Gulinac M, Velikova T, Dikov D. Multinucleated giant cells of bladder mucosa are modified telocytes: Diagnostic and immunohistochemistry algorithm and relation to PD-L1 expression score. World J Clin Cases 2023; 11(26): 6091-6104 [PMID: 37731584 DOI: 10.12998/wjcc.v11.i26.6091]
Corresponding Author of This Article
Milena Gulinac, MD, PhD, Assistant Professor, Doctor, General and Clinical Pathology, Medical University of Plovdiv, 15A Vassil Aprilov Blvd, Plovdiv 4002, Bulgaria. mgulinac@hotmail.com
Research Domain of This Article
Pathology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Cases. Sep 16, 2023; 11(26): 6091-6104 Published online Sep 16, 2023. doi: 10.12998/wjcc.v11.i26.6091
Multinucleated giant cells of bladder mucosa are modified telocytes: Diagnostic and immunohistochemistry algorithm and relation to PD-L1 expression score
Milena Gulinac, Tsvetelina Velikova, Dorian Dikov
Milena Gulinac, General and Clinical Pathology, Medical University of Plovdiv, Plovdiv 4002, Bulgaria
Milena Gulinac, Tsvetelina Velikova, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
Dorian Dikov, Pathology, Grand Hospital de l’Este Francilien, Jossigny 1000, France
Author contributions: Gulinac M and Dikov D contributed to conceptualization, investigation, and re-sources; Gulinac M contributed to data curation; Velikova T contributed to formal analysis; Gulinac M contributed to funding acquisition and methodology; Dikov D contributed to project administration; Velikova T contributed to software; Dikov D and Velikova T contributed to supervision; Gulinac M, Dikov D, and Ve-likova T contributed to validation; Velikova T contributed to visualization; Gulinac M contributed to writing-original draft; Dikov D and Velikova T contributed to writing-re-view & editing.
Supported bythe European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, No. BG-RRP-2.004-0008.
Institutional review board statement: The design of the study was approved by the Institutional Review Board of Department of General and Clinical Pathology, Medical University of Plovdiv (Approval No. 67/16.12.2022).
Informed consent statement: All subjects signed informed consent for the study.
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Milena Gulinac, MD, PhD, Assistant Professor, Doctor, General and Clinical Pathology, Medical University of Plovdiv, 15A Vassil Aprilov Blvd, Plovdiv 4002, Bulgaria. mgulinac@hotmail.com
Received: June 25, 2023 Peer-review started: June 25, 2023 First decision: July 18, 2023 Revised: August 16, 2023 Accepted: August 25, 2023 Article in press: August 25, 2023 Published online: September 16, 2023 Processing time: 74 Days and 17.8 Hours
Abstract
BACKGROUND
Multinucleated giant cells (MGCs) in bladder carcinomas are poorly studied.
AIM
To describe the function, morphogenesis, and origin of mononuclear and MGCs in urothelial carcinoma (UC) of the bladder in Bulgarian and French patients.
METHODS
Urothelial bladder carcinomas (n = 104) from 2016-2020 were analyzed retrospectively using immunohistochemical (IHC) and histochemical stain examination. Giant cells in the bladder stroma were found in 35.6% of cases, more often in high-grades.
RESULTS
We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers (vimentin, smooth muscle actin, Desmin, and CD34) and the macrophage marker CD68. Furthermore, IHC studies revealed the following profile of these cells: Positive for p16; negative for epithelial (CK AE1/AE3 and GATA-3), vascular (CD31), neural (PS100 and C-KIT), cambial, blastic (CD34-blasts and C-KIT), and immune markers (IG G, immunoglobulin G4, and PD-L1); no proliferative activity, possess no specific immune function, and cannot be used to calculate the Combined Positive Score scale.
CONCLUSION
In conclusion, the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant, although nonspecific, histological marker for chronic bladder damage, reflecting the chronic irritation or inflammation. Likewise, according to the morphological and IHC of the mono- and multinucleated giant cells in the bladder, they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.
Core Tip: Based on our results and data from the literature, we have developed and proposed an algorithm of histological, histochemical, and immunohistochemical (IHC) criteria, and also a generalized algorithm for the differential diagnosis of multinucleated giant cells (MGCs) in bladder urothelial carcinoma and benign or malignant lesions of other visceral organs. According to the data obtained by us in the morphological and IHC study, MGCS are modified telocytes. The reason for this modification is the chronic damage to the bladder mucosa (regardless of the etiological factor), which leads to the fusion of telocytes and their transformation into multinucleated cells. At the same time, they lose C-kit expression, penetrate phagocytic function, and begin to express p16, which is, as described in detail above, a sign of cellular aging.
