Human pathology最新文献

{"title":"Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) in the Adolescent and Young Adult Population: A Pediatric Center Experience.","authors":"Mariel Bedell, John M Skaugen, Yuri Nikiforov, Miguel Reyes-Múgica, Claudia M Salgado, Jeffrey P Simons, Qian Wang, Catherine K Gestrich","doi":"10.1016/j.humpath.2025.105951","DOIUrl":"https://doi.org/10.1016/j.humpath.2025.105951","url":null,"abstract":"<p><p>Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a well-demarcated tumor with follicular growth pattern and papillary thyroid carcinoma-like nuclear features. Only rare reports exist in the literature describing the clinicopathologic features and incidence of NIFTP in the adolescent and young adult age group. The aim of this study is to address these gaps in the literature and characterize NIFTPs arising in this population. We retrieved all cases of NIFTP diagnosed from 2017-2023 at the UPMC Children's Hospital of Pittsburgh. Clinical information, cytologic and histologic features, and molecular testing results were reviewed, alongside a literature review. We identified 10 cases of NIFTP in 8 females and 2 males with an age distribution of 15 to 26 years old out of 152 fine needle aspirates (6.6%). All nodules were classified as low to moderate malignant risk on sonography (TI-RADS 3 and 4: n=5 each). Cytologic reporting varied with Bethesda III (n=6) and IV (n=2) predominately. All cases exhibited RAS (n=7) or RAS-like (n=3) alterations on molecular testing. No disease recurrence was noted on follow-up (13-86 months, median 39 months). We describe the clinicopathologic and molecular features of NIFTP in our adolescent and young adult cohort and compare them with those published in the literature. We demonstrate that NIFTP is rare in young children and largely restricted to adolescents and young adults. Clinicopathologic features and behavior show marked resemblance to those of adult-diagnosed NIFTP and thus may benefit from similar conservative treatment modalities.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105951"},"PeriodicalIF":2.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238239","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":"Insights from single cell and bulk RNA sequencing: increased NOTCH signaling is correlated with oncogenic transformation of juxtaglomerular cells to juxtaglomerular cell tumors","authors":"Sounak Gupta MBBS, PhD ,&nbsp;Surendra Dasari PhD ,&nbsp;Wei Shen PhD ,&nbsp;Benjamin R. Kipp PhD ,&nbsp;Lori A. Erickson MD ,&nbsp;John C. Cheville MD","doi":"10.1016/j.humpath.2025.105939","DOIUrl":"10.1016/j.humpath.2025.105939","url":null,"abstract":"<div><div>Renin-expressing juxtaglomerular cells in the kidney are the cell of origin for rare juxtaglomerular cell tumors, and affected patients often experience prolonged diagnostic odysseys as they present with relatively nonspecific symptoms related to secondary hypertension. While <em>NOTCH1-3</em> gene rearrangements are the predominant molecular finding in similar (non-renin producing) “myopericytic” cell-derived glomus tumors that occur at renal and non-renal sites, such alterations have been reported in only isolated cases of juxtaglomerular cell tumors. As pathogenic mechanisms contributing to the oncogenic transformation of juxtaglomerular cells to renin-producing tumors are poorly defined due to their extreme rarity, we compared single cell RNA sequencing data for (non-neoplastic) juxtaglomerular cells to bulk whole transcriptomic data for a series of six fusion-negative juxtaglomerular cell tumors. Unsupervised clustering revealed substantial alterations in gene expression in juxtaglomerular cell tumors compared to their cell of origin, including significant over-expression of markers that are diagnostically relevant (<em>renin</em>/<em>GATA3</em>), and other (upregulated) markers of interest including <em>CD34</em>, <em>NOTCH2/3</em>, <em>PDGFRB</em>, <em>JAG1</em>, and <em>NTRK3</em>. Finally, the majority of juxtaglomerular cell tumors showed increased NOTCH pathway signaling. These findings help better define the pathologic basis of oncogenic transformation of juxtaglomerular cells to renin-expressing tumors and may be informative regarding therapeutic options in unresectable or rare cases of metastatic juxtaglomerular cell tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"165 ","pages":"Article 105939"},"PeriodicalIF":2.