Kara Tanaka MD, MFA, Neslihan Kayraklioglu MD, PhD, Emily Chan MD, PhD, Chien-Kuang C. Ding MD, PhD, Poonam Vohra MD
Background
Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria.
Methods
HPV-positive cases were identified by a retrospective review of surgical specimens that had UTCa confirmed by HPV in situ hybridization. Cases that had concurrent urine cytology were reviewed using TPS. Cytomorphologic features of high-grade urothelial carcinoma (HGUC) were evaluated as well as the presence of atypical squamous cells (ASCs) and basaloid features.
Results
Sixteen cytology specimens from eight patients with HPV-positive UTCa were included. On original diagnosis, none of the cytology specimens were suggested to be HPV-associated. TPS diagnostic criteria identified eight cases with at least atypical findings, including five HGUC cases, one case that was suspicious for HGUC, and two atypical urothelial cases. Common cytomorphologic features included basaloid clusters (six of eight cases; 75%) and ASCs (four of eight cases; 50%) that matched the corresponding surgical specimens. Most cases exhibited urothelial cell hyperchromasia (seven of eight cases; 88%), and hypochromasia was a frequently observed variant (four of eight cases; 50%), either alone or in addition to hyperchromasia.
Conclusions
HPV-positive UTCa can be identified reliably as HGUC by using TPS criteria; however, these cases may not be recognized as HPV-associated. The presence of basaloid cells or ASCs can help suggest screening for HPV in urine specimens. Larger scale studies are warranted to validate cytomorphologic differences and determine the impact of HPV infection on clinical outcomes for patients with UTCa.
{"title":"Utility of The Paris System for Reporting Urinary Cytology in patients with HPV-positive urinary tract carcinoma","authors":"Kara Tanaka MD, MFA, Neslihan Kayraklioglu MD, PhD, Emily Chan MD, PhD, Chien-Kuang C. Ding MD, PhD, Poonam Vohra MD","doi":"10.1002/cncy.22914","DOIUrl":"10.1002/cncy.22914","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HPV-positive cases were identified by a retrospective review of surgical specimens that had UTCa confirmed by HPV in situ hybridization. Cases that had concurrent urine cytology were reviewed using TPS. Cytomorphologic features of high-grade urothelial carcinoma (HGUC) were evaluated as well as the presence of atypical squamous cells (ASCs) and basaloid features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixteen cytology specimens from eight patients with HPV-positive UTCa were included. On original diagnosis, none of the cytology specimens were suggested to be HPV-associated. TPS diagnostic criteria identified eight cases with at least atypical findings, including five HGUC cases, one case that was suspicious for HGUC, and two atypical urothelial cases. Common cytomorphologic features included basaloid clusters (six of eight cases; 75%) and ASCs (four of eight cases; 50%) that matched the corresponding surgical specimens. Most cases exhibited urothelial cell hyperchromasia (seven of eight cases; 88%), and hypochromasia was a frequently observed variant (four of eight cases; 50%), either alone or in addition to hyperchromasia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HPV-positive UTCa can be identified reliably as HGUC by using TPS criteria; however, these cases may not be recognized as HPV-associated. The presence of basaloid cells or ASCs can help suggest screening for HPV in urine specimens. Larger scale studies are warranted to validate cytomorphologic differences and determine the impact of HPV infection on clinical outcomes for patients with UTCa.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua J. X. Li MBChB, Hiu Yu Cheng MSc, Conrad H. C. Lee MSc, Joanna K. M. Ng MBBS, Julia Y. Tsang PhD, Gary M. Tse MBBS
Background
Metastatic breast cancers are frequently encountered in cytology and require immunocytochemistry (ICC). In this study, traditional and multiplex ICC (mICC) for GATA-binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin (MMG) were performed with the aim of validating mICC in cell blocks, with further single-cell expression pattern analysis to identify the single markers and combinations of markers most sensitive in subtypes of breast cancer.
Methods
GATA3, GCDFP15, and MMG were paired with OptiView 3,3′-diaminobenzidine and Ventana DISCOVERY Purple and Blue, respectively, with cyclical and serial staining. Bright-field imaging was performed with the Mantra 2 system and analyzed with the inForm Tissue Finder (Akoya Biosciences). Cell detection and phenotyping were further confirmed by two pathologists.
