Journal of Pathology and Translational Medicine

Review Article

The evolving role of TRPS1 in dermatopathology: insights from the past 4 years: Mokhtar H. Abdelhammed, Woo Cheal Cho; Received September 11, 2025 Accepted November 25, 2025 Published online January 29, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.25 [Epub ahead of print]

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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 Articles

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.

Clinicopathological and molecular mechanisms of CLDN18.2 in gastric cancer aggressiveness: a high-risk population study with multi-omics profiling: Hengquan Wu, Mei Li, Gang Wang, Peiqing Liao, Peng Zhang, Luxi Yang, Yumin Li, Tao Liu, Wenting He; J Pathol Transl Med. 2026;60(1):47-57. Published online January 5, 2026; DOI: https://doi.org/10.4132/jptm.2025.09.11

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Abstract PDF Supplementary Material: Background
The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis.
Methods
A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms.
Results
CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis.
Conclusions
CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

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; J Pathol Transl Med. 2025;59(6):361-370. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.07

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Abstract PDF: Background
This study aimed to reclassify a subset of poorly differentiated salivary gland carcinoma that do not conform to any entities of the current World Health Organization (WHO) classification into the category of undifferentiated carcinoma (UDC) because they lack specific histologic differentiation or immunophenotype. Methods: Cases of salivary gland carcinomas from Asan Medical Center (2002–2020) that did not fit any existing WHO classification criteria and were diagnosed as poorly differentiated carcinoma, high-grade carcinoma, or UDC, were retrospectively reviewed. Immunohistochemical (IHC) staining for p40, neuroendocrine markers, androgen receptor (AR), and gross cystic disease fluid protein 15 (GCDFP-15) and Epstein-Barr virus (EBV) in situ hybridization (ISH) were performed. Clinical data were collected from the electronic medical records. Results: Six salivary gland carcinomas did not align with any specific entities and lacked distinct differentiation. Two of six cases displayed lymphoepithelial carcinoma (LEC)-like morphology but were negative or showed negligible immunoreactivity for p40 and EBV ISH, distinguishing them from LEC of the salivary gland. Two cases showed strong AR positivity, suggesting a potential overlap with salivary duct carcinoma (SDC) but lacked classic SDC morphologies and GCDFP-15 expression. No cases expressed neuroendocrine markers. Conclusions: This study proposes reclassifying these poorly differentiated or high-grade salivary gland carcinomas as UDC based on their indeterminate differentiation and IHC profiles. This may lead to a clearer diagnostic category and enhance our understanding of these high-grade tumors.

Unraveling the crucial role of CCL3 in nasopharyngeal carcinoma: bioinformatics and immunohistochemical insights: Xiaopeng Guo, Zhen Sun, Ya Liang, Aoshuang Chang, Junjun Ling, Houyu Zhao, Xianlu Zhuo; J Pathol Transl Med. 2025;59(5):281-290. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.23

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Abstract PDF: Background
C-C motif chemokine ligand 3 (CCL3) is a crucial chemokine that plays a fundamental role in the immune microenvironment and is closely linked to the development of various cancers. Despite its importance, there is limited research regarding the expression and function of CCL3 in nasopharyngeal carcinoma (NPC). Therefore, this study seeks to examine the expression of CCL3 and assess its clinical significance in NPC using bioinformatics analysis and experiments. Methods: The bioinformatics approach was employed to assess the expression and function of CCL3 in NPC. Subsequently, protein expression of CCL3 was detected in an NPC cohort using immunohistochemistry based on a tissue microarray. The relationship between CCL3 expression and clinical features was then investigated. Results: A total of 20 CCL3-related genes and 14 possible target genes were identified through bioinformatics analysis, many of which play crucial roles in pathways such as chemokine signaling pathway and transcriptional misregulation in cancer signaling pathways. CCL3 was found to be associated with drug resistance and various immune cell infiltrations. In NPC, CCL3 expression was significantly higher than normal controls, and high expression of CCL3 correlated with cervical lymph node metastasis, tumor recurrence, advanced clinical stage, and poor prognosis. Conclusions: CCL3 may be a key gene in the initiation and progression of NPC. It has the potential to serve as both a diagnostic biomarker and a therapeutic target for NPC.

The Automatable Activity–Based Approach to Complexity Unit Scoring as a task-specific model approach to monetizing outcomes of pathology artificial intelligence solutions: Stavros Pantelakos, Martha Nifora, Georgios Agrogiannis; J Pathol Transl Med. 2025;59(4):225-234. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.15

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Abstract PDF: Background
Cost-containment policies are increasingly affecting decision-making in healthcare. In this context, the need for monetization of digital health interventions has been recently emphasized. Previous studies have attempted to extrapolate cost containment in conjunction with the implementation of digital pathology solutions mostly on the basis of operational cost savings or diagnostic error reduction. However, no study has attempted to link a wider spectrum of potential diagnostic tasks performed by artificial intelligence algorithms to financial figures.
Methods
Herein, we employ a workload measurement tool for the purpose of monetizing particular outcomes associated with the implementation of a pathology artificial intelligence solution. A hundred and thirty-two prostate core biopsy samples were encoded for workload using the Automatable Activity–Based Approach to Complexity Unit Scoring. Subsequently, avoided workload, full-time equivalent gains, and corresponding cost savings were calculated assuming full clinical deployment of a well-developed prostate cancer screening tool.
Results
For a fixed percentage of negative cores and a steady yearly workload of prostate core biopsies, the estimated total avoided workload amounted to 4,291 complexity units per year, with an average avoidance of 16.25 complexity units per ascension number. The calculated full-time equivalent gains were 0.12, whereas projected cost savings were as high as €2,402.34 per year or €0.55 per complexity unit, which in turn would yield an average of €8.93 per ascension number.
Conclusions
The Automatable Activity–Based Approach to Complexity Unit Scoring appears to be a suitable economic evaluation tool for assessing the possible implementation of task-specific artificial intelligence solutions in a given histopathology laboratory or group of laboratories, considering it is a task-specific workload measurement tool per design.

Case Study

Cytological features of atypical adenomatous hyperplasia and adenocarcinoma in situ of the lung: a case report: Misa Takahashi, Seiya Homma, Chisato Setoguchi, Yoko Umezawa, Atsuhiko Sakamoto; J Pathol Transl Med. 2025;59(3):195-200. Published online May 9, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.09

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Abstract PDF: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) are generally treated as different lesions, depending on the differences in lesion size and histological findings. However, these differences are not absolute; thus, AAH and AIS are often difficult to distinguish. Moreover, whether AAH and AIS can be regarded as different lesions remains unknown because cytological specimens, especially those of AAH, are rare. In this study, we examined these uncommon cytological specimens and compared the cytological findings between AAH and AIS. We observed many common cytological features with no obvious differences between AAH and AIS. These findings suggest that these two distinct lesions can be grouped into a single category. Therefore, we propose creating a new cytological category.

Original Articles

Primary Merkel cell carcinoma of the salivary gland: a clinicopathologic study of four cases with a review of literature: Gyuheon Choi, Joon Seon Song, Hee Jin Lee, Gi Hwan Kim, Young Ho Jung, Yoon Se Lee, Kyung-Ja Cho; J Pathol Transl Med. 2025;59(3):171-179. Published online April 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.25

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Abstract PDF

Background
Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases.
Methods
Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis.
Results
All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases.
Conclusions
Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Citations

Citations to this article as recorded by

Parotid intranodal metastasis of Merkel cell carcinoma: a rare case report
Tong Gao, Dengshun Wang, Hongwei Yu, Yu’e Wang, Haibin Lu
BMC Oral Health.2025;[Epub] CrossRef

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 Articles

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.