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206249","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":"Evaluation of nuclear pseudoinclusions, GATA3, 34βE12, and GPNMB performances in CK7 diffuse positive clear cell renal cell neoplasms","authors":"Meihua Chen ,&nbsp;Yang Liu ,&nbsp;Yuankai Wu ,&nbsp;Haimin Xu ,&nbsp;Lei Dong ,&nbsp;Luting Zhou ,&nbsp;Xiaoqun Yang ,&nbsp;Xianwei Yang","doi":"10.1016/j.humpath.2025.105938","DOIUrl":"10.1016/j.humpath.2025.105938","url":null,"abstract":"<div><div>Recent studies have revealed histological diversity among clear cell renal cell neoplasms demonstrating diffuse CK7 positivity. While prior research established the utility of GATA3 and 34βE12 immunohistochemistry in clear cell papillary renal cell tumors (CCPRCT) and GPNMB in TSC/mTOR pathway-altered RCC with fibromyomatous stroma (TSC/mTOR RCC FMS), this study employed next-generation sequencing to analyze 36 CK7-diffuse positive clear cell renal neoplasms. These were classified as <em>ELOC</em>-mutated RCC (n = 17), TSC/mTOR RCC FMS (n = 12), CCPRCT (n = 4), and clear cell RCC (n = 3). Cystic architecture was uncommon in TSC/mTOR RCC FMS (2/12) and common in <em>ELOC</em>-mutated RCC (15/17), and nuclear pseudoinclusions were rare in <em>ELOC</em>-mutated RCC (1/17), but common in TSC/mTOR RCC FMS. GATA3 and 34βE12 expression was common in CCPRCT (2/4 and 4/4) and TSC/mTOR RCC FMS (5/11 and 8/11), though rare <em>ELOC</em>-mutated RCC exhibited focal expression (1/12 and 3/10). Limited weak cytoplasmic granular GPNMB expression occurred in one <em>ELOC</em>-mutated RCC and CCPRCT; however, diffuse GPNMB expression was exclusively identified in neoplasms with TSC/mTOR pathway alterations. These results emphasize that GATA3 and 34βE12 expression are not specific to CCPRCT, as they also occur in <em>ELOC</em>-mutated RCC and TSC/mTOR RCC FMS. While focal weak GPNMB expression may be observed in some <em>ELOC</em>-mutated RCC and CCPRCT, diffuse strong expression remains distinctive for TSC/mTOR pathway-altered neoplasms. The frequent nuclear pseudoinclusions observed in TSC/mTOR RCC FMS may aid differential diagnosis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"165 ","pages":"Article 105938"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102772","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":"Tumour budding and tumour-stroma ratio in hepatocellular carcinoma","authors":"Niklas Sarelin ,&nbsp;Valtteri Kairaluoma ,&nbsp;Juha Saarnio ,&nbsp;Joonas H. Kauppila ,&nbsp;Jan Böhm ,&nbsp;Heikki Huhta ,&nbsp;Juha P. Väyrynen ,&nbsp;Olli Helminen","doi":"10.1016/j.humpath.2025.105937","DOIUrl":"10.1016/j.humpath.2025.105937","url":null,"abstract":"<div><h3>Objectives</h3><div>Tumour budding has been linked with poor prognosis in hepatocellular carcinoma (HCC), while the prognostic value of tumour-stroma ratio (TSR) remains unclear. We assessed the prognostic value of tumour buds and TSR in HCC.</div></div><div><h3>Methods</h3><div>506 HCC cases were included. Survival analysis was performed separately for surgical (n=101) and non-surgical patients (n=405) based on the presence of tumour buds, and having low TSR (&lt;50 %) and high TSR (≥50 %). Bud-positive patients were further categorised according to tumour bud quantity (1–4 buds, 5–9 buds, and ≥10 buds), and the presence of tumour buds accross multiple sections of the same tumour was evaluated. We also analysed the correlation of tumour buds and TSR between biopsy and resection samples.