Human pathology最新文献

{"title":"ALK-rearranged renal cell carcinoma with nuclear mitotic apparatus protein 1 (NUMA1) as a fusion partner","authors":"Sounak Gupta MBBS, PhD (Associate Professor), Murli Krishna MD (Associate Professor), John C. Cheville MD (Professor)","doi":"10.1016/j.humpath.2024.04.007","DOIUrl":"10.1016/j.humpath.2024.04.007","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 75-76"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757612","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":"Letter to the Editor There are benefits of subtyping hepatocellular adenoma also in men. Following-up on the publication by González IA et al. Clinicopathologic characterization of hepatocellular adenomas in men: A multicenter experience. Hum Pathol. 2023","authors":"Christine Sempoux, Charles Balabaud, Annette SH. Gouw, Paulette Bioulac-Sage","doi":"10.1016/j.humpath.2024.05.003","DOIUrl":"10.1016/j.humpath.2024.05.003","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 77-78"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911752","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":"Inside front cover - Masthead","authors":"","doi":"10.1016/S0046-8177(24)00111-4","DOIUrl":"https://doi.org/10.1016/S0046-8177(24)00111-4","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Page IFC"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483301","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":"EPM2AIP1 immunohistochemistry is inadequate as a surrogate marker for MLH1 promoter hypermethylation testing in colorectal cancer","authors":"Bindu Challa ,&nbsp;Wendy L. Frankel ,&nbsp;Deborah Knight ,&nbsp;Rachel Pearlman ,&nbsp;Heather Hampel ,&nbsp;Wei Chen","doi":"10.1016/j.humpath.2024.06.017","DOIUrl":"10.1016/j.humpath.2024.06.017","url":null,"abstract":"<div><p><em>MLH1</em> promoter hypermethylation (MPH) analysis is an essential step in the universal tumor testing algorithm for Lynch syndrome, the most common inherited predisposition to colorectal cancer (CRC). MPH usually indicates sporadic CRC. <em>EPM2AIP1</em> gene shares the same promoter as <em>MLH1</em>, therefore MPH should also silence <em>EPM2AIP1</em> transcription leading to loss of protein expression on immunohistochemistry (IHC). It has been previously reported that EPM2AIP1 IHC can be used as a surrogate for MPH in endometrial cancer. Our goal was to evaluate the feasibility of EPM2AIP1 IHC as a surrogate for MPH in CRC. 101 microsatellite instable CRC cases were selected, including 19 cases from whole tumor sections and 82 cases from tissue microarrays. 74 cases were with MPH and 27 without MPH. All 74 cases with MPH showed absent MLH1 by IHC, but only 47 (64%) exhibited loss of expression of EPM2AIP1. Of the 27 cases without MPH, 9 (33%) cases had unexpected loss of EPM2AIP1 expression. Of note, 10 cases were <em>MLH1</em>-mutated Lynch syndrome without MPH, and 2 of these cases showed unexpected loss of EPM2AIP1 staining. Of the 6 cases with double somatic mutations of <em>MLH1</em> gene (without MPH), only 4 cases demonstrated intact expression of EPM2AIP1 as expected. Taken together, EPM2AIP1 loss was 64% sensitive and 67% specific for MPH, with an accuracy of 64%. We conclude that, unless stain quality improves with different clones or platforms, EPM2AIP1 IHC will likely not be useful as a surrogate test for MPH in CRC.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 74-77"},"PeriodicalIF":2.