Human pathology最新文献

{"title":"Morphologic correlates of genetic subtypes of acute myeloid leukemia.","authors":"Jessica Anderson-Calleja, Vida Ehyaee, Kamran M Mirza","doi":"10.1016/j.humpath.2026.106230","DOIUrl":"10.1016/j.humpath.2026.106230","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is increasingly defined by recurrent genetic alterations that determine disease classification, prognosis, and therapeutic strategy. Although definitive diagnosis of genetically defined subtypes relies on cytogenetic and molecular techniques, careful evaluation of bone marrow and peripheral blood morphologic findings remains an essential and immediate component of the diagnostic process. Many genetic lesions in AML are associated with reproducible morphologic findings that can guide early diagnostic suspicion, inform triage of ancillary testing, and anticipate biologic behavior. This review summarizes the major genetically defined subtypes of AML and delineates their characteristic morphologic correlates, emphasizing how integration of microscopic findings with cytogenetic and molecular data enhances diagnostic precision. By revisiting morphology through a genomic lens, we underscore its continued central role in contemporary hematopathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106230"},"PeriodicalIF":3.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of isochromosome 12p supports that pagetoid involvement of the rete testis represents spread of germ cell neoplasia in-situ.","authors":"Harini Venkatraman Ravisankar, Sounak Gupta, Carrie Brandt, Ryan Knudson, Patricia Greipp, Jennifer B Gordetsky, Giovanna Giannico, Muhammad T Idrees, Thomas M Ulbright, Andres M Acosta","doi":"10.1016/j.humpath.2026.106240","DOIUrl":"10.1016/j.humpath.2026.106240","url":null,"abstract":"<p><strong>Background: </strong>Pagetoid involvement of the rete testis (RT) in seminoma is widely interpreted as spread of germ cell neoplasia in situ (GCNIS) rather than true invasion; however, this concept is based largely on morphologic observations. Assessment of isochromosome 12p [i(12p)], a hallmark of invasive germ cell tumors that is absent in GCNIS, was used to determine the nature of pagetoid RT involvement.</p><p><strong>Methods: </strong>We retrospectively identified orchiectomy specimens with pure seminoma and pagetoid RT involvement from institutional archives. Isochromosome 12p status was assessed on formalin-fixed, paraffin-embedded tissues using fluorescence in situ hybridization (FISH) with a dual-color PKP2/D12Z3 probe. Pagetoid RT involvement, invasive seminoma, and intratubular seminoma (ITS) components were analyzed separately when present.</p><p><strong>Results: </strong>Sixteen tumors were included, with successful FISH analysis in 15 (94%). Pagetoid RT involvement was evaluable in 14 cases and demonstrated i(12p) in only 1 (∼7%), while the remaining 13 were negative. In contrast, invasive seminoma showed i(12p) in 5/14 cases (∼36%). All seminoma components negative for i(12p) showed polysomy 12, suggesting that these are mutually exclusive alterations. Cases with discordant results contained i(12p)-positive seminoma and i(12p)-negative pagetoid RT involvement. Intratubular seminoma (ITS) was present in 6 tumors, being positive for i(12p) in 2 (∼33%).</p><p><strong>Conclusions: </strong>The absence of i(12p) in pagetoid RT involvement supports its interpretation as spread of GCNIS rather than invasive tumor. Rare detection of i(12p) in RT involvement suggest that, occasionally, this lesion may represent retrograde invasion by seminoma or, more likely, in-situ progression of GCNIS.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106240"},"PeriodicalIF":3.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathologist-recommended molecular testing in endometrial cancer: A single-institution experience highlighting the recognition of POLE-Mutated carcinomas in post-menopausal and advanced stage patients, immunohistochemical pitfalls, and other clinically significant findings.","authors":"Anne M Mills, Laura Vidis, David K Carlson, Michael P Crawford, Akisha Glasgow-Austin, Vanessa L Smith, Kari L Ring, Eyas Alzayadneh","doi":"10.1016/j.humpath.2026.106237","DOIUrl":"10.1016/j.humpath.2026.106237","url":null,"abstract":"<p><p>Endometrial carcinomas cluster based on mismatch repair (MMR), TP53, and POLE exonuclease domain mutation status. Although TP53 and MMR deficiency have immunohistochemical surrogates, molecular testing is required to determine POLE status. Pathologists can identify candidates based on morphologic and immunohistochemical findings, however the outcome and limitations of pathologist-recommended molecular testing have not been