Human pathology最新文献

{"title":"Investigation of NPM1 mutation frequency in cutaneous blastic plasmacytoid dendritic cell neoplasms","authors":"Hanan Hamdan ,&nbsp;Alexa Siddon ,&nbsp;Maximiliano Ramia de Cap ,&nbsp;Sharon Germans ,&nbsp;Miguel D. Cantu ,&nbsp;Franklin Fuda ,&nbsp;Travis Vandergriff ,&nbsp;Nidhi Aggarwal ,&nbsp;Olga K. Weinberg","doi":"10.1016/j.humpath.2025.105766","DOIUrl":"10.1016/j.humpath.2025.105766","url":null,"abstract":"<div><h3>Background</h3><div>Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML) show overlapping clinicopathological presentations, which makes it challenging to differentiate on a small skin biopsy. <em>NPM1</em> mutations are the most common genetic lesions in AML, accounting for one third of cases and cause an aberrant cytoplasmic delocalization of <em>NPM1</em> mutants, which can be detected by an immunohistochemical stain. Frequency of <em>NPM1</em> mutations in BPDCN remains controversial. We aimed to investigate <em>NPM1</em> mutations in cutaneous BPDCN cases and compare them with cutaneous <em>NPM1</em> positive leukemia cutis cases.</div></div><div><h3>Methods</h3><div>From a multi-institutional search, we identified and analyzed 13 cases of cutaneous BPDCN and 19 cases of cutaneous myeloid sarcoma (7 of which were primary leukemia cutis) with <em>NPM1</em> mutations. We compared the clinical and pathological findings of these patients and identified distinguishing features between these groups.</div></div><div><h3>Results</h3><div>BPDCN patients presented at an older age, with lower white blood cell count, higher hemoglobin level, and elevated platelets counts as compared to cutaneous myeloid sarcoma patients (p &lt; 0.05). The bone marrow of patients in both groups was similarly involved at the time of diagnosis with no significant difference in rate; however, the percentage of involvement was significantly different among the two groups. Complex karyotype was more frequently seen in BPDCN patients (37.5 %) as compared with 15.7 % of cutaneous myeloid sarcoma patients (p &lt; 0.05). Mutational profile differed among the two groups with absence of <em>NPM1</em> mutations in BPDCN cases. Comparison of co-mutations detected in both groups revealed that BPDCN cases were significantly enriched in <em>IDH2, NRAS,</em> and <em>SRSF2</em> mutations.</div></div><div><h3>Conclusion</h3><div>We find that BPDCN patients present in a similar way to cutaneous AML patients but appear to uniformly lack <em>NPM1</em> mutations. Our study suggests that NPM1 can be used as a surrogate immunohistochemical stain to differentiate this rare disease from myeloid sarcoma in a rapid and cost-effective method.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105766"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852364","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":"Emerging manifestations of IL-17 immunomodulation in the gastrointestinal tract","authors":"Tiane Chen,&nbsp;Jacqueline E. Birkness-Gartman,&nbsp;Tatianna C. Larman","doi":"10.1016/j.humpath.2025.105782","DOIUrl":"10.1016/j.humpath.2025.105782","url":null,"abstract":"<div><div>Interleukin 17 (IL-17) is a proinflammatory cytokine that is commonly dysregulated in autoimmune diseases. Biologics targeting IL-17 (ixekizumab, secukinumab, brodalumab, bimekizumab) have been approved to treat conditions including psoriasis, psoriatic arthritis, and ankylosing spondylitis. Although inflammatory bowel disease (IBD) is characterized by dysregulated IL-17 signaling, IL-17 inhibitors have not shown benefit for IBD patients and are paradoxically associated with new-onset colitis. Here, we searched our biopsy archives and consult material to identify patients on IL-17 inhibitors with new-onset GI symptoms. Our final cohort included 5 patients, and most presented with new-onset bloody diarrhea that began from a few days to more than a year after IL-17 inhibitor initiation. Endoscopic impressions were similar to those in IBD, and histologic features included acute colitis, erosion/ulceration, crypt distortion, Paneth cell metaplasia, epithelial apoptosis, lamina propria lymphoplasmacytosis, and granulomas. Of 4 patients with follow-up, all received clinical diagnoses of IBD. IL-17 inhibitors were discontinued, and patients additionally required IBD therapeutic regimens for symptom resolution. Follow-up biopsies were available for 3 patients (maintained on IBD regimens) and showed normal mucosa; another patient developed a fistula. We conclude that patients on IL-17 inhibitors with new-onset colitis have a clinical and histologic spectrum that overlaps with IBD, primary immunodeficiencies, and other immunomodulatory therapies. The requirement of IBD biologics to achieve and maintain clinical/histologic remission in our cohort suggests that this process is more than a self-limited drug reaction. Future studies of expanded cohorts are required to determine whether IL-17 inhibitors unmask IBD in predisposed individuals or cause <em>de novo</em> IBD.