American Journal of Surgical Pathology最新文献

{"title":"Challenges in Diagnosing High-grade B-cell Lymphoma, NOS: Poor Interobserver Agreement on Its Morphologic Definition-An LLMPP Study.","authors":"Katrin S Kurz, Sarah L Ondrejka, Brett Collinge, Graham W Slack, Pedro Farinha, Andreas Rosenwald, Elias Campo, Catalina Amador, Timothy C Greiner, Philipp W Raess, Joo Y Song, Elaine S Jaffe, Dennis D Weisenburger, Wing C Chan, Klaus Beiske, Kai Fu, Jan Delabie, Stefania Pittaluga, Andrew L Feldman, Lisa M Rimsza, David W Scott, German Ott, James R Cook","doi":"10.1097/PAS.0000000000002565","DOIUrl":"10.1097/PAS.0000000000002565","url":null,"abstract":"<p><p>High-grade B-cell lymphoma, not otherwise specified (HGBCL, NOS), is defined by morphologic features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL). Lymphomas with a complex 11q aberration or concurrent MYC- and BCL2- or BCL6- rearrangements are excluded from this category. However, the reproducibility of the diagnosis of HGBCL, NOS is unknown to date. Expert hematopathologists of the Lymphoma/Leukemia Molecular Profiling Project reviewed 92 cases submitted as HGBCL, NOS. At least 3/4 hematopathologists reviewing cases independently confirmed the diagnosis in 30/92 (33%) cases, while 13 cases (14%) were reclassified as DLBCL. The remaining 49 cases were jointly reviewed by the consensus panel of 10 to 15 pathologists, confirming an additional 9 HGBCL, NOS. The remaining cases were reclassified as DLBCL or other aggressive B-cell lymphomas or were excluded due to insufficient material. In aggregate, only 39/92 (42%) of initially submitted cases were confirmed as HGBCL, NOS, demonstrating poor interobserver agreement. Interestingly, however, there were no significant differences between the initially submitted cohort and those ultimately confirmed by the pathology review panel concerning dark zone signature (DZsig) expression, frequency of MYC -rearrangements and cell of origin, among others. Despite the finding that pathologists can identify cytomorphological features associated with adverse biological characteristics, the poor reproducibility of high-grade morphology and molecular heterogeneity suggests that HGBCL, NOS does not represent a distinct clinicopathologic entity and that more objective markers of distinct biologic features, such as the DZsig, may better separate cases into relevant diagnostic categories than morphology alone.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"981-985"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147939370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Columnar Cell Subtype of Papillary Thyroid Carcinoma Is Characterized By A High Frequency of High-Grade Tumors That Exhibit Aggressive Clinicopathologic Features and Poor Outcomes: A Multicenter Study of 71 Cases.","authors":"Kartik Viswanathan, Bayan Alzumaili, Ahmed Lazim, Moaz K Mneinneh, Peter Sadow, Ronald Ghossein, Nicole A Cipriani, Bin Xu","doi":"10.1097/PAS.0000000000002551","DOIUrl":"10.1097/PAS.0000000000002551","url":null,"abstract":"<p><p>Papillary thyroid carcinoma, columnar cell subtype (PTC-CC) is a PTC characterized by nuclear pseudostratification and elongation. High-grade differentiated thyroid carcinoma is a novel classification of the WHO classification, defined by mitotic count ≥5/2 mm 2 and/or tumor necrosis, which may exhibit CC morphology and can be termed as high-grade PTC-CC (HGPTC-CC). In this multicenter retrospective study, we conducted a detailed clinicopathologic review in a retrospective cohort of 71 PTC-CC and HGPTC-CC. HGPTC-CC was common among tumors showing columnar cell morphology, accounting for 46% (33/71) of the entire cohort. Compared with PTC-CC, HGPTC-CC was significantly associated with male sex, infiltrative tumors, angioinvasion, microscopic extrathyroidal extension (ETE), positive resection margin, and advanced pT stage. Furthermore, HGPTC-CC had significantly shortened disease-specific survival (DSS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS). The 10-year DSS was 95% and 57%, the 10-year DMFS was 87% and 26%, and the 10-year RRFS was 85% and 55% for PTC-CC and HGPTC-CC, respectively. Among tumors with known BRAFV600E and RASQ61R status, BRAFV600E mutation was detected in 40% (19/47), whereas RASQ61R was identified in 15% (6/39). HGPTC-CC was associated with a significantly higher percentage of RASQ61R (PTC-CC 4%, HGPTC-CC 36%). In conclusion, a significant percentage (46%) of PTC-CCs are high-grade. HGPTC-CC is associated with adverse clinicopathologic features and poor outcomes. The impression of PTC-CC as an aggressive PTC subtype may be attributed to the high prevalence of high-grade histology in these