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Original Article

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; J Pathol Transl Med. 2024;58(6):331-340. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.12

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Abstract PDF Supplementary Material

Background
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.

Citations

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Misdiagnosed follicular adenoma with 11 year postoperative liver and lung metastases a case report and literature review
Kai-Li Yang, Heng-Tong Han, Shou-Hua Li, Xiao-Xiao Li, Ze Yang, Li-Bin Ma, Yong-Xun Zhao
Discover Oncology.2025;[Epub] CrossRef

Case Study

Uncommon granulomatous manifestation in Epstein-Barr virus–positive follicular dendritic cell sarcoma: a case report: Henry Goh Di Shen, Yue Zhang, Wei Qiang Leow; J Pathol Transl Med. 2025;59(2):133-138. Published online October 31, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.27

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Abstract PDF

Hepatic Epstein-Barr virus–positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) represents a rare form of liver malignancy. The absence of distinct clinical and radiological characteristics, compounded by its rare occurrence, contributes to a challenging diagnosis. Here, we report a case of a 54-year-old Chinese female with a background of chronic hepatitis B virus treated with entecavir and complicated by advanced fibrosis presenting with a liver mass found on her annual surveillance ultrasound. Hepatectomy was performed under clinical suspicion of hepatocellular carcinoma. Immunomorphologic characteristics of the tumor were consistent with EBV+ IFDCS with distinct non-caseating granulomatous inflammation. Our case illustrates the importance of considering EBV+ IFDCS in the differential diagnosis of hepatic inflammatory lesions. Awareness of this entity and its characteristic features is essential for accurately diagnosing and managing this rare neoplasm.

Citations

Citations to this article as recorded by

Mesenchymal Tumors of the Liver: An Update Review
Joon Hyuk Choi, Swan N. Thung
Biomedicines.2025; 13(2): 479. CrossRef
EBV-positive inflammatory follicular dendritic cell sarcoma occurring in different organs: a case report and literature review
Wenhua Bai, Chunfang Hu, Zheng Zhu
Frontiers in Oncology.2025;[Epub] CrossRef
Spleen EBV-positive inflammatory follicular dendritic cell sarcoma: a case report and literature review
Yi Xiao, Lanlan Li, Xiumei Zhan, Juner Xu, Yewu Chen, Qiuchan Zhao, Yinghao Fu, Xian Luo, Huadi Chen, Hao Xu
Frontiers in Oncology.2025;[Epub] CrossRef
Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma of the liver: clinical features, imaging findings and potential diagnostic clues
Gui-Ling Huang, Man-Qian Huang, Yu-Ting Zhang, Hui-Ning Huang, Hong-Tao Liu, Xiao-Qing Pei
Abdominal Radiology.2025;[Epub] CrossRef
Epstein‑Barr virus+ inflammatory follicular dendritic cell sarcoma with clonal immunoglobulin heavy chain gene rearrangement: A case report and literature review
Qian Ye, Juan Zhao, Jiao He, Weishan Zhang
Oncology Letters.2025; 31(2): 1. CrossRef
Primary hepatic follicular dendritic cell sarcoma: A case study and literature review
Junjie Zhu, Ying Liang, Li Zhang, Bingqi Li, Danfeng Zheng, Hangyan Wang
Journal of International Medical Research.2025;[Epub] CrossRef

Original Articles

Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning: Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat; J Pathol Transl Med. 2025;59(1):39-49. Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.14

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Abstract PDF Supplementary Material

Background
Although the criteria for follicular-pattern thyroid tumors are well-established, diagnosing these lesions remains challenging in some cases. In the recent World Health Organization Classification of Endocrine and Neuroendocrine Tumors (5th edition), the invasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as its own entity. It is crucial to differentiate this variant of papillary thyroid carcinoma from low-risk follicular pattern tumors due to their shared morphological characteristics. Proteomics holds significant promise for detecting and quantifying protein biomarkers. We investigated the potential value of a protein biomarker panel defined by machine learning for identifying the invasive encapsulated follicular variant of papillary thyroid carcinoma, initially using formalin- fixed paraffin-embedded samples.
Methods
We developed a supervised machine-learning model and tested its performance using proteomics data from 46 thyroid tissue samples.
Results
We applied a random forest classifier utilizing five protein biomarkers (ZEB1, NUP98, C2C2L, NPAP1, and KCNJ3). This classifier achieved areas under the curve (AUCs) of 1.00 and accuracy rates of 1.00 in training samples for distinguishing the invasive encapsulated follicular variant of papillary thyroid carcinoma from non-malignant samples. Additionally, we analyzed the performance of single-protein/gene receiver operating characteristic in differentiating the invasive encapsulated follicular variant of papillary thyroid carcinoma from others within The Cancer Genome Atlas projects, which yielded an AUC >0.5.
Conclusions
We demonstrated that integration of high-throughput proteomics with machine learning can effectively differentiate the invasive encapsulated follicular variant of papillary thyroid carcinoma from other follicular pattern thyroid tumors.

Citations

Citations to this article as recorded by

Misdiagnosed follicular adenoma with 11 year postoperative liver and lung metastases a case report and literature review
Kai-Li Yang, Heng-Tong Han, Shou-Hua Li, Xiao-Xiao Li, Ze Yang, Li-Bin Ma, Yong-Xun Zhao
Discover Oncology.2025;[Epub] CrossRef

Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified: Bogyeong Han, Sojung Lim, Jeemin Yim, Young Keun Song, Jiwon Koh, Sehui Kim, Cheol Lee, Young A Kim, Yoon Kyung Jeon; J Pathol Transl Med. 2024;58(2):59-71. Published online January 22, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.04

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Background
The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear.
Methods
Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL–not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed.
Results
TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054).
Conclusions
The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Citations

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T-bet: biological functions, molecular mechanisms, and therapeutic applications: a systematic review
Xiaowen Yang, Min Sun, Xinyi Tang, Xiaoyuan Zhang, Wenzhi Shen
Frontiers in Immunology.2026;[Epub] CrossRef
CXCR Family and Hematologic Malignancies in the Bone Marrow Microenvironment
Yanquan Liu, Huanwen Tang
Biomolecules.2025; 15(5): 716. CrossRef
Diagnostic and therapeutic pathways for lymphoma patients: expert consensus through Nominal Group Technique and Delphi methodology
Attilio Guarini, Valentina Bozzoli, Sabino Ciavarella, Michele Cimminiello, Francesca Donatelli, Angelo Fama, Vincenza Fernanda Fesce, Vincenzo Fraticelli, Francesco Gaudio, Giuseppina Greco, Augusto Martellini, Francesca Merchionne, Rosanna Maria Miccoli
Frontiers in Oncology.2025;[Epub] CrossRef
Prognostic Significance of TBX21 and GATA3 Subtype Classification in Indolent Adult T‐Cell Leukemia‐Lymphoma With Cutaneous Lesions
Kazuhiro Kawai, Youhei Uchida, Takuro Kanekura
The Journal of Dermatology.2025; 52(11): 1674. CrossRef

Identification of invasive subpopulations using spatial transcriptome analysis in thyroid follicular tumors: Ayana Suzuki, Satoshi Nojima, Shinichiro Tahara, Daisuke Motooka, Masaharu Kohara, Daisuke Okuzaki, Mitsuyoshi Hirokawa, Eiichi Morii; J Pathol Transl Med. 2024;58(1):22-28. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.21

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Abstract PDF

Background
Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells.
Methods
We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases.
Results
We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor.
Conclusions
Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.

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Biomedicine & Pharmacotherapy.2026; 194: 118945. CrossRef
Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning
Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat
Journal of Pathology and Translational Medicine.2025; 59(1): 39. CrossRef
Spatial Transcriptomics in Thyroid Cancer: Applications, Limitations, and Future Perspectives
Chaerim Song, Hye-Ji Park, Man S. Kim
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Reviews

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy: Hee Young Na, So Yeon Park; J Pathol Transl Med. 2022;56(6):319-325. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.29

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Abstract PDF

Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)” since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.

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Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning
Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat
Journal of Pathology and Translational Medicine.2025; 59(1): 39. CrossRef
Papillae, psammoma bodies, and/or many nuclear pseudoinclusions are helpful criteria but should not be required for a definitive cytologic diagnosis of papillary thyroid carcinoma: An institutional experience of 207 cases with surgical follow up
Tarik M. Elsheikh, Matthew Thomas, Jennifer Brainard, Jessica Di Marco, Erica Manosky, Bridgette Springer, Dawn Underwood, Deborah J. Chute
Cancer Cytopathology.2024; 132(6): 348. CrossRef
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Agnes Stephanie Harahap, Chan Kwon Jung
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Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
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Endocrine Pathology.2023; 34(3): 311. CrossRef

Follicular lymphoma: updates for pathologists: Mahsa Khanlari, Jennifer R. Chapman; J Pathol Transl Med. 2022;56(1):1-15. Published online December 27, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.29

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Abstract PDF

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.

