{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:52:02Z","timestamp":1791805922527,"version":"4.3.4"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Datta Meghe Institute of Higher Education and Research"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>The primary objective was to evaluate and compare the sensitivity and specificity of CD34 immunohistochemistry (IHC) versus conventional hematoxylin and eosin (H&amp;E) staining in detecting lymphovascular emboli (LVE) in oral squamous cell carcinoma (OSCC). The secondary objective was to correlate LVE detection with tumor size, grade, perineural invasion (PNI), depth of invasion (DOI), worst pattern of invasion (WPOI), and lymph node involvement, with or without extranodal extension (ENE).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methodology<\/jats:title>\n            <jats:p>A retrospective, cross-sectional comparative analysis based on archival cases from the period of January 2021 to December 2023, in pathology department in a tertiary care hospital in central India. A total of 93 patients diagnosed with OSCC were included. All cases had available formalin-fixed, paraffin-embedded (FFPE) tissue blocks. Inclusion criteria: histologically confirmed OSCC with adequate archived material from all age groups of both sexes. Exclusion criteria: non-oral head and neck malignancies and inadequate tissue blocks.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A total of 21 cases with LVE were detected. All these LVE were identified by CD34 immunohistochemistry, out of which, 20 cases were also detected by H&amp;E stain. CD34 identified only one additional case of LVE as compared to H&amp;E stain. The difference was not statistically significant (Chi-square\u2009=\u20090.03, <jats:italic>p<\/jats:italic>\u2009=\u20090.86). Significant correlations were observed between LVE and lymph node involvement (<jats:italic>p<\/jats:italic>\u2009=\u20090.0008), tumor grade (<jats:italic>p<\/jats:italic>\u2009=\u20090.0007), perineural invasion (<jats:italic>p<\/jats:italic>\u2009=\u20090.00006), depth of invasion (<jats:italic>p<\/jats:italic>\u2009=\u20090.0004), and WPOI (<jats:italic>p<\/jats:italic>\u2009=\u20090.00001). No significant correlation of the LVE was found with tumor size (<jats:italic>p<\/jats:italic>\u2009=\u20090.1005) or ENE (<jats:italic>p<\/jats:italic>\u2009=\u20090.19).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>CD34 IHC does not significantly improve detection of LVE over conventional H&amp;E staining in OSCC. However, LVE shows strong associations with several high-risk histopathological features, reaffirming its prognostic importance. In a properly processed sample with competent histopathologists, the routine use of CD34 may not be necessary for detecting LVE in cases of OSCC.<\/jats:p>\n            <jats:p>\n              <jats:italic>Trial registration<\/jats:italic>: This study is registered with the Clinical Trials Registry of India (ICMR-NIMS). The registration number is CTRI\/2024\/04\/065233.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s12672-025-03633-6","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T12:18:05Z","timestamp":1759234685000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative evaluation of CD34 immunohistochemistry and hematoxylin and eosin staining for detection of lymphovascular emboli in oral squamous cell carcinoma: a retrospective cross-sectional study in a developing country"],"prefix":"10.1007","volume":"16","author":[{"given":"Kajal","family":"Hatgaonkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Hatgaonkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratibha","family":"Dawande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Sonkusale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"3633_CR1","unstructured":"Mouth and oral cancer statistics. WCRF International. https:\/\/www.wcrf.org\/cancer-trends\/mouth-and-oral-cancer-statistics\/15.08.2024."},{"issue":"2","key":"3633_CR2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.pathol.2023.11.005","volume":"56","author":"S Balgobind","year":"2024","unstructured":"Balgobind S, Cheung VKY, Luk P, Low THH, Wykes J, Wu R, et al. Prognostic and predictive biomarkers in head and neck cancer: something old, something new, something borrowed, something blue and a sixpence in your shoe. Pathology. 