{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:10:29Z","timestamp":1768327829809,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovations of the Republic of Serbia","award":["451-03-137\/2025-03\/200113"],"award-info":[{"award-number":["451-03-137\/2025-03\/200113"]}]},{"name":"Faculty of Medicine in Ni\u0161","award":["INT-MFN no. 38\/20"],"award-info":[{"award-number":["INT-MFN no. 38\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Basal cell carcinoma (BCC) is the most common skin carcinoma, mainly occurring in older individuals. The aim of this study was to document the immunohistochemical distribution of CD34 in different histopathological types of BCC, as well as in the peritumoral and uninvolved skin of biopsy samples. Materials and Methods: Excisional biopsies of skin BCCs were routinely processed into paraffin blocks, and microtome sections were stained immunohistochemically for CD34. Results: A consistent finding in skin samples containing BCC was the absence of CD34 in the following extravascular structures: neoplastic cells, epidermis and its derivatives (except for the cells of the isthmic part of the outer hair follicle sheath), fibroblast-like cells of BCC tumor stroma, as well as in the papillary dermis in the tumor region. Fibroblast-like cells of the tumor stroma were variably CD34 immunopositive only in the nodular type of BCC. In all examined biopsies, part of the dermis adjacent to the BCC tumor mass (juxtatumoral zone) was characterized by pronounced CD34 immunopositivity. In the transitional zone of peritumoral skin and in marginal skin, CD34-positive connective tissue cells were observed in the periadnexal dermis around: sebaceous gland lobules, the secretory coils of eccrine sweat glands, the pilosebaceous canal, as well as in the perimysium of the arrector pili muscle. Fibrocytes of fibrous sheaths encasing the isthmic part of hair follicles were CD34 negative, interposed between highly positive epithelial cells of the outer hair follicle sheath and the fibroblasts of the local reticular dermis. The transitional zone and uninvolved skin contained CD34-positive fibroblast-like cells situated between secondary bundles of reticular dermis, as well as CD34-positive cell processes within these bundles. Conclusions: The observed pattern of CD34 positivity within the examined regions shows a specific distribution, providing insight into the adaptive responses of the skin to the tumoral process.<\/jats:p>","DOI":"10.3390\/medicina62010158","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T11:42:58Z","timestamp":1768304578000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical Pattern of CD34 Distribution in Different Types of Basal Cell Carcinoma and in Peritumoral Skin"],"prefix":"10.3390","volume":"62","author":[{"given":"Vladimir","family":"Petrovic","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 81, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 81, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan R.","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 81, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nata\u0161a","family":"Vidovic","sequence":"additional","affiliation":[{"name":"Center for Pathology and Pathological Anatomy, University Clinical Centre Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 48, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6038-9340","authenticated-orcid":false,"given":"Tijana","family":"Dencic","sequence":"additional","affiliation":[{"name":"Center for Pathology and Pathological Anatomy, University Clinical Centre Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 48, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-7047","authenticated-orcid":false,"given":"Ilija","family":"Golubovic","sequence":"additional","affiliation":[{"name":"Clinic for Digestive Surgery, University Clinical Centre Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 48, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav","family":"Milic","sequence":"additional","affiliation":[{"name":"Department for Forensic Medicine, Faculty of Medicine, University of Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 81, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Antovic","sequence":"additional","affiliation":[{"name":"Department for Forensic Medicine, Faculty of Medicine, University of Ni\u0161, Boulevard of Dr Zoran \u0110in\u0111i\u0107 81, 18000 Ni\u0161, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40487-022-00201-8","article-title":"Basal cell carcinoma: A narrative review on contemporary diagnosis and management","volume":"10","author":"Naik","year":"2022","journal-title":"Rev. Oncol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Karampinis, E., Georgopoulou, K.E., Kampra, E., Zafiriou, E., Lallas, A., Lazaridou, E., Apalla, Z., Behera, B., and Errichetti, E. (2024). Clinical and dermoscopic patterns of basal cell carcinoma and its mimickers in skin of color: A practical summary. Medicina, 60.","DOI":"10.3390\/medicina60091386"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.det.2022.07.005","article-title":"Basal cell carcinoma","volume":"41","author":"Heath","year":"2023","journal-title":"Dermatol. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3098940","DOI":"10.1155\/2018\/3098940","article-title":"Basal cell carcinoma arises from interfollicular layer of epidermis","volume":"2018","author":"Tan","year":"2018","journal-title":"J. Oncol."},{"key":"ref_5","first-page":"e45052","article-title":"The burden of skin cancers in Saudi Arabia through 2011\u20132022","volume":"15","author":"AlOtaibi","year":"2023","journal-title":"Cureus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaad.2022.03.023","article-title":"Advanced basal cell carcinoma: What dermatologists need to know about diagnosis","volume":"86","author":"Krakowski","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","unstructured":"Damjanov, I., and Linder, J. (1996). Skin. Anderson\u2019s Pathology, Mosby."