Citations

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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

Categorizing high-grade serous ovarian carcinoma into clinically relevant subgroups using deep learning–based histomic clusters: Byungsoo Ahn, Eunhyang Park; J Pathol Transl Med. 2025;59(2):91-104. Published online February 18, 2025; DOI: https://doi.org/10.4132/jptm.2024.10.23

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Abstract PDF Supplementary Material

Background
High-grade serous ovarian carcinoma (HGSC) exhibits significant heterogeneity, posing challenges for effective clinical categorization. Understanding the histomorphological diversity within HGSC could lead to improved prognostic stratification and personalized treatment approaches. Methods: We applied the Histomic Atlases of Variation Of Cancers model to whole slide images from The Cancer Genome Atlas dataset for ovarian cancer. Histologically distinct tumor clones were grouped into common histomic clusters. Principal component analysis and K-means clustering classified HGSC samples into three groups: highly differentiated (HD), intermediately differentiated (ID), and lowly differentiated (LD). Results: HD tumors showed diverse patterns, lower densities, and stronger eosin staining. ID tumors had intermediate densities and balanced staining, while LD tumors were dense, patternless, and strongly hematoxylin-stained. RNA sequencing revealed distinct patterns in mitochondrial oxidative phosphorylation and energy metabolism, with upregulation in the HD, downregulation in the LD, and the ID positioned in between. Survival analysis showed significantly lower overall survival for the LD compared to the HD and ID, underscoring the critical role of mitochondrial dynamics and energy metabolism in HGSC progression. Conclusions: Deep learning-based histologic analysis effectively stratifies HGSC into clinically relevant prognostic groups, highlighting the role of mitochondrial dynamics and energy metabolism in disease progression. This method offers a novel approach to HGSC categorization.

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Learning Disabilities in the 21st Century: Integrating Neuroscience, Education, and Technology for Better Outcomes
Syed Mohammed Basheeruddin Asdaq, Ahmad H. Alhowail, Syed Imam Rabbani, Naira Nayeem, Syed Mohammed Emaduddin Asdaq, Faiqa Nausheen
SAGE Open.2025;[Epub] CrossRef

PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma: Ranran Feng, Yilin Guo, Meilin Chen, Ziying Tian, Yijun Liu, Su Jiang, Jieyu Zhou, Qingluan Liu, Xiayu Li, Wei Xiong, Lei Shi, Songqing Fan, Guiyuan Li, Wenling Zhang; J Pathol Transl Med. 2025;59(1):68-83. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.27

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Abstract PDF Supplementary Material

Background
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

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The Potential Role of SP-G and PLUNC in Tumor Pathogenesis and Wound Healing in the Human Larynx
Aurelius Scheer, Lars Bräuer, Markus Eckstein, Heinrich Iro, Friedrich Paulsen, Fabian Garreis, Martin Schicht, Antoniu-Oreste Gostian
Biomedicines.2025; 13(5): 1240. CrossRef
Role of DEAD/DEAH-box helicases in immunity, infection and cancers
Rex Devasahayam Arokia Balaya, Saptami Kanekar, Shreya Kumar, Richard K. Kandasamy
Cell Communication and Signaling.2025;[Epub] CrossRef
CHIP modulates Wnt/β-catenin signalling in colorectal cancer through proteasomal degradation of DDX17
Sunny Kumar, Sayani Ghosh, Malini Basu, Mrinal K. Ghosh
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2025; 1872(8): 120049. CrossRef

Review

Next step of molecular pathology: next-generation sequencing in cytology: Ricella Souza da Silva, Fernando Schmitt; J Pathol Transl Med. 2024;58(6):291-298. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.22

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Abstract PDF

The evolving landscape of precision oncology underscores the pivotal shift from morphological diagnosis to treatment decisions driven by molecular profiling. Recent guidelines from the European Society for Medical Oncology recomend the use of next-generation sequencing (NGS) across a broader range of cancers, reflecting its superior efficiency and clinical value. NGS not only updates oncology testing by offering quicker, sample-friendly, and sensitive analysis but also reduces the need for multiple individual tests. Cytology samples, often obtained through less invasive methods, can yield high-quality genetic material suitable for molecular analysis. This article focuses on optimizing the use of cytology samples in NGS, and outlines their potential benefits in identifying actionable molecular alterations for targeted therapies across various solid tumors. It also addresses the need for validation studies and the strategies to incorporate or combine different types of samples into routine clinical practice. Integrating cytological and liquid biopsies into routine clinical practice, alongside conventional tissue biopsies, offers a comprehensive approach to tumor genotyping, early disease detection, and monitoring of therapeutic responses across various solid tumor types. For comprehensive biomarker characterization, all patient specimens, although limited, is always valuable.

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The World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology: Part 1 – Lymph Node
Immacolata Cozzolino, Mats Ehinger, Maria Calaminici, Andrea Ronchi, Mousa A. Al-Abbadi, Helena Barroca, Beata Bode-Lesniewska, David F. Chhieng, Ruth L. Katz, Oscar Lin, L. Jeffrey Medeiros, Martha Bishop Pitman, Arvind Rajwanshi, Fernando C. Schmitt, Ph
Acta Cytologica.2025; : 1. CrossRef
The impact of cytological preparation techniques on RNA quality: A comparative study on smear samples
Cisel Aydin Mericoz, Gulsum Caylak, Elif Sevin Sanioglu, Zeynep Seçil Satilmis, Ayse Humeyra Dur Karasayar, Ibrahim Kulac
Cancer Cytopathology.2025;[Epub] CrossRef
Reimagining cytopathology in the molecular era: Integration or fragmentation?
Sumanta Das, R. Naveen Kumar, Biswajit Dey, Pranjal Kalita
Cytojournal.2025; 22: 94. CrossRef

Original Articles

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

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

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Abstract PDF Supplementary Material

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

Citations

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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

Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets: Jeong Hwan Park, Su-Jin Shin, Hyun-Jung Kim, Sohee Oh, Yong Mee Cho; J Pathol Transl Med. 2024;58(6):321-330. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.31

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Abstract PDF

Background
Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms
Methods
We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets.
Results
We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063).
Conclusions
Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

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Tissue-Based Biomarkers Important for Prognostication and Management of Genitourinary Tumors, Including Surrogate Markers of Genomic Alterations
Leonie Beauchamp, Shreeya Indulkar, Eric Erak, Mohammad Salimian, Andres Matoso
Surgical Pathology Clinics.2025; 18(1): 175. CrossRef
Papillary renal neoplasm with reverse polarity: a case report and literature review
Diego Gonzalez, Kris Kokoneshi, Sam Kwon, Ryan Thomas Mathews, Ryan Michael Antar, Maher Ali, Abiye Kassa, Michael Whalen
Frontiers in Oncology.2025;[Epub] 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.

Original Article

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

Concurrent intestinal plasmablastic lymphoma and diffuse large B-cell lymphoma with a clonal relationship: a case report and literature review: Nao Imuta, Kosuke Miyai, Motohiro Tsuchiya, Mariko Saito, Takehiro Sone, Shinichi Kobayashi, Sho Ogata, Fumihiko Kimura, Susumu Matsukuma; J Pathol Transl Med. 2024;58(4):191-197. Published online June 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.05.14

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Abstract PDF: Herein, we report a case of plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL) that occurred concurrently in the large intestine. An 84-year-old female presented with a palpable rectal tumor and ileocecal tumor observed on imaging analyses. Endoscopic biopsy of both lesions revealed lymphomatous round cells. Hartmann’s operation and ileocecal resection were performed for regional control. The ileocecal lesion consisted of a proliferation of CD20/CD79a-positive lymphoid cells, indicative of DLBCL. In contrast, the rectal tumor showed proliferation of atypical cells with pleomorphic nuclei and abundant amphophilic cytoplasm, with immunohistochemical findings of CD38/CD79a/MUM1/MYC (+) and CD20/CD3/CD138/PAX5 (–). Tumor cells were positive for Epstein-Barr virus– encoded RNA based on in situ hybridization and MYC rearrangement in fluorescence in situ hybridization analysis. These findings indicated the rectal tumor was most likely a PBL. Sequencing analysis for immunoglobulin heavy variable genes indicated a common B-cell origin of the two sets of lymphoma cells. This case report and literature review provide new insights into PBL tumorigenesis.