Results
In the 36 cases studied, traditional ICC and mICC demonstrated good concordance (kappa coefficient, >0.5; p < .01) at three cutoffs (1%, 5%, and 50%), except for GATA3 at the 1% cutoff. Single-marker positivity outnumbered double-marker positivity and the exceedingly rare triple-marker positivity (<3%). GATA3 was the leading single marker–positive phenotype in all breast cancer subtypes, except for MMG in estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–positive (ER+/PR+/HER2+) breast cancers. Limited to two markers, GATA3/MMG included the greatest number of tumor cells for luminal breast cancers (ER+/PR+/HER2+, 60.6%; ER+/PR+/HER2+, 31.4%), whereas HER2-overexpressed breast cancers (27.4%) and triple-negative breast cancers (26.4%) favored the combination of GATA3/GCDFP15.
Conclusions
For a single marker, GATA3 displayed the highest sensitivity. The addition of MMG for hormone receptor-positive breast cancers and GCDFP15 for hormone receptor-negative breast cancers further increased sensitivity. The low proportion of multimarker-positive cells suggested that the coexpression observed with traditional ICC is attributable to intratumoral heterogeneity, not genuine coexpression.
{"title":"Single-cell multiplex immunocytochemistry in cell block preparations of metastatic breast cancer confirms sensitivity of GATA-binding protein 3 over gross cystic disease fluid protein 15 and mammaglobin","authors":"Joshua J. X. Li MBChB, Hiu Yu Cheng MSc, Conrad H. C. Lee MSc, Joanna K. M. Ng MBBS, Julia Y. Tsang PhD, Gary M. Tse MBBS","doi":"10.1002/cncy.22910","DOIUrl":"10.1002/cncy.22910","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metastatic breast cancers are frequently encountered in cytology and require immunocytochemistry (ICC). In this study, traditional and multiplex ICC (mICC) for GATA-binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin (MMG) were performed with the aim of validating mICC in cell blocks, with further single-cell expression pattern analysis to identify the single markers and combinations of markers most sensitive in subtypes of breast cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GATA3, GCDFP15, and MMG were paired with OptiView 3,3′-diaminobenzidine and Ventana DISCOVERY Purple and Blue, respectively, with cyclical and serial staining. Bright-field imaging was performed with the Mantra 2 system and analyzed with the inForm Tissue Finder (Akoya Biosciences). Cell detection and phenotyping were further confirmed by two pathologists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the 36 cases studied, traditional ICC and mICC demonstrated good concordance (kappa coefficient, >0.5; <i>p</i> < .01) at three cutoffs (1%, 5%, and 50%), except for GATA3 at the 1% cutoff. Single-marker positivity outnumbered double-marker positivity and the exceedingly rare triple-marker positivity (<3%). GATA3 was the leading single marker–positive phenotype in all breast cancer subtypes, except for MMG in estrogen receptor–positive, progesterone receptor–positive, and human epidermal growth factor receptor 2–positive (ER+/PR+/HER2+) breast cancers. Limited to two markers, GATA3/MMG included the greatest number of tumor cells for luminal breast cancers (ER+/PR+/HER2+, 60.6%; ER+/PR+/HER2+, 31.4%), whereas HER2-overexpressed breast cancers (27.4%) and triple-negative breast cancers (26.4%) favored the combination of GATA3/GCDFP15.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>For a single marker, GATA3 displayed the highest sensitivity. The addition of MMG for hormone receptor-positive breast cancers and GCDFP15 for hormone receptor-negative breast cancers further increased sensitivity. The low proportion of multimarker-positive cells suggested that the coexpression observed with traditional ICC is attributable to intratumoral heterogeneity, not genuine coexpression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of this study was to elucidate the frequency and cytologic features of positive peritoneal washing cytology (PWC) in cervical gastric-type adenocarcinoma (GAS) and to clarify the clinical significance of positive PWC.
Methods
The authors analyzed cases from their institution between 1991 and 2023 in which patients underwent surgery and PWC. The study included 62 patients who had cervical GAS (1991–2023; including seven patients with adenocarcinoma in situ and 26, 15, nine, and five patients with International Federation of Gynecology and Obstetrics 2018 stage I, II, III, and IV disease, respectively) and 100 patients who had usual-type endocervical adenocarcinoma (2007–2023; including 65, 15, and 20 patients with stage I, II, and III disease, respectively). The frequency of positive PWC results and cytologic features was assessed, and correlations between positive PWC results and clinicopathologic factors were examined, including prognosis, in the GAS group.