tumors. Careful examination for mitoses and necrosis is required for accurate diagnosis and prognostication in PTC-CC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"865-871"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited Availability of Short Tandem Repeat Genotype Testing in the United States for Diagnosis of Partial Hydatidiform Mole: A Dilemma for Practicing Precision Medicine.","authors":"Laura Warren, Laura J Tafe, W Patrick Devine, Joseph T Rabban","doi":"10.1097/PAS.0000000000002558","DOIUrl":"10.1097/PAS.0000000000002558","url":null,"abstract":"<p><p>The pathogenetic definition of a partial hydatidiform mole (PHM) is a diandric triploid gestation, thereby requiring short tandem repeat (STR) genotype testing for definitive diagnosis in formalin-fixed products of conception (POC) specimens. However, recent literature shows there is limited access to this test, even in high-income countries. Therefore, we hypothesized that in the United States, access to this test would be enriched in academic centers and commercial reference laboratories. We surveyed the Association for Molecular Pathology membership and directly queried selected commercial laboratories in the United States. The survey identified 13 laboratories (11 in academic centers, 2 in nonacademic centers, 0 commercial laboratories) that offered STR genotype testing for molar pregnancy diagnosis in formalin-fixed POC specimens. Four of the 13 laboratories did not accept specimens from pathologists outside of their health care system. Among the 9 who did, 8 first required that the specimen undergo formal diagnostic consultation in their surgical pathology department. Insufficient demand was the leading rationale reported by survey respondents from laboratories that did not offer this test at all. Separately, direct queries with client service representatives showed that only 1 of 16 selected commercial reference laboratories in the United States offered this test. Given the limited access to STR genotype testing, we propose a new reporting nomenclature system that reflects the level of diagnostic certainty for PHM, depending on whether the diagnosis is based on genotype analysis, ploidy analysis, or morphology alone. Further efforts are needed to educate pathologists who do have access to genotype analysis to select that test format rather than ploidy analysis to evaluate the concern for PHM.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"917-923"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic Pattern of Chromophobe Renal Cell Carcinoma is More Aggressive Than the Classic Pattern: A Comprehensive Morphologic and Genomic Analysis.","authors":"Abraam Zakhary, Vincent F P Castillo, Kiril Trpkov, Joy Morgan, Pamela Plant, Mashiat Mimosa, Shreya Patel, Mark El-Mallah, Michelle R Downes, George M Yousef, Kenneth Pace, Malek Hamdani, Rola M Saleeb","doi":"10.1097/PAS.0000000000002560","DOIUrl":"10.1097/PAS.0000000000002560","url":null,"abstract":"<p><p>Chromophobe renal cell carcinoma (chRCC) is generally considered an indolent malignancy; however, studies have produced conflicting results regarding the differences among its histologic patterns. The prognostic significance of eosinophilic morphology in chRCC remains controversial, in part due to inconsistent diagnostic criteria and inclusion of morphologic mimickers. Cases were classified by 3 expert genitourinary pathologists into eosinophilic, classic, and mixed chRCC patterns based on strict morphologic and immunohistochemical criteria (n=110). Clinicopathologic features, copy number variations (CNVs), and targeted sequencing of TP53 , PTEN , and RB1 were assessed, along with pathway analyses using RNAseq and multiplex gene expression profiling. Clinicopathological and survival analysis were assessed using GraphPad Prism. The final cohort included 24 eosinophilic, 47 classic, and 39 mixed chRCC. CNV frequencies were similar across patterns, while RB1 aberrations and enrichment of oncogenic pathways (TP53, PTEN, RB1, DNA repair, mTOR, and cell cycle) were increased in both mixed and eosinophilic chRCC, with the greatest prominence in eosinophilic chRCC. Clinically, eosinophilic chRCC and mixed chRCC were associated with larger tumour size, more advanced clinical stage, and significantly worse disease-free survival (DFS) and overall survival (OS) compared with classic chRCC. On multivariate analysis, histologic pattern and stage remained prognostic of DFS. Therefore, eosinophilic chRCC showed a distinct molecular phenotype with enriched oncogenic pathways and poorer outcomes, while mixed chRCC displayed an intermediate but similarly aggressive profile. These findings indicate that eosinophilic morphology has potentially more aggressive biology than classic chRCC, underscoring the need for the introduction of specific diagnostic criteria for eosinophilic chRCC and its differentiation clinically.