Fungal rhinosinusitis: a categorization and definitional schema addressing current controversies

Abstract

Background: Fungal (rhino-) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification.

Discussion: Key conclusions reached were: rhinosinusitis is preferred to sinusitis; acute invasive fungal rhinosinusitis is preferred to fulminant, or necrotizing and should refer to disease of <4 weeks duration in immunocompromised patients; both chronic invasive rhinosinusitis and granulomatous rhinosinusitis were useful terms encompassing locally invasive disease over at least 3 months duration, with differing pathology and clinical settings; fungal ball of the sinus is preferred to either mycetoma or aspergilloma of the sinuses; localized fungal colonization of nasal or paranasal mucosa should be introduced to refer to localized infection visualized endoscopically; eosinophilic mucin is preferred to allergic mucin; and allergic fungal rhinosinusitis (AFRS), eosinophilic fungal rhinosinusitis, and eosinophilic mucin rhinosinusitis (EMRS) are imprecise and require better definition. In particular, to implicate fungi (as in AFRS and EMRS), hyphae must be visualized in eosinophilic mucin, but this is often not processed or examined carefully enough by histologists, reducing the universality of the disease classification. A schema for subclassifying these entities, including aspirin-exacerbated rhinosinusitis, is proposed allowing an overlap in histopathological features, and with granulomatous, chronic invasive, and other forms of rhinosinusitis. Recommendations for future research avenues were also identified.

Figures

Fig. 1

(A) Acute invasive fungal sinusitis with bland infarcted area (×400). (B) Necrotizing inflammation with fibrin thrombi (×100). (C) Numerous hyphae of zygomycetes on hematoxylin and eosin stain (×100). (D) Fungal hyphae on Gomori methenamine-silver stain (×200).

Fig. 2

(A) Computed tomography scan of patient with chronic granulomatous fungal rhinosinusitis involving the right nasal cavity in a chronic invasive granulomatous fungal rhinosinusitis with bony destruction of paranasal sinuses extending into right orbit. (B) Extensive granulomatous process in a fibrotic background on hematoxylin and eosin stain (×100). (C) Fungal hyphae inside giant cells on periodic acid-Schiff stain (×400). (D) Fungal hyphae inside giant cells on Gomori methenamine-silver stain (×400).

Fig. 3

(A) Coronal computed tomography scan of immunosuppressed patient with amyloidosis and chronic invasive mucormycosis in chronic invasive fungal rhinosinusitis. Right ethmoid and pterygopalatine space involvement. (B) Nongranulomatous chronic inflammatory infiltrate with transverse section of fungal hyphae eosinophilic Splendore-Hoeppli phenomenon on hematoxylin and eosin stain (×200). (C) Periodic acid-Schiff stain (×400). (D) Gomori methenamine-silver stain (×200).

Fig. 4

(A) Computed tomography scan showing a fungus ball in the left maxillary sinus on coronal view with hyperdense secretions. (B) Gross photo of a fungal ball. (C) Fungal hyphae on periodic acid-Schiff stain (×200). (D) Gomori methenamine-silver stain (×200).

Fig. 5

(A) Computed tomography coronal scan showing recurrence of allergic fungal rhinosinusitis following prior surgery. Hyperdensity of mucin within right ethmoid and maxillary sinuses. (B) Allergic fungal sinusitis with allergic mucin (×100). (C) Fungal hyphae inside allergic mucin on periodic acid-Schiff stain (×400). (D) Gomori methenamine-silver stain showing hyphae within the mucin (×100).

Fig. 6

Histological images of eosinophilic mucin taken from two patients (top and bottom). The left panels show the mucin stained with Gomori methenamine-silver (GMS), and no hyphae or fungal elements are visible in these sections. The right panels are serial sections and show alternative ways of visualizing fungi. At the top a chitinase stain, which detects chitin present in all fungal cell walls, but not bacteria (note the septate hyphae) (×400). The bottom right shows a serial section of the right side GMS stain, but instead stained with an anti-Alternaria polyclonal antibody. Note again the lack of fungal visualization on GMS, which is in contrast to anti-Alternaria staining, and demonstrates not only the presence of intact fungi but also its remnants and fungal antigens. These images question the sensitivity of GMS staining to rule the presence of fungal matter, including hyphae (×200).

Fig. 7

The inter-relationships of various forms of chronic rhinosinusitis derived by consensus discussion. AFRS = allergic fungal rhinosinusitis; EMRS = eosinophilic mucin rhinosinusitis; EFRS = eosinophilic fungal rhinosinusitis; RS = rhinosinusitis.