Reação de células gigantes multinucleadas em carcinomas de células escamosas de lábio inferior: Estudo clínico-patológico e imunoistoquímico

Abstract

The multinucleated giant cells (MGCs) reaction has been reported in several epithelial malignancies. However, the nature and potential prognostic implication of this reaction in these neoplasms remain under discussion. In intra-oral squamous cell carcinoma (SCC), studies have suggested that MGCs may represent a foreign body reaction to the keratin produced by tumor cells and that, possibly, these cells are formed from the fusion of M2 macrophages. In the context of lower lip SCCs, there are no studies about a probable relationship between MGC reactions and the tumor progression (Pubmed Database, Scopus, Web of Science, LILACS, SIGLE – access on July 8, 2016). Thus, this study aimed to evaluate the frequency, distribution, and polarization profile (M1 - HLA-DR / M2 - CD163 ) of MGC reaction in 91 cases of lower lip SCC and to verify the association of this microscopic finding with clinicopathological parameters (tumor size, node metastasis, distant metastasis, clinical stage, and histopathological grade of malignancy). Under light microscopy, hematoxylin–eosin-stained histological sections were evaluated for the presence and distribution of MGCs reaction in high-power fields (HPFs). To evaluate the histopathological grade of malignancy, the systems proposed by Bryne et al. (1992) and the World Health Organization (WHO) (CARDESA et al., 2005) were used. Only cases containing MGCs reaction were included in the immunohistochemical study. The anti- CD68 antibody was used to confirm the monocytic/ macrophagic nature of the MGCs reaction. To identify the polarization profile of these cells, the percentage of HLA-DR and CD163 MGCs was established for each case. Thirty-six (39.6%) cases contained MGCs reaction. Significant associations between the presence of MGCs reaction and clinical parameters were not observed (p > 0.05). The occurrence of MGCs reaction in well and moderately differentiated cases (CARDESA et al., 2005) was 3.3 higher than in poorly differentiated cases (p = 0.006; PR: 3.30; 95% CI: 1.12-9.68). At the tumor invasive front (BRYNE et al., 1992), no associations between the presence of MGCs reaction and the histopathological grade of malignancy (p = 0.674), the nuclear pleomorphism (p = 0.359), the pattern of invasion (p = 0.277), and the inflammatory infiltrate (p = 0.653) were seen. Nonetheless, the occurrence of these cells in highly and moderately keratinized tumors at the invasive front was 2.03 higher than in lesions with minimal or no keratinization (p = 0.012; PR: 2.03; 95% CI: 1.11-3.71). Regarding the distribution analysis, eighteen (50%) cases had MGCs in up to 3 HPFs. Significant associations between the distribution of MGC reaction and the clinicopathological parameters were not observed (p > 0.05). Immunohistochemical analysis revealed that MGCs were CD68 in all cases. Furthermore, it was observed a predominance of HLA-DR over CD163 cells (p = 0.031). The findings of the current study suggest that MGCs reaction is not involved with tumor progression in lower lip SCCs. In these malignancies, MGCs tend to exhibit predominantly an M1 phenotype and may represent a foreign body reaction to the keratin produced by tumor cells.