Journal of Pathology and Translational Medicine最新文献

{"title":"Digital image analysis-based quantification of p53 immunohistochemistry in gastric cancer: a systematic comparison of three-tier cutoff-derivation strategies in tissue microarrays.","authors":"Jaeyoung Ahn, Kyungeun Kim, Hee-Jung Yang, Boram Song, Dong Hoon Kim, Yumin Chung, Seoung Wan Chae","doi":"10.4132/jptm.2026.08.13","DOIUrl":"https://doi.org/10.4132/jptm.2026.08.13","url":null,"abstract":"<p><strong>Background: </strong>p53 immunohistochemistry (IHC) is a common surrogate for TP53 alteration, but in gastric cancer, its concordance is imperfect and depends on a non-standardized cutoff. Digital pathology enables H-score quantification, yet neither its reproducibility nor the choice of cutoff- derivation strategy has been systematically compared.</p><p><strong>Methods: </strong>A semi-automated digital workflow quantified p53 IHC in tissue microarrays from 528 gastric cancer patients. Tumor cells were detected with a deep-learning model (InstanSeg), and nuclear staining was expressed as a continuous H-score (0-300). Reproducibility was assessed at each observer-dependent step. Five thresholding strategies were compared: manual cutoffs, tertiles, log-rank optimization, the extended Youden index, and volume under the receiver operating characteristic surface (VUS). The latter two strategies used the manual three-tier IHC interpretation as the reference standard.</p><p><strong>Results: </strong>Quantification was reproducible: two independent manual interpretations agreed in 91.7% of cores (κ = 0.845). The H-score was robust to the detection algorithm (intraclass correlation coefficient, 0.990) and to repeated threshold determination (0.954). H-scores were right-skewed (median, 45.5), and the strategies yielded distinct cutoffs (8.0-27.6 and 78.6-106.0). Log-rank optimization provided the widest separation but lost significance after multiplicity adjustment (p = .168). The extended Youden and VUS cutoffs were statistically indistinguishable. As a supporting check, all classifications showed nominal overall-survival separation, with low and overexpression faring similarly worse than wild-type.</p><p><strong>Conclusions: </strong>Digital p53 IHC quantification was reproducible at each observer-dependent step. The extended Youden and VUS criteria performed equivalently; therefore, we propose Youden as a reasonable default, pending validation and TP53 correlation.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal intramucosal carcinoma with lymphatic invasion and lymph node metastasis: a case report.","authors":"Joon Mee Kim, Lucia Kim, Jee Young Han, Suk Jin Choi, Jongbeom Shin, Sun Keun Choi","doi":"10.4132/jptm.2026.08.14","DOIUrl":"https://doi.org/10.4132/jptm.2026.08.14","url":null,"abstract":"<p><p>Colorectal intramucosal carcinoma (IMC) is considered to carry negligible risk of lymph node metastasis, reflecting the presumed absence of lymphatics within the lamina propria, and current guidelines endorse endoscopic resection alone as curative. We report a 64-year-old man in whom endoscopic submucosal dissection of a lower rectal tumor revealed a well-differentiated IMC with extensive lymphatic invasion confirmed by D2-40 immunostaining. Subsequent laparoscopic ultralow anterior resection showed no residual tumor at the primary site but confirmed metastasis in one of 12 regional lymph nodes. The tumor was microsatellite-stable, epidermal growth factor receptor-positive, and harbored a KRAS codon 13 mutation (G13X). The patient received adjuvant chemoradiotherapy and remained disease-free at 2 years. This case demonstrates that regional lymph node metastasis can occur in colorectal IMC even without conventional adverse histologic features such as poor differentiation or tumor budding, challenging current risk-stratification frameworks and supporting a more cautious approach when lymphatic invasion is identified.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric amphicrine carcinoma in the stomach: an unexpected presentation of MUTYH-associated polyposis.","authors":"Seungkyun Lee, Byung-Hoon Min, Young-Gon Kim, Soomin Ahn, Kyoung-Mee Kim","doi":"10.4132/jptm.2026.06.24","DOIUrl":"https://doi.org/10.4132/jptm.2026.06.24","url":null,"abstract":"<p><p>Amphicrine carcinomas of the stomach, defined by dual exocrine and neuroendocrine differentiation within the same neoplastic cell, are exceedingly rare. MUTYH-associated polyposis (MAP) is an autosomal recessive polyposis syndrome characterized by multiple colorectal adenomas and variable upper gastrointestinal involvement; however, amphicrine carcinomas have not been previously documented in this setting. We report a gastric amphicrine carcinoma arising in the background of extensive