American Journal of Surgical Pathology最新文献

{"title":"CPZ: A Highly Sensitive Diagnostic Biomarker for the Differentiation Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma, Particularly in Poorly Differentiated Hepatocellular Carcinoma.","authors":"Minying Deng, Rongkui Luo, Lingli Chen, Huimei Wang, Wen Huang, Qi Song, Dongxian Jiang, Lei Xu, Jieakesu Su, Chen Xu, Yingyong Hou","doi":"10.1097/PAS.0000000000002393","DOIUrl":"10.1097/PAS.0000000000002393","url":null,"abstract":"<p><p>Carboxypeptidase Z (CPZ) is a newly identified member of the metallopeptidase family, primarily reported in rats; however, its distribution in normal human tissues and expression characteristics in tumor tissues remain unclear. This study uses high-throughput and mass production technology for tissue microarray (TMA) to perform immunohistochemical staining of CPZ, for the first time delineating its distribution and expression in normal tissues and various tumors throughout the body, to discuss its potential pathologic value. CPZ exhibited varying degrees of cytoplasmic positive expression in the normal hepatocytes, pancreatic islets, and gallbladder epithelium, with no expression observed in other normal tissues. The positive expression rates of CPZ in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic liver tumors, and normal liver tissue were 90.8% (109/120), 27.7% (13/47), 0% (0/22), and 100% (81/81), respectively. The sensitivity and specificity for diagnosing HCC with any of the 3 markers (CPZ, arginase-1 (Arg-1), and hepatocyte paraffin antigen-1 (Hep Par-1)) positive were 96.7% (116/120) and 65.2% (45/69), respectively. The sensitivity and specificity for diagnosing HCC with all 3 markers positive were 70.8% (85/120) and 100% (69/69), respectively. The sensitivity and specificity for diagnosing HCC with both CPZ and Arg-1 positive were 79.2% (95/120) and 95.7% (66/69), respectively. The sensitivity and specificity for diagnosing HCC with both CPZ and Hep Par-1 positive were 76.7% (92/120) and 97.1% (67/69), respectively. The sensitivity and specificity for diagnosing HCC with both Arg-1 and Hep Par-1 positive were 72.5% (87/120) and 98.6% (68/69), respectively. The ROC curve indicated that the combined detection of CPZ, Arg-1, and Hep Par-1 had the best diagnostic value for HCC (AUC=0.939, P <0.001). However, for individual detection, CPZ had the highest AUC value among the 3 markers (AUC=0.908, P <0.001). CPZ was not observed to be positive in the majority of 897 cases of solid tumors. Utilizing the TMA repository, we propose for the first time that CPZ may serve as a useful adjunctive tool for the diagnosis or differential diagnosis of HCC in routine surgical pathology practice. CPZ shows a trend of superiority over Arg-1 and Hep Par-1, particularly in poorly differentiated HCC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"711-729"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794400","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":"Molecular Analysis of Cutaneous Sarcomatoid Neoplasms Frequently Identifies Melanoma Driver Variants.","authors":"Louise A Jackett, Catherine Mitchell, Cameron Snell, Chelsee Hewitt, Shravan Yellenki, Hayden Snow, David Speakman, Chris Angel, Christine Khoo, Jia-Min Pang, Serigne N Lo, Richard A Scolyer, Stephen Fox, David Gyorki","doi":"10.1097/PAS.0000000000002390","DOIUrl":"10.1097/PAS.0000000000002390","url":null,"abstract":"<p><p>Primary cutaneous neoplasms that lack definitive histologic and immunophenotypic evidence of differentiation are a heterogeneous group of tumors with diverse prognoses and management options. These include undifferentiated and dedifferentiated melanoma (UM/DM), atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), and sarcomatoid squamous cell carcinoma. Diagnosis requires careful correlation between the clinicopathologic and molecular features, and the finding of a MAPK pathway variant commonly associated with melanoma may support the diagnosis of melanoma over other tumors in this group. To examine the frequency of typical melanoma-associated MAPK pathway-related variants ( BRAF, NRAS, KIT, GNAQ, GNA11 ) among a cohort of primary cutaneous sarcomatoid neoplasms, we conducted a retrospective analysis