Journal of Pathology and Translational Medicine

Original Articles

HER2-low and ultralow breast cancer: interobserver challenges and lessons from a consensus study: Jiwon Koh, Yoon Jin Cha, Eun Yoon Cho, Ahwon Lee, Ja Seung Koo, So Yeon Park, Min Hwan Kim, Jae Ho Jeong, Gyungyub Gong; Received December 17, 2025 Accepted January 8, 2026 Published online March 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.08 [Epub ahead of print]

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Abstract PDF: Background
The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

Aquaporin 1 promotes proliferation and migration of tumor by up-regulating claudin-1 expression in colon cancer: Wei Wei Xie, Lin Xu, Qian Li, Dao Quan Zhang, Yu Bao Zhou; Received September 9, 2025 Accepted December 31, 2025 Published online March 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.01 [Epub ahead of print]

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Abstract PDF: Background
With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma: Konstantinos Christofidis, Rodanthi Fioretzaki, Stylianos Mavropoulos Papoudas, Nikolaos Charalampakis, Nikolaos Kavantzas, Dimitrios Schizas, Stratigoula Sakellariou; J Pathol Transl Med. 2026;60(2):263-279. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.20

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Abstract PDF Supplementary Material: Background
Gastric adenocarcinoma is a major cause of cancer mortality worldwide, and reliable biomarkers remain insufficient. This study investigates the immunohistochemical expression of progastrin (hPG) and annexin A2 (ANXA2) and the polarization of tumor-associated macrophages in gastric adenocarcinoma to explore their potential prognostic and biological significance. Methods: A retrospective analysis was conducted on formalin-fixed, paraffin-embedded tissue samples from 60 patients with gastric adenocarcinoma (primary tumors, lymph node metastases, and non-tumoral gastric mucosa) and gastric biopsies from 23 healthy controls. The expression of hPG and ANXA2 was quantified using the H-score, and the CD163/human leukocyte antigen–DR (HLA-DR) ratio was used to represent macrophage polarization (M2/M1). Statistical analyses included non-parametric tests, Spearman correlations, Kaplan-Meier survival curves, and Cox proportional-hazards models. Results: ANXA2 expression was significantly elevated in cancer cells from primary tumors and lymph node metastases, compared with the non-tumoral gastric mucosa tissues and gastric mucosa tissues from healthy controls. ANXA2 expression increased with the tumor grade. High ANXA2 levels were associated with shorter overall and disease-free survival, but they did not have independent prognostic value. Although hPG expression correlated positively with ANXA2, it showed no significant prognostic association. The CD163/HLA-DR ratio increased with tumor progression and negatively correlated with ANXA2, but it did not influence survival outcomes. Conclusions: This study is the first to demonstrate the adverse prognostic impact of ANXA2 overexpression in gastric adenocarcinoma tissues from Caucasian patients. Our results suggest that ANXA2 might have utility as a prognostic biomarker and therapeutic target, if further large-scale studies validate and expand our findings.

3-Dimensional reconstruction reveals frequent intraluminal growth of submucosal veins in surgically resected pT1 colorectal cancers: Jihyun Park, Mi-Ju Kim, Yeon Wook Kim, Byong-Wook Lee, Junyoung Shin, Jinho Shin, Chan-Gi Pack, Dong-Hoon Yang, Jihun Kim, In Ja Park, Ralph H. Hruban, Seung-Mo Hong; J Pathol Transl Med. 2026;60(2):246-262. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.19

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Abstract PDF: Background
Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

Correlation between HER2 gene copy number and immunohistochemistry categories in HER2-negative breast cancer: diagnostic utility for differentiating HER2-null, ultralow, and low tumors: Min Chong Kim, Young Kyung Bae; J Pathol Transl Med. 2026;60(2):193-201. Published online February 25, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.07

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Abstract PDF: Background
The recent recognition of human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancers (BCs) has expanded the therapeutic relevance of HER2 testing in the antibody-drug conjugate era. However, the biological continuum of HER2 expression measured by immunohistochemistry (IHC) and its relationship with the HER2 gene copy number remain unclear. Methods: We retrospectively analyzed 135 HER2-negative invasive BCs and reclassified them as HER2-null (IHC 0), HER2-ultralow (0+), or HER2-low (1+ or 2+ without amplification). HER2 gene copy number was determined using silver-enhanced in situ hybridization. Statistical analyses were performed to compare HER2 copy number among IHC categories and evaluate the discriminatory value of HER2 copy number for distinguishing IHC subgroups. Results: The mean HER2 copy number increased stepwise across IHC categories: 1.95 ± 0.54 (null), 2.03 ± 0.43 (ultralow), 2.25 ± 0.65 (low, 1+), and 3.29 ± 1.05 (low, 2+). Significant differences were observed between the ultralow and low groups (p = .003) and between the null and low groups (p < .001), but not between the null and ultralow groups or between the ultralow and 1+ groups. Conclusions: HER2 gene copy number was positively correlated with protein expression as reflected by IHC categories. Although HER2 gene copy number was statistically higher in HER2-low than in HER2-null tumors, the substantial overlap in copy number ranges likely limits its utility in distinguishing HER2-low from HER2- null BCs.

Prevalence of HER2-ultralow breast cancer in South Korea: a multicenter study by reassessment of HER2-zero cases: Min Chong Kim, Eun Yoon Cho, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Wan Seop Kim, Chungyeul Kim, Sun-Young Jun, Hye Jeong Choi, So Mang Lee, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; J Pathol Transl Med. 2026;60(2):184-192. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.22

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Abstract PDF Supplementary Material: Background
This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Review Article

The evolving role of TRPS1 in dermatopathology: insights from the past 4 years: Mokhtar H. Abdelhammed, Woo Cheal Cho; J Pathol Transl Med. 2026;60(2):129-143. Published online January 29, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.25

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Abstract PDF: Over the past 4 years, trichorhinophalangeal syndrome type 1 (TRPS1) has rapidly gained attention among practicing pathologists, with numerous studies emerging that both support and question its diagnostic utility. Initially regarded as a highly specific marker for tumors of mammary origin, TRPS1 is now recognized to have broader expression patterns, including in a variety of cutaneous neoplasms. This is likely due to embryologic parallels between breast tissue and skin adnexal structures, an overlap that was underappreciated in early investigations. Although TRPS1 lacks absolute specificity—even among cutaneous neoplasms—it can still offer meaningful diagnostic value when interpreted alongside conventional immunohistochemical markers and within the appropriate morphologic context. Noteworthy diagnostic applications include mammary Paget disease, primary extramammary Paget disease, rare adnexal neoplasms such as endocrine mucin-producing sweat gland carcinoma and primary cutaneous NUT adnexal carcinoma, and cutaneous metastases from breast carcinoma. In this review, we present the most comprehensive and up-to-date evaluation of the utility and limitations of TRPS1 immunohistochemistry in dermatopathology. Our aim is to deepen understanding of this emerging marker and provide practical guidance on its optimal integration with established immunohistochemical panels to enhance diagnostic accuracy in routine practice.

Original Article

PSMA expression in hepatic colorectal cancer metastasis: Eundong Park, Michel Kmeid, Xin Wang, Haiyan Qiu, Clifton G. Fulmer, Marcello P. Toscano, Nusret Bekir Subasi, Maciej Gracz, Hwajeong Lee; J Pathol Transl Med. 2026;60(1):107-123. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.20

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Abstract PDF Supplementary Material

Background
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of various malignancies, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, PSMA expression in hepatic CRC metastasis has not been studied in detail. Methods: The PSMA expression in primary CRC and corresponding hepatic metastasis was evaluated by immunohistochemistry in a metastatic CRC cohort (n = 56), which was divided into subgroups according to treatment history and timing of metastasis. Demographic and histological characteristics of primary CRC were collected and their relationships with PSMA expression were examined. Additionally, the PSMA expression in resected HCC (n = 76) was compared with that of hepatic CRC metastasis. Results: In primary CRC, PSMA level showed a positive association with tumor size. Lower PSMA expression in hepatic metastasis was associated with higher primary CRC grade, advanced pTNM stage at the time of CRC resection, presence of tumor deposit, and unresectability of metastatic lesion. PSMA expression in primary CRC correlated with that in hepatic metastasis only in concurrent and untreated metastasis subgroup. PSMA expression in primary CRC and hepatic metastasis, regardless of treatment history and timing of metastasis, was not significantly different from that of HCC. Conclusions: Several adverse pathological features of primary CRC were associated with a lower PSMA expression in hepatic metastasis. PSMA expression in hepatic metastasis correlated with that of primary CRC only in concurrent and untreated subgroup. Primary HCC and hepatic CRC metastasis show comparable levels of PSMA expression.

