds 100%) than the general population without thyroid cancer. Patients are long-lived and live for more than 20 years as thyroid cancer survivors, and for more than 40 years if treated at young age. How to avoid treatment-related complications is one of the important issues. Severe treatment-related complications shown in Table 3 (Reference 19). Treatments with the least to most related complications are as follows: 1) no surgery (follow-up), 2) unilateral surgery (lobectomy), 3) total thyroidectomy, and 4) total thyroidectomy + lymph node dissection. Therefore, we should not select total thyroidectomy with lymph node dissection due to concerns of recurrence or just in case. We should consider how to reduced treatment-related complications and select more conservative surgery as much as possible. >> Kitayama Is my thyroid cancer a slow growing cancer (abbreviated as a rabbit) or a very slow-growing type (abbreviated as a turtle) in Fig.1? How do you judge? >> Kakudo Very slow growth cancer by Welch (Reference 5) and IDLE by Essermann (Reference 6) are not disease names that correspond to histopathological criteria. These are concepts of cancers that do not progress and do not kill the patient, and do not require treatment. Finding and treating these by cancer screening harms society as a whole (psychologically intimidating the patient, harming the patient in the name of treatment, profits to doctors and hospitals, and negative economic impacts on the health care system and society). Epidemiologists are ringing a warning bell to the stop over-diagnosis and over-treatment of these tumors (5, 6, 11, 20-22). On the other hand, the histopathological risk classification using the Ki-67 proliferation index (Table 4) is carried out by immunohistochemical examination of surgical specimens. Thus, it is possible only for patients who underwent surgery. Thyroid borderline tumors with a Ki-67 labeling index less than 3% demonstrated almost no recurrence or metastasis. Low-risk cancer with a Ki-67 labeling index less than 5% can be cured if removed, moderate-risk cancer defined as a Ki-67 labeling index between 5 and 10% relapses in approximately 20% after surgery, and high-risk cancer with a Ki-67 labeling index between 10 and 30% has a high rate of recurrence and metastasis. High-risk thyroid cancer has a 5-year cause-specific survival rate of approximately 50%. I proposed this prognostic classification of thyroid tumors for designing post-surgical follow-up and further treatment. Many parts of borderline tumors and low-risk carcinoma in this classification overlap with Esserman’s IDLE and Welch’s very slow growing cancer, who advocated not to operate. The Ki-67 labeling index is evaluable only after surgery. Therefore, the borderline tumors and low-risk carcinoma in my classification are not exactly the same as IDLE and very slow growing cancer. Several methods assess tumor growth potential, which is useful in determining the surgical indication for thyroid cancer, determining the completeness of surgery, and predicting recurrent cases at different time points, 1) before surgery, 2) immediately after surgery, and 3) after relapse/metastasis (References 17, 23). How to measure/evaluate proliferative ability and how to predict/determine prognosis based on proliferative ability is shown in Table 5.

What can be elucidated from the pathology report?

>> Kakudo Let me explain the clinical flow of Kitayama’s case using Table 2 and Table 5. In the initial step of Kitayama’s case, there was a maximum probability of high-grade thyroid cancer of 3% (malignant lymphoma, C cell cancer, etc. in Table 1). FNA cytology confirmed that her thyroid nodules were papillary carcinomas and excluded high-grade cancers. There is a maximum risk of 5% of aggressive variants of papillary cancer, shown in Table 1, and moderate risk cancer, shown in Table 4. By histopathological examination of surgical specimens, these aggressive variants and moderate risk cancers were excluded, and it was confirmed it to be low-risk common (classic) papillary cancer. Therapeutic removal of the thyroid tumor and lymph nodes to confirm that the tumor is a low-risk tumor is also beneficial for the patient’s psychological state. Completeness of surgery can be examined using the surgical specimen (cut margins were negative for tumor, and no invasion over the thyroid capsule and lymph node capsule), and serum thyroglobulin (TG) measurements (TG value is low after total thyroidectomy) (Note 5). These results confirmed that this thyroid tumor was highly unlikely to recur and cause cancer death. I believe these observations created a great deal of leeway in the patient’s future life planning. For confirmation, I recommended that Dr. Kitayama undergo surgery instead of further follow-up. >> Kitayama Well, I remembered what I felt before surgery. It would be much better to be able to judge whether my thyroid tumor is a rabbit in need of treatment or a very slowly growing turtle by ultrasound or cytology. It would be great if the tumor is a turtle and surgery is not necessary. It was unfortunate that I was unable to confirm this without surgery because a postoperative specimen is necessary for definitive pathology diagnosis. At the moment, it is impossible. My thyroid cancer is probably a turtle, but I cannot eliminate the small possibility of moderate-risk cancer rabbits without surgery. I would choose surgery for a definitive diagnosis, whether it is a turtle or rabbit, using postoperative specimens. I agree with you that this step is useful, as removing the tumor is therapeutic and a low-risk tumor can be confirmed. It is essential to tell the patient that the prognosis is excellent after a definitive postoperative diagnosis. This information is a great help for the patient to have peace of mind for the rest of their life. Even after surgery, I would be delighted to know it was a turtle. I did not know much about what can be elucidated from the pathology report. After knowing the meanings, I am completely relieved. >> Kakudo I am pleased to hear that you understood my theory that the Ki-67 labeling index can predict the patients’ future. As Dr. Kitayama will have a healthy life expectancy, please think about your future life planning seriously. Of course, you can attend your children’s ceremonies and the faces of your grandchildren.