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

Exploring histological predictive biomarkers for immune checkpoint inhibitor therapy response in non–small cell lung cancer: Uiju Cho, Soyoung Im, Hyung Soon Park; J Pathol Transl Med. 2024;58(2):49-58. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.31

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Abstract PDF

Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

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Machine learning methods for histopathological image analysis: Updates in 2024
Daisuke Komura, Mieko Ochi, Shumpei Ishikawa
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Mohammad Pirouzbakht, Soroosh Hamzeh, Hamed Soleimani Samarkhazan
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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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Abstract PDF Supplementary Material

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
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Trichorhinophalangeal syndrome type 1 (TRPS1) in breast pathology: diagnostic utility and pitfalls
Atif Ali Hashmi, Edi Brogi, Hannah Y. Wen
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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
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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
Human Pathology.2024; 151: 105632. CrossRef
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Mouaz Alsawas, Fiorinda F. Muhaj, Phyu P. Aung, Priyadharsini Nagarajan, Woo Cheal Cho
The American Journal of Dermatopathology.2024; 46(12): 871. CrossRef
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Antonia-Carmen Georgescu, Tiberiu-Augustin Georgescu, Simona-Alina Duca-Barbu, Lucian Gheorghe Pop, Daniela Oana Toader, Nicolae Suciu, Dragos Cretoiu
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Expression of TRPS1 in Metastatic Tumors of the Skin: An Immunohistochemical Study of 72 Cases
Kassiani Boulogeorgou, Christos Topalidis, Triantafyllia Koletsa, Georgia Karayannopoulou, Jean Kanitakis
Dermatopathology.2024; 11(4): 293. CrossRef

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

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Abstract PDF

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

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Carbonic Anhydrase 12 as a Novel Prognostic Biomarker and Therapeutic Target for High‐Risk Follicular Thyroid Carcinoma
Masashi Tanida, Tsuyoshi Takashima, Shinichiro Tahara, Masaharu Kohara, Haruka Kanai, Masami Suzuki, Motoyuki Suzuki, Mitsuyoshi Hirokawa, Ayana Suzuki, Shinya Sato, Daisuke Okuzaki, Satoshi Nojima, Takahiro Matsui, Hidenori Inohara, Eiichi Morii
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Chaerim Song, Hye-Ji Park, Man S. Kim
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Review

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-Kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; J Pathol Transl Med. 2024;58(4):147-164. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.01

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Abstract PDF

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Apport de la génomique dans la prise en charge des cancers
Étienne Rouleau, Lucie Karayan-Tapon, Marie-Dominique Galibert, Alexandre Harlé, Isabelle Soubeyran
Revue Francophone des Laboratoires.2025; 2025(568): 67. CrossRef
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Moon Nyeo Park, Jinwon Choi, Rosy Iara Maciel de Azambuja Ribeiro, Domenico V. Delfino, Seong-Gyu Ko, Bonglee Kim
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Case Study

A rare goblet cell adenocarcinoma arising from Barrett’s esophagus: the first reported case in the esophagus: Chi Eun Oh, Sung Eun Kim, Sun-Ju Oh; J Pathol Transl Med. 2024;58(2):81-86. Published online January 8, 2024; DOI: https://doi.org/10.4132/jptm.2023.12.26

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Abstract PDF: Goblet cell adenocarcinoma (GCA) is a rare and distinctive amphicrine tumor comprised of goblet-like mucinous cells and neuroendocrine cells. It is believed to originate from pluripotent stem cells located at the base of crypts. GCA predominantly arises from the appendix, with a few reported cases in extra-appendiceal locations such as the colorectum, small intestine, and stomach. In this case report, we present a unique instance of a 64-year-old male who initially received a diagnosis of neuroendocrine carcinoma in the distal esophagus based on biopsy but, following resection, was subsequently re-diagnosed with GCA arising from Barrett’s esophagus.

Original Article

Elevated expression of Axin2 in intestinal metaplasia and gastric cancers: Dong Hui Lee, In Ho Jeong, Bogun Jang; J Pathol Transl Med. 2023;57(6):315-322. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.12

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Abstract PDF

Background
The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies.
Methods
Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined.
Results
Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001).
Conclusions
Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.

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A review of potential mechanisms and treatments of gastric intestinal metaplasia
Yueyao Wu, Kehan Zhang, Yichao Zheng, Haifeng Jin
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Hyun Lee, Sue Youn Kim, Ji Min Park, Seung-Hyun Jung, Ozgur Mete, Chan Kwon Jung
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AXIN2 variants, tooth agenesis, and cancer risk: a systematic review
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Case Study

EWSR1 rearranged primary renal myoepithelial carcinoma: a diagnostic conundrum: Nilay Nishith, Zachariah Chowdhury; J Pathol Transl Med. 2023;57(5):284-288. Published online September 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.08.08

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Abstract PDF

Primary renal myoepithelial carcinoma is an exceedingly rare neoplasm with an aggressive phenotype and Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement in a small fraction of cases. In addition to its rarity, the diagnosis can be challenging for the pathologist due to morphologic heterogeneity, particularly on the biopsy specimen. At times, immunohistochemistry may be indecisive; therefore, molecular studies should be undertaken for clinching the diagnosis. We aim to illustrate a case of primary myoepithelial carcinoma of the kidney with EWSR1-rearrangement in a 67-year-old male patient who presented with right supraclavicular mass, which was clinically diagnosed as carcinoma of an unknown primary. An elaborate immunohistochemical work-up aided by fluorescent in-situ hybridization allowed us to reach a conclusive diagnosis. This unusual case report advocates that one should be aware of the histological mimickers and begin with broad differential diagnoses alongside sporadic ones and then narrow them down with appropriate ancillary studies.

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Primary Ewing Sarcoma of the Kidney
João Lobo, Huiying He, Raheel Ahmed, Bassel Zein-Sabatto, Thomas Winokur, Shi Wei, Shuko Harada, Jesse K. McKenney, Jonathan L. Myles, Jane K. Nguyen, Christopher G. Przybycin, Sean R. Williamson, Cristina Magi-Galluzzi, Reza Alaghehbandan
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Original Article

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study: Seokhyeon Lee, Bohyun Kim, Minsun Jung, Kyung Chul Moon; J Pathol Transl Med. 2023;57(4):232-237. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.17

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Abstract PDF

Background
Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size.
Methods
We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression.
Results
High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC.
Conclusions
Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

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Loss of Aquaporin-1 in Tumor Cells Fosters Intrahepatic Cholangiocarcinoma Progression
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Case Study

Intrathyroidal metastasis of tonsillar squamous cell carcinoma masquerading as a primary thyroid tumor: Jai-Hyang Go; J Pathol Transl Med. 2023;57(4):242-245. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.16

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Abstract PDF

Intrathyroidal metastasis of tonsillar squamous cell carcinoma is rare. To date, only six cases have been reported in the literature. This case was unusual and presented with thyromegaly before the diagnosis of the primary tumor. A 55-year-old male patient was suspected to have a primary thyroid tumor with nodal metastasis. The thyroid gland was diffusely enlarged, with no discernible mass. Histologically, the thyroid parenchyma revealed extensive endolymphatic tumor emboli, which were positive for p40 and p16 in a background of chronic lymphocytic thyroiditis. Positron emission tomography–computed tomography revealed hypermetabolic activity in the right tonsillar region. Tonsillar biopsy revealed human papillomavirus–positive squamous cell carcinoma. The present case is the first reported case of intrathyroidal metastasis of tonsillar squamous cell carcinoma with an initial clinical presentation of thyroid enlargement before the primary tumor of tonsillar cancer was diagnosed.

