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. 2025 Mar 21;21(1):191.
doi: 10.1186/s12917-025-04637-8.

Immunohistochemical analysis of smooth muscle actin and CD31 in feline post-injection site fibrosarcomas: association with tumour grade, vascular density, and multinucleated giant cells

Mateusz Mikiewicz  1 , Iwona Otrocka-Domagała  2
Affiliations

Immunohistochemical analysis of smooth muscle actin and CD31 in feline post-injection site fibrosarcomas: association with tumour grade, vascular density, and multinucleated giant cells

Mateusz Mikiewicz et al. BMC Vet Res. .

Abstract

Background: Multinucleated giant cells are commonly observed in various malignancies; however their clinical and biological significance remains largely unexplored and it has been hypothesised that the cells may play a role in vascular mimicry, tumour progression and tumour survival. This study aimed to investigate the expression of smooth muscle actin and CD31 in feline post-injection site fibrosarcomas, focusing on relationships between multinucleated giant cells presence, tumour grade, and vascular density to elucidate their potential role in tumour progression.

Results: A total of 61 feline post-injection site fibrosarcomas, histologically graded into grades I, II, and III, were examined immunohistochemically. Smooth muscle actin immunoreactivity was detected in 57/61 (93.4%) cases. Multinucleated giant cells expressing CD31 were identified in 39/61 (63.9%) cases, predominantly in high-grade tumours, with a correlation observed between multinucleated giant cell presence, tumour grade, and mitotic index. Vascular density differed across tumour grades. A negative correlation between vascular density, tumour grade and necrosis score was identified. Additionally, a negative correlation was observed between multinucleated giant cells presence and vascular density.

Conclusions: The findings suggest a complex tumour microenvironment in which multinucleated giant cells and vascular mimicry may facilitate tumour survival under hypoxic conditions, potentially contributing to an aggressive tumour phenotype.

Keywords: CD31; Feline injection site fibrosarcoma; Immunohistochemistry; Multinucleated giant cell; Smooth muscle actin.

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Conflict of interest statement

Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: Ethics approval is not applicable under the Act of 15 January 2015 on the protection of animals used for scientific or educational purposes– Journal of Laws of the Republic of Poland (Journal of Laws 2015 item 266) and Local Ethics Committee for Animal Experiments. The study used archival specimens collected in the Department of Pathological Anatomy. Written informed consent was obtained from the owner or legal custodian of all animals described in this work for the procedures undertaken in this retrospective study. No animals or humans are identifiable within this publication, and therefore additional informed consent for publication was not required.

Figures

Fig. 1
Fig. 1
Feline injection-site fibrosarcoma. (A) Tumour cells show positive expression to SMA. SMA immunostaining with DAB, counterstaining with Mayer’s haematoxylin, 200× (B) Multinucleated giant cell show positive expression to CD31. CD31 immunostaining with DAB, counterstaining with Mayer’s haematoxylin, 400×
Fig. 2
Fig. 2
Feline injection-site fibrosarcoma. (A) Mean multinucleated giant cell count in grade I, II, and III tumours. Significantly higher multinucleated giant cell count was observed in grade III tumours compared to grade II (p = 0.004) and grade I (p = 0.017). (B) A positive correlation between multinucleated giant cell occurrence and tumour grade (r = 0.49; p = 0.000). (C) Mean multinucleated giant cell count compared to mitotic score. Significantly higher multinucleated giant cell count was observed in mitotic score 3 compared to mitotic score 1 (p = 0.022) and mitotic score 2 (p = 0.02). (D) A positive correlation between multinucleated giant cell count and mitotic score (r = 0.441; p = 0.000)
Fig. 3
Fig. 3
Feline injection-site fibrosarcoma. (A) Mean vascular density in grade I, II, and III tumours. Significantly higher vascular density was in grade II tumours compared to grade III (p = 0.000). (B) A negative correlation between vascular density and tumour grade (r=-0.444; p = 0.000). (C) Vascular density compared to necrosis score. Vascular density was significantly higher in necrosis score 0 compared to necrosis score 2 (p = 0.005). (D) A negative correlation between vascular density and necrosis score (r=-0.411; p = 0.001)
Fig. 4
Fig. 4
A negative correlation between the multinucleated giant cell count and vascular density (r=-0.262; p = 0.042)
See this image and copyright information in PMC

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