American Journal of Surgical Pathology最新文献

{"title":"Papillary Renal Neoplasm With Reverse Polarity Is a Distinct Distal Nephron-Derived Tumor With Unique Methylation Profile.","authors":"Kyung Park, Yuxiu Wang, Kisong Kim, Jonathan Serrano, Fei Chen, Varshini Vasudevaraja, Xiaojun Feng, Leili Mirsadraei, Matija Snuderl, Fang-Ming Deng","doi":"10.1097/PAS.0000000000002568","DOIUrl":"10.1097/PAS.0000000000002568","url":null,"abstract":"<p><p>Papillary renal neoplasm with reverse polarity (PRNRP) has been proposed as a distinct subtype of renal cell neoplasm with recurrent KRAS mutations and indolent behavior. However, its epigenetic landscape is poorly understood. In this study, 12 PRNRPs and a PRNRP initially diagnosed as \"papillary adenoma\" were analyzed. All 13 cases underwent targeted next-generation sequencing for driver mutations. Eleven PRNRPs were profiled using the Illumina MethylationEPIC array and compared with a reference cohort of 71 common renal cell tumors. KRAS mutations were identified in 12 of 13 (92%) cases of PRNRP. Copy-number analysis from methylation profiling showed that 9 of 11 (82%) PRNRPs lacked copy-number changes. Two cases showed a focal loss of chromosome 8 and a gain of chromosome 16, respectively. Unsupervised clustering based on methylation data showed that PRNRPs form a distinct epigenetic group, separate from papillary renal cell carcinomas (pRCCs) and other major renal tumors, but with the closest affinity to clear cell papillary renal cell tumors. In addition, DNA methylation analysis suggested PRNRP may arise from the distal nephron, in contrast to pRCC, which appears to recapitulate proximal tubules. These findings support PRNRP as a subtype of renal cell neoplasm with a distinct epigenetic signature.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1046-1054"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262908","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":"Clinicopathologic Study of 39 Mismatch Repair-deficient Sarcomas Demonstrates Recurrent Histologic Patterns and Supports Universal Screening of Pleomorphic Rhabdomyosarcoma, Uterine Leiomyosarcoma, and Undifferentiated and Unclassified Sarcomas.","authors":"Igor Odintsov, Jonathan A Nowak, Esther Baranov, Thierry Alcindor, Candace L Haddox, Vinayak Venkataraman, Lynette M Sholl, Suzanne George, Leona A Doyle, Mark Redston, David J Papke","doi":"10.1097/PAS.0000000000002579","DOIUrl":"10.1097/PAS.0000000000002579","url":null,"abstract":"<p><p>Mismatch repair-deficient (dMMR) sarcomas are rare and incompletely characterized. Here, we studied 39 sarcomas with high microsatellite instability (MSI-H) and/or biallelic MMR gene inactivation (21 MSH2 , 9 MLH1 , 4 PMS2 , 4 MSH6 , 1 EPCAM ). All tumors evaluated with immunohistochemistry (IHC; n = 36) showed loss of MMR protein expression. Eight sarcomas were index neoplasms among the 15 patients with documented Lynch syndrome. Eighteen of 1531 sarcomas (1.2%) in our sequencing database were dMMR, with enrichment in pleomorphic rhabdomyosarcoma (PRMS; 1/5), uterine leiomyosarcoma (LMS; 7/124; 5.6%), and unclassified/undifferentiated pleomorphic sarcoma (UPS; 6/259; 2.3%). MMR IHC screening of independent cases confirmed MMR deficiency in PRMS (2/20), uterine LMS (2/20), and unclassified/UPS (1/20). Two histologic patterns were identified among unclassified/UPS. Ten tumors, designated \"distinctive lobulated inflammatory sarcoma\" (DLIS), showed lobular architecture, florid inflammation, and histiocytoid, variably pleomorphic neoplastic cells. All 6 patients with DLIS and follow-up (median: 6.0 y; range: 3 mo to 8.6 y) were alive with no evidence of disease (ANED), and 2 DLIS responded completely to immune checkpoint inhibition. A morphologically different group of 6 unclassified high-grade sarcomas showed sheets of epithelioid-to-rhabdoid cells with eosinophilic cytoplasm; among 5 patients with follow-up (median: 1.1 y; range: 4 mo to 6.9 y), only 1 was ANED. Surprisingly, all 3 PRMS patients with follow-up (median: 5.7 y; range: 4.2 to 8.3 y) were ANED, including 