of 37 cases of immunohistologically unclassifiable primary cutaneous neoplasms, submitted for targeted NGS analysis. All cases lacked a history of a prior relevant tumor, were negative for melanocytic markers (S100, SOX10, HMB45, and Melan-A), or showed <5% staining with 1 or 2 of these markers. Other lineage markers were negative. We identified typical melanoma driver variants in 7 cases (7/37, 19%), including NRAS (5/37, 14%), KIT (1/37, 3%), and GNAQ (1/37, 3%). There were no significant differences in age, sex, tumor site, or mitotic rate between patients with and without a melanoma driver variant. Melanoma cases were thicker (16.3 vs. 9.25 mm, P =0.041) and more likely to show epithelioid cell phenotype ( P =0.008). In our cohort, nearly 20% of patients with immunohistologically unclassifiable cutaneous tumors could be reclassified as having primary UM/DM after molecular testing, thereby opening alternative management pathways.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"650-657"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778920","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":"Recurrent PDGFRB Mutations in Pulmonary Microcystic Fibromyxoma: A Clinicopathologic and Molecular Analysis of 3 Cases.","authors":"Ming Zhao, Qixing Gong, Xiaoyan Chen, Xiaona Yin, Rong Fang, Jiayun Xu, Xiao Cheng, Yingjing Wang","doi":"10.1097/PAS.0000000000002448","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002448","url":null,"abstract":"<p><p>Pulmonary microcystic fibromyxoma (PMF), a rare benign mesenchymal neoplasm first described in 2006, remains diagnostically challenging due to histologic overlap with a variety of primary/metastatic myxoid tumors of the lung and absence of lineage-specific markers. Its molecular pathogenesis has been undefined. In this study, we analyzed 3 PMF cases (2 males, 1 female; age 48 to 63 y) presenting as solitary peripheral lung nodules (1.5 to 3.5 cm), incidentally detected or associated with cough. Histologically, tumors showed microcystic architecture with bland stellate/spindled cells in fibromyxoid stroma, devoid of mitoses or necrosis. Immunohistochemistry uniformly excluded epithelial, myoepithelial, myogenic, neural, and vascular differentiation. Targeted DNA-sequencing identified recurrent PDGFRB mutations in all cases: 2 exon 12 in-frame deletions (P.W566_I569del, P.R565_I569del) and 1 exon 14 missense mutation (P.N666K), validated by Sanger sequencing. PDGFRB immunohistochemistry in one case revealed diffuse cytoplasmic/membranous reactivity, supporting constitutive signaling. Targeted RNA-based NGS revealed no evidence of pathogenic gene fusions. All patients remained recurrence-free after resection (mean follow-up: 81 mo). Our findings establish PDGFRB mutations as a molecular hallmark of PMF, further confirming the neoplastic nature of PMF and broadening the spectrum of PDGFRB-activating alterations in mesenchymal tumors. These mutations, clustering in regions critical for kinase autoinhibition, may serve as potential diagnostic tools to distinguish PMF from histologic mimics.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526077","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":"Comprehensive Analysis of 15 Cases of ELOC-RCC and Identification of Novel Mutation Site.","authors":"YuanKai Wu, HuiZhi Zhang, Yang Liu, XiangYun Li, ShiJie Deng, AnQi Li, ChaoFu Wang, Lei Dong, LuTing Zhou, HaiMin Xu, XiaoQun Yang","doi":"10.1097/PAS.0000000000002443","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002443","url":null,"abstract":"<p><p>ELOC-mutated renal cell carcinoma (ELOC-RCC), a newly recognized tumor entity in the fifth edition of the WHO Classification of Tumors of Urinary and Male Genital Organ Tumors (5th WHO Classification), presents morphologic and immunohistochemical (IHC) features overlapping those of clear cell RCC (ccRCC), RCC with fibromyomatous stroma (RCC-FMS), and clear cell papillary renal cell tumor (ccPRCT). Confirmation of an ELOC mutation is required for a definitive diagnosis. This study aims to enhance the understanding of ELOC-RCC's morphologic and molecular characteristics and to develop an affordable and practical panel for its preliminary differentiation based on morphologic