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Molecular and ultrastructural morphological analyses of highly metamorphosed Aspergillus fumigatus on human formalin-fixed paraffin-embedded tissue

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Abstract

Invasive fungal infections including invasive pulmonary aspergillosis (IPA) generally have a poor prognosis, because the fungi spread throughout various organs. Therefore, it is important to accurately identify the fungal species for treatment. In this article, we present the results of pathological and molecular morphological analyses that were performed to elucidate the cause of respiratory failure in a patient who died despite suspicion of IPA and treatment with micafungin (MCFG). Pathological analysis revealed the existence of cystic and linear fungi in lung tissue. The fungi were identified as Aspergillus fumigatus (A. fumigatus) by partial sequencing of genomic DNA. Correlative light microscopy and electron microscopy (CLEM) analysis confirmed that fungi observed with light microscopy can also be observed with scanning electron microscopy (SEM) using formalin-fixed paraffin-embedded tissue sections. SEM revealed an atypical ultrastructure of the fungi including inhomogeneous widths, rough surfaces, and numerous cyst-like structures of various sizes. The fungi showed several morphological changes of cultured A. fumigatus treated with MCFG that were previously reported. Our results indicate that integrated analysis of ultrastructural observation by SEM and DNA sequencing may be an effective tool for analyzing fungi that are difficult to identify by conventional pathological analysis.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Hirohisa Okushima and Yuko Hayakawa for the technical assistance with the ultrastructural analysis.

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS), KAKENHI Grant Number: JP22K06944 (T.A.).

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Authors and Affiliations

  1. Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University School of Medicine, Higashi 2-1-1-1, Midorigaoka, Asahikawa, 078-8510, Japan

    Kazuhiro Matsumoto, Masanori Goto, Yuki Kamikokura, Kumi Takasawa, Masayo Kamikokura & Akira Takasawa

  2. Department of Diagnostic Pathology, Asahikawa Medical University Hospital, Asahikawa, Japan

    Yuki Kamikokura

  3. Medical Laboratory and Blood Center, Asahikawa Medical University Hospital, Asahikawa, Japan

    Nobuyuki Kobayashi

  4. Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Tomoyuki Aoyama & Taro Murakami

  5. Division of Endocrinology, Metabolism, and Rheumatology Department of Internal Medicine, Asahikawa Medical University Hospital, Asahikawa, Japan

    Yuta Ikechi, Tomoki Kawahata, Kitaru Tanaka, Sayaka Takatori, Daisuke Fujishiro & Kensaku Okamoto

  6. Center for Integrated Medical Education and Regional Symbiosis, Asahikawa Medical University Hospital, Asahikawa, Japan

    Yuichi Makino

  7. Asahikawa Medical University Hospital, Asahikawa, Japan

    Yuji Nishikawa

Authors
  1. Kazuhiro Matsumoto
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  2. Masanori Goto
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  14. Kensaku Okamoto
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  15. Yuichi Makino
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Corresponding authors

Correspondence to Masanori Goto or Akira Takasawa.

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Matsumoto, K., Goto, M., Kamikokura, Y. et al. Molecular and ultrastructural morphological analyses of highly metamorphosed Aspergillus fumigatus on human formalin-fixed paraffin-embedded tissue. Med Mol Morphol 57, 326–332 (2024). https://doi.org/10.1007/s00795-024-00402-2

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