Modern Pathology最新文献

{"title":"Pathologic Features of Malignancies Presenting as Asymmetry on Mammography","authors":"Mohamed M.H. Kahila ,&nbsp;Allyson L. Chesebro ,&nbsp;Catherine S. Giess ,&nbsp;Esther Rhei ,&nbsp;Xuefei Hong ,&nbsp;Susan C. Lester","doi":"10.1016/j.modpat.2024.100612","DOIUrl":"10.1016/j.modpat.2024.100612","url":null,"abstract":"<div><div>The majority of breast cancers have a solid tumor growth pattern and are seen on mammography as dense masses with defined borders. Cancers detected as asymmetry are rare, and little has been published about their pathologic features. These cancers do not form discrete masses, and a border is not evident. This retrospective case series was undertaken to identify malignancies presenting as asymmetry, to describe their histologic and biologic features and to correlate these features with the mammographic appearance. During the 7.5 years of the study, 18,419 coreneedle biopsies were performed and 42 cases of malignancy presenting as asymmetry were diagnosed (0.2%). The majority were invasive carcinomas (30% or 71%), followed by ductal carcinoma in situ (9% or 21%) and lymphoma (3% or 7%). The invasive carcinomas could be divided into 3 groups: very small unifocal (T1a) carcinomas, larger unifocal carcinomas, and cases with multiple foci of invasion. The latter group had a higher rate of lymph node metastases and more stage III cancers. The invasive carcinomas were predominantly of special histologic types and associated with a minimal stromal response. In contrast, the cases of ductal carcinoma in situ tended to be of higher grade and elicited periductal fibrosis, which likely contributed to the increased density seen on mammography. Although most of the invasive carcinomas were of favorable biologic type (97%) and were stage I (67%), triple-negative carcinomas and stage III carcinomas were also detected. When evaluating core needle biopsies performed for asymmetry, pathologists should be aware that these cancers can have a subtle infiltrative appearance with little or no desmoplastic response, mirroring their appearance by imaging.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100612"},"PeriodicalIF":7.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Streamlines the Morphometric Characterization and Multiclass Segmentation of Nuclei in Different Follicular Thyroid Lesions: Everything in a NUTSHELL","authors":"Vincenzo L’Imperio ,&nbsp;Vasco Coelho ,&nbsp;Giorgio Cazzaniga ,&nbsp;Daniele M. Papetti ,&nbsp;Fabio Del Carro ,&nbsp;Giulia Capitoli ,&nbsp;Mario Marino ,&nbsp;Joranda Ceku ,&nbsp;Nicola Fusco ,&nbsp;Mariia Ivanova ,&nbsp;Andrea Gianatti ,&nbsp;Marco S. Nobile ,&nbsp;Stefania Galimberti ,&nbsp;Daniela Besozzi ,&nbsp;Fabio Pagni","doi":"10.1016/j.modpat.2024.100608","DOIUrl":"10.1016/j.modpat.2024.100608","url":null,"abstract":"<div><div>The diagnostic assessment of thyroid nodules is hampered by the persistence of uncertainty in borderline cases and further complicated by the inclusion of noninvasive follicular tumor with papillary-like nuclear features (NIFTP) as a less aggressive alternative to papillary thyroid carcinoma (PTC). In this setting, computational methods might facilitate the diagnostic process by unmasking key nuclear characteristics of NIFTP. The main aims of this work were to (1) identify morphometric features of NIFTP and PTC that are interpretable for the human eye and (2) develop a deep learning model for multiclass segmentation as a support tool to reduce diagnostic variability. Our findings confirmed that nuclei in NIFTP and PTC share multiple characteristics, setting them apart from hyperplastic nodules (HP). The morphometric analysis identified 15 features that can be translated into nuclear alterations readily understandable by pathologists, such as a remarkable internuclear homogeneity for HP in contrast to a major complexity in the chromatin texture of NIFTP and to the peculiar pattern of nuclear texture variability of PTC. A few NIFTP cases with available next-generation sequencing data were also analyzed to initially explore the impact of RAS-related mutations on nuclear morphometry. Finally, a pixel-based deep learning model was trained and tested on whole-slide images of NIFTP, PTC, and HP cases. The model, named NUTSHELL (NUclei from Thyroid tumors Segmentation to Highlight Encapsulated Low-malignant Lesions), successfully detected and classified the majority of nuclei in all whole-slide image tiles, showing comparable results with already well-established pathology nuclear scores. NUTSHELL provides an immediate overview of NIFTP areas and can be used to detect microfoci of PTC within extensive glandular samples or identify lymph node metastases. NUTSHELL can be run inside WSInfer with an easy rendering in QuPath, thus facilitating the democratization of digital pathology.