Yin P Hung, Komson Wannasai, Catherine B Meador, Maria L Ganci, Anna B Rider, Charlotte I Wang, Mari Mino-Kenudson
Aims
Pulmonary large cell neuroendocrine carcinoma (LCNEC) can be difficult to diagnose due to histological overlap with small cell lung carcinoma (SCLC). SCLC comprises multiple transcription factor-based subtypes. We aimed to evaluate the clinicopathological significance of transcription factor-based subtyping in pulmonary LCNEC.
Methods and results
We identified a consecutive series of 117 patients in 2010–2024 with samples diagnosed as pulmonary LCNEC (n = 70) or high-grade neuroendocrine carcinoma with combined or intermediate morphology (n = 47). Cytomorphological score was assessed as a weighted average from two areas. Immunohistochemistry (IHC) for ASCL1, NeuroD1, POU2F3, YAP1, and HNF4A was evaluated using H-scores, with subtype assignment based on the highest H-score. Next-generation sequencing (NGS) was performed in selected cases. IHC subtyping identified 73 (62%) ASCL1-dominant, 20 (17%) YAP1-dominant, 9 (8%) NeuroD1-dominant, 7 (6%) POU2F3-dominant, 2 (2%) HNF4A-dominant, and 6 (5%) quintuple-negative samples. While YAP1 was often co-expressed with other subtypes and HNF4A was frequently co-expressed with ASCL1, POU2F3 was mutually exclusive from ASCL1/NeuroD1/HNF4A. Unlike ASCL1/NeuroD1/POU2F3, YAP1 and HNF4A H-scores each correlated with large-cell morphology—both across the entire cohort and in the lung resection subgroup. NeuroD1 dominance was more common in tumours with combined/intermediate morphology than LCNEC. Some of the tumours with intermediate morphology straddling between prototypical LCNEC and SCLC harboured POU2F3 dominance, or EGFR or other non-KRAS driver mutations. In 19 patients with multiple samples (including nine with paired pre- and post-treatment samples), all showed concordant subtypes after accounting for codominance.
Conclusion
YAP1 and HNF4A expression correlated significantly with large-cell morphology.
{"title":"Transcription factor-based subtype assignment in pulmonary large cell neuroendocrine carcinoma","authors":"Yin P Hung, Komson Wannasai, Catherine B Meador, Maria L Ganci, Anna B Rider, Charlotte I Wang, Mari Mino-Kenudson","doi":"10.1111/his.70055","DOIUrl":"10.1111/his.70055","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Pulmonary large cell neuroendocrine carcinoma (LCNEC) can be difficult to diagnose due to histological overlap with small cell lung carcinoma (SCLC). SCLC comprises multiple transcription factor-based subtypes. We aimed to evaluate the clinicopathological significance of transcription factor-based subtyping in pulmonary LCNEC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We identified a consecutive series of 117 patients in 2010–2024 with samples diagnosed as pulmonary LCNEC (<i>n</i> = 70) or high-grade neuroendocrine carcinoma with combined or intermediate morphology (<i>n</i> = 47). Cytomorphological score was assessed as a weighted average from two areas. Immunohistochemistry (IHC) for ASCL1, NeuroD1, POU2F3, YAP1, and HNF4A was evaluated using <i>H</i>-scores, with subtype assignment based on the highest <i>H</i>-score. Next-generation sequencing (NGS) was performed in selected cases. IHC subtyping identified 73 (62%) ASCL1-dominant, 20 (17%) YAP1-dominant, 9 (8%) NeuroD1-dominant, 7 (6%) POU2F3-dominant, 2 (2%) HNF4A-dominant, and 6 (5%) quintuple-negative samples. While YAP1 was often co-expressed with other subtypes and HNF4A was frequently co-expressed with ASCL1, POU2F3 was mutually exclusive from ASCL1/NeuroD1/HNF4A. Unlike ASCL1/NeuroD1/POU2F3, YAP1 and HNF4A <i>H</i>-scores each correlated with large-cell morphology—both across the entire cohort and in the lung resection subgroup. NeuroD1 dominance was more common in tumours with combined/intermediate morphology than LCNEC. Some of the tumours with intermediate morphology straddling between prototypical LCNEC and SCLC harboured POU2F3 dominance, or <i>EGFR</i> or other non-<i>KRAS</i> driver mutations. In 19 patients with multiple samples (including nine with paired pre- and post-treatment samples), all showed concordant subtypes after accounting for codominance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>YAP1 and HNF4A expression correlated significantly with large-cell morphology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"810-830"},"PeriodicalIF":4.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fleur Cordier, Jo Van Dorpe, Raf Sciot, Uta Flucke, Joost Van Gorp, Maria Debiec-Rychter, Sarah Van Belle, Siebe Loontiens, Joni Van der Meulen, Bram Van Gaever, Liesbeth Ferdinande, Franceska Dedeurwaerdere, David Creytens
Context
Nodular fasciitis (NF), myositis ossificans/fibro-osseous pseudotumor of the digits (MO/FP) and aneurysmal bone cyst (ABC) are grouped under the category of ‘USP6-associated neoplasms’ (UANs) due to their shared characteristic of an underlying USP6 rearrangement.
