American Journal of Surgical Pathology最新文献

{"title":"Breast Carcinomas Resembling Acinic Cell Carcinoma: Comprehensive Analysis of 14 Cases and Review of the Literature.","authors":"Fengxia Qin, Jiazhen Li, Yi Zheng, Chengying Jiang, Yumian Jia, Hui Sun, Huiqin Xue, Xiaozi Wang, Lu Wang, Xiaolong Qian, Yun Niu, Hannah Y Wen, Xiaojing Guo","doi":"10.1097/PAS.0000000000002363","DOIUrl":"10.1097/PAS.0000000000002363","url":null,"abstract":"<p><p>Acinic cell carcinoma (AciCC) of the breast is an exceptionally rare subtype of invasive breast carcinoma, often exhibiting a triple-negative phenotype and relatively indolent behavior. Since the first case reported by Roncaroli and colleagues in 1996, no more than 60 additional cases have been described in English medical journals, usually as case reports or small case series. In this study, we presented an in-depth analysis of 14 cases of AciCC of the breast, including 4 pure AciCCs and 10 AciCCs mixed with other histologic types. We reported the clinicopathologic characteristics, histologic components, treatment modalities including response to neoadjuvant treatment in 3 patients, and outcomes. In addition, we assessed the expression of nuclear transcription factor nuclear receptor subfamily 4 group A member 3 by immunohistochemistry and gene rearrangements by fluorescence in situ hybridization, which has been implicated in AciCC of the salivary gland. All 14 cases were negative for nuclear receptor subfamily 4 group A member 3 expression, and no gene rearrangements were detected. We also conducted a thorough review of the literature to highlight advancements in understanding this rare breast cancer subtype. This study aims to enhance clinical knowledge of AciCC of the breast and contributed to growing evidence that AciCC of the breast and AciCC of the salivary glands appear to be unrelated entities, despite sharing a similar histologic appearance.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"448-457"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397919","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":"High-accuracy Detection of PD-L1 3'-UTR Disruption by Immunohistochemistry and Fluorescence in Situ Hybridization on Formalin-fixed Paraffin-embedded Sections.","authors":"Ayumi Fujimoto, Seiji Sakata, Keisuke Kataoka, Yasunori Kogure, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Satoko Baba, Dai Maruyama, Seishi Ogawa, Kengo Takeuchi","doi":"10.1097/PAS.0000000000002372","DOIUrl":"10.1097/PAS.0000000000002372","url":null,"abstract":"<p><p>Programmed death-ligand 1 (PD-L1/CD274) structural variation (SV) disrupting the 3'-untranslated region has been highlighted as being associated with PD-L1 overexpression. In the present study, we evaluated lymphoma tissue samples to investigate the applicability of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for detecting the PD-L1 SV involving the 3'-untranslated region. In total, 1052 lymphoma samples were screened using IHC, and 99 IHC screening-positive samples were evaluated with FISH (non-Hodgkin lymphoma [NHL, n=58] and Hodgkin lymphoma [HL, n=41]). Of these, 92 samples showed strong PD-L1 expression with 2 PD-L1 antibodies (E1J2J and SP142) (concordant PD-L1 IHC), whereas 7 samples showed strong PD-L1 expression only with E1J2J (discordant PD-L1 IHC). Abnormal FISH findings for PD-L1 were detected in all evaluated samples (51 NHLs and 41 HLs). A structural abnormality pattern was observed in 17 of the 51 evaluated NHL samples (33%). In contrast, all 41 HL samples showed a copy number abnormality pattern, with 1 exhibiting a structural abnormality pattern. Target-capture sequencing of the PD-L1 gene was performed on 73 of the 99 IHC screening-positive samples, comprising 41 NHLs and 32 HLs. PD-L1 SVs were detected in 16 (39%) of the 41 NHL samples and in only one of the 32 HL samples (3%). Samples exhibiting discordant PD-L1 IHC and/or FISH structural abnormality patterns were shown to harbor PD-L1 SV by target-capture sequencing, with positive and negative predictive values of 94% and 96%, respectively. Our approach is an alternative to target-capture sequencing for evaluating PD-L1 gene abnormalities.