Human pathology最新文献

{"title":"Hepatocyte nuclear factor 4α as a sensitive marker for uterine endocervical adenocarcinomas and their precursors","authors":"Yuri Noda ,&nbsp;Yoko Tokuyama ,&nbsp;Wataru Sumita ,&nbsp;Masato Kita ,&nbsp;Koji Tsuta","doi":"10.1016/j.humpath.2025.105714","DOIUrl":"10.1016/j.humpath.2025.105714","url":null,"abstract":"<div><h3>Context</h3><div>Hepatocyte nuclear factor (HNF)-4α is a marker of gastrointestinal tumor differentiation; however, its expression in endocervical tumors remains unclear.</div></div><div><h3>Objective</h3><div>We aimed to assess the utility of HNF4α expression as a marker for endocervical adenocarcinomas (ECAs) and adenocarcinoma in situs (AISs), and to establish a minimal panel for distinguishing them from nonneoplastic endocervical glandular lesions and metastases.</div></div><div><h3>Design</h3><div>HNF4α expression was analyzed immunohistochemically (positive, H-score ≥10) in 323 tissue samples: 57 endocervical neoplasms including 35 glandular neoplasms and 22 squamous neoplasms, 144 nonneoplastic endocervical lesions, and 122 tumors from other organs. The panel for distinguishing endocervical glandular neoplasms from nonneoplastic glands and from metastases comprised HNF4α, p16, CDX2, and SATB2; staining was assessed.</div></div><div><h3>Results</h3><div>HNF4α was expressed significantly in ECAs and AISs, both HPV-independent and -associated types, but not in nonneoplastic glandular and squamous lesions (<em>p</em> &lt; 0.05). The immunohistochemical detection sensitivity and specificity for endocervical ECA and AIS were 77% and 95%, respectively. For AIS alone, these were 79% and 94%, and for ECA alone, 75% and 94%, respectively. Either HNF4α(+) or p16(+) or double positive identified endocervical gland and squamous neoplasms (sensitivity, 96%; specificity, 76%). HNF4α(+) and SATB2(−) and CDX2(−) profiles suggested ECAs (sensitivity, 69%; specificity, 88%). HNF4α(+) and SATB2(+) or CDX2(+) profiles suggested adenocarcinomas of the gastrointestinal or genital tract (sensitivity, 81%; specificity, 88%).</div></div><div><h3>Conclusions</h3><div>HNF4α is a promising marker for detecting both HPV-independent and -associated ECAs and AIS with high accuracy. Its combination with p16, CDX2, and SATB2 has potential use in diagnostic panels.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105714"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970590","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":"Non-myxoid solid variant of extraskeletal myxoid chondrosarcoma: An underrecognized subtype","authors":"Sandra Gjorgova Gjeorgjievski,&nbsp;Jatin S. Gandhi,&nbsp;Armita Bahrami","doi":"10.1016/j.humpath.2025.105719","DOIUrl":"10.1016/j.humpath.2025.105719","url":null,"abstract":"<div><h3>Introduction</h3><div>Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma defined by <em>NR4A3</em> gene rearrangements, typically featuring uniform cells with eosinophilic cytoplasm and mild atypia, arranged in cords or clusters within a chondromyxoid stroma. A cellular variant, characterized by increased cellular density and a solid growth pattern, has been recognized.</div></div><div><h3>Methods</h3><div>We encountered three cases of round cell sarcomas, diagnosed as EMC based on <em>NR4A3</em> or <em>NR4A2</em> rearrangements. To identify additional pure solid EMC cases, we performed a retrospective review of our institutional files spanning 22 years, focusing on cases labeled as \"myxoid chondrosarcoma\" with \"cellular\" features. Histologic slides and clinical data were reviewed.</div></div><div><h3>Results</h3><div>In addition to the three study cases, 43 cases of EMC with cellular features were identified, none of which exhibited the exclusive round-to-spindle cell morphology seen in the study cases. The three unique cases involved two females and one male (ages 42–62) with tumors in the proximal extremities and trunk. The tumors (3.5–10 cm) were well-circumscribed and densely cellular. One tumor exhibited a biphasic pattern with distinct round and spindle cell areas, whereas the other two were composed purely of round/epithelioid cells. High-grade nuclear atypia and brisk mitotic activity (9–13 per 10 HPFs) were observed, with necrosis identified in one case. Next-generation sequencing revealed <em>TCF12::NR4A3</em>, <em>EWSR1::NR4A3</em>, and <em>EWSR1::NR4A2</em> fusions. Two patients developed metastases (lymph nodes and lungs), whereas one remained disease-free at last follow-up.