Almost all cases of pleuropulmonary blastoma (PPB), the most common lung malignancy in childhood, are related to biallelic pathogenic variants in DICER1, a gene encoding an RNase III involved in the biogenesis of micro-RNAs, organogenesis and tumor suppression.1 2 Over 70% of patients with PPB are affected by the pleiotropic DICER1-related tumour susceptibility syndrome caused by heterozygous germline DICER1 loss-of-function variants. After a second somatic DICER1 missense mutation has occurred, these individuals may develop PPB, other tumours and non-neoplastic conditions in the thyroid gland, genitourinary system, and several other extrapulmonary sites.2–4

During the first 7 years of life, PPB can progress through age-related, increasingly more aggressive, pathological types.2 5 6 Type I PPB is a peripheral, multilocular, cystic lesion with epithelium-covered stromal septa containing variable subepithelial aggregates of primitive malignant mesenchymal (blastemal) cells.2 It is diagnosed at a median age of 7 months and has a favourable postoperative 5-year overall survival (OS) of 98%, according to the International PPB/DICER1 Registry (IPPB/D1R).5 Instead, type II PPB is diagnosed at a median age of 35 months, has a 5-year OS of ≈70% and consists of a mixture of cystic areas and solid, grossly visible parts with sarcomatous elements and more numerous blastemal cells.1 2 6 Type III PPB, diagnosed at a median age of 39 months, has the worst outcome (5-year OS of 53%) being an entirely solid mass that, besides undifferentiated blastemal cells, may contain various sarcomatous tissues and sometimes clusters of anaplastic giant cells.1 2 6

Importantly, type I PPBs do not always progress but may remain as such or as multilocular or unilocular cystic lesion, named type Ir (regressed or non-progressed) PPB that is very similar …