1.Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma
Takashi MASUI ; Katsunari YANE ; Ichiro OTA ; Kennichi KAKUDO ; Tomoko WAKASA ; Satoru KOIKE ; Hirotaka KINUGAWA ; Ryuji YASUMATSU ; Tadashi KITAHARA
Journal of Pathology and Translational Medicine 2025;59(2):115-124
We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.
2.Erratum: Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study
Agnes Stephanie HARAHAP ; Mutiah MUTMAINNAH ; Maria Francisca HAM ; Dina KHOIRUNNISA ; Abdillah HASBI ASSADYK ; Husni CANGARA ; Aswiyanti ASRI ; Diah Prabawati RETNANI ; Fairuz QUZWAIN ; Hasrayati AGUSTINA ; Hermawan ISTIADI ; Indri WINDARTI ; Krisna MURTI ; Muhammad TAKBIR ; Ni Made MAHASTUTI ; Nila KURNIASARI ; Nungki ANGGOROWATI ; Pamela ABINENO ; Yulita Pundewi SETYORINI ; Kennichi KAKUDO
Journal of Pathology and Translational Medicine 2025;59(3):201-201
3.Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma
Takashi MASUI ; Katsunari YANE ; Ichiro OTA ; Kennichi KAKUDO ; Tomoko WAKASA ; Satoru KOIKE ; Hirotaka KINUGAWA ; Ryuji YASUMATSU ; Tadashi KITAHARA
Journal of Pathology and Translational Medicine 2025;59(2):115-124
We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.
4.Erratum: Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study
Agnes Stephanie HARAHAP ; Mutiah MUTMAINNAH ; Maria Francisca HAM ; Dina KHOIRUNNISA ; Abdillah HASBI ASSADYK ; Husni CANGARA ; Aswiyanti ASRI ; Diah Prabawati RETNANI ; Fairuz QUZWAIN ; Hasrayati AGUSTINA ; Hermawan ISTIADI ; Indri WINDARTI ; Krisna MURTI ; Muhammad TAKBIR ; Ni Made MAHASTUTI ; Nila KURNIASARI ; Nungki ANGGOROWATI ; Pamela ABINENO ; Yulita Pundewi SETYORINI ; Kennichi KAKUDO
Journal of Pathology and Translational Medicine 2025;59(3):201-201
5.Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma
Takashi MASUI ; Katsunari YANE ; Ichiro OTA ; Kennichi KAKUDO ; Tomoko WAKASA ; Satoru KOIKE ; Hirotaka KINUGAWA ; Ryuji YASUMATSU ; Tadashi KITAHARA
Journal of Pathology and Translational Medicine 2025;59(2):115-124
We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.
6.Erratum: Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study
Agnes Stephanie HARAHAP ; Mutiah MUTMAINNAH ; Maria Francisca HAM ; Dina KHOIRUNNISA ; Abdillah HASBI ASSADYK ; Husni CANGARA ; Aswiyanti ASRI ; Diah Prabawati RETNANI ; Fairuz QUZWAIN ; Hasrayati AGUSTINA ; Hermawan ISTIADI ; Indri WINDARTI ; Krisna MURTI ; Muhammad TAKBIR ; Ni Made MAHASTUTI ; Nila KURNIASARI ; Nungki ANGGOROWATI ; Pamela ABINENO ; Yulita Pundewi SETYORINI ; Kennichi KAKUDO
Journal of Pathology and Translational Medicine 2025;59(3):201-201
7.Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia
Hee Young NA ; Miyoko HIGUCHI ; Shinya SATOH ; Kaori KAMEYAMA ; Chan Kwon JUNG ; Su-Jin SHIN ; Shipra AGARWAL ; Jen-Fan HANG ; Yun ZHU ; Zhiyan LIU ; Andrey BYCHKOV ; Kennichi KAKUDO ; So Yeon PARK
Journal of Pathology and Translational Medicine 2024;58(6):331-340
This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.
8.Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study
Agnes Stephanie HARAHAP ; Mutiah MUTMAINNAH ; Maria Francisca HAM ; Dina KHOIRUNNISA ; Abdillah Hasbi ASSADYK ; Husni CANGARA ; Aswiyanti ASRI ; Diah Prabawati RETNANI ; Fairuz QUZWAIN ; Hasrayati AGUSTINA ; Hermawan ISTIADI ; Indri WINDARTI ; Krisna MURTI ; Muhammad TAKBIR ; Ni Made MAHASTUTI ; Nila KURNIASARI ; Nungki ANGGOROWATI ; Pamela ABINENO ; Yulita Pundewi SETYORINI ; Kennichi KAKUDO
Journal of Pathology and Translational Medicine 2024;58(6):299-309
Background:
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods:
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results:
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.
9.Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia
Hee Young NA ; Miyoko HIGUCHI ; Shinya SATOH ; Kaori KAMEYAMA ; Chan Kwon JUNG ; Su-Jin SHIN ; Shipra AGARWAL ; Jen-Fan HANG ; Yun ZHU ; Zhiyan LIU ; Andrey BYCHKOV ; Kennichi KAKUDO ; So Yeon PARK
Journal of Pathology and Translational Medicine 2024;58(6):331-340
This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.
10.Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study
Agnes Stephanie HARAHAP ; Mutiah MUTMAINNAH ; Maria Francisca HAM ; Dina KHOIRUNNISA ; Abdillah Hasbi ASSADYK ; Husni CANGARA ; Aswiyanti ASRI ; Diah Prabawati RETNANI ; Fairuz QUZWAIN ; Hasrayati AGUSTINA ; Hermawan ISTIADI ; Indri WINDARTI ; Krisna MURTI ; Muhammad TAKBIR ; Ni Made MAHASTUTI ; Nila KURNIASARI ; Nungki ANGGOROWATI ; Pamela ABINENO ; Yulita Pundewi SETYORINI ; Kennichi KAKUDO
Journal of Pathology and Translational Medicine 2024;58(6):299-309
Background:
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods:
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results:
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

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