and IHC features. Representing one of the largest cohorts of ELOC-RCC, this research involved a retrospective analysis of 56 suspected cases at Shanghai Ruijin Hospital from January 2022 to March 2024, identifying 15 cases through next-generation sequencing (NGS). We report an ELOC mutation site (c.274G>A, p.Glu92Lys), which has not been previously reported in the literature. NGS analysis also showed recurrent mutations in MAP2K4 and HRAS in ELOC-RCC, though their implications are not yet clear. In addition, we describe a case of ELOC-RCC with a PARP4 mutation. Our findings indicate that the \"basally polarized\" nuclear arrangement and the \"apical/apicolateral polarized\" staining patterns of CD10 and EMA offer valuable diagnostic clues for differentiating ELOC-RCC from low-grade ccRCC. Furthermore, the immunophenotypic profile of CD10+/AMACR+/GPNMB- appears helpful for differentiating ELOC-RCC from both ccPRCT and mTOR pathway-mutated RCC-FMS (mTOR-RCC-FMS). However, genetic testing remains indispensable, as evidenced by one CK7-negative ELOC-RCC case.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482889","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":"Renal Tumorigenesis via RAS/RAF/MAPK Pathway Alterations Beyond Papillary Renal Neoplasm With Reverse Polarity.","authors":"Jung Woo Kwon, Peng Wang, Pankhuri Wanjari, Dane Wuori, James Paik, Peter Pytel, Carrie Fitzpatrick, Melissa Y Tjota, Tatjana Antic","doi":"10.1097/PAS.0000000000002442","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002442","url":null,"abstract":"<p><p>RAS/RAF/MAPK signaling pathway is one of the best-defined cancer signaling pathways but its role in renal tumorigenesis is unknown outside of papillary renal neoplasm with reverse polarity (PRNRP), which harbors recurrent KRAS alteration. In 383 renal tumors with NGS performed at the University of Chicago and 406 tumors from the available TCGA PRCC/chromophobe RCC data sets, 6 and 9 renal tumors with RAS/RAF/MAPK pathway alteration were identified, respectively. KRAS was the most common gene to be altered (11/15) but alterations in BRAF (2/15), RAF1 (1/15), and NRAS (1/15) were also present. On the basis of morphology, the tumors were separated into 3 groups: classic PRNRPs (group 1), predominantly tubulocystic (group 2), and papillary with high-grade features (group 3). Although morphologically different, groups 1 and 2 shared many similarities in having (1) low-grade appearing eosinophilic tumor cells, (2) identical IHC profile (GATA3+/CK7+/CD117-/Vimentin-), (3) isolated KRAS alteration with no copy number variations, and (4) no proven metastatic potential. Group 3 showed predominantly papillary architecture composed of tumor cells with clear-to-eosinophilic cytoplasm and high-grade cytologic features. Unlike Group 1/2, 57% (4/7) of group 3 tumors showed additional gene alterations on top of RAS/RAF/MAPK pathway alteration and all group 3 tumors (7/7) showed significant copy number variations. On follow-up, 2 of the 7 (2/7) group 3 tumors have metastasized. One tumor with NRAS alteration showed unique morphology unlike any other tumors, composed of mixed tubulocystic and solid architecture with eosinophilic tumor cells. This tumor also showed significant copy number variations. The tumor was staged as pT4N1, displaying metastatic potential. This study shows that renal tumors with RAS/RAF/MAPK pathway alteration are heterogeneous morphologically, immunohistochemically, and molecularly. Although rare, recognition of this novel mechanism in renal tumorigenesis may be clinically important, as there are FDA-approved therapies that can target the RAS/RAF/MAPK pathway hyperactivation.