Immunohistochemical Detection of Francisella tularensis in Formalin-Fixed Paraffin-Embedded Tissue

Abstract

Tularemia is a zoonotic disease caused by Francisella tularensis. Histopathologic lesions of lymph nodes in cases of ulceroglandular tularemia include stellate microabscesses similar to those seen in cat-scratch disease or lymphogranuloma venereum. When the lung is involved, the pathology is that of an acute necrotizing pneumonia. Traditionally, diagnosis is based on serology, culture, and fluorescent antigen detection, but each of these methods presents problems. We studied formalin-fixed tissues from four tularemia cases as well as control tissues by using immunohistochemistry (IHC) for F. tularensis. Positive immunostaining was seen in all the tularemia cases examined. Three cases were fatal, and positive IHC staining could be seen in the lungs (bacteria in cellular debris, and intracellularly in alveolar macrophages, endothelia, and polymorphonuclear leukocytes), spleen (in necrotic areas), lymph nodes (in stellate abscesses), and liver (in Kupffer cells). The fourth patient had ulceroglandular tularemia, and the lymph node biopsy demonstrated the typical stellate microabscesses. By IHC, there was positive staining of bacteria in the abscesses and occasional macrophages and endothelial cells in nonnecrotic areas. In conclusion, F. tularensis can be detected by IHC in formalin-fixed tissue, which, if available as biopsy material, can be useful for diagnosis. IHC can be helpful in our understanding of tularemia pathogenesis because bacteria are visualized in the context of the surrounding tissue morphology.