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"490-498"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536607","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 and Genomic Analysis of Uterine Serous Carcinomas Arising From Endometrial Hyperplasia.","authors":"Tiffany Y Sia, Douglas H R Allison, Arnaud Da Cruz Paula, Edaise M da Silva, Qiqi Ye, Pier Selenica, Fresia Pareja, Hunter Green, Nadeem R Abu-Rustum, Britta Weigelt, Lora H Ellenson","doi":"10.1097/PAS.0000000000002401","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002401","url":null,"abstract":"<p><p>Uterine serous carcinoma (USC) typically arises from atrophic endometrium but may be associated with hyperplasia in 5% to 10% of cases. We sought to identify USC with concurrent hyperplasia and (i) define if these are clonally related, and (ii) determine if USC associated with hyperplasia is genetically distinct from USC without hyperplasia. Patients diagnosed with USC and hyperplasia from their hysterectomy specimen between January 1, 2014 and February 29, 2022 were identified. Hyperplasia and carcinoma were separately subjected to tumor-normal panel sequencing. Their repertoire of genetic alterations was compared with that of a separate cohort of atrophy-associated USCs. Of 267 USCs with clinical sequencing and slides available for review, 8 with concurrent carcinoma and hyperplasia had sufficient tissue for molecular studies. In 7 (87.5%) of these 8 cases, USC and hyperplasia were clonally related and shared multiple mutations, including TP53 in 4 cases (57%). In 1 case (USC4), USC and hyperplasia were unrelated at the genetic level, and the hyperplasia was TP53 wild-type. In another case (USC5), USC and TP53 wild-type hyperplasia shared 1 of 11 mutations while being distinct at the copy number level. The prevalence of ARID1A mutations was higher in hyperplasia-associated USC compared with atrophy-associated USC (43% vs. 0%, respectively; P=0.02). USC and co-occurring hyperplasia were clonally related in most cases, commonly harboring TP53 hotspot mutations in both components. These results suggest an alternative origin of tumorigenesis in this rare subset of endometrial cancers.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958425","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 Extensive Case Series of 21 CIC::DUX4, 18 BCOR::CCNB3 and 148 Ewing's Sarcomas From a Single Center.","authors":"Sirma Çetin, Gökçen Ünverengil, İsmail Yilmaz, Melin Aydan Ahmed, Miray Ülkü Yildirim, Eriş Özkan, Harzem Özger, Bilge Bilgiç","doi":"10.1097/PAS.0000000000002403","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002403","url":null,"abstract":"<p><p>In this study, we aimed to reclassify \"round cell sarcomas\" identified in the Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, between 2013 and 2023, using an immunohistochemical panel including CD99, NKX2.2, ETV4, WT1, DUX4, BCOR, CCNB3, and SS18-SSX antibodies, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). A total of 148 Ewing's sarcomas, 21 CIC::DUX4 sarcomas, and 18 BCOR::CCNB3 sarcomas were diagnosed. Histopathologic features such as pleomorphism, prominent nucleoli, wide clear/eosinophilic cytoplasm, myxoid/pink hyaline stroma, and spindle cell components were useful for differentiating the other two sarcomas from Ewing sarcoma. The intensity of CD99 antibody staining in CIC::DUX4 and BCOR::CCNB3 sarcomas varied. The NKX2.2 antibody was diffuse nuclear positive in 93% of Ewing sarcomas and negative in CIC::DUX4 and BCOR::CCNB3 sarcomas. The DUX4 antibody was diffuse nuclear positive in all CIC:DUX4 sarcomas. Survival in CIC::DUX4 sarcomas tended to be lower than in the other groups, although there was no statistically significant difference between the groups. The histopathologic regression response, indicating the histopathologic response to neoadjuvant therapy according to the Ewing sarcoma regimen, was similar among all three groups. For BCOR::CCNB3 sarcomas, the histopathologic regression response in patients treated with the Ewing regimen was as low as 30%, whereas those treated with non-Ewing regimens showed a higher histopathologic regression response of 70%. A tumor size of 5 cm and above was found to be a statistically significant negative factor for survival. Age, sex, and tumor location were not significant factors for survival.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952694","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 Epithelioid Angiomyolipoma: Prognostic Implications of Targeted Immunohistochemical and Molecular Markers in Conjunction with Clinicopathologic Features.","authors":"Ankur R Sangoi, Anandi Lobo, Shilpy Jha, Seema Kaushal, Ankit Tiwari, Aysha Mubeen, Robert Humble, Susan K Potterveld, Sean R Williamson, Mahmut Akgul, Sandy Srinivas, Sambit K Mohanty","doi":"10.1097/PAS.0000000000002411","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002411","url":null,"abstract":"<p><p>Epithelioid angiomyolipoma (eAML) is an uncommon subtype of angiomyolipoma, a subset of which can demonstrate malignant behavior. While some studies have