Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein. This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER. Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy that can present as a pulmonary or pleural mass. In most cases, pleuropulmonary blastoma is associated with germline mutations of the DICER1 gene. The International Pleuropulmonary Blastoma Registry is a valuable resource for information on this rare malignancy.[1,2] The following three subtypes of pleuropulmonary blastoma have been identified: Histologically, these tumors appear as a multilocular cyst with variable numbers of primitive mesenchymal cells beneath a benign epithelial surface, with skeletal differentiation in one-half of the cases.[4] This form of disease can be clinically and pathologically deceptive because of its resemblance to some developmental lung cysts, with over 10% discordance between local and central pathology review.[3] In the Pleuropulmonary Blastoma Registry experience, most Type I and Ir cysts are unilateral (74%), half are unifocal, and 55% are larger than 5 cm. Pneumothorax may be present at diagnosis in up to 30% of Type I and Ir pleuropulmonary blastoma cases.[2] Anaplasia is present in up to 60% of the cases.[6] In the Pleuropulmonary Blastoma Registry, the median age at diagnosis was 35 months, and distant metastases were present at the time of diagnosis in 7% of patients.[2] Median age at diagnosis in the Pleuropulmonary Blastoma Registry was 41 months, and distant metastases were present at the time of diagnosis in 10% of patients.[2] The Pleuropulmonary Blastoma Registry reported on 350 centrally reviewed and confirmed cases of pleuropulmonary blastoma over a 50-year period (see Table 1).[2] Molecular Features In one report, 15 of 16 pleuropulmonary blastoma tumors were positive for IGF1R expression by immunohistochemistry.[9] Genomic profiling showed amplification of the IGF1R gene in 4 of 16 pleuropulmonary blastoma tumors. All of these gene-amplified tumors were Type III. References: In a comprehensive analysis of 350 patients reported by the Pleuropulmonary Blastoma Registry, only two prognostic factors were identified: the type of pleuropulmonary blastoma and the presence of metastatic disease at diagnosis.[1] For more information, see Table 1. In three additional small cohort series, the ability to perform a complete surgical resection was also identified as a prognostic factor.[2,3,4] The presence of a germline DICER1 mutation is not a prognostic factor.[1] A retrospective study analyzed TP53 expression by immunohistochemistry (IHC) in patients with pleuropulmonary blastoma.[5] A total of 143 cases were included in the study, with the following distribution of pleuropulmonary blastoma Types: Type I, 23%; Type Ir, 14%; Type II, 32%; and Type III, 31%. Four groups of TP53 expression by IHC were recorded, which included 0%, 1% to 25%, 26% to 75%, and 76% to 100%. All Type I pleuropulmonary blastomas showed TP53 expressions of 0% to 25%, compared with Type III pleuropulmonary blastomas, which had higher TP53 expressions (>25%) (P < .0001). High TP53 expression (staining observed in >25% of the tumor cells) was significantly associated with age older than 1 year (P = .0033), neoadjuvant therapy (P = .0009), positive resection margin (P = .0008), and anaplasia (P < .0001). TP53 expression was significantly associated with recurrence-free survival (P < .0001) and overall survival (P = .0350). Higher TP53 expression was associated with a worse prognosis. References: Close to two-thirds of patients with pleuropulmonary blastoma have a germline DICER1 mutation. Approximately one-third of families of children with pleuropulmonary blastoma manifest a number of dysplastic and/or neoplastic conditions comprising the DICER1 syndrome.[1,2,3] Germline DICER1 mutations have been associated with the following:[1,2,3,4,5] The penetrance of DICER1 germline mutations associated with each pathologic condition is not well understood, but lung cysts, pleuropulmonary blastoma, and thyroid nodules are the most commonly reported manifestations in individuals who have loss-of-function mutations.[5] Most associated conditions occur in children younger than 10 years, although ovarian tumors and multinodular goiters are described in children and adults aged up to 30 years.[3,5] A study of 102 individuals with DICER1 germline mutations revealed a neoplasm risk of 5% by the age of 10 years and 19% by the age of 50 years.[8] Surveillance and screening recommendations have been proposed.