Journal of Pathology and Translational Medicine

Volume 59(4); July 2025

Review Articles

Multiple sclerosis: a practical review for pathologists: Rachel A. Multz, Pouya Jamshidi, Jared T. Ahrendsen; J Pathol Transl Med. 2025;59(4):203-213. Published online June 27, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.20

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Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system. It is a chronic disorder resulting in neurologic dysfunction that is disseminated both in time (multiple discrete episodes) and space (involving multiple sites). Histologically, MS is characterized by localized loss of myelin with relative preservation of axons. This review will discuss the epidemiology, clinical, laboratory, radiologic, and pathologic features of multiple sclerosis, as well as briefly touch on the differential diagnosis, treatment, and prognosis of the disease, especially as they relate to the pathologic interpretation of tissue specimens.

Citations

Citations to this article as recorded by

White Matter in Crisis: Oligodendrocytes and the Pathophysiology of Multiple Sclerosis
Mario García-Domínguez
Cells.2025; 14(18): 1408. CrossRef

Recent topics on thyroid cytopathology: reporting systems and ancillary studies: Mitsuyoshi Hirokawa, Ayana Suzuki; J Pathol Transl Med. 2025;59(4):214-224. Published online June 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.18

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Abstract PDF: As fine-needle aspiration techniques and diagnostic methodologies for thyroid nodules have continued to evolve and reporting systems have been updated accordingly, we need to be up to date with the latest information to achieve accurate diagnoses. However, the diagnostic approaches and therapeutic strategies for thyroid nodules vary across laboratories and institutions. Several differences exist between Western and Eastern practices regarding thyroid fine-needle aspiration. This review describes the reporting systems for thyroid cytopathology and ancillary studies. Updated reporting systems enhance the accuracy, consistency, and clarity of cytology reporting, leading to improved patient outcomes and management strategies. Although a single global reporting system is optimal, reporting systems tailored to each country is acceptable. In such cases, compatibility must be ensured to facilitate data sharing. Ancillary methods include liquid-based cytology, immunocytochemistry, biochemical measurements, flow cytometry, molecular testing, and artificial intelligence, all of which improve diagnostic accuracy. These methods continue to evolve, and cytopathologists should actively adopt the latest methods and information to achieve more accurate diagnoses. We believe this review will be useful to practitioners of routine thyroid cytology.

Original Articles

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.

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

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

Pancreatic cancer in liquid-based cytology: cytological features and cell block utility from 254 fine-needle aspiration samples: Jaeyong Min, Wookjin Oh, Baek-hui Kim; J Pathol Transl Med. 2025;59(4):249-261. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.27

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Abstract PDF Supplementary Material: Background
Despite the increasing use of liquid-based cytology (LBC) for pancreatic cancer diagnosis, relatively few studies have directly examined such research. This study analyzed the cytopathological features of pancreatic cancer in LBC and demonstrated the utility of cell blocks in diagnosing pancreatic lesions. Methods: A retrospective review identified LBC from 254 pancreatic fine-needle aspirations (FNAs) (221 patients). FNAs were categorized into five subgroups based on cytopathological, clinical, and histopathological findings. Two pathologists evaluated cytological features in LBC samples, cell blocks, and tissue slides. Comparative analysis assessed differences between groups. Results: Compared to benign lesions, LBC of pancreatic cancer more frequently showed a necrotic background, intermediate to high cellularity, mixed architecture, nuclear/cytoplasmic ratio >0.8, anisonucleosis >4:1, irregular and thick nuclear membranes, multinucleated tumor cells, hyperchromatic nuclei, coarse to clumped chromatin, and a prominent single nucleolus. In cases of conventional pancreatic ductal adenocarcinoma, the palliative treatment subgroup showed a higher incidence of necrotic background than the resection subgroup. In the cell block analysis, tumor cells not identified in LBC slides were detected in 16 FNAs. Additionally, 13 FNAs contributed to differential diagnosis: ancillary tests aided diagnosis in 12 FNAs, while histopathological evaluation of the cell block slide alone was helpful in one case. Conclusions: The cytological features of pancreatic cancer in LBC are similar to those observed in conventional smears, with a necrotic background suggesting advanced (unresectable) disease. The cell block methodology minimizes tumor cell loss and facilitates differential diagnosis by enabling ancillary testing.

Case Study

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

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

Newsletter

What’s new in medical renal pathology 2025: Updates on podocytopathy and immunofluorescence staining in medical kidney: Astrid Weins, Ibrahim Batal, Paola Romagnani, Geetika Singh, Rahul Raj, Nicole Andeen, Jonathan Zuckerman, Martina Uzzo, Mariam Priya Alexander, Anjali Satoskar; J Pathol Transl Med. 2025;59(4):269-272. Published online July 10, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.19

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Abstract PDF: Diffuse podocytopathy, including minimal change disease and primary focal segmental glomerulosclerosis, is a common cause of nephrotic syndrome in adults and children. It is increasingly recognized to be autoimmune-mediated associated with anti-nephrin and other emerging anti-slit diaphragm antibodies, and can recur in the kidney allograft. Immunofluorescence is routinely used in evaluation of kidney biopsies, and updates include those on fibrillar diseases, monoclonal staining, lupus-like staining, and use of antibody KM55 in IgA-dominant glomerulonephritis.

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