proposed histopathologic features predictive of aggressive behavior in eAML, there is limited data on the use of immunohistochemistry (IHC) and/or next-generation sequencing (NGS) to identify biomarkers for poor clinical outcome. Moreover, there is limited data on the proposed genetic dichotomy (tuberous sclerosis complex [TSC] alteration versus TFE3 rearrangement) of eAML. Clinicopathologic features (including purported histologic features associated with adverse outcome) of 30 eAML were recorded with IHC performed on 1 whole-slide section per tumor for the following markers (interpretations): p16 (positive or negative), p53 (wild type or mutant), TRIM63 ISH (>10% as positive or ≤10% as negative), ATRX (retained or lost), and RB1 (retained or lost). NGS was performed on 23 tumors. The 30 eAML tumors were from 30 patients (23 female, 7 male) of an age range 22 to 77 years (mean=51.9 y). Clinical follow-up was available from 27 patients (mean=36 mo). The features significantly associated with metastatic disease included ≥70% atypical epithelial cells (P=0.04), ≥2 mitotic figures per 10 high-power fields (P=0.0013), atypical mitotic figures (P=0.0003), and necrosis (P=0.0213). Other features such as local invasion, vascular invasion, tumor size, and immunohistochemical profile (p16, TRIM63, p53, ATRX, and RB1) showed no significant association with the development of metastasis. Interestingly, among the 7 tumors with clinical follow-up showing TFE3 rearrangement, 5 developed metastases (OR=4.50), while 6 of 14 TSC/MTOR mutated tumors with clinical follow-up had metastatic disease (OR=0.222). Notably, TRIM63 ISH showed high sensitivity (100%) for eAML with TFE3 rearrangement but with poor specificity (38%). The genetic dichotomy of eAML comes in the form of TSC/MTOR alterations or TFE3 rearrangement elucidated by NGS, both of which may be associated with poor outcome, and therefore show potential therapeutic implications. As eAML may show overlap with TFE3-rearranged/TFEB-altered renal cell carcinoma, shared TRIM63 ISH positivity for these tumor types represents an important potential diagnostic pitfall.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952217","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":"A Clinical, Morphologic, and Molecular Comparison of Bonafide Spitz Melanomas and ASTs in the Pediatric Population.","authors":"Haya Mary Beydoun, Julia Edwin Jeyakumar, Afua Addo, Shantel Olivares, Lili Zhao, Yangruijue Ma, Jennifer Ko, Armita Bahrami, Scott Florell, Larissa V Furtado, Klaus Busam, Pedram Gerami","doi":"10.1097/PAS.0000000000002381","DOIUrl":"10.1097/PAS.0000000000002381","url":null,"abstract":"<p><p>Pediatric Spitz melanoma (SM) with bonafide metastatic disease is rare. In this study, we assembled the largest cohort to date of pediatric SM with a verified Spitz-associated genomic driver and clinical follow-up demonstrating bonafide metastasis. We compared the clinical, morphologic, and molecular features of these SMs to a control cohort of 57 pediatric atypical Spitz tumors (ASTs). Pediatric SM patients were significantly older than AST patients (12 vs 8 years of age). While not statistically significant, SMs were more likely to be heavily pigmented (5/7 SMs vs 11/57 ASTs), to have a sheet-like growth pattern (3/7 SMs vs 8/57 ASTs), and have severe nuclear atypia (6/7 SMs vs 20/57 ASTs). SMs had significantly greater mitotic activity (avg of 4.3/mm 2 in SMs and 2.7/mm 2 in ASTs, P =0.008) and more frequent larger cell size ( P =0.006). However, none of these features were specific and could also be seen in ASTs. The presence of homozygous deletions of 9p21 in conjunction with TERT promoter hot spot mutations or PTEN deletions (n=2), as well as MYC overexpression or amplification (n=2) were only seen in the SMs and none of the ASTs. These findings were mutually exclusive in the SM group and mutually exclusive with the presence of complex chromosomal copy number aberrations, which were seen in the remaining 3 pediatric SMs. This study demonstrates that there are multiple pathways to malignancy for pediatric SMs and none of our commonly used biomarkers have a particularly high sensitivity. Hence, the optimal distinction of pediatric SM from ASTs will continue to require the integration of clinical, histologic, and molecular data.