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      Acute Invasive Fungal Rhinosinusitis: Frozen Section Histomorphology and Diagnosis with PAS Stain

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          Abstract

          Acute invasive fungal rhinosinusitis (AIFRS) is a fulminant infection in immunocompromised patients requiring rapid diagnosis (DX), frequently made on frozen section (FS) of sinonasal biopsies, followed by prompt surgical debridement. However, FS interpretation is often difficult and DX sometimes not possible. In this study we sought to characterize reasons for misinterpretation and methods to improve diagnostic accuracy. The FS slides from 271 biopsies of suspected AIFRS in a 16-year period were reviewed and the morphologic features evaluated for their utility in DX. Recurring specific patterns of necrosis were identified, which to our knowledge have not been described in the literature. Although they provide strong evidence for AIFRS, identifying fungus consistently in necrotic tissue is essential for DX. Clues to identifying fungus and pitfalls in misidentification were identified, but even with expert knowledge of these, a gap in accurate DX remained. The key to FS DX of AIFRS is to improve fungus identification in necrotic tissues. Methods had been sought in the past to stain fungus at FS without consistent success. The Periodic Acid Schiff’s Reaction for Fungi was modified by our histopathology department for use on frozen tissue (PASF-fs) resulting in effective staining of the fungus. It stained fungus on all 62 positive slides when applied retrospectively over hematoxylin and eosin (H&E) stained FSs and used prospectively at FS for DX. Although knowledge of histologic morphology on FS is important, the crucial value of this study is the novel use of PASF-fs to identify fungus in the DX of AIFRS.

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          The online version of this article (10.1007/s12105-018-0965-8) contains supplementary material, which is available to authorized users.

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          Most cited references16

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          Survival outcomes in acute invasive fungal sinusitis: a systematic review and quantitative synthesis of published evidence.

          Acute invasive fungal sinusitis (AIFS) is an aggressive and often fatal infection. Despite improvements in medical and surgical therapy, survival remains limited and the factors that contribute to patient outcomes remain poorly understood. The current study systematically reviews and quantitatively synthesizes the published literature to characterize prognostic factors associated with survival.
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            Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients.

            Rhino-orbital-cerebral disease is a significant manifestation of zygomycosis in solid organ transplant (SOT) recipients. However, its characteristics and outcome are not well addressed. SOT recipients with zygomycosis as per the European Organization for Research and Treatment in Cancer and the Mycoses Study Group criteria in a cohort study at our centers published previously and those identified with a PubMed search from the 1950s to November 2009 were studied. Patients with mycosis involving the sinuses, orbits, or central nervous system (CNS) were included. Patients comprised a total of 90 SOT recipients with rhino-orbital-cerebral zygomycosis, including 13 in our cohort and 77 in the literature. CNS disease occurred in 57% (51 of 90). Overall mortality was 52.3% (46 of 88), and the mortality in patients with CNS disease was 73.5% (36 of 49). In logistic regression analysis, older age (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.04-1.21, P=0.002) was associated with a higher mortality rate, whereas lipid formulations of amphotericin B compared with amphotericin B deoxycholate (OR 0.09, 95% CI 0.02-0.50, P=0.006) and surgery (OR 0.12, 95% CI 0.01-0.94, P=0.043) were independently associated with an improved survival even when controlled for CNS involvement and the era of diagnosis of disease. Rhino-orbital-cerebral zygomycosis, particularly CNS disease, is associated with substantial mortality rate in SOT recipients. Older age is a significant risk factor for mortality, whereas lipid formulations of amphotericin B and surgery improved outcomes.
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              Invasive fungal sinusitis: a 15-year review from a single institution.

              The aim of this study was to review our experience with patients with invasive fungal sinusitis (IFS) to determine outcomes and identify factors that may affect patient survival. A retrospective review was performed. Forty-three patients were identified accounting for 45 cases of IFS. The underlying reasons for immunosuppression were hematologic malignancy (28 patients), diabetes mellitus (10 patients), solid organ transplant (3 patients), chronic steroid use (3 patients), and acquired immunodeficiency syndrome (1 patient). Eight of 45 cases (18%) died of IFS. Of the 28 cases associated with hematologic malignanancy, 3 patients died of IFS (11%) and 4 patients (14%) died of other causes with persistent IFS. None of these 7 patients had recovery of their absolute neutrophil count, and all patients who recovered from IFS recovered to a normal absolute neutrophil count. Four of 10 (40%) diabetic patients died of IFS, and 66% of survivors had persistent neurological or visual morbidity. The imortality rate was 29% for patients infected with Mucor and 11% for patients injected with Aspergillus. We have found the overall mortality rate directly related to IFS to be 18%. The rate is higher for diabetic patients than for patients with hematologic causes for their immunosuppression. This is likely because of the higher index of suspicion and early diagnosis and treatment of patients with neutropenia and a less-fulminant, slower-progressing form of IFS from Aspergillus, apparently a less virulent fungus than Mucor. Intracranial involvement and failure to recover from neutropenia are the factors that led to poor prognosis in this series.
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                Author and article information

                Contributors
                717-531-3521 , hcrist@pennstatehealth.psu.edu
                Journal
                Head Neck Pathol
                Head Neck Pathol
                Head and Neck Pathology
                Springer US (New York )
                1936-055X
                1936-0568
                12 September 2018
                12 September 2018
                September 2019
                : 13
                : 3
                : 318-326
                Affiliations
                [1 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Department of Pathology, College of Medicine, , The Pennsylvania State University, ; 500 University Drive, Hershey, PA 17033-0850 USA
                [2 ]ISNI 0000 0001 2097 4281, GRID grid.29857.31, Division of Otolaryngology – Head and Neck Surgery, Department of Surgery, College of Medicine, , The Pennsylvania State University, ; Hershey, PA USA
                Author information
                http://orcid.org/0000-0001-9209-6932
                Article
                965
                10.1007/s12105-018-0965-8
                6684546
                30209746
                14eda9dc-266c-4dc0-b161-3fe2ca556469
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 20 July 2018
                : 7 September 2018
                Categories
                Original Paper
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2019

                Pathology
                acute invasive fungal rhinosinusitis,invasive fungal sinusitis,frozen section,diagnosis,fungus stain,pasf

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