Modern Pathology最新文献

{"title":"Shared Features of Obliterative Portal Venopathy, Normal Liver, and Chronic Liver Disease: A Histologic and Morphometric Analysis","authors":"Peizi Li ,&nbsp;Thomas D. Schiano ,&nbsp;Swan N. Thung ,&nbsp;Stephen C. Ward ,&nbsp;M. Isabel Fiel","doi":"10.1016/j.modpat.2025.100739","DOIUrl":"10.1016/j.modpat.2025.100739","url":null,"abstract":"<div><div>Obliterative portal venopathy (OPV) is a cause of noncirrhotic portal hypertension, and its diagnosis is challenging, as the features are heterogeneous, subtle, and may be mistaken as “normal.” We sought to compare OPV cases (n = 72; 326 total portal tracts [PT]) with 2 control groups: control group 1 comprised of normal liver (n = 40; 192 PTs) and control group 2 comprised of liver biopsies with chronic liver disease with OPV features (n = 40; 200 PTs). Morphometry was applied to determine the overall PT area and the luminal area of dystrophic portal veins (PVs). The frequency of absent native PVs was determined. Using trichrome-stained slides, approximately 5 PTs were randomly selected for morphometry utilizing Philips IntelliSite Pathology Solution 3.3. Clinical data were extracted from electronic health records. Of the 326 PTs in the OPV cases, phlebosclerosis was found in 31.6%, densely fibrotic PTs in 12.7%, dystrophic PVs in 31.4%, and absent native PVs in 44.5%. When comparing the OPV group with control group 1, dystrophic PVs, absent native PVs, phlebosclerosis, fibrotic PTs, greater luminal area of dystrophic PV, and a higher ratio of dystrophic PV area to PT area were more frequently found in the OPV group. No significant difference in overall PT area was found. When comparing control group 2 with OPV cases, densely fibrotic PTs were more frequent when compared with OPV cases. This study shows that absent native PVs are the most frequent feature in OPV. Other features that are less frequent but still significantly different from normal liver include dystrophic PVs, greater luminal area of dystrophic PVs, phlebosclerosis, and PT fibrosis. Except for densely fibrotic PTs in control group 2, all other features showed similar frequency as OPV. Pathologists should be aware that OPV features may be present in liver biopsies from both normal and chronic liver diseases.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 6","pages":"Article 100739"},"PeriodicalIF":7.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476731","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":"Clinical, Morphologic, and Genomic Findings in Spitz Tumors With RET Fusion: A Series of 31 Cases","authors":"Michele Donati ,&nbsp;Dimitrios Goutas ,&nbsp;Daniel Pissaloux ,&nbsp;Shantel Olivares ,&nbsp;Thibault Kervarrec ,&nbsp;Daniel Nosek ,&nbsp;Keisuke Goto ,&nbsp;Julie Lemahieu ,&nbsp;Siebe Loontiens ,&nbsp;Joni Van der Meulen ,&nbsp;Boulos Mansour ,&nbsp;Giuseppe Perrone ,&nbsp;Nicolas Macagno ,&nbsp;Pedram Gerami ,&nbsp;Dmitry V. Kazakov ,&nbsp;Arnaud De la Fouchardiere","doi":"10.1016/j.modpat.2025.100740","DOIUrl":"10.1016/j.modpat.2025.100740","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;em&gt;RET&lt;/em&gt;-fused Spitz neoplasms represent a rare and poorly characterized category of Spitz tumors. Here we describe the clinical, histologic, and molecular findings of 31 Spitz neoplasms with &lt;em&gt;RET&lt;/em&gt; fusion diagnosed as Spitz nevus (n = 16), atypical Spitz tumors (n = 13), and Spitz melanoma (n = 2). The lesions mainly occurred in children and young adults of both sexes with a predilection for the extremities. Microscopically, they were mainly symmetrical compound melanocytic neoplasms with a dome-shaped/slightly raised silhouette predominantly composed of epithelioid, spindled, and/or smaller nevoid melanocytes arranged in confluent nests. Dyscohesive