</div></div><div><h3>Results</h3><div>Positive tumour budding was not associated with increased 5-year overall mortality in multivariable analysis (HR 2.00, 95 % CI, 0.98–4.07), but was an independent risk factor for disease-specific mortality (HR 2.53, 95 % CI, 1.06–6.02, P = 0.036). The presence of ≥10 buds was an independent risk factor of overall- and disease-specific mortality in multivariable analysis. Tumour buds were found in 77% of slides in bud-positive patients. TSR was not linked with 5-year overall survival or disease-specific survival. Biopsy samples demonstrated a low sensitivity of 22 % in identifying tumour budding compared to the resection samples.</div></div><div><h3>Conclusion</h3><div>Tumour budding was an independent risk factor for disease-specific mortality in surgically treated HCC patients, with higher bud counts indicating poorer outcomes. Tumour buds were consistently found across slides. Furthermore, our results suggest that tumour buds are most reliably evaluated using resection samples.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"165 ","pages":"Article 105937"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102774","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":"CTNNB1 mutations in serum amyloid A-positive hepatocellular neoplasm/inflammatory hepatocellular adenoma arising in alcoholic cirrhosis","authors":"Motoko Sasaki ,&nbsp;Yasunori Sato ,&nbsp;Yasuni Nakanuma","doi":"10.1016/j.humpath.2025.105936","DOIUrl":"10.1016/j.humpath.2025.105936","url":null,"abstract":"<div><h3>Background</h3><div>Serum amyloid A-positive hepatocellular neoplasm (SAA-HN) arising in alcoholic cirrhosis is now regarded as a specific type of inflammatory hepatocellular adenoma (IHCA) associated with advanced liver disease. Since recent studies reported various glutamine synthetase (GS) expression patterns corresponding to <em>CTNNB1</em> mutations in β-catenin mutated HCA, SAA-HN/IHCAs were herein re-evaluated for <em>CTNNB1</em> mutations.</div></div><div><h3>Methods</h3><div>GS expression was examined in 33 SAA-HN/IHCAs (23 patients) and 15 IHCAs (14 patients) from our archives and classified into patterns (P) 1–3 (P1, a diffuse homogeneous pattern suggesting an exon 3-non-S45 mutation; P2, diffuse heterogeneous, suggesting an exon 3-S45 mutation; P3, rim and focal heterogeneous, suggesting exon-7/8 mutations) and P4 (negative). Hotspot genetic mutations in <em>CTNNB1</em>, exons-3, 7, and 8 were examined by direct sequencing.</div></div><div><h3>Results</h3><div>Thirty-three SAA-HN/IHCAs were classified into 3 P1, one P3, and 29 P4 and 15 HCAs into 3 P1, 1 P2, 2 P3, and 9 P4. A genetic analysis revealed 3 SAA-HN/IHCAs with <em>CTNNB1</em>, exon-3 mutations and 1 exon-7 mutation, consistent with GS expression patterns P1 and P3, respectively. Two SAA-HN/IHCAs were associated with <em>CTNNB1</em>, exon-8 mutation, and both were regarded as P4 based on GS expression patterns. No significant differences were observed in clinicopathological features between SAA-HN/IHCAs with and without <em>CTNNB1</em> mutations (p &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Some SAA-HN/IHCAs may be b-IHCA, exon-3 or exon-7/8 mutations. Careful evaluation of immunoreactivity for GS and a genetic analysis of <em>CTNNB1</em> mutations are crucial for the accurate diagnosis of b-IHCA, exon-3 mutation, for which the risk of malignant transformation is high, and better clinical management.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105936"},"PeriodicalIF":2.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064690","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":"GNAQ-/GNA14-mutated hepatic vascular malformation with capillary proliferation in adults and children","authors":"Anne Kristin Fischer ,&nbsp;Carina Heydt ,&nbsp;Janna Siemanowski-Hrach ,&nbsp;Vedat Alibegovic ,&nbsp;Kathrin Hauptmann ,&nbsp;Christian Vokuhl ,&nbsp;Reinhard Büttner ,&nbsp;Hans-Peter Fischer","doi":"10.1016/j.humpath.2025.105934","DOIUrl":"10.1016/j.humpath.2025.105934","url":null,"abstract":"<div><h3>Aims</h3><div>Congenital hepatic vascular malformation with capillary proliferation (HVMCP) is a rare pseudo-tumourous liver lesion, to date only known in children. Diagnostic pitfalls in infant and, for the first time, in adult cases are histomorphologically characterised and molecularly analysed on driver mutations playing a role in angiogenesis and angioproliferation.