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 pathogenic variants of the DICER1 gene. The International Pleuropulmonary Blastoma/DICER1 Registry is a valuable resource for information about this rare malignancy.[1,2] The following subtypes of pleuropulmonary blastoma have been identified: Type I Type I pleuropulmonary blastoma is a purely lung cystic neoplasm with subtle malignant changes that typically occurs in the first 2 years of life. Patients have a good prognosis. The median age at diagnosis for Type I tumors is 7 months,[3] and there is a slight male predominance. Transition from Type I to Type III occurs. However, a significant proportion of Type I lesions may not progress to Type II and Type III tumors.[2,4] Histologically, these tumors appear as a multilocular cyst with variable numbers of primitive mesenchymal cells beneath a benign epithelial surface. Skeletal differentiation occurs 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] Type Ir Type Ir was originally recognized in older siblings of patients with pleuropulmonary blastoma but can also be seen in very young children. A lung cyst in an older individual with a DICER1 variant or in a relative of a patient with pleuropulmonary blastoma is most likely to be Type Ir.[2] This is a purely cystic tumor that lacks a primitive cell component. The r designation signifies regression or nonprogression. In the International Pleuropulmonary Blastoma Registry experience, most Type I and Type Ir cysts are unilateral (74%), one-half are unifocal, and 55% are larger than 5 cm. Pneumothorax may be present at diagnosis in up to 30% of Type I and Type Ir pleuropulmonary blastoma cases.[2] Type II In the International Pleuropulmonary Blastoma Registry, the median age at diagnosis is 35 months, and distant metastases are present at the time of diagnosis in 7% of patients.[2] Type II exhibits both cystic and solid components. The solid areas have mixed blastomatous and sarcomatous features. Most of the cases exhibit rhabdomyoblasts, and nodules with cartilaginous differentiation are common.[5] Anaplasia is present in up to 60% of the cases.[6] Type III In the International Pleuropulmonary Blastoma Registry, the median age at diagnosis is 41 months, and distant metastases are present at the time of diagnosis in 10% of patients.[2] Type III is a purely solid neoplasm, with the blastomatous and sarcomatous elements described for Type II. Anaplasia is present in 70% of patients.[6,7,8] 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. The International Pleuropulmonary Blastoma Registry reported on 350 centrally reviewed and confirmed cases of pleuropulmonary blastoma over a 50-year period (see Table 1).[2] References: GermlineDICER1Pathogenic Variants Close to two-thirds of patients with pleuropulmonary blastoma have a germline DICER1 pathogenic variant. 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 pathogenic variants have been associated with the following:[1,2,3,4,5] The penetrance of DICER1 germline pathogenic variants associated with each pathological 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 variants.[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 pathogenic variants 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] Surveillance As with other cancer predisposition conditions, before individuals with DICER1 pathogenic variants 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 sex-specific preventive screening studies (see Table 2).[5] References: Presenting symptoms for children with 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] Imaging evaluation may include chest radiography, computed tomography, magnetic resonance imaging, and echocardiography. Primary, recurrent, and/or extracranial metastatic pleuropulmonary blastoma presents with an fluorine F 18-fludeoxyglucose–avid lesion on positron emission tomography imaging.[4] References: In a comprehensive analysis of 350 patients reported by the International Pleuropulmonary Blastoma Registry, only two prognostic factors were identified: the type of pleuropulmonary blastoma and the presence of metastatic disease at diagnosis.[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 pathogenic variant 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%. TP53 expression was determined by IHC and grouped as follows: 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. Comparisons of concordance statistics showed no significant difference in prognostication when using morphological types compared with TP53 expression groups (P = .647).[5] 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, according to subtype, are discussed below.[3,6] Type I and Type Ir Surgery is the treatment of choice for patients with Type I and Type Ir pleuropulmonary blastoma. In the International Pleuropulmonary Blastoma Registry series, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 90% and 98%, respectively, for Type I, and 96% and 100%, respectively, for Type Ir. Approximately 10% of cases progressed to Type II or Type III after surgery. However, adjuvant chemotherapy has been used in almost 40% of patients with Type I disease, and it may be useful for patients at increased risk of recurrence or progression.[3,4,7] The International Pleuropulmonary Blastoma/DICER1 Registry reported that between 2006 and 2022, there were 205 children who had centrally reviewed Type I or Type Ir pleuropulmonary blastoma. Of these children, 39% with Type I and 5% with Type Ir received chemotherapy.[7] Type II and Type III For patients with Type II and Type III pleuropulmonary blastoma, a multimodal sarcoma treatment approach is recommended. This approach usually includes rhabdomyosarcoma regimens and either upfront or delayed surgery.[3,4,8] Anthracycline-containing regimens appear to be the most effective.[4] In the Pleuropulmonary Blastoma Registry series, the 5-year DFS and OS rates were 59% and 71%, respectively, for Type II, and 37% and 53%, respectively, for Type III.[3] In this group of patients, approximately 50% of relapses occurred in the brain.[3] The International Pleuropulmonary Blastoma/DICER1 Registry reported the outcomes of children with Type II and Type III pleuropulmonary blastoma whose first treatment was ifosfamide, vincristine, dactinomycin, and doxorubicin (IVADo). From 1987 to 2021, 314 children with centrally confirmed Type II and Type III pleuropulmonary blastoma who received upfront chemotherapy were enrolled, 132 of whom (75 with type II and 57 with type III) received IVADo chemotherapy.[9] The role of radiation therapy is not well defined. While the use of radiation did not impact survival in the International Pleuropulmonary Blastoma Registry series, only 20% of patients with Type II and Type III received it.[3] References: A retrospective review included 35 children with Type II or Type III pleuropulmonary blastoma 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). 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] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists 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 children and adolescents with cancer.[2] At these 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. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies 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 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 in the United States. 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] In children and adolescents, the designation of a 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 diagnosed in children aged 0 to 14 years and 9.3% of the cancers diagnosed in adolescents aged 15 to 19 years. These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the low number 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. This summary was comprehensively reviewed. 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>. [PMID: 31593396] Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images. Disclaimer Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page. Contact Us More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us. Last Revised: 2024-08-23 This information does not replace the advice of a doctor. Ignite Healthwise, LLC 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 Ignite Healthwise, LLC.Topic Contents
Childhood Pleuropulmonary Blastoma Treatment (PDQ®): Treatment - Health Professional Information [NCI]
Types of Pleuropulmonary Blastoma
Type I Type Ir Type II Type II/III or III a Adapted from Messinger et al.[2]and Nelson et al.[3] Relative proportion of pleuropulmonary blastoma cases 33% 35% 32% Presence of germlineDICER1pathogenic variant 75% 83% 63% 75% Median age at diagnosis (months) 7 31 35 41 5-year overall survival rate 98% 100% 71% 53% Risk Factors and 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.[5] b When CT is performed, techniques to minimize radiation exposure should be used. 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 monthsb Lung cysts Cough Toddlers, if initial CT normal: Repeat between age 2.5 and 3 yearsb Pulmonary blastoma Fever If variant 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 variant 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
Prognostic Factors
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 (08 / 23 / 2024)
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]