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001254/pdfft?md5=2065ce484418098f703c02ffbdd3c01a&pid=1-s2.0-S0046817724001254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological differences between T-lymphoblastic leukemia/lymphoma, early T-precursor lymphoblastic leukemia/lymphoma, and mixed-phenotype acute leukemia with T lineage: An analysis of 41 adult cases","authors":"Yuka Takahashi MD, PhD ,&nbsp;Yuto Kaimi MD ,&nbsp;Hirokazu Taniguchi MD, PhD ,&nbsp;Tetsuro Ochi MD ,&nbsp;Haruhi Makino MD ,&nbsp;Shinichi Makita MD, PhD ,&nbsp;Noriko Iwaki MD, PhD ,&nbsp;Suguru Fukuhara MD, PhD ,&nbsp;Wataru Munakata MD, PhD ,&nbsp;Koji Izutsu MD, PhD ,&nbsp;Akiko Miyagi Maeshima MD, PhD","doi":"10.1016/j.humpath.2024.06.016","DOIUrl":"10.1016/j.humpath.2024.06.016","url":null,"abstract":"<div><p>The histopathological diagnosis of T-lymphoblastic leukemia/lymphoma, NOS (T-ALL), is based on morphology and positivity for CD3 and TdT. Early T-precursor lymphoblastic leukemia/lymphoma (ETP-ALL) and mixed-phenotype acute leukemia (MPAL), T/M, and/or B rarely occur and are usually diagnosed using flow cytometry. Using only formalin-fixed paraffin-embedded tissue raises the risk of misdiagnosis due to underestimation. Immunostaining markers for T cell (CD1a, CD4, CD5, CD8), B cell (CD19, CD10, CD22, CD79a), and stem/myeloid-related cell (CD33, CD34, CD117, MPO, lysozyme) diagnosed 25 T-ALL cases (61%), 7 MPAL (17%), 6 ETP-ALL (15%), and 3 near ETP-ALL (7%), with subsequent analysis of their clinicopathological characteristics. Patients with MPAL had significantly poorer 2-year progression-free survival (14.3% vs. 60.4%, P = 0.012) and 5-year overall survival (28.6% vs. 65.9%, P = 0.011) than did those with T-ALL, whereas ETP-ALL and near ETP-ALL did not. Of the seven patients with MPAL, three were classified as T/B, two as T/M, and two as T/M/B. Because most MPALs (6/7) share the ETP-ALL phenotype, immunohistochemistry for CD19 and MPO should be performed to avoid misdiagnosing MPAL as ETP-ALL. All three patients with TdT-negative MPAL died of the disease. Four patients with MPO-positive MPAL relapsed during the early phase (1–9 months). Five patients received the ALL regimen, but two patients received acute myeloid leukemia and lymphoma regimens, respectively. In this study, MPAL exhibited a poorer prognosis compared to T-ALL, unlike ETP-ALL. Thus, immunohistochemical classification with multiple antibody panels is useful for accurate diagnosis and treatment.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 78-85"},"PeriodicalIF":2.7,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467572","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":"DDR2 expression in breast cancer is associated with blood vessel invasion, basal-like tumors, tumor associated macrophages, regulatory T cells, detection mode and prognosis","authors":"Tor Audun Klingen MD, PhD (Senoir physician) ,&nbsp;Ying Chen MD, PhD (Senoir physician) ,&nbsp;Hans Aas MD (Senior physician) ,&nbsp;Lars A. Akslen MD, PhD (Professor, Senior physician)","doi":"10.1016/j.humpath.2024.06.009","DOIUrl":"10.1016/j.humpath.2024.06.009","url":null,"abstract":"<div><p>Discoidin Domain Receptor 2 (DDR2) is a receptor tyrosine kinase for collagen, stimulating epithelial-mesenchymal transition and stiffness in breast cancer. Here, we investigated levels of DDR2 in breast tumor cells in relation to vascular invasion, TIL subsets, macrophages, molecular tumor subtypes, modes of detection and prognosis. This retrospective, population-based series of invasive breast carcinomas from the Norwegian Screening Program in Vestfold County (Norway), period 2004–2009, included 200 screening patients and 82 cases detected in screening intervals. DDR2 was examined on core needle biopsies using a semi-quantitative, immunohistochemical staining index and dichotomized as low or high DDR2 expression. Counts of macrophages and TIL subsets were dichotomized based on immunohistochemistry using TMA. We also recorded blood or lymphatic vessel invasion (BVI or LVI) as present or absent by immunohistochemistry. High expression of DDR2 in tumor cells showed significant relation with high counts of CD163+ macrophages (p &lt; 0.001) and FOXP3 TILs (p = 0.011), presence of BVI (p = 0.028), high tumor cell proliferation by Ki67 (p = 0.033), ER negativity (p = 0.001), triple-negative cases (p = 0.038), basal-like features (p &lt; 0.001) as well as interval detection (p &lt; 0.001). By multivariate analysis, high DDR2 expression was related to reduced recurrence-free survival (HR, 2.3, p = 0.017), when examined together with histologic grading, lymph node assessment, tumor diameter, BVI, and molecular tumor subtype. This study supports a link between high DDR2 expression, high counts of macrophages by CD163 (tumor associated) and regulatory T cells by FOXP3 together with the presence of <span>BVI</span>, possibly indicating increased tumor motility and intravasation in aggressive breast tumors.