Objective
Our aim in this study is to investigate the diversity of USP6 rearrangements in UANs.
Design
We performed a clinicopathological and molecular investigation using targeted RNA sequencing on 124 cases of NF, 19 cases of MO/PF and 32 cases of ABC. Additionally, NF cases were scored for the presence of typical morphological features to assess their correlation with the detected USP6 fusion partner.
Results
In 85.4% of NF cases (88/103), we identified a USP6 rearrangement, with 46.6% exhibiting the classic MYH9::USP6 fusion and 53.4% displaying non-MYH9::USP6 fusions. Notably, classic histological features of NF strongly correlated with the presence of the MYH9::USP6 fusion, while specific NF locations (e.g. intramuscular, intra-articular and intradermal) were significantly associated with non-MYH9 fusions. This study identified 22 novel USP6 fusion partners, demonstrating the fusion diversity within UANs. Additionally, there was minimal overlap in USP6 fusion partners between different UAN types.
Conclusions
A significant entity- and location-specific USP6 fusion partner diversity was revealed among the UAN members. This supports the hypothesis that this diversity may be linked to the cell of origin. Additionally, molecular analysis can be valuable in diagnosing non-classical NF.
{"title":"A morphomolecular study of 175 ‘USP6-associated neoplasms’: The USP6 fusion partner strongly depends on morphology and location","authors":"Fleur Cordier, Jo Van Dorpe, Raf Sciot, Uta Flucke, Joost Van Gorp, Maria Debiec-Rychter, Sarah Van Belle, Siebe Loontiens, Joni Van der Meulen, Bram Van Gaever, Liesbeth Ferdinande, Franceska Dedeurwaerdere, David Creytens","doi":"10.1111/his.70057","DOIUrl":"10.1111/his.70057","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Context</h3>\u0000 \u0000 <p>Nodular fasciitis (NF), myositis ossificans/fibro-osseous pseudotumor of the digits (MO/FP) and aneurysmal bone cyst (ABC) are grouped under the category of ‘<i>USP6</i>-associated neoplasms’ (UANs) due to their shared characteristic of an underlying <i>USP6</i> rearrangement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our aim in this study is to investigate the diversity of <i>USP6</i> rearrangements in UANs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>We performed a clinicopathological and molecular investigation using targeted RNA sequencing on 124 cases of NF, 19 cases of MO/PF and 32 cases of ABC. Additionally, NF cases were scored for the presence of typical morphological features to assess their correlation with the detected <i>USP6</i> fusion partner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 85.4% of NF cases (88/103), we identified a <i>USP6</i> rearrangement, with 46.6% exhibiting the classic <i>MYH9::USP6</i> fusion and 53.4% displaying non-<i>MYH9::USP6</i> fusions. Notably, classic histological features of NF strongly correlated with the presence of the <i>MYH9::USP6</i> fusion, while specific NF locations (e.g. intramuscular, intra-articular and intradermal) were significantly associated with non-<i>MYH9</i> fusions. This study identified 22 novel <i>USP6</i> fusion partners, demonstrating the fusion diversity within UANs. Additionally, there was minimal overlap in <i>USP6</i> fusion partners between different UAN types.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A significant entity- and location-specific <i>USP6</i> fusion partner diversity was revealed among the UAN members. This supports the hypothesis that this diversity may be linked to the cell of origin. Additionally, molecular analysis can be valuable in diagnosing non-classical NF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"898-910"},"PeriodicalIF":4.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pedro Genaro Delgado Guillena, Miriam Cuatrecasas, Sheyla Montori, Nayra Felipez Varela, Joan Llach, Iva Archilla, Pablo Florez-Diez, Eva Barreiro-Alonso, Javier Tejedor-Tejada, Raquel Vicente, M Teresa Soria, Alaín Huerta, Silvia Patricia Ortega, Henar Nuñez, Oliver Patrón, Carolina Mangas, Diana Zaffalon, Luis Hernández, Luis Enrique Yip, Gadea Hontoria, Gonzalo Hijos, Maria Jose Domper-Arnal, Sara Zarraquiños, Alberto Herreros De Tejada, Alicia Córdoba, Anabella Cuestas, Glòria Fernández-Esparrach, Leticia Moreira, Eduardo Albéniz, EpiGASTRIC/EDGAR Consortium
Introduction
The risk stratification of gastric cancer (GC) is graded by assessing well-established precursor lesions, glandular atrophy (GA), and intestinal metaplasia (IM), resulting in both the operative link on gastritis assessment (OLGA), and intestinal metaplasia (OLGIM) systems. Although the OLGIM stage is reproducible among pathologists, the OLGA system is laborious to calculate and has poor reproducibility. In addition, it does not comprehensively address the severity of both GA and IM as recommended by the Sydney consensus. We aimed to propose the Operative Link on Gastric Intestinal Metaplasia and Glandular Atrophy Assessment (OLGIMA) system, which identifies OLGIM III–IV and upstages 0–II with advanced GA.