Results
Positive PWC results were significantly more frequent in patients who had GAS at 24% (15 of 62 patients) compared with 7% (seven of 100 patients) in those who had usual-type endocervical adenocarcinoma. The cytologic features of GAS included distinct cellular atypia (enlarged nuclei, nuclear irregularity) and frequent formation of spherical clusters (10 of 15 cases) without the golden-yellowish mucus commonly seen in cervical smears. A positive PWC result in GAS was significantly correlated with larger tumor size, parametrium invasion, lymph node metastasis, and elevated carbohydrate antigen 19-9 levels. In patients with stage I GAS, the PWC-positive group had significantly shorter disease-free survival and overall survival compared with the PWC-negative group.
Conclusions
Positive PWC findings are frequent in cervical GAS and are associated with pathologic factors indicative of tumor growth and progression. In patients who have stage I GAS, positive PWC results may indicate a poor prognosis, warranting further investigation.
研究背景本研究旨在阐明宫颈胃型腺癌（GAS）腹膜冲洗细胞学（PWC）阳性的频率和细胞学特征，并明确PWC阳性的临床意义：作者分析了其所在机构在 1991 年至 2023 年期间接受手术和 PWC 的病例。研究纳入了 62 例宫颈 GAS 患者（1991-2023 年；包括 7 例原位腺癌患者和 26 例、15 例、9 例和 5 例国际妇产科联盟 2018 年 I、II、III 和 IV 期疾病患者）和 100 例普通型宫颈内膜腺癌患者（2007-2023 年；包括 65 例、15 例和 20 例 I、II 和 III 期疾病患者）。评估了PWC阳性结果的频率和细胞学特征，并研究了GAS组中PWC阳性结果与临床病理因素（包括预后）之间的相关性：结果：PWC阳性结果在GAS患者中的出现率明显更高，为24%（62例患者中的15例），而在普通型宫颈内膜腺癌患者中仅为7%（100例患者中的7例）。GAS 的细胞学特征包括明显的细胞不典型性（核增大、核不规则）和经常形成球形团块（15 例中有 10 例），而没有宫颈涂片中常见的金黄色粘液。GAS 患者的 PWC 阳性结果与肿瘤体积增大、宫旁侵犯、淋巴结转移和碳水化合物抗原 19-9 水平升高有显著相关性。在 I 期 GAS 患者中，PWC 阳性组的无病生存期和总生存期明显短于 PWC 阴性组：结论：PWC 阳性结果在宫颈 GAS 中很常见，并且与表明肿瘤生长和进展的病理因素相关。对于 I 期 GAS 患者，PWC 阳性结果可能预示着不良预后，值得进一步研究。
{"title":"Intraoperative peritoneal cytology for cervical gastric-type adenocarcinoma: Cytopathology and clinical impact","authors":"Waku Takigawa MD, Hiroshi Yoshida MD, PhD, Shoichi Kitamura MD, Chika Tokutake CT, Madoka Kondo CT, Mizuho Fujima CT, Yasuo Shibuki CT, Mayumi Kobayashi-Kato MD, PhD, Yasuhito Tanase MD, PhD, Masaya Uno MD, PhD, Mitsuya Ishikawa MD, PhD","doi":"10.1002/cncy.22915","DOIUrl":"10.1002/cncy.22915","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study was to elucidate the frequency and cytologic features of positive peritoneal washing cytology (PWC) in cervical gastric-type adenocarcinoma (GAS) and to clarify the clinical significance of positive PWC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors analyzed cases from their institution between 1991 and 2023 in which patients underwent surgery and PWC. The study included 62 patients who had cervical GAS (1991–2023; including seven patients with adenocarcinoma in situ and 26, 15, nine, and five patients with International Federation of Gynecology and Obstetrics 2018 stage I, II, III, and IV disease, respectively) and 100 patients who had usual-type endocervical adenocarcinoma (2007–2023; including 65, 15, and 20 patients with stage I, II, and III disease, respectively). The frequency of positive PWC results and cytologic features was assessed, and correlations between positive PWC results and clinicopathologic factors were examined, including prognosis, in the GAS group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Positive PWC results were significantly more frequent in patients who had GAS at 24% (15 of 62 patients) compared with 7% (seven of 100 patients) in those who had usual-type endocervical adenocarcinoma. The cytologic features of GAS included distinct cellular atypia (enlarged nuclei, nuclear irregularity) and frequent formation of spherical clusters (10 of 15 cases) without the golden-yellowish mucus commonly seen in cervical smears. A positive PWC result in GAS was significantly correlated with larger tumor size, parametrium invasion, lymph node metastasis, and elevated carbohydrate antigen 19-9 levels. In patients with stage I GAS, the PWC-positive group had significantly shorter disease-free survival and overall survival compared with the PWC-negative group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Positive PWC findings are frequent in cervical GAS and are associated with pathologic factors indicative of tumor growth and progression. In patients who have stage I GAS, positive PWC results may indicate a poor prognosis, warranting further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thank You to Reviewers 2024","authors":"","doi":"10.1002/cncy.22913","DOIUrl":"https://doi.org/10.1002/cncy.22913","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 12","pages":"809-810"},"PeriodicalIF":2.