2024;56(2):170\u201385.","journal-title":"Pathology"},{"key":"3633_CR3","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.4103\/0019-509X.278971","volume":"57","author":"K Prabhash","year":"2020","unstructured":"Prabhash K, Babu G, Chaturvedi P, Kuriakose M, Birur P, Anand AK, et al. Indian clinical practice consensus guidelines for the management of squamous cell carcinoma of head and neck. Indian J Cancer. 2020;57:S1\u20135.","journal-title":"Indian J Cancer"},{"key":"3633_CR4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1758-3284-2-9","volume":"2","author":"W Jerjes","year":"2010","unstructured":"Jerjes W, Upile T, Petrie A, Riskalla A, Hamdoon Z, Vourvachis M, Karavidas K, Jay A, Sandison A, Thomas GJ, Kalavrezos N, Hopper C. Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol. 2010;2:9. https:\/\/doi.org\/10.1186\/1758-3284-2-9.","journal-title":"Head Neck Oncol"},{"key":"3633_CR5","doi-asserted-by":"publisher","first-page":"106387","DOI":"10.1016\/j.oraloncology.2023.106387","volume":"140","author":"J Comer","year":"2023","unstructured":"Comer J, Harris A, Hess A, Hitchcock K, Mendenhall W, Bates J, Dziegielewski P. Does lymphovascular invasion predict survival in oral cancer? A population-based analysis. Oral Oncol. 2023;140:106387. https:\/\/doi.org\/10.1016\/j.oraloncology.2023.106387.","journal-title":"Oral Oncol"},{"key":"3633_CR6","unstructured":"American Joint Committee on Cancer. ACS. 2023. http:\/\/www.cancerstaging.org. Accessed 20 Apr 2025."},{"key":"3633_CR7","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.jcrt_2720_22","author":"NM Gangane","year":"2024","unstructured":"Gangane NM, Ghongade PV, Patil BU, Manisha Atram. Oral cavity cancer incidence and survival trends: A population-based study. J Cancer Res Ther. 2024. https:\/\/doi.org\/10.4103\/jcrt.jcrt_2720_22.","journal-title":"J Cancer Res Ther"},{"key":"3633_CR8","doi-asserted-by":"publisher","first-page":"3905","DOI":"10.3390\/cancers15153905","volume":"15","author":"A Tan","year":"2023","unstructured":"Tan A, Taskin T. Tumor budding should be in oral cavity cancer reporting: A retrospective cohort study based on tumor microenvironment. Cancers. 2023;15:3905. https:\/\/doi.org\/10.3390\/cancers15153905.","journal-title":"Cancers"},{"issue":"4","key":"3633_CR9","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1001\/jamaoto.2016.3795","volume":"143","author":"R Cassidy","year":"2017","unstructured":"Cassidy R, Switchenko J, Jegadeesh N, et al. Association of lymphovascular space invasion with locoregional failure and survival in patients with Node-Negative oral tongue cancers. JAMA Otolaryngol Head Neck Surg. 2017;143(4):382\u20138. https:\/\/doi.org\/10.1001\/jamaoto.2016.3795.","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"key":"3633_CR10","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.4103\/crst.crst_119_23","volume":"7","author":"P Chaturvedi","year":"2024","unstructured":"Chaturvedi P, Prabhash K, Babu KG, Kuriakose M, Birur P, Anand AK, et al. Indian clinical practice consensus guidelines for the management of oral cavity cancer: update 2022. Cancer Res Stat Treat. 2024;7:S6\u201311. https:\/\/doi.org\/10.4103\/crst.crst_119_23.","journal-title":"Cancer Res Stat Treat"},{"issue":"3","key":"3633_CR11","doi-asserted-by":"publisher","first-page":"e238","DOI":"10.4317\/medoral.25114","volume":"27","author":"AP Alves","year":"2022","unstructured":"Alves AP, Paula DS, Lima LV, Dantas TS, Mota MR, Sousa FB, Silva PG. Is immunohistochemistry more sensitive than hematoxylin-eosin staining for identifying perineural or lymphovascular invasion in oral squamous cell carcinoma? A systematic review and meta-analysis. Med Oral Patol Oral Cir Bucal. 2022;27(3):e238\u201347. https:\/\/doi.org\/10.4317\/medoral.25114.","journal-title":"Med Oral Patol Oral Cir Bucal"},{"issue":"9","key":"3633_CR12","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1369\/jhc.2008.950790","volume":"56","author":"RK O\u2019Donnell","year":"2008","unstructured":"O\u2019Donnell RK, Feldman M, Mick R, Muschel RJ. Immunohistochemical method identifies lymphovascular invasion in a majority of oral squamous cell carcinomas and discriminates between blood and lymphatic vessel invasion. J Histochem Cytochem. 