Methods
A cross-sectional study of consecutive diagnostic gastroscopies in adults was designed. Systematic gastric biopsies were taken. The updated Sydney guidelines were used for histological grading of GA and IM. Higher GC risk was defined as OLGIM III–IV and advanced GA.
Results
The OLGIMA stage was assessed based on the most severe GA and/or IM findings in both antrum and corpus. We included 998 patients (median age 57; 64% women; 35% Helicobacter pylori infection). Thirty-nine (3.9%) patients had higher GC risk: 17 (1.7%) with OLGIM III–IV; 12 (1.2%) with advanced GA, and 10 (1%) meeting both criteria. Among OLGIM 0-II, 12 (1.2%) patients had advanced GA. The OLGIMA system upstaged 39 (3.9%) patients to III–IV, being more sensitive than OLGIM.
Conclusions
The new OLGIMA system identifies patients at higher GC risk (OLGIMA III–IV), encompassing all OLGIM III–IV patients, and upstaging those OLGIM 0–II with advanced GA. This approach addresses the OLGA and OLGIM limitations by integrating GA and IM severity as recommended by the Updated Sydney consensus.
{"title":"The OLGIMA system for gastric cancer risk assessment. A useful method based on the histological Sydney consensus","authors":"Pedro Genaro Delgado Guillena, Miriam Cuatrecasas, Sheyla Montori, Nayra Felipez Varela, Joan Llach, Iva Archilla, Pablo Florez-Diez, Eva Barreiro-Alonso, Javier Tejedor-Tejada, Raquel Vicente, M Teresa Soria, Alaín Huerta, Silvia Patricia Ortega, Henar Nuñez, Oliver Patrón, Carolina Mangas, Diana Zaffalon, Luis Hernández, Luis Enrique Yip, Gadea Hontoria, Gonzalo Hijos, Maria Jose Domper-Arnal, Sara Zarraquiños, Alberto Herreros De Tejada, Alicia Córdoba, Anabella Cuestas, Glòria Fernández-Esparrach, Leticia Moreira, Eduardo Albéniz, EpiGASTRIC/EDGAR Consortium","doi":"10.1111/his.70042","DOIUrl":"10.1111/his.70042","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The risk stratification of gastric cancer (GC) is graded by assessing well-established precursor lesions, glandular atrophy (GA), and intestinal metaplasia (IM), resulting in both the operative link on gastritis assessment (OLGA), and intestinal metaplasia (OLGIM) systems. Although the OLGIM stage is reproducible among pathologists, the OLGA system is laborious to calculate and has poor reproducibility. In addition, it does not comprehensively address the severity of both GA and IM as recommended by the Sydney consensus. We aimed to propose the Operative Link on Gastric Intestinal Metaplasia and Glandular Atrophy Assessment (OLGIMA) system, which identifies OLGIM III–IV and upstages 0–II with advanced GA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional study of consecutive diagnostic gastroscopies in adults was designed. Systematic gastric biopsies were taken. The updated Sydney guidelines were used for histological grading of GA and IM. Higher GC risk was defined as OLGIM III–IV and advanced GA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The OLGIMA stage was assessed based on the most severe GA and/or IM findings in both antrum and corpus. We included 998 patients (median age 57; 64% women; 35% <i>Helicobacter pylori</i> infection). Thirty-nine (3.9%) patients had higher GC risk: 17 (1.7%) with OLGIM III–IV; 12 (1.2%) with advanced GA, and 10 (1%) meeting both criteria. Among OLGIM 0-II, 12 (1.2%) patients had advanced GA. The OLGIMA system upstaged 39 (3.9%) patients to III–IV, being more sensitive than OLGIM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The new OLGIMA system identifies patients at higher GC risk (OLGIMA III–IV), encompassing all OLGIM III–IV patients, and upstaging those OLGIM 0–II with advanced GA. This approach addresses the OLGA and OLGIM limitations by integrating GA and IM severity as recommended by the Updated Sydney consensus.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"911-921"},"PeriodicalIF":4.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Costantino Ricci, Dario de Biase, Thais Maloberti, Agnese Orsatti, Thomas M Ulbright, Muhammad T Idrees, Esther Oliva, Kristine Cornejo, João Lobo, Kvetoslava Michalova, Maria Rosaria Raspollini, Sean R Williamson, Geert JLH van Leenders, Chia-Sui Kao, Fiona Maclean, Ankur R Sangoi, Adeboye O Osunkoya, Michelangelo Fiorentino, Antonio De Leo, Giovanni Tallini, Andres Martin Acosta
Aims