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Some online articles have suggested, without evidence, that high-dose infusions of vitamin C can cure cancer. Others have promised, falsely, that baking soda can cure prostate cancer or that cannabis oil can cure breast or lung cancer. Well before ivermectin was infamously touted as an (ineffective) intervention for the coronavirus disease 2019, a podcast wrongly asserted that the antiparasitic medication offered a cancer cure.</p><p>Experts have long warned of the noxious effects of online misinformation aimed at swaying elections and public opinion. The swirl of misinformation around cancer treatment and prevention may be less well studied, but researchers have begun raising alarms about the considerable harm that can come from advice that is, in some cases, literally toxic.</p><p>Skyler Johnson, MD, an assistant professor of radiation oncology at the University of Utah’s Huntsman Cancer Institute in Salt Lake City, experienced the phenomenon firsthand when his wife was diagnosed with cancer in 2011 while he was still in medical school. The couple encountered so many fact-free claims and false assertions online that Dr Johnson decided to study the effects of this flood of bad advice. Even after his wife was declared cancer-free, he realized that such misinformation, even from well-meaning friends and relatives, can lead to serious and avoidable harm.</p><p>Most disturbingly, he discovered, it can kill. In a highly cited study, Dr Johnson and his colleagues found that patients who relied entirely on unproven alternative cancer therapies were significantly more likely to die within 5 years than patients who used conventional treatments, such as chemotherapy, radiation, immunotherapy, and surgery.<span><sup>1</sup></span> For a subset of patients with breast or colorectal cancer who used alternative medicine, the mortality risk jumped roughly 5-fold. No matter how advanced cancer treatments might be, he says, “if patients aren’t willing to take those treatments, then we’ve done no good.”</p><p>When she read Dr Johnson’s study, Briony Swire-Thompson, PhD, director of the Psychology of Misinformation Lab in the Network Science Institute at Northeastern University in Boston, Massachusetts, had an epiphany. The cognitive psychologist had previously studied general and political misinformation, but she immediately understood the unique challenge posed by cancer misinformation. “That was, I think, an aha moment where I realized this is a topic where belief really has impact in people’s lives,” she says.</p><p>Dr Swire-Thompson characterizes <i>misinformation</i> as an umbrella term for all false information and <i>disinformation</i> as a subset of false information that is spread deliberately. The high anxiety accompanying a cancer diagnosis, coupled with cognitive fatigue and the fear of side effects from chemotherapy, radiation, or surgery, she notes, can make a patient more susceptible to a huckster trying to capitalize financially. “People are wi
{"title":"Researchers confront a rising tide of cancer misinformation","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.22909","DOIUrl":"10.1002/cncy.22909","url":null,"abstract":"<p>Some online articles have suggested, without evidence, that high-dose infusions of vitamin C can cure cancer. Others have promised, falsely, that baking soda can cure prostate cancer or that cannabis oil can cure breast or lung cancer. Well before ivermectin was infamously touted as an (ineffective) intervention for the coronavirus disease 2019, a podcast wrongly asserted that the antiparasitic medication offered a cancer cure.</p><p>Experts have long warned of the noxious effects of online misinformation aimed at swaying elections and public opinion. The swirl of misinformation around cancer treatment and prevention may be less well studied, but researchers have begun raising alarms about the considerable harm that can come from advice that is, in some cases, literally toxic.