NORD gratefully acknowledges Kris Ann Schultz, MD, and Gretchen Williams, BS, CCRP, Cancer and Blood Disorders Program of Children's Hospitals and Clinics of Minnesota, and the International Pleuropulmonary Blastoma Registry, for assistance in the preparation of this report.
SummaryPleuropulmonary blastoma (PPB) is a rare childhood cancer occurring in the chest, specifically in the lungs or in the coverings of the lungs called "pleura". Three subtypes of PPB exist and are called Type I, Type II, and Type III PPB. Type I PPB takes the form of one or more cysts in the lungs (air-filled pockets) and may be found in very young children with PPB (from birth to about 2 years of age). Type III PPB is entirely solid tumor. Type II PPB includes both cystic and solid parts. Types II and III PPB tend to be found more often after 2 years of age. Type Ir (the “r” stands for regressed/ regressing) is another type of PPB. Under the microscope Type Ir is similar to Type I PPB, but it does not have cancerous cells. Type I, II, and III PPB are usually found in children under the age of approximately 7-8 years; PPB occurs rarely in older children or teenagers, and even more rarely in adults, but Type Ir PPB may be found at any age. Children with Type I have a better outlook ("prognosis") than children with Types II and III PPB; most Type I PPB patients are cured (89%) but Type I PPB can sometimes recur (“come back”) as Type II or III PPB. Treatment for Type I consists of surgery and possibly chemotherapy. Treatment for Types II and III PPB consists of surgery and chemotherapy and possibly radiation therapy. At present, about 50-70% of children with Types II and III PPB are cured.
IntroductionPPB is a childhood cancer in the family of cancers called soft tissue cancers, which are scientifically called sarcomas. PPB is, therefore, a soft tissue sarcoma. Physicians classify diseases this way in order to compare features and to compare treatments. PPB occurs in the lungs and is the most common lung cancer of childhood but PPB has no connection to lung cancers in adults that are often related to tobacco use or asbestos exposure. Like many cancers, PPB can spread through the blood to other areas of the body. When a cancer spreads to another part of the body it is called a "metastasis" of the cancer. Types II and III PPB can metastasize. The most common location for a PPB metastasis is the brain. PPB may also spread to remaining part of the lung, bones, liver and rarely to other organs. PPB can also spread by growing directly into tissues next to the lung like the diaphragm.
Two different sets of symptoms are found in children with PPB, based generally on the child’s age and the type of PPB:
Respiratory Distress Symptoms:
These symptoms tend to be found in Type I PPB in infants and toddlers (under age 2 years). Respiratory distress or breathing difficulty (dyspnea) may be mild to severe. Large pockets of air in the chest may prevent normal breathing. The air may be in large pockets of air in the lung (cysts) that compress the normal lung. Air also sometimes escapes from cysts into the chest cavity (pneumothorax). A chest x-ray will discover these air pockets and further investigations will lead to surgery to remove them.
Pneumonia/General Illness Symptoms:
These symptoms tend to be found in children with Types II and III PPB. These children are usually older than 2 years of age. These are mostly solid-tumor or partly solid-partly cystic PPBs. Symptoms of a general illness which may appear to be pneumonia are cough, fever, difficulty breathing, fatigue, loss of energy and decreased appetite. Chest or abdominal pain may also occur. Occasionally there is weight loss. A chest x-ray will show a problem that may look like pneumonia (lung infection). Because PPB is rare and other condition of the lung are more common, PPB may not be suspected when a child has these symptoms. Children are often treated with antibiotics for 2-3 weeks, but they do not get better. Further investigations are done, such as a chest CT scan; these tests raise the possibility of a tumor in the chest/lung and surgery is done.
Sometimes PPB occurs without any other conditions in the individual or family but PPB may also be an indication of an underlying mutation in a DICER1 gene (see Related Disorders).
PPB occurs in boys and girls approximately equally. Children under the age of 7-8 years are most often affected, but rarely teenagers or young adults may be diagnosed with PPB. Other conditions sometimes associated with PPB may be seen in individuals throughout the life span (see Related Disorders).
When a child presents with symptoms of PPB, a chest x-ray may show an air filled pocket (cyst) or a solid mass. Chest CT may be performed to look at the lungs in more detail. Surgery, either a biopsy or removal of the cyst or mass, is performed to diagnose and often remove the tumor. Microscopic examination of the specimen is needed. Consultation with the International PPB Registry pathology specialists is often helpful in confirming the diagnosis.
After surgery to remove Type I PPB, some physicians recommend use of chemotherapy to attempt to remove any remaining small collections of malignant cells; some physicians recommend watchful waiting. Radiation therapy is not used for Type I PPB. If Type I PPB recurs in a child as Type II or Type III PPB, then the treatments for Types II and III disease must be used.