Testicular adult granulosa cell tumours (AGCTs) are rare and show several clinical–pathological differences with their ovarian counterparts. In a limited number of prior studies, FOXL2 p.Cys134Trp, the hallmark molecular alteration of ovarian AGCT, appeared to be infrequent in testicular AGCTs. However, the number of cases analysed to date is relatively small.
Methods and results
Twenty testicular AGCTs were analysed de novo using two different next-generation sequencing (NGS) panels that cover sex cord-stromal tumour (SCST)–relevant genes, including FOXL2, CTNNB1, FH and DICER1. Among 12 tumours (12/20; 60%) that were sequenced successfully, none harboured FOXL2 mutations. Eight tumours (8/12, 66.7%) showed a wild-type (WT) status for all genes assessed with the panels. Three tumours harboured pathogenic or likely pathogenic CTNNB1 alterations. One of these exhibited predominant spindle cell morphology, while the other two showed focal tubular architecture. Immunohistochemistry performed in one of these tumours with available material showed β-catenin expression in ~70% of tumor cell nuclei. The remaining AGCTs showed variants of uncertain significance (likely benign) in KIT and MED12. Considering the tumors asseseed in this study and those previously reported in the literature, only 2 of 29 neoplasms classified as testicular AGCTs have shown a FOXL2 p.Cys134Trp mutation to date.
Conclusions
The present study confirms that SCSTs classified as AGCTs differ from their ovarian counterparts in that they largely lack FOXL2 mutations.
{"title":"Adult granulosa cell tumours of the testis analogous to ovarian counterparts are exceptionally rare: analysis of a multicentric series and review of the literature","authors":"Costantino Ricci, Dario de Biase, Thais Maloberti, Agnese Orsatti, Thomas M Ulbright, Muhammad T Idrees, Esther Oliva, Kristine Cornejo, João Lobo, Kvetoslava Michalova, Maria Rosaria Raspollini, Sean R Williamson, Geert JLH van Leenders, Chia-Sui Kao, Fiona Maclean, Ankur R Sangoi, Adeboye O Osunkoya, Michelangelo Fiorentino, Antonio De Leo, Giovanni Tallini, Andres Martin Acosta","doi":"10.1111/his.70048","DOIUrl":"10.1111/his.70048","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Testicular adult granulosa cell tumours (AGCTs) are rare and show several clinical–pathological differences with their ovarian counterparts. In a limited number of prior studies, <i>FOXL2</i> p.Cys134Trp, the hallmark molecular alteration of ovarian AGCT, appeared to be infrequent in testicular AGCTs. However, the number of cases analysed to date is relatively small.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Twenty testicular AGCTs were analysed <i>de novo</i> using two different next-generation sequencing (NGS) panels that cover sex cord-stromal tumour (SCST)–relevant genes, including <i>FOXL2</i>, <i>CTNNB1</i>, <i>FH</i> and <i>DICER1</i>. Among 12 tumours (12/20; 60%) that were sequenced successfully, none harboured <i>FOXL2</i> mutations. Eight tumours (8/12, 66.7%) showed a wild-type (WT) status for all genes assessed with the panels. Three tumours harboured pathogenic or likely pathogenic <i>CTNNB1</i> alterations. One of these exhibited predominant spindle cell morphology, while the other two showed focal tubular architecture. Immunohistochemistry performed in one of these tumours with available material showed β-catenin expression in ~70% of tumor cell nuclei. The remaining AGCTs showed variants of uncertain significance (likely benign) in <i>KIT</i> and <i>MED12</i>. Considering the tumors asseseed in this study and those previously reported in the literature, only 2 of 29 neoplasms classified as testicular AGCTs have shown a <i>FOXL2</i> p.Cys134Trp mutation to date.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present study confirms that SCSTs classified as AGCTs differ from their ovarian counterparts in that they largely lack <i>FOXL2</i> mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"831-842"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Apocrine carcinoma (AC) is a rare and distinct subtype of invasive breast carcinoma, typically characterized by androgen receptor (AR) positivity and negative expression of oestrogen and progesterone receptors. This study aimed to clarify the metabolic and molecular characteristics of AC, with a particular focus on protein expression related to lipid metabolism and the frequency and nature of PIK3CA mutations.
