Histopathologic Insights Into Curvularia-Induced Chronic Granulomatous Fungal Sinusitis: A Guide for Surgical...

Chronic granulomatous fungal sinusitis is a rare, debilitating infection characterized by an enlarging mass affecting the orbit, nose, palate, and paranasal sinuses, with occasional intraorbital and intracranial extension. Most cases are reported in subtropical regions, with rare reports from the United States and Europe. Globally, Aspergillus flavus is the primary causative agent in >60% of cases, followed by other Aspergillus species and dematiaceous molds. This study highlights the histopathologic, microbiologic, and molecular diagnostic features of 6 cases with chronic granulomatous fungal sinusitis caused by the emerging pathogen Curvularia, predominantly affecting healthy African Americans in the Southeastern United States. Histopathological examination revealed multinucleated giant cells and noncaseating granulomatous inflammation. Short septate hyphae with bulbous swelling predominated, but there was significant variation in size, shape, and color, with half the cases lacking hyphal pigmentation. Lack of awareness of this emerging entity and variable morphology led to initial misidentification in 3 cases as hyaline septate hyphae (Fusarium), yeasts, and Blastomyces. All cases showed extracellular and intracellular (within multinucleated giant cells) hyphae and round forms with thick refractile cell walls lacking intracellular contents, yielding a characteristic "ghost shell" morphology, indicating fungal nonviability. Consistent with this finding, only 1 culture yielded a live isolate of Curvularia. In addition, 28S rRNA gene sequencing of formalin-fixed paraffin-embedded tissue was required for identification and identified Curvularia lunata (n = 4), Curvularia spicifera (n = 1), and Curvularia spp. (n = 1). One case with 2 hyphal morphologies also grew Aspergillus fumigatus, indicating coinfection. Chronic granulomatous fungal sinusitis, caused by the understudied and persistent pathogen Curvularia, is an emerging threat in immunocompetent hosts, characterized by pathogen persistence in critical facial and cranial structures, despite a significant host response. To accurately diagnose and guide treatment, surgical pathologists must be aware of its expanded geographic range, affected populations, and key histopathologic features, as described herein.