2 with complete responses of metastases to systemic therapy. We conclude that PRMS, uterine LMS, and unclassified/UPS showed sufficiently prevalent MMR deficiency to justify prospective MMR IHC screening for Lynch syndrome and to identify patients who might benefit from immune checkpoint inhibition. Histologic subtyping of unclassified sarcomas predicted prognosis and therapeutic response. We propose universal MMR IHC screening of (1) PRMS, (2) uterine LMS, (3) unclassified/UPS, and (4) any sarcoma in a patient with a personal or family history of Lynch syndrome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1029-1045"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148222623","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":"DLL3 Expression in a Genotyped Cohort of Sporadic Medullary Thyroid Carcinomas.","authors":"Maria Cristina Riascos, Fedaa Najdawi, Sara Ahmadi, Thomas J Roberts, Kartik Sehgal, Justine A Barletta","doi":"10.1097/PAS.0000000000002571","DOIUrl":"10.1097/PAS.0000000000002571","url":null,"abstract":"<p><p>Delta-like ligand 3 (DLL3) has been identified as a therapeutic target in high-grade neuroendocrine carcinomas, particularly small cell lung carcinoma. Data on DLL3 expression in medullary thyroid carcinoma (MTC) are limited; moreover, the relationship between DLL3 expression and MTC genotype has not been explored. We evaluated DLL3 expression (based on staining intensity and percentage of positive cells) in a genotyped cohort of sporadic MTC. In our cohort of 39 cases, 27 (69%) tumors were positive for DLL3, including 1 (4%) with low DLL3 expression, 10 (26%) with moderate expression, and 16 (41%) with high expression. DLL3 expression was significantly associated with grade ( P =0.036), presence of a RET mutation ( P =0.014), presence of lymph node metastases at diagnosis ( P <0.005), and disease progression ( P <0.005). All 9 (100%) high-grade tumors were positive for DLL3. In contrast, 18 (60%) of 30 low-grade tumors were DLL3 positive. DLL3 was positive in 17 (89%) of 19 RET -mutated tumors, 4 (50%) of 8 RAS -mutated tumors, and 6 (50%) of 12 RET/RAS wild-type tumors. All 24 primary tumors with associated lymph node metastases at diagnosis were positive for DLL3. Among cases with follow-up data (n=35), all 17 tumors with disease progression were DLL3 positive (13 RET -mutated tumors, 1 RAS -mutated tumor, and 3 RET/RAS wild-type tumors), including 5 with moderate expression and 12 with high expression. Most MTCs express DLL3; moreover, DLL3 expression is associated with lymph node metastases at diagnosis and disease progression, indicating that DLL3 may be an effective therapeutic target in MTC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1076-1085"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196970","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":"Ovarian Mucinous Neoplasms Associated With Mesonephric-like Lesions: An Updated Study With Novel Pathologic Features.","authors":"Colton Smith, Jonathan Dudley, Johanna Savage, Koen Van de Vijver, Liu Hong, Weihua Song, Gözde Kir, Katerina Kearns, Delaram Shakiba, Kathi H Adamson, Saron A Smith, Yun Wang, Mei Liu, Aijun Liu, Russell Vang, W Glenn McCluggage, Deyin Xing","doi":"10.1097/PAS.0000000000002573","DOIUrl":"10.1097/PAS.0000000000002573","url":null,"abstract":"<p><p>The coexistence of benign mesonephric-like proliferation (MLP), mesonephric-like hyperplasia (MLH), and mesonephric-like adenocarcinoma (MLA) with ovarian mucinous cystadenoma or mucinous borderline tumor (MBT) has been previously reported; however, this phenomenon is exceedingly rare, and understanding of the pathology and biology remains limited. Here we report additional cases, with an emphasis on expanded observations and novel pathologic features. This series included 9 cases: (1) 2 cases of mixed MLA and endometrioid adenocarcinoma associated with cystic mucinous neoplasm of lower gastrointestinal (GI) type (case 1) or mucinous cystadenoma (case 2); (2) 1 case of MLA associated with MBT and mucinous adenocarcinoma (case 3); (3) 4 