Citations

Citations to this article as recorded by

Incidental detection of PDAC via 18F-PSMA PET/CT in a patient with recurrent prostate cancer. A case report
Giordano Savelli, Mattia Bonacina, Alberto Soffientini, Elvira Archiati, Claudio Bnà, Alberto Zaniboni
Frontiers in Nuclear Medicine.2026;[Epub] CrossRef

Review Article

A comprehensive review of ossifying fibromyxoid tumor: insights into its clinical, pathological, and molecular landscape: Kyriakos Chatzopoulos, Antonia Syrnioti, Mohamed Yakoub, Konstantinos Linos; J Pathol Transl Med. 2026;60(1):6-19. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.02

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Abstract PDF: Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm first described in 1989. It typically arises in the superficial soft tissues of the extremities as a slow-growing, painless mass. Histologically, it is commonly characterized by a multilobular architecture composed of uniform epithelioid cells embedded in a fibromyxoid matrix, often surrounded by a rim of metaplastic bone. While classic cases are readily identifiable, the tumor's histopathological heterogeneity can mimic a range of benign and malignant neoplasms, posing significant diagnostic challenges. Molecularly, most OFMTs harbor PHF1 rearrangements, commonly involving fusion partners such as EP400, MEAF6, or TFE3. This review underscores the importance of an integrated diagnostic approach- incorporating histopathological, immunohistochemical, and molecular data- to accurately classify OFMT and distinguish it from its mimics. Expanding awareness of its morphologic and molecular spectrum is essential for precise diagnosis, optimal patient management, and a deeper understanding of this enigmatic neoplasm.

Original Article

Correlations and prognostic impacts of tumor spread through airspaces in surgically resected non–small cell lung cancer: a retrospective study from Jordan: Ola Abu Al Karsaneh, Amani Al-Rousan, Sofian Al Shboul, Mohammed El-Sadoni, Anas Hayajneh, Moath Alrjoub, Sura Al-Rawabdeh, Tareq Saleh; J Pathol Transl Med. 2026;60(1):92-106. Published online January 9, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.15

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Abstract PDF Supplementary Material: Background
Spread through air spaces (STAS) has been identified as an invasion pattern in non–small cell lung cancer (NSCLC). This study evaluated the association between tumor STAS and various clinicopathological parameters of NSCLC, with emphasis on the prognostic role of STAS. Methods: We evaluated 96 cases of NSCLC for STAS. STAS-positive cases were graded according to the distance between the edge of the primary tumor and the furthest STAS, in millimeters, or the number of alveoli separating STAS from the tumor. Results: STAS was observed in 33 patients (34.4%). In 28 cases, STAS was located in airspaces >3 alveoli away from the primary tumor. In 18 cases, STAS was found in airspaces > 2.5 mm away from the edge of the primary tumor. Morphologically, 18 cases of STAS demonstrated a solid nest pattern, eight showed a micropapillary cluster pattern, and seven exhibited a single-cell pattern. In multivariate analysis, only high tumor grade (p = .001) was independently associated with STAS in NSCLC. The presence of STAS (p = .047), lymphovascular invasion (p = .001), positive surgical margin (p = .021), adenocarcinoma histology (p = .020), and postoperative therapy (p = .049) showed a statistically significant lower overall survival (OS). However, multivariate analyses showed that STAS is not an independent predictor of OS in NSCLC. In addition, STAS-positive cases with an extension of >2.5 mm had significantly lower disease-free survival (DFS) (p = .018). Conclusions: The findings demonstrated that STAS is independently associated with a higher tumor grade and appears to have an adverse impact on OS and DFS in the examined subpopulation.

Review Article

Solitary fibrous tumor: an updated review: Joon Hyuk Choi; J Pathol Transl Med. 2026;60(1):20-46. Published online December 29, 2025; DOI: https://doi.org/10.4132/jptm.2025.10.08

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Abstract PDF: Solitary fibrous tumor (SFT) is a fibroblastic neoplasm characterized by a branching, thin-walled dilated staghorn-shaped (hemangiopericytoma-like) vasculature and a NAB2::STAT6 gene fusion. SFTs can occur in almost any anatomical location, including superficial and deep soft tissues, visceral organs, and bone. They most commonly occur in extrapleural locations, equally affect both sexes, and are typically present in adults. Although metastasis is rare, SFTs frequently show local recurrence. The diagnosis of SFTs is difficult because of their broad histological and morphological overlap with other neoplasms. An accurate diagnosis is important for guiding disease management and prognosis. Despite advances in molecular diagnostics and therapeutic strategies, the biological complexity and unpredictable clinical behavior of SFTs present significant challenges. This review provides an updated overview of SFT, with a focus on its molecular genetics, histopathological features, and diagnostic considerations.

Original Articles

Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea: Hye-Ra Jung, Junyoung Shin, Chong Woo Yoo, Eun Na Kim, Cheol Lee, Kyeongmin Kim, Ho-chang Lee, Yonghee Lee, Ji Hye Kim, Soo Jin Jung, Yumin Chung, Joo Yeon Kim, Hye Eun Park, Tae Hoen Kim, Wonae Lee, Min-Sun Cho, Ran Hong, Yoon Jung Choi, Younghee Choi, Young Sub Lee, Sang-Ryung Lee, Myunghee Kang, Young Jin Seo, Seung-Sook Lee, Yoon-Jung Hwang, Hyun-Jung Kim; J Pathol Transl Med. 2025;59(6):444-452. Published online November 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.10.21

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Abstract PDF: Background
Human papillomavirus (HPV) independent cervical malignancies (HPV-IDCMs) have recently been classified by the World Health Organization (WHO) 5th edition. These malignancies have historically received limited attention due to their rarity and the potential for evasion of HPV-based screening.
Methods
We retrospectively reviewed 5,854 biopsy-confirmed cervical malignancies from 22 institutions over 3 years (July 2020–June 2023). Histologic classification followed the WHO guidelines. HPV independence was confirmed by dual negativity for p16 and HPV; discordant cases (p16-positive/HPV-negative) underwent additional HPV testing using paraffin-embedded tissue. Cytological results were matched sequentially to histological confirmation.
Results
The prevalence of HPV-IDCM was 4.4% (257/5,854) overall and was 3.6% (208/5,805 cases) among primary cervical malignancy. Patient age of HPV-IDCM was 29 to 89 years (median, 57.79). Its histologic subtypes included primary adenocarcinoma (n = 116), endometrial adenocarcinoma (n = 35), squamous cell carcinoma (n = 72), metastatic carcinoma (n = 14), carcinoma, not otherwise specified (n = 10), neuroendocrine carcinoma (n = 3), and others (n = 7). Among 155 cytology-histological matched cases, the overall and primary Pap test detection rates were 85.2% (132/155) and 83.2% (104/125), respectively. The interval between cytology and histologic confirmation extended up to 38 months.
Conclusions
HPV-IDCMs comprised 3.6% of primary cervical malignancies with a high detection rate via cytology (83.2%). These findings affirm the value of cytological screening, particularly in patients with limited screening history or at risk for HPV-independent lesions, and may guide future screening protocols.

Adenomatoid odontogenic tumor: clinicopathological analysis of 34 cases from Karachi, Pakistan: Summaya Zafar, Sehar Sulaiman, Madeeha Nisar, Poonum Khan, Nasir Ud Din; J Pathol Transl Med. 2025;59(6):390-397. Published online October 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.11

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Abstract PDF: Background
Adenomatoid odontogenic tumor (AOT) is a benign slow-growing neoplasm of odontogenic epithelial origin that is relatively uncommon. Only a few studies have described its histological features. Hence, we aimed to describe the clinicopathological features of AOT in a cohort of patients. Methods: AOT cases diagnosed between 2009 and 2024 were searched electronically. Glass slides were retrieved from archives and were reviewed by two pathologists to record the associated morphological features. Other data including patient demographics and tumor site were collected by reviewing histopathology reports. Results: The age of patients ranged from 9 to 44 years (mean, 17.7 years), and most were female (55.9%). The maxilla (44.1%) was the most common tumor site. Histologically, a predominantly solid growth pattern (n = 34) accompanied by ducts with a cuboidal/columnar epithelial lining (n = 31), eosinophilic secretions (n = 31), calcifications (n = 31), lattice work pattern (n = 30), and cystic areas (n = 20) were observed. Less frequent features included calcifying epithelial odontogenic tumor (CEOT)–like areas (n = 13), osteodentin (n = 6), association with impacted tooth (n = 3), mucin in tubules (n = 7), fibrocollagenous stroma (n = 6), mucin in ducts (n = 3) and ossifying fibroma-like areas (n = 6). The association of ducts with a cuboidal/columnar epithelial lining, lattice work pattern, calcifications, and eosinophilic secretions with gingival tumors was statistically significant (p ≤ .05). Additionally, tooth tumors were significantly associated with CEOT-like areas (p = .03). Conclusions: Our study confirms the trends in the clinicopathological features of AOT in previous case reports. Our results suggest that AOTs usually exhibit a predominantly solid pattern with duct-like spaces. Only a few cases with CEOT-like and ossifying fibroma-like areas were observed, similar to infrequent cases reported in the past.

