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Original Article
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Hyalinizing trabecular tumors with areas resembling noninvasive follicular thyroid neoplasm with papillary‑like nuclear features: an immunohistochemical and molecular analysis
Risa Kanematsu, Mitsuyoshi Hirokawa, Ayana Suzuki, Miyoko Higuchi, Satomi Usuki, Hiroshi Kamma, Takashi Akamizu
J Pathol Transl Med. 2026;60(4):436-443.   Published online July 15, 2026
DOI: https://doi.org/10.4132/jptm.2026.06.07
  • 661 View
  • 7 Download
AbstractAbstract PDF
Background
The coexistence of hyalinizing trabecular tumor (HTT) and areas with a morphology of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) within a single thyroid nodule has not been previously reported. We aimed to determine whether such tumors represent two independent neoplasms or a single tumor exhibiting divergent morphology. Methods: Ten tumors containing both HTT and NIFTP-like areas were examined. The term “NIFTP-like” was used strictly as a descriptive morphological designation for areas that fulfill the histologic criteria of NIFTP. Immunohistochemical analyses of Ki-67 (MIB-1) and type IV collagen and targeted molecular testing were performed. Ten NIFTPs, 10 follicular adenomas, and three HTTs were used as controls. Results: HTT components consistently showed characteristic membranous Ki-67 staining and intra-trabecular type IV collagen deposition, whereas NIFTP-like areas lacked these features, except for focal apical Ki-67 staining. Intranuclear cytoplasmic inclusions in HTT were positive for type IV collagen. NIFTPs showed neither membranous Ki-67 nor intra-trabecular type IV collagen. Molecular analysis demonstrated identical profiles between HTT components and NIFTP-like areas: three tumors harbored PAX8::GLIS3 fusions, and none showed RAS mutations. Pure HTT controls exhibited the same pattern. Conclusions: Our findings indicate that these follicular-patterned areas represent a morphological variant within the spectrum of HTT rather than a true NIFTP-related component or two separate neoplasms. These findings expand the recognized histologic diversity of HTT and highlight a potential diagnostic pitfall in follicular-patterned thyroid tumors. Focal apical Ki-67 staining may serve as a useful clue for distinguishing HTT from NIFTP.
Review Article
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Recent topics on thyroid cytopathology: reporting systems and ancillary studies
Mitsuyoshi Hirokawa, Ayana Suzuki
J Pathol Transl Med. 2025;59(4):214-224.   Published online June 30, 2025
DOI: https://doi.org/10.4132/jptm.2025.04.18
  • 6,441 View
  • 350 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
As fine-needle aspiration techniques and diagnostic methodologies for thyroid nodules have continued to evolve and reporting systems have been updated accordingly, we need to be up to date with the latest information to achieve accurate diagnoses. However, the diagnostic approaches and therapeutic strategies for thyroid nodules vary across laboratories and institutions. Several differences exist between Western and Eastern practices regarding thyroid fine-needle aspiration. This review describes the reporting systems for thyroid cytopathology and ancillary studies. Updated reporting systems enhance the accuracy, consistency, and clarity of cytology reporting, leading to improved patient outcomes and management strategies. Although a single global reporting system is optimal, reporting systems tailored to each country is acceptable. In such cases, compatibility must be ensured to facilitate data sharing. Ancillary methods include liquid-based cytology, immunocytochemistry, biochemical measurements, flow cytometry, molecular testing, and artificial intelligence, all of which improve diagnostic accuracy. These methods continue to evolve, and cytopathologists should actively adopt the latest methods and information to achieve more accurate diagnoses. We believe this review will be useful to practitioners of routine thyroid cytology.

Citations

Citations to this article as recorded by  
  • Importance of clinical, ultrasound and cytological characteristics in predicting malignancy in thyroid nodules with indeterminate cytology
    Gabriel Gonçalves dos Santos, Wendy Muller Tirapani, Cínthia Minatel Riguetto, Icleia Siqueira Barreto, Denise Engelbrecht Zantut-Wittmann
    Annals of Medicine.2026;[Epub]     CrossRef
Original Article
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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
  • 7,021 View
  • 286 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • Carbonic Anhydrase 12 as a Novel Prognostic Biomarker and Therapeutic Target for High‐Risk Follicular Thyroid Carcinoma
    Masashi Tanida, Tsuyoshi Takashima, Shinichiro Tahara, Masaharu Kohara, Haruka Kanai, Masami Suzuki, Motoyuki Suzuki, Mitsuyoshi Hirokawa, Ayana Suzuki, Shinya Sato, Daisuke Okuzaki, Satoshi Nojima, Takahiro Matsui, Hidenori Inohara, Eiichi Morii
    Cancer Science.2026; 117(1): 257.     CrossRef
  • An emerging role of CD74 in thyroid follicular cells in Hashimoto´s thyroiditis
    Pablo Sacristán-Gómez, Ana Serrano-Somavilla, Nuria Sánchez de la Blanca, Andrea Álvarez-Rodríguez, Eduardo Martínez-Parra, Miguel Sampedro-Nuñez, Fernando Sebastián-Valles, Mónica Marazuela, Rebeca Martínez-Hernández
    Biomedicine & Pharmacotherapy.2026; 194: 118945.     CrossRef
  • Cell-state transitions and microenvironmental remodeling in thyroid cancer progression revealed by single-cell and spatial transcriptomics
    Xin Wang, Deshuang Tao, Jinming Xu, Wensi Liu, Zhiwu Ji, Hairui Zhou, Zhen Wang
    Frontiers in Immunology.2026;[Epub]     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
    Cells.2025; 14(12): 936.     CrossRef
  • A New Tool to Decrease Interobserver Variability in Biomarker Annotation in Solid Tumor Tissue for Spatial Transcriptomic Analysis
    Sravya Palavalasa, Emily Baker, Jack Freeman, Aditri Gokul, Weihua Zhou, Dafydd Thomas, Wajd N. Al-Holou, Meredith A. Morgan, Theodore S. Lawrence, Daniel R. Wahl
    Current Issues in Molecular Biology.2025; 47(7): 531.     CrossRef

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