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Case Study

Composite follicular lymphoma and classic Hodgkin lymphoma: Han-Na Kim, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul-Won Choi, Young Hyeh Ko; J Pathol Transl Med. 2022;56(1):57-60. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.09

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Abstract PDF

Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

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Original Article

Upward trend in follicular lymphoma among the Korean population: 10-year experience at a large tertiary institution: Meejeong Kim, Hee Sang Hwang, Hyungwoo Cho, Dok Hyun Yoon, Cheolwon Suh, Chan Sik Park, Heounjeong Go, Jooryung Huh; J Pathol Transl Med. 2021;55(5):330-337. Published online September 2, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.25

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Abstract PDF Supplementary Material

Background
Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) in Western countries. However, it is relatively rare in Asia. This study examined epidemiologic characteristics of FL in South Korea, with an emphasis on recent trends of increase in cases.
Methods
We retrospectively examined 239 cases of newly diagnosed FL at a large tertiary institution in Korea (Asan Medical Center, Seoul, Republic of Korea) between 2008 and 2017. Age-adjusted incidence rates and clinicopathological variables were analyzed, and joinpoint regression analysis was used to identify the changes.
Results
The age-adjusted incidence of FL significantly increased during the study period (p = .034), and the ratio of (relative incidence) patients with FL to patients with NHL increased from 4.28% to 9.35% in the same period. Over the 10-year study assessment duration, the proportion of patients with stage III/IV FL (p = .035) and expression of BCL2 (p = .022) or BCL6 (p = .039) significantly increased. From 2013–2017, the proportion of patients with highrisk Follicular Lymphoma International Prognostic Index (FLIPI) score increased (21.5% to 28.7%), whereas that of low-risk FLIPI decreased (55.4% to 38.6%), although those results were not statistically significant (p = .066).
Conclusions
We found an increasing incidence of FL, with a disproportionate increase in the incidence of high-stage disease and recent changes in the clinicopathologic features of the Korean patient population.

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Liang-Chun Chiu, Chih-Wen Lin, Hung-Ju Li, Jian-Han Chen, Fu-Cheng Chuang, Sheng-Fung Lin, Yu Chang, Yu-Chieh Su
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Case Study

Morphologic variant of follicular lymphoma reminiscent of hyaline-vascular Castleman disease: Jiwon Koh, Yoon Kyung Jeon; J Pathol Transl Med. 2020;54(3):253-257. Published online February 5, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.17

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Follicular lymphoma (FL) with hyaline-vascular Castleman disease (FL-HVCD)-like features is a rare morphologic variant, with fewer than 20 cases in the literature. Herein, we report a case of FL-HVCD in a 37-year-old female who presented with isolated neck lymph node enlargement. The excised lymph node showed features reminiscent of HVCD, including regressed germinal centers (GCs) surrounded by onion skin-like mantle zones, lollipop lesions composed of hyalinized blood vessels penetrating into regressed GCs, and hyalinized interfollicular stroma. In addition, focal areas of abnormally conglomerated GCs composed of homogeneous, small centrocytes with strong BCL2, CD10, and BCL6 expression were observed, indicating partial involvement of the FL. Several other lymphoid follicles showed features of in situ follicular neoplasia. Based on the observations, a diagnosis of FL-HVCD was made. Although FLHVCD is very rare, the possibility of this variant should be considered in cases resembling CD. Identification of abnormal, neoplastic follicles and ancillary immunostaining are helpful for proper diagnosis.

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Analysis of immunophenotypic features in hyaline vascular type Castleman disease
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Gurdip S Tamber, Myriam Chévarie‐Davis, Margaret Warner, Chantal Séguin, Carole Caron, René P Michel
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Original Articles

A Multi-institutional Study of Prevalence and Clinicopathologic Features of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) in Korea: Ja Yeong Seo, Ji Hyun Park, Ju Yeon Pyo, Yoon Jin Cha, Chan Kwon Jung, Dong Eun Song, Jeong Ja Kwak, So Yeon Park, Hee Young Na, Jang-Hee Kim, Jae Yeon Seok, Hee Sung Kim, Soon Won Hong; J Pathol Transl Med. 2019;53(6):378-385. Published online October 21, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.18

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Abstract PDF

Background
In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).
Methods
Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.
Results
The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAF^V600E mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).
Conclusions
The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.

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Andrés Coca-Pelaz, Juan P. Rodrigo, Abbas Agaimy, Dana M. Hartl, Göran Stenman, Vincent Vander Poorten, Antti A. Mäkitie, Mark Zafereo, Karthik N. Rao, Gregory W. Randolph, Alessandra Rinaldo, Alfio Ferlito
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Analysis of a pre-2017 follicular variant papillary thyroid carcinoma cohort reclassified as noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP): an 11-year retrospective single institution experience
Shaham Beg, Sana Irfan Khan, Isabella Cui, Theresa Scognamiglio, Rema Rao
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Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know
Jabir Alharbi, Thamer Alraddadi, Haneen Sebeih, Mohammad A Alessa, Haddad H Alkaf, Ahmed Bahaj, Sherif K Abdelmonim
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Seung Eun Lee, Mi-Sook Lee, Heejin Bang, Mi Young Kim, Yoon-La Choi, Young Lyun Oh
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Bayan A. Alzumaili, Lauren N. Krumeich, Reagan Collins, Timothy Kravchenko, Emad I. Ababneh, Adam S. Fisch, William C. Faquin, Vania Nosé, Maria Martinez-Lage, Gregory W. Randolph, Rajshri M. Gartland, Carrie C. Lubitz, Peter M. Sadow
Thyroid.2023; 33(5): 566. CrossRef
Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center
Paola Vignali, Agnese Proietti, Elisabetta Macerola, Anello Marcello Poma, Liborio Torregrossa, Clara Ugolini, Alessio Basolo, Antonio Matrone, Teresa Rago, Ferruccio Santini, Rossella Elisei, Gabriele Materazzi, Fulvio Basolo
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
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Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: Reclassification and outcome study
David Cubero Rego, Hwajeong Lee, Anne Boguniewicz, Timothy A. Jennings
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Francesca Maletta, Enrico Costantino Falco, Alessandro Gambella, Jasna Metovic, Mauro Papotti
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Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and Its Impact on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience: Milim Kim, Joung Eun Kim, Hyun Jeong Kim, Yul Ri Chung, Yoonjin Kwak, So Yeon Park; J Pathol Transl Med. 2018;52(3):171-178. Published online April 3, 2018; DOI: https://doi.org/10.4132/jptm.2018.04.03

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Abstract PDF

Background
This study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
Methods
Five thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions.
Results
Of the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance.
Conclusions
The decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.

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Spatial transcriptomics reveals prognosis‐associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment
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Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review
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Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis
Elina Haaga, David Kalfert, Marie Ludvíková, Ivana Kholová
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Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features and the risk of malignancy in The Bethesda System for the Reporting of Thyroid Cytopathology
Danielle Elliott Range, Xiaoyin “Sara” Jiang
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Did Introducing a New Category of Thyroid Tumors (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Decrease the Risk of Malignancy for the Diagnostic Categories in the Bethesda System for Reporting Thyroid Cytopathology?
Janusz Kopczyński, Agnieszka Suligowska, Kornelia Niemyska, Iwona Pałyga, Agnieszka Walczyk, Danuta Gąsior-Perczak, Artur Kowalik, Kinga Hińcza, Ryszard Mężyk, Stanisław Góźdź, Aldona Kowalska
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High risk of malignancy in cases with atypia of undetermined significance on fine needle aspiration of thyroid nodules even after exclusion of NIFTP
Sevgiye Kaçar Özkara, Büşra Yaprak Bayrak, Gupse Turan
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Yu‐Hsin Chen, Kristen L. Partyka, Rae Dougherty, Harvey M. Cramer, Howard H. Wu
Diagnostic Cytopathology.2020; 48(12): 1237. CrossRef
Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses
Hee Young Na, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park, Paula Soares
PLOS ONE.2020; 15(11): e0241597. CrossRef
How is noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) shaping the way we interpret thyroid cytology?
Michiya Nishino
Journal of the American Society of Cytopathology.2019; 8(1): 1. CrossRef
Cytological Diagnoses Associated with Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features According to the Bethesda System for Reporting Thyroid Cytopathology: A Systematic Review and Meta-Analysis
Massimo Bongiovanni, Luca Giovanella, Francesco Romanelli, Pierpaolo Trimboli
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Hee Young Na, Ji Won Woo, Jae Hoon Moon, June Young Choi, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park
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Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions: Kanghee Han, Hwa-Jeong Ha, Joon Seog Kong, Jung-Soon Kim, Jae Kyung Myung, Jae Soo Koh, Sunhoo Park, Myung-Soon Shin, Woo-Tack Song, Hye Sil Seol, Seung-Sook Lee; J Pathol Transl Med. 2018;52(2):110-120. Published online January 29, 2018; DOI: https://doi.org/10.4132/jptm.2018.01.17

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Abstract PDF

Background
It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions.
Methods
We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups.
Results
The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas.
Conclusions
This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.