Evaluation of potential prognostic significance of JUNB in human prostate cancer: a bioinformatic and histopathological study: Noha R. Noufal, Einas M. Yousef, Mohamed Taha; J Pathol Transl Med. 2025;59(5):291-305. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.06

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Abstract PDF Supplementary Material: Background
Prostate cancer is one of the most common malignancies in males worldwide. Serum prostate-specific antigen is a frequently employed biomarker in the diagnosis and risk stratification of prostate cancer; however, it is known for its low predictive accuracy for disease progression. New prognostic biomarkers are needed to distinguish aggressive prostate cancer from low-risk disease. This study aimed to identify and validate potential prognostic biomarkers of prostate cancer. Methods: Two prostate cancer datasets from the Gene Expression Omnibus were analyzed to identify differentially expressed genes between benign prostatic hyperplasia (BPH) and prostatic carcinoma. Immunohistochemistry was used to evaluate the JUNB proto-oncogene, a subunit of the AP-1 transcription factor (JUNB), in 70 prostate cancer patients and 10 BPH samples. Results: Our findings showed that JUNB was significantly enriched in prostate cancer-related pathways and biological processes. JUNB expression was considerably higher in prostatic adenocarcinoma patients than in BPH patients. Regarding JUNB expression in prostate cancer cases, lower levels of JUNB expression were associated with higher grades of prostatic adenocarcinoma. Lower JUNB expression was associated with a higher risk of prostatic adenocarcinoma progression and shorter overall survival. Conclusions: These results suggest that JUNB is a promising prognostic biomarker and a potential tumor suppressor in prostate cancer.

Review Article

Central nervous system tumors with BCOR internal tandem duplications: a systematic review of clinical, radiological, and pathological features in 69 cases: Ji Young Lee, Sung Sun Kim, Hee Jo Baek, Tae-Young Jung, Kyung-Sub Moon, Jae-Hyuk Lee, Kyung-Hwa Lee; J Pathol Transl Med. 2025;59(5):273-280. Published online September 1, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.23

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Abstract PDF Supplementary Material: Central nervous system tumors with BCL6 corepressor (BCOR) internal tandem duplications (ITDs) constitute a rare, recently characterized pediatric neoplasm with distinct molecular and histopathological features. To date, 69 cases have been documented in the literature, including our institutional case. These neoplasms predominantly occur in young children, with the cerebellum representing the most frequent anatomical location. Radiologically, these tumors present as large, well-circumscribed masses frequently demonstrating necrosis, hemorrhage, and heterogeneous enhancement. Histologically, they are characterized by a monomorphic cellular population featuring ependymoma-like perivascular pseudorosettes, myxoid stroma, and elevated mitotic activity. Immunohistochemically, these tumors exhibit sparse glial fibrillary acidic protein expression while consistently demonstrating positive staining for vimentin and CD56. The defining molecular hallmark is a heterozygous ITD within exon 15 of the BCOR gene, with insertions ranging from 9 to 42 amino acids in length. BCOR immunohistochemistry reveals nuclear positivity in 97.9% of examined cases, although this finding is not pathognomonic for BCOR ITDs. This comprehensive review synthesizes data from all published cases of this novel tumor entity, providing a detailed analysis of clinical presentation, neuroimaging findings, histopathological features with differential diagnostic considerations, therapeutic approaches, and prognostic outcomes.

Original Article

AMACR is a highly sensitive and specific immunohistochemical marker for diagnosing prostate cancer on biopsy: a systematic review and meta-analysis: Johannes Cansius Prihadi, Stevan Kristian Lionardi, Nicolas Daniel Widjanarko, Steven Alvianto, Fransiskus Xaverius Rinaldi, Archie Fontana Iskandar; J Pathol Transl Med. 2025;59(4):235-248. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.16

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Abstract PDF Supplementary Material

Background
Alpha-methylacyl-CoA racemase (AMACR) is the preferred biomarker for distinguishing malignant from benign glands in prostate biopsies, showing high sensitivity and specificity for prostate cancer. A meta-analysis of immunohistochemistry (IHC) for AMACR is essential to further assess its diagnostic accuracy across diverse sample sources. Methods: A systematic search of databases including MEDLINE, ScienceDirect, ProQuest, Google Scholar, and the Cochrane Library was performed, focusing on studies of AMACR to diagnose prostate cancer, particularly in biopsy samples analyzed through IHC over the last 20 years. Quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, followed by a meta-analysis of regions and subgroups to calculate summary estimates of diagnostic test accuracy. Results: In the final analysis, 37 studies, with a pooled size of 5,898 samples, were included from the examination of 94 full-text papers. Among them, 27 studies with similar sample sources and testing methodologies underwent meta-analysis, yielding a combined sensitivity estimate of 0.90 (95% confidence interval [CI], 0.86 to 0.93) and specificity of 0.91 (95% CI, 0.83 to 0.95), both with significant heterogeneity (p < .01). The region beneath the hierarchical summary receiver operating characteristic curve was 0.95 (95% CI, 0.93 to 0.97), positive likelihood ratio was 9.6 (95% CI, 5.3 to 17.4), negative likelihood ratio was 0.11 (95% CI, 0.08 to 0.15), and diagnostic odds ratio was 88 (95% CI, 42 to 181). Conclusions: Our meta-analysis findings substantiate AMACR as a highly accurate tool for diagnosing prostate cancer, specifically in biopsy samples, via immunohistochemical staining. Further studies involving diverse samples are needed to enhance our understanding of the AMACR diagnostic accuracy in a range of clinical settings.

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Citations to this article as recorded by

Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics
Jessica M. Logan, Victoria Malone, John J. O’Leary, Doug A. Brooks
International Journal of Molecular Sciences.2025; 26(24): 11786. CrossRef

Case Study

Acquired aberrant partial CD3 expression in recurrent Epstein-Barr virus–negative solitary plasmacytoma of tonsil: Chenchen Niu, Dong Ren, Truc Tran, Ashley Gamayo, Sherif Rezk, Xiaohui Zhao; J Pathol Transl Med. 2025;59(4):262-268. Published online May 15, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.17

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Abstract PDF: The aberrant expression of specific T-cell maker CD3 in B-cell neoplasms can be a potential diagnostic pitfall leading to a misclassification of cell lineage. Here, we report a case of recurrent solitary plasmacytoma with new aberrant expression of CD3. The neoplastic plasma cells of the recurrent tumor were kappa restricted, positive for CD138, MUM1, negative for CD20, cyclin D1, and Epstein-Barr virus. CD79a was positive in majority of the tumor cells, except for a small focus which was strongly positive for CD3, but negative for other T-cell markers (CD2, CD5, CD7, CD4, and CD8) and CD56. The neoplastic plasma cells of the original tumor were negative for CD3. To the best of our knowledge, only one case of recurrent plasmacytoma with aberrant expression of CD3 has been published, which revealed disease progression in the recurrence. However, we did not observe morphologic evidence of disease progression in our case.

Original Article

Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis: Van Hung Pham, Quoc Thang Pham, Minh Nguyen, Hoa Nhat Ngo, Thao Thi Thu Luu, Nha Dao Thi Minh, Trâm Đặng, Anh Tu Thai, Hoang Anh Vu, Dat Quoc Ngo; J Pathol Transl Med. 2025;59(2):125-132. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.01.18

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Abstract PDF Supplementary Material: Background
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

Case Study

Mucocele of the rectal stump: mucinous cystic neoplasm with low-grade dysplasia simulating low-grade appendiceal mucinous neoplasm: Hasan Basri Aydin, Maria Faraz, A. David Chismark, Haiyan Qiu, Hwajeong Lee; J Pathol Transl Med. 2025;59(2):139-146. Published online February 26, 2025; DOI: https://doi.org/10.4132/jptm.2024.12.27

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Abstract PDF: Mucoceles, commonly observed in the appendix, are mucin-filled, dilated structures arising from a range of etiologies. Cases associated with dysplastic or neoplastic epithelium can rupture and disseminate within the abdominopelvic cavity. Similar lesions in other parts of the colon are exceedingly rare, with only 16 colonic mucoceles having been reported. The first case of a colonic mucinous neoplasm with dysplasia resembling a low-grade appendiceal mucinous neoplasm involving rectal stump was described in 2016. Here, we present the second such case arising in the rectal stump, identified in a 44-year-old male with extensive surgical history. Microscopic examination revealed low-grade dysplastic epithelium lining the cyst and mucin dissecting into the stroma, without evidence of rupture or extramural mucin. The patient was followed for 16 months without recurrence or peritoneal disease. The exact etiology and outcome of these rare lesions remain unknown, requiring close follow-up.

