Intermediate Invasive Fungal Sinusitis, a Distinct Entity From Acute Fulminant and Chronic Invasive Fungal Sinusitis

Abstract

Background: The current classification system of invasive fungal sinusitis (IFS) includes acute (aIFS) and chronic (cIFS) phenotypes. Both phenotypes display histopathologic evidence of tissue necrosis, but differ by presence of angioinvasion, extent of necrosis, and disease progression. aIFS is defined by a rapid onset of symptoms, while cIFS slowly progresses over ≥12 weeks. However, a subset of IFS patients do not fit into the clinical presentation and histopathologic characteristics of either aIFS or cIFS. Objectives: To investigate the demographic, clinical, and histopathologic characteristics of a distinct subset of IFS. Methods: Retrospective review of patients with IFS from a single tertiary-care institution (2010-2020). Patients with symptoms for ≤4 weeks were classified as aIFS if they displayed endoscopic evidence of mucosal necrosis or fungal angioinvasion on pathology. Patients with slowly progressive IFS for ≥12 weeks were classified as cIFS. Patients with symptom duration between 4 and 12 weeks with evidence of invasive fungal disease were classified as a new entity and were further investigated. Results: Of the 8 patients identified, 50% were immunosuppressed at presentation. The mean symptom duration prior to presentation was 50.5 days (SD 16.8), and common symptoms included facial pain (100%), vision change (87.5%), and blindness (37.5%). Two patients (25%) died of their disease. Sites of fungal involvement confirmed by histopathology included sphenoid (62.5%) and ethmoid sinuses (12.5%), orbital apex (25%), optic nerve (12.5%), pterygopalatine fossa (12.5%), and clivus (12.5%). Fungal elements but without obvious angioinvasion, were identified in all specimens, and fungus balls (50%), granulomas (37.5%), and giant cells (25%) were also observed on histopathology. CT and MRI radiographic imaging showed findings consistent with orbital, intracranial, or skull base involvement in all patients. Conclusion: We propose intermediate IFS as a new subgroup of patients with IFS who do not fit into the standard classification of aIFS or cIFS.

Sinonasal Orbital Apex Syndrome, Horner Syndrome and Pterygopalatine Fossa Infection: A Case Report and Mini-Review

“…The pterygopalatine fossa was inflamed, expanded and widely communicated with the orbital apex via an inferior orbital fissure and with the lateral recess of the sphenoid sinus via dehiscence through the posterior wall. Most observed changes can result from a fungal ball evolving into invasive fungal RS causing orbital apex syndrome, pterygopalatine fossa infection and Horner syndrome [ 24 ]. The pathophysiology of clinical features is described in Table 3 .…”

“…Therefore, even extensive growth of the fungi could be only saprophytic colonization or fungal ball on one side of the spectrum or a fatal invasion of the central nervous system in invasive fungal RS on the other side of the spectrum [ 29 ]. Namely, the fungal ball can progress to acute invasive fungal RS [ 23 ] or to micro-invasive form, which was recently termed intermediate invasive fungal RS [ 24 ]. This is a possible explanation of pathogenesis in our patient.…”

RNA Sequencing and Gene Ontology Analysis in Acute Invasive Fungal Sinusitis

“…2 Recent case series have suggested the possibility that fungal sinusitis could be a spectrum of disease. 3,4 The possibility of progression from non-invasive fungal sinusitis to invasive disease is concerning given our lack of understanding of specific risk factors for disease development.…”