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АКТУАЛЬНІ ТЕНДЕНЦІЇ ДІАГНОСТИКИ ТА ЛІКУВАННЯ ФОЛІКУЛЯРНИХ НЕОПЛАЗІЙ ЩИТОПОДІБНОЇ ЗАЛОЗИ
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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
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Biomedicines.2021; 9(12): 1771. CrossRef
The Role of Fine Needle Aspiration Biopsy with Bethesda System in the Evaluation of Thyroid Nodules
Gizem AKKAŞ AKGÜN, Figen ASLAN
Anadolu Kliniği Tıp Bilimleri Dergisi.2021; 26(1): 23. CrossRef
Comprehensive DNA Methylation Profiling Identifies Novel Diagnostic Biomarkers for Thyroid Cancer
Jong-Lyul Park, Sora Jeon, Eun-Hye Seo, Dong Hyuck Bae, Young Mun Jeong, Yourha Kim, Ja Seong Bae, Seon-Kyu Kim, Chan Kwon Jung, Yong Sung Kim
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Hee Young Na, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park, Paula Soares
PLOS ONE.2020; 15(11): e0241597. CrossRef

The Intraoperative Immunohistochemical Staining of CD56 and CK19 Improves Surgical Decision for Thyroid Follicular Lesions: Ju Yeon Pyo, Sung-eun Choi, Eunah Shin, JaSeung Koo, SoonWon Hong; J Pathol Transl Med. 2017;51(5):463-470. Published online August 2, 2017; DOI: https://doi.org/10.4132/jptm.2017.05.25

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Abstract PDF

Background
When differential diagnosis is difficult in thyroid follicular lesions with overlapping histological features, the immunohistochemical staining can help confirm the diagnosis. We aimed to evaluate the effectiveness of rapid immunohistochemical stains of CD56 and cytokeratin 19 on frozen sections of thyroid follicular lesion and explore the possible gains and limitations of the practice. Methods: Eighty-six nodules of 79 patients whose intraoperative frozen sections were selected as the control group, and 53 nodules of 48 patients whose intraoperative frozen sections were subject to rapid immunohistochemistry were selected as the study group. Results: Five nodules (6%) in the control group were diagnosed as follicular neoplasm and six nodules (7%) were deferred. In the study group, six nodules (11%) were follicular neoplasm and none were deferred. Three nodules (4%) in the control group showed diagnostic discrepancy between the frozen and permanent diagnoses, but none in the study group. The average turnaround time for the frozen diagnosis of the control group was 24 minutes, whereas it was 54 minutes for the study group. Conclusions: Intraoperative rapid immunohistochemical stains significantly decreased the diagnostic discrepancy in this study. Considering the adverse effects of indefinite frozen diagnosis or discrepancy with permanent diagnoses, the intraoperative rapid immunohistochemical stain can help to accurately diagnose and hence provide guidance to surgical treatment.

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Case Study

Thymoma and Synchronous Primary Mediastinal Seminomas with Florid Follicular Lymphoid Hyperplasia in the Anterior Mediastinum: A Case Report and Review of the Literature: Hyang-im Lee, In-seok Jang, Kyung Nyeo Jeon, Gyung Hyuck Ko, Jong Sil Lee, Dong Chul Kim, Dae Hyun Song, Jeong-Hee Lee; J Pathol Transl Med. 2017;51(2):165-170. Published online February 2, 2017; DOI: https://doi.org/10.4132/jptm.2016.08.24

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Abstract PDF

Thymoma is the most common neoplasm of the anterior mediastinum and has malignant potential. Germ cell tumors (GCTs) found in the anterior mediastinum are usually benign, and malignant GCTs, such as seminomas, are rare. Histologically, mediastinal seminoma is indistinguishable from testicular seminoma except for site-associated morphological features such as lymphoid follicular hyperplasia. Therefore, excluding metastasis is very important. Recently, we treated a young adult patient with multiple thymic masses that occurred simultaneously. The patient underwent a thymectomy for the removal of the mediastinal masses, one of which was diagnosed as type B2 invasive thymoma, and two of which were diagnosed as primary mediastinal seminomas with massive follicular hyperplasia. The patient received adjuvant chemotherapy after surgical resection. To our knowledge, this is the first description of a thymoma and a mediastinal seminoma occurring simultaneously in the thymus. We present this case along with a literature review.

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Original Articles

Core Needle Biopsy Is a More Conclusive Follow-up Method Than Repeat Fine Needle Aspiration for Thyroid Nodules with Initially Inconclusive Results: A Systematic Review and Meta-Analysis: Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang; J Pathol Transl Med. 2016;50(3):217-224. Published online April 14, 2016; DOI: https://doi.org/10.4132/jptm.2016.02.15

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Abstract PDF

Background
This study investigated the appropriate management of thyroid nodules with prior non-diagnostic or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) through a systematic review and meta-analysis.
Methods
This study included 4,235 thyroid nodules from 26 eligible studies. We investigated the conclusive rate of follow-up core needle biopsy (CNB) or repeat fine needle aspiration (rFNA) after initial fine needle aspiration (FNA) with non-diagnostic or AUS/FLUS results. A diagnostic test accuracy (DTA) review was performed to determine the diagnostic role of the follow-up CNB and to calculate the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve.
Results
The conclusive rates of follow-up CNB and rFNA after initial FNA were 0.879 (95% confidence interval [CI], 0.801 to 0.929) and 0.684 (95% CI, 0.627 to 0.736), respectively. In comparison of the odds ratios of CNB and rFNA, CNB had more frequent conclusive results than rFNA (odds ratio, 5.707; 95% CI, 2.530 to 12.875). Upon subgroup analysis, follow-up CNB showed a higher conclusive rate than rFNA in both initial non-diagnostic and AUS/FLUS subgroups. In DTA review of followup CNB, the pooled sensitivity and specificity were 0.94 (95% CI, 0.88 to 0.97) and 0.88 (95% CI, 0.84 to 0.91), respectively. The AUC for the SROC curve was 0.981, nearing 1.
Conclusions
Our results show that CNB has a higher conclusive rate than rFNA when the initial FNA produced inconclusive results. Further prospective studies with more detailed criteria are necessary before follow-up CNB can be applied in daily practice.

Citations

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Smad1 Expression in Follicular Lymphoma: Jai Hyang Go; J Pathol Transl Med. 2015;49(3):243-248. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.03.30

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Abstract PDF: Background
Follicular lymphomas present with various immunohistologic patterns. The immunohistochemical markers used in the diagnosis of follicular lymphoma show variable degrees of sensitivity and specificity, and thus, additional germinal center markers are required. Smad1 has been reported to be overexpressed in follicular lymphoma, but little is known regarding the expression patterns of Smad proteins in human lymphoid tissue. Methods: In the present study, we performed immunohistochemistry for traditional germinal center markers and for Smad1 in human reactive lymphoid and follicular lymphoma tissues to investigate Smad1’s usefulness in the diagnosis of follicular lymphoma. Results: In the reactive germinal centers, most cells were positive for Smad1. Among the 27 follicular lymphoma cases, 17 of 21 (80%) were Smad1 positive, 17 of 27 (63%) were positive for CD10, and 23 of 27 (85%) were positive for Bcl6. Notably, three cases expressed CD10 only, and one only expressed Bcl6. All these cases were grade 3 tumors and showed follicular and diffuse growth patterns. Conclusions: These results indicate that Smad1 is a candidate as a germinal center marker. Furthermore, they suggest that the Smad signaling pathway might be involved in follicular lymphoma.

Case Study

Follicular Proliferative Lesion Arising in Struma Ovarii: Min Jee Park, Min A Kim, Mi Kyung Shin, Hye Sook Min; J Pathol Transl Med. 2015;49(3):262-266. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.03.26

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Abstract PDF

Malignant struma ovarii is extremely rare and difficult to diagnose histologically, particularly in cases of follicular carcinoma. This case study is intended to describe three cases of follicular proliferative lesion arising in struma ovarii that we experienced. The first case was clearly malignant given the clinical picture of multiple recurrences, but there was little histological evidence of malignancy. Our second case featured architectural and cellular atypia and necrosis and was diagnosed as malignant despite the absence of vascular and stromal invasion. Our third case exhibit-ed solid microfollicular proliferation without any definite evidence of malignancy (even the molecular data was negative); however, we could not completely exclude malignant potential after conducting a literature review. In cases such as our third case, it has been previously suggested that a diagnostic term recognizing the low-grade malignant potential, such as “proliferative stromal ovarii” or “follicular proliferative lesion arising in the stromal ovarii” would be appropriate.

