# Pleuropulmonary blastoma
**Pleuropulmonary blastoma** (PPB) is a rare, aggressive malignant tumor of the intrathoracic mesenchyme, arising in the lung, pleura, or both, that occurs almost exclusively in infants and young children, most often before age 6 or 7.[1](https://www.orpha.net/en/disease/detail/64742) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) It is the most common primary malignant neoplasm of the lung in childhood, yet it accounts for only 0.25% to 0.5% of primary pulmonary malignancies in children.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) • [3](https://pubmed.ncbi.nlm.nih.gov/35164911/) More than 65% of affected children carry a heterozygous germline mutation in the *DICER1* gene, making PPB the sentinel disease of the DICER1 tumor predisposition syndrome (OMIM 601200).[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/)
| Key fact | Detail |
|---|---|
| Definition | Aggressive, malignant, dysontogenetic neoplasm of intrathoracic (pulmonary, pleural, or combined) mesenchyme in young children[1](https://www.orpha.net/en/disease/detail/64742) |
| Subtypes | Type I purely cystic; type Ir regressed cystic without primitive cells; type II cystic and solid; type III purely solid[1](https://www.orpha.net/en/disease/detail/64742) • [5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) |
| Genetic cause | Heterozygous germline *DICER1* mutation in over 65% of cases; identified as the genetic cause in 2009[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/) |
| Median age at diagnosis | 7 months (type I), 31 months (Ir), 35 months (II), 41 months (III)[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) |
| 5-year overall survival | 98% (type I), 100% (Ir), 71% (II), 53% (III)[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) |
| Diagnostic accuracy | Of 868 thoracic tumors submitted to the International Registry from 1987 to 2022, 79% (685/868) were confirmed as PPB by central pathology review[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC13274514) |
| Inheritance | Autosomal dominant; about 87% of germline pathogenic variants are inherited from a parent[1](https://www.orpha.net/en/disease/detail/64742) • [6](https://pmc.ncbi.nlm.nih.gov/articles/PMC13274514) |
| Classification codes | ICD-10 C34.x; ICD-11 2C25.Y XH2FY9; OMIM 601200; ORPHA 64742[1](https://www.orpha.net/en/disease/detail/64742) |
## Clinical presentation
The earliest manifestation is usually one or more lung cysts, recognized in the first year of life and sometimes even prenatally; on imaging alone these are difficult to distinguish from non-neoplastic cysts of early childhood.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) Children beyond infancy more often present with respiratory symptoms caused by a mass filling the chest, and symptoms frequently mimic respiratory infection, pneumothorax, or a lung malformation.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) [Pneumothorax](https://www.edgepedia.org/pneumothorax) may be present at diagnosis in up to 30% of type I and Ir cases.[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) The tumor is usually located in the lung but may extend to the mediastinum, diaphragm, or parietal pleura.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/)
## Types and progression
PPB is classified by macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum: type I (purely cystic), type II (cystic and solid), and type III (purely solid).[1](https://www.orpha.net/en/disease/detail/64742) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) A fourth category, type Ir (regressed), is a purely cystic lesion lacking the primitive small-cell component; it was originally recognized in older siblings of patients and is the most likely finding in an older individual with a *DICER1* variant or a relative of a PPB patient.[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq)
**Progression defines the tumor's natural history.** Type I lesions may progress to the more malignant types II and III, which are associated with central nervous system and bone metastasis.[1](https://www.orpha.net/en/disease/detail/64742) In the Registry's 350-case series, cystic PPB progressed to type II or III in 11 of 115 cases (10%) at a median of 23 months (range 3 to 53 months) after diagnosis, and all type I deaths followed such progression.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/) Not all cystic type I lesions progress; some regress to type Ir.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) The most common metastatic sites in advanced disease are within the thorax or the central nervous system, with bone, liver, and lymph nodes also involved.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/)
## DICER1 and the familial tumor predisposition syndrome
PPB is often part of the pleuropulmonary blastoma family tumor and dysplasia syndrome, an autosomal dominant condition caused by germline loss-of-function mutations in *DICER1*, a gene on chromosome 14q32.13 whose protein product is a ribonuclease III enzyme essential for producing microRNAs.[1](https://www.orpha.net/en/disease/detail/64742) • [8](https://pmc.ncbi.nlm.nih.gov/articles/PMC8695383/) Tumors typically carry biallelic variants: an inherited loss-of-function allele plus a tumor-specific missense mutation affecting the RNase IIIb domain, following the Knudson two-hit model.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC13274514) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) The estimated prevalence of pathogenic *DICER1* variants in the general population is about 1 in 10,600.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC8695383/)