Citations

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Metastasis to Thyroid from Recurrent Head and Neck Squamous Cell Carcinoma: A Case Series and Review of Literature
Avneet Kaur, Rohit Nayyar, Harit Kumar Chaturvedi, Akshat Malik
Indian Journal of Surgical Oncology.2025; 16(1): 122. CrossRef
Metastatic oropharyngeal squamous cell carcinoma to the thyroid: A case report and review of literature
Hannah Walker, Jed Speers, Milena Fabry, Sameep Kadakia
American Journal of Otolaryngology.2024; 45(4): 104306. CrossRef

Original Articles

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma: Joon Seon Song, Yeseul Kim, Yoon-Se Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):158-165. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.03.13

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Abstract PDF

Background
The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA).
Methods
Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody.
Results
Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression.
Conclusions
Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Citations

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Pleomorphic Adenoma with Epithelial Atypia, Apocrine Metaplasia, and/or In situ/Intracapsular Salivary Duct Carcinoma Are Indolent Lesions with Good Prognosis: A Proposal for Unified Nomenclature and Clinical Observation
Grayson G. Cole, Matt Levin, David Ferber, Spencer C. Roark, Peter M. Sadow, Daniel Lubin, Julie Guilmette, Jason R. Pettus, Adam S. Fisch, Dipti P. Sajed, Fouad R. Zakka, Mark W. Lingen, Nicole A. Cipriani
Head and Neck Pathology.2025;[Epub] CrossRef
Progression of Nasopharyngeal Pleomorphic Adenoma to Carcinoma Ex Pleomorphic Adenoma With Metastases: A Case Report
Krystsina Zhukovich, Alisher Tashbayev, Vladimir Osipov
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Ziyad Alsugair, Jimmy Perrot, Françoise Descotes, Jonathan Lopez, Anne Champagnac, Daniel Pissaloux, Claire Castain, Mihaela Onea, Philippe Céruse, Pierre Philouze, Charles Lépine, Marie-Delphine Lanic, Marick Laé, Valérie Costes-Martineau, Nazim Benzerdj
American Journal of Surgical Pathology.2024; 48(5): 551. CrossRef

Postmortem lung and heart examination of COVID-19 patients in a case series from Jordan: Maram Abdaljaleel, Isra Tawalbeh, Malik Sallam, Amjad Bani Hani, Imad M. Al-Abdallat, Baheth Al Omari, Sahar Al-Mustafa, Hasan Abder-Rahman, Adnan Said Abbas, Mahmoud Zureigat, Mousa A. Al-Abbadi; J Pathol Transl Med. 2023;57(2):102-112. Published online March 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.01.30

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Abstract PDF: Background
Coronavirus disease 2019 (COVID-19) has emerged as a pandemic for more than 2 years. Autopsy examination is an invaluable tool to understand the pathogenesis of emerging infections and their consequent mortalities. The aim of the current study was to present the lung and heart pathological findings of COVID-19–positive autopsies performed in Jordan.
Methods
The study involved medicolegal cases, where the cause of death was unclear and autopsy examination was mandated by law. We included the clinical and pathologic findings of routine gross and microscopic examination of cases that were positive for COVID-19 at time of death. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed through molecular detection by real-time polymerase chain reaction, serologic testing for IgM and electron microscope examination of lung samples.
Results
Seventeen autopsies were included, with male predominance (76.5%), Jordanians (70.6%), and 50 years as the mean age at time of death. Nine out of 16 cases (56.3%) had co-morbidities, with one case lacking such data. Histologic examination of lung tissue revealed diffuse alveolar damage in 13/17 cases (76.5%), and pulmonary microthrombi in 8/17 cases (47.1%). Microscopic cardiac findings were scarcely detected. Two patients died as a direct result of acute cardiac disease with limited pulmonary findings.
Conclusions
The detection of SARS-CoV-2 in postmortem examination can be an incidental or contributory finding which highlights the value of autopsy examination to determine the exact cause of death in controversial cases.

Reviews

Perspectives on single-nucleus RNA sequencing in different cell types and tissues: Nayoung Kim, Huiram Kang, Areum Jo, Seung-Ah Yoo, Hae-Ock Lee; J Pathol Transl Med. 2023;57(1):52-59. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.19

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Abstract PDF

Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues and alterations in disease states. For certain cell types and conditions, there are difficulties in isolating intact cells for transcriptome profiling due to their fragility, large size, tight interconnections, and other factors. Single-nucleus RNA sequencing (snRNA-seq) is an alternative or complementary approach for cells that are difficult to isolate. In this review, we will provide an overview of the experimental and analysis steps of snRNA-seq to understand the methods and characteristics of general and tissue-specific snRNA-seq data. Knowing the advantages and limitations of snRNA-seq will increase its use and improve the biological interpretation of the data generated using this technique.

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Single-cell and spatial sequencing application in pathology: Yoon-Seob Kim, Jinyong Choi, Sug Hyung Lee; J Pathol Transl Med. 2023;57(1):43-51. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.12

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Abstract PDF

Traditionally, diagnostic pathology uses histology representing structural alterations in a disease’s cells and tissues. In many cases, however, it is supplemented by other morphology-based methods such as immunohistochemistry and fluorescent in situ hybridization. Single-cell RNA sequencing (scRNA-seq) is one of the strategies that may help tackle the heterogeneous cells in a disease, but it does not usually provide histologic information. Spatial sequencing is designed to assign cell types, subtypes, or states according to the mRNA expression on a histological section by RNA sequencing. It can provide mRNA expressions not only of diseased cells, such as cancer cells but also of stromal cells, such as immune cells, fibroblasts, and vascular cells. In this review, we studied current methods of spatial transcriptome sequencing based on their technical backgrounds, tissue preparation, and analytic procedures. With the pathology examples, useful recommendations for pathologists who are just getting started to use spatial sequencing analysis in research are provided here. In addition, leveraging spatial sequencing by integration with scRNA-seq is reviewed. With the advantages of simultaneous histologic and single-cell information, spatial sequencing may give a molecular basis for pathological diagnosis, improve our understanding of diseases, and have potential clinical applications in prognostics and diagnostic pathology.

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Original Articles

Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma: Wael Abdo Hassan, Ahmed Kamal ElBanna, Noha Noufal, Mohamed El-Assmy, Hany Lotfy, Rehab Ibrahim Ali; J Pathol Transl Med. 2023;57(2):88-94. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.06

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Abstract PDF

Background
Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma.
Methods
A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil- to-lymphocyte ratio were evaluated.
Results
The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non–muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors.
Conclusions
Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression.