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105782"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903737","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":"CD47 expression in classic follicular lymphoma is associated with event-free survival","authors":"Ayako Kume ,&nbsp;Sheren Younes ,&nbsp;Olivia Colace ,&nbsp;Iman Hussain ,&nbsp;Etienne Mahe ,&nbsp;Rong Lu ,&nbsp;Ranjana H. Advani ,&nbsp;Adnan Mansoor ,&nbsp;Yasodha Natkunam","doi":"10.1016/j.humpath.2025.105792","DOIUrl":"10.1016/j.humpath.2025.105792","url":null,"abstract":"<div><div>CD47 inhibits host cell phagocytosis by macrophages, leading to immune evasion. Upregulation of CD47 in many cancers including hematopoietic neoplasms correlates with poor prognosis. We evaluated CD47 expression in classic follicular lymphoma (FL) to ascertain its potential utility for targeted therapy. A cohort of 97 cases were studied by immunohistochemistry using a rabbit anti-CD47 monoclonal antibody and the results were correlated with clinicopathologic features, gene expression and clinical outcome. Our findings show that high CD47 expression (H-score ≥150) was significantly associated with a worse event-free survival at 12 months EFS12 and EFS24 months (<em>P</em> = 0.023 and 0.009 respectively), although no correlation was seen with overall survival (OS; <em>P</em> = 0.175) or other clinicopathologic parameters. In multivariate analysis, H-score retained its impact on both EFS12 and EFS24 (<em>P</em> = 0.027 and 0.0.012, respectively). Gene expression profiling revealed 11 genes that showed statistically significant differences in CD47-high versus CD47-low expressors in univariate but not in multivariate analysis and included <em>MAPK12</em> and <em>CCND2</em>. Validation in larger case cohorts is required to further support the potential application of CD47-targeted approaches in patients with FL and to explore novel therapeutic strategies. In addition, differentially expressed genes in CD47-high versus CD47-low expressors raises potential areas of interest for further study.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105792"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144069278","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":"TFE3/TFEB altered renal cell carcinomas in end-stage renal disease setting: A single institution clinicopathological study of 4 cases","authors":"Andrea Mladenovic,&nbsp;Lara R. Harik,&nbsp;Kristin K. Deeb,&nbsp;Elizabeth M. Genega,&nbsp;Faisal Saeed,&nbsp;Jatin S. Gandhi","doi":"10.1016/j.humpath.2025.105783","DOIUrl":"10.1016/j.humpath.2025.105783","url":null,"abstract":"<div><h3>Introduction</h3><div>Translocation renal cell carcinoma (tRCC) are morphologically distinct tumors having an underlying disease defining molecular alterations (commonly <em>TFE3/TFEB</em> gene alterations). Their occurrence in the setting of end stage renal disease (ESRD) has been rarely reported. This study was undertaken to assess the occurrence of <em>TFE3/TFEB</em> altered RCCs in ESRD setting at our institution.</div></div><div><h3>Design</h3><div>By retrospective review, we searched our pathology database for tRCC in ESRD setting over a 14-year period. We analyzed and documented the clinical, histopathological, immunohistochemical, and molecular findings in these tumors.</div></div><div><h3>Results</h3><div>Out of 223 patients of ESRD associated with RCCs, we found 4 cases of molecularly confirmed <em>TFE3/TFEB</em>-altered RCCs. Three of four patients were on pharmacologic immunosuppression (2 for underlying SLE and 1 for prior liver transplant). The ages ranged from 36 to 74 years (median 48 years) with an equal sex ratio. Tumors were solitary and ranged in size from 1.3 to 4.7 cm (median 2 cm). All four cases were confined to the kidney (pT1) and did not exhibit any necrosis, small vessel invasion, or sarcomatoid/rhabdoid features. The tumors exhibited characteristic morphology (solid, nested and papillary architectures with clear and eosinophilic cytoplasm in <em>TFE3</em>-rearranged RCCs, and biphasic morphology with basement membrane-like material in <em>TFEB</em>-altered RCCs). On immunohistochemistry, tumors consistently expressed cathepsin-K (3/3) &amp; Melan-A (3/3). On molecular studies one case was confirmed via FISH study (<em>TFEB</em> gene rearrangement) and three cases were confirmed via RNA fusionplex (<em>PRCC::TFE3</em>, <em>MED15::TFE3</em> and <em>MALAT1::TFEB</em> fusion transcripts). The median follow-up was 13 months (range 10–95 months), none of the 4 patients had any local or metastatic recurrences. One patient died of other comorbidities. Background kidney in all 4 patients exhibited variable features of ESRD.