**Associated conditions** extend well beyond the lung. Germline *DICER1* variants predispose to pediatric cystic nephroma, Sertoli-[Leydig cell](https://www.edgepedia.org/leydig-cell) tumor and other ovarian sex cord-stromal tumors, botryoid embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, thyroid nodules and thyroid cancer, ciliary body medulloepithelioma, pituitary blastoma, and pineoblastoma.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC6721434/) PPB can also be associated with multilocular cystic nephroma or other neoplasms.[1](https://www.orpha.net/en/disease/detail/64742) Because any of these tumors may be the presenting manifestation of the syndrome, *DICER1* testing is recommended for all individuals with PPB of any type and for children with bilateral, septated, or multiple lung cysts.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC6721434/)
## Diagnosis
Diagnosis is challenging because pure cystic lesions resemble [congenital pulmonary airway malformation](https://www.edgepedia.org/congenital-pulmonary-airway-malformation) (CPAM), pulmonary sequestration, and simple lung cysts, while solid lesions must be distinguished from other pediatric tumors such as rhabdomyosarcoma.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) The historic term type IV CPAM is now recognized as the same clinical and pathologic entity as type I PPB.[10](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793797) Central pathology review has proved critical: in the Registry's 35-year review, 21% of submitted cases (183/868) were not PPB, and among confirmed cases the subtype distribution was 17% type Ir, 28% type I, 30% type II, and 25% type III.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC13274514)
**Workup** requires histology, usually by core-needle (16 to 18 Gauge) or open surgical biopsy, and chest computed tomography with contrast for all types; types II and III additionally require abdominal CT, brain MRI, and radionuclide bone scan for metastatic evaluation.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) No tumor markers are currently available.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) Molecular testing for *DICER1* variants can clarify ambiguous cases and guide surveillance of the patient and relatives.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC13274514)
## Treatment and outcomes
Surgery is the treatment of choice for type I and Ir disease, with complete resection of the involved lung lobe; adjuvant chemotherapy is generally reserved for complicating circumstances such as tumor spillage, incomplete resection, or local invasion.[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC6721434/) In the Registry series, surgery alone and surgery plus chemotherapy gave similar progression risks for cystic disease (11% versus 9%), and chemotherapy had no effect on overall survival for types I and Ir.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/)
Types II and III require a multimodal sarcoma approach combining chemotherapy, usually regimens similar to those used for rhabdomyosarcoma, with surgery performed upfront or after neoadjuvant treatment.[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) Anthracycline-containing regimens such as IVADo (ifosfamide, vincristine, dactinomycin, and doxorubicin) appear to be the most effective; in an EXPeRT analysis, patients given doxorubicin had a 5-year progression-free survival of 70% versus 31.3% without it.[5](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq) • [11](https://pubmed.ncbi.nlm.nih.gov/24041875/) Complete tumor resection is a main prognostic factor.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/) In the 350-case Registry report, 5-year overall survival was 71% for type II and 53% for type III, with central nervous system involvement in about 59% of relapses.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/)
## History and distinction from pulmonary blastoma
PPB was first established as a distinct entity in 1988, when Manivel and colleagues described 11 children with a solid intrathoracic neoplasm whose blastematous and sarcomatous features distinguished it from the adult biphasic [pulmonary blastoma](https://www.edgepedia.org/pulmonary-blastoma).[12](https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819970701%2980%3A1%3C147%3A%3AAID-CNCR20%3E3.0.CO%3B2-X) The International Pleuropulmonary Blastoma Registry, established in 1987, later revealed the familial predisposition and the extrapulmonary tumors of the syndrome.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/) In 2009, Hill and colleagues identified heterozygous germline *DICER1* mutations as the first known genetic cause.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/)
The adult tumor called pulmonary blastoma is a separate disease: a biphasic sarcomatoid lung carcinoma occurring almost exclusively in adults, with a peak incidence in the fourth decade, a marked female predominance (70% of cases), and frequent association with tobacco smoking.[13](https://www.orpha.net/en/disease/detail/64741) PPB is also distinct from infantile pulmonary teratoid tumor.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/)
## References
1. [Pleuropulmonary blastoma, Orphanet (ORPHA:64742)](https://www.orpha.net/en/disease/detail/64742)
2. [Pleuropulmonary blastoma: Evolution of an entity as an entry into a familial tumor predisposition syndrome, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9743680/)
3. [Multimodality Imaging of Pleuropulmonary Blastoma: Pearls, Pitfalls, and Differential Diagnosis, PubMed](https://pubmed.ncbi.nlm.nih.gov/35164911/)
4. [Pleuropulmonary Blastoma: A Report on 350 Central Pathology-Confirmed Cases by the International Pleuropulmonary Blastoma Registry, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4293209/)
5. [Childhood Pleuropulmonary Blastoma Treatment (PDQ), National Cancer Institute](https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq)
6. [Pleuropulmonary Blastoma (PPB) and Diagnostic Pitfalls: A Report from the International PPB/DICER1 Registry, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC13274514)
7. [Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9813943/)
8. [DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8695383/)
9. [Current Management of Pleuropulmonary Blastoma: A Surgical Perspective, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6721434/)
10. [Can Computed Tomography Scans Reliably Distinguish Pleuropulmonary Blastoma From Congenital Lung Malformations? JAMA Network Open](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793797)
11. [Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report, PubMed](https://pubmed.ncbi.nlm.nih.gov/24041875/)
12. [Pleuropulmonary blastoma, Priest et al., Cancer 1997, Wiley](https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819970701%2980%3A1%3C147%3A%3AAID-CNCR20%3E3.0.CO%3B2-X)
13. [Pulmonary blastoma, Orphanet (ORPHA:64741)](https://www.orpha.net/en/disease/detail/64741)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Respiratory conditions › Pulmonary neoplasms*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license