</div></div><div><h3>Methods and results</h3><div>We histomorphologically characterised 4 early childhood and 2 adult cases, which showed malformed venous, cavernous and dissecting CD34-positive, GLUT1-negative capillary formations, followed by trabecular disarrangement of the involved liver parenchyma. As shown exemplarily, infant cases can lead to misdiagnosis as Glypican 3-positive hepatoblastoma. In adults, broadened capillarized liver trabecules might imitate hepatocellular carcinoma and dense capillary formations can resemble endothelial tumours, particularly hepatic small vessel neoplasia. In all cases, vascular malformation was the diagnostic key feature. Custom hybrid-capture-based sequencing assays were conducted, covering a broad range of genes active in angiogenesis and angioproliferation. Of the cases, 3, including 1 adult case, showed pathogenic activating driver mutations in <em>GNAQ</em>/<em>GNA14</em>. One adult lesion proved to be wild-type. Two wedge biopsies did not allow for molecular analysis.</div></div><div><h3>Conclusions</h3><div>HVMCP has to be differentiated from true vascular neoplasms, particularly from hepatic congenital haemangioma, hepatic infantile haemangioma and hepatic small vessel neoplasia but also from solid malignant hepatocellular tumours. Recognition of the underlying vascular malformation might disclose the pseudotumourous nature even in biopsies. Detection of driver mutations in the Gqα-protein-coding gene family with activation of the downstream MAPK/ERK pathway may open up a future treatment option for non-resectable lesions with MAPK/ERK inhibitors.</div></div><div><h3>Clinical trial number</h3><div>Ethic Votum BioMaSota No.13-091.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"165 ","pages":"Article 105934"},"PeriodicalIF":2.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064733","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":"Undifferentiated embryonal sarcoma of the liver: A clinicopathological and genomic study of 10 cases from a single institution","authors":"Paul Zamiara ,&nbsp;Nick Shillingford ,&nbsp;Larry L. Wang ,&nbsp;Ryan J. Schmidt ,&nbsp;Gordana Raca ,&nbsp;Shengmei Zhou","doi":"10.1016/j.humpath.2025.105935","DOIUrl":"10.1016/j.humpath.2025.105935","url":null,"abstract":"<div><h3>Aims</h3><div>Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy with limited clinicopathological and genomic characterization. This study aimed to investigate the genomic abnormalities in a cohort of UESL cases.</div></div><div><h3>Methods</h3><div>We analyzed ten UESL cases diagnosed at our institution from 2018 to 2025. Tumor specimens underwent DNA and RNA-based next-generation sequencing using the OncoKids® panel, along with chromosomal microarray analysis.</div></div><div><h3>Results</h3><div>The median age at diagnosis was 13.0 years (range: 0.8–18.3), and the median tumor size was 14.4 cm (range: 7.5–26.0). Lung metastases were present in three patients, and six tumors exhibited capsule rupture. Histology revealed pleomorphic, hyperchromatic oval, spindle, or stellate-shaped cells, with CD56 positivity. <em>TP53</em> was the sole recurring mutated gene, identified in nine of ten cases. Biallelic <em>TP53</em> inactivation (mutation plus copy number loss, <em>n</em> = 7) correlated with greater chromosomal complexity compared to monoallelic <em>TP53</em> mutations (<em>n</em> = 2). Segmental gain at 19q13.42-q13.43, including chromosome 19 microRNA cluster (C19MC), was observed only in tumors with biallelic <em>TP53</em> inactivation. No clinically significant RNA fusions were detected. All patients underwent tumor resection and ARST0332-based chemotherapy; four of six patients with tumor rupture also received whole abdominal radiation. At a median follow-up of 32.0 months (range: 3.0–81.2), all nine patients with follow-up were alive.