Human pathology最新文献

{"title":"Glutamine synthetase staining patterns in cirrhosis","authors":"Eric D. Nguyen,&nbsp;Chien-Kuang Cornelia Ding,&nbsp;Sarah E. Umetsu,&nbsp;Linda D. Ferrell,&nbsp;Kwun Wah Wen","doi":"10.1016/j.humpath.2024.105655","DOIUrl":"10.1016/j.humpath.2024.105655","url":null,"abstract":"<div><p>Advanced liver fibrosis can regress following the elimination of causative injuries. Glutamine synthetase (GS) immunohistochemical expression is normally in centrizonal perivenular hepatocytes but can be present in periportal hepatocytes in cases of regressed cirrhosis. This study identified periportal staining and investigated the spectrum of GS staining patterns seen in a range of cirrhotic livers with varying disease processes. The hematoxylin and eosin and GS-stained slides of 88 liver resection/explant specimens with advanced fibrosis cases by different causes were reviewed, and trichrome and orcein stains were used to classify cases as progressive, indeterminate, or regressive. Periportal GS staining was seen in 97% of regressive cases and 84% progressive or indeterminate cases. Liver resection specimens with periportal GS staining showed a variety of patterns, including predominantly perivenular, predominantly periseptal, and perinodular staining. The GS periseptal pattern is more common in regressed cirrhosis compared to progressive cases. The perinodular staining was seen in 16 cases resulting from various etiologies, including biliary atresia, steatotic liver disease, primary biliary cholangitis, and viral hepatitis, 75% of which demonstrated cholestasis. This study further subclassified GS staining patterns of “periportal” pattern in cirrhotic liver. Compared to orcein/trichrome staining, GS immunohistochemical staining is not as useful in distinguishing regressed cases from non-regressed cases.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105655"},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153885","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":"Fluorescence in-situ hybridization assessment of spindle cell-rich testicular sex cord stromal tumors demonstrates multiple chromosomal gains across histologic subtypes","authors":"Andres Martin Acosta ,&nbsp;Christopher D.M. Fletcher ,&nbsp;Lynette M. Sholl ,&nbsp;Geert JLH. van Leenders ,&nbsp;Esther Oliva ,&nbsp;Kristine M. Cornejo ,&nbsp;Federico Repetto ,&nbsp;Katrina Collins ,&nbsp;Muhammad T. Idrees ,&nbsp;Michelle S. Hirsch ,&nbsp;Kiril Trpkov ,&nbsp;Thomas M. Ulbright ,&nbsp;Julia A. Bridge","doi":"10.1016/j.humpath.2024.105652","DOIUrl":"10.1016/j.humpath.2024.105652","url":null,"abstract":"<div><p>Spindle cell-rich testicular sex cord-stromal tumors (TSCSTs) comprise a group that includes mostly (but not exclusively): myoid gonadal stromal tumor (MGST), adult granulosa cell tumor (AGCT), and unclassified TSCST. These entities demonstrate histopathologic overlap, and prior genomic studies have failed to identify specific oncogenic drivers. Results of DNA sequencing suggest that different types of spindle cell-rich TSCSTs harbor a recurrent pattern of chromosomal gains. However, these results have not been validated by alternative methods and the extent of these changes within individual tumors remains unknown. We used a combination of commercially available fluorescence in-situ hybridization (FISH) probes (3q11.2, 6p24.3, 6q11.1, 6q23, 7q11.21-q11.22, 9p21.3, 11q13.3, 17p11.2) to enumerate a subset of chromosomes identified as altered (gained) in prior studies. We analyzed 10 cases (3 MGST, 4 unclassified TSCST, 3 AGCT), including 7 that had been previously sequenced. FISH demonstrated gains of chromosomes 3, 6, 7, 9, and 11 above the pre-established threshold (25%) in 50%, 80%, 70%, 20%, and 40% of cases, respectively, with gains of chromosome 17 being present in only 1 unclassified TSCST. The proportion of cells with chromosomal gains ranged from 26% to 60%. Tumors with available copy number data from prior genomic analyses showed a partial discordance between FISH and sequencing results. This study demonstrates that spindle-cell rich TSCSTs harbor a recurrent pattern of chromosomal gains, which are present in variable subsets of neoplastic cells. Further studies are needed to determine if these chromosomal changes represent a mechanism relevant for oncogenesis or a secondary event.