cases of MLA associated with MBT (cases 4 and 5) or mucinous cystadenoma (cases 6 and 7); and (4) 2 cases of MLP/MLH associated with MBT (cases 8 and 9). All mesonephric-like lesions were diffusely positive for PAX8 and either diffusely (7 cases) or focally (2 cases) positive for GATA3. Focal TTF-1 expression was observed in 4 cases (4/9, 44.4%). All mucinous tumors, except for case 1, showed either focal (4 cases) or diffuse (4 cases) PAX8 positivity. Molecular analysis in case 1 revealed a common KRAS p.G12A driver mutation in all 3 tumor components (MLA, endometrioid adenocarcinoma, and mucinous tumor), indicating clonal relatedness. In contrast, pathogenic somatic mutations in ARID1A , DNMT3A , PIK3CA , and TET2 were detected only in the MLA and endometrioid adenocarcinoma, but not in the mucinous tumor component, suggesting lineage-specific differentiation. Notably, case 1 represents the first reported example of a mesonephric-like lesion associated with a mucinous tumor exhibiting lower GI morphology and immunophenotype. Case 3 represents the first case with mucinous adenocarcinoma in this scenario. Case 9 represents the first reported instance in which both ovaries were independently involved by MLP/MLH and MBT. The presence of benign MLP/MLH alongside MLA suggests that the former may represent noncancerous precursor lesions with the potential to develop into MLA; they may represent benign (MLP) or borderline (MLH) mesonephric-like lesions. Whether mesonephric-like lesions serve as precursors of ovarian mucinous tumors remains debated, but their coexistence in the ovary, as documented in 20 cases to date (including previously published cases and the current series), may represent a unique biological process and provide an ideal model for investigating mechanisms of transdifferentiation and tumorigenesis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1086-1096"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025674","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":"HOXB13 Is a Sensitive and Specific Diagnostic Marker for Myxopapillary Ependymoma.","authors":"Meng Zhang, Huanli Duan, Wanting Wang, Lihong Zhao, Min Gao, Leiming Wang, Lianghong Teng","doi":"10.1097/PAS.0000000000002581","DOIUrl":"10.1097/PAS.0000000000002581","url":null,"abstract":"<p><p>Myxopapillary ependymoma (MPE) is a rare spinal tumor that remains undercharacterized in systematic investigations. Accurate distinction from histologic mimics in the conus-cauda-filum terminale region is challenging. This study aimed to describe the clinicopathologic features and outcomes of a large single-center MPE cohort, evaluate the diagnostic utility of HOXB13 immunohistochemistry (IHC), and explore the molecular profiles of atypical cases through methylation clustering. HOXB13 IHC was performed on 45 MPEs, 44 spinal ependymomas (SEs), and 35 other nonependymal spinal tumors. Fourteen atypical cases (MPEs with weak HOXB13 or high-level involvement, and HOXB13-positive SEs) were analyzed by DNA methylation microarray with t-SNE and random forest clustering. HOXB13 expression was semiquantitatively graded (0 to 2). Strong positivity was seen in 97.8% (44/45) of MPEs, but only 4.5% (2/44) of SEs and 11.4% (4/35) of nonependymal tumors. Sensitivity and specificity for MPE diagnosis were 97.8% and 92.4%. Methylation clustering showed strong HOXB13 expression aligned with the MPE methylation class (EPN_MPE). Notably, 3 typical MPEs were misclustered due to fresh hemorrhage, stromal sclerosis, or dural components, whereas 2 HOXB13-strong lumbar SEs fell into the EPN_MPE class. MPE patients had 100% 10-year overall survival and 75% progression-free survival (PFS), but PFS was significantly shorter than that of SE patients ( P < 0.01). HOXB13 is a highly specific and sensitive IHC marker for MPE. Histologic artifacts can interfere with methylation-based classification, emphasizing the need for tissue quality assessment and microdissection when indicated. HOXB13 IHC is a simple, reliable diagnostic tool that improves accuracy when added to routine IHC panels.