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Role of gene sequencing in classifying struma ovarii: BRAF p.G469A mutation and TERT promoter alterations favour malignant struma ovarii
Sophie Neyrand, Alexis Trecourt, Jonathan Lopez, Pierre Alexandre Just, Françoise Descotes, Françoise Borson‐Chazot, Isabelle Ray‐Coquard, Myriam Decaussin‐Petrucci, Mojgan Devouassoux‐Shisheboran
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Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations
Roberta Poli, Maria Scatolini, Enrico Grosso, Francesca Maletta, Marco Gallo, Daniele Liscia, Anna Nelva, Flora Cesario, Giuseppe Forte, Jasna Metovic, Marco Volante, Emanuela Arvat, Mauro Papotti
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Proliferative struma ovarii: A rare case report
Shankhanila Mazumdar, GaganKumar Rangari, Neeraj Dhameja, NishaRani Agrawal
International Journal of Clinicopathological Correlation.2021; 5(2): 85. CrossRef
Malignant struma ovarii presenting with follicular carcinoma: A case report with molecular analysis
Takafumi Tsukada, Hiroshi Yoshida, Mitsuya Ishikawa, Yuka Asami, Kouya Shiraishi, Tomoyasu Kato
Gynecologic Oncology Reports.2019; 30: 100498. CrossRef
A Rare Case: Struma Ovarii in a 14-Year-Old Girl
Elif Iltar, Isin Ureyen, Tayfun Toptas, Melike Savas, Sema Çekiç, Aysel Uysal
Journal of Adolescent and Young Adult Oncology.2018; 7(1): 134. CrossRef
Proliferative Highly Differentiated Follicular Carcinoma Of Ovarian Origin (Hdfco) Presenting Long After Bilateral Oophorectomy
Natalie M. Liu, Neda Moatamed, Racquel S. Bueno, Wendy L. Sacks
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Original Article

The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 δ in Follicular Thyroid Carcinoma: Min Hye Jang, Kyeong Cheon Jung, Hye Sook Min; J Pathol Transl Med. 2015;49(2):112-117. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.31

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Abstract PDF

Background
Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy and its differential diagnosis includes follicular adenoma (FA) and adenomatous goiter (AG). Several ancillary markers have been suggested to aid in the diagnosis of FTC, but the successful use of these methods still needs to be validated. Methods: In the present study, we verified the immunoexpression of HMGA2, CEACAM6, survivin, and SFN/14-3-3 δ in lesions including 41 AGs, 72 FAs, and 79 FTCs. We evaluated their diagnostic usefulness, combined with galectin 3, Hector Battifora mesothelial 1 (HBME1), cytokeratin 19, and cyclin D1, in diagnosing FTC. Results: The expressions of HBME1 (65.8%) and HMGA2 (55.7%) were significantly higher in FTCs than in FAs and AGs (p<.001 and p=.005, respectively). HBME1 was the only marker that was more frequently expressed in FTCs than in FAs (p=.021) and it was more frequently expressed in follicular neoplasms than in AGs (p<.001). Among the novel markers, the combination of HMGA2 and HBME1 showed the highest sensitivity (72.2%) and specificity (76.1%) for diagnosing FTC. CEACAM6, survivin, and SFN/14-3-3 δ were barely expressed in most cases. Conclusions: Our present results show that only HMGA2 can be beneficial in differentiating FTC using the novel markers.

Citations

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HMGA2 promotes nasopharyngeal carcinoma progression and is associated with tumor resistance and poor prognosis
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Bo Hyun Kim, Seong Jang Kim, Mijin Kim, Sang‐Woo Lee, Shin Young Jeong, Kyoungjune Pak, Keunyoung Kim, In Joo Kim
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Esmeralda Castelblanco, Carles Zafon, Javier Maravall, Pilar Gallel, Montserrat Martinez, Ismael Capel, Maria Rosa Bella, Irene Halperin, Jordi Temprana, Carmela Iglesias, Manel Puig-Domingo, Mercedes Robledo, Xavier Matias-Guiu, Didac Mauricio
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Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma
Yourha Kim, Min-Hee Kim, Sora Jeon, Jeeyoon Kim, Chankyung Kim, Ja Seong Bae, Chan Kwon Jung, Yves St-Pierre
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Survivin DEx3 as a biomarker of thyroid cancers: A study at the mRNA and protein level
Joanna Waligórska-Stachura, Nadia Sawicka-Gutaj, Maciej Zabel, Mirosław Andrusiewicz, Paweł Gut, Agata Czarnywojtek, Marek Ruchała
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Case Study

Follicular Dendritic Cell Sarcoma of the Inflammatory Pseudotumor-like Variant Presenting as a Colonic Polyp: Shien-Tung Pan, Chih-Yuan Cheng, Nie-Sue Lee, Peir-In Liang, Shih-Sung Chuang; Korean J Pathol. 2014;48(2):140-145. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.140

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Abstract PDF

Follicular dendritic cell (FDC) sarcoma is rare and is classified either as conventional type or inflammatory pseudotumor (IPT)-like variant. Extranodal presentation is uncommon and nearly all gastrointestinal FDC tumors are of the conventional type. IPT-like variant tumors occur almost exclusively in the liver and spleen and are consistently associated with Epstein-Barr virus (EBV). Here we report the case of a 78-year-old woman with an IPT-like FDC sarcoma presenting as a pedunculated colonic polyp. Histologically, scanty atypical ovoid to spindle cells were mixed with a background of florid lymphoplasmacytic infiltrate, which led to an initial misdiagnosis of pseudolymphoma. These atypical cells expressed CD21, CD23, CD35, and D2-40, and were positive for EBV by in situ hybridization, confirming the diagnosis. The patient was free of disease five months after polypectomy without adjuvant therapy. Although extremely rare, the differential diagnosis for colonic polyp should include FDC sarcoma to avoid an erroneous diagnosis. A review of the 24 cases of IPT-like FDC sarcoma reported in the literature reveal that this tumor occurs predominantly in females with a predilection for liver and spleen, and has a strong association with EBV.

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Daichi KITAGUCHI, Katsuji HISAKURA, Taiki SATO, Masanao KURATA, Tatsuya ODA, Nobuhiro OHKOHCHI
Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2017; 78(3): 527. CrossRef
Clinicopathological features of inflammatory pseudotumour‐like follicular dendritic cell tumour of the abdomen
Yanyang Chen, Huijuan Shi, Hui Li, Tiantian Zhen, Anjia Han
Histopathology.2016; 68(6): 858. CrossRef
A Rare Case of Follicular Dendritic Cell Sarcoma with Pseudochylous Effusion and Review of Literature From India
Kamal Kant Sahu, Gaurav Prakash, Sandeep Rao, Amanjit Bal, Pankaj Malhotra, Jasmina Ahluwalia, Rakesh K. Vashistha
Indian Journal of Hematology and Blood Transfusion.2015; 31(2): 307. CrossRef
Epstein-Barr virus–associated inflammatory pseudotumor presenting as a colonic mass
Shunyou Gong, Iwona Auer, Rajan Duggal, Stefania Pittaluga, Mark Raffeld, Elaine S. Jaffe
Human Pathology.2015; 46(12): 1956. CrossRef
Response of follicular dendritic cell sarcoma to gemcitabine and docetaxel: report of two cases and literature review
Robert M Conry
Clinical Sarcoma Research.2014;[Epub] CrossRef

Original Article

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy: Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh; Korean J Pathol. 2013;47(1):61-66. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.61

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Abstract PDF

Background

This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC.

Methods

Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case.

Results

Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimoto's thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%.

