NORD is very grateful to Gretchen Williams, BS, CCRP, Research Coordinator, Hematology/Oncology Dept., Children's Hospitals and Clinics of Minnesota & the International PPB Registry, for assistance in the preparation of this report.
Synonyms of Pleuropulmonary Blastoma
- cystic mesenchymal hamartoma
- mesenchymal cystic hamartoma
- pediatric pulmonary blastoma
- pulmonary rhabdomyosarcoma
- rhabdomyosarcoma in lung cyst
- PPB family tumor susceptibility syndrome
Pleuropulmonary blastoma (PPB) is a rare childhood cancer occurring in the chest, specifically in the lungs or in the coverings of the lungs called "pleura". PPB occurs almost exclusively in children under the age of approximately 7-8 years and rarely in older children, in teenagers and more rarely in adults. Three subtypes of PPB exist and are called type I, type II, and type III PPB. Type I PPB takes the form of cysts in the lungs (air-filled pockets) and occurs in the youngest children with PPB (from birth to about 2 years of age). Type II PPB has cysts and solid tumor. Type III PPB is entirely solid tumor. Types II and III PPB tend to occur after age 2 years. Children with type I PPB can have the disease come back. If type I PPB comes back, it usually happens within about 4 years of the original diagnosis, and it is usually type II or III when it recurs. Children with type I PPB have a better outlook ("prognosis") than children with types II and III PPB; most type I PPB patients are cured (more than 80%). Treatment for type I consists of surgery and possibly chemotherapy; for Types II and III PPB surgery, chemotherapy and possibly radiation therapy is recommended. At present, about 50-60% of types II and III children are cured.
PPB 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. PPB is related to, or in the broad family of, cancers such as cancers of muscle, cartilage, and connective tissues. Physicians classify diseases this way in order to compare features and to compare treatments. Often treatments that are effective for one member of a family of cancers are effective for other members of that family.
PPB occurs in the lungs so PPB can be called a lung cancer, but PPB has no connection whatsoever with lung cancers in adults that are often related to tobacco use.
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. Less common metastasis occurs in the bones, the liver, remaining parts of the lung, and other organs. It is not known why PPB has this pattern of spread to brain, liver, or bones. PPB can also spread by growing directly into tissues next to the lung like the diaphragm.
PPB family cancer syndrome: In about 25% of children with PPB, there are other childhood cancers or abnormalities in the PPB patient or in their families. This is called the PPB family cancer syndrome. This can include lung cysts, kidney cysts, ovarian or testicular tumors in children or young adults, thyroid tumors (sometimes malignant), and various other cancers and non-malignant (non cancerous) diseases. It is not known what causes the abnormalities in these children and families, but research is underway to discover the presumed genetic basis for this tendency to childhood cancers or other abnormalities. It should be emphasized that many children and adults in these families have no medical problems.
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 PPBs and air-filled cysts are not causing the symptoms.
Symptoms of a general illness which appears to be pneumonia are present: cough, fever, mild to moderate respiratory distress, perhaps some chest pain, perhaps abdominal pain, fatigue, malaise, loss of energy and decreased appetite (anorexia) are common. Occasionally there is weight loss. A chest x-ray will show a problem that is often considered to be pneumonia (pneumonia is an area of infection within the lung and it can look almost exactly like a tumor mass in the lung). Because PPB is so rare, it is not a diagnosis most physicians even consider 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.
The cause of PPB is not known. Most cases, about 75%, are called "sporadic" which means that they occur in a child completely at random. In the other 25% of cases, the PPB is part of a tendency within the child or the family to have childhood abnormalities. These abnormalities can be lung cysts, kidney cysts, thyroid lumps (sometimes cancerous) and various other childhood cancers. Most individuals in these families are completely normal. In the child who happens to develop PPB, there may have been no other suggestion of abnormality before the PPB occurs; in other words, there was no reason to be suspicious that a problem would happen. Only if a child in a known PPB family had lung or kidney cysts would there be a reason to suspect a PPB might occur. Such a situation is extremely rare.
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 develop PPB. No child would be suspected in advance of developing PPB unless he or she came from one of the very rare families in which there is a PPB or lung cysts or kidney cysts (called "cystic nephroma" which is also very rare). These situations are so rare that almost no physician can be expected to be experienced with them.