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Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy
Renan J. Teixeira, Vinícius G. de Souza, Bruna P. Sorroche, Victor G. Paes, Fabiana A. Zambuzi-Roberto, Caio A.D. Pereira, Vinicius L. Vazquez, Lidia M.R.B. Arantes
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Association between alteration of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, cancer antigen-125 and surgical outcomes in advanced stage ovarian cancer patient who received neoadjuvant chemotherapy
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Prognostic value of neutrophil-to-lymphocyte ratio in patients with non–muscle-invasive bladder cancer with intravesical Bacillus Calmette–Guérin immunotherapy: a systematic review and meta-analysis
Jiaguo Huang, Li Lin, Dikai Mao, Runmiao Hua, Feifei Guan
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Update on the Mechanism of Action of Intravesical BCG Therapy to Treat Non-Muscle-Invasive Bladder Cancer
Mohamad Abou Chakra, Yi Luo, Igor Duquesne, Michael A O'Donnell
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Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis
Chunhua Xu, Fenfang Wu, Lailing Du, Yeping Dong, Shan Lin
Frontiers in Immunology.2023;[Epub] CrossRef
Chitinase 3-like-1 Expression in the Microenvironment Is Associated with Neutrophil Infiltration in Bladder Cancer
Ling-Yi Xiao, Yu-Li Su, Shih-Yu Huang, Yi-Hua Chen, Po-Ren Hsueh
International Journal of Molecular Sciences.2023; 24(21): 15990. CrossRef

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

Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea: Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha; J Pathol Transl Med. 2022;56(6):334-341. Published online October 27, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.22

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Abstract PDF

Background
Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non–small cell lung cancers (NSCLCs).
Methods
A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images.
Results
In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively.
Conclusions
BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.

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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
Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study
Chankyung Kim, Shipra Agarwal, Andrey Bychkov, Jen-Fan Hang, Agnes Stephanie Harahap, Mitsuyoshi Hirokawa, Kennichi Kakudo, Somboon Keelawat, Chih-Yi Liu, Zhiyan Liu, Truong Phan-Xuan Nguyen, Chanchal Rana, Huy Gia Vuong, Yun Zhu, Chan Kwon Jung
Virchows Archiv.2024; 484(4): 645. CrossRef
BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin, Ahrong Kim
Medicina.2023; 59(6): 1085. CrossRef
Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy
Chan Kwon Jung
Journal of Pathology and Translational Medicine.2023; 57(4): 208. CrossRef

Case Study

Papillary and medullary thyroid carcinomas coexisting in the same lobe, first suspected based on fine-needle aspiration cytology: a case report: Hyun Hee Koh, Young Lyun Oh; J Pathol Transl Med. 2022;56(5):301-308. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.03

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Abstract PDF

Because different types of thyroid malignancies have distinct embryological origins, coexisting tumors are rarely observed. We describe a coexisting papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) first suspected by fine-needle aspiration cytology (FNAC). A 57-year-old female presented with an irregular mass in the right thyroid lobe. The cytopathologic findings of fine-needle aspiration showed two components: a papillary-like arrangement consisting of cells with pale enlarged nuclei indicative of PTC and loose clusters comprised of oval cells with granular chromatin indicative of MTC. The diagnosis of a coexisting PTC and MTC was initially confirmed by calcitonin immunocytochemistry and later after total thyroidectomy. Although some surgical case reports of PTC and MTC coexisting in either the same or different lobes have been documented, a case suspected by FNAC before the surgery has rarely been reported. Because appropriate treatment and prognosis of PTC and MTC are different, cytopathologists should be aware of this rare entity.

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Evaluation of Diagnostic Accuracy of Medullary Thyroid Carcinoma Using Fine‐Needle Aspiration Cytology—Based on a Single Tertiary Centre Experience
Si‐Yi Chen, Dong‐Mei Gu
Cytopathology.2026;[Epub] CrossRef
Synchronous papillary and medullary thyroid carcinoma with distinct genetic mutations: A case report
Huanyu Jiang, Lijuan Zhou, Gang Zou, Haidong Zhang, Zhenkun Yu
Oral Oncology.2025; 161: 107191. CrossRef
Coexisting papillary and medullary thyroid carcinomas in a 60 year old male: a case report
Allahdad Khan, Anam Malik, Abdul Ahad Riaz, Muhammad Hussnain Sadiq, Muhammad Shahzaib Arshad, Alka Rani, Ibrahim Nagmeldin Hassan
Annals of Medicine & Surgery.2025; 87(10): 6740. CrossRef
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
Coexisting Medullary and Papillary Thyroid Carcinomas: A Case of Dual Neoplasia With a High Risk of Misdiagnosis
Santiago Sierra Castillo, Maria A Henao Rincón, David Aristizabal Colorado, David Alexander Vernaza Trujillo, Alin Abreu Lomba
Cureus.2024;[Epub] CrossRef

Original Articles

Evaluation of the characteristics of multiple human papillomavirus (HPV) infections identified using the BD Onclarity HPV assay and comparison with those of single HPV infection: Jinhee Kim, Moonsik Kim, Ji Young Park; J Pathol Transl Med. 2022;56(5):289-293. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.02

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Abstract PDF Supplementary Material

Background
Human papillomavirus (HPV) infection is a major cause of cervical cancer and associated precursor lesions. Multiple HPV genotype infections have been reported. However, their clinicopathological characteristics still remain elusive.
Methods
For this study, 814 consecutive patients who had undergone colposcopy and HPV genotyping test using BD Onclarity HPV assay were retrospectively selected. Clinicopathological parameters of multiple HPV infections were compared with those of single HPV infection.
Results
Multiple HPV infections were found in 110 out of 814 cases (13.5%). Multiple HPV infections were associated with a significantly higher incidence of high-grade intraepithelial lesions (HSILs) compared with single HPV infection. Other high-risk HPV genotypes, in addition to HPV 16, were found more frequently in the multiple HPV infections group; these included HPV 51, 52, 33/58, 56/59/66, and 35/39/68. No specific coinfection pattern was not identified. Additionally, the number of HPV genotypes in multiple HPV infections was not associated with the progression to HSIL or squamous cell carcinoma.
Conclusions
Multiple HPV infections have distinct clinicopathological characteristics (compared with single HPV infection). As their biological behavior is uncertain, close and frequent follow-up is warranted.

Citations

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The Prevalence of Multi-Type Infections Among Human Papillomavirus Types in Korean Women
Jang Mook Kim, Hee Seung Song, Jieun Hwang, Jae Kyung Kim
Pathogens.2025; 14(4): 369. CrossRef
Multiple high-risk human papillomavirus infections exacerbate cervical lesion risk: epidemiological evidence from suining, Sichuan
Yaling Jing, Jianhui Chen, Fang Lin, Xiaonan Huang, Yulin Liu, Mingcai Zhao, Chuan Ye, Lianfang Zhao, Xiaofang Liu, Jiayan Yang
Virology Journal.2025;[Epub] CrossRef
The cervical cancer related distribution, coinfection and risk of 15 HPV types in Baoan, Shenzhen, in 2017–2023
Rukai Li, Weiwei Meng, Yunhai Zuo, Yanli Xu, Shaonan Wu
Virology Journal.2024;[Epub] CrossRef
Molecular findings and virological assessment of bladder papillomavirus infection in cattle
Francesca De Falco, Anna Cutarelli, Francesca Luisa Fedele, Cornel Catoi, Sante Roperto
Veterinary Quarterly.2024; 44(1): 1. CrossRef
Patterns of single and multiple HPV infections in female: A systematic review and meta-analysis
Dan Zhou, Jing Xue, Yaqiong Sun, Liling Zhu, Ming Zhao, Meimei Cui, Min Zhang, Jingjing Jia, Limei Luo
Heliyon.2024; 10(17): e35736. CrossRef
Age distribution of patients with multiple High-Risk Human Papilloma Virus (HR-HPV) genotypes and HPV vaccine recommendations by age
Gülçin Çetin Uysal, Nil Tekin
Family Practice and Palliative Care.2024; 9(3): 80. CrossRef
Relative distribution of HPV genotypes in histological cervical samples and associated grade lesion in a women population over the last 16 years in Burgundy, France
Christelle Auvray, Serge Douvier, Odile Caritey, Jean-Baptiste Bour, Catherine Manoha
Frontiers in Medicine.2023;[Epub] CrossRef
Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions
Qinli Luo, Xianghua Zeng, Hanyi Luo, Ling Pan, Ying Huang, Haiyan Zhang, Na Han
BMC Infectious Diseases.2023;[Epub] CrossRef

Cytopathologic features of human papillomavirus–independent, gastric-type endocervical adenocarcinoma: Min-Kyung Yeo, Go Eun Bae, Dong-Hyun Kim, In-Ock Seong, Kwang-Sun Suh; J Pathol Transl Med. 2022;56(5):260-269. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.07.05

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Abstract PDF

Background
Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.
Methods
Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.
Results
Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.
Conclusions
Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.