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482890","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":"International Society of Urological Pathology Consensus on Cancer Precursor Lesions. Working Group 1: The Prostate.","authors":"Kenneth A Iczkowski, Angelo M De Marzo, Neeraj Agarwal, David M Berman, Alessia Cimadamore, Samson W Fine, Nancy Greenland, Francesca Khani, Massimo Loda, Tamara L Lotan, Murali Varma, Arul Chinnaiyan, Gianluca Giannarini, Jiaoti Huang, Rodolfo Montironi, George J Netto, Adeboye O Osunkoya, Timothy Ratliff, Glen Kristiansen, Liang Cheng, Geert J L H van Leenders","doi":"10.1097/PAS.0000000000002430","DOIUrl":"10.1097/PAS.0000000000002430","url":null,"abstract":"<p><p>Working Group 1 at ISUP's Cancer Precursors meeting (September 2024) evaluated 5 putative precursors of invasive prostate cancer: high-grade prostatic intraepithelial neoplasia (HGPIN), intraductal carcinoma (IDC), atypical intraductal proliferation (AIP), atypical adenomatous hyperplasia (AAH)/adenosis, and proliferative inflammatory atrophy (PIA). Objectives were to compile recent evidence, interrogate current practices, and vote on recommendations, with 67% approval defined as consensus. Consensus was reached against the reporting of the low-grade form of PIN. HGPIN need not be reported when concomitant cancer or atypical small acinar proliferation suspicious for cancer exists adjacent to it, for biopsy or prostatectomy specimens. Finally, while the clinical significance of unifocal HGPIN in biopsies remains uncertain, there is stronger evidence for multifocal isolated HGPIN as a predictor of subsequent cancer detection. By consensus, multifocal HGPIN should continue being reported. Slight refinement was achieved regarding IDC criteria. The consensus opinion was that a dense cribriform to solid proliferation need not demonstrate marked nuclear atypia/ pleomorphism to qualify as IDC. The inverse scenario of marked atypia without dense cribriform/solid proliferation fell just short (65%) of consensus for IDC. Redesignating cribriform HGPIN as AIP achieved consensus. AIP found alone or with grade group 1 cancer warrants an explanatory comment. However, agreement was not attained to report AIP in the presence of invasive cancer, in either needle biopsy or prostatectomy. Finally, the optional reporting of PIA or AAH/adenosis in biopsies as pertinent negatives both fell short of consensus. This guidance should help pathologists standardize reporting, staying focused on the clinically actionable aspects of these lesions.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367797","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":"MUC4-positive Fibroblastoma: A Distinctive Hyalinized Spindle Cell Neoplasm With Aberrant Nuclear Beta-catenin Expression and Frequent Biallelic Inactivation of APC.","authors":"Federico Repetto, Igor Odintsov, Lynette M Sholl, Jason L Hornick, William J Anderson","doi":"10.1097/PAS.0000000000002441","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002441","url":null,"abstract":"<p><p>Among soft tissue tumors, MUC4 is expressed in low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma, and is regarded as a specific and sensitive marker for these malignant entities. These tumors are driven by oncogenic fusions involving FUS or EWSR1 as a 5' partner and CREB3L1 or CREB3L2 as a 3' partner. In this study, we describe the clinicopathologic and molecular features of a distinctive fibroblastic soft tissue neoplasm characterized by consistent co-expression of MUC4 and beta-catenin, and frequent underlying APC inactivation without evidence of EWSR1 or FUS rearrangements. Fifteen hyalinized spindle cell neoplasms with MUC4 and aberrant nuclear beta-catenin co-expression were identified from our institutional archives. The cohort comprised 15 adult patients (6 female, 9 male) with a median age of 40 years (range: 20 to 61). Tumors arose in the extremities (n=9), trunk (n=5), and retroperitoneum (n=1), with a median size of 8.5 cm (range: 2.8 to 18.0 cm). The tumors consisted of a hypocellular proliferation of spindled-to-stellate fibroblastic cells in a variably hyalinized collagenous stroma. No atypia, fascicular growth, or myxoid stroma was present. Targeted DNA sequencing was successfully performed on 8 tumors. In addition, 8 tumors underwent FISH testing to assess for FUS and/or EWSR1 rearrangement. In the majority of tumors, DNA sequencing demonstrated APC inactivation (7/8; 88%). In 6 of these cases, 2 concurrent deleterious APC alterations were present, indicative of biallelic inactivation. No rearrangements involving FUS or EWSR1 were identified by NGS and/or FISH. Clinical follow-up data were available for 4 patients, with no local recurrences or metastases reported, including 1 patient followed for 8 years. No patients had a known history of familial adenomatous polyposis. We describe a novel fibroblastic soft tissue neoplasm characterized by co-expression of MUC4 and beta-catenin and frequent underlying APC inactivation, for which we propose the name \"MUC4-positive fibroblastoma.