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1129-1137"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434862","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":"Biallelic ARID1A Alterations : A Promising Novel Biomarker for Risk Stratification and Management in Pediatric Malignant Hepatocellular Tumors.","authors":"Kalyani R Patel, Martin Urbicain, Stephen F Sarabia, Cintia R Perez, Angela M Major, Kevin E Fisher, Angshumoy Roy, Frederic Askin, Andras Heczey, Andres F Espinoza, Sanjeev A Vasudevan, Pavel Sumazin, Dolores H Lopez-Terrada","doi":"10.1097/PAS.0000000000002578","DOIUrl":"10.1097/PAS.0000000000002578","url":null,"abstract":"<p><p>Somatic mutations and copy number alterations of the adenine-thymine (AT)-rich interactive domain-containing protein 1A ( ARID1A ), a tumor suppressor gene, are associated with poor prognosis in many cancers, including adult hepatocellular carcinomas (HCC). In this study, ARID1A protein expression, clinicopathologic features, and outcomes were investigated in 59 pediatric malignant hepatocellular tumors (2004 to 2022) relative to ARID1A mutation and copy number status. Additional studies were performed on the impact of the loss of ARID1A protein expression on genomic instability, immune-cell infiltration, and PD-L1 protein expression. Twenty-three of the 59 (38.9%) children with malignant hepatocellular tumors (age: 0.4 to 13.8 y, M:F=2:1) harbored ARID1A alterations (mutations and/or copy number alterations). Nine tumors (15.2%) with biallelic alterations ( ARID1A -/-) showed higher metastasis at presentation ( P =0.01), were frequently CHIC high-risk ( P =0.05), had aggressive histology (HCN-NOS and HCC) ( P =0.002), and were negative for ARID1A immunohistochemistry (IHC) (100%). ARID1A loss by IHC was 100% sensitive and 98% specific, with 90% positive and 100% negative predictive value for ARID1A -/- tumors. ARID1A-negative tumors showed higher chromosomal instability ( P =0.04), immune infiltrates ( P =0.005), and PD-L1 expression by IHC ( P =0.05). Patients with both ARID1A-negative and ARID1A-negative/PD-L1-positive tumors showed the lowest disease-specific survival in the intermediate and high CHIC-risk and all PRETEXT subgroups ( P =ns ) . The association of biallelic ARID1A alterations with high-risk features and poor outcomes identifies ARID1A as a potential new biomarker in the risk stratification of children with malignant hepatocellular tumors. ARID1A IHC is a reliable tool to identify these aggressive tumors. Associated PD-L1 expression may offer new therapeutic options via checkpoint inhibitors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1106-1119"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148256996","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":"Folate Receptor Alpha Expression Across the Spectrum of Serous Tubal Lesions: An Adjunct Biomarker for Distinguishing Serous Tubal Intraepithelial Carcinoma From Serous Tubal Intraepithelial Lesions.","authors":"Yan Feng, Rujia Fan, Zhigang Yao, Zeng Yuan, Ruijiao Zhao, Yuxin Liu, M Ruhul Quddus, Oluwole Fadare, Jayanthi Lea, Beihua Kong, Wenxin Zheng","doi":"10.1097/PAS.0000000000002612","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002612","url":null,"abstract":"<p><p>Folate receptor alpha (FRα) is highly expressed in tubo-ovarian high-grade serous carcinoma (HGSC), but its expression in serous tubal intraepithelial carcinoma (STIC) and earlier tubal lesions has not been systematically characterized. We evaluated FRα expression across the spectrum of fallopian tube lesions and assessed its potential as an adjunctive diagnostic biomarker. Immunohistochemistry was performed on 408 tubal epithelial samples from 262 patients, including 52 normal fallopian tube samples, 110 secretory cell expansions (SCE), 88 secretory cell outgrowths (SCOUT), 72 serous tubal intraepithelial lesions (STIL), and 56 STICs. An additional 30 HGSCs were included for comparison. FRα expression was assessed using the percentage score ≥2+ (PS2+) system. Associations with germline BRCA