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105652"},"PeriodicalIF":2.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106926","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":"Hairy cell leukemia with an atypical extranodal presentation: A clinicopathological analysis of four cases","authors":"Valentina Sangiorgio ,&nbsp;Andrea Palasciano ,&nbsp;Valentina Tabanelli ,&nbsp;Eva Giné ,&nbsp;Luca Guerra ,&nbsp;Fabio Pagni ,&nbsp;Alessandra Casiraghi ,&nbsp;Ivana Casaroli ,&nbsp;Gerard Frigola ,&nbsp;Laura Magnano ,&nbsp;Carlo Gambacorti-Passerini ,&nbsp;Enrico Derenzini ,&nbsp;Anna Vanazzi ,&nbsp;Elias Campo","doi":"10.1016/j.humpath.2024.105651","DOIUrl":"10.1016/j.humpath.2024.105651","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"152 ","pages":"Article 105651"},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094977","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":"Gradual telomere shortening in the tumorigenesis of pancreatic and hepatic mucinous cystic neoplasms","authors":"You-Na Sung ,&nbsp;Marija Stojanova ,&nbsp;Seungbeom Shin ,&nbsp;HyungJun Cho ,&nbsp;Christopher M. Heaphy ,&nbsp;Seung-Mo Hong","doi":"10.1016/j.humpath.2024.105653","DOIUrl":"10.1016/j.humpath.2024.105653","url":null,"abstract":"<div><p>Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 ± 0.78), ovarian-type stroma (2.90 ± 0.93), non-mucinous lining epithelium (2.84 ± 0.79), mucinous lining epithelium (2.49 ± 0.93), and adenocarcinoma (1.19 ± 0.59), respectively (P &lt; 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P &lt; 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"152 ","pages":"Article 105653"},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094978","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":"Genomic analysis reveals molecular characterization of CD30+ and CD30− extranodal natural killer/T-cell lymphomas (ENKTLs)","authors":"Xiaoying Zhang ,&nbsp;Ke Liang ,&nbsp;Haiyan Chen ,&nbsp;Long Liu ,&nbsp;Ruirui Liu ,&nbsp;Chunxue Wang ,&nbsp;Cuijuan Zhang","doi":"10.1016/j.humpath.2024.105650","DOIUrl":"10.1016/j.humpath.2024.105650","url":null,"abstract":"<div><p>Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is prevalent in the Asian population; however, little is known about its molecular characteristics. In this study, we examined the CD30 expression in ENKTLs and then performed whole exome sequencing on ten CD30⁺ ENKTL and CD30⁻ ENKTL paired samples. CD30 was positive in 55.74% of the ENKTLs. Single nucleotide and insertion/deletion polymorphism analyses revealed that 53.41% of the somatic mutations in CD30⁺ ENKTLs were shared with CD30⁻ ENKTLs, including mutations in <em>SERPINA9</em>, <em>MEGF6</em>, <em>MUC6</em>, and <em>KDM5A</em>. Frequently mutated genes were primarily associated with cell proliferation and migration, the tumor microenvironment, energy and metabolism, epigenetic modulators, vascular remodeling, and neurological function. PI3K-AKT, cAMP, cGMP-PKG, and AMPK pathways were enriched in both CD30⁺ and CD30⁻ ENKTLs. Copy number variation analysis identified a unique set of genes in CD30⁺ ENKTLs, including T-cell receptor genes (<em>TRBV6-1</em> and <em>TRBV8</em>), cell cycle-related genes (<em>MYC</em> and <em>CCND3</em>), immune-related genes (<em>GPS2</em>, <em>IFNA14</em>, <em>TTC38</em>, and <em>CTSV</em>), and a large number of ubiquitination-related genes (<em>USP32</em>, <em>TRIM23</em>, <em>TRIM2</em>, <em>DUSP7</em>, and <em>UBE2QL1</em>). <em>BCL10</em> mutation was identified in 6/10 CD30⁺ ENKTLs and 7/10 CD30⁻ ENKTLs. Immunohistochemical analysis revealed that the expression pattern of BCL10 in normal lymphoid tissues was similar to that of BCL2; however, its expression in ENKTL cells was significantly higher (67.92% vs. 16.98%), implying the potential application of BCL10 inhibitors for treating ENKTLs. These results provide new insights into the genetic characteristics of CD30⁺ and CD30⁻ ENKTLs, and could facilitate the clinical development of novel therapies for ENKTL.