2008;56(9):803\u201310. https:\/\/doi.org\/10.1369\/jhc.2008.950790.","journal-title":"J Histochem Cytochem"},{"issue":"1","key":"3633_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijom.2021.03.007","volume":"51","author":"M Mascitti","year":"2022","unstructured":"Mascitti M, Togni L, Caponio VCA, Zhurakivska K, Bizzoca ME, Contaldo M, et al. Lymphovascular invasion as a prognostic tool for oral squamous cell carcinoma: a comprehensive review. Int J Oral Maxillofac Surg. 2022;51(1):1\u20139. https:\/\/doi.org\/10.1016\/j.ijom.2021.03.007.","journal-title":"Int J Oral Maxillofac Surg"},{"key":"3633_CR14","doi-asserted-by":"publisher","first-page":"3828","DOI":"10.1038\/s41598-023-30939-8","volume":"13","author":"Q Huang","year":"2023","unstructured":"Huang Q, Huang Y, Chen C, et al. Prognostic impact of lymphovascular and perineural invasion in squamous cell carcinoma of the tongue. Sci Rep. 2023;13:3828. https:\/\/doi.org\/10.1038\/s41598-023-30939-8.","journal-title":"Sci Rep"},{"key":"3633_CR15","doi-asserted-by":"crossref","unstructured":"Huang S, Zhu Y, Cai H, Zhang Y, Hou J. Impact of lymphovascular invasion in oral squamous cell carcinoma: a meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;131(3):319-328.e1. doi.org\/10.1016\/j.0000.2020.10.026.","DOI":"10.1016\/j.oooo.2020.10.026"},{"issue":"1","key":"3633_CR16","doi-asserted-by":"publisher","first-page":"e52233","DOI":"10.7759\/cureus.52233","volume":"16","author":"SJ Khan","year":"2024","unstructured":"Khan SJ, Gawande M, Hande AH, Patil SK, Sonone AM. Correlation of pattern of invasion, stromal inflammation and lymphovascular invasion with histopathological grading in oral squamous cell carcinoma: A retrospective study. Cureus. 2024;16(1):e52233. https:\/\/doi.org\/10.7759\/cureus.52233.","journal-title":"Cureus"},{"issue":"2","key":"3633_CR17","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1007\/s12105-023-01531-3","volume":"17","author":"M Yasuda","year":"2023","unstructured":"Yasuda M, Chiodo C, Lilley C, Mehrotra S, Ananthanarayanan V, Ziegler A, Thorpe E. Relationship between worst pattern of invasion and extranodal extension in oral tongue squamous cell carcinomas. Head Neck Pathol. 2023;17(2):460\u20136. https:\/\/doi.org\/10.1007\/s12105-023-01531-3.","journal-title":"Head Neck Pathol"},{"issue":"3","key":"3633_CR18","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1177\/00034894231211116","volume":"133","author":"AE Moore","year":"2024","unstructured":"Moore AE, Alvi SA, Tarabichi O, Zhu VL, Buchakjian MR. Role of lymphovascular invasion in oral cavity squamous cell carcinoma regional metastasis and prognosis. Annals of otology. Rhinology Laryngology. 2024;133(3):300\u20136. https:\/\/doi.org\/10.1177\/00034894231211116.","journal-title":"Rhinology Laryngology"},{"key":"3633_CR19","doi-asserted-by":"publisher","unstructured":"Rahat M, Aslam Shahzad U, Ara N, Ud Din H, Parveen B, Khan N, Munir S, Mumtaz H. Worst pattern of invasion in oral squamous cell carcinoma: an independent prognostic indicator. J Oral Biol Craniofac Res 2025 May-Jun;15(3):638\u201344. https:\/\/doi.org\/10.1016\/j.jobcr.2024.12.008.","DOI":"10.1016\/j.jobcr.2024.12.008"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-03633-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-025-03633-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-025-03633-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T12:18:06Z","timestamp":1759234686000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-025-03633-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3633"],"URL":"https:\/\/doi.org\/10.1007\/s12672-025-03633-6","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,30]]},"assertion":[{"value":"6 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors confirm that the study was approved by the institutional research ethics committee- DMIHER(DU) via letter number DMIHER(DU)\/2024\/105 and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The authors affirm that informed consent was obtained from all individual to participate in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors affirm that informed consent was obtained from all individual for publication of their data and histological images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1793"}}