{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:15:27Z","timestamp":1790187327259,"version":"4.1.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Bari Aldo Moro"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diffuse Large B-Cell Lymphoma (DLBCL) presents a high clinical and biological heterogeneity, and the tumor microenvironment chracteristics are important in its\u00a0 progression. The aim of this study was to evaluate tumor T, B cells, macrophages and mast cells distribution in GBC and ABC DLBCL subgroups\u00a0through a set of morphometric parameters allowing to provide a quantitative evaluation of the morphological features of the spatial patterns generated by these inflammatory cells. \u00a0 Histological ABC and GCB samples were immunostained for CD4, CD8, CD68, CD 163, and tryptase in order to determine both percentage and position of positive cells in the tissue characterizing their spatial distribution. The results evidenced that cell patterns generated by CD4-, CD8-, CD68-,\u00a0CD163- and tryptase-positive cell profiles exhibited a significantly higher uniformity index in ABC than in GCB\u00a0subgroup. The positive-cell distributions appeared clustered in tissues from GCB, while in tissues from ABC such a feature was lower or absent. The combinations of spatial statistics-derived parameters can lead to better predictions of tumor cell infiltration than any classical morphometric method providing a more accurate description of the functional status of the tumor, useful for patient prognosis.<\/jats:p>","DOI":"10.1007\/s10238-021-00716-w","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T21:04:49Z","timestamp":1620335089000},"page":"573-578","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Different spatial distribution of inflammatory cells in the tumor microenvironment of ABC and GBC subgroups of diffuse large B cell lymphoma"],"prefix":"10.1007","volume":"21","author":[{"given":"Diego","family":"Guidolin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Tamma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Annese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Tortorella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ingravallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Gaudio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommasina","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pellegrino","family":"Musto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgina","family":"Specchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4768-8431","authenticated-orcid":false,"given":"Domenico","family":"Ribatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"716_CR1","doi-asserted-by":"publisher","first-page":"5019","DOI":"10.1182\/blood-2011-01-293050","volume":"117","author":"E Campo","year":"2011","unstructured":"Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117:5019\u201332.","journal-title":"Blood"},{"key":"716_CR2","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.critrevonc.2012.12.009","volume":"87","author":"M Martelli","year":"2013","unstructured":"Martelli M, Ferreri AJM, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA. Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol. 2013;87:146\u201371.","journal-title":"Crit Rev Oncol Hematol"},{"key":"716_CR3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1053\/j.semdp.2011.04.001","volume":"28","author":"C Schneider","year":"2011","unstructured":"Schneider C, Pasqualucci L, Dalla-Favera R. Molecular pathogenesis of diffuse large B-cell lymphoma. Sem Diagnos Pathol. 2011;28:167\u201377.","journal-title":"Sem Diagnos Pathol"},{"key":"716_CR4","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/nature07968","volume":"459","author":"M Compagno","year":"2009","unstructured":"Compagno M, Lim WK, Grunn A, et al. Mutations of multiple genes cause deregulation of NF-\u03baB in diffuse large B-cell lymphoma. Nature. 2009;459:717\u201321.","journal-title":"Nature"},{"key":"716_CR5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/ng.518","volume":"42","author":"RD Morin","year":"2010","unstructured":"Morin RD, Johnson NA, Severson TM, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42:181\u20135.","journal-title":"Nat Genet"},{"key":"716_CR6","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1056\/NEJMoa012914","volume":"346","author":"A Rosenwald","year":"2002","unstructured":"Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937\u201347.","journal-title":"N Engl J Med"},{"key":"716_CR7","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.tranon.2018.12.008","volume":"12","author":"R Tamma","year":"2019","unstructured":"Tamma R, Ingravallo G, Albano F, et al. STAT-3 RNAscope determination in human diffuse large B-cell lymphoma. Transl Oncol. 2019;12:545\u20139.","journal-title":"Transl Oncol"},{"key":"716_CR8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nri1995","volume":"7","author":"H Yu","year":"2007","unstructured":"Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007;7:41\u201351.","journal-title":"Nat Rev Immunol"},{"key":"716_CR9","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1080\/10428194.2019.1678154","volume":"61","author":"R Tamma","year":"2019","unstructured":"Tamma R, Ingravallo G, Gaudio F, et al. STAT3, tumor microenvironment, and microvessel density in diffuse large B cell lymphomas. Leuk Lymphoma. 2019;61:567\u201374.","journal-title":"Leuk Lymphoma"},{"key":"716_CR10","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH image to imageJ: 25 years of image analysis. Nat Methods. 2012;9:671\u20135.","journal-title":"Nat Methods"},{"key":"716_CR11","first-page":"85","volume":"11","author":"AC Ruifrok","year":"2003","unstructured":"Ruifrok AC, Katz RL, Johnston DA. Comparison of quantification of histochemical staining by hue-saturation-intensity (HSI) transformation and color-deconvolution. Appl Immunohistochem Mol Morphol. 2003;11:85\u201391.","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"716_CR12","first-page":"6","volume-title":"The image processing handbook","author":"J Russ","year":"2011","unstructured":"Russ J. The image processing handbook. Boca Raton: Taylor & Francis; 2011. p. 6."