1.Clinicopathological profile of high-grade differentiated thyroid carcinoma in an Indonesian tertiary hospital
Novita ; Agnes Stephanie HARAHAP ; Maria Francisca HAM ; Alfianto WIDIONO ; Chan Kwon JUNG
Journal of Pathology and Translational Medicine 2026;60(3):338-348
High-grade differentiated thyroid carcinoma (HGDTC) is a recently recognized entity in the 2022 World Health Organization classification, representing a more aggressive subtype of differentiated thyroid carcinoma. Previously, high-grade features such as increased mitotic activity and tumor necrosis were often overlooked, despite being important independent prognostic factors. Although rare, HGDTC carries significant diagnostic, prognostic, and therapeutic implications. Data remain limited in Indonesia. Methods: This retrospective descriptive study reviewed 565 thyroid carcinoma cases diagnosed at Cipto Mangunkusumo Hospital from 2019 to 2024. Eleven cases (1.9%) met HGDTC criteria. Clinicopathological characteristics, histologic subtypes, Ki-67 proliferation index, molecular alterations, treatment modalities, and clinical outcomes were analyzed. Results: Patients had a mean age of 54.6 years, with a female-to-male ratio of 2.7:1. Papillary thyroid carcinoma was the main type (90.9%), with the tall cell subtype predominating. Mean tumor size was 6.4 cm. Lymphatic invasion, vascular invasion, and extrathyroidal extension were present in 54.5%, 18.2%, and 45.5% of cases, respectively. All tumors showed necrosis. Mean mitotic count was 3 per 2 mm². The Ki-67 index ranged from 5% to 45% (median, 14%). BRAFV600E and TERT promoter mutations were detected in 18.2% and 36.4% of cases, respectively, with co-mutations in 18.2%. Six cases (54.5%) had metastases at time of diagnosis. During a mean follow-up of 20.5 months, one patient (9.1%) developed new vertebral metastases and all patients (100%) remained alive. Conclusions: HGDTC presents with more aggressive characteristics and a worse prognosis. Accurate diagnosis, molecular profiling, and long-term monitoring are essential for optimal management.
2.Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie HARAHAP ; Maria Francisca HAM ; Retno Asti WERDHANI ; Erwin Danil JULIAN ; Rafi ILMANSYAH ; Chloe Indira Arfelita MANGUNKUSUMSO ; Tri Juli Edi TARIGAN
Journal of Pathology and Translational Medicine 2025;59(3):149-160
Background:
Core needle biopsy (CNB) improves diagnostic accuracy by providing precise tissue sampling for histopathological evaluation, overcoming the limitation of inconclusive fine-needle aspiration results. This study evaluated the diagnostic performance of CNB in assessing thyroid nodules, with additional analysis of the benefits of BRAF V600E and RAS Q61R immunohistochemical (IHC) markers.
Methods:
This retrospective study enrolled patients with thyroid nodules who underwent CNB at Dr. Cipto Mangunkusumo Hospital, Jakarta, from July 2022 to July 2024. CNB diagnoses were classified using the Korean Thyroid Association Criteria. Diagnostic efficacy was evaluated for neoplastic and malignant lesions, both independently and with BRAF V600E and RAS Q61R IHC. The correlation between nodule size and postoperative diagnosis was also analyzed.
Results:
A total of 338 thyroid nodule samples was included, and 52.7% were classified as CNB category II. In the 104 samples with postoperative diagnoses, category IV was the most prevalent (39.4%). CNB demonstrated a sensitivity of 74% and a specificity of 100% for neoplastic lesions and 23.8% sensitivity and 100% specificity for malignant lesions. Combining CNB with BRAF V600E and RAS Q1R IHC increased the sensitivity to 77% for neoplastic lesions and 28.8% for malignant lesions. Larger nodules (>3 cm) were significantly associated with neoplastic (p = .005) and malignant lesions (p = .004).
Conclusions
CNB performs well in identifying neoplastic lesions, with or without BRAF V600E and RAS Q61R IHC, but its low sensitivity for malignant lesions warrants caution. While CNB categories V–VI indicate malignancy, the possibility of malignancy in categories I–IV should not be overlooked.
3.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
4.Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie HARAHAP ; Maria Francisca HAM ; Retno Asti WERDHANI ; Erwin Danil JULIAN ; Rafi ILMANSYAH ; Chloe Indira Arfelita MANGUNKUSUMSO ; Tri Juli Edi TARIGAN
Journal of Pathology and Translational Medicine 2025;59(3):149-160
Background:
Core needle biopsy (CNB) improves diagnostic accuracy by providing precise tissue sampling for histopathological evaluation, overcoming the limitation of inconclusive fine-needle aspiration results. This study evaluated the diagnostic performance of CNB in assessing thyroid nodules, with additional analysis of the benefits of BRAF V600E and RAS Q61R immunohistochemical (IHC) markers.
Methods:
This retrospective study enrolled patients with thyroid nodules who underwent CNB at Dr. Cipto Mangunkusumo Hospital, Jakarta, from July 2022 to July 2024. CNB diagnoses were classified using the Korean Thyroid Association Criteria. Diagnostic efficacy was evaluated for neoplastic and malignant lesions, both independently and with BRAF V600E and RAS Q61R IHC. The correlation between nodule size and postoperative diagnosis was also analyzed.
