Association study between clinicopathological variables and periodontal breakdown in gingival pyogenic granuloma.

OBJECTIVE: The aim was to investigate a possible association between the immunoexpression of interleukin (IL)-4 and clinicopathological parameters with the periodontal breakdown observed in gingival pyogenic granuloma (PG). MATERIALS AND METHODS: Paraffin-embedded samples of gingival PG (n = 46) were prepared for histological and immunohistochemical assessment. Demographic and clinical parameters were assessed by criteria based on age stratum, gender, smoking habit, evolution course, location, lesion size, macroscopic appearance, predisposing factors, recurrence, and periodontal breakdown. Histological assessment included the appearance of epithelial lining, microvessel density, inflammatory infiltrate density, interstitial fibrosis, and histological arrangement. A staining intensity distribution (SID) score was used to assess IL-4 immunoreactivity. The association between candidate predictor variables and periodontal breakdown was analyzed individually and adjusted for confounding using a bivariate binary logistic regression model. RESULTS: Mean IL-4 SID values were significantly increased for long-standing and large lesions, presence of periodontal breakdown, high microvessel density, and moderate-to-severe inflammatory infiltrate density. While bivariate and univariate analyses revealed a positive association of the evolution course ≥12 months, lesion size >1 cm, high microvessel density, moderate-to-severe inflammatory infiltrate density, and IL-4 SID score ≥8.04 with periodontal breakdown, after bivariate logistic regression analysis, only the evolution course ≥12 months, moderate-to-severe inflammatory infiltrate density, and IL-4 SID score ≥8.04 remained as robust predictors of periodontal damage. Confounding and interaction effects between candidate predictor variables were also noted. CONCLUSION: These findings suggest that while evolution course, inflammatory infiltrate density, and the overexpression of IL-4 may act as predictors of periodontal breakdown in gingival PG, there are mutual confounding and synergistic biological interactive effects with respect to the lesion size and microvessel density in the susceptible host that may be also associated with the bone resorption and tissue destruction. CLINICAL RELEVANCE: Although the first-line therapy of gingival PG continues to be the surgical excision, this approach poses unwanted complications such as severe mucogingival defects and recurrence. Hence, early diagnosis and detection of these three significant predictor variables as well as timely surgical excision might help prevent the periodontal tissue destruction observed in some of these lesions.

Assessment of clinicopathological characteristics and immunoexpression of COX-2 and IL-10 in oral pyogenic granuloma.

OBJECTIVE: The aim was to investigate the relationship between patient clinical background, histological features, and immunoexpression of COX-2 and IL-10 in oral pyogenic granuloma (PG). DESIGN: Paraffin-embedded samples of oral PG (n=57) were prepared for histological and immunohistochemical assessment. Based on the histological features, the samples were categorised into lobular capillary hemangioma (LCH) and non-LCH subtypes. The epithelial lining, angiogenic index, inflammatory infiltrate density, and interstitial fibrosis, were assessed in haematoxylin-eosin stained sections. In addition, the marker expression estimation (stained cells/total cell number) was used to assess immunoreactivity for each sample. RESULTS: Although there were no significant differences between histological subtypes regarding demographic and clinical parameters, mean values of microvessel count and inflammatory infiltrate density were significantly greater in the non-LCH PG subtype. Also, whilst cellular immunolocalisation patterns of COX-2 and IL-10 were similar, mean values of expression estimation of each immunomarker were significantly higher in non-LCH PGs in comparison with LCH subtypes. Furthermore, significant variations for immunohistochemical parameters were evident regarding to angiogenic index and inflammatory infiltrate density, but not concerning demographic and clinical data. Finally, linear regression analysis showed a significant positive correlation between the expression estimation of the two immunomarkers. CONCLUSION: These findings suggest a role for COX-2 and IL-10 in the etiopathogenesis of oral PG and indicate that LCH and non-LCH histological subtypes represent different stages in the evolution of a single lesion with varying degrees of proliferative, angiogenic, and inflammatory activity.