},{"key":"716_CR13","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.canlet.2008.07.032","volume":"273","author":"D Guidolin","year":"2009","unstructured":"Guidolin D, Nico B, Crivellato E, Marzullo A, Vacca A, Ribatti D. Tumoral mast cells exhibit a common spatial distribution. Cancer Lett. 2009;273:80\u20135.","journal-title":"Cancer Lett"},{"key":"716_CR14","first-page":"67","volume-title":"Methods in molecular biology","author":"D Guidolin","year":"2020","unstructured":"Guidolin D, Tortorella C, Ribatti D. Spatial statistics-based image analysis methods for the study of vascular morphogenesis. In: Ribatti D, editor. Methods in molecular biology. New York: Springer, US; 2020. p. 67\u201388."},{"key":"716_CR15","volume-title":"Spatial statistics. Wiley series in probability and statistics","author":"BD Ripley","year":"1981","unstructured":"Ripley BD. Spatial statistics. Wiley series in probability and statistics. Hoboken: Wiley; 1981."},{"key":"716_CR16","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1007\/s12032-011-0123-6","volume":"29","author":"Q-c Cai","year":"2011","unstructured":"Cai Q-c, Liao H, Lin SX, et al. High expression of tumor-infiltrating macrophages correlates with poor prognosis in patients with diffuse large B-cell lymphoma. Med Oncol. 2011;29:2317\u201322.","journal-title":"Med Oncol"},{"key":"716_CR17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/j.1365-2141.2007.06612.x","volume":"138","author":"G Hedstr\u00f6m","year":"2007","unstructured":"Hedstr\u00f6m G, Berglund M, Molin D, et al. Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell lymphoma. Br J Haematol. 2007;138:68\u201371.","journal-title":"Br J Haematol"},{"key":"716_CR18","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1016\/j.leukres.2014.09.007","volume":"38","author":"C Marinaccio","year":"2014","unstructured":"Marinaccio C, Ingravallo G, Gaudio F, et al. Microvascular density, CD68 and tryptase expression in human Diffuse Large B-Cell Lymphoma. Leu Res. 2014;38:1374\u20137.","journal-title":"Leu Res"},{"key":"716_CR19","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/(SICI)1097-0215(20000115)85:2%3C171::AID-IJC4%3E3.0.CO;2-W","volume":"85","author":"D Ribatti","year":"2000","unstructured":"Ribatti D, Vacca A, Marzullo A, et al. Angiogenesis and mast cell density with tryptase activity increase simultaneously with pathological progression in B-cell non-Hodgkin\u2019s lymphomas. Int J Cancer. 2000;85:171\u20135.","journal-title":"Int J Cancer"},{"key":"716_CR20","doi-asserted-by":"crossref","unstructured":"Ben Youssef B. Visualization of spatial patterns of cells using a 3-D simulation model for multicellular tissue growth. 2014 International conference on multimedia computing and systems (ICMCS): IEEE, 2014.","DOI":"10.1109\/ICMCS.2014.6911255"},{"key":"716_CR21","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.bpj.2009.03.067","volume":"97","author":"G Cheng","year":"2009","unstructured":"Cheng G, Markenscoff P, Zygourakis K. A 3D hybrid model for tissue growth: the interplay between cell population and mass transport dynamics. Biophys J. 2009;97:401\u201314.","journal-title":"Biophys J"},{"key":"716_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-8-140","author":"M Tambasco","year":"2010","unstructured":"Tambasco M, Eliasziw M, Magliocco AM. Morphologic complexity of epithelial architecture for predicting invasive breast cancer survival. J Transl Med. 2010. https:\/\/doi.org\/10.1186\/1479-5876-8-140.","journal-title":"J Transl Med"},{"key":"716_CR23","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/1952","volume":"4","author":"JW Baish","year":"1998","unstructured":"Baish JW, Jain RK. Cancer, angiogenesis and fractals. Nat Med. 1998;4:984\u2013984.","journal-title":"Nat Med"},{"key":"716_CR24","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/path.5310","volume":"249","author":"R Colling","year":"2019","unstructured":"Colling R, Pitman H, Oien K, et al. Artificial intelligence in digital pathology: a roadmap to routine use in clinical practice. J Pathol. 2019;249:143\u201350.","journal-title":"J Pathol"},{"key":"716_CR25","doi-asserted-by":"crossref","unstructured":"Pham B, Gaonkar B, Whitehead W, et al. Cell counting and segmentation of immunohistochemical images in the spinal cord: comparing deep learning and traditional approaches. 2018 40th annual international conference of the IEEE engineering in medicine and biology society (EMBC): IEEE, 2018.","DOI":"10.1109\/EMBC.2018.8512442"},{"key":"716_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15798-4","author":"S Blom","year":"2017","unstructured":"Blom S, Paavolainen L, Bychkov D, et al. Systems pathology by multiplexed immunohistochemistry and whole-slide digital image analysis. Sci Rep. 2017. https:\/\/doi.org\/10.1038\/s41598-017-15798-4.","journal-title":"Sci Rep"},{"key":"716_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75180-9","author":"JA Bull","year":"2020","unstructured":"Bull JA, Macklin PS, Quaiser T, et al. Combining multiple spatial statistics enhances the description of immune cell localisation within tumours. Sci Rep. 2020. https:\/\/doi.org\/10.1038\/s41598-020-75180-9.","journal-title":"Sci Rep"},{"key":"716_CR28","volume-title":"Image analysis and mathematical morphology","author":"J Serra","year":"1981","unstructured":"Serra J. Image analysis and mathematical morphology. London: Academic Press; 1981."}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-021-00716-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-021-00716-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-021-00716-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T11:24:34Z","timestamp":1633951474000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-021-00716-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["716"],"URL":"https:\/\/doi.org\/10.1007\/s10238-021-00716-w","relation":{},"ISSN":["1591-8890","1591-9528"],"issn-type":[{"value":"1591-8890","type":"print"},{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,6]]},"assertion":[{"value":"17 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2021","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 declared no potential conflicts of interest with respect to the research, authorship and\/or publication of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}