[5] References: As with other cancer predisposition conditions, before individuals with DICER1 mutations are screened, factors that must be considered include typical age of onset of each disease, potential benefits of early detection, and risks and availability of screening modalities. A consensus panel convened by the International Pleuropulmonary Blastoma Registry has proposed guidelines for surveillance. In addition to imaging-based surveillance, individuals and families can be counseled at each visit regarding potential signs and symptoms of DICER1-associated conditions and undergo appropriate age- and gender-specific preventive screening studies (see Table 2).[1] References: Presenting symptoms for pleuropulmonary blastoma are not specific. They commonly include the following: The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the heart/great vessels, mediastinum, diaphragm, and/or pleura.[1,2] Tumor embolism is a known risk, and radiographic evaluation of the central circulation is performed to identify potentially fatal embolic complications.[3] Primary, recurrent, and/or extracranial metastatic pleuropulmonary blastoma presents with a fluorine F 18-fluorodeoxyglucose (18F-FDG)–avid lesion on positron emission tomography imaging.[4] References: There are no standard treatment options for childhood pleuropulmonary blastoma. Current treatment regimens for these rare tumors have been informed by consensus opinion. The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network–European Registry) published comprehensive recommendations for the diagnosis and treatment of pleuropulmonary blastoma in children and adolescents.[1] Treatment options for childhood pleuropulmonary blastoma include the following: A complete surgical resection is required for cure.[2] Data from the International Pleuropulmonary Blastoma Registry and the European Cooperative Study Group for Pediatric Rare Tumors suggest that adjuvant chemotherapy may reduce the risk of recurrence.[3]; [4][Level of evidence C1] Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma.[3,4,5] Some general treatment considerations from the International Pleuropulmonary Blastoma Registry include the following:[3,6] References: A retrospective review included children with a diagnosis of pleuropulmonary blastoma Type II and Type III and progressive or recurrent disease who were registered in national and European databases and trials (2000–2018).[1] Patients had a median age of 3.9 years (range, 0.5–17.8 years). The median time to progression was 0.58 years (range, 0.02–1.27 years) from diagnosis despite surgery, chemotherapy (n = 9), and radiation therapy (n = 1). All of these patients died. Patients were diagnosed with recurrent disease at a median age of 4.3 years (range, 1.7–15.1 years) and had a median delay to relapse of 1.03 years (range, 0.03–2.95 years). Recurrent disease occurred locally (n = 12), in combined sites (locally and metastatic) (n = 1), and in metastatic sites (n = 13), including the central nervous system (n = 11) and unspecified sites (n = 2). The 5-year event-free survival rate and overall survival (OS) rate for patients with recurrent disease were both 37% (± 19%; 95% confidence interval). Local therapy (surgery and radiation therapy) had a favorable impact on OS (P = .03 and .02, respectively). References: Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website. Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[1] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life: For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care. The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website. Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3,4,5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer. Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare. The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows: Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of the cancers in adolescents aged 15 to 19 years. These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers. Information about these tumors may also be found in sources relevant to adults with cancer. References: The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. Clinical Presentation and Diagnostic Evaluation This section was renamed from Clinical Presentation. Added text to state that primary, recurrent, and/or extracranial metastatic pleuropulmonary blastoma presents with a fluorine F 18-fluorodeoxyglucose–avid lesion on positron emission tomography imaging (cited Hagedorn et al. as reference 4). This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages. Purpose of This Summary This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood pleuropulmonary blastoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. Reviewers and Updates This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH). Board members review recently published articles each month to determine whether an article should: Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary. The lead reviewers for Childhood Pleuropulmonary Blastoma Treatment are: Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries. Levels of Evidence Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Permission to Use This Summary PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]." The preferred citation for this PDQ summary is: PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Pleuropulmonary Blastoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lung/hp/child-pleuropulmonary-blastoma-treatment-pdq. Accessed <MM/DD/YYYY>. 