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Novel genetic characteristics of multifocal micronodular pneumocyte hyperplasia (MMPH): a case report with frequent BRAF mutations analyzed by next-generation sequencing supporting benign behaviors of MMPH

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Abstract

A woman in her 30s, who was clinically diagnosed with tuberous sclerosis complex, underwent lung transplantation due to lymphangioleiomyomatosis with concomitant multifocal micronodular pneumocyte hyperplasia (MMPH). Histologically, MMPH lesions demonstrated variety in histology; some showed homogenous cells with mild nuclear atypia and elastic fibers proliferation, and the others showed enlarged nuclei without elastic fibers. Because the natural history of MMPH is not well characterized, we used next-generation sequencing to perform a comprehensive genetic analysis for the MMPH lesions to explore their malignant potential. Regardless of their histological variety, three of four lesions had BRAF missense mutations, especially the types frequently detected in atypical adenomatous hyperplasia that is considered to be benign rather than a precursor of adenocarcinoma. None of them had major driver mutations of lung adenocarcinoma, except for BRAF mutations. In conclusion, our study of the lesions from this patient indicated the benign characteristic of MMPH.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgments

This work was carried out (in part) at the Intractable Disease Research Center, Juntendo University.

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Authors and Affiliations

  1. Department of Anatomic Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Chihiro Inoue, Ryoko Saito, Yuto Yamazaki & Hironobu Sasano

  2. Personalized Medical Center, Tohoku University Hospital, Sendai, Miyagi, Japan

    Chihiro Inoue

  3. Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan

    Ryoko Saito, Fumiyoshi Fujishima, Mika Watanabe & Hironobu Sasano

  4. Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan

    Satsuki Kishikawa & Takuo Hayashi

  5. Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan

    Toshio Kumasaka

  6. Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan

    Takehiro Yamada & Hisashi Oishi

Authors
  1. Chihiro Inoue
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  2. Ryoko Saito
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  3. Satsuki Kishikawa
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  4. Takuo Hayashi
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  5. Toshio Kumasaka
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  6. Takehiro Yamada
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  7. Hisashi Oishi
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  8. Yuto Yamazaki
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  9. Fumiyoshi Fujishima
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  10. Mika Watanabe
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  11. Hironobu Sasano
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Contributions

All the authors have contributed significantly to the content of the manuscript. CI and RS conceived and designed the study; CI drafted the manuscript; TH, TK, FF, and MW assisted in the pathological diagnosis of the present case; TH, SK, and YY assisted in the genetic experiments; TY and HO participated in the collection of clinical data; RS and HS supervised all studies; RS, TH, and HS edited the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Ryoko Saito.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

The experiment reported here was conducted in agreement with the Declaration of Helsinki and was approved by the Ethics Committee of Tohoku University (Miyagi, Japan) and that of Juntendo University (Tokyo, Japan). Requirement of informed consent was waived.

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This article is part of the Topical Collection on Quality in Pathology

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Inoue, C., Saito, R., Kishikawa, S. et al. Novel genetic characteristics of multifocal micronodular pneumocyte hyperplasia (MMPH): a case report with frequent BRAF mutations analyzed by next-generation sequencing supporting benign behaviors of MMPH. Virchows Arch 479, 637–641 (2021). https://doi.org/10.1007/s00428-020-03013-1

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  • DOI: https://doi.org/10.1007/s00428-020-03013-1

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