Conclusions

This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

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2019 Practice guidelines for thyroid core needle biopsy: a report of the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association
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Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses
Hee Young Na, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park, Paula Soares
PLOS ONE.2020; 15(11): e0241597. CrossRef
Core needle biopsy of thyroid nodules: outcomes and safety from a large single-center single-operator study
Jooae Choe, Jung Hwan Baek, Hye Sun Park, Young Jun Choi, Jeong Hyun Lee
Acta Radiologica.2018; 59(8): 924. CrossRef
Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions
Kanghee Han, Hwa-Jeong Ha, Joon Seog Kong, Jung-Soon Kim, Jae Kyung Myung, Jae Soo Koh, Sunhoo Park, Myung-Soon Shin, Woo-Tack Song, Hye Sil Seol, Seung-Sook Lee
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Comparison of the Diagnostic Efficacy of Ultrasound‐Guided Core Needle Biopsy With 18‐ Versus 20‐Gauge Needles for Thyroid Nodules
Hye Shin Ahn, Mirinae Seo, Su Min Ha, Hee Sung Kim
Journal of Ultrasound in Medicine.2018; 37(11): 2565. CrossRef
Subclassification of Bethesda Atypical and Follicular Neoplasm Categories According to Nuclear and Architectural Atypia Improves Discrimination of Thyroid Malignancy Risk
Joel Xue Yi Lim, Min En Nga, Dedrick Kok Hong Chan, Wee Boon Tan, Rajeev Parameswaran, Kee Yuan Ngiam
Thyroid.2018; 28(4): 511. CrossRef
The expression profile of integrin receptors and osteopontin in thyroid malignancies varies depending on the tumor progression rate and presence of BRAF V600E mutation
Galina Chernaya, Nina Mikhno, Tatiana Khabalova, Svetlana Svyatchenko, Lyudmila Mostovich, Sergey Shevchenko, Lyudmila Gulyaeva
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Core Needle Biopsy of the Thyroid: 2016 Consensus Statement and Recommendations from Korean Society of Thyroid Radiology
Dong Gyu Na, Jung Hwan Baek, So Lyung Jung, Ji-hoon Kim, Jin Yong Sung, Kyu Sun Kim, Jeong Hyun Lee, Jung Hee Shin, Yoon Jung Choi, Eun Ju Ha, Hyun Kyung Lim, Soo Jin Kim, Soo Yeon Hahn, Kwang Hwi Lee, Young Jun Choi, Inyoung Youn, Young Joong Kim, Hye Sh
Korean Journal of Radiology.2017; 18(1): 217. CrossRef
Radiofrequency ablation of small follicular neoplasms: initial clinical outcomes
Su Min Ha, Jin Yong Sung, Jung Hwan Baek, Dong Gyu Na, Ji-hoon Kim, Hyunju Yoo, Ducky Lee, Dong Whan Choi
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A meta‐analytic review of the Bethesda System for Reporting Thyroid Cytopathology: Has the rate of malignancy in indeterminate lesions been underestimated?
Patrizia Straccia, Esther Diana Rossi, Tommaso Bizzarro, Chiara Brunelli, Federica Cianfrini, Domenico Damiani, Guido Fadda
Cancer Cytopathology.2015; 123(12): 713. CrossRef
Impact of NRAS Mutations on the Diagnosis of Follicular Neoplasm of the Thyroid
Ja-Seong Bae, Seung Kyu Choi, Sora Jeon, Yourha Kim, Sohee Lee, Youn Soo Lee, Chan Kwon Jung
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Diagnosis of Thyroid Follicular Neoplasm: Fine-Needle Aspiration Versus Core-Needle Biopsy
Ra Gyoung Yoon, Jung Hwan Baek, Jeong Hyun Lee, Young Jun Choi, Min Ji Hong, Dong Eun Song, Jae Kyun Kim, Jong Ho Yoon, Won Bae Kim
Thyroid.2014; 24(11): 1612. CrossRef

Case Report

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report: Jung-Soo Pyo, Guhyun Kang, Sung-Im Do, Seoung Wan Chae, Kyungeun Kim, Sang Hyuk Lee, Yoon-La Choi, Joon Hyuk Choi, Jin Hee Sohn, Dong-Hoon Kim; Korean J Pathol. 2012;46(3):306-310. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.306

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Abstract PDF

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7×4.5×1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

Citations

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Extranodal Follicular Dendritic Cell Sarcoma of the Head and Neck Region: A Clinicopathological Study of 7 Cases
Nasir Ud Din, Zubair Ahmad, Shabina Rahim, Karen Fritchie, Muhammad Usman Tariq, Arsalan Ahmed
International Journal of Surgical Pathology.2023; 31(6): 1067. CrossRef
Cytomorphology of follicular dendritic cell sarcoma: a report of 7 cases with an emphasis on the diagnostic challenges
Cody Weimholt, Jalal B. Jalaly, Cedric Bailey
Journal of the American Society of Cytopathology.2023; 12(3): 229. CrossRef
Follicular dendritic cells
Seham A. Abd El‐Aleem, Entesar Ali Saber, Neven M. Aziz, Hani El‐Sherif, Asmaa M. Abdelraof, Laiche Djouhri
Journal of Cellular Physiology.2022; 237(4): 2019. CrossRef
Clinicopathological characteristics of extranodal follicular dendritic cell sarcoma: A report of two cases
Xing Zhao, Dayong Sun, Gang Zhang
Oncology Letters.2021;[Epub] CrossRef
Cytological diagnosis of follicular dendritic cell sarcoma: A case report and review of literature
A. Dutta, P. Arun, P. Roy, I. Arun
Cytopathology.2018; 29(5): 461. CrossRef
Follicular dendritic cells and related sarcoma
Fabio Facchetti, Luisa Lorenzi
Seminars in Diagnostic Pathology.2016; 33(5): 262. CrossRef
Extranodal follicular dendritic cell sarcoma: A clinicopathological report of four cases and a literature review
RUI-FEN WANG, WEI HAN, LEI QI, LI-HUI SHAN, ZHENG-CAI WANG, LI-FENG WANG
Oncology Letters.2015; 9(1): 391. CrossRef
Follicular Dendritic Cell Sarcoma of Parapharyngeal Space: A Case Report and Review of the Literature
Turki Al-Hussain, Muhammad Saleem, Suresh Babu Velagapudi, Mohammad Anas Dababo
Head and Neck Pathology.2015; 9(1): 135. CrossRef
Clinical and pathological features of head and neck follicular dendritic cell sarcoma
Ji Li, Min-Li Zhou, Shui-Hong Zhou
Hematology.2015; 20(10): 571. CrossRef

Original Article

Availability of Immunohistochemistry in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma.: Ji Yun Jeong, Jung Sik Jang, Yoon Kyung Sohn, Jin Hyang Jung, Yi Kyeong Chun, Ji Young Park; Korean J Pathol. 2010;44(1):48-55.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.48

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Abstract PDF

BACKGROUND
Making the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) is often difficult, and there are no accurate immunohistochemical or molecular markers. The purpose of this study is to evaluate performing immunohistochemistry to make the diagnosis of FVPTC.
METHODS
A total of 249 thyroid lesions were studied. We made the tissue microarray, and we assessed the expression of HBME-1, galectin-3, CD56, and p63.
RESULTS
Galectin-3, HBME-1, and p63 were positive in 79.7%, 79.7%, and 15.9% of the FVPTC, respectively. These immunohistochemical features of FVPTC were between those of classic papillary thyroid carcinoma (CPTC) and those of non-PTC. The CD56 expression was positive in 75.4% of the FVPTC, which is much higher than that of the CPTC (28.3%), and even higher than that of the non-PTC lesions (60%). Comparing FVPTC with CPTC, the expression of galectin-3 was significantly higher and the expression of CD56 was significantly lower in the CPTCs. Comparing the FVPTC with follicular carcinoma (FC), the expression of all the markers was significantly higher in the FVPTC. Comparing PTC with FC, the expression of CD56 was lower and the expressions of the other markers were higher in the PTCs.
CONCLUSIONS
Galectin-3, HBME-1, and p63 can help make the diagnosis of FVPTC, and a cocktail of these markers can be even more useful. But CD56 is not thought to be useful to make the diagnosis of FVPTC.

Citations

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A Case of Multifocal Papillary Thyroid Carcinoma Consisting of One Encapsulated Follicular Variant withBRAFK601E Mutation and Three Conventional Types withBRAFV600E Mutation
Wook Youn Kim, Young Sin Ko, Tae Sook Hwang, Hye Seung Han, So Dug Lim, Wan Seop Kim, Seo Young Oh
Korean Journal of Pathology.2013; 47(3): 293. CrossRef

Case Report

Cytology of Follicular Dendritic Cell Sarcoma on Intraoperative Touch Imprint Smears: A Case Report.: Ju Young Song, Xian Ji Jin, Jee Young Han, Lucia Kim, In Suh Park, Joon Mee Kim, Young Chae Chu, Suk Jin Choi; Korean J Pathol. 2009;43(6):589-593.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.589

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Abstract PDF

Follicular dendritic cell (FDC) sarcoma is a neoplastic proliferation of FDCs. Because its cytologic findings can vary widely, both the cytomorphology and histopathology of FDC sarcoma can impose a significant diagnostic dilemma. We present cytologic features of FDC sarcoma assessed by intraoperative touch imprint. Intra-abdominal lymphadenopathies were noted in 54-year-old male with hepatitis B-virus associated liver cirrhosis. In contrast to cytologic features of classical FDC sarcoma, the tumor cells featured a large epithelioid or Reed-Sternberg cell-like shape scattered in a background with abundant inflammatory cells, which led to a mistaken diagnosis of malignant lymphoma. However, in accordance with cytologic features previously described in the literature, the tumor cells were characterized by a fragile cytoplasm with cytoplasmic processes in dendritic or reticulated patterns reminiscent of the ultrastructural features of FDC. Cytoplasmic features rendering nuclei with a tendency to form clusters or syncytial aggregates associated with reactive lymphocytes appear to be the most valuable finding in diagnosis of FDC sarcoma.

