Human pathology最新文献

{"title":"Enteric glial cell remodeling at diagnosis is associated with reduced mucosal inflammation at follow-up in pediatric ulcerative colitis.","authors":"Harry J Rosenberg, Dongfang Yang, Riti S Bhalla, Phinnara Has, Michael I Herzlinger, Jason M Shapiro, Murray B Resnick","doi":"10.1016/j.humpath.2026.106265","DOIUrl":"10.1016/j.humpath.2026.106265","url":null,"abstract":"<p><p>Enteric glial cells (EGCs) comprise a key component of the enteric nervous system (ENS), and there is currently no standardized approach to characterizing EGCs in human gastrointestinal (GI) disease. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic GI disorders in which predicting responsiveness to treatment is an ongoing challenge. We use glial-specific immunohistochemistry (IHC) for SOX10 to assess EGC patterns in IBD colon and whether these patterns correspond to early histologic outcomes in pediatric patients. Approximately half (22 of 47) of pediatric UC patients in our cohort demonstrate ectopically located non-basal glial aggregates (NBGAs) in colonic mucosa. Pediatric UC patients with NBGAs are more likely to exhibit improved mucosal pathology (OR 8.00, p = 0.0048) at approximately 1-year follow-up compared to UC patients without NBGAs. Patients with NBGAs show reduced Geboes Score and Nancy Histological Index values at follow-up compared to diagnosis (p = 0.011, p = 0.0071, respectively), while patients without NBGAs do not show reduced scores. UC patients with NBGAs are more likely to demonstrate reduced fecal calprotectin at follow-up compared to patients without NBGAs (OR 12.2, p = 0.01). These findings stratify pediatric UC patients based on EGC profiles and initial clinical course, and they may help guide therapeutic decisions early in disease. The study is the first to implement a routine approach to documenting EGCs in GI mucosal pathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106265"},"PeriodicalIF":3.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968214","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":"Comparative distribution of HPV genotypes in penile and vulvar squamous cell carcinomas with basaloid or warty (condylomatous) features.","authors":"Diego F Sánchez, María José Fernández-Nestosa, Sofía Cañete-Portillo, Antonella Lobatti, Leticia Santacruz, Belén Lloveras, Jaume Ordi, Laia Allemany, Nubia Muñoz, Sylvia de Sanjosé, Xavier Bosch, Antonio L Cubilla","doi":"10.1016/j.humpath.2026.106266","DOIUrl":"10.1016/j.humpath.2026.106266","url":null,"abstract":"<p><p>Current paradigm is the classification of penile and vulvar carcinomas in HPV-associated and HPV-independent. About 30-50% of invasive carcinomas at both sites are HPV-associated. The aim of the study was to compare HPV genotypes in both neoplasias. HPV positive invasive penile (161 cases) and vulvar (221 cases) carcinomas were evaluated. They were pathologically classified as basaloid, warty-basaloid and warty carcinomas. HPV detection and genotyping of whole tissue sections was done using SPF-10/DEIA/LiPA25 system (version 1). The distribution of HPV-associated subtypes of invasive penile and vulvar carcinomas was similar. Twenty-one HPV genotypes were identified, 16 and 15 in penile and vulvar sites, respectively. HPV16 was equally frequent (80 vs 76%). Genotypes other than HPV16 shared by both tumors were HPVs 18, 31, 33, 45, 52, 53, 56, 58 and 73. There were, however, dissimilarities in HPV genotype distribution. HPVs 6, 35, 51, 55, 59 and 74 were found only in our penile cohort, whereas HPVs 11, 26, 30, 39, 44 were unique to our vulvar both tumors were HPVs 18, 31, 33, 45, 52, 53, 56, 58 and 73. Most HPV genotypes corresponded to those covered by current vaccines. HPV genotypes not covered by current HPV vaccines were 8 and 7 in penile and vulvar tumors, respectively, representing 10 and 7% of all patients in each category. However, there were genotypes identified only in our penile (6 of 21, 29%) and vulvar (5 of 21, 24%) tumors cohort. The differences found would have a minimal impact on current vaccination programs, which would cover around 90 and 93% of penile and vulvar cancer patients, respectively.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106266"},"PeriodicalIF":3.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955863","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":"Detection of androgen receptor (AR) splice variants across diverse prostatic and non-prostatic tumor types using the TruSight Oncology 500 (TSO500) assay.","authors":"Beth A Pitel, Surendra Dasari, Amber L Pryzbylski, Daniel S Childs, Dijana Poljak, Michael Keeney, Katherine Geiersbach, Peter C Lucas, Jacob J Orme, Elisabeth I Heath, Rumeal D Whaley, Joaquin J Garcia, Lori A Erickson, John C Cheville, Wei Shen, Gang Zheng, Hussam Al-Kateb, Benjamin R Kipp, Kevin C Halling, Emmanuel S Antonarakis, Sounak Gupta","doi":"10.1016/j.humpath.2026.106260","DOIUrl":"10.1016/j.humpath.2026.106260","url":null,"abstract":"<p><strong>Background: </strong>Androgen Receptor splice variants (AR-Vs) are known biomarkers of resistance to hormone therapy in prostate (CaP) and breast cancer (BC). However, pancancer interrogations of AR-Vs are lacking.