investigated. We evaluated endometrial carcinomas diagnosed from 1/2022-9/2025 in which molecular testing was recommended in the pathologist's comment. Sequencing was recommended in 38 and pursued in 16 (42%). Testing impacted classification in 50% (8/16): four were POLE-mut, and four were TP53-abnormal (p53-abn) or MMR-deficient (MMRd) with molecular findings discordant with immunostaining. All POLE-mut cases were multiple classifiers diagnosed in patients >50; half were stage III; POLE-mut status down-staged one. Impactful immunohistochemical-molecular discordances occurred in two p53-abn and two no specific molecular profile (NSMP) tumors. Other unexpected molecular findings included an NSMP carcinoma with a BRCA2 mutation leading to confirmation of a germline syndrome and an MMR-deficient malignancy with TSC2 alterations which was reclassified from high-grade carcinoma to malignant PEComa. Adverse outcomes were seen in 0% of POLE-mut, 33% of p53-abn, and 67% of NSMP carcinomas. These findings suggest potential value of pathologist-directed molecular testing for identifying POLE-mut endometrial cancers, particularly in post-menopausal patients with abnormal p53 and high-grade histology, and in selected stage III patients, in whom these features might not prompt clinical consideration for molecular work-up. They also illustrate limitations of immunohistochemical surrogates and ProMisE classification, the potential for aggressive behavior in NSMP tumors with POLE-like histomorphology, and the role of molecular testing in identifying clinically impactful mutations beyond POLE.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106237"},"PeriodicalIF":3.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic patterns of metastatic lymph nodes and recurrence patterns in resected pN1-2 lung adenocarcinoma.","authors":"Masayoshi Watanabe, Tetsuro Taki, Shunta Tsuchida, Kotaro Nomura, Masataka Kawai, Masashi Wakabayashi, Yoichi Ohtaki, Tomohiro Miyoshi, Kenta Tane, Yuki Matsumura, Keiju Aokage, Yukiko Sasahara, Michiko Nagamine, Shingo Sakashita, Naoya Sakamoto, Keisuke Asakura, Masahiro Tsuboi, Genichiro Ishii","doi":"10.1016/j.humpath.2026.106232","DOIUrl":"10.1016/j.humpath.2026.106232","url":null,"abstract":"<p><strong>Aims: </strong>Histologic grading of the primary tumor (PT) is an established prognostic factor in lung adenocarcinoma; however, the clinical relevance of histologic patterns in metastatic lymph nodes (MLNs) remains unclear. This study investigated whether MLN histology is associated with recurrence patterns after complete resection.</p><p><strong>Methods: </strong>We retrospectively analyzed 120 patients with pN1-2 lung adenocarcinoma who underwent complete resection at a single institution. Predominant histologic patterns of PTs and MLNs were categorized as low grade (lepidic), intermediate grade (papillary or acinar), or high grade (solid or micropapillary). Survival outcomes and recurrence patterns (locoregional vs distant) were compared across MLN histologic groups.</p><p><strong>Results: </strong>Predominant histologic patterns were frequently discordant between PTs and MLNs (McNemar test, P = 0.01; κ = 0.25). High-grade PTs were associated with significantly shorter recurrence-free survival (RFS) than intermediate-grade tumors (P = 0.02), whereas MLN histology was not associated with RFS (P = 0.70). PT histology was not significantly related to recurrence site. In contrast, intermediate-grade MLNs showed a significantly higher incidence of locoregional recurrence than high-grade MLNs (P = 0.04), which was confirmed by cumulative incidence analysis (P = 0.02). Distant recurrence rates were comparable between the two groups (P = 0.39).</p><p><strong>Conclusions: </strong>While histologic grading of the primary tumor reflects overall tumor aggressiveness and prognosis, the histologic architecture of metastatic lymph nodes may be associated with recurrence patterns rather than survival outcomes. These findings suggest that MLN morphology may provide complementary pathological information regarding patterns of locoregional recurrence after surgical resection.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106232"},"PeriodicalIF":3.