Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive and life-threatening condition that predominantly affects immunocompromised patients. Historically, the disease-specific survivorship has been less than 50% at 3 months; however, more recent studies have found survivorship to approximate 60% over the same time interval.1 Consequently, early diagnosis is of paramount importance as it permits timely surgical debridement and administration of systemic anti-fungal therapy to increase the probability of survival. The evaluating clinician must have a high degree of suspicion, as AIFRS often presents with nonspecific signs and symptoms. The gold standard for diagnosis is pathologic confirmation of mucosal invasion by fungal organisms within the sinonasal mucosa via biopsy at the bedside or in the operating room. Delays in biopsy may setback treatment and contribute to increased morbidity and mortality.2 Though computed tomography (CT) and magnetic resonance imaging can be acquired rapidly, the changes on imaging suggestive of AIFRS may not present until later in the disease course. Visualization of mucosa through bedside nasal endoscopy is frequently used to evaluate for changes including mucosal pallor, crusting, discoloration, and frank necrosis.3 However, despite the ubiquitous use of bedside nasal endoscopy, the role of routine bedside, endoscopically-guided nasal biopsy has not yet been established. In consideration of these advances, this best practices report evaluates the role of routine bedside endoscopic nasal biopsy in obtaining a timely and accurate histologic diagnosis of AIFRS. Studies pertaining to the use of bedside biopsy in the diagnosis of AIFRS published in the peer-reviewed literature published between 2000 and 2021 were identified by searching the PubMed database. The search string used was: “(((acute invasive fungal rhinosinusitis) OR (acute invasive fungal sinusitis)) AND ((biopsy) OR (early diagnosis)))”. This search yielded 178 results. Articles that were non-English, case reports or descriptive case series, incorporated chronic invasive fungal sinusitis diagnoses, did not use bedside biopsy, or failed to quantify biopsy outcomes were excluded. The resulting four references were incorporated in this literature review (Table I).2-5 4 Silveira et al. conducted a single-center retrospective study using a standardized protocol of universal serial nasal endoscopy and bedside biopsy of suspicious areas in potential AIFRS cases presenting with immunocompromise and >48 hours of fever of unknown origin and concurrent sinonasal symptoms.4 Of the 43 patients in the study cohort, 32 cases (74.4%) had positive and 11 (25.6%) had negative frozen-section bedside biopsies. The sensitivity of frozen-section biopsy was 90.6%, specificity 72.7%, positive predictive value 90.6%, negative predictive value 72.7%, and accuracy of 86%. However, the results of this study were predicated on the identification of mucosal abnormalities on nasal endoscopy through serial examination introducing potential delay in AIFRS diagnosis, though time-to-surgery was not evaluated.4 The potential for missing an AIFRS diagnosis secondary to unremarkable nasal endoscopy was investigated by Payne et al. in a retrospective review of 131 patients with suspected AIFRS based on underlying immunodeficiency and concern for sinusitis accrued over 15 years at a single institution.5 Eighty-four percent (n = 110) underwent biopsy—though there was no differentiation between bedside and operating room biopsies—with AIFRS confirmed in 37.2% (n = 41) of the biopsied cohort. The middle turbinate is frequently involved in cases of AIFRS and biopsy in this scenario has a sensitivity of 75% to 86% for AIFRS diagnosis, but the middle turbinate may not be involved and disease may be localized exclusively within the paranasal sinuses.3, 5 Indeed, Payne et al. noted that nasal endoscopy was normal in 60% of patients biopsied (n = 66/110) and in 29.7% of those ultimately diagnosed with AIFRS on biopsy (n = 12/41). In cases with unremarkable endoscopy, objective immunocompromise (absolute neutrophil count [ANC] <500/μL) or abnormal CT findings were found in 68.2% and 23.6% of those biopsied, and 82.9% and 36.8% of proven AIFRS cases, respectively. The likelihood of missing a diagnosis of AIFRS in a patient with low clinical suspicion is small and there were no missed AIFRS diagnoses among patients who did not demonstrate severe neutropenia, concerning imaging findings or abnormalities on nasal endoscopy.5 The case for biopsy in situations with borderline or normal nasal endoscopy is often bolstered by high clinical suspicion suggested by severe neutropenia (ANC <1,000/μL) and/or CT findings.1, 5 In a retrospective review of presumed AIFRS—based on predisposing immunocompromise with concurrent fever of unknown origin and/or abnormal paranasal sinus CT and/or sinonasal symptoms—Lagos et al. performed universal nasal endoscopy in all 50 potential cases.3 Forty-one cases (82%) underwent biopsy, of which 90.2% were performed at bedside. Biopsy was indicated if there were mucosal abnormalities on endoscopy, specifically crusting, necrosis and macroscopic hyphae, and/or abnormal imaging findings with MRI used in cases of high clinical suspicion with unremarkable endoscopy to detect abnormalities in areas that could not be visualized endoscopically, such as the paranasal sinuses or pterygopalatine fossa.3 Despite the use of both imaging and endoscopic data in concert with clinical findings, AIFRS was missed in one of nine biopsied cases (11.1% false-negative rate). The potential for bedside biopsy to miss AIFRS diagnoses was highlighted by Fernandez et al. in their single-center retrospective review of proven AIFRS. Bedside biopsy was performed in 7 of 19 cases, and 28.5% (n = 2) of biopsies were non-diagnostic. These cases were, ultimately, diagnosed by biopsy obtained in the operating room.2 The potential for non-diagnostic bedside biopsy highlights the importance of early imaging, which may discern disease that would be missed on endoscopy alone and can facilitate early decision-making. The same study highlighted the potential role for bedside biopsy in augmenting the diagnostic ability of nasal endoscopy. In 2 of 19 (10.5%) cases with “doubtful” endoscopy, bedside biopsy resulted in the confirmatory diagnosis.2 The literature indicates that bedside biopsy has high levels of accuracy in the setting of abnormal mucosal targets identified on nasal endoscopy, but is also subject to potential false-negative results, particularly in the unoperated patient whose sinuses may harbor occult disease hidden to endoscopy or identified on imaging but inaccessible at the bedside. Optimal diagnostic workup for AIFRS entails the use of 1) clinical signs and symptoms (e.g., pain, fever), 2) nasal endoscopy findings, 3) objective evidence of immunocompromised status (e.g., neutropenia), and 4) imaging findings to stratify patients into low or high clinical suspicion for AIFRS. As demonstrated in the literature, abnormalities in these areas could suggest underlying AIFRS and suspicion for this diagnosis is unlikely to be allayed by negative results on routine bedside biopsy. In conclusion, routine bedside biopsy has a limited role in the evaluation of patients with suspected AIFRS and that clinical suspicion should warrant comprehensive sinonasal evaluation and targeted biopsy in the operating room. All of the included studies are level IV evidence (five retrospective case series).
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Open Access
Aug 24, 2023
Anushia Ashokan + 6