Results:
A total of 338 thyroid nodule samples was included, and 52.7% were classified as CNB category II. In the 104 samples with postoperative diagnoses, category IV was the most prevalent (39.4%). CNB demonstrated a sensitivity of 74% and a specificity of 100% for neoplastic lesions and 23.8% sensitivity and 100% specificity for malignant lesions. Combining CNB with BRAF V600E and RAS Q1R IHC increased the sensitivity to 77% for neoplastic lesions and 28.8% for malignant lesions. Larger nodules (>3 cm) were significantly associated with neoplastic (p = .005) and malignant lesions (p = .004).
Conclusions
CNB performs well in identifying neoplastic lesions, with or without BRAF V600E and RAS Q61R IHC, but its low sensitivity for malignant lesions warrants caution. While CNB categories V–VI indicate malignancy, the possibility of malignancy in categories I–IV should not be overlooked.
5.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
6.Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie HARAHAP ; Maria Francisca HAM ; Retno Asti WERDHANI ; Erwin Danil JULIAN ; Rafi ILMANSYAH ; Chloe Indira Arfelita MANGUNKUSUMSO ; Tri Juli Edi TARIGAN
Journal of Pathology and Translational Medicine 2025;59(3):149-160
Background:
Core needle biopsy (CNB) improves diagnostic accuracy by providing precise tissue sampling for histopathological evaluation, overcoming the limitation of inconclusive fine-needle aspiration results. This study evaluated the diagnostic performance of CNB in assessing thyroid nodules, with additional analysis of the benefits of BRAF V600E and RAS Q61R immunohistochemical (IHC) markers.
Methods:
This retrospective study enrolled patients with thyroid nodules who underwent CNB at Dr. Cipto Mangunkusumo Hospital, Jakarta, from July 2022 to July 2024. CNB diagnoses were classified using the Korean Thyroid Association Criteria. Diagnostic efficacy was evaluated for neoplastic and malignant lesions, both independently and with BRAF V600E and RAS Q61R IHC. The correlation between nodule size and postoperative diagnosis was also analyzed.
Results:
A total of 338 thyroid nodule samples was included, and 52.7% were classified as CNB category II. In the 104 samples with postoperative diagnoses, category IV was the most prevalent (39.4%). CNB demonstrated a sensitivity of 74% and a specificity of 100% for neoplastic lesions and 23.8% sensitivity and 100% specificity for malignant lesions. Combining CNB with BRAF V600E and RAS Q1R IHC increased the sensitivity to 77% for neoplastic lesions and 28.8% for malignant lesions. Larger nodules (>3 cm) were significantly associated with neoplastic (p = .005) and malignant lesions (p = .004).
Conclusions
CNB performs well in identifying neoplastic lesions, with or without BRAF V600E and RAS Q61R IHC, but its low sensitivity for malignant lesions warrants caution. While CNB categories V–VI indicate malignancy, the possibility of malignancy in categories I–IV should not be overlooked.
7.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
8.Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma
Chan Kwon JUNG ; Agnes Stephanie HARAHAP
Endocrinology and Metabolism 2025;40(6):830-850
High-grade differentiated thyroid carcinoma (HGDTC) is a recently codified entity in the 2022 World Health Organization Classification of Endocrine Tumors, defined by a mitotic count of ≥5 mitoses per 2 mm² and/or tumor necrosis in a carcinoma that retains papillary, follicular, or oncocytic differentiation without anaplastic morphology. Although uncommon, HGDTC presents significant diagnostic and therapeutic challenges. This review summarizes current evidence regarding histopathologic recognition, molecular features, prognostic determinants, and evolving treatment paradigms. Particular attention is given to pattern-specific pitfalls such as high-grade papillary thyroid carcinoma, the diffuse sclerosing subtype, and the prognostic influence of the invasion phenotype (encapsulated versus infiltrative). Subcentimeter papillary carcinomas exhibiting increased mitotic activity alone should not be overinterpreted as HGDTC. An integrated, stepwise approach is proposed to enhance diagnostic reproducibility, refine risk stratification, and optimize multidisciplinary management in clinical practice.
9.Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning
Agnes Stephanie HARAHAP ; Chan Kwon JUNG
Journal of Pathology and Translational Medicine 2024;58(5):205-213
Background:
While fine needle aspiration cytology (FNAC) plays an essential role in the screening of thyroid nodules, core needle biopsy (CNB) acts as an alternative method to address FNAC limitations. However, diagnosing thyroid CNB samples can be challenging due to variations in background and levels of experience. Effective training is indispensable to mitigate this challenge. We aim to evaluate the impact of an educational program on improving the accuracy of CNB diagnostics.
Methods:
The 2-week observational program included a host mentor pathologist with extensive experience and a visiting pathologist. The CNB classification by The Practice Guidelines Committee of the Korean Thyroid Association was used for the report. Two rounds of reviewing the case were carried out, and the level of agreement between the reviewers was analyzed.
Results:
The first-round assessment showed a concordance between two pathologists for 247 thyroid CNB specimens by 84.2%, with a kappa coefficient of 0.74 (indicating substantial agreement). This finding was attributed to the discordance in the use of categories III and V. After peer learning, the two pathologists evaluated 30 new cases, which showed an overall improvement in the level of agreement. The percentage of agreement between pathologists on thyroid CNB diagnosis was 86.7%, as measured by kappa coefficient of 0.80.
Conclusions
This educational program, consisting of guided mentorship and peer learning, can substantially enhance the diagnostic accuracy of thyroid CNB. It is useful in promoting consistent diagnostic standards and contributes to the ongoing development of global pathology practices.
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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