melanocytes within the nests in the upper part of the lesions, prominent Kamino bodies, giant multinucleated melanocytes, variable pigmentation, and increased vascularity with vascular ectasia were frequent features. RNA sequencing detected 9 different 5’ (N-terminus) fusion partners, including &lt;em&gt;KIF5B&lt;/em&gt; (n = 8), &lt;em&gt;LMNA&lt;/em&gt; (n = 7), &lt;em&gt;CCDC6&lt;/em&gt; (n = 6), &lt;em&gt;OPTN&lt;/em&gt; (n = 3), &lt;em&gt;MYO5A&lt;/em&gt; (n = 2), and &lt;em&gt;NCOA4&lt;/em&gt;, &lt;em&gt;ERC1&lt;/em&gt;, &lt;em&gt;MYH9&lt;/em&gt;, &lt;em&gt;AGAP3&lt;/em&gt; (n = 1). Of these, &lt;em&gt;OPTN&lt;/em&gt;::&lt;em&gt;RET&lt;/em&gt; and &lt;em&gt;AGAP3&lt;/em&gt;::&lt;em&gt;RET&lt;/em&gt; represent novel fusions, and 3 further 5’ fusion partners, namely &lt;em&gt;NCOA4&lt;/em&gt;, &lt;em&gt;ERC1,&lt;/em&gt; and &lt;em&gt;MYH9&lt;/em&gt;, have never been reported in Spitz tumors. Although as a whole group, the tumors showed a heterogeneous histopathologic presentation, correlation of the morphologic features and the 5' fusion partners demonstrated certain associations. Nevoid melanocytes were exclusively encountered in cases with KIF5B fusion partner. Neuroid-like appearances with intersecting fascicles of spindled cells typified both &lt;em&gt;MYO5A&lt;/em&gt;-fused cases. Epithelioid melanocyte population dominated cases with &lt;em&gt;LMNA&lt;/em&gt; and &lt;em&gt;CCDC6&lt;/em&gt; fusion partners. Transepidermal elimination/floating intraepidermal nests of pigmented spindled and epithelioid melanocytes were observed in the &lt;em&gt;OPTN&lt;/em&gt; subgroup. The remaining cases with less frequent 5’ fusion partners manifested in general more atypical histopathologic features, including nuclear pleomorphism, high mitotic count, atypical mitoses, and sheet-like growth pattern. Melanoma fluorescence in situ hybridization probe kit targeting &lt;em&gt;RREB1, MYC, CDKN2A,&lt;/em&gt; and &lt;em&gt;CCND1&lt;/em&gt;, was negative for copy number variation in 4 cases tested, including 2 cases with complete p16 nuclear loss on immunohistochemistry. Array comparative genomic hybridization was performed in 3 lesions and detected numerous segmental chromosomal imbalances in 2 of them that were diagnosed as Spitz melanoma. DNA and RNA sequencing detected several further genomic alterations, including &lt;em&gt;POU2F3&lt;/em&gt; overexpression in 3 highly pigmented lesions. Further studies are needed to confirm possible correlations between the microscopic features and a particular fusion partner (or additional genetic events) in &lt;em&gt;RET&lt;/em&gt;-fus","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100740"},"PeriodicalIF":7.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476728","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":"Prognostic Value of Tumor-Stroma Ratio in a Screened Stage II Colon Cancer Population: Intratumoral Site-Specific Assessment and Tumor Budding Synergy","authors":"Maria Pihlmann Kristensen ,&nbsp;Ulrik Korsgaard ,&nbsp;Signe Timm ,&nbsp;Torben Frøstrup Hansen ,&nbsp;Inti Zlobec ,&nbsp;Henrik Hager ,&nbsp;Sanne Kjær-Frifeldt","doi":"10.1016/j.modpat.2025.100738","DOIUrl":"10.1016/j.modpat.2025.100738","url":null,"abstract":"<div><div>The tumor-stroma ratio (TSR) has shown a prognostic value in various cancers, including colon cancer. This retrospective, multicenter cohort study aimed to investigate the prognostic value of TSR in a screened stage II colon cancer population, both independently and in combination with tumor budding. The cohort included 497 patients who underwent surgical resection for stage II colon cancer. TSR was determined based on the procedures proposed by van Pelt et al, and tumor budding was evaluated according to the guidelines from the International Tumor