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A Comparative Analysis of Usual- and Gastric-Type Cervical Adenocarcinoma in a Japanese Population Reveals Distinct Clinicopathological and Molecular Features with Prognostic and Therapeutic Insights
Umme Farzana Zahan, Hasibul Islam Sohel, Kentaro Nakayama, Masako Ishikawa, Mamiko Nagase, Sultana Razia, Kosuke Kanno, Hitomi Yamashita, Shahataj Begum Sonia, Satoru Kyo
International Journal of Molecular Sciences.2025; 26(15): 7469. CrossRef
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, Y
Journal of Pathology and Translational Medicine.2025; 59(6): 444. CrossRef
Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus–Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern
Bong Kyung Bae, Hyunsik Bae, Won Kyung Cho, Byoung-Gie Kim, Chel Hun Choi, Tae-Joong Kim, Yoo-Young Lee, Jeong-Won Lee, Hyun-Soo Kim, Won Park
International Journal of Gynecological Pathology.2024; 43(5): 447. CrossRef
Tall‐columnar glandular cells in SurePath™ liquid‐based cytology Pap sample: Learning from mimics/pitfalls
Nalini Gupta, Vanita Jain, Radhika Srinivasan, Tulika Singh
Cytopathology.2024; 35(4): 510. CrossRef

Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing: Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2022;56(5):249-259. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.06.11

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Abstract PDF Supplementary Material

Background
Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR–tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations.
Methods
We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response.
Results
EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation–positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases.
Conclusions
Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.

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Comparison of tissue-based and plasma-based testing for EGFR mutation in non–small cell lung cancer patients
Yoon Kyung Kang, Dong Hoon Shin, Joon Young Park, Chung Su Hwang, Hyun Jung Lee, Jung Hee Lee, Jee Yeon Kim, JooYoung Na
Journal of Pathology and Translational Medicine.2025; 59(1): 60. CrossRef
Localization of epidermal growth factor receptor-mutations using PNA:DNA probes in clinical specimens from patients with non-small cell lung cancer
Haruo Miyata, Hajime Shigeto, Tomoatsu Ikeya, Tadashi Ashizawa, Akira Iizuka, Yasufumi Kikuchi, Chie Maeda, Akari Kanematsu, Kazue Yamashita, Kenichi Urakami, Yuji Shimoda, Takeshi Nagashima, Keiichi Ohshima, Yasuhisa Ohde, Mitsuhiro Isaka, Takashi Sugino
Scientific Reports.2025;[Epub] CrossRef
Molecular characteristics and responses to EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients with EGFR exon 19 insertions
Yang Li, Yunfeng Ni, Feng Lv, Yan Shi, Yedan Chen, Xiaoying Wu, Jiaohui Pang, Long Huang, Yang Shao, Tao Wang, Jie Min, Yang Song
BMC Medicine.2025;[Epub] CrossRef
Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Histo-pillar strip for optimal histogel block construction and biomarker analysis in 3D-lung cancer patient-derived organoids
Sang-Yun Lee, Eunyoung Lee, Ji-O Ryu, Kyuhwan Kim, Yongki Hwang, Bosung Ku, Seok Whan Moon, Mi Hyoung Moon, Kyung Soo Kim, Kwanyong Hyun, Jeong Uk Lim, Chan Kwon Park, Sung Won Kim, Chang Dong Yeo, Dong Woo Lee, Seung Joon Kim
Biofabrication.2024; 16(4): 045017. CrossRef

Review

Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies: Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon; J Pathol Transl Med. 2022;56(4):173-186. Published online July 4, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.16

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Abstract PDF

Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

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Renu Singh, Md Ali Osama, Rachana Meena, Shailaja Shukla, Jagdish Chandra
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Soundarya Ravi, Anu K. Devi, Prabhu Manivannan, Debasis Gochhait, Rakhee Kar, Neelaiah Siddaraju
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Kafil Akhtar, Gowthami Nagendhran, Anjum Ara, Masheera Akhtar
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Case Study

Hepatic carcinoma expressing inhibin: case report of a proposed novel entity and review of the literature: Antonia Syrnioti, Evangelia Athanasiou, Prodromos Hytiroglou; J Pathol Transl Med. 2022;56(4):225-230. Published online June 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.04.07

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Abstract PDF

Hepatic carcinoma expressing inhibin is a recently described neoplasm with varied architecture, including trabecular, pseudoglandular, follicular/microcystic, organoid, solid and tubular patterns of growth. We report a case of hepatic carcinoma expressing inhibin that occurred in a 47-year-old woman presenting with epigastric and back pain. The tumor was located in the left hepatic lobe and measured 12 cm in diameter. On immunohistochemical stains, the neoplastic cells were positive for inhibin, as well as cytokeratins 7, 8/18 and 19. There was mild focal expression of synaptophysin, and lack of expression of hepatocytic markers. The histogenesis of hepatic carcinoma expressing inhibin is presently uncertain. From a practical point of view, this neoplasm can potentially cause diagnostic pitfalls by simulating other primary or metastatic tumors, such as hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and follicular carcinoma of thyroid gland. Performing inhibin immunostain could assist in the differential diagnosis of liver tumors with unusual histologic features.

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Cytologic Findings of Cholangioblastic Variant of Intrahepatic Cholangiocarcinoma: A Rare Variant and Cytologic Pitfall
Eleonora Fiorletta Quiroga, Maria Luisa C. Policarpio‐Nicolas
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Original Article

Correlation between myoferlin expression and lymph node metastasis in papillary thyroid carcinoma: Ji Min Na, Dong Chul Kim, Dae Hyun Song, Hyo Jung An, Hyun Min Koh, Jeong-Hee Lee, Jong Sil Lee, Jung Wook Yang, Min Hye Kim; J Pathol Transl Med. 2022;56(4):199-204. Published online May 11, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.19

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Abstract PDF: Background
Myoferlin is a multifunctional protein expressed in various normal and cancer cells, with novel oncogenic roles being newly discovered. Recently, correlations have been found between myoferlin expression and unfavorable prognosis in various carcinomas. This study investigated the prognostic role of myoferlin expression in papillary thyroid carcinoma (PTC), specifically that associated with nodal metastasis.
Methods
We collected clinicopathological data and PTC tissues from 116 patients who had been admitted to Gyeongsang National University Hospital in 2010. Immunohistochemical analysis was performed on surgical specimen-derived tissue microarray blocks. Myoferlin expression was graded, and the relationship between expression level and pathological features of tumors based on the American Joint Committee on Cancer staging system was evaluated.
Results
Of the 116 patient samples, 100 cases exhibited positive myoferlin expression. Higher grade of myoferlin expression was correlated with lower T category group (p = .010). Presence of lymph node metastasis was determined to be significantly correlated with low-grade myoferlin expression (p = .019), with no significant difference between pN1a and pN1b tumors.
Conclusions
Our study revealed an adverse correlation between myoferlin expression and pathological features of PTC, evidence of the potential prognostic role of myoferlin in PTC lymph node metastasis.