</div></div><div><h3>Conclusion</h3><div>We describe a round cell subtype of EMC, distinct from the traditional cellular variant, characterized by a sheet-like proliferation of large, uniform round-to-epithelioid cells and the absence of chondromyxoid stroma. This potentially underrecognized subtype requires molecular testing for accurate diagnosis. Moreover, the presence of <em>NR4A2</em> fusions, although rare, suggests that the absence of <em>NR4A3</em> rearrangements does not entirely exclude EMC.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105719"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004626","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":"Expression evaluated by digital image analysis techniques of PRAME more than MCM6 is associated with poor prognosis in neuroblastoma: A pilot study with 84 cases","authors":"Samuel Touioui ,&nbsp;Emmanuel Desandes ,&nbsp;Leo Jannot ,&nbsp;Ludovic Mansuy ,&nbsp;Delphine Clabaut ,&nbsp;Michel Peuchmaur ,&nbsp;Nathalie Rioux-leclercq ,&nbsp;Pierre Khneisser ,&nbsp;Pierre-Alain Thiebaut ,&nbsp;Mathieu Gallo ,&nbsp;Christophe Nemos ,&nbsp;Gudrun Schleiermacher ,&nbsp;Pascal Chastagner ,&nbsp;Herve Sartelet","doi":"10.1016/j.humpath.2025.105718","DOIUrl":"10.1016/j.humpath.2025.105718","url":null,"abstract":"<div><div>Neuroblastoma is a common childhood tumor originating from neural crest progenitors with variable clinical behavior. Despite improved overall survival, factors such as stage, histoprognosis, <em>MYCN</em> status, and age still influence outcome. MCM6 regulates DNA replication and contributes to cancer progression. PRAME, first identified in melanoma, also acts on cell replication, epithelial-mesenchymal transition, and cell migration and has been associated with poor outcomes in several cancers, including neuroblastoma, using molecular biology techniques. The study aims to investigate MCM6 and PRAME expression and prognostic roles in neuroblastoma.</div><div>A retrospective study was conducted, which included data of 84 patients with neuroblastoma diagnosed between 2000 and 2022, sourced from the pediatric tumor registry. Patient's characteristics and prognostic tumor factors were collected. Expression of MCM6 and PRAME proteins was evaluated using digital image analysis techniques. Univariate and multivariate analyses were performed using Cox regression to assess the impact of protein expression on survival and their associations with these prognostic factors.</div><div>A total of 84 children diagnosed with neuroblastoma were included. MCM6 and PRAME were associated with unfavorable histologies (p = 0.03). PRAME was associated with bone marrow metastases (p &lt; 0.01), high mitotic-karyorrhectic index (p = 0.04), and poor histoprognosis (p &lt; 0.01).</div><div>PRAME and MCM6 expression was correlated with several neuroblastoma prognostic factors. PRAME was significantly (p = 0.05) associated with poor event-free survival (EFS) and not significantly (p = 0.08) associated with overall survival (OS). Although statistical significance was not reached in multivariate analysis, the trends strongly suggested that the overexpression of MCM6 and PRAME was correlated with decreased survival.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105718"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023281","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":"Clinicopathologic characterization of hormone-receptor positive, human epidermal growth factor receptor 2 Null, Ultralow, and Low breast carcinoma in the metastatic setting","authors":"Raza S. Hoda,&nbsp;Patrick J. McIntire","doi":"10.1016/j.humpath.2025.105735","DOIUrl":"10.1016/j.humpath.2025.105735","url":null,"abstract":"<div><div>HER2-directed therapy landscape is rapidly evolving. Patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2) Low and HER2 Ultralow demonstrate clinically meaningful progression-free survival improvement with HER2-directed antibody drug conjugates. Herein, we assess rates of hormone receptor-positive (HR+), HER2 Null, HER2 Ultralow, and HER2 Low metastatic breast carcinoma (MBC) and review clinical and pathologic aspects of primary tumors. We retrospectively reviewed all patients diagnosed with HR+/HER2- MBC metastatic breast carcinoma between 01/2023-12/2023 and characterized patients with HER2 Low, Ultralow, and Null results. 