Comparative Immunohistochemical Analysis of Macrophage Phenotypes in Cutaneous Sarcoid Granuloma, Suture Granuloma, and Lipogranuloma

Abstract

Granulomas are composed of a heterogeneous population of resident and recruited macrophages according to the type of lesion, extent of injury, and local tissue environment (eg, involved site and interaction with infiltrating lymphocytes). Although macrophage phenotypes in various types of granulomas have been previously described, the experimental conditions varied across studies, precluding a comparative and comprehensive understanding of granulomas. This study was conducted to comparatively analyze the expression of markers of the M1 and M2 phenotypes in macrophages that compose various types of granulomas, including epithelioid lesions, under strict conditions. Surgical specimens of cutaneous sarcoidosis (11 lesions), suture granuloma (10 lesions), and subcutaneous lipogranuloma (12 lesions) were immunohistochemically stained for CD11c, CD206, CD163, and CD10. The expression of these markers in macrophages composing each type of granuloma was scored and statistically analyzed. Granuloma macrophages were mostly immunoreactive for CD11c and CD206 in all the examined cases, although many intermingling CD206-negative cells were observed in 5 cases of lipogranuloma. CD163 and CD10 were diffusely expressed in macrophages composing suture granuloma and lipogranuloma, whereas they were not expressed in epithelioid cells in cutaneous sarcoidosis. Meanwhile, “interstitial” macrophages around epithelioid granulomas revealed moderate to marked CD163 expression in 7 lesions of cutaneous sarcoidosis. These results indicate significant differences of expression of CD163 and CD10 between cutaneous sarcoidosis and suture granuloma/lipogranuloma; CD163 and CD10 are downregulated after the epithelioid transformation of macrophages in cutaneous sarcoidosis.