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid nodules of uncertain malignant potential non-conforming to World Health Organization diagnostic criteria - clinicopathologic and molecular characterization of 39 cases.","authors":"Shaden N Hamada, Peter M Sadow, William C Faquin, Adam S Fisch, Gregory W Randolph, Marika D Russell, Bayan A Alzumaili","doi":"10.1016/j.humpath.2026.106239","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106239","url":null,"abstract":"<p><p>Thyroid tumors of uncertain malignant potential (UMP) are recognized by the World Health Organization (WHO) as tumors of borderline malignancy, encompassing follicular tumor of uncertain malignant potential (FT-UMP) and well-differentiated tumor of uncertain malignant potential (WDT-UMP). Tumors classified as UMP have questionable capsular invasion (CI) and/or angioinvasion (AI); however, biological uncertainty extends beyond the possibility for invasiveness alone. We conducted a retrospective, single-center study of all thyroid tumors diagnosed as UMP (2005-2025). Upon review of our institutional UMP cohort, we identified 39 tumors that lack questionable CI and/or AI, and therefore, would not meet WHO-defined UMP criteria. This retrospective analytic group of borderline thyroid nodules (BTN) was used to interrogate the overlap between non-invasive follicular-patterned thyroid lesions and worrisome morphologic and/or molecular features. BTN show features of neoplasia (solid growth or microfollicular architecture, papillary thyroid carcinoma (PTC)-like nuclear atypia, oncocytic morphology, conspicuous mitoses, and/or abnormal molecular results) with or without procedural artifacts (mechanically disrupted capsule, squamous metaplasia or ischemic necrosis). BTN were diagnosed in 0.1% of thyroid surgeries; median age 55 years and 1.3:1 female-to-male ratio. Median tumor size was 4 cm. RAS or RAS-like variants were most frequent (25%), followed by gene fusions (10%). Negative molecular testing was identified in 10% of BTN and high-risk gene alterations, including TERT promoter and PIK3CA, were seen in 20%. Most patients underwent hemithyroidectomy (62%), with median follow-up of 2.5 years (range 1-12.5 years), and no recurrences or metastases were documented. Our findings suggest indolent behavior of BTN and support conservative management, such as hemithyroidectomy. Longer-term, multi-institutional studies will refine risk stratification and management strategies, with possible consideration for expanding UMP diagnostic criteria.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106239"},"PeriodicalIF":3.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine cell proliferation in gastric and gastroesophageal carcinomas following neoadjuvant therapy: Frequency and association with clinicopathological parameters and prognosis.","authors":"Serra Begum Emecen, Burcin Pehlivanoglu, Sulen Sarioglu, Anil Aysal, Zekai Serhan Derici, Koray Atila, Tugba Yavuzsen, Faruk Recep Ozalp, Barbaros Aydin, Ozgul Sagol","doi":"10.1016/j.humpath.2026.106235","DOIUrl":"10.1016/j.humpath.2026.106235","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the frequency of neuroendocrine cell proliferation (NCP) in the tumor bed and adjacent mucosa in gastric and gastroesophageal junction carcinomas that had received neoadjuvant therapy, and to elucidate its prognostic significance.</p><p><strong>Material and methods: </strong>In 83 patients diagnosed with gastric or gastroesophageal junction adenocarcinoma who had received neoadjuvant therapy, the presence and the extent of NCP in the tumor bed and adjacent mucosa was examined and scored by chromogranin A immunohistochemistry and the association of this proliferation with other clinicopathological parameters was statistically analyzed.</p><p><strong>Results: </strong>NCP was seen in the damaged, reparative or tumor-infiltrated mucosa in the tumor bed and the normal mucosa adjacent to the tumor in 46 cases (55.4%), as score 1 in 23 (27.7%), score 2 in 13 (15.7%) and score 3 in 10 (12%). This proliferation was not statistically associated with intestinal metaplasia (p = 0.683) and atrophy (p = 0.414). ypT stage was significantly correlated with NCP (p = 0.015) however there was no significant association between NCP and survival. No statistically significant association was found between the other clinicopathological parameters and NCP.</p><p><strong>Conclusion: </strong>Non-neoplastic NCP both in the tumor bed and surrounding gastric mucosa is observed in a subset of cases following neoadjuvant therapy, and it does not appear to have any prognostic significance. However, further investigation is required to explore the cause of this proliferation.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106235"},"PeriodicalIF":3.