Original Article

Association study of TYMS gene expression with TYMS and ENOSF1 genetic variants in neoadjuvant chemotherapy response of gastric cancer: Khadijeh Arjmandi, Iman Salahshourifar, Shiva Irani, Fereshteh Ameli, Mohsen Esfandbod; J Pathol Transl Med. 2025;59(2):105-114. Published online February 25, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.05

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Abstract PDF

Background
The present research was designed to study the associations between genetic variants of TYMS and ENOSF1 genes with TYMS and ENOSF1 gene expression in neoadjuvant chemotherapy response among patients with gastric cancer. Methods: Formalin-embedded and paraffin-fixed matched tumor and normal gastric cancer tissue samples from patients who received neoadjuvant 5-fluorouracil (5-FU) treatment were obtained. DNA and RNA were extracted for all samples. A 28-bp variable number tandem repeat (VNTR) at the 5' untranslated region of TYMS gene and rs2612091 and rs2741171 variants in the ENOSF1 gene were genotyped for normal tissue samples. The real-time polymerase chain reaction method was used to study the expression of ENOSF1 and TYMS genes in both normal and tumor tissues. Data were analyzed using REST 2000 and SPSS ver. 26.0 software programs. Results: A significant association between TYMS 2R3R VNTR genotypes and 5-FU therapy was found (p = .032). The 3R3R and 2R2R genotypes were significantly associated with increased and decreased survival time, respectively (p = .003). The 3R3R genotype was significantly associated with TYMS overexpression (p < .001). Moreover, a significant association was found between the rs2612091 genotype and treatment outcome (p = .017). Conclusions: This study highlights the impact of TYMS and ENOSF1 genes as predictive indicators for survival and response to 5-FU–based neoadjuvant chemotherapy in gastric cancer patients.

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Innovative biomaterial strategies for mitigating radiotherapy toxicity: multidimensional mechanistic interventions of nano-microscale materials and hydrogels
Yifan Liu, Fengdi Jiang, Jie Song, Huaijin Qiao, Junlong Dai, Hao Bai, Shuyu Zhang
Coordination Chemistry Reviews.2026; 549: 217313. CrossRef
Mebendazole impairs the expression and function of enzymes in nucleotide metabolism pathways, leading to Selective Cytotoxicity, Cell Cycle Arrest, and Damage to Cell Morphology in Gastric Cancer
Emerson Lucena da Silva, Felipe Pantoja Mesquita, Pedro Victor da Rocha Lima, José Hélio de Araújo Filho, Francisco Laio de Oliveira, Ana Beatriz da Lima, Pedro Filho Noronha Souza, Raquel Carvalho Montenegro
Chemico-Biological Interactions.2026; 430: 111973. CrossRef

Review

Cervical intraepithelial neoplasia and cervical cytology in pregnancy: Ji-Young Kim, Jeong Yun Shim; J Pathol Transl Med. 2024;58(6):283-290. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.17

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Abstract PDF

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

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HPV in Pregnancy: Implications for Screening, Vaccination, and Maternal–Fetal Health
Suman Kumar, Swati, Swati Salila, Akanksha Raj, Pratima Gupta, Neha Sharad, Nidhi Chaudhary
Journal of Pregnancy.2026;[Epub] CrossRef
The significance of biological samples from pregnant women in cervical intraepithelial neoplasia
Xue Mi, Maharjan Rashmi, Zangyu Pan, Di Wu, Jinwei Miao
Frontiers in Medicine.2025;[Epub] CrossRef
Oncologic and pregnancy outcomes of cervical high-grade intraepithelial lesions and delivery mode
Olga P. Matylevich, Ilya A. Tarasau, Sviatlana Y. Shelkovich, Aliaksandr F. Martsinkevich
Academia Oncology.2025;[Epub] CrossRef

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.

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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

Review

Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes: Agnes Stephanie Harahap, Chan Kwon Jung; J Pathol Transl Med. 2024;58(6):265-282. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.11

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Abstract PDF

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

Citations

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Oncocytic Thyroid Tumours With Pathogenic FLCN Mutations Mimic Oncocytic Papillary Thyroid Carcinoma on Fine‐Needle Aspiration
Adeel M. Ashraf, Faisal Hassan, Adrian A. Dawkins, Julie C. Dueber, Derek B. Allison, Thèrése J. Bocklage
Cytopathology.2026; 37(1): 108. CrossRef
Using a new type of visible light-based emission fluorescence microscope to identify the benign and malignant nature of thyroid tissue during the surgical process: Analysis of diagnostic results
Yu Miao, Liu Xiaowei, Li Muyang, Gao Jian, Chen Lu
Photodiagnosis and Photodynamic Therapy.2026; 57: 105324. CrossRef
Clinical Behavior of Aggressive Variants of Papillary Thyroid Carcinoma: A Retrospective Case–Control Study
Jovan Ilic, Nikola Slijepcevic, Katarina Tausanovic, Bozidar Odalovic, Goran Zoric, Marija Milinkovic, Branislav Rovcanin, Milan Jovanovic, Matija Buzejic, Duska Vucen, Boban Stepanovic, Sara Ivanis, Milan Parezanovic, Milan Marinkovic, Vladan Zivaljevic
Cancers.2026; 18(2): 345. CrossRef
Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shin Je Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyo
International Journal of Thyroidology.2025; 18(1): 30. CrossRef
Structure-based molecular screening and dynamic simulation of phytocompounds targeting VEGFR-2: a novel therapeutic approach for papillary thyroid carcinoma
Shuai Wang, Lingqian Zhang, Wenjun Zhang, Xiong Zeng, Jie Mei, Weidong Xiao, Lijie Yang
Frontiers in Pharmacology.2025;[Epub] CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyon
Endocrinology and Metabolism.2025; 40(3): 307. CrossRef
A Case of Warthin-Like Variant of Papillary Thyroid Cancer
Amy Chow, Israa Laklouk
Cureus.2025;[Epub] CrossRef
Propensity score-matched analysis of the ‘2+2’ parathyroid strategy in total thyroidectomy with central neck dissection
Hao Gong, Simei Yao, Tianyuchen Jiang, Yi Yang, Yuhan Jiang, Zhujuan Wu, Anping Su
Frontiers in Endocrinology.2025;[Epub] CrossRef
Cytological Findings in Pediatric Thoracic Tumors: A Review of Diagnostic Insights and Pitfalls
Parikshaa Gupta, Pranab Dey
Acta Cytologica.2025; : 1. CrossRef

Original Articles

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers: Ji-Ae Lee, Hye Eun Park, Hye-Yeong Jin, Lingyan Jin, Seung Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Jung Ho Kim, Gyeong Hoon Kang; J Pathol Transl Med. 2025;59(1):50-59. Published online October 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.26

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Abstract PDF Supplementary Material: Background
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

International Academy of Cytology standardized reporting of breast fine-needle aspiration cytology with cyto-histopathological correlation of breast carcinoma: Shweta Pai; J Pathol Transl Med. 2024;58(5):241-248. Published online September 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.14

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Abstract PDF: Background
The International Academy of Cytology (IAC) has developed a standardized approach for reporting the findings of breast fine-needle aspiration cytology (FNAC). Accordingly, there are five chief categories of breast lesions, C1 (insufficient material), C2 (benign), C3 (atypical), C4 (suspicious), and C5 (malignant). The prognostication and management of breast carcinoma can be performed readily on the basis of this classification system. The aim of this study was to classify various breast lesions into one of the above-named categories and to further grade the C5 lesions specifically using the Robinson system. The latter grades were then correlated with modified Scarff-Bloom-Richardson (SBR) grades.
Methods
This retrospective study was undertaken in the pathology department of a hospital located in the urban part of the city of Bangalore. All FNAC procedures performed on breast lumps spanning the year 2020 were included in the study.
Results
A total of 205 breast lesions was classified according to the IAC guidelines into C1 (6 cases, 2.9%), C2 (151 cases, 73.7%), C3 (13 cases, 6.3%), C4 (5 cases, 2.5%), and C5 (30 cases, 14.6%) groups. The C5 cases were further graded using Robinson’s system. The latter showed a significant correlation with the SBR system (concordance=83.3%, Spearman correlation=0.746, Kendall’s tau-b=0.736, kappa=0.661, standard error=0.095, p≤.001).
Conclusions
A standardized approach for FNAC reporting of breast lesions, as advocated for by the IAC, improves the quality and clarity of the reports and assures diagnostic reproducibility on a global scale. Further, the cytological grading of C5 lesions provides reliable cyto-prognostic scores that can help assess a tumor’s aggressiveness and predict its histological grade.

Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study: Agnes Stephanie Harahap, Mutiah Mutmainnah, Maria Francisca Ham, Dina Khoirunnisa, Abdillah Hasbi Assadyk, Husni Cangara, Aswiyanti Asri, Diah Prabawati Retnani, Fairuz Quzwain, Hasrayati Agustina, Hermawan Istiadi, Indri Windarti, Krisna Murti, Muhammad Takbir, Ni Made Mahastuti, Nila Kurniasari, Nungki Anggorowati, Pamela Abineno, Yulita Pundewi Setyorini, Kennichi Kakudo; J Pathol Transl Med. 2024;58(6):299-309. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.25; Correction in: J Pathol Transl Med 2025;59(3):201

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Abstract PDF Supplementary Material

Background
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

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Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef

Case Study

Colorectal cancer with a germline BRCA1 variant inherited paternally: a case report: Kyoung Min Kim, Min Ro Lee, Ae Ri Ahn, Myoung Ja Chung; J Pathol Transl Med. 2024;58(6):341-345. Published online September 5, 2024; DOI: https://doi.org/10.4132/jptm.2024.08.14

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Abstract PDF

BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient’s father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

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Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations
Ravi Patel, Ganesh Kumar, Yash Shah, Dushyant Singh Dahiya, Sumant Inamdar
ACG Case Reports Journal.2026;[Epub] CrossRef

Original Articles

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer: Jinahn Jeong, Deokhoon Kim, Yeon-Mi Ryu, Ja-Min Park, Sun Young Yoon, Bokyung Ahn, Gi Hwan Kim, Se Un Jeong, Hyun-Jung Sung, Yong Il Lee, Sang-Yeob Kim, Yong Mee Cho; J Pathol Transl Med. 2024;58(5):229-240. Published online August 9, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.13

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Abstract PDF Supplementary Material

Background
Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable.
Methods
To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed.
Results
Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%.
Conclusions
These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Citations

Citations to this article as recorded by

Computational pathology in bladder cancer: A scoping review
Michael Superdock, Sara E Wobker, Iain Carmicheal, William Y Kim
Bladder Cancer.2026;[Epub] CrossRef
Pre-analytical Best Practices for RNA Sequencing from Small Biopsies and Cytologic Specimens
Gloria Hopkins Sura, Kelly B. Engel, Sarah R. Greytak, Sandra M. Gaston, Kelsey Dillehay McKillip, Abhilasha Rao, Ping Guan, W. Fraser Symmans, Rachael Clark, Maria Arcila, Sayak Ghatak, Karol Bomsztyk, Lokesh Agrawal
Molecular Diagnosis & Therapy.2026;[Epub] CrossRef

Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning: Agnes Stephanie Harahap, Chan Kwon Jung; J Pathol Transl Med. 2024;58(5):205-213. Published online July 24, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.24

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Abstract PDF

Background
While fine needle aspiration cytology (FNAC) plays an essential role in the screening of thyroid nodules, core needle biopsy (CNB) acts as an alternative method to address FNAC limitations. However, diagnosing thyroid CNB samples can be challenging due to variations in background and levels of experience. Effective training is indispensable to mitigate this challenge. We aim to evaluate the impact of an educational program on improving the accuracy of CNB diagnostics.
Methods
The 2-week observational program included a host mentor pathologist with extensive experience and a visiting pathologist. The CNB classification by The Practice Guidelines Committee of the Korean Thyroid Association was used for the report. Two rounds of reviewing the case were carried out, and the level of agreement between the reviewers was analyzed.
Results
The first-round assessment showed a concordance between two pathologists for 247 thyroid CNB specimens by 84.2%, with a kappa coefficient of 0.74 (indicating substantial agreement). This finding was attributed to the discordance in the use of categories III and V. After peer learning, the two pathologists evaluated 30 new cases, which showed an overall improvement in the level of agreement. The percentage of agreement between pathologists on thyroid CNB diagnosis was 86.7%, as measured by kappa coefficient of 0.80.
Conclusions
This educational program, consisting of guided mentorship and peer learning, can substantially enhance the diagnostic accuracy of thyroid CNB. It is useful in promoting consistent diagnostic standards and contributes to the ongoing development of global pathology practices.

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Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie Harahap, Maria Francisca Ham, Retno Asti Werdhani, Erwin Danil Julian, Rafi Ilmansyah, Chloe Indira Arfelita Mangunkusumso, Tri Juli Edi Tarigan
Journal of Pathology and Translational Medicine.2025; 59(3): 149. CrossRef

Liquid-based cytology features of pancreatic acinar cell carcinoma: comparison with other non-ductal neoplasms of the pancreas: Minji Kwon, Seung-Mo Hong, Kyoungbun Lee, Haeryoung Kim; J Pathol Transl Med. 2024;58(4):182-190. Published online July 9, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.25

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Abstract PDF: Background
Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm, which shares many cytomorphological features with other non-ductal pancreatic neoplasms such as pancreatic neuroendocrine neoplasm (PanNEN) and solid-pseudopapillary neoplasm (SPN). Due to the relative rarity of these tumors, pathologists are less familiar with the cytological features, especially on liquid-based cytology (LBC) which has been relatively recently introduced for endoscopic ultrasound-guided fine needle aspiration specimens.
Methods
We evaluated the detailed cytological features of 15 histologically confirmed ACC (7 conventional smears [CS], 8 LBC), and compared them with the LBC features of SPN (n = 9) and PanNEN (n = 9).
Results
Compared with CS, LBCs of ACC demonstrated significantly less bloody background. All ACCs demonstrated prominent nucleoli and macronucleoli on LBC. On comparison with the LBC features of SPN and PanNEN, most ACCs demonstrated a necrotic background with apoptotic debris while PanNEN and SPN did not show these features. Acinar structures were predominantly observed in ACC, while frequent pseudopapillary structures were seen only in SPN. Prominent nucleoli and macronucleoli were only seen in ACC.
Conclusions
ACC had characteristic cytological features that could be observed on LBC preparations, such as high cellularity, necrotic/apoptotic background, nuclear tangles, acinar arrangement of cells, and macronucleoli. These findings also help distinguish ACC from PanNEN and SPN on LBC. It is important to be familiar with these features, as an accurate diagnosis on endoscopic ultrasound–guided fine needle aspiration cytology would have impact on the management of the patient.

Case Study

Intravascular schwannoma as an extremely unusual cause of vein obstruction: a case report: Luis Miguel Chinchilla-Tábora, Beatriz Segovia Blázquez, José María Sayagués, Marta Rodríguez González, Joaquín González-Rivero, José Antonio Muñoz León, Andrea Beatriz Jiménez Pérez, Idalia González Morais, Diego Bueno-Sacristán, María Dolores Ludeña; J Pathol Transl Med. 2024;58(5):249-254. Published online July 3, 2024; DOI: https://doi.org/10.4132/jptm.2024.05.15

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Abstract PDF: The blood vessel lumen is an extremely rare location for a benign peripheral nerve sheath tumor like schwannoma. Less than 10 cases have been previously reported. In this report, we present a case of a 68-year-old woman who had a soft tissue nodule at the posterior calf of her left leg during a physical examination. Pathological examination was performed after complete surgical excision. The patient underwent follow-up for 12 months after surgery without evidence of recurrence or any other complication. This is the first case of intravascular schwannoma reported as a cause of vein obstruction. Microscopically, the tumor was composed of Schwann spindle cells that were immunoreactive for S100 protein and SOX10. This tumor was surrounded by a well-defined vascular smooth muscle wall. Prospective series are required to improve the knowledge on the underlying mechanisms of intravascular schwannoma development.

Original Article

The importance of histomorphological features and ERG expression in the diagnosis of malignancy in cases with atypical small acinar proliferation: Gizem Teoman, Ayten Livaoglu, Hatice Kucuk, Afs ¸ın Rahman Murtezaoglu; J Pathol Transl Med. 2024;58(3):134-140. Published online May 14, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.18

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Abstract PDF: Background
Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy.
Methods
Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically.
Results
Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002).
Conclusions
Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

Review

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee; J Pathol Transl Med. 2024;58(3):103-116. Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15

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Abstract PDF Supplementary Material

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

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Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J. M. Sullman, Nahid Eskandari
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D.R. Castillo, M. Guo, P. Shah, M. Hazeltin, D. Tai, F. Al-Manaseer, S. Mlamba, D. Perez, S. Yeremian, S. Guzman, R. Mannan, C. Crook, C. Lau, N. Tawar, G. Brar, M. Raoof, Y. Woo, S.P. Wu, D. Li
ESMO Gastrointestinal Oncology.2025; 10: 100261. CrossRef
Best Practice PD-L1 Staining and Interpretation in Gastric Cancer Using PD-L1 IHC PharmDx 22C3 and PD-L1 IHC PharmDx 28-8 Assays, with Reference to Common Issues and Solutions
Soomin Ahn, Inwoo Hwang, Yuyeon Kim, Somin Lee, Yunjoo Cho, So Young Kang, Deok Geun Kim, Jeeyun Lee, Kyoung-Mee Kim
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Tomoya Nakanishi, Motohiro Imano, Masashi Kohda, Hiroaki Kato, Naoko Kounami, Atsushi Yamada, Masuhiro Terada, Yoko Hiraki, Osamu Shiraishi, Atsushi Yasuda, Masayuki Shinkai, Takushi Yasuda
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V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
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Original Articles

TRPS1 expression in non-melanocytic cutaneous neoplasms: an immunohistochemical analysis of 200 cases: Yi A. Liu, Phyu P. Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L. Curry, Carlos A. Torres-Cabala, Doina Ivan, Victor G. Prieto, Qingqing Ding, Woo Cheal Cho; J Pathol Transl Med. 2024;58(2):72-80. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.23

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Background
Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.
Methods
Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit anti-human antibody.
Results
TRPS1 expression was present in almost all cases of SCC (94%), with a median H-score of 200, while it was either absent or only focally present in most BCCs (90%), with a median H-score of 5. The difference between BCCs and SCCs in H-score was significant (p < .001). All MCCs (100%) lacked TRPS1 expression. TRPS1 expression was frequently seen in most adnexal neoplasms, benign and malignant, in variable intensity and proportion but was consistently absent in apocrine carcinomas. All endocrine mucin-producing sweat gland carcinomas (EMPSGCs) (100%, 6/6) showed diffuse and strong TRPS1 immunoreactivity, with a median H-score of 300, which was significantly different (p < .001) than that of BCCs.
Conclusions
Our study shows that TRPS1 may be an effective discriminatory marker for BCCs and SCCs. It also has a role in distinguishing BCCs from EMPSGCs.