</p><p><strong>Methods: </strong>The MayoComplete Solid Tumor Panel, with DNA and RNA subpanels targeting 515 and 55 genes, respectively, was used to profile 5573 solid tumors. Relevant clinicopathologic and molecular features were summarized for tumors with detectable AR-Vs.</p><p><strong>Results: </strong>AR-Vs were identified in 46 of 5573 (0.8%) tumors from 28 males and 18 females with a mean age of 68 years (range, 11 to 98). AR-Vs were enriched in CaP (24/132, 18.2%), BC (17/208, 8.2%), and salivary duct carcinomas (2/38, 5.3%), with rare occurrences in a lacrimal gland carcinoma and juvenile granulosa cell tumor. While AR-V7 was observed in all 46 tumors (100%), AR-V7 in the absence of other AR-Vs was seen in only 2 (of 46, 4.3%) tumors. Associated AR alterations in CaP included AR amplification (n = 3) and AR ligand binding domain (LBD) mutations (n = 2), while associated ESR1 variants in BC included ESR1 LBD mutations (n = 2) and ESR1 rearrangements (n = 2). Of patients with accessible medical records, 2/8 (25%) CaP patients had AR-Vs post-therapy with AR signaling inhibitors. Similarly, 5/6 (83.3%) BC patients had AR-Vs post-hormonal therapy. Notably, all 14 patients had multiple AR-V species.</p><p><strong>Conclusions: </strong>Our results demonstrate enrichment of AR-Vs in prostate, breast, and salivary duct carcinomas, with rare occurrences in a lacrimal gland carcinoma and juvenile granulosa cell tumor. Multiple AR-Vs were frequently seen in the same tumor. Detection of AR-Vs may be clinically significant in prostate cancer and additional data is needed for other tumor types.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106260"},"PeriodicalIF":3.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944790","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":"Co-occurrence of bronchiolar adenoma and lung adenocarcinoma: a study of nine cases revealing distinct clonal origins via integrated histologic, immunophenotypic and molecular analysis.","authors":"Shaoling Li, Yan Huang, Zhengwei Dong, Junhong Guo, Wei Wu, Likun Hou, Quan Li, Chunyan Wu","doi":"10.1016/j.humpath.2026.106261","DOIUrl":"10.1016/j.humpath.2026.106261","url":null,"abstract":"<p><strong>Purpose: </strong>This study sought to elucidate the possible biological association between BA and lung adenocarcinoma through an analysis of cases in which both lesions coexist within the same specimen.</p><p><strong>Methods: </strong>In our cohort, the BA and lung cancer components of nine concurrent-type BAs were microdissected using the Millisect system and subjected to whole-exome sequencing (WES). Their histopathological, immunohistochemical, and genomic profiles were comparatively evaluated.</p><p><strong>Results: </strong>Histopathologically, the BA regions of concurrent-type BAs exhibited a classic bilayered architecture, composed of continuous luminal and basal cell layers. The adjacent monolayered concurrent components were diagnosed as adenocarcinoma in situ (AIS, N = 4), minimally invasive adenocarcinoma (MIA, N = 2), and invasive adenocarcinoma (ADC, N = 3). Immunohistochemically, both luminal and basal cells in BA regions expressed thyroid transcription factor 1 (TTF1), albeit with more heterogeneous staining intensity compared to that observed in tumor components. Molecularly, EGFR mutations were the most frequently identified in either BA or tumor components, or in both (Case 9). In BA components, mutations included exon 19 p.S752F, exon 19 deletions (p.L747_T751delinsP and p.E746_T751delinsVP), and compound G719C/S768I mutations. Tumor components harbored exon 28 S1130C, exon 19 indel (p.E746_S752delins), and exon 18 p.G719C mutations. Notably, only three cases demonstrated limited overlap of mutations and copy number variations (CNVs) between the two components. Phylogenetic analysis revealed that six cases shared truncal alterations in genes including KMT2A, PIK3CA, SETD2, MITF, PBRM1, and SRSF3, one case harbored a shared canonical EGFR mutation (p.G719C), with an additional p.S768I alteration uniquely detected in the BA component.</p><p><strong>Conclusion: </strong>There is insufficient evidence to support BA as a premalignant lesion for lung adenocarcinoma base on morphological and molecular variables, and they may represent distinct pathological entities.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106261"},"PeriodicalIF":3.