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.jaad.2016.06.020","article-title":"Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: A retrospective cohort study","volume":"75","author":"Goldenberg","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Radu, P., Zurzu, M., Paic, V., Bratucu, M., Garofil, D., Tigora, A., Georgescu, V., Prunoiu, V., Pasnicu, C., and Popa, F. (2023). CD34\u2014Structure, functions and relationship with cancer stem cells. Medicina, 59.","DOI":"10.3390\/medicina59050938"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00441-023-03811-4","article-title":"CD34 protein: Its expression and function in inflammation","volume":"393","author":"Rodrigues","year":"2023","journal-title":"Cell Tissue Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exphem.2020.05.004","article-title":"A sticky wicket: Defining molecular functions for CD34 in hematopoietic cells","volume":"86","author":"Hughes","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hassanpour, M., Salybekov, A.A., Kobayashi, S., and Asahara, T. (2023). CD34 positive cells as endothelial progenitor cells in biology and medicine. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1128134"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1159\/000452214","article-title":"Immunohistochemical heterogeneity of the endothelium of blood and lymphatic vessels in the developing human liver and in adulthood","volume":"203","year":"2017","journal-title":"Cells Tissues Organs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1001\/archderm.1994.01690050057008","article-title":"CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma","volume":"130","author":"Kirchmann","year":"1994","journal-title":"Arch. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1016\/j.bbagen.2012.07.002","article-title":"Biochemistry of epidermal stem cells","volume":"1830","author":"Eckert","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.25259\/IJDVL_468_2022","article-title":"Expression of Ber-EP4 and CD34 can distinguish clear-cell basal cell carcinoma from trichilemmoma: A case series","volume":"90","author":"Mitra","year":"2023","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/DAD.0000000000001117","article-title":"CD34 and BerEP4 are helpful to distinguish basaloid tricholemmoma from basal cell carcinoma","volume":"40","author":"Turnbull","year":"2018","journal-title":"Am. J. Dermatopathol."},{"key":"ref_18","first-page":"831","article-title":"CD34+ stromal cells\/fibroblasts\/fibrocytes\/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology","volume":"29","author":"Valladares","year":"2014","journal-title":"Histol. Histopathol."},{"key":"ref_19","unstructured":"Petrovi\u0107, V. (2015). Light Microscopic and Immunohistochemical Study of Tumor Stroma Organization in Different Histopathological Types of Human Cutaneous Basal Cell Carcinoma. [Ph.D. Thesis, University in Ni\u0161, Faculty of Medicine]."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1016\/j.ajpath.2016.06.020","article-title":"Altered dermal fibroblasts in systemic sclerosis display podoplanin and CD90","volume":"186","author":"Nazari","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4236\/ojpathology.2014.43018","article-title":"The role of Bcl-2, CD10 and CD34 expression in differentiation between basal cell carcinoma and trichoepithelioma","volume":"4","author":"Raheem","year":"2014","journal-title":"Open J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1001\/archderm.1991.04510010091009","article-title":"The human progenitor cell antigen (CD34) is localized on endothelial cells, dermal dendritic cells, and perifollicular cells in formalin-fixed normal skin, and on proliferating endothelial cells and stromal spindle-shaped cells in Kaposi\u2019s sarcoma","volume":"127","author":"Nickoloff","year":"1991","journal-title":"Arch. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1600-0560.1998.tb01770.x","article-title":"Diagnostic value of CD34 immunostaining in desmoplastic trichilemmoma","volume":"25","author":"Illueca","year":"1998","journal-title":"J. Cutan. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1600-0560.2008.01212.x","article-title":"CD34-reactive tumors of the skin: An updated review of an ever-growing list of lesions","volume":"36","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4999\/uhod.10044","article-title":"Histopathological characteristics may not be useful in the differential diagnosis between basal cell carcinoma and benign tumors of cutaneous appendages originating from hair follicle","volume":"21","author":"Sengul","year":"2011","journal-title":"Int. J. Hematol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/modpathol.2012.96","article-title":"Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: Evaluation using tissue microarray samples","volume":"25","author":"Tebcherani","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1016\/j.jtha.2023.07.005","article-title":"Cancer-associated fibroblasts promote venous thrombosis through podoplanin\/CLEC-2 interaction in podoplanin-negative lung cancer mouse model","volume":"21","author":"Shirai","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"ref_28","first-page":"838","article-title":"The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer","volume":"51","author":"Pan","year":"2022","journal-title":"Zhonghua Bing Li Xue Za Zhi"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00428-020-02909-2","article-title":"Clinicopathological features to distinguish malignant solitary fibrous tumors of the prostate from prostatic stromal tumors","volume":"478","author":"Xu","year":"2021","journal-title":"Virchows Arch."