Methods
We analysed tissue specimens from 40 cases with AC and 59 cases with other breast cancer subtypes (ER+/HER2−, ER+/HER2+, ER−/HER2+ and triple-negative breast cancer [TNBC]). Immunohistochemistry was performed for a panel of lipid metabolism-related proteins including FASN, AMACR, ACOX1, ACSL1 and catalase. mRNA Expression of ACSL1 was assessed by RT-qPCR and PIK3CA mutations were analysed via targeted sequencing.
Results
AC showed significantly higher expression of enzymes involved in fatty acid synthesis and peroxisomal β-oxidation compared to other subtypes. Notably, ACSL1 was upregulated at both protein and mRNA levels, and catalase was upregulated at the protein level, indicating an increase in peroxisomes. PIK3CA Mutations, particularly the hotspot p.H1047R variant, were detected at a significantly higher frequency in AC (68.4%) compared to the other subtypes: ER+/HER2− (52.6%), ER+/HER2+ (27.3%), ER−/HER2+ (50.0%) and TNBC (33.3%) (P < 0.05).
Conclusions
AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β-oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.
{"title":"Apocrine carcinoma of the breast: distinctive metabolic reprogramming and high-frequency PIK3CA mutations revealed by molecular and immunohistochemical analysis","authors":"Harumi Nakamura, Yoji Kukita, Nobuyoshi Kittaka, Hiroki Kusama, Takahiro Nakayama, Yasuhiro Tamaki, Ken-ichi Yoshida, Kei Kunimasa, Fumio Imamura, Toshinari Yagi","doi":"10.1111/his.70024","DOIUrl":"10.1111/his.70024","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Apocrine carcinoma (AC) is a rare and distinct subtype of invasive breast carcinoma, typically characterized by androgen receptor (AR) positivity and negative expression of oestrogen and progesterone receptors. This study aimed to clarify the metabolic and molecular characteristics of AC, with a particular focus on protein expression related to lipid metabolism and the frequency and nature of PIK3CA mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed tissue specimens from 40 cases with AC and 59 cases with other breast cancer subtypes (ER+/HER2−, ER+/HER2+, ER−/HER2+ and triple-negative breast cancer [TNBC]). Immunohistochemistry was performed for a panel of lipid metabolism-related proteins including FASN, AMACR, ACOX1, ACSL1 and catalase. mRNA Expression of ACSL1 was assessed by RT-qPCR and PIK3CA mutations were analysed via targeted sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AC showed significantly higher expression of enzymes involved in fatty acid synthesis and peroxisomal β-oxidation compared to other subtypes. Notably, ACSL1 was upregulated at both protein and mRNA levels, and catalase was upregulated at the protein level, indicating an increase in peroxisomes. PIK3CA Mutations, particularly the hotspot p.H1047R variant, were detected at a significantly higher frequency in AC (68.4%) compared to the other subtypes: ER+/HER2− (52.6%), ER+/HER2+ (27.3%), ER−/HER2+ (50.0%) and TNBC (33.3%) (<i>P</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β-oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"790-809"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roselyne Choiniere, Willem P A Boellaard, Marij Dinkelman-Smit, Geert J L H van Leenders
Background and Objectives
Testicular frozen section examination on excisional biopsy (FSEB) is an underused pathological and surgical approach, considering the increasing number of small benign testicular lesions found on radical orchidectomy specimens. This study aims to determine the diagnostic accuracy of FSEB and to provide a pathological summary of the most frequent diagnoses and pitfalls.
Methods
We report the pathological findings and definitive outcome of 135 FSEB for small testicular masses performed between 2005 and 2024 in a single institute.