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 29-35"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446077","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":"Prognostic significance of micronest in cancer stroma in resected lung squamous cell carcinoma","authors":"Yasunori Kaminuma ,&nbsp;Tokiko Nakai ,&nbsp;Keiju Aokage ,&nbsp;Tetsuro Taki ,&nbsp;Tomohiro Miyoshi ,&nbsp;Kenta Tane ,&nbsp;Joji Samejima ,&nbsp;Saori Miyazaki ,&nbsp;Naoya Sakamoto ,&nbsp;Shingo Sakashita ,&nbsp;Motohiro Kojima ,&nbsp;Reiko Watanabe ,&nbsp;Masahiro Tsuboi ,&nbsp;Genichiro Ishii","doi":"10.1016/j.humpath.2024.06.010","DOIUrl":"10.1016/j.humpath.2024.06.010","url":null,"abstract":"<div><p>Tumor budding in the cancer stroma has been reported to be a prognostic factor in non-small cell lung cancer. Micronest in cancer stroma (MICS) is often observed as a formation that is larger and more conspicuous than budding, but its clinicopathologic significance is unclear. In this study, we aimed to examine the clinicopathological significance of MICS in lung squamous cell carcinoma (LSqCC).</p><p>A total of 198 consecutive patients with pathologically diagnosed LSqCC (anyT N0-1M0) were enrolled in this study. MICS were defined as those that met the following criteria: (1) consisting of 5–200 tumor cells or less than 200 μm in diameter and (2) more than 200 μm away from the adjacent main lesion. The prognostic impact of the presence or absence of MICS and the characteristics of MICS-forming cancer cells were evaluated by immunohistochemistry (IHC).</p><p>MICS was observed in 57 patients (28.8%), and overall survival (OS) and recurrence-free survival (RFS) were significantly shorter in the MICS-positive group (OS: 44.4% vs. 84.4%, p &lt; 0.001; RFS: 30.0% vs. 82.6%, p &lt; 0.001). Univariate and multivariate analyses revealed that the presence of MICS was an independent poor prognostic factor for OS (hazard ratio [HR] 3.54, p &lt; 0.001) and RFS (HR 4.99, p &lt; 0.001). Immunohistochemistry showed that the expression levels of the cell-cell adhesion molecule E-cadherin and hypoxia-induced protein GLUT-1 were significantly decreased in cancer cells forming MICS lesions compared to the tumor component excluding MICS within the same tumor (non-MICS lesions).</p><p>Our data show that MICS is a distinct morphological feature with important biological and prognostic significance.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 20-28"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446079","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":"Molecular and morphologic characterization of intraductal tubulopapillary neoplasms of pancreas with novel potentially targetable fusions","authors":"Irena Manukyan,&nbsp;Susan J. Hsiao,&nbsp;Ladan Fazlollahi,&nbsp;Helen Remotti,&nbsp;Mahesh M. Mansukhani","doi":"10.1016/j.humpath.2024.06.014","DOIUrl":"10.1016/j.humpath.2024.06.014","url":null,"abstract":"<div><p>Intraductal tubulopapillary neoplasms (ITPNs) are rare pancreatic tumors with distinct histological and molecular features. Distinction of ITPN from other pancreatic neoplasms is crucial given the known favorable prognosis and the high frequency and diversity of potentially targetable fusions in ITPN. While the histological features of ITPN are well documented, there are few reports on the cytological features, and molecular characterization of ITPN. The authors reported three cases diagnosed in their laboratory between 2016 and 2021. Clinical data, cytomorphological and histological features, with immunophenotypic and molecular characterizations of these cases are described and compared with those