fundic gland polyposis in a patient with MAP. Endoscopy revealed a 3.5-cm flat elevated lesion in the gastric fundus amid extensive fundic gland polyposis. Histologically, the tumor consisted of a single population of cells exhibiting combined glandular and neuroendocrine differentiation without zonal or biphasic architecture, and many of these cells demonstrated true amphicrine morphology. Immunohistochemistry confirmed co-expression of cytokeratin and the neuroendocrine markers chromogranin A and synaptophysin in the same cell population. Germline targeted next-generation sequencing identified biallelic MUTYH variants in trans (c.733C>T, p.Arg245Cys [likely pathogenic]; c.842C>T, p.Ala281Val [variant of uncertain significance]), supporting a diagnosis of MAP. To our knowledge, this is the first reported case of a gastric amphicrine carcinoma in a MAP patient, expanding the spectrum of MAP-associated upper gastrointestinal neoplasia and underscoring the importance of vigilant endoscopic surveillance in hereditary polyposis syndromes.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-driven adipokine signaling in breast cancer: mechanistic insights, therapeutic challenges, and opportunities for precision oncology.","authors":"Vadakke Kunnumma Soonu, Praveen Kumar Shenoy, Valiyaparampil Gopi Deepak Roshan, Vipin Gopinath, Krishnan Sreejith","doi":"10.4132/jptm.2026.06.30","DOIUrl":"10.4132/jptm.2026.06.30","url":null,"abstract":"<p><p>Breast cancer is the leading cause of illness and death among women worldwide, with more than 2.3 million new cases diagnosed each year. The incidence and fatality rates are steadily increasing, notably in Asian countries. Obesity has been established as a major and growing risk factor for breast cancer progression. The World Health Organization reports that adult obesity rates have doubled since 1990. Obesity promotes tumor growth by inhibiting adipokine production and activating cancer-promoting pathways. In obese people, the microenvironment surrounding breast cancer cells is drastically altered. This is mostly due to the malfunctioning of adipocytes (fat cells) and macrophages. These defective cells' adipokines alter signaling pathways required for cancer cell proliferation, survival, and inflammation. This dysregulation has a significant role in tumor development, metastasis, and resistance to traditional cancer treatments, particularly in obese patients. This review highlights the role of adipokines in breast cancer, with a focus on disease progression, therapeutic challenges, and knowledge gaps. Clarifying how obesity alters tumor biology is key to advancing personalized and effective treatments for obese patients.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":"476-492"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What's new in neoplastic pulmonary pathology 2026: updates on grading, staging and molecular testing.","authors":"Andreas Tiefenbacher, Luka Brčić","doi":"10.4132/jptm.2026.07.28","DOIUrl":"10.4132/jptm.2026.07.28","url":null,"abstract":"<p><p>Neoplastic pulmonary pathology has continued to advance in recent years, including the introduction of histologic grading systems for both adenocarcinoma and squamous cell carcinoma, implementation of the UICC TNM 9th Edition classification, expanded molecular testing requirements, refinements in neuroendocrine tumor classification, and improvements in mesothelioma diagnostics. This newsletter summarizes the most important developments relevant to practicing pathologists.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"60 5","pages":"587-591"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spread through air spaces as a marker of nonlinear evolutionary trajectories in lung cancer: implications for the 9th edition TNM classification.","authors":"Jin-Haeng Chung","doi":"10.4132/jptm.2026.06.16","DOIUrl":"10.4132/jptm.2026.06.16","url":null,"abstract":"<p><p>Recent advancements in the diagnosis and therapeutic management of lung cancer have contributed to an evolution in pathological reporting standards. The 8th edition of the TNM classification of lung tumors has introduced the invasive size of adenocarcinoma-rather than total tumor size-as the primary determinant for staging. Concurrently, histological grading criteria proposed by the International Association for the Study of Lung Cancer (IASLC), based on predominant and highest-grade architectural patterns, appear to offer improved clinical utility over legacy systems. In addition, tumor spread through air spaces (STAS) has emerged as an actively investigated pattern of invasion, characterized by the presence of neoplastic cells beyond the main tumor mass within the adjacent pulmonary parenchyma. STAS is frequently observed in advanced-stage