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100608"},"PeriodicalIF":7.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Conflicting Prognostic Role of the Stroma–Tumor Ratio in Breast Cancer Molecular Subtypes","authors":"Suzan F. Ghannam ,&nbsp;Shorouk Makhlouf ,&nbsp;Mansour Alsaleem ,&nbsp;Catrin Sian Rutland ,&nbsp;Cinzia Allegrucci ,&nbsp;Nigel P. Mongan ,&nbsp;Emad A. Rakha","doi":"10.1016/j.modpat.2024.100607","DOIUrl":"10.1016/j.modpat.2024.100607","url":null,"abstract":"<div><div>The tumor microenvironment plays a key role in tumor progression. The proportion of the stroma-to-tumor cells (stroma-tumor ratio [STR]) has a variable prognostic significance in breast cancer (BC) molecular classes. In this study, we evaluated the mechanisms of stroma formation and composition in different molecular subtypes, which could explain the different prognostic values. This study interrogated 2 large well-characterized BC cohorts. Firstly, an in-house BC cohort (n = 822) encompassing all BC molecular subtypes from the Nottingham series was used. In each subtype, stromal assessment was carried out, and tumors were assigned to 2 groups: high and low STR, and further correlation with tumor characteristics and patient outcomes was investigated. The contribution of tumor-infiltrating lymphocytes (TILs) to the stroma has also been studied. Secondly, the public domain data set (The Cancer Genome Atlas data [TCGA], n = 978) was used as a validation cohort and for differential gene expression (DGE) analysis. DGE was performed to identify a set of genes associated with high STR in the 3 main molecular subtypes. High STR was associated with favorable patient outcomes in the whole cohort and in the luminal subtype, whereas high STR showed an association with poor outcomes in triple-negative BC (TNBC). No association with outcome was found in the HER2 enriched BC. DGE analysis identified various pathways in luminal and TNBC subtypes, with immune upregulation and hypoxia pathways enriched in TNBC, and pathways related to fibrosis and stromal remodeling enriched in the luminal group instead. Low STR accompanied by high TILs was shown to carry the most favorable prognosis in TNBC. In line with the DGE results, TILs played a major prognostic role in the stroma of TNBC but not in the luminal or HER2-enriched subtypes. The underlying molecular mechanisms and composition of the stroma in BC are variable in the molecular subtypes and explain the difference in its prognostic significance.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100607"},"PeriodicalIF":7.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroid Synoviocytic Neoplasm: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of a Distinctive Tumor of Synoviocytes","authors":"Erica Y. Kao ,&nbsp;Fisun Ardic ,&nbsp;Numrah Fadra ,&nbsp;Jessica D. Hohenstein ,&nbsp;Rohini Mopuri ,&nbsp;Doris E. Wenger ,&nbsp;Lukas Streich ,&nbsp;Lisa M. Hines ,&nbsp;Andrew L. Folpe","doi":"10.1016/j.modpat.2024.100598","DOIUrl":"10.1016/j.modpat.2024.100598","url":null,"abstract":"<div><p>Tumors resembling tenosynovial giant cell tumor (TGCT) but additionally forming chondroid matrix are rare and most often involve the temporomandibular joint (TMJ). We studied 21 tumors consisting of synoviocytes (large, eosinophilic mononuclear cells containing hemosiderin) and chondroid matrix to better understand these unusual neoplasms. The tumors occurred in 10 males and 11 females, in the age group of 31 to 80 years (median, 50 years) and involved the TMJ region (16), extremities (4), and spine (1). As in conventional TGCT, all were composed of synoviocytes, small histiocytes, foamy macrophages, siderophages, and osteoclast-like giant cells in variably hyalinized background. Expansile nodules of large, moderately atypical synoviocytes were present, in addition to “chondroblastoma-like,” “chondroma-like,” or “phosphaturic mesenchymal tumor-like” calcified matrix. The synoviocytes expressed clusterin (17/19) and less often desmin (3/15). The tumors were frequently CSF1 positive by