Peace of mind for the patient

>> Kitayama Come to think of it, dermatologists have a similar disease. Basal cell carcinoma is a tumor that does not metastasize/relapse and is cured after removal. However, even if the clinical diagnosis is basal cell carcinoma, it is necessary to confirm the excised specimen for definitive diagnosis. In the dermatology clinic, complete excision is performed for the time being. The diagnosis of basal cell carcinoma is confirmed by looking at the pathology specimen. After that, the dermatologist usually says, “It was okay; I was able to confirm that it was basal cell carcinoma. I removed all of it, so it has been cured.” This explanation is prepared in order for the patient to feel secure. The tumor names for skin cancer clearly distinguishes cancer with a risk of recurrence and metastasis from that cured by removal. If thyroid cancer made this distinction clear, patients may feel more peace of mind. >> Kakudo I think it is “problematic” to name both tumors as papillary cancers without distinguishing between cases with possible recurrence/cancer death and those with no recurrence/cancer death. More than 80% of papillary cancers do not recur and more than 99% of Stage I papillary cancer do not kill the patient. By naming them as cancer, many patients develop a “fear of recurrence/cancer death,” as Dr. Kitayama experienced. These patients often accept unnecessary over-surgery and radioiodine treatments because of the terminology. These overtreatments increase the rate of significant treatment-related complications and life-long thyroid hormone replacement therapy. In 2015, the NIFTP international conference was held in Boston, USA, and Ms. Kathryn B Wall (Thyroid Cancer Survivor Association Inc.) participated as a representative of the patient association and expressed her opinion. “If the non-invasive encapsulated papillary thyroid cancer follicular variant is a tumor that does not recur and the patient does not die, I strongly hope that the word cancer should not be included in the diagnosis.” The diagnostic name NIFTP was born. I thought we needed to hear more from the patient. I am working on renaming this low-risk tumor from cancer to borderline tumor (Reference 24-27). However, from surgeons and pathologists, there is strong opposition such as “Strangely, the patient does not have cancer and does not die,” “It is cancer because many have metastases,” “It is dangerous if the patient understands it is not cancer and does not come to the hospital,” “Patients are in trouble if they cannot use cancer insurance,” “It is also safer for the patient and doctor. Who should take responsibility if there is recurrence and the patient complains,” or “Shouldn’t it be cancer because cancer is better for hospital profit?” I downgraded very low-risk thyroid cancers (papillary microcarcinoma, encapsulated papillary carcinoma, and capsular invasion only follicular carcinoma) to a borderline tumor category independent of papillary thyroid cancer. However, there was resistance among clinicians/pathologists about referring to non-cancer/no operation as benign. Then, I proposed the risk stratification of thyroid carcinomas into low-risk, moderate-risk, and high-risk cancers using the Ki-67 labeling index. However, it did not distinguish between cancers causing death and those that did not recur or cause death. The distinction by name in dermatology between basal cell carcinoma with no recurrence and squamous cell carcinoma with possible recurrence is a good solution. It may be more comfortable for patients to use a completely different name, as in the dermatology field.


Note 1: The ultrasonographic diagnosis was papillary thyroid cancer. Irregular shapes, unclear boundaries, coarseness, heterogeneity, microcalcifications, etc., are suspected to be malignant on ultrasonography. Note 2: Operating on lesions less than 1 cm is optional, but if they are greater than 1 cm, surgical treatment is indicated, and if there is lymph node metastasis/extrathyroid extension, surgery is usually recommended. Note 3: If possible lobectomy is desired, there is a large difference in the patient burden (Table 3) between total thyroidectomy and lobectomy on one side (surgery to leave the other side). Most papillary cancer patients in Japan are treated by lobectomy. As this patient had lesions on both sides, it was decided that both should be excised. Note 4: Thyroid cancer has a favorable prognosis. According to a report by Ito et al. (Reference 4), the tumor-specific 10-year survival rate of Stage I papillary cancer was 99.8% and the 20-year survival rate was 99.3%. The prognosis of control subjects without thyroid cancer was similar. Although papillary thyroid cancer is called cancer, it has a different prognosis from other gastric cancers, colon cancer, lung cancer, etc. For example, Stage I lung cancer has a 5-year survival rate of 80% or less and 20% or more of patients die of lung cancer within 5 years, whereas thyroid cancer causes 0.7% of patients to die within 20 years. There is a greater than 2% chance of dying in 20 years at any age, and with Stage I thyroid cancer, most patients die of diseases other than thyroid cancer. Note 5: Normal thyroid follicular epithelium and well-differentiated cancers (papillary cancer and follicular cancer) produce thyroglobulin and secrete it into the blood. Thus, serum thyroglobulin is used as a tumor marker for thyroid cancer recurrence after total thyroidectomy. Thyroglobulin is usually low (< 2 ng/ml) in patients who underwent complete total thyroidectomy because they do not have thyroid tissue. However, it increases when there is metastasis/recurrence or thyroid tissue remains. The change in this value is considered to correlate with the amount of tumor tissue and tumor growth rate, and the doubling time of thyroglobulin is used to measure the tumor growth rate and determine the prognosis (Reference 23).