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929880","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":"L1CAM expression in eosinophilic solid and cystic renal cell carcinoma: clinicopathologic and immunophenotypic insights from a multicenter cohort.","authors":"Selva Kabul, Busra Yaprak Bayrak, Busra Ozbek, Elif Ozsagir, Nazif Alperen Yıldırım, Ece Ozturk, Hamed Jafarzadeh, Burcu Biltekin, Melek Buyukgok, Nuran Sungu, Murat Oktay, Ganime Coban, Kemal Kosemehmetoglu, Andres M Acosta, Liang Cheng, Mahmut Akgul","doi":"10.1016/j.humpath.2026.106263","DOIUrl":"10.1016/j.humpath.2026.106263","url":null,"abstract":"<p><p>Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a recently recognized eosinophilic renal neoplasm characterized by distinctive morphologic, immunophenotypic, and molecular features, including frequent TSC/mTOR pathway alterations. Recently, L1 cell adhesion molecule (L1CAM) has gained increasing recognition as a diagnostically and biologically relevant marker in selected eosinophilic renal neoplasms; however, its expression profile in ESC-RCC has not been systematically investigated. We aimed to evaluate L1CAM expression in a multicenter cohort of ESC-RCCs and correlate the findings with clinicopathologic and immunophenotypic features. A retrospective multicenter cohort of 11 ESC-RCCs was collected. Clinicopathologic and immunophenotypic findings were recorded. Immunohistochemistry for L1CAM was performed on representative whole tissue sections and semi-quantitatively scored based on the percentage of positive tumor cells. The cohort included 9 female and 2 male patients with a median age of 50 years (range, 39-79). L1CAM expression was identified in 7 of 11 tumors (63.6%), including 5 cases with diffuse membranous (3+) staining and 2 cases with intermediate (2+) staining; no tumor showed only focal (1+) expression. All tumors showed the characteristic morphology of ESC-RCC and expressed KRT20, irrespective of L1CAM status. Among tumors evaluated with additional markers, SDHB expression was retained in all 6 tested tumors and GATA3 was negative in all 5 tested tumors. Molecular testing was not performed in this cohort. Follow-up was available for all 11 patients (median, 10 months), with all patients alive without disease at last follow-up. Our findings expand the known immunophenotypic spectrum of ESC-RCC by demonstrating L1CAM expression in a substantial subset of tumors. However, because L1CAM expression is neither sensitive nor specific for ESC-RCC, positive or negative staining does not support or exclude the diagnosis and does not currently justify routine use of L1CAM in the diagnostic evaluation of morphologically suspected ESC-RCC.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106263"},"PeriodicalIF":3.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929862","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":"Sarcomatoid malignancies with strong PD-L1 expression often represent dedifferentiated or undifferentiated melanomas.","authors":"Aubre D Gilbert, Ryanne A Brown, David D W Twa, Alex Q Lee, Clara Hao, Hubert D Lau, John M Gross, Nam Bui, Xiaohua Qian, Fei Dong, Gregory W Charville","doi":"10.1016/j.humpath.2026.106264","DOIUrl":"10.1016/j.humpath.2026.106264","url":null,"abstract":"<p><p>Despite recent studies showing that dedifferentiated and undifferentiated melanoma (DM/UM) mimic sarcoma histologically, DM/UM continue to pose a diagnostic challenge owing to their under-recognition and frequent misclassification. To address this pitfall, we studied 22 cases of DM/UM initially classified as sarcoma. The patients were typically male (18/22) and older than 55 years (median 65 years, range 40-89 years), often lacking a history of melanoma (15/22). All but one case (21/22) presented with evidence of metastasis, and sites of disease frequently included lymph node basins, especially axilla (10/22). The tumors variably showed spindled and rhabdoid cytomorphology, collagenous or myxoid stroma, and fascicular architecture, imitating sarcoma; all tumors exhibited an intratumoral inflammatory component ranging from moderate to brisk. Molecular testing demonstrated alterations involving BRAF (7/22), NRAS/HRAS (10/22), NF1 (4/14), and TERT promoter (9/13). High tumor mutational burden was present in 13/13 cases (mean 21.8 mutations/Mb) and a UV-related mutational signature was found in 8/8. By immunohistochemistry, 55% (12/22) were negative for melanocytic markers, in keeping with undifferentiated melanoma. Two cases (2/17) were positive for desmin, while SATB2 was positive in 2/2 cases, including one with osteoid. The cohort showed strong expression of PD-L1 in all 22 cases (CPS 80-100, mean 93). In contrast, a separate cohort of 87 sarcomas of varying histotype had an average CPS of 5.6 (median CPS 0), including only three cases with CPS >50. Ten patients received PD-L1-targeted immunotherapy with partial or complete response in 80%. These findings emphasize pitfalls in distinguishing DM/UM from sarcoma and highlight the utility of PD-L1 immunohistochemistry in accurately diagnosing and effectively treating DM/UM.