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Metastatic Vulvar Paget's Disease Presenting in a Supraclavicular Lymph Node: A Diagnostic Challenge on Fine Needle Aspiration Cytology
Thiri Htoo Aung, Neha Seth, Anam Khan, Kasturi Das
Diagnostic Cytopathology.2026;[Epub] CrossRef
The evolving role of TRPS1 in dermatopathology: insights from the past 4 years
Mokhtar H. Abdelhammed, Woo Cheal Cho
Journal of Pathology and Translational Medicine.2026; 60(2): 129. CrossRef
Trichorhinophalangeal syndrome type 1 (TRPS1) in breast pathology: diagnostic utility and pitfalls
Atif Ali Hashmi, Edi Brogi, Hannah Y. Wen
Diagnostic Pathology.2025;[Epub] CrossRef
Refining NTRK Fusion Detection in Papillary Thyroid Carcinoma Through Pan-TRK Immunohistochemistry and Histopathologic Features
Hyun Lee, Sue Youn Kim, Ji Min Park, Seung-Hyun Jung, Ozgur Mete, Chan Kwon Jung
Endocrine Pathology.2025;[Epub] CrossRef
Endocrine mucin-producing sweat gland carcinoma: Case report and literature review
Nan Guo, Zhenlin Fan, Yitong Chen, Qian Li, Limin Guo
European Journal of Ophthalmology.2025;[Epub] CrossRef
Updates on utility of immunohistochemistry in diagnosis of metastatic breast cancer
Hongxia Sun, Aysegul A. Sahin, Qingqing Ding
Human Pathology.2025; 162: 105821. CrossRef
Primary Cutaneous NUT Adnexal Carcinoma With BRD4::NUTM1 Fusion: A 19-Year Follow-Up
Elsayed Ibrahim, Richard K. Yang, Maria A. Gubbiotti, Victor G. Prieto, Woo Cheal Cho
The American Journal of Dermatopathology.2025; 47(9): 731. CrossRef
Primary mucinous carcinoma of the skin with co-expression of TRPS1 and GATA3: a case report
Liling Song, Ning Zhu, Lei Jiang, Dong Gao, Guohua Yu
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Diagnostic Algorithm for Secondary Extramammary Paget Disease from Institutional Cases and Literature Review
Salin Kiratikanon, Ayaka Fukui, Masahiro Hirata, Jakob M. T. Moran, Masakazu Fujimoto, Mai P. Hoang
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TRPS1 Expression Is Frequently Seen in a Subset of Cutaneous Mesenchymal Neoplasms and Tumors of Uncertain Differentiation: A Potential Diagnostic Pitfall
Moon Joo Kim, Yi A. Liu, Yunyi Wang, Jing Ning, Woo Cheal Cho
Dermatopathology.2024; 11(3): 200. CrossRef
TRPS1 expression in MPNST is correlated with PRC2 inactivation and loss of H3K27me3
Rossana Lazcano, Davis R. Ingram, Gauri Panse, Alexander J. Lazar, Wei-Lien Wang, Jeffrey M. Cloutier
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Mouaz Alsawas, Fiorinda F. Muhaj, Phyu P. Aung, Priyadharsini Nagarajan, Woo Cheal Cho
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A Comprehensive Review of TRPS1 as a Diagnostic Immunohistochemical Marker for Primary Breast Carcinoma: Latest Insights and Diagnostic Pitfalls
Antonia-Carmen Georgescu, Tiberiu-Augustin Georgescu, Simona-Alina Duca-Barbu, Lucian Gheorghe Pop, Daniela Oana Toader, Nicolae Suciu, Dragos Cretoiu
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BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy: Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim; J Pathol Transl Med. 2023;57(6):323-331. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.22

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Abstract PDF Supplementary Material

Background
Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations.
Methods
To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype.
Results
Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype.
Conclusions
In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

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Youngeun Yoo, Jihun Kim, In Hye Song
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Predictive value of homologous recombination-related gene mutations in survival outcomes of first-line nivolumab plus chemotherapy for gastric cancer
Yuna Lee, Hyung-Don Kim, Sun Young Lee, Hyungeun Lee, Jaewon Hyung, Meesun Moon, Jinho Shin, Young Soo Park, Tae Won Kim, Min-Hee Ryu
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Review

The Asian Thyroid Working Group, from 2017 to 2023: Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai; J Pathol Transl Med. 2023;57(6):289-304. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.04

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Abstract PDF Supplementary Material

The Asian Thyroid Working Group was founded in 2017 at the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea. This group activity aims to characterize Asian thyroid nodule practice and establish strict diagnostic criteria for thyroid carcinomas, a reporting system for thyroid fine needle aspiration cytology without the aid of gene panel tests, and new clinical guidelines appropriate to conservative Asian thyroid nodule practice based on scientific evidence obtained from Asian patient cohorts. Asian thyroid nodule practice is usually designed for patient-centered clinical practice, which is based on the Hippocratic Oath, “First do not harm patients,” and an oriental filial piety “Do not harm one’s own body because it is a precious gift from parents,” which is remote from defensive medical practice in the West where physicians, including pathologists, suffer from severe malpractice climate. Furthermore, Asian practice emphasizes the importance of resource management in navigating the overdiagnosis of low-risk thyroid carcinomas. This article summarizes the Asian Thyroid Working Group activities in the past 7 years, from 2017 to 2023, highlighting the diversity of thyroid nodule practice between Asia and the West and the background reasons why Asian clinicians and pathologists modified Western systems significantly.

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Letter: “High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis” by Fung et al
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Thyroid Nodules with Nuclear Atypia of Undetermined Significance (AUS-Nuclear) Hold a Two-Times-Higher Risk of Malignancy than AUS-Other Nodules Regardless of EU-TIRADS Class of the Nodule or Borderline Tumor Interpretation
Dorota Słowińska-Klencka, Bożena Popowicz, Joanna Duda-Szymańska, Mariusz Klencki
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Response to Kakudo et al.: “High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis”
Man Him Matrix Fung, Ching Tang, Gin Wai Kwok, Tin Ho Chan, Yan Luk, David Tak Wai Lui, Carlos King Ho Wong, Brian Hung Hin Lang
Thyroid®.2025; 35(5): 597. CrossRef
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Sarah C. Brennan, Matti L. Gild, Venessa Tsang
Clinical Thyroidology®.2025; 37(5): 165. CrossRef
Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid
Rita Luis, Balamurugan Thirunavukkarasu, Deepali Jain, Sule Canberk
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Are we ready to bridge classification systems? A comprehensive review of different reporting systems in thyroid cytology
Esther Diana Rossi, Liron Pantanowitz
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Aggressive Types of Malignant Thyroid Neoplasms
Maria Boudina, Eleana Zisimopoulou, Persefoni Xirou, Alexandra Chrisoulidou
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Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia
Hee Young Na, Miyoko Higuchi, Shinya Satoh, Kaori Kameyama, Chan Kwon Jung, Su-Jin Shin, Shipra Agarwal, Jen-Fan Hang, Yun Zhu, Zhiyan Liu, Andrey Bychkov, Kennichi Kakudo, So Yeon Park
Journal of Pathology and Translational Medicine.2024; 58(6): 331. CrossRef

Original Article

Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation: Jun Sang Shin, Tae-Gyu Kim, Young Hwa Kim, So Yeong Eom, So Hyun Park, Dong Hyun Lee, Tae Jun Park, Soon Sang Park, Jang-Hee Kim; J Pathol Transl Med. 2023;57(6):305-314. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.09

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Abstract PDF Supplementary Material

Background
Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.
Methods
Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.
Results
Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.
Conclusions
Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

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Huajie Mao, Wanning Liu, Yuanyuan Su, Yuxuan Ma, Xiaodi Zhao, Yuanyuan Lu
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Senescence, Aging and Disease Throughout the Gastrointestinal System
Sofia Ferreira-Gonzalez, Tomonori Matsumoto, Eiji Hara, Stuart J. Forbes
Gastroenterology.2025; 169(7): 1357. CrossRef
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Aging and disease.2024;[Epub] CrossRef
Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE)
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Case Studies

Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors: Chankyung Kim, Yang-Guk Chung, Chan Kwon Jung; J Pathol Transl Med. 2023;57(5):278-283. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.07.13

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Abstract PDF

Schwannomas are benign, slow-growing peripheral nerve sheath tumors commonly occurring in the head, neck, and flexor regions of the extremities. Although most schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. Reporting pathologists should be aware that schwannomas can exhibit a broad spectrum of morphological patterns. Clinical and radiological examinations can show correlation and should be performed, in conjunction with ancillary tests, when appropriate. Furthermore, deferring a definitive diagnosis until excision may be necessary for small biopsy specimens and frozen sections. This report underscores these challenges through examination of two unique schwannoma cases, one predominantly cellular and the other myxoid, both of which posed significant challenges in histological interpretation.