chromogenic in situ hybridization (8/13) but at best weakly positive for CSF1 by immunohistochemistry (0/3). Background small histiocytes were CD163 positive (12/12). All were FGF23 negative (0/10). Cells within lacunae showed a synoviocytic phenotype (clusterin positive; S100 protein and ERG negative). RNA-Seq was successful in 13 cases; fusions were present in 7 tumors, including <em>FN1::TEK</em> (5 cases); <em>FN1::PRG4</em> (2 cases); and <em>MALAT1::FN1</em>, <em>PDGFRA::USP35</em>, and <em>TIMP3::ZCCHC7</em> (1 case each). Three tumors contained more than 1 fusion (<em>FN1::PRG4</em> with <em>TIMP3::ZCCHC7</em>, <em>FN1::TEK</em> with <em>FN1::PRG4</em>, and <em>FN1::TEK</em> with <em>MALAT1::FN1</em>). Clinical follow-up (17 patients; median follow-up duration 38 months; range 4-173 months) showed 13 (76%) to be alive without evidence of disease and 4 (24%) to be alive with persistent/recurrent local disease. No metastases or deaths from disease were observed. We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term “chondroid synoviocytic neoplasm,” rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 11","pages":"Article 100598"},"PeriodicalIF":7.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acral Fibrochondromyxoid Tumor: A Clinicopathologic and Molecular Genetic Study of 37 Cases","authors":"Carina A. Dehner ,&nbsp;Hadley Pearson ,&nbsp;Shahd S. Almohsen ,&nbsp;Ying-Chun Lo ,&nbsp;Judith Jebastin Thangaiah ,&nbsp;Jorge Torres-Mora ,&nbsp;Ruifeng (Ray) Guo ,&nbsp;Jonathan C. Baker ,&nbsp;Andrew L. Folpe ,&nbsp;Ahmed K. Alomari ,&nbsp;Brendan C. Dickson ,&nbsp;Steven D. Billings ,&nbsp;Michael Michal ,&nbsp;Elizabeth G. Demicco ,&nbsp;Karen J. Fritchie ,&nbsp;John S.A. Chrisinger","doi":"10.1016/j.modpat.2024.100599","DOIUrl":"10.1016/j.modpat.2024.100599","url":null,"abstract":"<div><p>Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent <em>THBS1::ADGRF5</em> fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that tumor cells were positive for CD34 (25/27; 93%) and ERG (27/27; 100%), whereas negative for S100 protein (0/31). Molecular analysis revealed evidence of a <em>THBS1::ADGRF5</em> fusion in 17 of 19 (89%) successfully tested tumors. Clinical follow-up was available in 8 cases (median: 97 months), with multiple local recurrences in 1 case at 276, 312, and 360 months. We conclude that AFCMT is a distinct entity with reproducible morphologic, immunohistochemical, and molecular genetic features that should be differentiated from other similar appearing acral mesenchymal neoplasms.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100599"},"PeriodicalIF":7.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0893395224001790/pdfft?md5=ae76ad642139c78c0c55b0c2764e6472&pid=1-s2.0-S0893395224001790-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted DNA Sequencing in Diagnosis of Malignant Phyllodes Tumors With Emphasis on Tumors With Keratin and p63 Expression","authors":"Julia Ye ,&nbsp;Talent Theparee ,&nbsp;Gregory R. Bean ,&nbsp;Cooper D. Rutland ,&nbsp;Christopher J. Schwartz ,&nbsp;Poonam Vohra ,&nbsp;Grace Allard ,&nbsp;Aihui Wang ,&nbsp;Elizabeth M. Hosfield ,&nbsp;Yan Peng ,&nbsp;Yunn-Yi Chen ,&nbsp;Gregor Krings","doi":"10.1016/j.modpat.2024.100593","DOIUrl":"10.1016/j.modpat.2024.100593","url":null,"abstract":"<div><div>The differential diagnosis of malignant spindle cell neoplasms in the breast most frequently rests between malignant phyllodes tumor (MPT) and metaplastic carcinoma (MBC). Diagnosis of MPT can be challenging due to diffuse stromal overgrowth, keratin (CK) and/or p63 immunopositivity, and absent CD34 expression, which can mimic MBC, especially in core biopsies. Distinction of MPT from MBC has clinical implications, with differences in surgical approach, chemotherapy, and radiation. In this study, we evaluated MPTs (78 tumors, 64 patients) for stromal CK, p63, and CD34 expression and profiled a subset (n = 31) by targeted next-generation DNA sequencing, with comparison to MBC (n = 44). Most MPTs (71%) were CK+ and/or p63+, including 32% CK+ (25/77 focal) and 65% p63+ (32/66 focal, 10/66 patchy, and 1/66 diffuse). Thirty percent of MPTs expressed both CK and p63 (20/66), compared with 95% of MBCs (40/42, <em>P</em> &lt; .001). CK and/or p63 were positive in CD34+ and CD34− MPTs. Recurrent genetic aberrations in MPTs involved <em>TERT</em>, <em>TP53</em>, <em>MED12</em>, <em>CDKN2A</em>, chromatin modifiers, growth factor