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. 2024 Jun 14;79(7):644-651.
doi: 10.1136/thorax-2023-221024.

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

Alexander T Nelson  1   2   3   4 , Lauren M Vasta  5 , Dave Watson  6 , Jung Kim  5 , Anne K Harris  2   3   4 , Ana F Best  7 , Laura A Harney  8 , Ann G Carr  8 , Nicole Frederickson  2   3   4 , Louis P Dehner  9 , Christian P Kratz  10 , Kelly N Hagedorn  11 , William A Mize  11 , Alexander Ling  12 , Yoav H Messinger  2   3   4 , D Ashley Hill  9   13 , Kris Ann P Schultz  14   3   4 , Douglas R Stewart  5
Affiliations

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

Alexander T Nelson et al. Thorax. .

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.

Keywords: Imaging/CT MRI etc; Lung Cancer; Paediatric Lung Disaese; Rare lung diseases.

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Conflict of interest statement

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.

Figures

Figure 1:
Figure 1:
Lollipop plot of variant distribution within the DICER1 gene among participants with (top) and without (bottom) lung cysts for all participants (A) and one randomly selected family member (B).
Figure 2:
Figure 2:
Representative cross-sectional imaging of lung cysts. (A) Unilocular cyst (white arrow) in the lingula of an adolescent. (B) Multiseptated cyst (white arrow) in the right upper lobe of an adolescent, resected and diagnosed as type Ir pleuropulmonary blastoma.
Figure 3:
Figure 3:
Histogram of number of cysts per participants with lung cysts (n = 42).
Figure 4:
Figure 4:
Color heatmap with distribution of all lung cysts by lung lobe origin and size of cyst (n = 72).
See this image and copyright information in PMC

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References

    1. Kim J, Field A, Schultz KAP, Hill DA, Stewart DR. The prevalence of DICER1 pathogenic variation in population databases. Int J Cancer. 2017;141(10):2030–2036. - PMC - PubMed
    1. Stewart DR, Best AF, Williams GM, et al. Neoplasm Risk Among Individuals With a Pathogenic Germline Variant in DICER1. J Clin Oncol. 2019;37(8):668–676. - PMC - PubMed
    1. Hill DA, Ivanovich J, Priest JR, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009;325(5943):965. - PMC - PubMed
    1. González IA, Stewart DR, Schultz KAP, Field AP, Hill DA, Dehner LP. DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol. 2022;35(1):4–22. - PMC - PubMed
    1. Brenneman M, Field A, Yang J, et al. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model. F1000Res. 2015;4:214. - PMC - PubMed

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