Citations

Citations to this article as recorded by

Cytomorphology of follicular dendritic cell sarcoma: a report of 7 cases with an emphasis on the diagnostic challenges
Cody Weimholt, Jalal B. Jalaly, Cedric Bailey
Journal of the American Society of Cytopathology.2023; 12(3): 229. CrossRef
A Cytological Review of Follicular Dendritic Cell-Derived Tumors with Emphasis on Follicular Dendritic Cell Sarcoma and Unicentric Castleman Disease
José A. Jiménez-Heffernan, Cristina Díaz del Arco, Magdalena Adrados
Diagnostics.2022; 12(2): 406. CrossRef
Cytological diagnosis of follicular dendritic cell sarcoma: A case report and review of literature
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Cytopathology.2018; 29(5): 461. CrossRef

Original Article

Cytologic Features of Folliculars Adenoma and Follicular Carcinoma of the Thyroid: A Study on the Likelihood of Cytologic Diagnosis by Fine Needle Aspiration Cytology.: Hee Dae Park, Woon Sun Park, Sun Hee Kim, Seock Hyun Choi, Young Hye Cho, Sung Hee Kang, Kyung Bun Lee, Dong Hoon Kim, Seoung Wan Chae, Jin Hee Shon; J Pathol Transl Med. 2008;19(2):152-159.; DOI: https://doi.org/10.3338/kjc.2008.19.2.152

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Abstract PDF

Fine-needle aspiration cytology (FNAC) cannot differentiate follicular adenoma from follicular carcinoma since this distinction can only be based on the presence of capsular or vascular invasion, and this cannot be detected on a cytologic smear. The goal of this study was to define the diagnostic cytologic findings of follicular neoplasm and the possibility of diagnosing follicular neoplasm by performing FNAC. The cases of histologically diagnosed follicular adenoma and follicular carcinoma on the thyroidectomy specimens were retrieved. Among them, the cases with preoperative FNAC that was done within 3 months of the operation were finally selected. Then we reviewed the FNAC and histologic slides of 19 cases: 9 follicular adenomas and 10 follicular carcinomas. Our results suggest that for cases of follicular neoplasm, the aspirates show high or abundant cellularity, frequent follicle formation and occasional cellular atypism of the follicular cells. However, the atypism is more pronounced and more frequently noticed in the cases of follicular carcinoma, which reveals more higher anisocytosis (7/10, 70%), nuclear pleomorphism (9/10, 90%), coarse clumping of chromatin (8/10, 80%) and cellular overlapping (8/10, 80%).

Citations

Citations to this article as recorded by

Practical and challenging issue in thyroid cytopathology
Qianqian Zhang, Belen Padial Urtueta, Elisabetta Merenda, Gabriele Rotondaro, Noemi Morelli, Alessia Piermattei, Patrizia Straccia, Federica Cianfrini, Angela Feraco, Alessia Granitto, Antonino Mule, Esther Diana Rossi
Human Pathology.2025; : 106019. CrossRef
Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy
Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh
Korean Journal of Pathology.2013; 47(1): 61. CrossRef

Case Reports

Epstein-Barr virus-associated Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor in the Spleen of a Patient with Diffuse Large B Cell Lymphoma: A Case Report and Review of the Literature.: Sun Och Yoon, Hyoungsuk Ko, Baek hui Kim, Ghee Young Kwon, Yoon Kyung Jeon, Chul Woo Kim; Korean J Pathol. 2007;41(3):198-202.

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Abstract PDF: We report a case of an Epstein-Barr virus (EBV)-associated inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDC tumor). The tumor occurred in the spleen of a 64-year-old woman with a history of a diffuse large B-cell lymphoma (DLBCL) of neck nodes that presented four years ago. The splenectomy specimen revealed a 5 cm-sized, tan-colored and well-circumscribed mass. Histologically, spindle or ovoid cells with large vesicular nuclei were admixed with abundant inflammatory cells. Immunohistochemically, spindle cells were positive for FDC marker CD35, but negative for CD20, CD30 and ALK. EBV was detected almost exclusively in spindle cells by EBER in situ hybridization. IPT-like FDC tumors are rare, and are recognized as a distinctive clinicopathologic variant of FDC tumors. Among only 18 similar cases reported in the English language literature, the present case is the first case of a patient with a history of DLBCL.

An Unusual Stroma-Rich Variant of Castleman's Disease of the Hyaline-Vascular Type: A Case Report.: Ji Han Jung, Gyeongsin Park, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee; Korean J Pathol. 2007;41(4):266-270.

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Abstract PDF: The stroma-rich variant of Castleman's disease of the hyaline-vascular type (CDHV) is a rare entity that shows overgrowth of a variety of stromal cells in the widened interfollicular (IF) area. We report here on a case of a stroma-rich variant of CDHV in an 18-year-old man who presented with an asymptomatic solitary neck mass he'd had for 1 year. Histologically, an enlarged lymph node fulfilled the criteria of CDHV, along with vague nodularity of a widened IF area. The nodular lesion consisted of numerous vessels and a proliferation of spindle cells. Immunohistochemically, the spindle cells were positive for vimentin and smooth muscle actin, they were negative for desmin, CD21, CD34, CD68, ALK-1, and S-100 protein. This stromal lesion is typically hyperplastic and clinically benign, and it must be distinguished from neoplastic stromal proliferation associated with Castleman's disease because of its potential for recurrence and metastasis.

Original Articles

Preferential Expression of CD44 in Thyroid Papillary Carcinoma.: jung Yeon Kim, Jinye Yoo, Hyejae Cho; Korean J Pathol. 2001;35(4):314-318.

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Abstract PDF: BACKGROUND
Papillary carcinoma is one of the most common malignant thyroid tumors and an important prognostic factor is the lymph node status. CD44 is a cell adhesion molecule and is associated with metastasis. The purpose of this study was to discover whether CD44 is valuable in the diagnosis of the papillary carcinoma, and whether Ki-67 and p53 are correlated with CD44 in the papillary carcinoma.
METHODS
We studied CD44, Ki-67 and p53 expressions in 34 cases of formalin-fixed paraffin embedded papillary thyroid carcinomas, and 20 cases of the follicular neoplasm using mouse anti-CD44 (H-CAM), Ki-67 and p53 monoclonal antibodies. RESULTS: Most of the papillary carcinomas expressed diffuse and intense membrane staining of CD44 (32/34 cases, 94.1%). Focal scattered immunoreactivity was observed in the follicular neoplasm (8/20 cases, 40.0%). The staining patterns of CD44 were similar in both follicular adenoma and carcinoma. Both groups with or without lymph node metastasis showed similar expression patterns for CD44. There were no differences in Ki-67 and p53 staining between papillary carcinomas and follicular neoplasms.
CONCLUSIONS
The result shows that papillary carcinomas preferentially display the CD44 antigen, and it is a useful diagnostic tool in the equivocal cases. There is no correlation among CD44, Ki-67 and p53 expressions in the papillary carcinoma.

Infantile Myofibromatosis(Congenital Generalized Fibromatosis): Associated with multiple congenital malformations and basaloid follicular hamartomas in the skin.: Eun Sook Nam, Yoo Hun Kim, Han Kyeom Kim, Insun Kim, Je Geun Chi; Korean J Pathol. 1995;29(6):776-782.

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Abstract PDF: Infantile myofibromatosis with systemic involvement is a very rare disease and is characterized by numerous nodules composed of spindle cells of a myofibroblastic nature. There are often disseminated throughout the subcutis, muscle, skeleton and viscera. We report an autopsy case of infantile myofibromatosis in a stillborn female fetus of 32 weeks of gestation. The nodules, Imm to 2 cm, were found over the whole body and viscera. The involved viscera were the heart, tongue, esophagus, gastrointestinal tract, portal areas of the liver, spleen anc pancreas. There were also associated malformations, viz., frontal meningoencephalocele, flexion defer-mities, syndactyly, cleft palate, agenesis of corpus callosum, pachygyria, diaphragmatic hemia, renal hypoplasia, etc. Multiple basaloid follicular hamartomas of the skin were noted on the face and extremeties. There are no previous reports in the literature of infantile myofibromatosis in conjunction with the above skin lesion and congenital malformations.

Case Report

Interfollicular Hodgkin's Lymphoma: A case report.: Lee So Maeng, Kyung Mee Kim, You Mee Kang, Chang Seok Kang, Sang In Shim; Korean J Pathol. 1995;29(6):804-806.

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Abstract PDF: An unusual pattern of focal involvement of lymph nodes by Hodgkin's disease is described using the name Interfollicular Hodgkin's Disease. It is characterized by florid reactive follicular hyperplasia which overshadows involvement of the interfollicular zones by Hodgkin's desease. The importance of interfollicular Hodgkin's disease rests on its misdiagnosis as a benign lesion. We report a case of interfollicular Hodgkin's disease in a 34-year-old female patient in the inguinal area. The lymph nodes showed reactive follicular hyperplasia. The focal interfollicular spaces were invaded by Hodgkin's disease. The Reed-Stemberg cells stained positively with CD15 and CD30 antibody in the immunohistochemical stain. An in situ hybridization study looking for EBV was negative in these R-S cells.

Original Article

Fine Needle Aspiration Cytologic Features of Follicular Lymphoma.: Jin Haeng Chung, Hwa Jeong Ha, Sun Hoo Park, Jae Soo Koh, Min Suk Kim, Seung Sook Lee, Kyung Ja Cho; J Pathol Transl Med. 2002;13(2):60-65.