Budding Consensus Conference. Our findings demonstrate that patients with tumors categorized as having a high proportion of stroma (&gt;50% stroma area) had a shorter 5-year time to recurrence (hazard ratio [HR], 1.95; <em>P</em> = .05), recurrence-free survival (HR, 1.63; <em>P</em> = .02), and overall survival (HR, 1.05; <em>P</em> = .07) compared with those with tumors categorized as having a low proportion of stroma (≤50% stroma area). The prognostic effect was specific to TSR determination at the deepest invasive front of tumor and lost significance as the examination area expanded. Combining TSR and tumor budding further improved prognostic stratification. Tumors with high stromal content and high-grade budding exhibited a significantly more aggressive risk profile and poorer 5-year survival outcomes compared with those with stroma-low and budding-low tumors (time to recurrence: HR, 4.47; <em>P</em> &lt; .01; recurrence-free survival: HR, 2.71; <em>P</em> &lt; .01; and overall survival: HR, 2.20; <em>P</em> = .01). The study highlights the importance of standardized procedures for TSR assessment and suggests that evaluating both TSR and tumor budding could improve prognostic accuracy and aid in clinical decision-making.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 6","pages":"Article 100738"},"PeriodicalIF":7.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458678","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":"Genomic Characteristics Related to Histology-Based Immune Features in Breast Cancer","authors":"Yoon Jin Cha ,&nbsp;Constandina E. O’Connell ,&nbsp;Benjamin C. Calhoun ,&nbsp;Brooke M. Felsheim ,&nbsp;Aranzazu Fernandez-Martinez ,&nbsp;Cheng Fan ,&nbsp;Christian Brueffer ,&nbsp;Christer Larsson ,&nbsp;Åke Borg ,&nbsp;Lao H. Saal ,&nbsp;Charles M. Perou","doi":"10.1016/j.modpat.2025.100736","DOIUrl":"10.1016/j.modpat.2025.100736","url":null,"abstract":"<div><div>The immune cell component of the tumor microenvironment is an important modulator of tumor progression. In patients with breast cancer, tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS) represent core aspects of antitumor immunity, both increasingly recognized for clinical relevance. In this study, we evaluated immune-related histology features using whole-slide hematoxylin and eosin (H&amp;E) images of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data set (n = 1035) and analyzed these distinct features relative to gene expression, PAM50 subtypes, and patient survival. H&amp;E images were evaluated for TILs, plasma cells (PCs), high-endothelial venule-associated lymphoid aggregates (HALA), and mature TLS. For HALA and TLS, location relative to the tumor (nontumor, peritumor, and intratumor) was determined. HER2-enriched (HER2E) and basal-like breast tumors exhibited the highest mean TILs and the presence of PCs. HALA were present in 35.1% of cases and TLS in 6.5% of cases, also predominantly in HER2E and basal-like tumors. We derived gene expression signatures for 10 histologically defined immune features and tested their clinical significance using transcriptomic and survival data from the Sweden Cancerome Analysis Network – Breast (SCAN-B) cohort. Signatures related to TILs, PCs, HALA/TLS, TLS, and specifically intratumor HALA and TLS were associated with better survival in HER2E and basal-like tumors. Peritumor HALA/TLS and nontumor signatures were nonsignificant or associated with worse outcomes. Furthermore, we compared the immune microenvironment of high-TIL (TILs &gt; 10%) tumors from TCGA-BRCA by PAM50 subtype through supervised analyses of 200+ immune gene expression signatures, and unique immune features were identified for each subtype. In high-TIL luminal tumors, enriched immune signatures had little relation to prognosis. High-TIL HER2E and basal-like tumors had distinct immune signatures linked to improved survival, related to B and T cells, respectively. Overall, PAM50 subtypes of breast cancer exhibit distinct immune microenvironments, both histologically and molecularly. These differences in immune properties should be considered when developing precise treatment strategies to achieve optimal therapeutic efficacy for patients.