</div></div><div><h3>Conclusions</h3><div><em>TP53</em> mutation is a defining molecular event in UESL, with biallelic inactivation linked to increased chromosomal complexity and C19MC locus gain. Despite its aggressive nature, favorable outcomes are achievable with multimodal therapy.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"165 ","pages":"Article 105935"},"PeriodicalIF":2.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058328","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":"Clinicopathological characteristics and immune infiltration analysis of esophagogastric junction adenocarcinoma with alterations in SWI/SNF complex","authors":"Na Cheng ,&nbsp;Bingzhi Wang ,&nbsp;Jiaqi Xu,&nbsp;Ziyue Wang,&nbsp;Liyan Xue","doi":"10.1016/j.humpath.2025.105930","DOIUrl":"10.1016/j.humpath.2025.105930","url":null,"abstract":"<div><h3>Background</h3><div>Alterations in SWI/SNF complex were mostly detected in poorly differentiated or undifferentiated gastric/esophagogastric junction adenocarcinoma (EGJA). However, there was a lack of studies investigating these alterations in a consecutive series of cases regardless of the morphology. Therefore, our study aimed to clarify the clinicopathological, prognostic, molecular and immune infiltration characteristics of a consecutive series cases with altered SWI/SNF complex in EGJA.</div></div><div><h3>Methods</h3><div>We retrospectively analysed 266 patients who underwent surgery without neoadjuvant therapy. Tissue microarrays were constructed for evaluating molecular markers (INI1, ARID1A, BRM, BRG1, MLH1, PMS2, MSH2, MSH6, EGFR, c-MET, HER2, p53 and PD-L1) and immune cell markers (CD3, CD4, CD8, CD68 and CD163). Immune cell counts were quantified using Qupath.</div></div><div><h3>Results</h3><div>Among the 266 patients, 36 (13.5 %) cases exhibited alterations in SWI/SNF complex. Specifically, 14 (5.3 %) cases were identified with ARID1A alteration, 21 (7.9 %) cases with BRG1 alteration, 7 (2.7 %) cases with altered BRM and 2 (0.8 %) cases with INI1 alteration. Alterations in ARID1A correlated with deficient mismatch repair (dMMR) (p &lt; 0.001), increased CD3⁺T-cell (p = 0.017) and relatively increased CD8⁺ T-cell infiltration (p = 0.057), whereas alterations of BRG1 correlated with reduced CD3⁺T-cell infiltration(p = 0.036). There were no significant differences in clinicopathological or prognostic characteristics in EGJA patients with or without SWI/SNF or its subunits alterations.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that the SWI/SNF complex demonstrates a notable frequency of alteration within the consecutive series of cases of EGJA. Alterations in ARID1A and BRG1 may correlate with distinct tumor microenvironment, which may provide new insights for optimizing treatment strategies in patients with SWI/SNF complex alterations.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105930"},"PeriodicalIF":2.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052947","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":"Interdisciplinary analysis of cues to triage gastric lymphoid proliferations: Role of the surgical pathologist revisited","authors":"Radhika Sekhri ,&nbsp;Xuejun Tian ,&nbsp;Jiani Chai ,&nbsp;Preeti Malik ,&nbsp;Ukuemi Edema ,&nbsp;Hania Shakeri ,&nbsp;Yungtai Lo ,&nbsp;Nicole C. Panarelli","doi":"10.1016/j.humpath.2025.105931","DOIUrl":"10.1016/j.humpath.2025.105931","url":null,"abstract":"<div><div>Surgical pathologists who examine gastric biopsies must triage exuberant lymphoid infiltrates for hematopathology consultation, a task that should account for resource and time utilization. We assembled all