reported in the literature. All 3 cases were diagnosed as ITPN based on the microscopic presence of intraductal nodules composed of tightly packed small tubular glands lined by cuboidal cells lacking apparent mucin. On molecular profiling <em>KRAS</em> and <em>TP53</em> variants were found in Case 1, FGFR2-INA fusion in Case 2, and STARD3NL-BRAF fusion was detected in Case 3. Immunohistochemistry (IHC) revealed that the neoplastic cells in Case 1 were MUC2 positive and MUC6 negative, but in Cases 2 and 3, were negative for MUC2 and positive for MUC6. These results demonstrate the immunophenotypic and molecular variabilities of histologically similar pancreatic neoplasms. The absence of alterations characteristic of more common pancreatic neoplasms should prompt the consideration of fusion studies in morphologically relevant cases. The combination of morphological, IHC, and molecular analyses is important for reliable identification of ITPN given its potential clinical management implications.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 36-41"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446078","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":"VHL-mutated papillary cystadenoma of the mesosalpinx with omental tumor deposits and immunophenotypic overlap with mesothelioma","authors":"","doi":"10.1016/j.humpath.2024.06.011","DOIUrl":"10.1016/j.humpath.2024.06.011","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105617"},"PeriodicalIF":2.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446080","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":"Loss of ATRX and DAXX in pancreatic neuroendocrine tumors: Association with recurrence risk, cellular phenotype, and heterogeneity","authors":"Yoichi Yasunaga ,&nbsp;Mariko Tanaka ,&nbsp;Junichi Arita ,&nbsp;Kiyoshi Hasegawa ,&nbsp;Tetsuo Ushiku","doi":"10.1016/j.humpath.2024.06.015","DOIUrl":"10.1016/j.humpath.2024.06.015","url":null,"abstract":"<div><p>Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of neoplasms in terms of biological behavior. This study aims to develop a practical algorithm based on emerging biomarkers, including chromatin-remodeling molecules DAXX/ATRX/H3K36me3, in conjunction with established prognostic factors, such as WHO grade and size. In immunohistochemical analyses, 18 of the 111 (16.2%) primary PanNETs showed DAXX or ATRX loss in a mutually exclusive manner. DAXX/ATRX loss was significantly correlated with higher recurrence risk and better predicted postoperative recurrence than WHO grade. We proposed a novel algorithm for stratifying patients with resectable PanNET into three groups according to recurrence risk: (A) WHO Grade 1 and ≤2 cm (very low-risk); for the others, (B) retained DAXX/ATRX (low-risk) and (C) DAXX/ATRX complete/heterogeneous loss (high-risk). Furthermore, we elucidated the intratumoral heterogeneities of PanNETs. Among cases with DAXX or ATRX loss, nine cases demonstrated heterogeneous loss of expression of DAXX/ATRX/H3K36me3. The majority of cases with DAXX/ATRX loss, either homogeneous or heterogeneous loss, showed uniform α-cell-like phenotype (ARX1+/PDX1−). In cases of metastatic or recurrent tumors, the expression pattern was identical to that observed in at least part of the primary tumor. In some instances, the expression pattern differed among different metastatic or recurrent tumors of the same patient. In summary, we propose a clinically useful and practical algorithm for postoperative recurrence risk stratification in PanNETs, by combining DAXX/ATRX status with WHO grade and size. Moreover, our findings highlighted the frequent spatiotemporal heterogeneity of chromatin-remodeling molecule expression in PanNETs with an α-cell phenotype, offering insights into tumorigenesis.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 51-57"},"PeriodicalIF":2.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001230/pdfft?md5=2900c1437649f16b77683703d88bd24d&pid=1-s2.0-S0046817724001230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}