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100736"},"PeriodicalIF":7.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433375","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":"Erythroblastic Sarcoma in Adults and Children: Different Pathways to the Same Destination.","authors":"Megan J Fitzpatrick, Ji Yuan, Ioana Capa, Jacob R Bledsoe, Clayton E Kibler, Catherine Tucker, Wen Shuai, Nana P Matsumoto, Gord Guo Zhu, Yi Ding, Xiaojun Wu, Wei Wang, Zhihong Hu, Liuyan Jiang, Yueping Jia, Yang Zhao, Yuihui Lin, Xuejun Tian, Carlos A Galliani, Girish Venkataraman, Sanjana Mehrotra, Paola Dal Cin, Mary M Haag, Bradford Siegele, Weiwei Zhang, Endi Wang, Irene Castañeda-Sánchez, Qian-Yun Zhang, Antonio R Perez-Atayde, Ken H Young, Sam Sadigh, Huan-You Wang, Robert P Hasserjian, L Jeffrey Medeiros, Zenggang Pan","doi":"10.1016/j.modpat.2025.100716","DOIUrl":"https://doi.org/10.1016/j.modpat.2025.100716","url":null,"abstract":"<p><p>Erythroblastic sarcoma (ES), the mass-forming presentation of acute erythroid leukemia, is a rare and challenging diagnosis. Given the limited number of published cases, the diagnostic criteria, immunophenotype, and molecular characteristics are not well defined. We describe 56 cases of ES (36 adult and 11 pediatric cases from our cohort, and 9 pediatric cases from the literature). The median age was 60 years among adults and 1.8 years among children. An association with prior cytotoxic therapy or myeloid neoplasm was documented in 10/36 (28%) and 25/36 (69%) adults, respectively, but was not reported in children. Bones were the most common site of involvement among adults (16/36, 44%), whereas soft tissue or central nervous system involvement was most common among children (each 9/20, 45%). Adult and pediatric ES shared similar morphologic features with all cases showing mass formation of erythroblasts and/or involvement of body fluids. Immunophenotypic analysis showed that blasts were positive for CD71 (49/49, 100%), GLUT1 (12/12, 100%), CD43 (37/39, 95%), E-cadherin (38/44, 86%), and CD117 (39/51, 76%) but were mostly negative for CD45 (15/48, 31% positive). Strong and diffuse P53 expression was common among adults (21/24, 88%) and absent among children (3/10, 30% with dim/subset positivity). Although a complex karyotype was common in adult (15/17, 88%) and pediatric ES (8/12, 68%), TP53 mutations were exclusively seen in adult ES (17/19, 89%), at least 11 of which (65%) were biallelic. Instead, pediatric ES was enriched for gene fusions; specific fusions were identified in 10 cases, 7 of which involved NFIA rearrangement. The prognosis was poor among both age groups; 29/37 (78%) patients died from disease with a median overall survival of 3 months. Overall, these results show that adult and pediatric ES have overlapping morphologic and immunophenotypic features but distinct molecular profiles suggesting diverging pathogenesis.</p>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":" ","pages":"100716"},"PeriodicalIF":7.