Intraepithelial Macrophage Expressing CD163 Is a Histopathological Clue to Evaluate the Malignant Potency of Oral Lichenoid Condition: A Case Report and Immunohistochemical Investigation

Abstract

Oral lichenoid conditions (OLC), including oral lichen planus (OLP), oral lichenoid lesions and oral lichenoid dysplasia, differ in pathogenesis and biological malignancy. However, distinguishing them based on clinical or histological features is difficult. It is well known that CD163+ macrophages are associated with oral cancer aggressiveness. We recently demonstrated that CD163+ macrophages of noncancerous lesions infiltrate the stroma, not the intraepithelial area. In this report, we describe a case of OLC that was not detected as malignant by the first local biopsy. Furthermore, we evaluated the malignant potency of OLC by retrospectively comparing the histological findings between local biopsy and resected specimens focusing on CD163+ macrophages. A 72-year-old man with a white lesion in the unilateral buccal mucosa was diagnosed with OLP through the biopsy although invasive cancer was detected two years later. Intraepithelial CD163+ macrophages were found not only on the resected specimen but also biopsy. This is the first report to demonstrate that intraepithelial CD163+ macrophages may be noteworthy indicators to identify the malignant potency of OLC.

Alteration of Macrophage Infiltrating Compartment: A Novel View on Oral Carcinogenesis

“…Our retrospective immunohistochemical analysis using TL biopsy specimens and consecutive resected specimens revealed that the TL with invasive cancer had significantly higher numbers of intraepithelial CD163 + macrophages than the TL with noninvasive cancer [84]. We recently observed intraepithelial CD163 + macrophages in a case of oral lichenoid disease with malignant potency [94]. Interestingly, Weber et al [81] demonstrated that malignant transformation of OL is significantly associated with macrophage infiltration toward the epithelium using not only CD163 but also CD11c, which is an M1-related marker.…”

“…Further investigation of the role of macrophages in periodontitis-related oral carcinogenesis using human samples is required. CD206 + macrophages were overtly less in number when compared with CD163 + macrophages in OL [78] The lower level of infiltration of CD204 + macrophages compared with CD68 + and CD163 + macrophages in CIS [79] The correlation of CD204 + macrophages with the recurrence and cancerization of oral epithelial precancerous lesions [80] Macrophage polarization CD163 + macrophages in OL express STAT1, which is known as an M1-related marker [62] The association of malignant transformation of OL not only with CD163 but also with CD11c [81] The proportions of CD163 + or CD68 + macrophages coexpressed with SIRPα were increased in OL compared with OSCC [82] Compared with CD163 + macrophages, iNOS + macrophages were more commonly distributed in the subepithelial stroma of OL [83] Distribution of macrophages Macrophages in phagocyte dysplastic epithelial cells [86,87] Macrophages in oral normal epithelium were rare [88] Infiltration of macrophages into the subepithelial stroma of OL [62,78,82,83,[88][89][90][91] The immunosuppressive activity of the M2 macrophages is particularly important in the early stages of lip carcinogenesis [92] Observations of intraepithelial macrophages in CIS [79,93] High numbers of intraepithelial CD163 + macrophages were observed in TL with invasive cancer compared with TL with noninvasive cancer [84] Malignant transformation of OL correlated with macrophage infiltration toward the epithelium [81] Intraepithelial CD163 + macrophages were observed in OLD with malignant potency [94] Macrophages and risk factors of oral cancer Incisional biopsy-induced tissue trauma skewed macrophage polarization toward the M2 phenotype [96] Macrophage-derived MMP12 in remodeling events in the connective tissue of AC [98] The relationship between macrophages involved in periodontitis and oral carcinogenesis remains to be clarified [no previous report] CD, cluster of differentiation; TL, tongue leukoplakia; OL, oral leukoplakia; SIRPα, signal regulatory protein α; OSCC, oral squamous cell carcinoma; CIS, carcinoma in situ; iNOS, inducible n...…”

Tongue Cancer Cell-Derived CCL20 Induced by Interaction With Macrophages Promotes CD163 Expression on Macrophages

“…Therefore, there is sufficient evidence to support that CD163 is the most important TAM marker of TSCC. We also previously reported the CD163-positive macrophages related to the malignant behavior of oral precancerous lesions (21,22,70). By contrast, reliable human M1 macrophage markers for immunohistochemistry have not been established (6).…”

The Immune Cells in the Development of Oral Squamous Cell Carcinoma

“…Oral dysplastic lesions can recruit macrophages by expression of human beta-defensin 3 [27], and an increase in macrophages and myeloid-derived suppressive cells (MDSCs) corre-lates with malignant progression, in particular by M2 macrophage polarization [12,24,[28][29][30][31]. In several studies, M2 were characterized by CD163+ and CD204+ and correlated with the presence of FoxP3 and CD25+ lymphocytes; specifically, both cell types increased with the worsening of dysplasia [15,30].…”