Results
The median tumour size was 0.9 cm (Interquartile Range [IQR] 0.5–1.3 cm). The most common FSEB diagnoses were Leydig cell hyperplasia/tumour (n = 37; 28%) and seminoma (n = 36; 27%). On FSEB, benign diagnoses represented 58% of cases which allowed us to avoid 81 unnecessary radical orchidectomies. The sensitivity and specificity of FSEB for malignancy were 100% and 96.3%, respectively. Excluding three indeterminate cases on FSEB, the concordance rate was 97.7% (129/132). On definitive assessment, the majority of cases were benign (84/135, 62%) and 51 (38%) cases were malignant. The three indeterminate cases were ultimately confirmed as benign. There were three false-positive diagnoses of (favoured) malignancy and no false negatives.
Conclusions
FSEB is accurate for patient management of small testicular lesions, allowing us to save young men from unnecessary radical orchidectomy. We provide an in-depth overview of the most prevalent pathological diagnoses encountered.
{"title":"Testicular mass frozen section examination: Pathological insights and diagnostic accuracy","authors":"Roselyne Choiniere, Willem P A Boellaard, Marij Dinkelman-Smit, Geert J L H van Leenders","doi":"10.1111/his.70049","DOIUrl":"10.1111/his.70049","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Testicular frozen section examination on excisional biopsy (FSEB) is an underused pathological and surgical approach, considering the increasing number of small benign testicular lesions found on radical orchidectomy specimens. This study aims to determine the diagnostic accuracy of FSEB and to provide a pathological summary of the most frequent diagnoses and pitfalls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We report the pathological findings and definitive outcome of 135 FSEB for small testicular masses performed between 2005 and 2024 in a single institute.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median tumour size was 0.9 cm (Interquartile Range [IQR] 0.5–1.3 cm). The most common FSEB diagnoses were Leydig cell hyperplasia/tumour (<i>n</i> = 37; 28%) and seminoma (<i>n</i> = 36; 27%). On FSEB, benign diagnoses represented 58% of cases which allowed us to avoid 81 unnecessary radical orchidectomies. The sensitivity and specificity of FSEB for malignancy were 100% and 96.3%, respectively. Excluding three indeterminate cases on FSEB, the concordance rate was 97.7% (129/132). On definitive assessment, the majority of cases were benign (84/135, 62%) and 51 (38%) cases were malignant. The three indeterminate cases were ultimately confirmed as benign. There were three false-positive diagnoses of (favoured) malignancy and no false negatives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FSEB is accurate for patient management of small testicular lesions, allowing us to save young men from unnecessary radical orchidectomy. We provide an in-depth overview of the most prevalent pathological diagnoses encountered.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"843-853"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhenyu Xu, Heyuan Zhu, Xiaojie Wang, Yongqin Tang, Ying Huang, Pan Chi, Yanwu Sun
Background
Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) does not eliminate tumor recurrence risk, with distant metastasis remaining a critical challenge. This study aimed to identify novel prognostic factors for risk stratification in pCR patients after nCRT.
Methods
We enrolled 149 LARC patients who achieved pCR between 2016 and 2020. Acellular mucin pools (AMP) were classified by the deepest tissue layer of AMP (A0: absent; A1: within the muscularis propria; A2: exceeding the muscularis propria). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and recurrence patterns.
Results
After a median follow-up of 75.3 months, the 5-year OS and DFS rates were 95.3% and 89.9%, respectively. Among 15 recurrence events, all were distant metastases (80% pulmonary). AMP were present in 17.4% (26/149) of patients. Multivariate analysis identified AMP exceeding the muscularis propria (HR = 3.996, 95% CI: 1.073–14.660, P = 0.039), preoperative neutrophil-to-lymphocyte ratio (NLR) >4.4 (HR = 3.658, 95% CI: 1.304–10.263, P = 0.014) and tumour distance from the anal verge on pretreatment magnetic resonance imaging (MRI) (HR = 0.667, 95% CI: 0.481–0.925, P = 0.015) as independent predictors of distant metastasis-free survival (DMFS). A nomogram integrating these factors showed robust discriminative performance for 1-, 3-, and 5-year DMFS (AUC = 0.689, 0.815, 0.795). Meanwhile, AMP exceeding the muscularis propria (HR = 6.632, P = 0.010) and pretreatment MRI-assessed tumour distance from the anal margin (HR = 0.614, P = 0.018) were independent predictors for pulmonary metastasis.