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603595","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":"NTRK1 Gene Fusions Are Frequent in Juvenile Xanthogranuloma.","authors":"Elisabeth Schlögl, Helga Hürner-Unterberger, Ingrid Simonitsch-Klupp, Gabriele Amann, Jaqueline Blank-Foltin, Barbara Neudert, Lisa Wozelka-Oltjan, Christine Haberler, Georg Ebetsberger-Dachs, Leonhard Müllauer","doi":"10.1097/PAS.0000000000002405","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002405","url":null,"abstract":"<p><p>Juvenile Xanthogranuloma (JXG) is a rare form of non-Langerhans cell histiocytosis. The most common known gene mutations affect the mitogen-activated protein (MAP) kinase, phosphoinositide 3-kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. We present a case of congenital JXG in a premature newborn from a dicygotic twin pregnancy with subdermal infiltrates on the chest, hepatosplenomegaly, ascites, pancytopenia, and petechiae on the abdomen and extremities. Next-generation sequencing of tissue from a subdermal infiltrate revealed a tropomyosin 3::neurotrophic tyrosine kinase receptor (TPM3::NTRK1) gene fusion. Therefore, a retrospective analysis of 34 additional non-Langerhans cell histiocytoses (16 JXG, 3 adult xanthogranuloma and 1 benign cephalic histiocytosis, both clinical subtypes of JXG, as well as 13 Rosai-Dorfman and 1 Erdheim-Chester disease) for NTRK1, 2 and 3 aberrations was performed. This analysis revealed an NTRK1 gene fusion in 4 additional JXGs and 1 adult xanthogranuloma. In conclusion, NTRK1 gene fusions are moderately common in JXG (6/21; 28.6% in our series). This finding places JXG in the category of proliferative diseases with one of the highest frequencies of NTRK gene rearrangements. Therefore, NTRK gene fusions should be included in a gene panel test for difficult-to-treat JXG. Given the potential of NTRK gene fusions as a therapeutic target, NTRK inhibitors may represent a novel effective treatment for JXG with a challenging clinical course.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965696","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":"Utility of Protein Kinase C Beta II Immunohistochemistry in Differential Diagnosis of Ewing Sarcoma.","authors":"Jerzy Lasota, Martyna Krupińska, Maciej Kaczorowski, Małgorzata Chłopek, Zdenek Kinkor, Marian Švajdler, Raul Perret, Gregory W Charville, Martina Bradová, Kris Ylaya, Małgorzata Wesołowska, Magdalena Rozmus-Piętoń, Janusz Ryś, Michael Michal, Michal Michal, Markku Miettinen","doi":"10.1097/PAS.0000000000002400","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002400","url":null,"abstract":"<p><p>The diagnosis of Ewing sarcoma can be challenging, particularly when the tumor is present in an atypical location and resembles histologic mimics. The hallmark feature of Ewing sarcoma is chromosomal translocation, t(11;22)(q24;q12), involving EWSR1 and ETS gene family members. For decades, fluorescence in situ hybridization with a break-apart EWSR1 probe has been the diagnostic gold standard. However, EWSR1 rearrangements have been identified in other malignancies; thus, the detection of chimeric EWSR1 transcripts has become a preferable approach. Occasionally, insufficient tissue, severe RNA degradation, or economic constraints hamper molecular testing. This study evaluated Protein Kinase C Beta II (PKC β II) expression in >1000 tumors and assessed the utility of PKC β II immunohistochemistry in the differential diagnosis of Ewing sarcoma. Tumors harboring EWSR1::FLI1 (n=26), EWSR1::ERG, EWSR1::ETV4 (n=1), and FUS::ERG (n=6) fusions were evaluated, revealing strong diffuse immunoreactivity, although a patchy pattern was seen in 3 cases. Undifferentiated round cell sarcomas (n=46), including BCOR-, CIC-, NFATC2-, NUTM1-, and PATZ1 rearranged/fusion-sarcomas were negative. Two of the 130 synovial sarcomas, including 1 with a poorly differentiated morphology, showed diffuse, moderate-to-strong positivity. One of the 26 poorly differentiated carcinomas from the head and neck region, probably small cell lung carcinoma metastasis, showed strong PKC β II expression. Neuroblastomas (>50%) expressed PKC β II, although none showed a strong diffuse pattern. Diffuse moderate-to-strong immunoreactivity was observed in 2 sarcomatoid mesotheliomas and 2 metastatic melanomas. Diffuse but weak staining was observed in 73% (11/15) of the T-cell lymphoblastic lymphomas, including 10 CD99-positive cases. Similarly, weak predominantly patchy staining was seen in half (40/80) of other non-Hodgkin lymphomas and sporadically in embryonal rhabdomyosarcoma, Merkel cell carcinoma, small cell lung carcinoma, and Wilms tumor. Thus, diffuse and strong PKC β II immunoreactivity appears to be a reliable diagnostic marker for distinguishing classic Ewing sarcoma from histologic mimics.