title: Multinucleated giant cell reaction in lower lip squamous cell carcinoma: a clinical, morphological, and immunohistochemical study.
abstract: BACKGROUND
  Multinucleated giant cell (MGC) reactions have been identified in several malignancies, but their frequency and significance in lower lip squamous cell carcinoma (SCC) are not established. This study evaluated the MGC reactions and their association with clinicopathological parameters in lower lip SCCs. The polarization profile of these cells (M1 or M2 macrophages) was also assessed.
  
  
  METHODS
  The presence and distribution of MGC reactions in high-power fields (400×) were evaluated in hematoxylin/eosin-stained histological sections of 91 lower lip SCCs. The histopathological grade of malignancy was evaluated using two grading systems (World Health Organization [WHO] and Malignancy Grading of the Deep Invasive Margins). The histiocytic nature (CD68) and polarization profile (M1-HLA-DR+ or M2-CD163+) of MGCs were evaluated by immunohistochemistry.
  
  
  RESULTS
  Multinucleated giant cell reaction was identified in 36 (39.6%) cases, and its frequency was 3.3 times higher in well/moderately differentiated tumors than in poorly differentiated tumors (WHO grading system) (P = 0.006). For Malignancy Grading of the Deep Invasive Margins, the frequency was 2.03 times higher in highly/moderately keratinized tumors than in tumors with minimal/no keratinization (P = 0.012). No significant associations were observed between the presence/distribution of MGCs and clinical parameters (tumor size, lymph node metastasis, distant metastasis, and clinical stage) (P > 0.05). All MGCs were positive for CD68 and there was a predominance of HLA-DR+over CD163+MGCs (P = 0.031).
  
  
  CONCLUSIONS
  Multinucleated giant cell reactions may not be involved in tumor progression in lower lip SCCs. In this microenvironment, MGCs tend to exhibit a predominantly M1 phenotype and may represent a foreign body reaction to SCC keratin pearls.
authors.affiliation: Postgraduate Program in Dentistry, State University of Paraíba, Campina Grande, PB, Brazil.
authors.forename: Hellen Bandeira de Pontes
authors.identifier: http://orcid.org/0000-0002-6596-5220
authors.initials: HBP
authors.lastname: Santos
authors.affiliation: Postgraduate Program in Oral Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Márcia Cristina da Costa
authors.initials: MCDC
authors.lastname: Miguel
authors.affiliation: Postgraduate Program in Oral Pathology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Leão Pereira
authors.initials: LP
authors.lastname: Pinto
authors.affiliation: Postgraduate Program in Dentistry, State University of Paraíba, Campina Grande, PB, Brazil.
authors.forename: Manuel Antonio
authors.initials: MA
authors.lastname: Gordón-Núñez
authors.affiliation: Postgraduate Program in Dentistry, State University of Paraíba, Campina Grande, PB, Brazil.
authors.forename: Pollianna Muniz
authors.initials: PM
authors.lastname: Alves
authors.affiliation: Postgraduate Program in Dentistry, State University of Paraíba, Campina Grande, PB, Brazil.
authors.forename: Cassiano Francisco Weege
authors.initials: CFW
authors.lastname: Nonaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005260:Female; D015726:Giant Cells / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008048:Lip Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: giant cells; immunohistochemistry; lip neoplasms; neoplasm staging; squamous cell carcinoma