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1097\/PAS.0000000000002108","article-title":"Solitary fibrous tumor of the pancreas: Analysis of 9 cases with literature review","volume":"47","author":"Yavas","year":"2023","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/1759-7714.13248","article-title":"Prognostic impact of CD34 and SMA in cancer-associated fibroblasts in stage I\u2013III NSCLC","volume":"11","author":"Schulze","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Flores, L., Guti\u00e9rrez, R., Gonz\u00e1lez-G\u00f3mez, M., Garc\u00eda, M.P., D\u00edaz-Flores, L., Carrasco, J.L., and Mart\u00edn-Vasallo, P. (2021). CD34+ stromal cells\/telocytes as a source of cancer-associated fibroblasts (CAFs) in invasive lobular carcinoma of the breast. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073686"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1080\/15384047.2021.2017222","article-title":"Cancer-associated fibroblasts derived extracellular vesicles promote angiogenesis of colorectal adenocarcinoma cells through miR-135b-5p\/FOXO1 axis","volume":"23","author":"Dai","year":"2022","journal-title":"Cancer Biol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Catteau, X., Simon, P., Vanhaeverbeek, M., No\u00ebl, J.-C., and Noe, J. (2013). Variable stromal periductular expression of CD34 and smooth muscle actin (SMA) in intraductal carcinoma of the breast. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057773"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00428-020-02835-3","article-title":"Prognostic relevance of the loss of stromal CD34 positive fibroblasts in invasive breast carcinoma","volume":"477","author":"Westhoff","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Barb, A.C., Fenesan, M.P., Pirtea, M., Margan, M.M., Tomescu, L., Ceban, E., Cimpean, A.M., and Melnic, E. (2023). Reassessing breast cancer-associated fibroblasts (CAFs) interactions with other stromal components and clinico-pathologic parameters by using immunohistochemistry and digital image analysis. Cancers, 15.","DOI":"10.3390\/cancers15153823"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Guo, C.R., Han, R., Xue, F., Xu, L., Ren, W.G., Li, M., Feng, Z., Hu, B.-C., and Peng, Z.-M. (2022). Expression and clinical significance of CD31, CD34, and CD105 in pulmonary ground glass nodules with different vascular manifestations on CT. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.956451"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Calik, J., Sauer, N., Giedziun, P., Piotrowska, A., Tumi\u0142owicz, M., Wojnar, A., and Dzi\u0119giel, P. (2024). Correlating dermatoscopic features with immunohistochemical markers in basal cell carcinoma: A comprehensive analysis of 100 cases in the Caucasian population. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1429865"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mustafa, S., Koran, S., and AlOmair, L. (2022). Insights into the role of matrix metalloproteinases in cancer and its various therapeutic aspects: A review. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.896099"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Laronha, H., and Caldeira, J. (2020). Structure and function of human matrix metalloproteinases. Cells, 9.","DOI":"10.3390\/cells9051076"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hou, W. (2025). Role of TGF\u03b2-activated cancer-associated fibroblasts in the resistance to checkpoint blockade immunotherapy. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1602452"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ghahremanifard, P., Chanda, A., Bonni, S., and Bose, P. (2020). TGF-\u03b2 mediated immune evasion in cancer\u2014Spotlight on cancer-associated fibroblasts. Cancers, 12.","DOI":"10.3390\/cancers12123650"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.trecan.2024.11.005","article-title":"Functional heterogeneity of fibroblasts in primary tumors and metastases","volume":"11","author":"Cheng","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lan, X., Li, W., Zhao, K., Wang, J., Li, S., and Zhao, H. (2025). Revisiting the role of cancer-associated fibroblasts in tumor microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1582532"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Flores, L., Guti\u00e9rrez, R., Garc\u00eda, M.P., Gonz\u00e1lez-G\u00f3mez, M., Rodr\u00edguez-Rodriguez, R., Hern\u00e1ndez-Le\u00f3n, N., and Carrasco, J.L. (2021). CD34+ stromal cells\/telocytes in normal and pathological skin. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147342"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.aanat.2011.11.007","article-title":"Skin telocytes","volume":"194","author":"Rusu","year":"2012","journal-title":"Ann. Anat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1046\/j.1523-1747.2003.12550_2.x","article-title":"CD34 in human hair follicle","volume":"121","author":"Poblet","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/jid.2011.355","article-title":"Human dermis harbors distinct mesenchymal stromal cell subsets","volume":"132","author":"Vaculik","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/j.1365-2249.2006.03064.x","article-title":"Cytokines differentially regulate ICAM-1 and VCAM-1 expression on human gingival fibroblasts","volume":"144","author":"Hosokawa","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Reina, M., and Espel, E. (2017). Role of LFA-1 and ICAM-1 in cancer. Cancers, 9.","DOI":"10.20944\/preprints201709.0146.v1"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/JLB.2MR0220-549R","article-title":"ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis","volume":"108","author":"Bui","year":"2020","journal-title":"J. Leukoc. Biol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T12:03:38Z","timestamp":1768305818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/1\/158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["medicina62010158"],"URL":"https:\/\/doi.org\/10.3390\/medicina62010158","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}