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant chemotherapy remodels the three-dimensional vascular architecture and immune microenvironment in pancreatic ductal adenocarcinoma.","authors":"Yoshiki Nishiyama, Keno Kudo, Michi Izawa, Shintaro Goto, Kenta Ogasawara, Daiki Kasai, Satoru Tsuruta, Yusuke Wakasa, Hayato Nagase, Hiroshi Kijima, Kenichi Hakamada, Kiyoko Oshima, Keinosuke Ishido, Tadashi Yoshizawa","doi":"10.1016/j.humpath.2026.106238","DOIUrl":"10.1016/j.humpath.2026.106238","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME) and poor treatment responsiveness. Although neoadjuvant chemotherapy (NAC) can improve clinical outcomes, its effects on the TME, particularly the interplay between vascular remodeling and immune reprogramming, remain poorly understood. This study examined the impact of NAC on both the immune cell composition and vascular structure of PDAC.</p><p><strong>Methods: </strong>Immunohistochemistry of immune cell infiltration was performed in PDAC tissues resected from 56 patients. In a separate cohort of 26 patients, three-dimensional vascular analysis using tissue clearing and confocal imaging was performed alongside immunohistochemistry-based evaluation of vessel proportions. Immunohistochemistry was used to evaluate CD4⁺ T cells, CD8⁺ T cells, FoxP3⁺ regulatory T cells, CD163⁺ macrophages, CD34⁺ pan-endothelial cells, and CD105⁺ tumor-associated endothelial cells. Vascular morphology, including vessel length, surface area, and volume, was quantified by three-dimensional reconstruction. All comparisons were performed at the patient level.</p><p><strong>Results: </strong>NAC-treated tissues exhibited increased CD4⁺ and stromal CD8⁺ T cell infiltration, a reduced FoxP3⁺/CD4⁺ ratio, and an increased tumoral CD8⁺/CD163⁺ ratio. NAC was associated with shorter vessel length and a selective reduction in CD105⁺ tumor-associated vessels, with unchanged total CD34⁺ vessel density. These changes were generally more pronounced in patients with a better treatment response.</p><p><strong>Conclusion: </strong>NAC was associated with coordinated TME remodeling involving both immune and vascular components. This integrated remodeling might contribute to the development of an immunologically activated tumor phenotype and support the rationale for combination strategies with immunotherapy in PDAC.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106238"},"PeriodicalIF":3.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: Concordance between immunohistochemistry and chromogenic in situ hybridization in 140 Cases.","authors":"Valentina Angerilli, Jessica Gasparello, Monia Niero, Lucia Zanatta, Carlotta Ceccon, Marianna Sabbadin, Giovanni Morana, Alice Boscolo, Marco Bortolotti, Adolfo Favaretto, Enrico Dalla Bona, Michele Scopellitti, Giacomo Zanus, Matteo Fassan","doi":"10.1016/j.humpath.2026.106234","DOIUrl":"10.1016/j.humpath.2026.106234","url":null,"abstract":"<p><strong>Background: </strong>HER2 represents an actionable target in a subset of biliary tract cancers (BTCs), particularly extrahepatic cholangiocarcinoma (eCCA) and gallbladder carcinoma (GBC). Recent approval of zanidatamab for HER2-positive BTC has further highlighted the clinical relevance of accurate HER2 assessment.</p><p><strong>Methods: </strong>HER2 status was evaluated in 140 consecutive surgically resected BTCs collected between 2020 and 2025 (87 eCCAs and 53 GBCs) using immunohistochemistry (IHC) and dual chromogenic in situ hybridization (DISH). HER2 expression was scored according to gastric cancer criteria, and HER2 positivity was defined following HERIZON-BTC-01 criteria. Selected cases were additionally analyzed using a combined IHC-DISH approach.</p><p><strong>Results: </strong>HER2 expression was 0 in 72.9% of cases, 1+ in 12.1%, 2+ in 8.6%, and 3+ in 6.4%. HER2 positivity was observed in 9.2% of eCCAs and 9.4% of GBCs. ERBB2 amplification was consistently identified in all IHC 3+ tumors and in a subset of IHC 2+ and, rarely, 1+ cases. The mean ERBB2/CEP17 ratio was significantly higher in HER2 3+ tumors than in amplified HER2 2+/1+ tumors (6.2 vs 3.9; p = 0.001). Combined IHC-DISH analysis confirmed concordance between HER2 overexpression and ERBB2 amplification within the same tumor cells. HER2 expression frequently showed intratumoral heterogeneity, often involving less than 50% of tumor cells.</p><p><strong>Conclusions: </strong>HER2 alterations occur in a subset of eCCA and GBC and show substantial biological heterogeneity, including lower-level amplification and intratumoral heterogeneity, with potential implications for HER2 assessment and patient selection.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106234"},"PeriodicalIF":3.