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"894-905"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Value of Systematic Versus Targeted Sampling in Prostate Cancer Detection and the Identification of Adverse Pathologic Features: A Retrospective Review of Over 1400 Combined Prostate Biopsies.","authors":"Ngoc-Nhu Jennifer Nguyen, Vincent F Castillo, Ekaterina Olkhov-Mitsel, Rola M Saleeb, Theodorus van der Kwast, Michelle R Downes","doi":"10.1097/PAS.0000000000002564","DOIUrl":"10.1097/PAS.0000000000002564","url":null,"abstract":"<p><p>The value of systematic biopsy (SBx) versus targeted biopsy (TBx) in the detection of prostate cancer and its adverse pathologic (AP) features was compared using a multi-institutional cohort of combined prostate biopsies with treatment-naive prostatic adenocarcinoma (N=1402, time period 2022 to 2025). Analyzed features included the highest International Society of Urological Pathology grade group (GG), clinically insignificant prostate cancer (CIPC, defined as GG1), clinically significant prostate cancer (CSPC, defined as GG ≥2), and AP (overall GG ≥3, cribriform/intraductal carcinoma, ductal features, extraprostatic extension, and/or seminal vesicle invasion). Compared with SBx, TBx more frequently had the highest GG cancer (81.2% vs. 58.8%, P <0.001), CSPC (61.9% vs. 46.9%, P <0.001), and AP (29.2% vs. 21.0%, P <0.001), and less CIPC (31.7% vs. 47.9%, P <0.001). The differences in the frequency of the aforementioned features remained significant when analyzing PI-RADS 4 (n=750) and 5 (n=420) lesions separately. PI-RADS 3 lesions (n=149) showed significant differences between sampling methods for CIPC ( P =0.036) and highest GG ( P =0.020) only, and transrectal ultrasound-guided biopsies (n=51) for CIPC ( P =0.003) only. For PI-RADS 2 lesions (n=7), standard magnetic resonance imaging (n=1), microultrasound (n=6) and positron emission tomography-guided biopsies (n=13), the sample was too small to draw definitive conclusions. If SBx were omitted, the rates of missed CSPC and AP would be 6.8% and 3.4%, respectively. Omission of TBx would result in missed rates of 22.0% for CSPC and 11.6% for AP. While the detection of CSPC and AP was best achieved using combined biopsy, the TBx only approach merits consideration in PI-RADS 4-5 lesions to decrease CIPC diagnoses.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"972-980"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TTF-1 Is a Sensitive and Specific Immunohistochemical Marker for Autoimmune Gastritis.","authors":"Deepa Kumari, Fazilet Yilmaz, Dongfang Yang, Li J Wang, Evgeny Yakirevich, Murray B Resnick, Khaled J Alkhateeb","doi":"10.1097/PAS.0000000000002562","DOIUrl":"10.1097/PAS.0000000000002562","url":null,"abstract":"<p><p>Autoimmune gastritis (AIG) is an inflammatory disorder that leads to corpus-restricted mucosal atrophy and is associated with the formation of well-differentiated neuroendocrine tumors and, possibly, gastric adenocarcinoma. The early histologic findings of disease are not specific, and the diagnosis may require correlation with autoantibody serology. Recent evidence demonstrated the upregulation of lung differentiation genes in AIG. Here, we assess the expression of TTF-1, a marker of lung differentiation, in 75 biopsies of AIG, 36 biopsies of multifocal atrophic gastritis (MAG), 29 biopsies of Helicobacter pylori gastritis, 10 biopsies of reactive gastropathy, and 10 normal gastric biopsies. TTF-1 was expressed in metaplastic mucinous glands in 52 (69.3%) corpus biopsies of AIG, with most showing at least moderate-intensity (2+) staining. TTF-1 staining was frequently observed in biopsies with partial atrophy (75%) and in those without intestinal metaplasia (66.7%) or enterochromaffin-like (ECL) cell hyperplasia (66.7%). Two (5.6%) corpus biopsies with MAG demonstrated focal weak (1+) TTF-1 expression. ECL cells and antral mucosa were consistently negative for TTF-1. Staining was absent in all other study groups. The sensitivity and specificity of TTF-1 for AIG were 69.3% and 97.7%, respectively. When at least moderate-intensity staining (2+) was considered positive, TTF-1 was 61.3% sensitive and 100% specific for AIG. These findings demonstrate that immunohistochemistry for TTF-1 can be used to confirm the diagnosis of AIG, particularly in the absence of typical histologic features of established disease, and that it may reduce the need for confirmatory serologic tests in the earlier histologic phases of disease.