</p><p>Skyler Johnson, MD, an assistant professor of radiation oncology at the University of Utah’s Huntsman Cancer Institute in Salt Lake City, experienced the phenomenon firsthand when his wife was diagnosed with cancer in 2011 while he was still in medical school. The couple encountered so many fact-free claims and false assertions online that Dr Johnson decided to study the effects of this flood of bad advice. Even after his wife was declared cancer-free, he realized that such misinformation, even from well-meaning friends and relatives, can lead to serious and avoidable harm.</p><p>Most disturbingly, he discovered, it can kill. In a highly cited study, Dr Johnson and his colleagues found that patients who relied entirely on unproven alternative cancer therapies were significantly more likely to die within 5 years than patients who used conventional treatments, such as chemotherapy, radiation, immunotherapy, and surgery.<span><sup>1</sup></span> For a subset of patients with breast or colorectal cancer who used alternative medicine, the mortality risk jumped roughly 5-fold. No matter how advanced cancer treatments might be, he says, “if patients aren’t willing to take those treatments, then we’ve done no good.”</p><p>When she read Dr Johnson’s study, Briony Swire-Thompson, PhD, director of the Psychology of Misinformation Lab in the Network Science Institute at Northeastern University in Boston, Massachusetts, had an epiphany. The cognitive psychologist had previously studied general and political misinformation, but she immediately understood the unique challenge posed by cancer misinformation. “That was, I think, an aha moment where I realized this is a topic where belief really has impact in people’s lives,” she says.</p><p>Dr Swire-Thompson characterizes <i>misinformation</i> as an umbrella term for all false information and <i>disinformation</i> as a subset of false information that is spread deliberately. The high anxiety accompanying a cancer diagnosis, coupled with cognitive fatigue and the fear of side effects from chemotherapy, radiation, or surgery, she notes, can make a patient more susceptible to a huckster trying to capitalize financially. “People are wi","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 10","pages":"603-604"},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng-Chieh Chen MSc, Shou-Cheng Lu MSc, Yu-Kang Chang PhD, Chyi-Huey Bai PhD, Ke-Yu Hsiao MSc, Kang-Yun Lee MD, PhD, Yuan-Hung Wang PhD
Background
Lung cancer is the leading cause of cancer-related mortality worldwide. Screening high-risk populations for lung cancer with low-dose computed tomography (LDCT) reduces lung cancer mortality. Bronchoscopy is a diagnostic procedure used to monitor patients suspected of having lung cancer after LDCT. Rapid on-site evaluation (ROSE) can improve the diagnostic accuracy of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA), although its diagnostic value remains unclear. In this meta-analysis, the authors evaluated the diagnostic accuracy of ROSE during bronchoscopy.
Methods
The PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the diagnostic accuracy of ROSE for lung cancer during bronchoscopy. Studies evaluating the performance of ROSE and articles providing sufficient data for constructing a 2 × 2 table on a per-lesion basis were included. A meta-analysis was conducted using a bivariate random-effects model.
Results
In total, 32 studies involving 8243 lung lesions were included with a pooled sensitivity of 91.8% and a pooled specificity of 94.9%. Subgroup analysis of 12 studies involving 2929 specimens from patients who underwent computed tomography revealed a pooled sensitivity of 93.8% and a pooled specificity of 96%. Further subgroup analysis of seven studies on the diagnostic outcomes of ROSE for intrathoracic or mediastinal lymph nodes through EBUS-TBNA for lung cancer staging revealed a pooled sensitivity of 90.1% and a pooled specificity of 96.9%.
Conclusions
ROSE exhibited high sensitivity and specificity for diagnosing lung cancer during bronchoscopy. It also exhibited high sensitivity in detecting lung cancer in patients undergoing LDCT and higher specificity for nodal staging with EBUS-TBNA.