Case Study

Clinically undetected plasmacytoid urothelial carcinoma of the urinary bladder with non-mass-forming metastases in multiple organs: an autopsy case: Yuya Asano, Kosuke Miyai, Shinya Yoshimatsu, Makoto Sasaki, Katsunori Ikewaki, Susumu Matsukuma; J Pathol Transl Med. 2022;56(4):217-224. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.03.15

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Abstract PDF

This case report outlines a clinically undetected urinary bladder plasmacytoid urothelial carcinoma (PUC) with multiple metastases detected at autopsy. An 89-year-old man presented with edema in the lower limbs. Pleural fluid cytology revealed discohesive carcinomatous cells, although imaging studies failed to identify the primary site of tumor. The patient died of respiratory failure. Autopsy disclosed a prostate tumor and diffusely thickened urinary bladder and rectum without distinct tumorous lesions. Histologically, the tumor consisted of acinar-type prostate adenocarcinoma with no signs of metastasis. Additionally, small, plasmacytoid tumor cells were observed in the urinary bladder/rectum as isolated or small clustering fashions. These metastasized to the lungs, intestine, generalized lymph nodes in a non-mass-forming manner. Combined with immunohistochemical studies, these tumor cells were diagnosed PUC derived from the urinary bladder. Both clinicians and pathologists should recognize PUC as an aggressive histological variant, which can represent a rapid systemic progression without mass-forming lesions.

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Severe Rectal Stenosis as the First Clinical Appearance of a Metastasis Originating from the Bladder: A Case Report and Literature Review
Claudiu Daha, Eugen Brătucu, Ioan Burlănescu, Virgiliu-Mihail Prunoiu, Hortensia-Alina Moisă, Ștefania Ariana Neicu, Laurențiu Simion
Life.2025; 15(5): 682. CrossRef
Carcinomatous Meningitis and Hydrocephalus in Plasmacytoid Urothelial Carcinoma of the Urinary Bladder With Extremely Elevated CA19-9 Levels
Fumiaki Henmi, Kayako Ukai, Atsuhito Nakayama, Yutaka Takazawa, Yoshikazu Uesaka
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Original Articles

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury: Badr Alzahrani, Mohamed M. S. Gaballa, Ahmed A. Tantawy, Maha A. Moussa, Salma A. Shoulah, Said M. Elshafae; J Pathol Transl Med. 2022;56(2):81-91. Published online March 2, 2022; DOI: https://doi.org/10.4132/jptm.2021.12.27

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Abstract PDF

Background
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
Methods
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Results
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
Conclusions
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.

Citations

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A novel mouse model of myositis-associated interstitial lung disease was established by using TLR9 agonist combined with muscle homogenate
Ling Bai, Jiarui Zhu, Wenlan Ma, Peipei Zhao, Feifei Li, Cen Zhang, Sigong Zhang
Clinical and Experimental Immunology.2025;[Epub] CrossRef
Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis
Glenda Trujillo, Alicia Regueiro-Ren, Chunjian Liu, Buqu Hu, Ying Sun, Farida Ahangari, Vitoria Fiorini, Genta Ishikawa, Karam Al Jumaily, Johad Khoury, John McGovern, Chris J. Lee, Xue Yan Peng, Taylor Pivarnik, Huanxing Sun, Anjali Walia, Samuel Woo, Sh
American Journal of Respiratory and Critical Care Medicine.2025; 211(1): 91. CrossRef
CD103+ dendritic cell–fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Hannah Carter, Rita Medina Costa, Taylor S. Adams, Talon M. Gilchrist, Claire E. Emch, Monica Bame, Justin M. Oldham, Steven K. Huang, Angela L. Linderholm, Imre Noth, Naftali Kaminski, Bethany B. Moore, Stephen J. Gurczynski
JCI Insight.2025;[Epub] CrossRef
The Mitigated Effect of the Combination of Metformin and Stearic Acid to Ameliorate Bleomycin‐Induced Pulmonary Fibrosis in Rats via Inhibiting Gal‐3/Smad3/α‐SMA and TNF‐α/NF‐κβ Signaling Pathways
Maha M. Salem, Nermin S. Youssef, Mai El Keiy, Abeer A. Khamis
Journal of Biochemical and Molecular Toxicology.2025;[Epub] CrossRef
Unraveling the Interactive Role of Mitochondrial Dysfunction in Promoting Macrophage Polarization in Pulmonary Fibrosis
Jiajia Zou, Junling Jian, Dehua Ge, Bin Zhou, Jiaxiang Zhang
Journal of Biochemical and Molecular Toxicology.2025;[Epub] CrossRef
Mechanisms underlying dose-limiting toxicities of conventional chemotherapeutic agents
Mohammad Amin Manavi, Mohammad Hosein Fathian Nasab, Razieh Mohammad Jafari, Ahmad Reza Dehpour
Journal of Chemotherapy.2024; 36(8): 623. CrossRef
Innate Immune Response-Mediated Inflammation in Viral Pneumonia
Weiwei Ni, Xin Wei, Rui Wu
Journal of Pediatric Infectious Diseases.2024; 19(03): 140. CrossRef
Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats
Arian Amirkhosravi, Maryamossadat Mirtajaddini Goki, Mahmoud Reza Heidari, Somayyeh Karami-Mohajeri, Maryam Iranpour, Maryam Torshabi, Mitra Mehrabani, Ali Mandegary, Mehrnaz Mehrabani
Scientific Reports.2024;[Epub] CrossRef
Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2
Mei-xia Xu, Tao Xu, Ning An
Current Medical Science.2024; 44(5): 964. CrossRef
Study of Recombinant Interleukin-1 Receptor Antagonist Compositions Biological Activity After Injection and Inhalation in Mouse Model of Pulmonary Inflammation
Alexander M. Ischenko, Ksenia A. Nekrasova, Denis S. Laptev, Dmitry V. Bobkov, Alexander A. Kolobov, Andrey S. Simbirtsev
Cytokines and inflammation.2024; 21(3): 153. CrossRef
TLR9: A friend or a foe
Mona M. Saber, Nada Monir, Azza S. Awad, Marwa E. Elsherbiny, Hala F. Zaki
Life Sciences.2022; 307: 120874. CrossRef

Frequency of PIK3CA mutations in different subsites of head and neck squamous cell carcinoma in southern Thailand: Arunee Dechaphunkul, Phatcharaporn Thongwatchara, Paramee Thongsuksai, Tanadech Dechaphunkul, Sarayut Lucien Geater; J Pathol Transl Med. 2022;56(3):126-133. Published online February 28, 2022; DOI: https://doi.org/10.4132/jptm.2022.01.04

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Abstract PDF

Background
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have been reported in many cancers, including head and neck squamous cell carcinoma (HNSCC). The frequency of these mutations varies among tumor locations and might be relevant to treatment outcomes among HNSCC. In this study, we examined the frequency of PIK3CA mutations in the different subsites of HNSCC.
Methods
Ninety-six fresh biopsy specimens were investigated for mutations in PIK3CA exons 4, 9, and 20 using allele-specific real-time polymerase chain reaction. Patient characteristics and survival were analyzed and compared between specimens with or without PIK3CA mutations.
Results
The study included primary tumors originating from the oral cavity (n=63), hypopharynx (n=23), and oropharynx (n=10). We identified mutations in 10.4% of patients (10 of 96 specimens). The overall mutational frequency was 17.4% (4/23) and 9.5% (6/63) in the hypopharynx and oral cavity, respectively. No patients with oropharyngeal carcinoma had mutations. Among the 10 mutant specimens, five were missense mutations (exon 9 [E545K] in two samples and exon 20 [H1047R] in three samples) and five were silent mutations in exon 20 (T1025T). Mutations were not found in exon 4. Among 84 patients with available clinical data, we found no significant differences in clinical characteristics and survival based on the presence or absence of PIK3CA mutations.
Conclusions
The results indicate that PIK3CA mutations are involved in HNSCC carcinogenesis, and the hypopharynx should be considered a primary site of interest for future studies, particularly in Southeast Asian populations.