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duct Quest: An international survey of genitourinary and community pathologists reveals diagnostic uncertainties in separating atypical intraductal proliferation from high-grade prostatic intraepithelial neoplasia and intraductal carcinoma of the prostate.","authors":"Marit Bernhardt, Isabella Federica Bollen, Emily Chan, Liang Cheng, Katrina Collins, Michelle Downes, Nancy Greenland, Kenneth A Iczkowski, Laura Jufe, Charlotte Kweldam, Geert van Leenders, Gladell P Paner, Joanna Perry-Keene, Anna Katrin Scherping, Toyonori Tsuzuki, Murali Varma, Sean R Williamson, Sara Wobker, Ming Zhou, Xiaolin Zhou, Rajal B Shah, Glen Kristiansen","doi":"10.1016/j.humpath.2026.106233","DOIUrl":"10.1016/j.humpath.2026.106233","url":null,"abstract":"<p><p>Atypical intraductal proliferations of the prostate encompass a spectrum from high-grade prostatic intraepithelial neoplasia (HGPIN) to intraductal carcinoma of the prostate (IDCP), the latter being strongly associated with aggressive prostate cancer. The recent WHO classification introduced atypical intraductal proliferation (AIP) to describe lesions intermediate between HGPIN and IDCP. To assess current diagnostic practice and variability prior to implementation of new consensus recommendations, we surveyed 541 pathologists from four national and international pathology societies (Genitourinary Society of Pathology (GUPS), International Society of Urological Pathology (ISUP), British Association of Urological Pathology (BAUP), and German Division of the International Academy of Pathology (GDIAP)). Participants widely supported the Guo/Epstein criteria for diagnosing IDCP and generally agreed that when IDCP is found in the absence of high-grade cancer on needle biopsy, unsampled high-grade cancer is almost always present, reinforcing its role as an exclusion criterion for active surveillance. However, opinions varied on whether IDCP is a precursor lesion or a growth pattern of invasive cancer. Participants reviewed 25 images of intraductal lesions classified as benign, HGPIN, AIP, or IDCP. Consensus (>2/3 agreement) was reached in only 36% of cases, and no AIP case achieved consensus. Grouping lesions into low-grade (benign/HGPIN) versus high-grade (AIP/IDCP) categories increased consensus to 88%. Consensus was higher for AIP + IDCP (60%) than for HGPIN + AIP (32%), suggesting closer diagnostic alignment of AIP with IDCP. These findings highlight persistent interobserver variability and the need for clearer diagnostic criteria, education, and further biological characterization of AIP and IDCP.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106233"},"PeriodicalIF":3.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological differences between idiopathic and secondary interstitial pneumonia: An elastic fiber-oriented deep learning analysis.","authors":"Hiroyuki Katsuragawa, Hiroaki Ito, Tomohiro Handa, Ryo Sakamoto, Daisuke Nakajima, Hiroshi Date, Hironori Haga, Akihiko Yoshizawa","doi":"10.1016/j.humpath.2026.106236","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106236","url":null,"abstract":"<p><p>Fibrotic interstitial lung diseases (ILDs) are classified into histopathological patterns by the idiopathic interstitial pneumonia (IIP) classification, and not only IIP but also secondary interstitial pneumonia (SIP) are evaluated based on the classification system, and the final integrated diagnosis is established through multidisciplinary discussion. However, distinguishing IIP from SIP is often challenging. This study aimed to investigate differences in collagen and elastic fiber composition between idiopathic and secondary ILDs using machine-learning-based quantitative analysis. We analyzed 780 Elastica van Gieson (EVG)-stained whole-slide images obtained from 93 patients with fibrotic ILDs who underwent lung transplantation using the HALO-AI. Fibrotic areas were identified, and collagen and elastic fiber areas were quantitatively measured. Among the elastic fibers, the area of elastic fiber aggregation was identified based on the increased density and dark staining intensity on EVG staining. Although no significant differences were observed between IIP and SIP in the collagen fiber area or total elastic fiber area, the elastic fiber aggregation area/fibrosis area ratio was significantly higher in SIP, particularly in the lower lobes (P = 0.0010). Similar findings were observed in the subgroup analyses of usual interstitial pneumonia pattern and nonspecific interstitial pneumonia pattern, in which secondary cases demonstrated significantly greater elastic fiber aggregation than idiopathic cases in both the upper and lower lobes. In conclusion, SIPs exhibit greater elastic fiber aggregation than IIPs. These findings suggest that assessments of the quantity and structural characteristics of elastic fibers help to facilitate the differential diagnosis of ILDs and provide novel insights into disease pathogenesis.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106236"},"PeriodicalIF":3.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}