99 samples from 95 patients showed HR+/HER2- MBC. Seventy (70.7%) patients had HR+/HER2 Low MBC, 21 (21.2%) had HR+/HER2 Ultralow MBC, and 8 (8.1%) had HR+/HER2 Null MBC. HR and HER2 status of primary breast carcinoma were available in 56 (56.6%) of 99 samples. Primary and metastatic breast carcinoma samples shared the same HER2 status in 39 (69.6%) of 56 cases. Two (4.1%) of HER2 Low and 1 (33.3%) of HER2 Ultralow primary breast carcinoma cases showed shift to HER2 Null in the metastatic setting, and 3 (75%) of HER2 Null primary breast carcinoma cases showed shift to HER2 Ultralow or HER2 Low. Our one-year single-institution retrospective study shows majority of MBC are HR+/HER2 Low, followed by HR+/HER2 Ultralow. While majority of primary and metastatic breast carcinoma samples share similar HER2 status, patients may show change in HER2 status on metastatic tumor samples and repeat biomarker testing on metastatic samples may meaningfully guide HER2-directed antibody drug conjugate therapy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105735"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471659","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":"Beta-2-microglobulin positive tumor cells and CD8 positive lymphocytes are associated with outcome in post-neoadjuvant colorectal cancer resections","authors":"Soo Hyun Lee ,&nbsp;Amaya Pankaj ,&nbsp;Omer Yilmaz ,&nbsp;Vikram Deshpande ,&nbsp;Osman Yilmaz","doi":"10.1016/j.humpath.2025.105737","DOIUrl":"10.1016/j.humpath.2025.105737","url":null,"abstract":"<div><div>Locally advanced colorectal cancers are treated with neoadjuvant therapy (NAT), which has been shown to alter the characteristics of the tumor including size, lymph node yield, and histologic grade. We seek to interrogate the effect of NAT on the immune microenvironment. We compared 190 patients with colorectal adenocarcinoma treated with NAT with those without NAT (n = 926). We evaluated clinicopathologic and molecular factors and performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2M), CD8, CD163, LAG3, PD-L1, and FoxP3. Patients in the NAT group were younger (60.9 vs 67.9, <em>p</em> &lt; 0.001) and more often male (59.5 vs. 47.9, <em>p</em> = 0.004) than those in the non-NAT group. Tumors in the NAT group were smaller (3.5 vs 4.7 cm, <em>p</em> &lt; 0.001), less often high grade (6.5% vs. 16.2%, <em>p</em> = 0.001), more frequently in the rectum (68.9% vs. 6.6%, <em>p</em> &lt; 0.001) and associated with lower lymph node yields (<em>p</em> = 0.002); however, the incidence of extramural venous invasion, perineural invasion, and AJCC stage 3–4 disease were not different. Immune cells positive for CD8 (<em>p</em> = 0.011) were significantly lower in the NAT group. A high number of CD8⁺ cells and higher expression of B2M in tumor cells showed a significant survival benefit in both NAT and non-NAT group. NAT is associated with an immune-low tumor environment. CD8⁺ cells and tumor B2M expression may help identify a subset of immune high-tumors following NAT. This identification could aid in determining patients who may benefit from conservative management of colorectal carcinomas.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105737"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483126","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":"Re-evaluation of histopathological factors for the outcome of salivary duct carcinoma patients: A multi-institutional retrospective study of 240 cases in a Japanese cohort","authors":"Kimihide Kusafuka ,&nbsp;Eiji Nakatani ,&nbsp;Satoshi Baba ,&nbsp;Yoshifumi Arai ,&nbsp;Matsuyoshi Maeda ,&nbsp;Koji Yamanegi ,&nbsp;Takayuki Murase ,&nbsp;Hiroshi Inagaki ,&nbsp;Yoshiro Otsuki ,&nbsp;Kensuke Suzuki ,&nbsp;Hiroshi Iwai ,&nbsp;Yoshiaki Imamura ,&nbsp;Shoji Yamanaka ,&nbsp;Ichiro Ito ,&nbsp;Midori Sato ,&nbsp;Morito Kurata ,&nbsp;Tsutomu Daa ,&nbsp;Tomonori Kawasaki ,&nbsp;Ryo Kawata ,&nbsp;Yuri Tachibana ,&nbsp;Makoto Suzuki","doi":"10.1016/j.humpath.2025.105736","DOIUrl":"10.1016/j.humpath.2025.105736","url":null,"abstract":"<div><h3>Aims</h3><div>Salivary duct carcinoma (SDC) is a relatively common, high-grade salivary gland malignancy that can often occur as a carcinomatous component of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to elucidate the histological factors which are related to the outcome of SDC.