\"</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473812","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":"Serous Borderline Tumors of the Testis and Paratestis: A Clinicopathologic Study of 19 Tumors Emphasizing Morphologic Spectrum and Clinical Outcome.","authors":"Ali Shahabi, Aleksei Konstantinov, Jesse K McKenney, Jason Lane, Chia-Sui Kao, Sean R Williamson, Reza Alaghehbandan, Liang Cheng, Ankur R Sangoi, Emily Chan, Kristine M Cornejo, Christopher G Przybycin","doi":"10.1097/PAS.0000000000002439","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002439","url":null,"abstract":"<p><p>Serous borderline tumors of the testis and paratestis are rare, and experience with these neoplasms is limited. We report a series of 19 tumors, emphasizing their morphologic spectrum and clinical behavior. Eighteen tumors (95%) had conventional serous borderline tumor morphology identical to ovarian serous borderline tumors, and 1 case (5%) had a pattern resembling the epithelial subtype of noninvasive implants of serous borderline tumor. A component of micropapillary serous borderline tumor was present in 6 tumors (31%), including 1 that was exclusively micropapillary. Five tumors (26%) had associated autoimplants. Microinvasion was identified in 4 tumors (21%). One tumor had associated low-grade serous carcinoma, and 1 tumor had associated high-grade serous carcinoma. Immunohistochemical stains demonstrated diffuse expression of PAX8 in 12 of 12 (100%) cases. Estrogen receptor was diffusely positive in 11 of 12 (92%) cases and progesterone receptor was positive in 8 of 9 (89%) cases. D2-40 was negative in 7 of 9 (78%) cases and calretinin was negative in 11 of 11 cases (100%). Clinical follow-up data were available in 9 patients (47%) with pure serous borderline tumors, of which 4 had micropapillary features (44%), 3 had microinvasion (33%), and 2 had autoimplants (22%). None of these 9 patients experienced adverse outcomes related to serous borderline tumor over the follow-up period (mean: 94 mo, median: 85 mo, range: 17 to 204 mo). Serous borderline tumors of the testis and paratestis are identical morphologically to their ovarian counterparts and can be associated with similar histologic phenomena (microinvasion, autoimplants, and micropapillary features). Although they can develop associated serous carcinoma, we conclude that serous borderline tumors of the testis and paratestis (when pure) appear to show indolent behavior.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282006","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":"IgM Immunohistochemical Expression is a Potential Risk Factor for Extracutaneous Dissemination in Patients With Primary Cutaneous Follicle Center Lymphoma.","authors":"Anne M R Schrader, Ruben A L de Groen, Rein Willemze, Patty M Jansen, Koen D Quint, Tom van Wezel, Ronald van Eijk, Dina Ruano, Cornelis P Tensen, Arjan Diepstra, Anke van den Berg, Lianne Koens, Naomi Kakiailatu, Maarten H Vermeer, Joost S P Vermaat","doi":"10.1097/PAS.0000000000002436","DOIUrl":"10.1097/PAS.0000000000002436","url":null,"abstract":"<p><p>Primary cutaneous follicle center lymphoma (PCFCL) is a type of cutaneous B-cell lymphoma with an indolent behavior and a 5-year disease-specific survival of 95%. Given the difficulty of identifying patients at risk for developing extracutaneous dissemination (ECD), this study aimed to identify predictors in the clinical presentation, histopathology, immune phenotype, and genetic profile of PCFCL patients by comparing those who developed ECD with those whose disease remained skin limited (SL) during follow-up. After review of clinical data and histopathology, a total of 13 ECD-PCFCL patients and 15 SL-PCFCL patients with varying treatments were included from the Dutch Cutaneous Lymphomas Registry. At diagnosis, all patients presented with classic PCFCL lesions on the trunk or head-and-neck region, and histology indicated a