Pleuropulmonary blastoma: A report on 350 central pathology–confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry

Abstract

Background Pleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases. Methods Patients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported. Germline DICER1 mutations were sought with Sanger sequencing. Results There were 435 cases, and a central review confirmed 350 cases to be PPB; 85 cases (20%) were another entity. Thirty-three percent of the 350 PPB cases were type I or type I regressed (type Ir), 35% were type II, and 32% were type III or type II/III. The median ages at diagnosis for type I, type II, and type III patients were 8, 35, and 41 months, respectively. The 5-year overall survival (OS) rate for type I/Ir patients was 91%; all deaths in this group were due to progression to type II or III. OS was significantly better for type II versus type III (P=.0061); the 5-year OS rates were 71% and 53%, respectively. Disease-free survival (DFS) was also significantly better for type II versus type III (P=.0002); the 5-year DFS rates were 59% and 37%, respectively. The PPB type was the strongest predictor of outcome. Metastatic disease at the diagnosis of types II and III was also an independent unfavorable prognostic factor. Sixty-six percent of the 97 patients tested had a heterozygous germline DICER1 mutation. In this subset, the DICER1 germline mutation status was not related to the outcome. Conclusion Cystic type I/Ir PPB has a better prognosis than type II, and type II has a better outcome than type III. Surveillance of DICER1 carriers may allow the earlier detection of cystic PPB before its progression to type II or III PPB and thereby improve outcomes.

Epithelial inactivation of Yy1 abrogates lung branching morphogenesis

“…Cystic lesions characterize several pulmonary diseases such as congenital cystic adenomatoid malformation (CCAM) and pleuropulmonary blastoma (PPB), the latter being a rare dysontogenetic neoplasm of childhood evolving from a cystic to a solid state over time. Mutations in the human DICER1 gene are found in PPB patients (Hill et al, 2008;Messinger et al, 2015). Analysis of lung tissue from CCAM patients revealed no major changes in YY1 expression.…”

PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood

“…An overgrowth syndrome has been reported in some children where the pathogenic variants are mosaic and affect the RNase IIIb domain (18). PPB presents in four main forms (19). Type I PPB is a purely cystic lesion presenting at a median age of 8 months at diagnosis.…”

“…type III PPB is a purely solid, aggressive primitive neoplasm with a median age of 41 months at diagnosis. The fourth type of PPB, type Ir, is a purely cystic tumor devoid of malignant cells and thought to represent regressed or nonprogressed type I PPB (19). Type I PPB has a 5-year overall survival (OS) of 89%, but it may progress to type II or III PPB.…”

“…Types II and III PPB are treated with aggressive chemotherapy and often radiation. Despite aggressive therapy, these are associated with an OS of only 74% and 53%, respectively (19). The median age of diagnosis for type Ir PPB is 47 months, with an OS of 100% (19).…”

“…Despite aggressive therapy, these are associated with an OS of only 74% and 53%, respectively (19). The median age of diagnosis for type Ir PPB is 47 months, with an OS of 100% (19). The pathophysiology of PPB presents an opportunity for surveillance and early diagnosis of PPB in its earliest and most curable form (20).…”