status and age were evaluated. FRα expression was detectable in normal fallopian tube epithelium but usually below the high-expression threshold. In contrast, expression was increased in STIC and HGSC, with high PS2+ scores in 73.2% and 76.7% of cases, respectively. Earlier tubal lesions showed predominantly low or negative/very low expression. No significant difference in FRα expression was observed between STIC and HGSC. BRCA-mutated STIC and HGSC showed higher FRα expression than their BRCA nonmutated counterparts, whereas earlier lesions showed no such association. In normal fallopian tube epithelium, FRα expression decreased with age. These findings demonstrate that FRα upregulation is established at the STIC stage and maintained in invasive HGSC. Diffuse high-level expression is uncommon in STIL and earlier lesions, suggesting that FRα may serve as an adjunct biomarker for distinguishing STIC from morphologically overlapping lesions. When interpreted in conjunction with morphology, p53, and Ki-67, FRα may improve diagnostic confidence along the STIL-to-STIC spectrum. The early and sustained upregulation of FRα in STIC also raises interesting questions regarding the timing of FRα-targeted interventions.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872707","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":"Hypertrophic Lichen Sclerosus: A Form of \"Atypical\" Lichen Sclerosus in the Pathway to HPV-Independent Squamous Cell Carcinoma of the Vulva.","authors":"Susanne K Jeffus, Carli Cox, Sara C Shalin, Brannon Broadfoot, Charles M Quick","doi":"10.1097/PAS.0000000000002574","DOIUrl":"10.1097/PAS.0000000000002574","url":null,"abstract":"<p><p>Hypertrophic lichen sclerosus (HLS) is poorly characterized. A recent study described an atypical form of LS (p53 wild type) with a CK17/D2-40 immunohistochemical profile intermediate between classic LS and differentiated vulvar intraepithelial neoplasia (dVIN). Our study aims to characterize HLS through IHC and molecular profiling to determine if it is a classic or atypical LS lesion. We reviewed HLS diagnosed in 12 biopsies (2014 to 2025) and 5 resections for vulvar squamous cell carcinoma (vSCC) (1998 to 2015) from our institution (mean patient age 59; range: 37 to 97). We defined HLS by nonexophytic acanthosis, hyperkeratosis +/- parakeratosis, granular layer retention, irregular dermal-epidermal junction, lack of severe basal layer atypia, homogenization of the superficial dermis, and +/- lichenoid inflammatory infiltrate. In the 5 resections, CK17 expression was suprabasal in 4 (80%) and superficial in 1 (20%) of HLS adjacent to vSCC. D2-40 intensity was moderate in all 5 (100%). All 5 vSCC were p16-/p53 aberrant with intense D2-40 expression and showed diffuse CK17 in 4 (80%) and suprabasal staining in 1 (20%). All 12 HLS biopsies were p16-; 7 (58%) were p53 wild type and 5 (42%) were aberrant. Seven (58%) showed CK17 suprabasal staining; 5 (42%) were diffuse. D2-40 intensity ranged from absent (1/12; 8%) to faint (3/12; 25%) to moderate (3/12; 25%) to intense (5/12; 42%). Frequently altered genes were SDHA (3/6; 50%) and TP53 (2/6; 33%). HLS shows neither the classic morphology of LS nor dVIN but can be p53 aberrant/mutant. Because of its CK17/D2-40 immunophenotype, it should be considered as atypical LS.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1055-1066"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136431","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":"Absent Cyclin D1 Expression in Myeloid Sarcomas Distinguishes From Malignant Histiocytic Neoplasms: When Morphologic Ambiguity is Deceptive.","authors":"Alyssa M Lee, Neha Seth, Wayne Tam, Liuyan Jiang, Jithma P Abeykoon, Dongni Yi, Rebecca L King, Kaaren K Reichard, Ronald S Go, Gaurav Goyal, Diana M Morlote, Karen L Rech, Aishwarya Ravindran","doi":"10.1097/PAS.0000000000002570","DOIUrl":"10.1097/PAS.0000000000002570","url":null,"abstract":"<p><p>Myeloid sarcoma (MS) is a tumor mass involving any extramedullary site composed of myeloid-lineage blasts with myeloid, myelomonocytic, or