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Paediatric lung disease
Original research
Prevalence of lung cysts in adolescents and adults with a germline DICER1 pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1 Registry
  1. Alexander T Nelson1,2,3,4,
  2. Lauren M Vasta5,
  3. Dave Watson6,
  4. Jung Kim5,
  5. Anne K Harris2,3,4,
  6. Ana F Best7,
  7. Laura A Harney8,
  8. Ann G Carr8,
  9. Nicole Frederickson2,3,4,
  10. Louis P Dehner9,
  11. Christian P Kratz10,
  12. Kelly N Hagedorn11,
  13. William A Mize11,
  14. Alexander Ling12,
  15. Yoav H Messinger2,3,4,
  16. D Ashley Hill9,13,
  17. Kris Ann P Schultz2,3,4,
  18. Douglas R Stewart5
  1. 1University of Minnesota Medical School, Minneapolis, Minnesota, USA
  2. 2International Pleuropulomary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, Minnesota, USA
  3. 3International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, Minnesota, USA
  4. 4Cancer and Blood Disorders, Children's Minnesota, Minneapolis, Minnesota, USA
  5. 5Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
  6. 6Research Institute, Children's Minnesota, Minneapolis, Minnesota, USA
  7. 7Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  8. 8Westat Inc, Rockville, Maryland, USA
  9. 9Lauren V. Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA
  10. 10Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Niedersachsen, Germany
  11. 11Department of Radiology, Children's Minnesota, Minneapolis, Minnesota, USA
  12. 12Department of Radiology, NIH Clinical Center, Bethesda, Maryland, USA
  13. 13ResourcePath LLC, Sterling, Virginia, USA
  1. Correspondence to Dr Kris Ann P Schultz, Cancer and Blood Disorders, Children's Minnesota, Minneapolis, Minnesota, USA; krisann.schultz{at}childrensmn.org

Abstract

Background Pleuropulmonary blastoma (PPB), the hallmark tumour associated with DICER1-related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline DICER1 pathogenic/likely pathogenic (P/LP) variants.

Methods Individuals were enrolled in the National Cancer Institute Natural History of DICER1 Syndrome study, the International PPB/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline DICER1 P/LP variant with first chest CT at 12 years of age or older were selected for this analysis.

Results In the combined databases, 110 individuals with a germline DICER1 P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB.

Conclusion Lung cysts are common in adolescents and adults with germline DICER1 variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.

  • Imaging/CT MRI etc
  • Lung Cancer
  • Paediatric Lung Disaese
  • Rare lung diseases

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/thorax-2023-221024

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • DAH, KAPS and DRS are joint senior authors.

    • Contributors ATN, LMV, KAPS and DRS take full responsibility for the content of the manuscript including the data and analyses. All authors contributed to the design of the study. ATN, LMV, AKH, LAH, AGC, NF, KNH, AL, YHM, DAH, KAPS and DRS contributed to the acquisition of data. ATN, LMV, DW, AKH, KAPS and DRS contributed to the development of the analysis plan. ATN, LMV and DW performed the analysis. ATN, LMV, JK, AFB and KNH contributed to data visualisation. All authors contributed to the interpretation of data. ATN, LMV, KAPS and DRS drafted the manuscript. DAH, KAPS and DRS supervised the study. All authors critically revised the manuscript and approved the final version for submission.

    • Funding The International PPB/DICER1 Registry is supported by the Pine Tree Apple Classic Fund, Children’s Minnesota Foundation, Mendon F Schutt Foundation and Rein in Sarcoma. This analysis was supported by a grant from the Children’s Minnesota Internal Research Grant Program and supported by funding from the National Institutes of Health’s National Cancer Institute grants 1R37CA244940 and 2R01CA143167 and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, Rockville. Dr Kratz has been supported by the Deutsche Kinderkrebsstiftung (DKS-2021.25).

    • Competing interests Dr Hill is the owner of ResourcePath LLC, a company which does research and development of laboratory tests including for DICER1-related cancers. The work is unrelated to the information presented in this article. Dr Stewart provides telegenetics services for Genome Medical, Inc, in accordance with relevant National Cancer Institute policies. The remaining authors have no conflicts to disclose.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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