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965758","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":"Combined Gout and Pseudogout Demonstrate Unique Clinicopathologic Features Compared to Those With Only Gout.","authors":"Sandra Gjorgova Gjeorgjievski, Josephine K Dermawan, John D Reith, Scott E Kilpatrick","doi":"10.1097/PAS.0000000000002406","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002406","url":null,"abstract":"<p><p>Although monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystals have been documented together in synovial fluid, there are no descriptions regarding their simultaneous histologic presence within the same tophi. Furthermore, the incidence, significance, and clinicopathologic features of such patients have not been analyzed. We retrospectively reviewed consecutive cases of pathologic specimens over an ~4-year period with a confirmed histologic diagnosis of \"gout\" or \"gouty tophi\", focusing on concomitantly documented CPPD. A total of 159 gout cases involved 156 patients, including 127 males and 29 females (ratio 4.4:1), with ages ranging from 14 to 99 years (median 67). Nine (5.7%) patients (6 males; 3 females; ratio 2:1; age range 49 to 91 years, median 74) had evidence of both gout and CPPD crystals within the same tophaceous deposits. Concomitant gout/CPPD were more commonly associated with the upper extremities (5 [3, hands; 2, elbows]) than lower extremities (4, feet). Seven patients had a prior history of gout and 1 CPPD. The 150 cases from 147 patients of gout alone occurred in 121 males and 26 females (ratio 4.7:1), with ages ranging from 14 to 99 years (median 67). Gout alone was far more common in the lower extremities (109 cases) than the upper extremities (41). For combined gout/pseudogout, deposits of CPPD were intimately associated with the gouty tophi, deposited in irregular, curvilinear to serpiginous aggregates onto a significantly higher volume of uric acid crystals but never observed away from the tophaceous deposits. Confirmation of the uric acid crystals required polarization of unstained sections. In conclusion, the presence of concomitant CPPD and gouty crystals in the same tophaceous deposits is infrequently observed in pathology specimens. Compared with gout only, preliminary data suggests that patients with combined gout/pseudogout tophi are more likely to be older, female, and exhibit upper extremity involvement. Most such patients also have a prior history of gout.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971341","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":"HER2 mRNA Score From Quantitative ERBB2 mRNA Expression of Oncotype Dx : Can It Replace the HER2 Immunohistochemistry?","authors":"Hyunwoo Lee, Jai Min Ryu, Se Kyung Lee, Byung Joo Chae, Jonghan Yu, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Yoon Ah Cho, Eun Yoon Cho","doi":"10.1097/PAS.0000000000002396","DOIUrl":"10.1097/PAS.0000000000002396","url":null,"abstract":"<p><p>As novel human epidermal growth factor receptor-2 (HER2) and drug conjugates have proven to be effective treatments for both HER2-positive breast cancer (BC) and HER2-low BC, the need to develop more accurate methods to quantify HER2 status has increased. We compared the correlation between the HER2 mRNA score (HS), obtained using the Oncotype DX (ODX) test, and HER2 immunohistochemistry (IHC) to verify the accuracy of HER2 quantification and its correlation with clinicopathologic characteristics. We retrospectively collected ODX test data from 1524 estrogen-receptor positive, HER2-negative patients with BC. No significant differences in clinicopathologic characteristics, including ODX Recurrence Score (RS), were observed between HER2-0 and HER2-low BC. The median HS value of the HER2-low subgroup was significantly higher than that of the HER2-0 subgroup ( P <0.001) and increased significantly between the 4 subgroups classified by HER2 IHC ( P <0.001). The receiver operating characteristic curve showed acceptable utility in distinguishing HER2-0 from HER2-low (area under the curve=0.76) and HER2-null and HER2-ultralow subgroups (area under the curve=0.81), but the overlap between subgroups was also prominent. After defining 8.9 as a suboptimal cutoff mRNA score, multivariate analysis revealed that low Ki-67 (<20%) and RS (≤25) were statistically associated with higher HS (>8.9), whereas progesterone receptor negativity, high Ki-67, high nuclear grade, lower HS, and older age (>50 y) were statistically associated with high RS. Our study revealed that HS is significantly associated with HER2 IHC results and clinicopathologic parameters other than HER2 IHC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762816","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}