</div></div><div><h3>Conclusion</h3><div><em>TFE3/TFEB-</em>altered RCCs are rarely encountered in ESRD. Morphological and immunohistochemical findings of tRCC in ESRD replicate those found in sporadic settings. To the best of our knowledge, our study is the first to identify <em>TFEB</em>-rearranged RCCs in an ESRD setting.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105783"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936519","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":"Role of genomic analysis in the classification of well differentiated hepatocellular lesions","authors":"Fahire Goknur Akarca,&nbsp;James P. Grenert,&nbsp;Sanjay Kakar","doi":"10.1016/j.humpath.2025.105794","DOIUrl":"10.1016/j.humpath.2025.105794","url":null,"abstract":"<div><h3>Background</h3><div>The distinction of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) from well-differentiated hepatocellular carcinoma (WD-HCC) in noncirrhotic liver can be challenging. High-grade dysplastic nodule (HGDN) in cirrhosis can have overlapping features with WD-HCC. In some cases, HCA diagnosis is evident but glutamine synthetase (GS) staining is indeterminate for β-catenin activation, which does not allow reliable risk assessment. This study examines the role of genomic analysis in better categorization of WD hepatocellular lesions (WDHL).</div></div><div><h3>Design</h3><div>Genomic analysis using capture-based NGS assay was done in 23 WDHLs that could not be definitely classified based on morphology, reticulin stain and IHC, and were designated as ‘atypical hepatocellular neoplasms’ (AHNs). GS staining was classified as diffuse homogeneous (moderate to strong staining in &gt;90 % of tumor cells), diffuse heterogeneous (50–90 %), not diffuse (&lt;50 %) and borderline (not clear if more or less than 50 %).</div></div><div><h3>Results</h3><div>The genomic profile provided additional information for the diagnosis and/or risk assessment enabling a benign diagnosis in 15/23 cases (66 %) and HCC in 4/23 cases (17 %), while the diagnosis remained as atypical in the remaining 4 cases. Of the 4 cases with final HCC diagnosis, findings were suspicious but not diagnostic based on morphology/IHC; additional changes like <em>TERT</em> promoter mutation (n = 2), <em>AXIN</em> mutation (n = 1), <em>CDKN2A</em> loss (n = 2) and copy number alterations (n = 3) helped to support HCC. Of the 15 cases with a final benign diagnosis, the status of β-catenin activation was unclear based on GS stain in 8 cases, 2 of which showed <em>CTNNB1</em> exon 7 mutation, 1 showed <em>CTNNB1</em> exon 8 mutation, while genomic changes in 5 cases did not show any evidence of Wnt activation. FNH-like features were seen in 2 cases, but the genomic changes excluded FNH (<em>CTNNB1</em> and <em>ARID1A</em> mutation). The final diagnosis was unchanged from the initial diagnosis of AHN in 4/23 cases (17 %) as the molecular findings did not favor HCC.</div></div><div><h3>Conclusion</h3><div>Genomic changes were helpful in characterization of WDHLs, supporting HCC in 17 % of cases and clarifying β-catenin activation status in all 7 cases with borderline GS staining. Genomic changes are not specific but can provide diagnostic clues in selected challenging cases that cannot be classified on morphology and IHC. Given the significant treatment implications of distinguishing between HCC and benign/premalignant entities, routine use of genomic analysis in diagnostically challenging settings should be considered.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105794"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077609","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)00094-2","DOIUrl":"10.1016/S0046-8177(25)00094-2","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105807"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125282","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(25)00091-7","DOIUrl":"10.1016/S0046-8177(25)00091-7","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"158 ","pages":"Article 105804"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125292","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":"Challenges in papillary tumors of breast.","authors":"Raza S