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692879","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":"Genomic Profiling Uncovers a Broader Spectrum of Dermatofibrosarcoma Protuberans: Implications for Diagnosis and Therapy","authors":"Steven Christopher Smith ,&nbsp;Kieran Sweeney ,&nbsp;Mark G. Evans ,&nbsp;Kartik Angara ,&nbsp;Celia Reynolds ,&nbsp;Brandee Price ,&nbsp;Soo J. Park ,&nbsp;Andrew Elliott ,&nbsp;Matthew J. Oberley ,&nbsp;Sosipatros A. Boikos ,&nbsp;Armita Bahrami","doi":"10.1016/j.modpat.2025.100737","DOIUrl":"10.1016/j.modpat.2025.100737","url":null,"abstract":"<div><div>Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous neoplasm driven by <em>PDGFB</em> or, rarely, <em>PDGFD</em> gene fusions. In some cases, DFSP progresses to a fibrosarcomatous form with metastatic potential, which may respond to tyrosine kinase inhibitors. This study explores whether comprehensive genomic profiling can reveal a broader clinical, anatomic, and pathologic spectrum for DFSP. Using the database of a large tumor sequencing reference laboratory, we identified tumors with <em>PDGFB</em> or <em>PDGFD</em> fusions and reviewed their histologic features, clinical information, exome sequencing data, and copy number alterations. Statistical significance was determined using Mann-Whitney <em>U</em> and Fisher exact tests. A total of 59 cases with <em>PDGFB</em> or <em>PDGFD</em> fusions were identified: 55 <em>COL1A1::PDGFB</em>, 3 <em>EMILIN2::PDGFD</em>, and 1 <em>COL1A2::PDGFB</em>. The cohort included 51 primary tumors and 8 metastases (31 males, 28 females, median age 49 years). Primary tumors were mainly located in the skin and soft tissues, including 35 in the trunk, 9 in the head and neck, and 9 in the extremities. Additionally, 6 tumors arose in visceral organs (4 in the uterus, 1 in the cervix, and 1 in the lung). Among cases with slides available for pathology review, 21 were classified as classic DFSP and 31 as fibrosarcomatous-DFSP (FS-DFSP). Notably, 21 tumors (36%) were initially misclassified, often due to atypical locations or histology. FS-DFSPs displayed a higher incidence of genomic alterations beyond <em>PDGFB</em>/<em>PDGFD</em> (75% vs 23.8%; <em>P</em> = .0005), including <em>TERT</em> promoter and <em>NF1</em> variants, and demonstrated a significantly elevated tumor mutational burden (<em>P</em> = .0037) and TERT mRNA expression (1.27 vs 0.13 transcripts per million; <em>P</em> &lt; .0001) compared with classic DFSPs. These findings underscore the value of genomic profiling for recognizing FS-DFSPs with unusual clinical or histologic features, particularly in guiding targeted therapy. Furthermore, by identifying molecular features specific to fibrosarcomatous variants, such as <em>TERT</em> reactivation, this study offers insights into potential molecular drivers of tumor progression in DFSP.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 4","pages":"Article 100737"},"PeriodicalIF":7.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433381","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":"Dysplasia in Pediatric Patients with Inflammatory Bowel Disease Shows Distinct Clinicopathologic Features Compared With that in Adult Patients","authors":"Dorukhan Bahceci ,&nbsp;Shaomin Hu ,&nbsp;Xiaoyan Liao ,&nbsp;Lindsay Alpert ,&nbsp;Hwajeong Lee ,&nbsp;Huaibin Mabel Ko ,&nbsp;Adam L. Booth ,&nbsp;Gregory Y. Lauwers ,&nbsp;Won-Tak Choi","doi":"10.1016/j.modpat.2025.100735","DOIUrl":"10.1016/j.modpat.2025.100735","url":null,"abstract":"<div><div>Due to its rarity, there is limited information on the clinicopathologic features of dysplasia in pediatric patients with inflammatory bowel disease (IBD). The existing surveillance guidelines for these patients do not include dysplasia as a potential risk factor for colorectal cancer, and there is no clear guidance on the optimal strategy for detecting dysplasia. As such, we analyzed the clinicopathologic features of 20 patients with IBD who developed at least 1 instance of dysplasia (n = 56) before the age of 21 years. The results were then compared with data from a previously published adult cohort, which included 315 