predominance of centrocytes admixed with centroblasts. IgM expression was significantly more frequent in ECD-PCFCL (54%) than in SL-PCFCL (7%; P =0.006). Targeted next-generation sequencing (NGS) with a 200 B-cell lymphoma-related gene panel demonstrated known PCFCL-like mutations in both groups. In addition, ECD-PCFCL demonstrated an enrichment of mutations associated with the activated B-cell genotype, including MYD88 (n=2), and some unique mutations, such as in ERBB4 (n=4). In conclusion, this study identified IgM expression at diagnosis as a potential biomarker for extracutaneous spread in PCFCL. In IgM-positive cases, genetic testing may be warranted. Patients with uncommon mutational profiles, such as those resembling the ABC-DLBCL genotype, may particularly benefit from closer follow-up and consideration of more aggressive treatment, including immuno-polychemotherapy. As these observations were made in a limited number of patients, our results require validation in an independent cohort.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"931-941"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282004","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":"Genomic Signatures of Gastric Adenocarcinoma By Tumor Location-Modified Laurén Classification: Highlighting the Molecular Heterogeneity of Mixed-Type Tumors.","authors":"Harrison M Drebin, Henry Walch, Edaise M Da Silva, Shoji Shimada, Walid Chatila, Miseker Abate, Santosha Vardhana, Michael Berger, Murray F Brennan, Daniel Coit, Vivian E Strong, Laura H Tang","doi":"10.1097/PAS.0000000000002432","DOIUrl":"10.1097/PAS.0000000000002432","url":null,"abstract":"<p><p>Tumor location-modified Laurén classification (mLC) of gastric adenocarcinoma (GAC) integrates Laurén histologic subtype and tumor location. mLC has been previously proposed and clinically validated as an independent prognostic indicator. However, the genomic signatures of GAC within the mLC system are unknown, particularly among mixed tumors. This study aimed to characterize the genomic signatures of GAC using the mLC system and to elucidate the genomic patterns of morphologically distinct components of mixed tumors. Treatment-naive GAC tumors were classified according to the mLC into 4 subgroups: proximal-intestinal, distal-intestinal, diffuse, and mixed types. The latter included 2 components: mixed-intestinal and mixed-signet ring. Sections of formalin-fixed, paraffin-embedded tissues were subjected to next-generation targeted sequencing. Tumors from 103 patients were included. The proximal-intestinal (n=28), distal-intestinal (n=34), and diffuse (n=25) subgroups exhibited distinct genomic alteration patterns. Among microsatellite stable cases, the proximal-intestinal subgroup was enriched for alterations in TP53 , ERBB2, CDKN2A , and SMAD4 , whereas the diffuse subgroup had significantly more alterations in CDH1 and ARID1A . The distal-intestinal subgroup had significantly more TP53 alterations than the diffuse subgroup. At the pathway level, both the proximal-intestinal and distal-intestinal subgroups had significantly higher TP53 pathway alterations than the diffuse subgroup. The proximal-intestinal subgroup had a significantly higher percentage of cell cycle, PI3K, and TGF-ß alterations than the diffuse subgroup. Both the mixed-intestinal and mixed-signet ring components of mixed tumors (n=16) exhibited alteration patterns that partially resembled those of the distal-intestinal and diffuse subgroups. The matched components of mixed tumors shared some, but not all, alterations. Overall, this study demonstrated distinct genomic patterns among the proximal-intestinal, distal-intestinal, and diffuse subgroups in the mLC system. The gene alteration patterns in the mixed-intestinal and mixed-signet ring components of mixed tumors exhibited partial similarities with both the distal-intestinal and diffuse subgroups. Furthermore, this study emphasizes how employing a multisampling approach can uncover the molecular heterogeneity of histologically distinct components of mixed-type tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"948-955"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289381","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}