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106264"},"PeriodicalIF":3.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919799","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":"Solitary fibrous tumors involving the prostate and periprostatic region A multi-institutional cohort of 33 cases with literature review.","authors":"Katrina Collins, Luca Cima, Elena Marastoni, Matteo Brunelli, Busra Yaprak Bayrak, Yasemin Yuyucu Karabulut, Deniz Baycelebi, Begum Gunes, Gunes Guner Gebes, Kemal Kosemehmetoglu, Mahmut Akgul, Michelle S Hirsch, Fiona Maclean, Adeboye O Osunkoya, Ankur Sangoi, Andres Matoso","doi":"10.1016/j.humpath.2026.106249","DOIUrl":"10.1016/j.humpath.2026.106249","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Solitary fibrous tumor (SFT) is a mesenchymal neoplasm characterized by NAB2::STAT6 fusion and nuclear STAT6 expression. Primary SFT of the prostate is rare, and its biological behavior remains incompletely defined. We present a multi-institutional cohort and comprehensive literature review to better characterize clinicopathologic features, management, and outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;We analyzed 33 patients with prostatic SFTs from multiple institutions, integrating clinical, radiologic, histopathologic, immunohistochemical, and follow-up data. A systematic review of published cases was performed, and findings were contextualized using established risk models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patients ranged from 30 to 93 years (mean, 59; median, 61). Tumor sizes ranged from 0.6 to 19.5 cm (mean, 6.8; median, 5.75). Presenting symptoms included urinary obstruction, pelvic fullness, elevated PSA, or incidental detection. In two patients, the tumor caused urinary obstruction requiring transurethral resection. Location adjacent to the seminal vesicles was noted in several patients with one growing as a large mass into the pelvis. In several patients, the SFT was an incidental finding on needle biopsy performed for elevated PSA. Histologically, all tumors demonstrated classic SFT morphology with a spindle cell proliferation and patternless architecture. Tumor borders varied, with both well-circumscribed and infiltrative patterns observed. Cellularity ranged from low to high, and nuclear atypia was most often mild to moderate. Mitotic activity was generally low (&lt;5 mitoses/10 HPF in most cases), although two tumors showed elevated indices (12 and 15/10 HPF). Necrosis was identified in 5 tumors and was focal in 3. STAT6 was positive in 27/27 tested cases (100%), and CD34 was positive in all cases with available results (31/31, 100%). Management was primarily surgical. Only three tumors in this cohort developed metastatic disease, limiting the ability to confirm or refute the applicability of the Demicco risk stratification model. Metastatic cases occurred in relatively older patients, two of the three were &gt;5 cm with focal necrosis, and two had increased mitotic activity (&gt;4/10 HPF), while the third was 4.5 cm without necrosis but showed a high mitotic count. No overtly high-grade morphology or consistent morphologic predictors of metastasis were identified in this series. Follow-up was available in 16 patients (10-171 months; mean, 38; median, 29). Aside from the three patients who developed metastatic disease, all others were alive and without recurrence or metastasis at last contact.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This is among the largest reported cohorts of prostatic SFTs. These tumors, though rare in the prostate, appear to display similar morphologic and immunophenotypic features to SFTs in other anatomic sites. While generally indolent, rare cases may metastasize. Accurate diagnosis relies on a c","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106249"},"PeriodicalIF":3.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850638","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":"Is duodenal gastric heterotopia actually oxyntic metaplasia? An age-stratified prevalence study.","authors":"Zhe Ran Susan Duan, Helena Tomac Pavosevic, Stephen M Lagana","doi":"10.1016/j.humpath.2026.106250","DOIUrl":"10.1016/j.humpath.2026.106250","url":null,"abstract":"<p><p>The presence of oxyntic (body-type) glands in the duodenum is conventionally termed \"gastric heterotopia\" and is presumed to represent a congenital developmental anomaly. In contrast, gastric foveolar metaplasia of the duodenum is widely accepted as an acquired, reactive process. If duodenal gastric heterotopia were truly congenital, its prevalence should remain stable across age groups; if it is metaplastic in nature, prevalence should increase with age. A retrospective natural language search was performed for