Type II and III PPB are both serious (aggressive) malignancies. Surgery is the first step in treatment but sometimes due to the size and location of the tumor, only biopsy can be performed. This would be followed by chemotherapy to attempt to shrink the remaining tumor and remove the malignant cells left behind after surgery. Sometimes radiation therapy is also used.
The chemotherapy drugs usually used for treatment of PPB are the same or similar to drugs used for more common childhood cancers. Even though PPB is rare, pediatric cancer specialists have experience using these drugs. Their use in PPB patients is guided by their use in other children.
The use of radiation therapy is highly individualized in PPB patients. In general if there is a small area of tumor which could not be removed by surgery and which does not seem to disappear with chemotherapy, then radiation may be considered. Radiation can damage lung tissue so the doses and locations of radiation therapy are limited by the radiation oncology team. When PPB spreads to the brain, surgery followed by radiation therapy is often advised.
When the kinds of standard treatments outlined above are not successful at eliminating PPB, other therapies are often tried. Chemotherapy drugs for which there is not as much experience in PPB may be recommended. Sometimes new chemotherapy drugs are tried experimentally. Families will always be told the nature of the drugs which are being recommended for use in their child.
Another possible therapy for PPB is high dose chemotherapy followed by autologous stem cell transplantation. This overall approach may be useful in cases where PPB has not been eliminated by more standard therapy.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Research into the inheritance patterns in PPB patients and their families has already led to the understanding that the DICER1 gene mutation is the reason why some families have a tendency to develop PPB or other problems. Specific screening for PPB and other conditions known to be related to PPB may be requested for anyone who has the DICER1 gene mutation. This research is ongoing. Please contact the International PPB Registry for more information about this study:
The International Pleuropulmonary Blastoma Registry
Email contact: [email protected]
Phone: 612-813-7115 Gretchen Williams, BS, CCRP or Kris Ann Schultz, MD
Children’s Hospital and Clinics of Minnesota
2545 Chicago Ave. S.
Minneapolis, MN 55404
SELECT JOURNAL ARTICLES
Brenneman M, Field A, Yang J et al. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model. F1000Research 2015;4:214.
Dehner LP, Messinger YH, Schultz KAP, Williams GM, Wikenheiser-Brokamp K, Hill DA. Pleuropulmonary blastoma: the evolution of an entity as an entry into a familial tumor predisposition syndrome. Pediatr Dev Pathol 2015;18:504-11.
Messinger YH, Stewart DR, Priest JR, Williams GM, Harris A, Schultz KAP, Yang J, Doros L, Rosenberg PS, Hill DA, Dehner LP. Pleuropulmonary blastoma: a report on 350 central pathology confirmed PPB cases by the International PPB Registry. Cancer 2015;121(2):276–85.
Pappo AS, Furman WL, Schultz KA, Ferrari A, Helman L, Krailo MD. Rare tumors in children: progress through collaboration. J Clin Oncol 2015: 33(27):3047-54.
Pashankar F, Bisogno G, Ribeiro R, Messinger Y, Schultz KA, Rodriguez-Galindo C. The role of registries and tumor banking in rare pediatric tumors. Curr Pediatr Rep 2015;3(2):128-36.
Sabapathy DG, Guillerman RP, Orth RC, Zhang W, Messinger Y, Foulkes W, Priest JR, Annapragada AV. Radiographic screening of infants and young children with genetic predisposition for rare malignancies: the case of DICER1 mutations and pleuropulmonary blastoma. Am J Roentgenol 2015;204(4):W475-82.
Wagh PK, Gardner MA, Ma X, Callahan M, Shannon JM, Wert SE, Messinger YH, Dehner LP, Hill DA, Wikenheiser-Brokamp KA. Cell-and developmental stage-specific Dicer1 ablation in the lung epithelium models of cystic pleuropulmonary blastoma. J Pathol 2015; 236(1):41-52.
Yin Y, Castro AM, Hoekstra M, Yan TJ, Kanakamedala AC, Dehner LP, Hill DA, Ornitz D. Fibroblast growth factor 9 regulation by MicroRNAs controls lung development and links DICER1 loss to the pathogenesis of pleuropulmonary blastoma. PLoS Genet. 2015 May 15;11(5):e1005242.
Pugh TJ, Yu W, Yang J, Field A, Ambrogio L, Carter SL, Cibulskis K, Giannikopoulos P, Kiezun A, Kim J, McKenna A, Nickerson E, Getz G, Hoffher S, Messinger YH, Dehner LP, Roberts CWM, Rodriguez-Galindo C, Williams GM, Rossi CT, Meyerson M, Hill DA. Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two-hit DICER1 loss resulting in retention of 5p-derived miRNA hairpins. Oncogene 2014;33:5295-5302.