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Oral and maxillofacial schwannoma (OMSCH): An institutional study of 102 patients
Lingli Huang, Wenya Zhu, Qicheng Ye, Shengwen Liu, Hao Lu, Wenjun Yang, Wanlin Xu
Journal of Stomatology Oral and Maxillofacial Surgery.2026; 127(3): 102678. CrossRef
Plexiform Schwannoma Over the Anterior Chest Wall: A Clinicopathological Review
Debojyoti Sasmal, Saswata Barenya, Hinglaj Saha, Pankaj Kumar Halder
Amrita Journal of Medicine.2025; 21(2): 95. CrossRef
Giant Retroperitoneal Schwannoma: Case Report and Review of the Literature
Magdalena Alexieva, Evgeni V Mekov, Silvia Ivanova, Alexandrina Vlahova, Georgi Yankov
Cureus.2025;[Epub] CrossRef
Breast schwannoma: review of entity and differential diagnosis
Sandra Ixchel Sanchez, Ashley Cimino-Mathews
Journal of Pathology and Translational Medicine.2025; 59(6): 353. CrossRef

Hepatic small vessel neoplasm: not totally benign, not yet malignant: Madison Miranda, David Howell, Tony El Jabbour; J Pathol Transl Med. 2023;57(5):273-277. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.19

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Abstract PDF

Hepatic small vessel neoplasm (HSVN) is a rare vascular tumor with few reports in the literature. While imaging findings may show characteristic enhancement patterns, limited available literature may not reveal the full potential for image-based diagnosis. Histologically, HSVN mimics other entities, though certain morphologic and immunohistochemical findings provide clues for diagnosis. However, HSVN still provides diagnostic challenges, especially on core biopsies with limited material for morphologic and molecular evaluation. While current recommendations are surgical resection and close observation, the long-term course of the tumor is unknown. We report a case of HSVN in a liver with additional feature of organized lymphoid aggregates necessitating additional hematopathology consultation and workup to rule out concurrent entities.

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Reviews

Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy: Chan Kwon Jung; J Pathol Transl Med. 2023;57(4):208-216. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.20

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Abstract PDF

As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.

Citations

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Evaluation and Management of Thyroid Nodules: A Joint Consensus Statement From the British Thyroid Association (BTA), British Association of Endocrine and Thyroid Surgeons (BAETS) and Collaborating Bodies
Ram Moorthy, Saba P. Balasubramanian, Kate Farnell, Mairead Kelly, Gitta Madani, Mufaddal Moonim, Carla Moran, Julia Priestley, Michael Stechman, Emma Watts, Kristien Boelaert
Clinical Endocrinology.2026;[Epub] CrossRef
Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital
Agnes Stephanie Harahap, Maria Francisca Ham, Retno Asti Werdhani, Erwin Danil Julian, Rafi Ilmansyah, Chloe Indira Arfelita Mangunkusumso, Tri Juli Edi Tarigan
Journal of Pathology and Translational Medicine.2025; 59(3): 149. CrossRef
Risk Stratification of Thyroid Nodules Diagnosed as Follicular Neoplasm on Core Needle Biopsy
Byeong-Joo Noh, Won Jun Kim, Jin Yub Kim, Ha Young Kim, Jong Cheol Lee, Myoung Sook Shim, Yong Jin Song, Kwang Hyun Yoon, In-Hye Jung, Hyo Sang Lee, Wooyul Paik, Dong Gyu Na
Endocrinology and Metabolism.2025; 40(4): 610. CrossRef
Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules
Heeseung Sohn, Kennichi Kakudo, Chan Kwon Jung
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A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules
Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na
Endocrinology and Metabolism.2024; 39(1): 61. CrossRef
The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy
Hye Hyeon Moon, Sae Rom Chung, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Jeong Hyun Lee, Jung Hwan Baek
Endocrinology and Metabolism.2024; 39(2): 300. CrossRef
Core needle biopsy for thyroid nodules assessment-a new horizon?
David D Dolidze, Serghei Covantsev, Grigorii M Chechenin, Natalia V Pichugina, Anastasia V Bedina, Anna Bumbu
World Journal of Clinical Oncology.2024; 15(5): 580. CrossRef
Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(5): 205. CrossRef
A simplified four-tier classification for thyroid core needle biopsy
M. Paja, J. L. Del Cura, R. Zabala, I. Korta, Mª T. Gutiérrez, A. Expósito, A. Ugalde
Journal of Endocrinological Investigation.2024; 48(4): 895. CrossRef

A stepwise approach to fine needle aspiration cytology of lymph nodes: Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee; J Pathol Transl Med. 2023;57(4):196-207. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.12

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Abstract PDF Supplementary Material

The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Citations

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From smear to diagnosis: the impact of ancillary techniques in lymph node fine-needle cytology
Elisabetta Maffei, Giuseppe Di Motta, Angela D’Ardia, Riccardo Ruotolo, Valentina Giudice, Alessandro Caputo, Pio Zeppa
Journal of the American Society of Cytopathology.2026; 15(2): 120. CrossRef
The Critical Role of Ancillary Testing in Fine-Needle Aspiration of Lymph Nodes, Thymus, and Spleen
Diana A. Baptista, Helena Barroca, Fernando C. Schmitt
Acta Cytologica.2026; : 1. CrossRef
Primary cutaneous squamous cell carcinoma of the neck mimicking tuberculous lymphadenitis
Lin Zhang, Zhenjiang Zhang, Huichun Ji
Discover Oncology.2026;[Epub] CrossRef
Development and Validation of Explainable Artificial Intelligence System for Automatic Diagnosis of Cervical Lymphadenopathy From Ultrasound Images
Ming Xu, Yubiao Yue, Zhenzhang Li, Yinhong Li, Guoying Li, Haihua Liang, Di Liu, Xiaohong Xu, Mohamadreza (Mohammad) Khosravi
International Journal of Intelligent Systems.2025;[Epub] CrossRef
Application of the Sydney system for classification and reporting lymph node cytopathology: a retrospective analysis at a tertiary centre
Ashok Teja Kummari, Pramod Kumar Pamu, Krishna Kiran Ganna, Param Jyothi, Sadashivudu
International Journal of Research in Medical Sciences.2025;[Epub] CrossRef
Diagnostic approach to FNA biopsy of cystic lesions of the head and neck
Stefen Andrianus, Olivia Leung, Zubair Baloch
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Applicability of Fine-Needle Aspiration Biopsy of Lymph Nodes Using WHO Reporting System: Comparison between Pediatric and Adult Brazilian Populations
Leonardo Fávaro Ficoto, Deolino João Camilo Júnior, Gustavo Resende Nora, Vitor Bonetti Valente, Daniel Galera Bernabé, José Cândido Caldeira Xavier-Júnior
Acta Cytologica.2025; : 1. CrossRef
Intraoperative cytological assessment of sentinel lymph nodes in gynecologic cancer: diagnostic accuracy and limitations
O. V. Pankova, S. V. Vtorushin, M. V. Klimova, D. S. Pismenny, M. O. Ochirov, L. A. Kolomiets, V. M. Perelmuter
Siberian journal of oncology.2025; 24(5): 72. CrossRef
Cytopathologic Diagnosis of Non-Neoplastic Inflammatory Disorders of Lymphoid Organs
Joy M. Hoang, Havva Gokce Terzioglu, Matthew L. Kleinjan, Tatjana Antic, Nalini Gupta, Manish Rohilla, Radhika Srinivasan, Arvind Rajwanshi, Eva M. Wojcik, Güliz A. Barkan, Mark A. Russell, Swati Mehrotra
Acta Cytologica.2025; : 1. CrossRef
Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma
Joshua J. X. Li, Gary M. Tse
Cytopathology.2024; 35(2): 218. CrossRef
Response to comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
Journal of Pathology and Translational Medicine.2024; 58(1): 43. CrossRef
Comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Elisabetta Maffei, Valeria Ciliberti, Pio Zeppa, Alessandro Caputo
Journal of Pathology and Translational Medicine.2024; 58(1): 40. CrossRef
The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center
Iyad Hassan, Lina Hassan, Nahed Balalaa, Mohamad Askar, Hussa Alshehhi, Mohamad Almarzooqi
Diagnostics.2024; 14(10): 1026. CrossRef
Efficiency of Fine-Needle Aspiration (FNA) in Relation to Tru-Cut Biopsy of Lateral Neck Swellings
Mohammed S Al Olaimat, Fahad S Al Qooz, Zaid R Alzoubi, Elham M Alsharaiah, Ali S Al Murdif, Mohammad O Alanazi
Cureus.2024;[Epub] CrossRef
Pitfalls in the Cytological Diagnosis of Nodal Hodgkin Lymphoma
Uma Handa, Rasheeda Mohamedali, Rajpal Singh Punia, Simrandeep Singh, Ranjeev Bhagat, Phiza Aggarwal, Manveen Kaur
Diagnostic Cytopathology.2024; 52(12): 715. CrossRef
Rapid 3D imaging at cellular resolution for digital cytopathology with a multi-camera array scanner (MCAS)
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npj Imaging.2024;[Epub] CrossRef

Case Study

Metastatic choroidal melanoma in the breast: a case report and review of the literature: Loay Abudalu, Vinisha Malhotra, Nabila Nasir, Sami Titi; J Pathol Transl Med. 2023;57(4):238-241. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.07

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Abstract PDF: The breast is an unusual site for metastases, accounting for less than 2% of malignant breast lesions but include those from malignant melanomas, carcinomas, sarcomas, and lymphomas from various organs. We diagnosed a very rare case of metastatic choroidal melanoma for a 67-year-old female who presented with a right breast lump and who had been previously diagnosed with choroidal melanoma-monosomy 3 in 2017. To the best of our knowledge, only five such cases have been published so far, with one in a male patient.