and node-positive non-small cell lung cancer and often correlates with distant metastasis. Recognizing its clinical relevance, the IASLC Staging Project recently recommended incorporating STAS as a histologic T descriptor in the 9th edition of the TNM classification. Expanding upon this framework, this review explores STAS not merely as a prognostic indicator, but as a potential reflection of divergent evolutionary trajectories influenced by underlying driver mutations. Accordingly, this review aims to comprehensively synthesize the prevailing controversies and recent academic milestones regarding STAS, the current limitations in preoperative STAS risk prediction, the logistical hurdles of intraoperative diagnosis, and critically evaluates the need for prospective clinical trials to validate STAS as a predictive biomarker for adjuvant systemic therapy.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"60 5","pages":"463-475"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchial lesions in a high serum IgA mouse model: pulmonary venular IgA deposition and spatially distinct lymphoid cell aggregation.","authors":"Areum Kim, Minhyeok Lee, Yohan Park, Wan Jin Hwang, Hyeseung Lee, Joo Heon Kim, Jin Man Kim, Yong Min Kim, Jin Sun Park, Junguee Lee","doi":"10.4132/jptm.2026.06.01","DOIUrl":"10.4132/jptm.2026.06.01","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin A (IgA) nephropathy is a systemic immune complex-mediated disease primarily affecting the kidneys, yet pulmonary involvement remains poorly characterized. This study investigated pulmonary structural alterations, IgA deposition, immune cell distribution, and the impact of chronic environmental immune stimulation.</p><p><strong>Methods: </strong>High-IgA (HIGA) mice and BALB/c controls were examined under baseline conditions and following chronic particulate matter (PM) exposure. Histopathology, immunofluorescence, immunohistochemistry, and lectin-based assays were used to assess pulmonary IgA deposition, lymphoid cell aggregation, and immune activation.</p><p><strong>Results: </strong>Compared with BALB/c controls, HIGA mice exhibited pulmonary venular remodeling characterized by thickening of the venular tunica media and IgA deposition within the smooth muscle layer. Under baseline conditions, lymphoid cell aggregation in HIGA mice was predominantly localized to peribronchial regions, whereas IgA deposition and C3a deposition were confined to pulmonary venules with minimal spatial overlap. Following PM exposure, HIGA mice developed additional perivenular lymphoid cell aggregation that spatially corresponded with IgA deposition, whereas BALB/c mice showed predominantly peribronchial aggregation. PM exposure was associated with increased pulmonary Toll-like receptor 9 (TLR9) expression in both strains. In HIGA mice, TLR9-positive immune cells and interleukin-6 (IL6) expression were enriched in perivenular lymphoid cell aggregates.</p><p><strong>Conclusions: </strong>Pulmonary IgA deposition in HIGA mice is associated with vascular remodeling and compartment-specific immune cell distribution, particularly under environmental stimulation. These findings support an association between IgA deposition and localized immune activation in the lung. However, the causal roles of TLR9 and IL6 in this process remain to be determined.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":"516-526"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148457154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrosarcoma of bone masquerading as fibrous dysplasia: diagnostic pitfall and molecular correlates of aggressive behavior.","authors":"Wangpan J Shi, Brady K Huang, Li Lei","doi":"10.4132/jptm.2026.05.29","DOIUrl":"10.4132/jptm.2026.05.29","url":null,"abstract":"<p><p>Low-grade fibro-osseous lesions can be challenging to classify. A 33-year-old man presented with synchronous lesions involving the ilium and T2 vertebra. Because of an impending pathologic fracture, he received several doses of denosumab. Initial biopsies showed bland fibro-osseous lesions lacking GNAS or MDM2 alterations and were favored to represent polyostotic fibrous dysplasia. Subsequent iliac curettage revealed a fascicular spindle cell proliferation with subtle atypia and focal ossification, leading to a revised diagnosis of low-grade fibrosarcoma. Re-biopsy of the T2 lesion demonstrated a similar spindle cell proliferation without ossification. Sequencing identified copy number gains involving KIT, PDGFRA, and TERT. At 16-month follow-up, two metastatic pulmonary nodules developed, one responsive to chemotherapy. The patient remains alive with disease at 27 months after presentation. This case highlights a diagnostic pitfall in which low-grade fibrosarcoma with denosumab-associated ossification may mimic fibrous dysplasia and underscores the prognostic value of molecular profiling beyond histologic grading.