Conclusions
AMP exceeding the muscularis propria and high pretreatment NLR are complementary prognostic markers that refine risk stratification in pCR patients, enabling personalized surveillance and treatment strategies to improve outcomes.
背景：局部晚期直肠癌（LARC）的新辅助放化疗（nCRT）后病理完全缓解（pCR）并不能消除肿瘤复发的风险，远处转移仍然是一个关键的挑战。本研究旨在确定nCRT后pCR患者风险分层的新预后因素。方法：我们在2016年至2020年期间招募了149例实现pCR的LARC患者。脱细胞粘蛋白池（AMP）按AMP的最深组织层进行分类（A0：无；A1：在固有肌层内；A2：超过固有肌层）。主要终点为无病生存期（DFS）；次要终点包括总生存期（OS）和复发模式。结果：中位随访75.3个月后，5年OS和DFS分别为95.3%和89.9%。在15例复发事件中，均为远处转移（80%为肺转移）。17.4%（26/149）的患者存在AMP。多因素分析发现，AMP超过固有肌层（HR = 3.996, 95% CI: 1.073-14.660, P = 0.039）、术前中性粒细胞与淋巴细胞比值（NLR） bbb4.4 （HR = 3.658, 95% CI: 1.304-10.263, P = 0.014）和前处理磁共振成像（MRI）肿瘤距离肛门边缘（HR = 0.667, 95% CI: 0.481-0.925, P = 0.015）是远处无转移生存（DMFS）的独立预测因子。综合这些因素的nomogram显示了1年、3年和5年DMFS的稳健判别性能（AUC = 0.689, 0.815, 0.795）。AMP超过固有肌层（HR = 6.632, P = 0.010）和预处理mri评估肿瘤距肛缘的距离（HR = 0.614, P = 0.018）是肺转移的独立预测因子。结论：AMP超过固有肌层和高预处理NLR是完善pCR患者风险分层的补充预后标志物，使个性化监测和治疗策略能够改善预后。
{"title":"Acellular mucin pools and neutrophil-to-lymphocyte ratio: unveiling hidden aggressiveness in pathological complete response after chemoradiotherapy for rectal cancer","authors":"Zhenyu Xu, Heyuan Zhu, Xiaojie Wang, Yongqin Tang, Ying Huang, Pan Chi, Yanwu Sun","doi":"10.1111/his.70050","DOIUrl":"10.1111/his.70050","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) does not eliminate tumor recurrence risk, with distant metastasis remaining a critical challenge. This study aimed to identify novel prognostic factors for risk stratification in pCR patients after nCRT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 149 LARC patients who achieved pCR between 2016 and 2020. Acellular mucin pools (AMP) were classified by the deepest tissue layer of AMP (A0: absent; A1: within the muscularis propria; A2: exceeding the muscularis propria). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and recurrence patterns.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After a median follow-up of 75.3 months, the 5-year OS and DFS rates were 95.3% and 89.9%, respectively. Among 15 recurrence events, all were distant metastases (80% pulmonary). AMP were present in 17.4% (26/149) of patients. Multivariate analysis identified AMP exceeding the muscularis propria (HR = 3.996, 95% CI: 1.073–14.660, <i>P</i> = 0.039), preoperative neutrophil-to-lymphocyte ratio (NLR) >4.4 (HR = 3.658, 95% CI: 1.304–10.263, <i>P</i> = 0.014) and tumour distance from the anal verge on pretreatment magnetic resonance imaging (MRI) (HR = 0.667, 95% CI: 0.481–0.925, <i>P</i> = 0.015) as independent predictors of distant metastasis-free survival (DMFS). A nomogram integrating these factors showed robust discriminative performance for 1-, 3-, and 5-year DMFS (AUC = 0.689, 0.815, 0.795). Meanwhile, AMP exceeding the muscularis propria (HR = 6.632, <i>P</i> = 0.010) and pretreatment MRI-assessed tumour distance from the anal margin (HR = 0.614, <i>P</i> = 0.018) were independent predictors for pulmonary metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AMP exceeding the muscularis propria and high pretreatment NLR are complementary prognostic markers that refine risk stratification in pCR patients, enabling personalized surveillance and treatment strategies to improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"854-867"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irena Antonia Ungureanu, Megane Le Quang, Rihab Azmani, Marie Ancelle, Henri Margot, Guillaume Chotard, François Le Loarer, Nathalène Truffaux
Introduction
Myofibromas are part of the pericytic tumour family, which includes myopericytomas, glomus tumours and angioleiomyomas. While they typically display benign behaviour when arising in the skin and subcutaneous tissues of the head and neck, rare aggressive variants have been reported, particularly those with visceral or intracranial involvement. The most frequently identified molecular alterations in myofibromas are PDGFRB gain-of-function mutations, primarily single-nucleotide substitutions.