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"954-963"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidradenoma in Axillary Lymph Nodes: A Diagnostic Pitfall Mimicking Metastatic Carcinoma.","authors":"Gregory R Bean, Leandra G Kingsley, Jennifer Tan, Cooper D Rutland, Rachel Lin, Julia A Bridge, Paras B Patel, Poonam Vohra, Gregor Krings, Yunn-Yi Chen","doi":"10.1097/PAS.0000000000002553","DOIUrl":"10.1097/PAS.0000000000002553","url":null,"abstract":"<p><p>Axillary lymph nodes are a common site of metastatic carcinoma, particularly from the breast. Epithelial inclusions within axillary lymph nodes are uncommon but well recognized, most frequently encountered as small, incidental clusters of mammary-type epithelium; squamous, Müllerian, and mixed types are also sporadically identified. Hidradenoma is a benign adnexal neoplasm classically composed of epidermoid/squamoid, intermediate/basaloid, and mucinous cells that most commonly originates in the skin but can arise in the breast parenchyma, with morphologic and genetic features that overlap with mucoepidermoid carcinoma. Rare instances of hidradenomas within pelvic and axillary lymph nodes have been reported, raising the specter of metastasis. We report 3 cases of axillary lymph node hidradenoma presenting without a concurrent breast or cutaneous lesion. Morphology, immunohistochemistry, and molecular studies were evaluated. Two cases were found to harbor CRTC1::MAML2 rearrangements, while a rarer CRTC3::MAML2 fusion was identified in a third case. Following excision, the 3 patients were without evidence of residual disease, with clinical follow-up of ∼2 years each. Recognition of this entity is essential to avoid misclassification as metastatic carcinoma and prevent overtreatment.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"912-916"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Spectrum of Ubiquitin-specific Proteases-Fused Neoplasms: A Clinicopathologic and Molecular Study of USP2- and USP8-Rearranged Spindle Cell Tumors.","authors":"Diane Frankel, Anne-Claire Marsan-Fratini, François Le Loarer, Corinne Bouvier, Alexandra Meurgey, Aline Baltrès, Aurélie Houlier, Daniel Pissaloux, Sophie El Zein, Sarah Watson, Jeremy Garcia, Delphine Guillemot, Gaëlle Pierron, Franck Tirode, Marie Karanian, Nicolas Macagno","doi":"10.1097/PAS.0000000000002557","DOIUrl":"10.1097/PAS.0000000000002557","url":null,"abstract":"<p><p>Mesenchymal spindle cell tumors represent a heterogeneous group of neoplasms defined by distinct clinicopathologic features and diverse molecular alterations. While USP6 rearrangements are well-established in nodular fasciitis and related entities, fusions involving other ubiquitin-specific proteases, such as USP2 and USP8 , have only recently emerged. Prompted by sporadic reports of USP8 fusions in matrix-rich neoplasms, we aimed to characterize the clinicopathologic and molecular spectrum of USP2/USP8-rearranged mesenchymal tumors. We retrospectively analyzed 19 tumors, evaluating clinical, histopathologic features, immunohistochemical profiles, whole-transcriptome RNA sequencing, and DNA methylation profiling. Nineteen tumors were identified, harboring either USP8 (n=12) or USP2 (n=7) fusions. The cohort included patients aged 3 to 70 years (median: 32). Tumors primarily affected the distal extremities, with the notable exception of 2 intracardiac cases in pediatric patients, harboring USP8 fusions ( CBLB :: USP8 and SPPL2A :: USP8 ). Histologically, all cases were composed of bland spindle cells arranged in either a myofibromatous or an inflammatory pattern; notably, USP2-fused tumors exhibited an exclusively myofibromatous morphology. Immunohistochemically, SMA was frequently expressed, while desmin, h-caldesmon, ALK, ROS1, panTRK, and CD34 were consistently negative. Transcriptomic analysis demonstrated proximity to myofibroma and nodular fasciitis profiles, rather than forming a distinct USP2/8-specific cluster. No cases showed malignant behavior or recurrence during the available follow-up period. USP2/8-rearranged neoplasms represent a morphologically diverse but biologically indolent subset of myofibroblastic tumors. They exhibit significant overlap with USP6-associated lesions and PDGFR-altered myofibromas. Recognizing these fusions is critical to avoid diagnostic pitfalls and overtreatment, particularly when they present in unusual sites, such as the heart.