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"152 ","pages":"Article 105650"},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072585","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":"Therapeutic indications for antibody-drug conjugates estimated from HER2 and p53 expressions in endometrial carcinoma","authors":"Junya Nakajima ,&nbsp;Mitsutake Yano ,&nbsp;Sumika Zaitsu ,&nbsp;Kouichi Kamada ,&nbsp;Akira Yabuno ,&nbsp;Kosei Hasegawa ,&nbsp;Eiji Kobayashi ,&nbsp;Masanori Yasuda","doi":"10.1016/j.humpath.2024.105649","DOIUrl":"10.1016/j.humpath.2024.105649","url":null,"abstract":"<div><h3>Objective</h3><p>While human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma—especially in the p53 aberrant type— conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression.</p></div><div><h3>Methods</h3><p>Immunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive.</p></div><div><h3>Results</h3><p>Of the HER2-positive cases, &gt;50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (<em>p</em> = 0.007) and overall survival (OS) (<em>p</em> = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (<em>p</em> &lt; 0.001) and OS (<em>p</em> &lt; 0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183–5.971, <em>p</em> = 0.008) as an independent prognostic factor.</p></div><div><h3>Conclusions</h3><p>This study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"152 ","pages":"Article 105649"},"PeriodicalIF":2.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999794","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":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(24)00155-2","DOIUrl":"10.1016/S0046-8177(24)00155-2","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105646"},"PeriodicalIF":2.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012760","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)00152-7","DOIUrl":"10.1016/S0046-8177(24)00152-7","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105643"},"PeriodicalIF":2.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012757","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":"Association of both BCL2 positive and negative follicular lymphoma to clasical Hodgkin lymphoma and/or gray zone lymphoma","authors":"Francisco Javier Díaz de la Pinta MD ,&nbsp;Rebeca Manso PhD ,&nbsp;Isabel Betancor Fernández MD ,&nbsp;Daniel Morillo Giles MD ,&nbsp;Manuela Mollejo MD, PhD ,&nbsp;Socorro Maria Rodriguez-Pinilla MD, PhD","doi":"10.1016/j.humpath.2024.105639","DOIUrl":"10.1016/j.humpath.2024.105639","url":null,"abstract":"<div><p>We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"152 ","pages":"Article 105639"},"PeriodicalIF":2.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995685","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":"Idiopathic hyalinizing fibrosclerosis: A systemic steroid-resistant condition distinct from IgG4-related disease","authors":"Yoh Zen,&nbsp;Deepak Joshi","doi":"10.1016/j.humpath.2024.105638","DOIUrl":"10.1016/j.humpath.2024.105638","url":null,"abstract":"<div><p>Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was &lt;10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was &lt;30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of ‘idiopathic hyalinizing fibrosclerosis’ for this under-recognized, rare, systemic condition.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105638"},"PeriodicalIF":2.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916513","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}