肺癌是全球癌症相关死亡的首要原因。使用低剂量计算机断层扫描（LDCT）对高风险人群进行肺癌筛查可降低肺癌死亡率。支气管镜检查是用于监测低剂量计算机断层扫描后疑似肺癌患者的诊断程序。快速现场评估（ROSE）可提高支气管内超声引导下经支气管针吸术（EBUS-TBNA）的诊断准确性，但其诊断价值仍不明确。在这项荟萃分析中，作者评估了支气管镜检查期间 ROSE 的诊断准确性。
{"title":"Diagnostic performance of rapid on-site evaluation during bronchoscopy for lung cancer: A comprehensive meta-analysis","authors":"Cheng-Chieh Chen MSc, Shou-Cheng Lu MSc, Yu-Kang Chang PhD, Chyi-Huey Bai PhD, Ke-Yu Hsiao MSc, Kang-Yun Lee MD, PhD, Yuan-Hung Wang PhD","doi":"10.1002/cncy.22908","DOIUrl":"10.1002/cncy.22908","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung cancer is the leading cause of cancer-related mortality worldwide. Screening high-risk populations for lung cancer with low-dose computed tomography (LDCT) reduces lung cancer mortality. Bronchoscopy is a diagnostic procedure used to monitor patients suspected of having lung cancer after LDCT. Rapid on-site evaluation (ROSE) can improve the diagnostic accuracy of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA), although its diagnostic value remains unclear. In this meta-analysis, the authors evaluated the diagnostic accuracy of ROSE during bronchoscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the diagnostic accuracy of ROSE for lung cancer during bronchoscopy. Studies evaluating the performance of ROSE and articles providing sufficient data for constructing a 2 × 2 table on a per-lesion basis were included. A meta-analysis was conducted using a bivariate random-effects model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 32 studies involving 8243 lung lesions were included with a pooled sensitivity of 91.8% and a pooled specificity of 94.9%. Subgroup analysis of 12 studies involving 2929 specimens from patients who underwent computed tomography revealed a pooled sensitivity of 93.8% and a pooled specificity of 96%. Further subgroup analysis of seven studies on the diagnostic outcomes of ROSE for intrathoracic or mediastinal lymph nodes through EBUS-TBNA for lung cancer staging revealed a pooled sensitivity of 90.1% and a pooled specificity of 96.9%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ROSE exhibited high sensitivity and specificity for diagnosing lung cancer during bronchoscopy. It also exhibited high sensitivity in detecting lung cancer in patients undergoing LDCT and higher specificity for nodal staging with EBUS-TBNA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen-Yu Hsiao MD, PhD, Nabil F. Saba MD, Daniel Lubin MD, Amy Chen MD, Qiuying Shi MD, MS
Background
ThyroSeq offers the opportunity to stratify the risk of malignancy (ROM) in the characterization of indeterminate thyroid nodules, especially those categorized as atypia of undetermined significance (AUS). However, whether ThyroSeq interpretations correlate with cytologic features, management, and surgical outcome remains unclear.
Methods
Thyroid fine-needle aspiration specimens categorized as AUS and follicular neoplasm (FN) from 2017 to 2021 were identified from a cytology database search. Patient clinical information and ThyroSeq results were collected and correlated with resection diagnosis if available.
Results
A total of 520 cases were classified as AUS and 111 cases were classified as FN. Within the AUS lesions, 190 cases (36.5%) were subcategorized as cytologic atypia (III-C), 109 cases (21.0%) as architectural atypia (III-A), 138 cases (26.5%) as both cytologic and architectural atypia (III-CA), and 69 cases (13.0%) as oncocytic cell aspirate (III-O). Category III-C showed the highest malignancy rate (16.7%; p = .29), and a higher ThyroSeq-defined probability of cancer or noninvasive follicular thyroid neoplasms with papillary-like nuclear features. Notably, within III-C, intermediate-risk mutations led to a significantly higher malignancy rate (46.7%; p = .0012). Conversely, III-A had the lowest malignancy rate (9.7%) but this was significantly increased by concurrent high-risk mutations (62.5%). BRAFV600E-like mutations were frequently associated with III-C and classical papillary thyroid carcinoma in histology. RAS-like mutations were the most common alterations across all subcategories, and were frequently associated with follicular-patterned lesions.
Conclusions
Atypia subcategories have differential ThyroSeq-defined ROMs and histologic outcomes. Combining atypia subcategory interpretation, ThyroSeq-defined ROMs and molecular results aids in optimal clinical management for indeterminate thyroid lesions.