Schultz KAP, Harris A, Williams GM, Baldinger S, Doros L, Valusek P, Frazier AL, Dehner LP, Messinger Y, Hill DA. Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer 2014;61(9):1695-7.
Schultz KA, Yang J, Doros L, Williams GM, Harris A, Stewart DR, Messinger Y, Field A, Dehner LP Hill DA. DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome: a unique constellation of neoplastic conditions Pathol Case Rev 2014;19(2):90–100.
Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, Barfoot R, Burke A, Chisholm J, Hewitt M, Jenkinson H, King D, Morland B, Pizer B, Prescott K, Saggar A, Side L, Traunecker H, Vaidya S, Ward P, Futreal PA, Vujanic G, Nicholson AG, Sebire N, Priest JR, Pritchard-Jones K, Houlston R, Turnbull C, Stiller C, Stratton MR, Douglas J, Rahman N. DICER1 syndrome – clarifying the diagnosis, clinical features and management implications of a pleiotropic tumor predisposition syndrome. J Med Genet 2011;48:273-78.
Schultz KAP, Pacheco MC, Yang J, Williams GM, Messinger Y, Hill DA, Dehner LP, Priest JR. Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: A report from the International Pleuropulmonary blastoma Registry. Gynecol Oncol 2011;122(2):246-50.
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ. DICER1 mutations in familial pleuropulmonary blastoma. Science 2009;325:965.
Priest JR, Williams GM, Hill AD, Dehner LP, Jaff? A. Pulmonary Cysts in Early Childhood and the Risk of Malignancy. Pediatr Pulmonol 2009;44(1):14-30.
Hill DA, Jarzembowski JA, Lennerz JK, Priest JR, Williams G, Schoettler P, Dehner LP. Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the International Pleuropulmonary Blastoma Registry. Am J Surg Pathol 2008;32(2):282-295.
Pai S, Eng HL, Lee SY, Hsaio CC, Huang WT, Huang SC, Hill DA, Dehner LP, Priest JR. Correction: Pleuropulmonary blastoma, not rhabdomyosarcoma in a congenital lung cyst [Letter to the Editor]. Pediatr Blood Cancer 2007;48(3):370-371.
Priest JR, Magnuson J, Williams GM, Abromowitch M, Byrd R, Sprinz P, Finkelstein M, Moertel CL, Hill DA. Cerebral metastasis and other central nervous system complications of pleuropulmonary blastoma. Pediatr Blood Cancer 2007;49(3):266-273.
Priest JR, Hill DA, Williams GM, Moertel CM, Messinger Y, Finkelstein MJ, Dehner LP. Type I pleuropulmonary blastoma: A report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 2006;24:4492-4498.
Dehner LP. Beware of “degenerating” congenital pulmonary cysts [Letter to the Editor]. Pediatr Surg Int 2005;21:123-124.
Hill DA. USCAP Specialty Conference, case 1: Type I Pleuropulmonary blastoma. Pediatr Dev Pathol 2005;8:77-84.
Priest JR, McDermott MB, Bhatia S, Watterson J, Manivel JC, Dehner LP. Pleuropulmonary blastoma. A clinicopathologic study of 50 cases. Cancer 1997;80:147-61.
Priest JR, Watterson J, Strong L, Huff V, Woods WG, Byrd RL, Friend SH, Newsham I, Amylon MD, Pappo A, Mahoney DH, Langston C, Heyn R, Kohut G, Freyer DR, Bostrom B, Richardson MS, Barredo J, Dehner LP. Pleuropulmonary blastoma: a marker for familial disease. J Pediatr 1996;128(2):220-4.
McDermott MB, Dehner LP, Priest JR. Reply to Lopez-Andreu JA et al. Pleuropulmonary blastoma and congenital cystic malformations. J Pediatr 1996;129(5):772-5.
Dehner LP, Watterson J, Priest JR. Pleuropulmonary blastoma. A unique intrathoracic-pulmonary neoplasm of childhood. Perspectives in Pediatric Pathology 1995;18:214-226.
Dehner LP. Pleuropulmonary blastoma is THE pulmonary blastoma of childhood. Semin Diagn Pathol 1994;11(2):144-51.
Manivel JC, Priest JR, Watterson J, et al. Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood. Cancer 1988;62:1516-1526.
Doros L, Schultz KA, Stewart DR, et al. DICER1-Related Disorders. 2014 Apr 24. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK196157/ Accessed April 25, 2016.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100