Hoda, Hannah Y Wen","doi":"10.1016/j.humpath.2025.105759","DOIUrl":"10.1016/j.humpath.2025.105759","url":null,"abstract":"<p><p>This review addresses common diagnostic challenges associated with papillary breast tumors-a rare but significant category of breast lesions. Despite their low incidence, papillary tumors are frequently encountered in breast pathology consultation practice due to their overlapping terminology and perplexing immunohistochemical results. Issues regarding assessment of invasive carcinoma in the setting of solid papillary carcinoma and encapsulated papillary carcinoma are covered. Emerging entities, such as tall cell carcinoma with reversed polarity and invasive lobular carcinoma mimicking solid papillary carcinoma, are discussed. Additionally, pragmatic guidance is provided for managing papillary breast tumors on needle core biopsy. Herein, we aim to provide clarity and confidence to surgical pathologists dealing with papillary breast tumors-mammary Medusa-equipping them with practical knowledge to better navigate this complex area of breast pathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105759"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673631","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 urethral adenocarcinoma harbors recurrent KRAS and EGFR alterations","authors":"Ting Zhao,&nbsp;A. John Iafrate,&nbsp;Chin-Lee Wu","doi":"10.1016/j.humpath.2025.105771","DOIUrl":"10.1016/j.humpath.2025.105771","url":null,"abstract":"<div><div>Primary urethral adenocarcinoma is an extremely rare malignancy with an unclear pathogenesis. Previously, we reported 4 brachytherapy-associated (BA) urethral mucinous adenocarcinomas that developed following treatment for prostate cancer. In the present study, we report one additional BA and 3 radiation-independent (RI) urethral adenocarcinomas. The aim of this study is to explore the molecular alterations and to compare the clinicopathologic features.</div><div>RNA sequencing was performed on 5 tumors, and a next-generation sequencing (NGS)-based fusion assay was used to identify gene fusions in 6 tumors. Additionally, NGS-based targeted genomic DNA sequencing was employed to analyze one metastatic BA tumor and one metastatic RI tumor.</div><div>The 8 patients had a mean age of 67 (range: 37–87) years, with one being female in the RI cohort. Cystoscopy revealed the following urethral findings: a papillary lesion (4/7), mass causing obstruction (1/7) and irregular friable tissue (2/7). Seven patients underwent urethrectomy with cystectomy/prostatectomy/hysterectomy. The mean tumor size was 3.4 cm (range: 1.5–6.5). Adenocarcinoma in situ was noted in 5 tumors. All 5 BA tumors originated from the prostatic urethra, with 4 showing mucinous morphology and one enteric morphology, and showed moderate to poor differentiation and tumor stages of pT2 (2/4), pT3 (1/3) and pT4 (1/4). Two patients developed metastasis, one at 3.3 and one at 4.2 years after diagnosis, and all patients were alive at a median follow-up of 4.5 (range: 2–14) years. In contrast, 3 RI tumors arose from bulbar, prostatic, or female mid/distal urethra, presenting as enteric, mucinous, and not otherwise specified (NOS) subtypes, with well to moderate differentiation and a tumor stage of pT4 (2/2). Two died of the disease, while one was alive without disease at a median follow-up of 4 (range: 2.2–14.5) years. All tumors were diffusely positive for CK20, CDX2 (7/7), and AMACR (3/3), and lacked nuclear β-catenin expression (5/5). Most expressed CK7 (5/7). <em>KRAS</em> mutations (p.Gly12Val and p.Gly13Asp) were observed in one BA mucinous tumor and one RI NOS tumor with the p.Gly13Asp mutation also detected in the metastatic RI tumor. The <em>EGFR</em> p.Ser784Phe mutation was detected in one RI enteric tumor. <em>TP53</em> p.Val172Phe, <em>CDKN2A</em> p.Leu32_Leu37del, and amplifications of <em>EGFR</em> and <em>MDM2</em>, were identified in a metastatic BA enteric tumor. No fusion transcripts were identified.</div><div>In conclusion, urethral adenocarcinoma harbors recurrent <em>KRAS</em> and <em>EGFR</em> alterations, independent of prior radiotherapy. RI tumors appear to be associated with a worse prognosis compared to BA tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105771"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791258","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)00064-4","DOIUrl":"10.1016/S0046-8177(25)00064-4","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"157 ","pages":"Article 105777"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851942","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}