Case presentation
Herein, we report two cases of myofibroma: one aggressive case with central nervous system involvement in a newborn, exhibiting a monophasic morphology, and a second, subcutaneous case in an adult. RNA sequencing was performed on both tumours, and data analysis was conducted using a four-pipeline fusion-calling approach (Arriba, FusionCatcher, FusionMap and STAR-Fusion). This analysis identified a novel somatic internal tandem duplication (ITD) in the NOTCH3 gene, affecting exons 26 and 27, specifically involving the C-terminal heterodimerization domain of the NOTCH3 receptor. Unsupervised hierarchical clustering demonstrated that myofibromas with ITDs segregate distinctly from conventional myofibromas and other pericytic tumours.
Discussion and conclusion
Our findings suggest that NOTCH3 ITDs represent a novel oncogenic mechanism in pericytic tumour pathogenesis, likely driving constitutive activation of the NOTCH signalling pathway. Given the potential therapeutic relevance, particularly in aggressive or life-threatening cases with CNS involvement, our findings highlight the importance of extensive molecular profiling. Targeted therapy with NOTCH inhibitors may represent a promising strategy in the management of aggressive cases of ITD-driven pericytic tumours.
{"title":"Novel NOTCH3 alteration expanding the molecular spectrum of pericytic tumours: report of two cases","authors":"Irena Antonia Ungureanu, Megane Le Quang, Rihab Azmani, Marie Ancelle, Henri Margot, Guillaume Chotard, François Le Loarer, Nathalène Truffaux","doi":"10.1111/his.70051","DOIUrl":"10.1111/his.70051","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Myofibromas are part of the pericytic tumour family, which includes myopericytomas, glomus tumours and angioleiomyomas. While they typically display benign behaviour when arising in the skin and subcutaneous tissues of the head and neck, rare aggressive variants have been reported, particularly those with visceral or intracranial involvement. The most frequently identified molecular alterations in myofibromas are <i>PDGFRB</i> gain-of-function mutations, primarily single-nucleotide substitutions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case presentation</h3>\u0000 \u0000 <p>Herein, we report two cases of myofibroma: one aggressive case with central nervous system involvement in a newborn, exhibiting a monophasic morphology, and a second, subcutaneous case in an adult. RNA sequencing was performed on both tumours, and data analysis was conducted using a four-pipeline fusion-calling approach (Arriba, FusionCatcher, FusionMap and STAR-Fusion). This analysis identified a novel somatic internal tandem duplication (ITD) in the <i>NOTCH3</i> gene, affecting exons 26 and 27, specifically involving the C-terminal heterodimerization domain of the NOTCH3 receptor. Unsupervised hierarchical clustering demonstrated that myofibromas with ITDs segregate distinctly from conventional myofibromas and other pericytic tumours.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and conclusion</h3>\u0000 \u0000 <p>Our findings suggest that <i>NOTCH3</i> ITDs represent a novel oncogenic mechanism in pericytic tumour pathogenesis, likely driving constitutive activation of the NOTCH signalling pathway. Given the potential therapeutic relevance, particularly in aggressive or life-threatening cases with CNS involvement, our findings highlight the importance of extensive molecular profiling. Targeted therapy with NOTCH inhibitors may represent a promising strategy in the management of aggressive cases of ITD-driven pericytic tumours.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 4","pages":"922-927"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C. Bastian, Werner Kempf, David Elder MB, ChB, FRCPA, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud de la Fouchardière, Alexander J. Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C. Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M. Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty
The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: ‘Tumours of the nail unit’ and ‘Metastases to skin’, along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.
{"title":"WHO classification of skin tumours: key updates in the fifth edition","authors":"Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C. Bastian, Werner Kempf, David Elder MB, ChB, FRCPA, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud de la Fouchardière, Alexander J. Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C. Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M. Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty","doi":"10.1111/his.15562","DOIUrl":"10.1111/his.15562","url":null,"abstract":"<p>The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: ‘Tumours of the nail unit’ and ‘Metastases to skin’, along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"88 3","pages":"555-568"},"PeriodicalIF":4.1,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Seven years as Editor: what I have learned","authors":"Daniel M Berney","doi":"10.1111/his.70031","DOIUrl":"https://doi.org/10.1111/his.70031","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"87 6","pages":"787-788"},"PeriodicalIF":4.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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