Original Scientific Article Spirocercosis caused by Spirocerca lupi has a global distribution and mainly infects dogs although other carnivores may be affected as well. The research aimed to ascertain the proportion of cellular proliferation/apoptosis within the parasiteinduced nodules and to categorize the inflammatory cells by CD3 (for T lymphocytes), CD20 (for B lymphocytes), and CD68 (for macrophages) markers. The study included 152 Iranian mixed-breed dogs (87 males and 65 females) examined for esophageal spirocercosis. The dogs underwent hematological investigations and Telemann concentration stool exams to detect the parasites’ eggs. The normal and nodular esophagi underwent TUNEL assay, histopathology, and immunohistochemical staining for GDNF, p53, Ki67, CD3, CD20, and CD68. According to our findings, 31 out of 152 dogs (20.39%) were diagnosed with spirocercosis based on clinical examinations and stool exams, while 20 out of 152 dogs (13.16%) had nodular esophagi in necropsy. Normal and nodular esophageal tissue samples (n=64) were collected from necropsied dogs. Histopathology confirmed non-neoplastic parasitic nodular lesions. Immunohistochemically, increased GDNF, Ki67, CD3, CD20, and CD68 expression was significant (p<) in nodular tissue compared to normal tissue. However, the expression of p53 was not significant (p>0.05). Given the results of Ki67 expression and TUNEL assay, the rate of proliferation (6-8 times)/apoptosis (2-3 times) significantly increased (p<) in the infected tissue compared to normal tissue. The results indicated that the GDNF as a neurotrophic growth factor may play an important role in the pathogenesis of nodular spirocercosis in dogs. Meanwhile, a high proliferation/apoptosis rate in the parasitic nodular compared to normal esophagi may stimulate inducing neoplastic transformation in normal esophageal tissue. https://macvetrev.mk/LoadArticlePdf/361 2025-03-15 39 51 https://doi.org/10.2478/macvetrev-2025-0014 Spirocerca lupi non-neoplastic nodules GDNF apoptosis cellular proliferation Sara Amoorahim false 1 Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran AUTHOR Amir Amniattalab amir.amniattalab@iau.ac.ir false 2 Department of Pathology, Faculty of Veterinary Medicine, Urmia Branch, Islamic Azad University, Urmia, Iran LEAD_AUTHOR Oryan, A., Sadjjadi, S.M., Mehrabani, D., Kargar, M. (2008). Spirocercosis and its complications in stray dogs in Shiraz, southern Iran. Vet Med-Czech. 53(11): 617-624. 1 https://doi.org/10.17221/1866-VETMED Dvir, E., Kirberger, R.M., Malleczek, D. (2001). 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