</div></div><div><h3>Methods and results</h3><div>We conducted a comprehensive histological review of 240 SDC cases and we analyzed the association between the histomorpholgical parameters and the clinical outcomes to identify new histological prognostic factors. The majority of cases involved the parotid glands (n = 197 cases). SDC showed a marked male predilection (M/F = 5.3:1), and the median age was 66 years-old. This study included 110 <em>de novo</em> cases and 130 CXPA cases. Multivariate analysis revealed that only the pathological stage was significantly associated with overall survival (OS), whereas previously reported histological parameters, such as poorly differentiated clusters, nuclear polymorphism, and mitotic index were not significantly associated with OS and progression-free survival (PFS). Vascular invasion (V [+]) was significantly associated with PFS, and lymphatic invasion was associated with late lymph node metastases. Even in the same pathological stage, V (+) cases always had the worse PFS than V (−) cases.</div></div><div><h3>Conclusions</h3><div>The histopathological review determined that as distant metastasis relapse was the most important prognostic factor in patients with SDC, V (+) status was also a significant outcome indicator.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105736"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483134","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":"Primary adenocarcinoma of the urinary tract and its precursors: Diagnostic criteria and classification","authors":"Fanni Santa ,&nbsp;Mahmut Akgul ,&nbsp;Elie Tannous ,&nbsp;Richard R. Pacheco ,&nbsp;Andrea R. Lightle ,&nbsp;Sambit K. Mohanty ,&nbsp;Liang Cheng","doi":"10.1016/j.humpath.2025.105734","DOIUrl":"10.1016/j.humpath.2025.105734","url":null,"abstract":"<div><div>Primary adenocarcinoma of the urinary bladder is a rare malignancy, comprising up to 2% of bladder cancers, predominantly in males. Its rarity and similarity to urothelial carcinoma and secondary adenocarcinomas pose diagnostic challenges. A comprehensive literature review was conducted on the diagnosis, classification, morphological and immunophenotypic characteristics, and molecular profiles of primary adenocarcinoma, urachal adenocarcinoma, and precursor lesions.</div><div>Primary adenocarcinoma exhibits diverse morphological patterns, including enteric, mucinous, signet ring cell, and mixed types. Immunohistochemistry is useful in differentiating primary adenocarcinoma from metastatic adenocarcinomas and secondary involvement. Genetic studies reveal mutations common in colorectal and bladder adenocarcinomas (<em>KRAS, TP53, PIK3CA</em>) and novel primary adenocarcinoma-specific mutations (<em>OR2L5</em>). Urachal adenocarcinoma shares morphological features with primary adenocarcinoma but typically occurs in younger patients with unique genomic and distinct immunoprofile. Potential precursor lesions include villous adenoma, cystitis glandularis, and intestinal metaplasia, and warrant close clinical follow-up. Despite advances in histopathological and molecular diagnostics, primary adenocarcinoma remains challenging to diagnose due to its rarity and morphological heterogeneity. Ongoing research into its molecular characteristics is essential to refine diagnostic criteria and therapeutic approaches. Thorough clinical and pathological assessment is crucial for accurate diagnosis, classification, and clinical management.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105734"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483127","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(25)00030-9","DOIUrl":"10.1016/S0046-8177(25)00030-9","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105743"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535189","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":"Ovarian epithelioid tumor with FUS::CREM fusion and multilineage protein expression: Report of a case in the EWSR1/FUS-CREB tumor spectrum","authors":"J. Kenneth Schoolmeester ,&nbsp;Sounak Gupta ,&nbsp;Jennifer M. Boland ,&nbsp;Hussam Al Kateb ,&nbsp;Amy A. Swanson","doi":"10.1016/j.humpath.2024.105712","DOIUrl":"10.1016/j.humpath.2024.105712","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105712"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964617","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":"Vulvar and vaginal leiomyosarcomas: Immunohistochemical, molecular genetic and MDM2 fluorescence in situ hybridization analysis of three cases","authors":"Nooshin K. Dashti ,&nbsp;Sounak Gupta ,&nbsp;Amy A. Swanson ,&nbsp;Gary L. Keeney ,&nbsp;Michael Michal ,&nbsp;J. Kenneth Schoolmeester","doi":"10.1016/j.humpath.2024.105713","DOIUrl":"10.1016/j.humpath.2024.105713","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"155 ","pages":"Article 105713"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948179","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}