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Questions can also be submitted to Cancer.gov through the website's Email Us. Last Revised: 2023-12-15 This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.Topic Contents
Childhood Pleuropulmonary Blastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI]
Types of Pleuropulmonary Blastoma and Other DICER1-Associated Neoplasms
Type I Type Ir Type II Type II/III or III a Adapted from Messinger et al.[2,3] Relative proportion of pleuropulmonary blastoma cases 33% 35% 32% Presence of germlineDICER1mutation 75% 83% 63% 75% Median age at diagnosis (months) 7 31 35 41 5-year overall survival 98% 100% 71% 53% Prognostic Factors
Risk Factors
Surveillance
System Associated Condition Signs/Symptoms to Consider Screening: Clinical and Radiographic CBME = ciliary body medulloepithelioma; CT = computed tomography; CXR = chest x-ray; ERMS = embryonal rhabdomyosarcoma; MRI = magnetic resonance imaging; NCMH = nasal chondromesenchymal hamartoma; PPB = pleuropulmonary blastoma; SLCT = Sertoli-Leydig cell tumor; US = ultrasonography. a Adapted from Schultz et al.[1] b When CT is performed, techniques to minimize radiation exposure should be employed. As novel MRI techniques are developed that will eventually allow detection of small cystic lesions, transition to nonradiation containing cross-sectional imaging should be considered. Central nervous system and head and neck (excluding thyroid) – Macrocephaly – Pineoblastoma: Headache, emesis, diplopia, decreased ability for upward gaze, altered gait – Physical examination. – Pineoblastoma – Precocious puberty – Annual routine dilated ophthalmologic examination (generally unsedated) with visual acuity screening from age 3 years through at least age 10 years. – Pituitary blastoma – Pituitary blastoma: Cushing syndrome – Further testing if clinically indicated. – CBME – CBME: Decreased visual acuity and leukocoria – Recommend urgent MRI for any symptoms of intracranial pathology. – NCMH – NCMH: Nasal obstruction Thyroid – Multinodular goiter – Visible or palpable thyroid nodule(s) – Baseline thyroid US by age 8 years, then every 3 years or with symptoms/findings on physical examination. – Persistent cervical lymphadenopathy – Differentiated thyroid cancer – Hoarseness – With anticipated chemotherapy or radiation therapy: Baseline US and then annually for 5 years, decreasing to every 2–3 years if no nodules are detected. – Dysphagia – Neck pain – Cough Lung – PPB – Tachypnea – CXR at birth and every 4–6 months until age 8 years, every 12 months at age 8–12 years; consider a chest CT at age 3–6 months.b – Lung cysts – Cough – Toddlers, if initial CT normal: Repeat between age 2.5 and 3 years.b – Pulmonary blastoma – Fever – If mutation detected at age >12 years, consider baseline CXR or chest CT. – Pain – Pneumothorax Gastrointestinal – Small intestine polyps – Signs of intestinal obstruction – Education regarding symptoms recommended. Renal – Wilms tumor – Abdominal or flank mass and/or pain – Abdominal US every 6 months until age 8 years, then every 12 months until age 12 years. – Renal sarcoma – Cystic nephroma – Hematuria – If mutation detected at age >12 years, consider baseline abdominal US. Female reproductive tract – SLCT – Hirsutism – For females beginning at age 8–10 years: Pelvic and abdominal US every 6–12 months at least until age 40 years. – Gynandroblastoma – Virilization – End of interval is undetermined, but current oldest patient withDICER1-associated SLCT was aged 61 years. – Cervical ERMS – Abdominal distension, pain, or mass – Education regarding symptoms strongly recommended. Clinical Presentation and Diagnostic Evaluation
Treatment of Childhood Pleuropulmonary Blastoma
Treatment of Progressive or Recurrent Pleuropulmonary Blastoma
Treatment Options Under Clinical Evaluation for Childhood Pleuropulmonary Blastoma
Special Considerations for the Treatment of Children With Cancer
Latest Updates to This Summary (12 / 15 / 2023)
About This PDQ Summary
Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein.Childhood Pleuropulmonary Blastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI]