Is That Nodular Lesion Truly Sterile?

Granulomatous/pyogranulomatous nodules that are not neoplastic and for which no organism can be cultured or identified by histological examination are a diagnostic and therapeutic challenge. Sterile pyogranuloma/ granuloma syndrome (SPGS) is such a disorder, but it is possible that organisms (eg, Leishmania spp, Mycobacterium spp, Nocardia spp, Actinomyces spp, Serratia spp) may provide persistent antigenic stimulation in some cases and cause a granulomatous inflammatory reaction. In this study, 40 canine skin biopsies diagnosed as sterile lesions with a granulomatous/pyogranulomatous pattern were reevaluated; real-time PCR was used to detect Leishmania spp, Mycobacterium spp, Nocardia spp, and Serratia marcescens. In addition, special stains and anti-Bacillus Calmette–Guerin (BCG) and Leishmania spp immunohistochemistry were performed. Histological review, special stains, and immunohistochemistry did not reveal any infectious agents. Real-time PCR was negative for Mycobacterium spp and Nocardia spp but positive for Leishmania spp in 4 biopsies and S marcescens in 2 samples. The cases with positive results were not histologically distinct from those with negative findings. These results provide further evidence that diagnosis of noninfectious granulomatous/ pyogranulomatous skin lesions could result from chronic antigenic stimulation from pathogens in skin lesions. 

This report drives home the point that sterile pyogranulomatous inflammation is not sterile until every rock and stone is turned over. A careful search for an underlying cause is mandatory because many underlying causes can be life- threatening. The direction of the investigation is often guided by the patient’s global health and other pertinent information (eg, travel history). In an otherwise healthy pet with skin disease, a common cause is foreign body reaction to hair shafts. This is common in dogs with pododermatitis or other areas of inflamed appositional skin. Pyogranulomatous reactions will also occur with Demodex spp mites and resolving calcinosis cutis. Additional tissue sections may need to be submitted. When this type of inflammation is observed, pathologists typically order special stains and look for fungal and bacterial organisms. Tissue culture may reveal infectious agents but, depending on the organism, this can take weeks. Once real-time PCR testing becomes widely available, it will allow for rapid, widespread screening for many infectious agents.—Karen A. Moriello, DVM, DACVD