all cases diagnosed as \"gastric heterotopia\" in duodenal biopsies at a single academic medical center over a 10-year period (6/2013-4/2023). The prevalence of gastric heterotopia was calculated for each decade of life. Of 44,637 patients with duodenal biopsies, 846 (1.90%) had gastric heterotopia. The prevalence rose from 0.22% in patients aged 0-10 years to 4.05% in patients aged 91-100 years, representing an approximately 20-fold increase. The Spearman correlation between age group and prevalence was 0.988. The strong, monotonic relationship between patient age and prevalence of duodenal oxyntic glands is less consistent with a congenital process and instead supports a metaplastic etiology. The term \"oxyntic metaplasia\" is proposed as a more pathophysiologically accurate descriptor for this finding.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106250"},"PeriodicalIF":3.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857286","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":"Morphologic correlates of genetic subtypes of acute myeloid leukemia.","authors":"Jessica Anderson-Calleja, Vida Ehyaee, Kamran M Mirza","doi":"10.1016/j.humpath.2026.106230","DOIUrl":"10.1016/j.humpath.2026.106230","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is increasingly defined by recurrent genetic alterations that determine disease classification, prognosis, and therapeutic strategy. Although definitive diagnosis of genetically defined subtypes relies on cytogenetic and molecular techniques, careful evaluation of bone marrow and peripheral blood morphologic findings remains an essential and immediate component of the diagnostic process. Many genetic lesions in AML are associated with reproducible morphologic findings that can guide early diagnostic suspicion, inform triage of ancillary testing, and anticipate biologic behavior. This review summarizes the major genetically defined subtypes of AML and delineates their characteristic morphologic correlates, emphasizing how integration of microscopic findings with cytogenetic and molecular data enhances diagnostic precision. By revisiting morphology through a genomic lens, we underscore its continued central role in contemporary hematopathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106230"},"PeriodicalIF":3.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840041","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":"Assessment of isochromosome 12p supports that pagetoid involvement of the rete testis represents spread of germ cell neoplasia in-situ.","authors":"Harini Venkatraman Ravisankar, Sounak Gupta, Carrie Brandt, Ryan Knudson, Patricia Greipp, Jennifer B Gordetsky, Giovanna Giannico, Muhammad T Idrees, Thomas M Ulbright, Andres M Acosta","doi":"10.1016/j.humpath.2026.106240","DOIUrl":"10.1016/j.humpath.2026.106240","url":null,"abstract":"<p><strong>Background: </strong>Pagetoid involvement of the rete testis (RT) in seminoma is widely interpreted as spread of germ cell neoplasia in situ (GCNIS) rather than true invasion; however, this concept is based largely on morphologic observations. Assessment of isochromosome 12p [i(12p)], a hallmark of invasive germ cell tumors that is absent in GCNIS, was used to determine the nature of pagetoid RT involvement.</p><p><strong>Methods: </strong>We retrospectively identified orchiectomy specimens with pure seminoma and pagetoid RT involvement from institutional archives. Isochromosome 12p status was assessed on formalin-fixed, paraffin-embedded tissues using fluorescence in situ hybridization (FISH) with a dual-color PKP2/D12Z3 probe. Pagetoid RT involvement, invasive seminoma, and intratubular seminoma (ITS) components were analyzed separately when present.</p><p><strong>Results: </strong>Sixteen tumors were included, with successful FISH analysis in 15 (94%). Pagetoid RT involvement was evaluable in 14 cases and demonstrated i(12p) in only 1 (∼7%), while the remaining 13 were negative. In contrast, invasive seminoma showed i(12p) in 5/14 cases (∼36%). All seminoma components negative for i(12p) showed polysomy 12, suggesting that these are mutually exclusive alterations. Cases with discordant results contained i(12p)-positive seminoma and i(12p)-negative pagetoid RT involvement. Intratubular seminoma (ITS) was present in 6 tumors, being positive for i(12p) in 2 (∼33%).</p><p><strong>Conclusions: </strong>The absence of i(12p) in pagetoid RT involvement supports its interpretation as spread of GCNIS rather than invasive tumor. Rare detection of i(12p) in RT involvement suggest that, occasionally, this lesion may represent retrograde invasion by seminoma or, more likely, in-situ progression of GCNIS.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106240"},"PeriodicalIF":3.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792458","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}