{"title":"Risk stratification of ThyroSeq results in indeterminate thyroid lesions: A single-institution experience of clinicopathologic correlation with cytologic findings","authors":"Wen-Yu Hsiao MD, PhD, Nabil F. Saba MD, Daniel Lubin MD, Amy Chen MD, Qiuying Shi MD, MS","doi":"10.1002/cncy.22905","DOIUrl":"10.1002/cncy.22905","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>ThyroSeq offers the opportunity to stratify the risk of malignancy (ROM) in the characterization of indeterminate thyroid nodules, especially those categorized as atypia of undetermined significance (AUS). However, whether ThyroSeq interpretations correlate with cytologic features, management, and surgical outcome remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thyroid fine-needle aspiration specimens categorized as AUS and follicular neoplasm (FN) from 2017 to 2021 were identified from a cytology database search. Patient clinical information and ThyroSeq results were collected and correlated with resection diagnosis if available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 520 cases were classified as AUS and 111 cases were classified as FN. Within the AUS lesions, 190 cases (36.5%) were subcategorized as cytologic atypia (III-C), 109 cases (21.0%) as architectural atypia (III-A), 138 cases (26.5%) as both cytologic and architectural atypia (III-CA), and 69 cases (13.0%) as oncocytic cell aspirate (III-O). Category III-C showed the highest malignancy rate (16.7%; <i>p</i> = .29), and a higher ThyroSeq-defined probability of cancer or noninvasive follicular thyroid neoplasms with papillary-like nuclear features. Notably, within III-C, intermediate-risk mutations led to a significantly higher malignancy rate (46.7%; <i>p</i> = .0012). Conversely, III-A had the lowest malignancy rate (9.7%) but this was significantly increased by concurrent high-risk mutations (62.5%). <i>BRAF</i><sup><i>V600E</i></sup>-like mutations were frequently associated with III-C and classical papillary thyroid carcinoma in histology. <i>RAS</i>-like mutations were the most common alterations across all subcategories, and were frequently associated with follicular-patterned lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Atypia subcategories have differential ThyroSeq-defined ROMs and histologic outcomes. Combining atypia subcategory interpretation, ThyroSeq-defined ROMs and molecular results aids in optimal clinical management for indeterminate thyroid lesions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Writing our way through academia: Our journey as young faculty and book authors","authors":"Terrance James Lynn MD, Swikrity U. Baskota MD","doi":"10.1002/cncy.22902","DOIUrl":"10.1002/cncy.22902","url":null,"abstract":"","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trichorhinophalangeal syndrome 1 (TRPS1) expression in primary breast and other solid tumors has been investigated but its role as a marker in metastatic tumors is unclear. The objective of this study was to evaluate the sensitivity and specificity of TRPS1 as a breast cancer immunomarker in metastatic tumors that originated from breast, Müllerian, lung, gastrointestinal (GI), and pancreatic primary tumors with cell blocks from fine-needle aspiration (FNA) and effusion specimens.
Methods
Cell blocks were immunostained with anti-TRPS1 monoclonal antibody (clone EPR16171). Histochemical scores (H scores) (proportion × intensity; range, 0–300) were assigned; H scores of ≥10 were considered positive. Overall, 160 specimens were examined, including 127 FNAs (35 breast, 25 Müllerian, 36 lung, and 31 GI and pancreatic carcinomas) and 33 effusion specimens (18 breast, 12 Müllerian, one lung, and two GI carcinomas).
Results
TRPS1 was positive in 51 of 53 (96%) metastatic breast carcinomas and in 28 of 107 (26.2%) nonbreast metastatic tumors. Metastatic breast carcinoma showed the highest mean H score of 247.35, compared to 45.36 in Müllerian, 8.4 in lung, and 5.88 in GI tumors. The sensitivity and specificity of TRPS1 for identifying a breast origin in metastatic tumors was 96.22% and 72.89%, respectively.
Conclusions
Despite high overall sensitivity, TRPS1 showed lower specificity as a breast immunomarker because of its expression in nonbreast tumors. The mean H score in nonbreast tumors was significantly lower than in metastatic breast tumors. It is important to recognize the broad range of expression of TRPS1 in metastatic breast and nonbreast tumors to avoid an incorrect determination of a metastatic tumor’s organ of origin.