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":"60 5","pages":"578-586"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a prognostic prediction model for tumor recurrence or progression in gastrointestinal stromal tumors: integrating inflammatory blood indices with 5 mm2 versus 50 high-power field mitotic counts.","authors":"Waratchaya Tirasarnvong, Thammasin Ingviya, Paramee Thongsuksai","doi":"10.4132/jptm.2026.06.15","DOIUrl":"10.4132/jptm.2026.06.15","url":null,"abstract":"<p><strong>Background: </strong>The behavior of gastrointestinal stromal tumors varies according to tumor size, location, mitotic rate, and rupture. Traditional mitotic counting in 50 high-power fields (HPF; 5.3 mm2) may overestimate progression risk, as 5 mm2 corresponds to 20-25 HPF under modern microscopy. However, the 50-HPF method remains widely used. This study evaluated the impact of two mitotic counting methods on risk classification and developed a prognostic model combining inflammatory biomarkers with clinicopathological factors.</p><p><strong>Methods: </strong>We retrospectively analyzed 150 patients who underwent resection at Songklanagarind Hospital between 2009 and 2021. Patients who had received neoadjuvant therapy or had a second primary cancer were excluded. Mitosis was evaluated using both methods. Clinicopathological and serum biomarker data were collected. The primary outcome was 5-year disease-free or progression-free survival. The model was developed using forward stepwise variable selection based on the time-dependent area under the curve and internally validated by bootstrapping.</p><p><strong>Results: </strong>The 50-HPF method overestimated the Armed Forces Institute of Pathology classification in 14.2% of cases. A model incorporating tumor size, location, rupture, mitotic count within 5 mm2, and systemic immune-inflammation index achieved the highest area under the curve of 0.939 in both training and validation sets, outperforming previous models. The 5-mm2 method demonstrated superior performance to the 50-HPF method across all models (0.939 vs. 0.919 for the proposed model).</p><p><strong>Conclusions: </strong>Mitotic counting in 50 HPF overestimated risk classification in certain cases. Incorporating systemic immune-inflammation index and using a 5 mm2 mitotic count enhanced prognostic model performance.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":"527-538"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ki-67 index and galectin-3 as surrogate markers for predicting disease-free survival in luminal-type breast carcinoma treated with neoadjuvant chemotherapy.","authors":"Ho-Chang Lee, Wonshik Han, Seock-Ah Im, In Ae Park","doi":"10.4132/jptm.2026.06.22","DOIUrl":"10.4132/jptm.2026.06.22","url":null,"abstract":"<p><strong>Background: </strong>Residual cancer burden (RCB) is an important marker for patients with breast carcinoma treated with neoadjuvant chemotherapy (NACT). However, the association between RCB and prognosis is relatively less significant in residual luminal-type breast carcinoma (LTBC). Associations between clinicopathological variables, including RCB class, and immunohistochemical (IHC) markers with disease-free survival (DFS) were analyzed.</p><p><strong>Methods: </strong>Expression of Ki-67, calreticulin, clusterin, galectin-3, mucin-1, and p27 was assessed in tissue microarray slides of 55 post-NACT resection specimens from LTBC patients treated with docetaxel and doxorubicin. Patients' age, pre-NACT progesterone receptor status, lymphovascular invasion, histologic grade, ypT category, ypN category, RCB class, and IHC markers were analyzed for their association with DFS using Kaplan-Meier analysis and Cox proportional hazards models.</p><p><strong>Results: </strong>Twenty of the 55 patients developed recurrence or distant metastasis. A Ki-67 index > 2.7% and high galectin-3 expression were associated with shorter DFS on Kaplan-Meier analysis (p < .001 and p = .018, respectively). Other clinicopathological and IHC markers were not significantly associated with DFS. In the multivariate Cox proportional hazards model, a Ki-67 index > 2.7% (hazard ratio, 7.23; p < .001) and high galectin-3 expression (hazard ratio, 4.51; p = .007) remained independent predictors of shorter DFS.</p><p><strong>Conclusions: </strong>The Ki-67 index and high galectin-3 expression in post-NACT resection specimens may serve as surrogate markers for predicting recurrence in LTBC.</p>","PeriodicalId":46933,"journal":{"name":"Journal of Pathology and Translational Medicine","volume":" ","pages":"539-548"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}