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"943-953"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Grade Nasopharyngeal Papillary Adenocarcinoma: Toward a Better Molecular, Epigenetic, and Clinicopathological Understanding With Ontological Perspective.","authors":"Eric Lagrue, Nazim Benzerdjeb, Marick Laé, Marie-Delphine Lanic, Daniel Pissaloux, Fabienne Narducci, Hamza Benderradji, Anne Champagnac, Clémentine Decamps, Yvan Nicaise, Emmanuelle Uro-Coste, Valérie Costes-Martineau, Charles Lépine","doi":"10.1097/PAS.0000000000002561","DOIUrl":"10.1097/PAS.0000000000002561","url":null,"abstract":"<p><p>This study reports 6 cases of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) reviewed by the REFCOR network, integrating clinicopathological, genetic, and epigenetic analyses to refine our understanding of its histogenesis and biological behavior. Our 6 cases were located in the nasopharynx. Histologically, 5 cases had a frank papillary architecture, whereas 1 case showed a mixed papillary and tubular architecture. Papillary and tubular structures were covered by a single layer of epithelium of nonciliated cuboidal or columnar neoplastic cells. Squamous differentiation foci were present in 2 cases. Neither desmoplastic stroma, vascular invasion, nor perineural invasion was seen. All cases expressed TTF1. Neither local recurrence nor metastasis occurred in any of our cases, nor in the literature when only TTF1-positive cases are considered. At the molecular level, in the 3 cases that underwent CGH array and RNA sequencing, we did not find significant molecular anomalies. Our 3 LGNPPAs with DNA methylation analysis were closely grouped on the UMAP with posterior pituitary tumors. Furthermore, comparison of LGNPPA and low-grade non-ITAC sinonasal adenocarcinoma transcriptomes highlighted CNS-related genes as significantly upregulated in LGNPPAs. In conclusion, our transcriptomic and epigenetic data suggest a putative link to a shared progenitor with pituicyte-derived tumors. Our clinicopathological findings are consistent with the literature, highlighting a very indolent behavior.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"924-933"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteroblastic and Hepatoid Colorectal Carcinomas are Aggressive Cancers With a Distinctive Immunophenotype, While Clear Cell Carcinoma Appears to Represent Clear Cell Change in Conventional Colorectal Cancer.","authors":"Fahad Khan, Alexandros D Polydorides, John D Paulsen, Wei Chen, Jennifer Vazzano, Aaron Huber, David Papke, Nima Sharifai, Kristen Stashek, Ignacio Ruz-Caracuel, Daniela Allende, Kelsey McHugh, Jinru Shia, Teri A Longacre, Deepti Dhall, Elias Makhoul, Michael J Lee, Katrina Collins, Thomas M Ulbright, M Lisa Zhang, Maria Westerhoff, Zu-Hua Gao, Karen Matsukuma, Won-Tak Choi, Sanjay Kakar, Runjan Chetty, Klaudia Nowak, Stefano Serra, Xuchen Zhang, Wei Chen, Raul S Gonzalez","doi":"10.1097/PAS.0000000000002555","DOIUrl":"10.1097/PAS.0000000000002555","url":null,"abstract":"<p><p>Enteroblastic, hepatoid, and clear cell carcinomas are rare subtypes of colorectal carcinoma (CRC) with histologic and immunohistochemical (IHC) overlap. We assessed 37 CRCs that possibly represent these subtypes. Provisional criteria for each subtype, along with case photomicrographs and IHC data, were circulated among the authors to provide diagnostic interpretations. Based on plurality consensus, the carcinomas were classified as enteroblastic (n=13), hepatoid (n=6), and clear cell (n=18). Unanimous agreement was reached in 18% (3 clear cell, 3 hepatoid). Interobserver analysis revealed a mean pairwise Cohen κ of 0.63 (range: 0.32 to 0.91), with the hepatoid subtype eliciting the greatest consensus. Clear cell areas were the most likely to intermix with areas of conventional CRC ( P <0.001). Seven patients (20%) had inflammatory bowel disease (mostly linked to enteroblastic CRC). Twenty-three of 34 patients (68%) had nodal metastasis, and 12 (32%) had distant metastasis (mostly to the liver) at presentation. Median recurrence-free survival was 17 months, with enteroblastic cases the most likely to recur (54%, P =0.015). Median follow-up length was 27 months, with 14 patients (40%) dying of disease (representing 7 enteroblastic, 4 hepatoid, and 3 clear cell CRC). Mutations were identified in TP53 (n=8) , APC (n=3) , FBXW7 (n=2), and KRAS (n=1). Inflammatory bowel disease significantly worsened recurrence-free survival on multivariate analysis, while distant metastasis significantly worsened both recurrence-free and overall survival on multivariate analysis. Enteroblastic, hepatoid, and clear cell CRC demonstrate morphologic and IHC overlap, leading to interobserver variability in diagnosis. Given potential differences in clinical correlations and outcomes, more refined criteria are likely necessary.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"883-893"},"PeriodicalIF":4.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}