{"title":"Trichorhinophalangeal syndrome 1 expression in breast and nonbreast metastases from Müllerian, lung, gastrointestinal tract, and pancreatic primary tumors by immunohistochemistry with cytology cell block specimens","authors":"Deepak Donthi MD, MPH, Qiong Gan MD, PhD, Qing Qing Ding MD, PhD, Savitri Krishnamurthy MD","doi":"10.1002/cncy.22901","DOIUrl":"10.1002/cncy.22901","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Trichorhinophalangeal syndrome 1 (TRPS1) expression in primary breast and other solid tumors has been investigated but its role as a marker in metastatic tumors is unclear. The objective of this study was to evaluate the sensitivity and specificity of TRPS1 as a breast cancer immunomarker in metastatic tumors that originated from breast, Müllerian, lung, gastrointestinal (GI), and pancreatic primary tumors with cell blocks from fine-needle aspiration (FNA) and effusion specimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cell blocks were immunostained with anti-TRPS1 monoclonal antibody (clone EPR16171). Histochemical scores (H scores) (proportion × intensity; range, 0–300) were assigned; H scores of ≥10 were considered positive. Overall, 160 specimens were examined, including 127 FNAs (35 breast, 25 Müllerian, 36 lung, and 31 GI and pancreatic carcinomas) and 33 effusion specimens (18 breast, 12 Müllerian, one lung, and two GI carcinomas).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TRPS1 was positive in 51 of 53 (96%) metastatic breast carcinomas and in 28 of 107 (26.2%) nonbreast metastatic tumors. Metastatic breast carcinoma showed the highest mean H score of 247.35, compared to 45.36 in Müllerian, 8.4 in lung, and 5.88 in GI tumors. The sensitivity and specificity of TRPS1 for identifying a breast origin in metastatic tumors was 96.22% and 72.89%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite high overall sensitivity, TRPS1 showed lower specificity as a breast immunomarker because of its expression in nonbreast tumors. The mean H score in nonbreast tumors was significantly lower than in metastatic breast tumors. It is important to recognize the broad range of expression of TRPS1 in metastatic breast and nonbreast tumors to avoid an incorrect determination of a metastatic tumor’s organ of origin.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"132 12","pages":"799-808"},"PeriodicalIF":2.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Starr MD, Youley Tjendra MD, Jaylou M. Velez Torres MD, Carmen Gomez-Fernandez MD, Samer N. Khader MD, Esra Karslioglu-French MD, Linwah Yip MD, Sally E. Carty MD, John M. Skaugen MD, Yuri E. Nikiforov MD, PhD, Raja R. Seethala MD, N. Paul Ohori MD
Introduction
Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined.
Materials and Methods
Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant.
Results
The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0–81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic–histologic correlation revealed malignant outcome in 88.5% of resected cases.
Conclusions
Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.
导言：甲状腺细胞病理学病例被诊断为可疑恶性肿瘤（SFM）后，通常会进行切除手术。然而，分子检测提供的细节可能会带来更多的启示。本研究对两家常规使用ThyroSeq v3（TSV3）的机构的SFM病例的分子图谱进行了研究。材料与方法经机构审查委员会批准后，从两家机构的数据库中检索了有TSV3结果的SFM甲状腺细胞病理学病例。计算包括恶性肿瘤分子衍生风险（MDROM）在内的分子信息、细胞学与组织学相关数据以及其他相关参数。结果核心数据集包括 114 个通过 TSV3 质量保证的 SFM 病例。所有 TSV3 结果均报告为基因组改变的阳性或阴性，除 5 例病例外，其他病例均提供了恶性肿瘤的概率估计。总体合并基线 MDROM 为 75.7%（95% CI，70.0-81.4），与 Bethesda 系统公布的恶性肿瘤风险（74%）相当。切除组和未切除组的合并 MDROMs 有显著统计学差异（79.0% vs 58.6%; p = .0153）。有趣的是，两家机构切除组的 MDROMs 也有统计学差异（75.0% vs 85.3%; p = .020）。细胞学-组织学相关性显示，88.5%的切除病例有恶性结果。结论 对SFM病例的分子分析表明，高风险基因组改变与组织学上明显的肿瘤相关，导致恶性结果较基线增加。MDROM分析表明，两家机构对滤泡型肿瘤的细胞病理学实践模式存在差异。
{"title":"Parsing the thyroid cytopathology suspicious for malignancy diagnosis through molecular-derived risk of malignancy and other related parameters: Insights into nodule characteristics and practice patterns","authors":"David Starr MD, Youley Tjendra MD, Jaylou M. Velez Torres MD, Carmen Gomez-Fernandez MD, Samer N. Khader MD, Esra Karslioglu-French MD, Linwah Yip MD, Sally E. Carty MD, John M. Skaugen MD, Yuri E. Nikiforov MD, PhD, Raja R. Seethala MD, N. Paul Ohori MD","doi":"10.1002/cncy.22904","DOIUrl":"10.1002/cncy.22904","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a <i>p</i> <.05 considered significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0–81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; <i>p</i> = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; <i>p</i> = .020). Cytologic–histologic correlation revealed malignant outcome in 88.5% of resected cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.22904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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