A Study of Oral Irritation Fibroma with Special Reference to Clinicopathological and Immunohistochemical Features of Stromal Spindle Cells

Background. Oral irritation fibromas (OIFs) are benign fibroblastic proliferations arising from the oral mucosa in response to chronic irritation. Although the nature of fibroblast proliferation has been well studied in wound repair, details of the histopathogenesis of spindle cells in relation to their immunohistochemical features and distribution in OIF are unclear. Methods. Forty cases of OIF were investigated and the spindle cells were examined in detail. The stromas were classified histopathologically, and stained histochemically by the alcian blue (pH-2.5)-PAS double-staining method. Immunohistochemistry was performed using antibodies against vimentin, α-smooth muscle actin (α-SMA), desmin, S-100β, myoD1, and collagen type I and III. Results. Histopathologically, the stromas of OIFs were classified into five types : mature, immature fibroblastic, immature inflammatory, myxoid and mixed type. Inflammation was only seen in a minority of cases with no mitotic figures or any sign of necrosis. Histochemically, the myxoid type stained basophilic while the collagen of other OIF types stained acidophilic. Immunohistochemically, the spindle cells of the mature type expressed vimentin constantly (V phenotype). In contrast, the spindle cells of the immature fibroblastic type expressed α-SMA (VA phenotype) and the immature inflammatory type expressed desmin (VD phenotype). Interestingly, the spindle cells of the myxoid type expressed S-100β (N phenotype), while the mixed type exhibited α-SMA and S-100β positive cells (VA/N phenotype). MyoD1 was expressed constantly in spindle cells of the immature inflammatory and fibroblastic types, but its expression was weak in the mixed type. MyoD1 was not expressed in the mature or myxoid types. All 40 cases stained positive for collagen type III, while collagen type I was detected predominantly in the mature type and only weakly in the other types. Conclusion. These results suggest that spindle cells of OIFs transiently express myofibroblastic characteristics, particular the VA, VD and VA/N phenotypes, through the expression of α-SMA, desmin and myoD1. Thus, with the onset of trauma (weak or chronic irritation) a myofibroblastic stromal reaction appears to be evoked in undifferentiated mesenchymal cells, and collagen type III is produced. As the healing progress proceeds, collagen type III levels decline, collagen type I is secreted and the phenotypic features of myofibroblasts disappear, as seen in the V phenotype. The myxoid type expressed immunohistochemical features of neural differentiation while the mixed type expressed features considered to be of dual origin. The immunohistochemical findings also revealed that the growth of OIF was time-dependent.