receptors/ligands, and phosphoinositide-3 kinase (PI-3K) and MAPK pathway genes. Only <em>MED12</em> (39%, 12/31) and <em>SETD2</em> (13%, 4/31) were exclusively mutated in MPTs and not MBCs (<em>P</em> &lt; .001 and <em>P</em> = .044, respectively), whereas <em>PIK3R1</em> mutations were only found in MBCs (37%, 13/35, <em>P</em> &lt; .001). Comparative literature review additionally identified <em>ARID1B</em>, <em>EGFR</em>, <em>FLNA</em>, <em>NRAS</em>, <em>PDGFRB</em>, <em>RAD50</em>, and <em>RARA</em> alterations enriched or exclusively in MPTs vs MBCs. <em>MED12</em> was mutated in MPTs with diffuse stromal overgrowth (53%, 9/17), CD34− MPTs (41%, 7/17), and CK+ and/or p63+ MPTs (39%, 9/23), including 36% of CD34− MPTs with CK and/or p63 expression. Overall, <em>MED12</em> mutation and/or CD34 expression were observed in 68% (21/31) MPTs, including 61% (14/23) of CK+ and/or p63+ tumors. Our results emphasize the prevalence of CK and p63 expression in MPTs and demonstrate the diagnostic utility of next-generation DNA sequencing, especially in MPTs with confounding factors that can mimic MBC.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 12","pages":"Article 100593"},"PeriodicalIF":7.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Squamoid Eccrine Ductal Carcinoma Displays Ultraviolet Mutations and Intermediate Gene Expression Relative to Squamous Cell Carcinoma, Microcystic Adnexal Carcinoma, and Porocarcinoma","authors":"Paul W. Harms ,&nbsp;Mason Runge ,&nbsp;May P. Chan ,&nbsp;Chia-Jen Liu ,&nbsp;Zhaoping Qin ,&nbsp;Francis Worden ,&nbsp;Dan R. Robinson ,&nbsp;Arul M. Chinnaiyan ,&nbsp;Scott A. Mclean ,&nbsp;Kelly L. Harms ,&nbsp;Douglas R. Fullen ,&nbsp;Rajiv M. Patel ,&nbsp;Aleodor A. Andea ,&nbsp;Aaron M. Udager","doi":"10.1016/j.modpat.2024.100592","DOIUrl":"10.1016/j.modpat.2024.100592","url":null,"abstract":"<div><p>Squamoid eccrine ductal carcinoma is a rare infiltrative tumor with morphologic features intermediate between squamous cell carcinoma (SCC) and sweat gland carcinomas such as microcystic adnexal carcinoma. Although currently classified as a sweat gland carcinoma, it has been debated whether squamoid eccrine ductal carcinoma is better classified as a variant of SCC. Furthermore, therapeutic options for patients with advanced disease are lacking. Here, we describe clinicopathologic features of a cohort of 15 squamoid eccrine ductal carcinomas from 14 unique patients, with next-generation sequencing DNA profiling for 12 cases. UV signature mutations were the dominant signature in the majority of cases. <em>TP53</em> mutations were the most highly recurrent specific gene alteration, followed by mutations in <em>NOTCH</em> genes. Recurrent mutations in driver oncogenes were not identified. By unsupervised comparison of global transcriptome profiles in squamoid eccrine ductal carcinoma (n = 7) to SCC (n = 10), porocarcinoma (n = 4), and microcystic adnexal carcinoma (n = 4), squamoid eccrine ductal carcinomas displayed an intermediate phenotype between SCC and sweat gland tumors. Squamoid eccrine ductal carcinoma displayed significantly higher expression of 364 genes (including certain eccrine markers) and significantly lower expression of 525 genes compared with other groups. Our findings support the classification of squamoid eccrine ductal carcinoma as a carcinoma with intermediate features between SCC and sweat gland carcinoma.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 11","pages":"Article 100592"},"PeriodicalIF":7.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant Sertoli-Leydig Cell Tumor With CTNNB1 Mutation Arising in a Cryptorchid Testis","authors":"Mariko Yasui ,&nbsp;Yoshinao Kikuchi ,&nbsp;Yoshiki Mikami ,&nbsp;Takako Kiyokawa ,&nbsp;Kosuke Miyai ,&nbsp;Maiko Tsuchiya ,&nbsp;Shiori Watabe ,&nbsp;Tomoyuki Kaneko ,&nbsp;Taketo Kawai ,&nbsp;Tohru Nakagawa ,&nbsp;Yuko Sasajima ,&nbsp;Hiroshi Uozaki","doi":"10.1016/j.modpat.2024.100587","DOIUrl":"10.1016/j.modpat.2024.100587","url":null,"abstract":"","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 10","pages":"Article 100587"},"PeriodicalIF":7.1,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spread Through Air Spaces: Interresponder Agreement and Comparison Between Pulmonary and General Pathologists","authors":"Michelle Garlin-Politis ,&nbsp;Anjali Saqi ,&nbsp;Mari Mino-Kenudson","doi":"10.1016/j.modpat.2024.100596","DOIUrl":"10.1016/j.modpat.2024.100596","url":null,"abstract":"<div><p>Spread