cases of chronic gastritis sent by surgical pathologists to hematopathology due to concern for low-grade lymphoma over a 4-year interval. The cases were ultimately classified as reactive (n = 37), atypical (n = 9), or lymphoma (n = 18). A surgical pathologist assessed lymphoid aggregates for their distribution and density, the presence of lymphoepithelial lesions, destruction of native structures, and monocytoid and/or centrocytoid and/or high grade cytology. Endoscopic findings, <em>Helicobacter pylori</em> infection, and any history of lymphoma were documented. Most reactive infiltrates displayed only one of the aforementioned concerning features, whereas atypical cases tended to have at least two and lymphomas at least 3 histologic hallmarks of lymphoma. Logistic regression analysis showed that history of lymphoma, and presence of &gt;3 concerning histologic features were significantly associated with final classification of atypical or lymphoma. The presence of full thickness lymphoid infiltrates approached significance. Combination of these three features produced an area under a receiver operating characteristic (ROC) curve of 0.9, indicating excellent discrimination between reactive and atypical lymphoid infiltrates/lymphomas. We conclude that surgical pathologists can reliably triage gastric lymphoid infiltrates for consultation and ancillary studies by combining clinical data with evaluation of histologic features.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105931"},"PeriodicalIF":2.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033229","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":"Leukemic phase of MYC/BCL2 double-hit high-grade B-cell lymphoma: A report of 35 cases","authors":"L. Jeffrey Medeiros,&nbsp;Jing Zhou,&nbsp;Xiaoqiong Wang,&nbsp;Wei Wang,&nbsp;Guilin Tang,&nbsp;Shimin Hu","doi":"10.1016/j.humpath.2025.105933","DOIUrl":"10.1016/j.humpath.2025.105933","url":null,"abstract":"<div><div>We report 35 patients who had a leukemic phase of diffuse large B-cell lymphoma/high-grade B-cell lymphoma with <em>MYC</em> and <em>BCL2</em> rearrangements, also known as double-hit lymphoma (DHL). There were 23 men and 12 women with a median age of 57 years (range, 29–82). Eight patients had an established DHL diagnosis and subsequently developed a leukemic phase of disease and 27 presented with DHL and a leukemic phase of disease at initial diagnosis. Thirty patients had not received any therapy specific for DHL at time of diagnosis. For these 30 patients, the median leukocyte count was 16.6 × 10⁹/L (range, 1.6–191.3) and the median percentage of lymphoma cells in the blood was 39 % (range, 10–97). Many patients presented with a clinical picture mimicking acute leukemia. Laboratory studies revealed elevated serum lactate dehydrogenase levels in all patients assessed, with a median level of 7507 U/L (range, 377–39,022). All patients had bone marrow involvement, with a median of 82% lymphoma cells in aspirate smears and approximately 80% replacement in biopsy specimens. Twenty-nine of 31 (94%) patients with complete information had extramedullary disease, most commonly lymph nodes. Immunophenotypic analysis showed a CD10-positive, germinal center B-cell immunophenotype in 34 cases. Conventional cytogenetic analysis was successful in 27 cases, all showing a complex karyotype. <em>MYC</em> partners were known in 22 cases, with immunoglobulin (IG) gene partners in 19 and non-IG partners in 3 cases. Despite treatment with chemotherapy regimens, overall survival was poor with a median of 7 months from onset of leukemic phase of disease. In summary, a small subset of patients with DHL can present with or develop a leukemic phase of disease which is a harbinger of very poor prognosis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"164 ","pages":"Article 105933"},"PeriodicalIF":2.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029534","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}