monocytic differentiation. Distinguishing MS from malignant histiocytic neoplasms (MHNs) is diagnostically challenging due to morphologic and immunophenotypic overlap, particularly for MS with monocytic differentiation, which can mimic MHNs, especially the subtypes of histiocytic sarcoma and interdigitating dendritic cell sarcoma, leading to potential misdiagnosis and inappropriate management. Cyclin D1 overexpression is implicated in MHNs, but its utility in differentiating these entities has not been systematically characterized. We evaluated cyclin D1 immunostaining in 43 MS cases and 30 MHNs. The median age at MS diagnosis was 59 years (range: 0.1 to 90), while the median age at MHN diagnosis was 62 years (range: 9 to 90), with heterogeneous sites of involvement. Cyclin D1 evaluation showed 100% MHNs with strong cyclin D1 positivity in ≥50% tumor cells, compared with 7% MS with weak-to-intermediate positivity in a minor subset of tumor cells. Additional immunohistochemical evaluation showed no difference in PU.1 expression in MHNs (93%) versus MS (84%) but demonstrated a higher proportion of OCT2-positivity in MHNs over MS (52% vs. 23%, P <0.05). Our study demonstrates a high sensitivity (100%) and specificity (93%) in utilizing cyclin D1 to distinguish MHNs (mature phenotype) from MS (immature phenotype) in diagnostic practice. It is particularly valuable in challenging scenarios of MS with the absence of immature/myeloid lineage-defining markers (MPO, CD34, or CD117) and provides a cost-effective tool to resolve this diagnostic pitfall, ensuring an accurate subclassification.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1067-1075"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248856","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":"Highly Vascularized Scars in Cases of Regressed Testicular Germ Cell Tumors: An Occasional Mimic of Hemangioma and a Diagnostic Pitfall.","authors":"Thomas M Ulbright, Ani Toklu, Andres M Acosta","doi":"10.1097/PAS.0000000000002569","DOIUrl":"10.1097/PAS.0000000000002569","url":null,"abstract":"<p><p>We identified 34 cases of regressed testicular germ cell tumors with highly vascularized scars; in 4 cases, the blood vessels were so prominent that hemangioma rather than germ cell tumor regression was considered, a misinterpretation that could result in clinical mismanagement since patients with regressed germ cell tumors require evaluation for metastases and, at a minimum, surveillance. The patients were 16 to 67 years old (median, 37) and usually presented with masses or metastases. Eleven of 12 cases of partial regression had a seminoma component, and seminoma was found in 5 of 7 different cases with sampled metastases. On microscopic examination, the cases usually showed numerous small blood vessels and a variably prominent lymphoplasmacytic infiltrate within scars, often with the greatest vessel concentration at the scar periphery. In 4 cases, a diffuse pattern of numerous, closely packed, small, round or slit-like vessels in fibrous stroma simulated hemangiomas, but with a lymphocyte-rich background. Quantification of the vessel concentration within the scar in the 30 cases where hemangioma was not mimicked showed an average increase in vessel density of 2.6 (range: 1.2 to 8.0) over non-neoplastic parenchyma. For the 4 \"hemangiomatoid\" cases, this ratio exceeded 6. The testis surrounding the scars showed, in all cases, the atrophic changes common to testes harboring germ cell neoplasia in situ-derived germ cell tumors. We conclude that highly vascularized testicular scars caused by regression of testicular germ cell tumors can occasionally show such a high concentration of blood vessels that they mimic hemangiomas. Seminoma is the most common germ cell tumor type to induce this florid reaction. Recognition of this phenomenon is important for proper clinical management.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1120-1128"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025640","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}