1. Lloyd RV, Osamura RY, Klöppel G, et al. (editors) WHO Classification of Tumours of Endocrine Organs (4th edition). IARC: Lyon, France, 2017. 2. Kakudo K, Bychkov A, Bai Y, et al.: The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives. Pathol Int 68:641-664, 2018. 3. Tuttle RM et al. Updated American join committee on cancer/tumor-node-metastasis staging system for differentiated and anaplastic thyroid cancer (eighth edition): What changed and why? Thyroid 27:751-756, 2017. 4. Ito Y et al.: Prognostic value of the 8th edition of the tumor-node-metastasis classification for patients with papillary thyroid carcinoma: a single-institution study at a high-volume center in Japan. Endocr J 65:707-716, 2018. 5. Welch HG, Black WC.: Overdiagnosis in cancer. J Natl Cancer Inst. 2010; 102:605-613. 6. Esserman LJ, Thompson IM, Reid B et al.: Addressing overdiagnosis and overtreatment in cancer: a prescription for change. Lancet Oncol 2014; 15:e234-242. 7. Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003; 13:381-387. 8. Sugitani I, Toda K, Yamada K, et al. Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg 2010; 34:1222-1231 . 9. Miyauchi A, Kudo T, Ito Y et al.: Natural history of papillary thyroid microcarcinoma: Kinetic analyses on tumor volume during active surveillance and before presentation. Surgery. 2019; 165:25-30. 10. Haugen BR, Alexander EK, Bible KC, et al. American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26:1-134. 11. US Preventive Services Task Force: Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 317:1882-1887, 2017. 12. Sugitani I, Ito Y, Miyauchi A et al.: Active surveillance versus immediate surgery: Questionnaire survey on the current treatment strategy for adult patients with low-risk papillary thyroid microcarcinoma in Japan. Thyroid. 2019; 29:1563-1571. 13. The Japan Thyroid Association, Guidelines for Clinical Practice for the management of Thyroid Nodules in Japan 2013, Nankodo Co, Ltd, Tokyo, Japan: pp 1-277, 2013. (in Japanese) 14. Japanese Society of Thyroid Surgery, Japan Association of Endocrine Surgeons. Guidelines for the Management of Thyroid Tumors. 2nd ed. Tokyo, Japan 2018. (in Japanese) 15. Shimura H:Thyroid nodules in Japanese population, incidence and diagnosis.-Data from medical checkup-Japan Thyroid Association Journal, 1:109-113,2010.(in Japanese) 16. Ito Y, Miyauchi A, Oda H et al. Appropriateness of the revised Japanese guidelines’ risk classification for the prognosis of papillary thyroid carcinoma: a retrospective analysis of 5,845 papillary thyroid carcinoma patients. Endocr J 66:127-134, 2019. 17. Kakudo K, Wakasa T, Ohta Y et al. Prognostic classification of thyroid follicular cell tumors using Ki-67 labeling Index: How to report high-risk thyroid carcinomas? Endocr J 62:1-12, 2015. 18. Du B, Wang F, Wu L et al.: Cause-specific mortality after diagnosis of thyroid cancer: a large population-based study. Endocrine 2020 [Online ahead of print] 19. Conzo G, Avenia N, Ansaldo GL et al.: Surgical treatment of thyroid follicular neoplasms: results of a retrospective analysis of a large clinical series. Endocrine 55:530-538, 2017. 20. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 2014; 140:317-322. 21. Ahn HS, Kim HJ, Welch HG 2014 Korea’s thyroid-cancer “epidemic”–screening and overdiagnosis. N Engl J Med 2014; 371:1765-1767. 22. Welch HG, Doherty GM. Saving Thyroids – Overtreatment of Small Papillary Cancers. N Engl J Med 2018; 379:310-312. 23. Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y et al.: Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid 21:707-716, 2011. 24. Kakudo K, Bai Y, Liu Z, Li Y and Ito Y: Classification of thyroid follicular cell tumors. – with special reference to borderline lesions- Endocr J, 59:1-12, 2011. 25. Kakudo K, Bai Y, Liu Z, Ozaki T. Encapsulated papillary thyroid carcinoma, follicular variant: a misnomer. Pathol Int. 62:155-160, 2012. Review. 26. Nikiforov YE, Seethala RR, Tallini G, et al.: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma. A paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncol 2:1023-1029, 2016. 27. Ohba K, Mitsutake N, Matsuse M, et al.: Encapsulated papillary thyroid tumor with delicate nuclear changes and a KRAS mutation as a possible novel subtype of borderline tumor. J Pathol Transl Med. 53:136-141. 2019.


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