dysplastic lesions from 167 consecutive adult patients with IBD. The study group consisted of 11 men and 9 women, with a mean age of 11 years at the time of IBD diagnosis. The mean age at the time of the first dysplasia diagnosis was 18 years for the study group compared with 54 years for the adult group. The study group had a lower incidence of ulcerative colitis (65% vs 92% in the adult group, <em>P</em> &lt; .001), but the proportion of patients with concurrent primary sclerosing cholangitis was nearly double that of the adult group (25% vs 13%, <em>P</em> = .129). Dysplasia in the study group was more likely to be nonconventional (38%, <em>P</em> = .047) and invisible or flat (50%, <em>P</em> &lt; .001) compared with the adult group (25% and 24%, respectively). High-risk nonconventional dysplastic subtypes, including crypt dysplasia (13%, <em>P</em> = .016), goblet cell–deficient dysplasia (11%, <em>P</em> = .010), and hypermucinous dysplasia (9%, <em>P</em> = .009), were more common in the study group than in the adult group (4%, 3%, and 2%, respectively). The mean duration from IBD diagnosis to the first dysplasia diagnosis was significantly shorter in the study group (8 years) than in the adult group (16 years) (<em>P</em> = .005). Although dysplastic lesions in the adult group were more likely to present as high-grade dysplasia at initial diagnosis (17% vs 4% in the study group, <em>P</em> = .008), the rate of advanced neoplasia (high-grade dysplasia or colorectal cancer) on follow-up was similar between the 2 groups (26% in the adult group vs 22% in the study group, <em>P</em> = 1.000). In conclusion, dysplasia in pediatric patients with IBD is often associated with nonconventional features (including the high-risk subtypes), an invisible/flat appearance, concurrent primary sclerosing cholangitis, and early development (within 8 years of IBD diagnosis).</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 6","pages":"Article 100735"},"PeriodicalIF":7.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433372","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":"Classification of Fibroepithelial Lesions of the Breast in Core Needle Biopsy With Implications for Further Management","authors":"Emad A. Rakha ,&nbsp;Cecily Quinn ,&nbsp;Wendy Raymond ,&nbsp;Kimberly H. Allison ,&nbsp;Sunil S. Badve ,&nbsp;Edi Brogi ,&nbsp;Grace Callagy ,&nbsp;Emmanuelle Charafe-Jauffret ,&nbsp;Chih Jung Chen ,&nbsp;Yunn-Yi Chen ,&nbsp;Laura C. Collins ,&nbsp;Gábor Cserni ,&nbsp;Lounes Djerroudi ,&nbsp;Shabnam Jaffer ,&nbsp;Maria Pia Foschini ,&nbsp;Helenice Gobbi ,&nbsp;Mihir Gudi ,&nbsp;Oi Harada ,&nbsp;Janina Kulka ,&nbsp;Hajime Kuroda ,&nbsp;Puay Hoon Tan","doi":"10.1016/j.modpat.2025.100734","DOIUrl":"10.1016/j.modpat.2025.100734","url":null,"abstract":"<div><div>Fibroepithelial lesions (FELs) of the breast represent a diverse group of biphasic tumors with varying morphologies and clinical behavior. The classification of FELs is mainly based on a constellation of diagnostic criteria, and intralesional heterogeneity is not uncommon. Therefore, reporting FELs in a core needle biopsy (CNB) with limited tissue material can be challenging as not all the features may be represented for assessment. Differentiating a classic fibroadenoma from a well-sampled phyllodes tumor (PT) is generally straightforward. However, cellular fibroadenoma, morphologically heterogeneous benign PT, and myoid hamartoma can overlap histologically. Accurate grading of PT is also challenging on CNB and carries significant management implications. In this article, we provide an overview and propose a pragmatic approach to reporting FELs on CNB, particularly for lesions with overlapping features. Guidance using the UK/European “B” classification of FELs alongside descriptive reporting of the various lesions, is also presented to aid in management decisions.