through air spaces (STAS), an important prognostic indicator included in the 2015 World Health Organization classification, is defined as micropapillary, solid, and/or single tumor cell clusters beyond the edge of the main mass and distinct from processing artifacts. This study aimed to assess the interresponder agreement on current STAS criteria vs artifacts, identify discrepancies, and compare responses between pulmonary and general pathologists. A multiple-choice online questionnaire illustrating multiple criteria for STAS vs artifacts was available internationally for 6 days to Pulmonary Pathology Society members, thoracic pathology course attendees, and International Association for the Study of Lung Cancer pathology committee members. Additional 4 questions gathered demographic and practice setting information. One hundred thirty-six unique responses were analyzed. The majority were from North America and Europe (42.6% and 30.2%), practicing pulmonary pathology (70.6%) in academia (64.7%), and with &gt;20 years of experience (31.6%). Excluding trainees, the greatest overall agreement was in defining solid and micropapillary tumor clusters of STAS located ≥3 alveolar spaces from the main tumor edge (91.5%) and recognizing strips of ciliated cells as artifacts (97.7%). Lesser agreement on STAS was evident when tumor cell clusters were immediately adjacent to the tumor edge, a single tumor cell cluster was present at the tissue edge, tumor cell clusters were jagged edged, or tumor cell clusters were admixed with ciliated cell strips (artifacts). There was no significant difference in agreements on STAS for multiple criteria between pulmonary and general pathologists. Significant interresponder agreement on STAS vs artifacts was achieved only for a few criteria. To improve the reproducibility of STAS vs artifacts, areas of lesser agreement require further clarification.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 11","pages":"Article 100596"},"PeriodicalIF":7.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Immunofluorescence-Guided Segmentation Model in Hematoxylin and Eosin Images Is Enabled by Tissue Artifact Correction Using a Cycle-Consistent Generative Adversarial Network","authors":"Marcel Wiedenmann ,&nbsp;Mariya Barch ,&nbsp;Patrick S. Chang ,&nbsp;Jennifer Giltnane ,&nbsp;Tyler Risom ,&nbsp;Andries Zijlstra","doi":"10.1016/j.modpat.2024.100591","DOIUrl":"10.1016/j.modpat.2024.100591","url":null,"abstract":"<div><p>Despite recent advances, the adoption of computer vision methods into clinical and commercial applications has been hampered by the limited availability of accurate ground truth tissue annotations required to train robust supervised models. Generating such ground truth can be accelerated by annotating tissue molecularly using immunofluorescence (IF) staining and mapping these annotations to a post-IF hematoxylin and eosin (H&amp;E) (terminal H&amp;E) stain. Mapping the annotations between IF and terminal H&amp;E increases both the scale and accuracy by which ground truth could be generated. However, discrepancies between terminal H&amp;E and conventional H&amp;E caused by IF tissue processing have limited this implementation. We sought to overcome this challenge and achieve compatibility between these parallel modalities using synthetic image generation, in which a cycle-consistent generative adversarial network was applied to transfer the appearance of conventional H&amp;E such that it emulates terminal H&amp;E. These synthetic emulations allowed us to train a deep learning model for the segmentation of epithelium in terminal H&amp;E that could be validated against the IF staining of epithelial-based cytokeratins. The combination of this segmentation model with the cycle-consistent generative adversarial network stain transfer model enabled performative epithelium segmentation in conventional H&amp;E images. The approach demonstrates that the training of accurate segmentation models for the breadth of conventional H&amp;E data can be executed free of human expert annotations by leveraging molecular annotation strategies such as IF, so long as the tissue impacts of the molecular annotation protocol are captured by generative models that can be deployed prior to the segmentation process.</p></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"37 11","pages":"Article 100591"},"PeriodicalIF":7.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}