Citations

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Comprehensive Genomic Profiling of Sinonasal Carcinomas: Identification of Common Mutations and Potential Targets for Therapy
Gabriel Bitar, Beau Hsia, Saif Alshaka, Bastien A. Valencia, Jeeho Kim, Mariko Sato, John Crawford, Michael L. Levy, Sean Polster, Vijay A. Patel
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Owona Pascal Emmanuel, Mengue Ngadena Yolande Sandrine, Bilanda Danielle Claude, Ayissi Mbomo Rigobert-Espoir, Oluwafemi Adeleke Ojo, Ella Armand Fils, Bidingha A Goufani Ronald, Bindzi Georges Michel, Dzeufiet Djomeni Paul Désiré, Tariq Aziz, Abdulhakeem
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A retrospective study of laryngeal squamous cell carcinoma and the significance of the PIK3CA mutation for survival
Akinobu Kubota, Nobuyuki Bandoh, Takashi Goto, Michihisa Kono, Ryosuke Sato, Shiori Suzuki, Shota Sakaue, Ryuhei Takeda, Shuto Hayashi, Misaki Hayashi, Daisuke Araki, Shogo Baba, Yasutaka Kato, Miki Takahara, Hiroshi Nishihara, Hajime Kamada
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Sankha Bhattacharya
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Case Studies

Adrenal hemangioblastoma: Joo-Yeon Koo, Kyung-Hwa Lee, Joon Hyuk Choi, Ho Seok Chung, Chan Choi; J Pathol Transl Med. 2022;56(3):161-166. Published online February 28, 2022; DOI: https://doi.org/10.4132/jptm.2021.12.28

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Abstract PDF

Hemangioblastoma (HB) is a rare benign tumor that most commonly occurs in the cerebellum. HB is composed of neoplastic stromal cells and abundant small vessels. However, the exact origin of stromal cells is controversial. Extraneural HBs have been reported in a small series, and peripheral HBs arising in the adrenal gland are extremely rare. Herein, we report a case of sporadic adrenal HB in a 54-year-old woman. The tumor was a well-circumscribed, yellow mass measuring 4.2 cm in diameter. Histologically, the tumor was composed of small blood vessels and vacuolated stromal cells with clear cytoplasm. On immunohistochemical stain, the stromal cells were positive for S-100 protein, neuron-specific enolase, and synaptophysin. The tumor did not reveal mutation of VHL alleles. We herein present a case of HB of the adrenal gland and review of the literature.

Citations

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Familial Von Hippel–Lindau Disease: A Case Series of Cerebral Hemangioblastomas with MRI, Histopathological, and Genetic Correlations
Claudiu Matei, Ioana Boeras, Dan Orga Dumitriu, Cosmin Mutu, Adriana Popescu, Mihai Gabriel Cucu, Alexandru Calotă-Dobrescu, Bogdan Fetica, Diter Atasie
Life.2025; 15(11): 1649. CrossRef

Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice: Evi Abada, Ifeoma C. Anaya, Othuke Abada, Anthony Lebbos, Rafic Beydoun; J Pathol Transl Med. 2022;56(2):97-102. Published online January 21, 2022; DOI: https://doi.org/10.4132/jptm.2021.10.28

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Abstract PDF

Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

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Colorectal Adenocarcinoma with Enteroblastic Differentiation: A Report of Two Cases
Yusuke Nakamura, Hiroyuki Fukuda, Yasuo Ishida
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Aboje Adugba, Dominic Obotu Ayegba, Mansour Al Moundhri, Kareem Al Rezk, Rawan AlMallah, Ramesh Babu Telugu, Abdallah Al Farai
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Exploring the Multifunctional Role of Alpha-Fetoprotein in Cancer Progression: Implications for Targeted Therapy in Hepatocellular Carcinoma and Beyond
Hyunjung Kim, Minji Jang, Eunmi Kim
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Sato Nishida, Tomohiro Takeda, Tatsuya Shonaka, Shoichiro Mizukami, Masahide Otani, Mizuho Ohara, Chikayoshi Tani, Kimiharu Hasegawa, Yuki Kamikokura, Mishie Tanino, Hideki Yokoo
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Tairan Wang, Yan Jin, Mengyao Wang, Boya Chen, Jinyu Sun, Jiaying Zhang, Hui Yang, Xinyao Deng, Xingyue Cao, Lidong Wang, Yuanyuan Tang
Molecular Medicine.2024;[Epub] CrossRef
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Hae Rin Lee, Gwang Ha Kim, Dong Chan Joo, Moon Won Lee, Bong Eun Lee, Kyung Bin Kim
The Ewha Medical Journal.2024;[Epub] CrossRef
Colorectal adenocarcinoma with clear cell changes: immunohistological and molecular findings in three cases
Andreas Gocht, Carsten Heidel, Jutta Kirfel, Rita Vesce, Pamela Lazar-Karsten, Helen Pasternack, Madelaine Melzer, Phillip Hildebrand, Nicole Warkentin, Hendrik Schimmelpenning, Verena-Wilbeth Sailer
Virchows Archiv.2024; 485(3): 569. CrossRef
Ureteral Metastasis of Colonic Adenocarcinoma with Enteroblastic Differentiation: A Rare Case to be Distinguished from Clear Cell Adenocarcinoma of the Urinary Tract
Hiroshi Minato, Akane Yoshikawa, Sho Tsuyama, Kazuyoshi Katayanagi, Kengo Hayashi, Yusuke Sakimura, Hiroyuki Bando, Tomohiro Hori, Yosuke Kito
International Journal of Surgical Pathology.2023; 31(8): 1553. CrossRef
Beyond liver cancer, more application scenarios for alpha-fetoprotein in clinical practice
Chenyu Ma, Yuexinzi Jin, Yuhan Wang, Huaguo Xu, Jiexin Zhang
Frontiers in Oncology.2023;[Epub] CrossRef
AIEgens assisted label free DNA supersandwich immunoassay for ultrasensitive α-fetoprotein detection
Xiaowen Ou, Jingman Dai, Yiting Huang, Xiaoqin Xiong, Zhi Zheng, Xiaoding Lou, Fan Xia
Giant.2022; 11: 100110. CrossRef
Rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features arising in a patient with ulcerative colitis: a case report
Takako Kihara, Ryuichi Kuwahara, Kurando Kusunoki, Tomohiro Minagawa, Yuki Horio, Motoi Uchino, Hiroki Ikeuchi, Seiichi Hirota
World Journal of Surgical Oncology.2022;[Epub] CrossRef

An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing: Bogyeong Han, Sehui Kim, Jiwon Koh, Jeong Mo Bae, Hongseok Yun, Yoon Kyung Jeon; J Pathol Transl Med. 2022;56(2):92-96. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.15

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Abstract PDF

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.

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PD-L1+diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquiredPMS2mutation
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