The mutual value of histopathology and ITS sequencing in the diagnosis of mucormycosis.
ITS sequencing
histopathology
molecular pathology
mucormycosis
mycology
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
08 Jan 2024
08 Jan 2024
Historique:
revised:
29
11
2023
received:
25
09
2023
accepted:
13
12
2023
medline:
9
1
2024
pubmed:
9
1
2024
entrez:
9
1
2024
Statut:
aheadofprint
Résumé
Mucormycosis is a fast-progressing disease with a high mortality rate. The most important factor determining survival of patients is early and accurate diagnosis. Although histopathology often recognises invasive mould infections at first, histomorphology alone is insufficient in providing an accurate diagnosis. Unbiased molecular methods to detect and identify fungi are promising, yet their role in complementing routine histopathological workflows has not been studied sufficiently. We performed a retrospective single-centre study examining the clinical value of complementing histopathology with internal transcribed spacer (ITS) sequencing of fungal DNA in the routine diagnosis of mucormycosis. At our academic centre, we identified 14 consecutive mucormycosis cases diagnosed by histopathology and subsequent ITS sequencing. Using histomorphological examination, fungal hyphae could be detected in all cases; however, morphological features were unreliable regarding specifying the taxa. Subsequent ITS sequencing identified a remarkable phylogenetic diversity among Mucorales: the most common species was Rhizopus microsporus (six of 14; 42.9%), followed by Lichtheimia corymbifera (three of 14, 21.4%) and single detections of Rhizopus oryzae, Actinomucor elegans, Mucor circinelloides, Rhizomucor pusillus and Rhizomucor miehei (one of 14; 7.1%, respectively). In one case, we additionally detected Pneumocystis jirovecii in the same lung tissue specimen, suggesting a clinically relevant co-infection. Fungal culture was performed in 10 cases but yielded positive results in only two of 10 (20%), revealing its limited value in the diagnosis of mucormycosis. Our study demonstrates that a combination of histopathology and ITS sequencing is a practically feasible approach that outperforms fungal culture in detecting Mucorales in tissue-associated infections. Therefore, pathologists might adapt diagnostic workflows accordingly when mucormycosis is suspected.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.
Références
Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin. Infect. Dis. 2005; 41; 634-653.
Hoenigl M, Seidel D, Carvalho A et al. The emergence of COVID-19 associated Mucormycosis: a review of cases from 18 countries. Lancet Microbe. 2022; 3; e543-e552.
Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden RT, Kontoyiannis DP. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin. Infect. Dis. 2012; 54; S55-S60.
Thornton CR. The potential for rapid antigen testing for mucormycosis in the context of COVID-19. Expert Rev. Mol. Diagn. 2023; 1-7. https://doi.org/10.1080/14737159.2023.2233906.
Potenza L, Vallerini D, Barozzi P et al. Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients. Blood 2011; 118; 5416-5419.
Burnham-Marusich AR, Hubbard B, Kvam AJ et al. Conservation of mannan synthesis in fungi of the zygomycota and ascomycota reveals a broad diagnostic target. mSphere 2018; 3; e00094-18.
Cornely OA, Alastruey-Izquierdo A, Arenz D et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European confederation of medical mycology in cooperation with the mycoses study group education and research consortium. Lancet Infect. Dis. 2019; 19; e405-e421.
Sangoi AR, Rogers WM, Longacre TA, Montoya JG, Baron EJ, Banaei N. Challenges and pitfalls of morphologic identification of fungal infections in histologic and cytologic SpecimensA ten-year retrospective review at a single institution. Am. J. Clin. Pathol. 2009; 131; 364-375.
Halwachs B, Madhusudhan N, Krause R et al. Critical issues in mycobiota analysis. Front. Microbiol. 2017; 8; 180.
Zacharias M, Kashofer K, Wurm P et al. Host and microbiome features of secondary infections in lethal Covid-19. Science 2022; 25; 104926. https://doi.org/10.1016/j.isci.2022.104926.
Guenter S, Gorkiewicz G, Halwachs B et al. Impact of ITS-based sequencing on antifungal treatment of patients with suspected invasive fungal infections. J. Fungi 2020; 6; 43.
Tamura K, Nei M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol. Biol. Evol. 1993; 10; 512-526.
Tamura K, Stecher G, Kumar S. MEGA11: molecular evolutionary genetics analysis version 11. Mol. Biol. Evol. 2021; 38; msab120.
Stecher G, Tamura K, Kumar S. Molecular evolutionary genetics analysis (MEGA) for MacOS. Mol. Biol. Evol. 2020; 37; 1237-1239.
Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin. Infect. Dis. 2012; 54; S16-S22.
Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E, Petrikkos G. Challenges in the diagnosis and treatment of mucormycosis. Med. Mycol. 2018; 56; S93-S101.
Vitale RG, de Hoog GS, Schwarz P et al. Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales. J. Clin. Microbiol. 2012; 50; 66-75.
Schwarz P, Bretagne S, Gantier J-C et al. Molecular identification of zygomycetes from culture and experimentally infected tissues. J. Clin. Microbiol. 2006; 44; 340-349.