Pyostomatitis vegetans: cellular immune profile and expression of IL-6, IL-8 and TNF-alpha

Abstract

The aim of this study was to investigate the cellular immune profile and the expression of IL-6, IL-8 and TNF-alpha in tissue biopsies of pyostomatitis vegetans (PV). Working hypothesis was that knowledge of the cellular immune profile and role of mediators such as IL-6, IL-8 AND TNF-alpha may contribute to a better understanding of the pathogenesis of this rare entity. Archival tissues from three patients with clinically and histologically confirmed PV were studied. Analysis of the immune profile of the cellular infiltrate and expression of IL-6 and IL-8 were evaluated by immunohistochemistry. ISH was performed to evaluate the expression of TNF-alpha. Biopsy tissues from erythema multiforme, recurrent aphthous stomatitis, lichen planus and normal buccal mucosa were analyzed as controls. All patients were affected by multiple mucosal ulcerations and yellow pustules mainly located in the vestibular, gingival and palatal mucosa. Histopathologically, all specimens showed ulcerated epithelium with characteristic intraepithelial and/or subepithelial microabscesses containing abundant eosinophils plus a mixed infiltrate composed of lymphocytes and neutrophils. Cellular immune profile of the inflammatory infiltrate revealed a predominance of T-lymphocytes, mainly of cytotoxic (CD3+/CD8+) phenotype, over B-cells. CD20+ B-lymphocytes were also identified to a lesser degree among the lymphoid cells present in the lamina propria. Overexpression of IL-6 and TNF-alpha was found in both epithelial and inflammatory mononuclear cells. IL-8 expression was shown in the mononuclear cells scattered among the inflammatory infiltrate. Similar findings of overexpression of IL-6, IL-8 and TNF-alpha were, however, found in control tissues. In PV lesions, the inflammatory infiltrate shows a predominance of cytotoxic lymphocytes. Expression of IL-6, IL-8 and TNF-alpha, although not specific to PV, appears up-regulated thus these cytokines would represent a suitable therapeutic target. However, the complexity of the cytokine network and their numerous functions require further studies in order to confirm our findings.

Fig. 1

aPatient 1 Multiple mucosal ulcerations and yellow pustules are visible on the lower vestibular and gingival mucosa; bPatient 3 Ulcers and irregular yellow pustules on the soft palate

Fig. 2

Patient 1a Hyperplastic epithelium with characteristic intraepithelial and/or subepithelial micro abscesses (H&E, original magnification ×10); b at higher magnification abundant eosinophils plus a mixed infiltrate mainly formed by mononuclear cells, neutrophils ad plasma cells are visible (H&E, original magnification ×40)

Fig. 3

Patient 1a The inflammatory infiltrate shows a predominance of cytotoxic CD8+ T-lymphocytes (×40); b very few CD4+ T-lymphocytes are evident in the lamina propria (×40); c CD20+ B-lymphocytes (×40); d CD79a+ cells are well visible in the lamina propria (×40); e IL-6 positivity is present in the cytoplasm of inflammatory mononuclear cells and epithelial cells mainly of the lower third of the epithelial lamina (×10); f IL-8 expression is evident mainly in the cytoplasm of inflammatory mononuclear cells (×40); g By ISH analysis, TNF-α appears markedly expressed in the cytoplasm of both epithelial and inflammatory mononuclear cells (×10)

Fig. 4

Control tissue, Case 2a predominance of cytotoxic CD8+ T-lymphocytes in the inflammatory infiltrate (×10); b fewer CD4+ T-lymphocytes are present in the lamina propria (×10); c few scattered CD20+ B-lymphocytes are evident (×10); d CD79a+ cells are absent (×10); e IL-6 positivity is shown in the cytoplasm of inflammatory mononuclear cells and epithelial cells (×10); f IL-8 expression is evident among inflammatory mononuclear cells; g TNF-α appears expressed in both epithelial lamina and inflammatory infiltrate (×10)

Fig. 5

Control tissue, normal buccal mucosaa rare cytotoxic CD8+ T-lymphocytes around capillaries and at the basal membrane level (×10); b rare CD4+ T-lymphocytes at the basal membrane level (×10); c scattered CD20+ B-lymphocytes at the basal membrane level (×10); d IL-6 positivity around capillaries (×10); e IL-8 positivity around capillaries (×10)