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100734"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414094","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":"Prognostic Implications of Magee Equation 3 and Residual Cancer Burden in Patients Receiving Neoadjuvant Chemotherapy for Hormone Receptor-Positive HER2-Negative Breast Cancer","authors":"Thais Perez Vazquez ,&nbsp;Rodrigo Gonçalves ,&nbsp;Juliana Pierobon Gomes da Cunha ,&nbsp;Fernando Wladimir Silva Rivas ,&nbsp;Fernando Nalesso Aguiar ,&nbsp;Edmund Chada Baracat ,&nbsp;José Roberto Filassi","doi":"10.1016/j.modpat.2025.100733","DOIUrl":"10.1016/j.modpat.2025.100733","url":null,"abstract":"<div><div>Breast cancer (BC) presents significant molecular heterogeneity, complicating prognosis and treatment strategies. Although molecular testing enhances our understanding of BC, high costs can limit accessibility in certain health care settings. This retrospective cohort study evaluates the prognostic value of Magee equation 3 (ME3) and residual cancer burden (RCB) in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC treated at the Instituto do Câncer do Estado de São Paulo from January 2011 to January 2024. We included 203 women, with a mean age of 50.2 years, diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC (stages I-III), who completed neoadjuvant chemotherapy followed by surgery. ME3 scores were categorized as low (&lt;18), intermediate (18-25), and high (&gt;25), whereas RCB was classified into 4 groups (0, 1, 2, or 3). Associations between ME3 and RCB categories were analyzed using χ² and Cochran-Mantel-Haenszel tests. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with log-rank tests. Prior to neoadjuvant chemotherapy, 60.1% of patients had tumors &gt;5 cm, 69.5% had positive lymph nodes, and 85.7% had invasive carcinoma of nonspecial type, with a mean Ki67 index of 35.5%. Analysis revealed that 22.2% of patients had ME3 &gt;25, 39.9% had ME3 18-25, and 37.9% had ME3 &lt;18. A significant inverse association was found between RCB and ME3 (<em>P</em> &lt; .0001). At a median follow-up of 91.4 months (range: 8-157 months), significant associations were noted for OS (log-rank <em>P</em> = .0059) and DFS (log-rank <em>P</em> = .0028) with ME3 categories; patients with low ME3 showed better outcomes. In patients with RCB-3, those with ME3 &lt;18 had a lower risk of recurrence compared with those with ME3 18-25 (hazard ratio: 4.70, 95% CI: 2.00-11.02; <em>P</em> = .0004) and ME3 &gt; 25 (hazard ratio: 5.18, 95% CI: 1.85-14.15; <em>P</em> = .0017). Similarly, lower risks of death were observed for ME3 &lt; 18 versus higher ME3 categories. In conclusion, ME3 significantly correlates with OS and DFS, suggesting that it may serve as a valuable alternative to molecular assays in resource-limited settings. Combining ME3 with RCB enhances individualized risk stratification, providing a more precise prognostic assessment for patients with high RCB.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 6","pages":"Article 100733"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382897","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":"MAD::NUT Fusion Sarcoma: A Sarcoma Class With NUTM1, NUTM2A, and NUTM2G Fusions and Possibly Distinctive Subtypes","authors":"David J. Papke Jr. ,&nbsp;John S.A. Chrisinger ,&nbsp;Christopher A. French ,&nbsp;Anthony Crymes ,&nbsp;Thomas C. Krivak ,&nbsp;Ricardo E. Estape ,&nbsp;Mahesh Seetharam ,&nbsp;Reema A. Patel ,&nbsp;William N. O'Connor ,&nbsp;Anthony W. Chi ,&nbsp;Pablo Gutman ,&nbsp;Stephan Singer ,&nbsp;Chul Kim ,&nbsp;David A. Bryant ,&nbsp;Matthew J. Oberley ,&nbsp;Tolulope Adeyelu ,&nbsp;Julia A. Bridge ,&nbsp;Mark