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Abstract PDF: The accuracy of fine needle aspiration cytology(FNAC) for the diagnosis of follicular lymphoma was investigated by a review of 13 FNAC specimens from 10 patients. All patients included in this study were confirmed by surgical biopsy preceded by FNAC. Three aspirates were unsatisfactory because of scanty cellularity. Among the remaining 10 cases, 5(50%) were diagnosed as lymphoma, 3(30%) as reactive hyperplasia, one(10%) as metastatic small cell carcinoma, and one(10%) as granulomatous inflammation. Cytologic distinction between follicular lymphoma and reactive hyperplasia is very difficult with cytomorphology alone. Compared to reactive hyperplasia, the characteristic cytologic features such as relatively homogeneous cellular constituent, paucity of tingible body macrophages and lymphohistiocytic aggregates, and less mitotic activity in follicular lymphoma are important findings to prevent false negative diagnosis. In addition, lymphoglandular bodies are useful in distinguishing malignant epithelial tumor from lymphoid lesion.

Case Report

Macrofollicular Variant of Papillary Thyroid Carcinoma with Extensive Hemorrhage.: Haeryoung Kim, SoonWon Hong, Kwang Gil Lee, Eun Kyung Kim, Cheong Soo Park, Woung Youn Chung, Woo Ick Yang; J Pathol Transl Med. 2004;15(1):60-64.

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Abstract PDF: BACKGROUND
The macrofollicular variant of papillary thyroid carcinoma (MVPC) is characterized by macrofollicles occupying more than half of the tumor and demonstrating nuclear features of classic papillary carcinoma. It is difficult to recognize on fine needle aspiration (FNA) cytology due to the paucity of aspirated neoplastic cell clusters, especially when the tumor is associated with extensive areas of hemorrhage.
CASE
A 34-year-old female presented with a well-demarcated nodule in the thyroid gland, diagnosed as a benign nodule on ultrasonography and computed tomography. FNA cytology smear revealed a few small aggregates of follicular cells with morphological features suspicious for papillary carcinoma, set in a background of hemorrhage, inflammatory cells, and hemosiderin-laden macrophages. Intraoperative frozen section revealed macrofollicular nests filled with hemorrhage and composed of follicular cells demonstrating nuclear clearing and grooves.
CONCLUSION
MVPC is a rare but distinctive variant of papillary carcinoma, which is easily mistaken for adenomatous goiter or benign macrofollicular neoplasm on radiologic findings. The cytopathologist should alert oneself on encountering benign radiologic findings and any smear composed of scant numbers of follicular cells with nuclear features suspicious for papillary carcinoma despite the bland-looking background of hemorrhage and hemosiderin-laden macrophages, and recommend intraoperative frozen sections for a definite diagnosis.

Original Articles

Expressions of Id-1 and Id-2 in Hyperplastic Thyroid Tissue and Thyroid Carcinoma.: Young A Kim, Young Joo Park, Do Joon Park, Seong Hoe Park, Ji Eun Kim; Korean J Pathol. 2006;40(1):60-65.

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Abstract PDF: BACKGROUND
Id proteins are a family of helix-loop-helix proteins and are regarded to be negative regulators of cell differentiation. In general, Id-1 and Id-2 expressions are upregulated during tumor development and progression in a variety of neoplasms, and these expressions may be associated with aggressive tumor behavior. However, little is known about the roles of Id-1 and Id-2 in thyroid neoplasms.
METHODS
The expressions of Id-1 and Id-2 were assessed immunohistochemically in 310 normal, hyperplastic, and neoplastic thyroid tissues using tissue microarrays.
RESULTS
Normal thyroid tissues rarely expressed Id-1 or Id-2. Moreover, whilst Id-1 expression was more elevated in malignant thyroid tissue than in hyperplastic thyroid tissue, Id-2 expression was more variable. No significant differences were observed between histologic subtypes of thyroid carcinomas with respect to Id-1 or Id-2 expression. Follicular adenomas showed higher expressions of Id-1 and Id-2 than thyroid carcinomas. No significant association was found between clinicopathological parameters and Id-1 expression, though Id-2 expression was significantly reduced in metastatic, stage IV tumors.
CONCLUSION
The expressions of Id-1 and Id-2 were elevated in hyperplastic and neoplastic thyroid tissues. However, neither appears suitable as a marker of malignancy or an aggressive phenotype, although Id-2 expression in advanced thyroid carcinomas may reflect a favorable prognosis.

A study of Digital Image Analysis of Chromatin Texture for Discrimination of Thyroid Neoplastic Cells.: Sang Woo Juhng, Jae Hyuk Lee, Eun Kyung Bum, Chang Won Kim; J Pathol Transl Med. 1996;7(1):23-30.

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Abstract PDF: Chromatin texture, which partly reflects nuclear organization, is evolving as an important parameter indicating cell activation or transformation. In this study, chromatin pattern was evaluated by image analysis of the electron micrographs of follicular and papillary carcinoma cells of the thyroid gland and tested for discrimination of the two neoplasms. Digital grey images were converted from the electron micrographs; nuclear images, excluding nucleolus and intranuclear cytoplasmic inclusions, were obtained by segmentation; grey levels were standardized; and grey level histograms were generated. The histograms in follicular carcinoma showed Gaussian or near-Gaussian distribution and had a single peak, whereas those in papillary carcinoma had two peaks(bimodal), one at the black zone and the other at the white zone. In papillary carcinoma. the peak in the black zone represented an increased amount of heterochromatin particles and that at the white zone represented decreased electron density of euchromatin or nuclear matrix. These results indicate that the nuclei of follicular and papillary carcinoma cells differ intheir chromatin pattern and the difference may be due to decondensed chromatin and/or matrix substances.

Demonstration of TCM-9 Monoclonal Antibody in Follicular Neoplasm of Thyroid.: Yun Jung Kim, Jung Weon Shim, Hye Kyung Ahn, Young Euy Park; J Pathol Transl Med. 1996;7(2):134-137.

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Abstract PDF: Monoclonal antibody(TCM-9) against human thyroid cancers have been studied by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody(TCM-9) that is known to have strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid does not bind to native or mature human thyroglobulin(Tg). We used to TCM-9 antibody by immunohistochemical staining on 5 follicular cancer, 2 follicular adenoma, 1 follicular neoplasm with suspicious invasion, 2 papillary cancer to ascer- tain being of help in differentiation between follicular carcinoma and adenoma. Reactivity of TCM-9 was observed in follicular carcinoma and papillary carcinoma but not observed in follicular adenoma. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer.

Case Report

Fine Needle Aspiration Cytology of Parathyroid Neoplasms: A Review of Three Cases.: Lucia Kim, Jee Young Han, In Suh Park, Suk Jin Choi, Joon Mee Kim, Young Chae Chu; J Pathol Transl Med. 2007;18(1):74-80.

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Abstract PDF: Parathyroid tumors may be difficult to distinguish from thyroid follicular lesions, especially when a tumor is nonfunctioning. We report here two cases of asymptomatic parathyroid carcinoma preoperatively misdiagnosed as thyroid follicular lesions, and one case of parathyroid adenoma showing hyperparathyroidism, and review the cytologic features favoring the diagnosis of parathyroid neoplasm. The cytologic findings that are characterized by clean background, monomorphic small cells, cohesive three-dimensional papillary clusters, small tight clusters with scattered naked nuclei, and well-defined clear cytoplasm favor a diagnosis for the parathyroid lesions. Cytologic findings such as macrofollicular structure, presence of colloid and macrophages, and presence of perivacuolar cytoplasmic granules on May-Grunwald-Giemsa stain support a diagnosis of a thyroid follicular lesion. The cytomorphology of parathyroid tumors is so variable that the distinction from a thyroid lesion cannot be based on the presence or absence of a single feature only but on the cytologic features as a whole.

Original Articles

An Ultrastructural Morphometric study of Follicular Center Lymphocytes of the palatine Tonsil: Reinvestigation of the Lukes-Collins' Classification of Malignant lymphoma.: Min Cheol Lee, Jong Han Shin; Korean J Pathol. 1994;28(5):493-505.

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Abstract PDF: The model of lymphocyte differentiation described for Lukes-Collins' classification of non-Hodgkin's lymphoma is related particularly to morphological alterations of nuclei of follicular center lymphocytes by antigenic stimulation. The authors carried out ultrastructural and morphometric studies to investigate morphological alterations during lymphocyte transformation on the nuclear profiles of follicular center, parafollicular and mantle zone lymphocytes in ten tonsillectomy cases of chronic hypertrophic tonsillitis. The nuclear parameters measured included nuclear area, contour index, frequency invagination and cleft, depth of invagination and nuclear diameters. Follicular centers contained a mixed population of lymphocytes consisting of untransformed (type 1), partially transformed (type 2) and fully transformed (type 3) lymphocytes. During lymphocyte transformation in both follicular, and parafollicular and mantle zones, the nuclei had a gradual and progressive increase in size. The nuclear contour index of type 2 nuclei of both follicular and parafollicular and mantle zones tended to be higher than those of type 1 and 3, indicating a greater degree of irregularity and variability of nuclear profiles. Invaginated and cleaved lymphocytes were not confined to me transformed lymphocytes. A considerable portion of lymphocytes had invaginations and clefts in parafollicular and mantle zone as well as follicular center. No difference on the depth of invagination was noted in type 1, type 2 and type 3 lymphocytes. The results indicate that some promise of the Lukes-Collins conepts of follicular center cells and the process of lymphocyte transformation in follicular centers may be necessary to revise

Establishment and Characterization of an Epstein-Barr Virus-negative B-cell Line from a Patient with Dissemination of Peripheral Blood and Bone Marrow by Malignant Lymphoid Cell.: Ho Jong Jeon, Mi Ja Lee, Yu Kyung Jeong, Yoo Hwan Park, Choon Hae Chung, Yoon Kyung Oh, Chul Heel Choi, Sang Woo Cheong; Korean J Pathol. 1996;30(9):792-809.