Expression of CD34 and CD105 as markers for angiogenesis in oral vascular malformations and pyogenic granulomas.

The objective of this study was to assess angiogenic activity by analyzing anti-CD105 and anti-CD34 immunostaining in 20 cases of vascular malformations (VMs) and 20 cases of oral pyogenic granulomas (OPG). In addition, the usefulness of these markers for the differential diagnosis of these two oral tumors was evaluated. The results showed no significant difference in mean microvessel count between the anti-CD105 (P = 0.803) and anti-CD34 (P = 0.279) antibody. The mean number of vessels was 18.75 and 59.72 for oral VMs immunostained with anti-CD105 and anti-CD34 antibody, respectively, whereas in OPG the mean number was 20.22 and 48.09, respectively. CD34 was found to be more effective than CD105 in identifying blood vessels. However, the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this study supports the role of angiogenic factors in the etiopathogenesis of oral VMs and PG, but the results showed that quantification of angiogenesis cannot be used as a marker for the differential diagnosis of these two types of lesions.

Mesenchymal stem cells and adipogenesis in hemangioma involution.

Hemangioma is a benign tumor of infancy whose hallmark is rapid growth during the first year of life followed by slow regression during early childhood. The proliferating phase is characterized by abundant immature endothelial cells, the involuting phase by prominent endothelial-lined vascular channels and endothelial apoptosis, and the involuted phase by few remaining capillary-like vessels surrounded by loose fibrofatty tissue. Nothing is known about the mechanisms that contribute to the adipogenesis during this spontaneous regression. We postulated that mesenchymal stem cells (MSCs) reside in the tumor and preferentially differentiate into adipocytes. To test this hypothesis, we isolated MSCs from 14 proliferating and five involuting hemangiomas by taking advantage of the well known selective adhesion of MSCs to bacteriologic dishes. These hemangioma-derived MSCs (Hem-MSCs) are similar to MSCs obtained from human bone marrow, expressing the cell surface markers SH2 (CD105), SH3, SH4, CD90, CD29, smooth muscle alpha-actin, and CD133 but not the hematopoietic markers CD45 and CD14 or the hematopoietic/endothelial markers CD34, CD31, and kinase insert domain receptor (KDR). Hem-MSCs exhibited multilineage differentiation with robust adipogenic potential that correlated with the proliferating phase. The numbers of adipogenic Hem-MSCs were higher in proliferating-phase than in involuting-phase tumors and higher than in normal infantile skin. Furthermore, Hem-MSCs exhibited a random pattern of X-chromosomal inactivation, indicating that these cells are not clonally derived. In summary, we have identified MSCs as a novel cellular constituent in infantile hemangioma. These MSCs may contribute to the adipogenesis during hemangioma involution.

Mast cells in angiolipomas and hemangiomas of human skin: are they important for angiogenesis?

To characterize the potential role of mast cells (MC) in angiogenesis, this study tests the hypothesis that MC may be more abundant in angiolipomas than in classic lipomas. MC counts were compared in 13 subcutaneous angiolipomas and 15 subcutaneous classic lipomas stained with Giemsa. Angiolipomas had ten times as many MC as did classic lipomas (25.34 +/- 2.83 versus 2.41 +/- 0.37 per mm2, mean +/- SE). To clarify whether this difference was primary (angiogenic activity) or secondary to the increased vascularity, MC were counted in 8 longstanding cutaneous capillary hemangiomas versus 13 cutaneous capillary hemangiomas of recent onset (pyogenic granulomas). If MC were mediating primary angiogenesis, one would expect them to be present in greater numbers in early than in late hemangiomas. To the contrary, however, long-standing hemangiomas were found to have significantly more MC than had those of recent onset (52.48 +/- 14.99 versus 6.59 +/- 3.37 per mm2, mean +/- SE). These results suggest that MC may not play an essential, early role in the proliferation of blood vessels in angiolipomas and hemangiomas, but rather may be related to maturation of blood vessels in these tumors.