Original Articles

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Abstract PDF Supplementary Material

Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Citations

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Management of squamous cell carcinoma of unknown primary in the head and neck: current evidence-based diagnostic and treatment strategies
Marcel Kloppenburg, Matthias Santer, Lukas Schmutzler, Felix Johnson, Benedikt Hofauer, Teresa Steinbichler
memo - Magazine of European Medical Oncology.2026; 19(1): 45. CrossRef
Differenzierung von benignen und malignen Halszysten – eine diagnostische Herausforderung
Christina Sauter, Matthias Sand, Karim Plath, Michaela Maria Plath
Laryngo-Rhino-Otologie.2025; 104(05): 296. CrossRef
Unlocking the Hidden: Advancing Imaging Techniques in Diagnosing Cancers of Unknown Primary in the Head and Neck Region
Daniela Messineo, Filippo Valentini, Giovanni Francesco Niccolini, Federica Zoccali, Francesca Ripari, Enrico Marotta, Marcello Caratozzolo, Pasquale Frisina
Applied Sciences.2025; 15(4): 2194. CrossRef
Characterization of undifferentiated carcinoma of the salivary gland: clinicopathological and immunohistochemical analyses in comparison with lymphoepithelial carcinoma
Sangjoon Choi, Gyuheon Choi, Hee Jin Lee, Joon Seon Song, Yoon Se Lee, Seung-Ho Choi, Kyung-Ja Cho
Journal of Pathology and Translational Medicine.2025; 59(6): 361. CrossRef
Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef

Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer: Sujin Park, Junsik Kim, Woncheol Jang, Kyoung-Mee Kim, Kee-Taek Jang; J Pathol Transl Med. 2023;57(2):113-122. Published online March 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.02.01

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Abstract PDF

Background
Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression.
Methods
We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually.
Results
The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression.
Conclusions
This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef
Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification
Lin Zheng, Yusi Yang, Jie Liu, Tianliang Zhao, Xin Zhang, Lihua Chen
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Review

A standardized pathology report for gastric cancer: 2nd edition: Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho; J Pathol Transl Med. 2023;57(1):1-27. Published online January 15, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.23

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Abstract PDF Supplementary Material

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

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Shidi Miao, Hexiang Dong, Jinyang Feng, Yuyang Jiang, Mengzhuo Sun, Zengyao Liu, Qiujun Wang, Xuemei Ding, Ruitao Wang
International Journal of Medical Informatics.2026; 212: 106348. CrossRef
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Original Article

The proteomic landscape shows oncologic relevance in cystitis glandularis: Jun Yong Kim, Dohyun Han, Hyeyoon Kim, Minsun Jung, Han Suk Ryu; J Pathol Transl Med. 2023;57(1):67-74. Published online December 22, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.24

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Abstract PDF

Background
The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear.
Methods
We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation.
Results
We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG.
Conclusions
Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

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Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma
Jun Yong Kim, Jae Seok Lee, Dohyun Han, Ilias P. Nikas, Hyeyoon Kim, Minsun Jung, Han Suk Ryu
Heliyon.2024; 10(15): e35475. CrossRef
KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis
Minsun Jung, Bohyun Kim, Jae Seok Lee, Jun Yong Kim, Dohyun Han, Kwangsoo Kim, Sunah Yang, Eun Na Kim, Hyeyooon Kim, Ilias P. Nikas, Sohyeon Yang, Kyung Chul Moon, Hyebin Lee, Han Suk Ryu
Pathobiology.2024; : 1. CrossRef

Reviews

Biomarker testing of cytology specimens in personalized medicine for lung cancer patients: Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2022;56(6):326-333. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.17

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Abstract PDF

Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.

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Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions
Yuesong Wu, Rou Xue, Xiangwen Luo, Jiangnan Liao, Zongbo Zhang, Jinhai Deng, Teng Liu, Xin Li, Zhe‐Sheng Chen, Mingzhu Yin
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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: 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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318 Download
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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
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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
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Original Articles

Diagnostic distribution and pitfalls of glandular abnormalities in cervical cytology: a 25-year single-center study: Jung-A Sung, Ilias P. Nikas, Haeryoung Kim, Han Suk Ryu, Cheol Lee; J Pathol Transl Med. 2022;56(6):354-360. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.09.05

8,986 View
156 Download
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Abstract PDF

Background
Detection of glandular abnormalities in Papanicolaou (Pap) tests is challenging. This study aimed to review our institute’s experience interpreting such abnormalities, assess cytohistologic concordance, and identify cytomorphologic features associated with malignancy in follow-up histology.
Methods
Patients with cytologically-detected glandular lesions identified in our pathology records from 1995 to 2020 were included in this study.
Results
Of the 683,197 Pap tests performed, 985 (0.144%) exhibited glandular abnormalities, 657 of which had tissue follow-up available. One hundred eighty-eight cases were cytologically interpreted as adenocarcinoma and histologically diagnosed as malignant tumors of various origins. There were 213 cases reported as atypical glandular cells (AGC) and nine cases as adenocarcinoma in cytology, yet they were found to be benign in follow-up histology. In addition, 48 cases diagnosed with AGC and six with adenocarcinoma cytology were found to have cervical squamous lesions in follow-up histology, including four squamous cell carcinomas. Among the cytomorphological features examined, nuclear membrane irregularity, three-dimensional clusters, single-cell pattern, and presence of mitoses were associated with malignant histology in follow-up.
Conclusions
This study showed our institute’s experience detecting glandular abnormalities in cervical cytology over a 25-year period, revealing the difficulty of this task. Nonetheless, the present study indicates that several cytological findings such as membrane irregularity, three-dimensional clusters, single-cell pattern, and evidence of proliferation could help distinguishing malignancy from a benign lesion.

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“Atypical Glandular Cells” on Cervical Cytology: Correlation Between Glandular Cell Component Volume and Histological Follow‐Up
Havva Gokce Terzioglu, Alessa Aragao, Julieta E. Barroeta
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Expertise in Gynecological Pathology Impacts Diagnosis of Atypical Glandular Cell Category in Cervical Cytology
Havva Gökce Terzioglu, Alessa Aragao, Julieta E. Barroeta
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Fatih Mehmet Kaya, Şafak Ersöz, Cihan Comba, Ömer Demir
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Prognostic and clinicopathological significance of Fusobacterium nucleatum in colorectal cancer: a systemic review and meta-analysis: Younghoon Kim, Nam Yun Cho, Gyeong Hoon Kang; J Pathol Transl Med. 2022;56(3):144-151. Published online May 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.13

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147 Download
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Abstract PDF Supplementary Material

Background
Fusobacterium nucleatum has been identified to promote tumor progression in colorectal cancer (CRC). However, association between F. nucleatum and prognostic or clinicopathological features has been diverse among studies, which could be affected by type of biospecimen (formalin-fixed paraffin-embedded or fresh frozen [FF]).
Methods
Articles were systemically reviewed for studies that included the correlation between F. nucleatum and prognosis or clinicopathological features in CRC.
Results
Ten articles, eight studies with survival-related features involving 3,199 patients and nine studies with clinical features involving 2,655 patients, were eligible for the meta-analysis. Overall survival, disease-free survival, and cancer-specific survival were all associated with worse prognosis in F. nucleatum–high patients (p<.05). In subgroup analysis, only studies with FF tissues retained prognostic significance with F. nucleatum. In meta-analysis of clinicopathological variables, F. nucleatum level was associated with location within colon, pT category, MLH1 hypermethylation, microsatellite instability status, and BRAF mutation regardless of type of biospecimen. However, lymph node metastasis and KRAS mutation was only associated with F. nucleatum level in FF-based studies.
Conclusions
In conclusion, type of biospecimen could affect the role of F. nucleatum as a biomarker associated with clinicopathological features and prognosis.

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