G. Evans","doi":"10.1016/j.modpat.2025.100729","DOIUrl":"10.1016/j.modpat.2025.100729","url":null,"abstract":"&lt;div&gt;&lt;div&gt;&lt;em&gt;NUT&lt;/em&gt; fusion–associated cancers are heterogeneous and include NUT carcinoma and an emerging group with non-&lt;em&gt;BRD4/BRD3/NSD3&lt;/em&gt; fusion partners. In this study, we characterized 11 tumors harboring &lt;em&gt;MAD&lt;/em&gt;::&lt;em&gt;NUT&lt;/em&gt; fusions (10/11 in female patients; median age: 48 years; range: 1-67 years), all histologically different from NUT carcinoma. Eight cases were identified via sequencing database review and 3 were diagnosed prospectively. Eight (73%) patients presented with multifocal disease, including 6 with disseminated peritoneal tumors; 3 (27%) presented with solitary colonic, pulmonary, or orbital masses. Nine (82%) tumors harbored &lt;em&gt;NUTM1&lt;/em&gt; fusions, with &lt;em&gt;MXI1&lt;/em&gt; (5/9; 56%), &lt;em&gt;MXD4&lt;/em&gt; (2/9; 22%), and &lt;em&gt;MGA&lt;/em&gt; (2/9; 22%). One tumor each harbored &lt;em&gt;MXD4&lt;/em&gt;::&lt;em&gt;NUTM2G&lt;/em&gt; and &lt;em&gt;MXI1&lt;/em&gt;::&lt;em&gt;NUTM2A&lt;/em&gt; fusions. The 9 &lt;em&gt;MXD4&lt;/em&gt;/&lt;em&gt;MXI1&lt;/em&gt;-rearranged sarcomas were high-grade, with epithelioid-to-spindle cell cytomorphology, amphophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Histologic features included infiltrative growth (7/7 assessable tumors), rhabdoid morphology (7/9; 78%), prominent collagen (3/9; 33%), multinucleated tumor cells (2/9; 22%), and myxoid stroma (1/9; 11%). &lt;em&gt;MXD4&lt;/em&gt;/&lt;em&gt;MXI1&lt;/em&gt;-rearranged sarcomas expressed desmin (3/7; 43%) and keratin(s) (3/7; 43%), and not p63 (6 tumors), CD34 (5 tumors), or S-100 (5 tumors). The adult &lt;em&gt;MGA&lt;/em&gt;::&lt;em&gt;NUTM1&lt;/em&gt; fusion sarcoma exhibited some cytologic overlap with &lt;em&gt;MXD4&lt;/em&gt;/&lt;em&gt;MXI1&lt;/em&gt;-rearranged sarcomas but showed lower grade myxoid spindle cell regions, microcystic spaces, and S-100 expression. The pediatric &lt;em&gt;MGA&lt;/em&gt;::&lt;em&gt;NUTM1&lt;/em&gt; fusion sarcoma was low-grade with CD34/S-100 coexpression. Immunohistochemistry demonstrated NUTM1 expression in &lt;em&gt;NUTM1&lt;/em&gt;-rearranged sarcomas (5/5), and weak and no expression in &lt;em&gt;NUTM2A&lt;/em&gt;- and &lt;em&gt;NUTM2G&lt;/em&gt;-rearranged sarcomas, respectively. Gene expression profiling demonstrated sarcomas with &lt;em&gt;MXD4&lt;/em&gt;/&lt;em&gt;MXI1&lt;/em&gt;::&lt;em&gt;NUTM1&lt;/em&gt;/&lt;em&gt;NUTM2A&lt;/em&gt;/&lt;em&gt;NUTM2G&lt;/em&gt; fusions clustered separately from NUT carcinoma. Follow-up was available for 9 patients (82%; median length: 1.8 years; range: 2 months to 8.2 years). Four of 7 patients with &lt;em&gt;MXD4&lt;/em&gt;/&lt;em&gt;MXI&lt;/em&gt;&lt;em&gt;1&lt;/em&gt;-rearranged sarcomas died of disease (median survival: 1.3 years; range: 5 months to 4.8 years), 1 entered hospice at 2 months, 1 was alive with pericardial masses at 2.8 years, and 1 was alive with no evidence of disease at 8.2 years. The adult with the &lt;em&gt;MGA&lt;/em&gt;::&lt;em&gt;NUTM1&lt;/em&gt; fusion sarcoma died of other causes at 4.5 years; the child was alive without disease at 11 months. We conclude that &lt;em&gt;MAD&lt;/em&gt;::&lt;em&gt;NUT&lt;/em&gt; fusions define a sarcoma class distinct from NUT carcinoma. Among this group, &lt;em&gt;MGA&lt;/em&gt;::&lt;em&gt;NUTM1&lt;/em&gt; fusion sarcomas might represent a distinctive subset. NUTM1 immunohistochemistry does not reliably detect &lt;em&gt;NUTM2A&lt;/em&gt;/&lt;em&gt;NUTM2G&lt;/em&gt;-rearranged sarcomas.","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 5","pages":"Article 100729"},"PeriodicalIF":7.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374448","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}