Pathological features of invasive oral aspergillosis in patients with hematologic malignancies

Little is known about the characteristic macroscopic and microscopic changes that take place during the progression of oral invasive aspergillosis in immunocompromised patients. The aim of this study was to determine the relationship between the oral and histopathologic findings in these patients. Such a study would aid in understanding the early development of subsequent progression of the disease.

Twelve patients with hematologic malignancies who developed invasive oral aspergillosis were studied. The condition was divided into three stages according to the oral findings at the time biopsy procedures were performed. Tissue sections from biopsy specimens were stained with hematoxylin and eosin for histopathologic study and the findings were evaluated in relation to the oral findings. Fungal cultures of biopsy specimens were also performed to confirm the causative organisms.

The diagnosis of oral aspergillosis was established in terms of both histologic and microbiologic evidence in all 12 patients. In the early stage (three patients), isolated areas of violaceous marginal gingiva consisted of degenerated epithelium and connective tissue infiltrated by fungal hyphae. In the advanced stage (four patients), the violaceous marginal gingiva had become transformed into gray necrotic lesions that extended to the attached gingiva. The necrotic lesions showed ulceration and were covered by a pseudomembrane containing fungal hyphae. At the base of the ulcers, connective tissue was occupied by proliferating fungal hyphae, with vascular invasion being observed. In the late stage (five patients), the ulcerated lesions had progressed, showing destruction of the alveolar bone and surrounding facial muscles, with infiltration of fungal hyphae unto the tissues. No inflammatory cellular reaction was observed until the hematologic status of the patients improved.

These findings indicate that invasive oral aspergillosis has three distinctive clinicopathological stages. Recognition of the different stages of invasive Aspergillus infections is helpful for correct diagnosis of the disease.