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Abstract PDF: A human malignant lymphoid cell line(JeKo-1) was established from a Korean patient with retroperitoneal tumor presenting peripheral blood and bone marrow involvement by malignant lymphoid cells. This cell line was established from peripheral blood, and the cell line had the identical immunophenotypic features as malignant cells from the peripheral blood. The established cell line had features of a mature B-cell phenotype with no evidence for commitment to other lineages. The JeKo-1 grows in suspension with a doubling time of 33 hours. By light and electron microscopic examination, the established cells had a follicular center showing, a small, cleaved, lymphoid appearance, and had a large amount of cytoplasm containing few vacuoles and an irregular cytoplasmic membrane. Immunophenotypic analyses with monoclonal antibodies using flow cytometry showed a monoclonal IgM kappa and CD5- B-cell phenotype. The cells were non-reactive for T-cells and myeloid/monocyte antigens, and no evidence of Epstein-Barr virus nuclear antigen by polymerase chain reaction. DNA analysis showed a hypodiploid stemline with a DNA index of 0.83. The established cells were strongly reactive for bcl-2 and c-myc onco-protein, but lacked expression of multidrug resistance gene protein, p-glycoprotein by Western blot analysis. Karyotypic analysis of JeKo-1 showed 40-41 chromosomes. This cell line should be a valuable tool to study the dissemination of malignant lymphoma into the peripheral blood and bone marrow.

Case Report

Angiofollicular Lymph Node Hyperplasia(Castleman's disease): 3 cases report.: Jeong Hee Park, Gil Ro Han, Hee Jin Chang, Jin Hee Sohn, Jung Il Suh; Korean J Pathol. 1992;26(3):298-305.

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Abstract PDF: Angiofollicular lymph node hyperplasia(AFLNH) was first described in 1956 by Castleman et al. It was initially reported as a solitary mediastinal mass but multicentric and extranodal disease is now well known. Histologically two distinct variants, e.g. the hyaline vascular type and the plasma cell type, of AFLNH are recognized. And the plasma cell type is typically associated with clinical syndrome consisting of fever, anemia, elevated erythrocyte sedimentation rate and polyclonal hypergammaglobulinemia. Recently, we experineced three cases of AFLNH. Histologically, two cases were hyaline vascular type, that were presented as a right supraclavicular mass of 49-year-old female, and as an anterior mediastinal mass of 53-year-old female. The remaining one case was plasma cell type that was presented as a left axillary mass of 63-year-old male. The former two cases showed typical features of hyaline vascular type but in case 1, exuberant proliferation of hyalinized vessels of capillary size was characteristic feature. The latter case of plasma cell type characteristically showed clinical syndrome consisting of fever, hypoalbuminemia, polyclonal hypergammaglobulinemia. All cases were presented as a single mass and they were well after surgical excision.

Original Articles

Morphometric Study on Fine Needle Aspirates from Follicular Adenoma and Follicular Carcinoma of the Thyroid.: Young Chae Chu, Hee Jung Cha, Soo Kee Min, Joon Mee Kim, Tae Sook Hwang; J Pathol Transl Med. 1998;9(1):63-68.

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Abstract PDF: Fine needle aspiration cytology of "cold" nodules of the thyroid has proved to be of great value in their preoperative diagnosis. Most types of thyroid tumors are readily recognizable from characteristic cellular patterns in the smears of needle aspirates. But follicular neoplasms present some problems because the cytomorphology of the adenomas frequently is same as in carcinoma. For differentiation of benign from malignant follicular neoplasms of the thyroid we tested the usefulness of two objective parameters - nuclear area and perimeter - by morphometry. This study was made on fine needle aspirates from 30 cases with cytologic diagnosis of follicular neoplasm of thyroid. The histologic classification was follicular adenoma in 22 cases and follicular carcinoma in 8 cases. As a reference group we used seven caes with nodular hyperplasia. The smears of aspirates were stained by Papanicolaou method. On each slide 200 randomly selected cells with intact nuclei were measured. The mean value of nuclear area are 25.32+/-5.50 micrometer2, 34.08+/-7.50 micrometer2 and 39.97+/-6.63 micrometer2 in nodular hyperplasia, follicular adenoma, and follicular carcinoma, respectively. The mean value of perimeter are 19.48+/-2.26 micrometer, 22.95+/-2.65 micrometer and 24.78+/-2.23 micrometer in nodular hyperplasia, follicular adenoma and follicular carcinoma, respectively. The mean nuclear areas and perimeters of cells from follicular adenoma were significantly larger than those from nodular hyperplasia (p<0.05). The mean nuclear areas and perimeters of cells from follicular carcinoma were larger than those from follicular adenoma but the differences are not significant statistically(p<0.05). Therefore, morphometric assessment alone is inadequate to predict malignancy in thyroid aspirates.

A Study on the Cytologic Features of Fine Needle Aspiration Cytology in the Thyroid Follicular Neoplasm and Nodular Goiter.: Jin Ye Yoo, Hye Jae Cho, Il Hyang Ko; J Pathol Transl Med. 1998;9(1):69-78.

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Abstract PDF: There is a lot of difficulty in the diagnosis of follicular lesions of the thyroid by fine needle aspiration cytology(FNAC). The main purpose of this report is offering more guidance regarding the cytologic appearance to distinguish follicular neoplasm from nodular goiter and laying stress on the presence of mixed group. The histologic and cytologic findings of 23 follicular neoplasms and 13 nodular (adenomatous) goiters were reviewed. Histologic specimens were classified into the microfollicular(MIF), mixed(MIX), and nodular goiter(NG) groups. The comparison of histologic patterns with histologic diagnosis revealed that all the lesions with predominantly microfollicular, trabecular, or solid pattern were follicular carcinoma and all the lesions with predominantly macrofollicular pattern were nodular goiter. The distinguishing cytologic features for the MIF group were irregular cell arrangement in cell groups(100%, p=0.00001), absence of atrophic follicular cells(100%, p=0.0007), abundant microfollicles(100%, p=0.002), pleomorphic nuclei(100%, p=0.002), not predominant syncytial smear pattern(100%, p=0.002), heterochromatin(100%, p=0.032), absence of macrofollicles(100%, p=0.038), scant colloid(100%, p=0.04), clear background(83%, p=0.00006), and uniform sized follicles(83%, p=0.014). And regular cell arrangement(honeycomb appearance) in cell groups(85%, p=0.0000), atrophic change of follicular cells(69%, p=0.0002), syncytial smear pattern(54%, p=0.006), monomorphic nuclei(85%, p=0.008), and hemorrhagic background(100%, p=0.027) were characteristic features of the NG group. Seventeen out of 36 cases(47%) were the MIX group composed of combined cytologic features of the MIF and NG groups. Therefore the frequent presence of the MIX group is considered to be main cause of the difficultyin the diagnosis of follicular lesions by FNAC. The mixed morphologic feature may support the hypothesis of a biologic "continuum" between nodular goiter and follicular neoplasm of thyroid gland.

SPARC Expression in Thyroid Follicular Adenomas and Carcinomas.: Chung Yeul Kim, Seong Jin Cho, Min Kyung Kim, Yang Seok Chae; Korean J Pathol. 2000;34(12):1016-1021.

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Abstract PDF: SPARC, secreted protein acidic and rich in cysteine, is a extracellular matrix-associated protein implicated in the modulation of cell adhesion, migration, cell cycle regulation, and angiogenesis. SPARC is expressed in fibrocytes and endothelial cells involved in tissue repair and invasive malignant tumors in the gastrointestinal tract, breast, lung, kidney, adrenal cortex, ovary, and brain. This study was aimed to characterize the different expression of SPARC in the thyroid follicular adenomas and follicular carcinomas. Immunohistochemical staining was performed in paraffin-embedded tissues of 25 follicular adenomas and 15 follicular carcinomas of the thyroid gland. Immunohistochemically, SPARC was not expressed in the 19 follicular adenoma and 2 follicular carcinoma but highly expressed in the 6 follicular adenoma and 13 follicular carcinoma. These findings suggest that SPARC is a potential diagnostic marker of follicular carcinoma and is helpful to distinguish follicular carcinoma from follicular adenoma without vascular or capsular invasion.

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