Congenital Lung Cysts: PPB, especially types I and II PPB, are also related to lung cysts (air pockets), also sometimes called blebs or bullae in the lung. Some cysts are on the surface of the lung and some are deep inside the lung. The cysts may be large or small and may be in one or both lungs. The cysts related to PPB are most often considered congenital cysts, that is, cysts present at birth. PPB forms in these cysts. It also may be that a child was not born with the cysts but that PPB itself causes lung cysts to appear and enlarge. The cysts in which PPB is found are very similar to other childhood lung cysts that will never become PPB. Lung cysts in children in general and lung cysts in children with PPB are most commonly called congenital cystic adenomatoid malformation (CCAM) of the lung; more recently they have been called congenital pulmonary airway malformation (CPAM). There are several types of CCAM and CPAM. These CCAM types are not the same as the three PPB types.
It should be emphasized that many children who have lung cysts such as CCAM never develop PPB. The percentage of children with lung cysts who develop PPB is not known, but most children with cysts will not develop PPB. Also, PPB can occur in children who do not have lung cysts in advance. Most children who develop PPB have not had lung cysts in advance.
The relationship between lung cysts and the development of PPB is not understood. What is known is that in some young children with lung cysts (generally under age 2 years), PPB type I may be found in tiny amounts in walls (lining) of the cysts. As children with lung cysts reach age 3 to 4 years, the PPB is not likely to remain type I but is likely to have developed (progressed) into type II or III PPB. It is believed that lung cysts which start as type I PPB actually progress through worsening stages into type II and then type III PPB as a child gets older. Because PPB is rare, and because type I PPB is present in such tiny amounts in the walls of cysts, children with surgery for cysts are sometimes diagnosed with CCAM, when in fact after the surgical specimen is examined under the microscope it is determined the diagnosis is in fact type I PPB. Surgery alone sometimes cures type I PPB. If a lung cyst returns months or a few years later, it is discovered to have been type I PPB and not really CCAM.
PPB is exceptionally rare and few physicians have had any experience with it. At most, only 10-20 cases are diagnosed in the United States each year, as compared to many hundreds of cases of childhood leukemia. It often takes some time for the diagnosis of PPB to be made because no one suspects it. In type I PPB (cystic PPB), there is no suspicion of a cancer. The young patient has some breathing difficulties and a chest x-ray shows air pockets (cysts) in the lungs. Surgery is done on the cysts. Under the microscope, the cysts appear only slightly abnormal. Only very close evaluation will show that the walls of the cysts contain very small collections of malignant cells. In types II and III PPB, the diagnosis is sometimes delayed by 2 to 4 weeks because the child seems to have pneumonia. When antibiotics do not help, further studies are done, usually a chest CAT scan, and surgery shows a mass (tumor) that is easily identified under the microscope as malignant. However, PPB is so unusual that many pathologists do not immediately recognize that the malignancy is PPB. Consultation with the PPB Registry pathology specialists is often necessary.
PPB is rare and no large studies of treatment have been possible. Thus there is no truly standard therapy. When faced with such a situation, pediatric cancer specialists (oncologists) choose treatment for cancers of a similar type. The successes and failures of these choices are discussed among physicians and some agreements about how to treat PPB emerge.
Type I PPB: Type I PPB is not usually suspected in advance when surgery is done to remove lung cysts. Cysts wall are usually removed as completely as possible. After surgery for cysts, some physicians recommend use of chemotherapy to attempt to remove any remaining small collections of malignant cells; some physicians recommend watchful waiting. Radiation therapy (sometimes called cobalt 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: Type II and III PPB are very serious (aggressive) malignancies. Surgery to remove as much disease as possible is usually the first step in treatment. This would be followed by chemotherapy to attempt to remove any malignant cells left behind after surgery. Sometimes radiation therapy is also used. When a PPB tumor is so large that complete surgery cannot be attempted (a fairly common situation), a biopsy is done to make the diagnosis and then chemotherapy is used to shrink the tumor so that a second surgery has a greater chance of removing the disease. Then more chemotherapy and possible radiation therapy would be used.
The chemotherapy drugs chosen for treatment of PPB are the same drugs used for more common childhood cancers in the same general family of cancers as PPB, which are called soft tissue sarcomas. Even though PPB is rare, all pediatric cancer specialists have experience using these drugs. Their use in PPB patients is guided by their use in other children. In this sense, there is nothing usual about PPB treatment.
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 is damaging to lung tissue and so large amounts of radiation to a child's entire chest cannot be used. If PPB spreads to the brain, it is most often treated with radiation after surgery.
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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Research into genetic (DNA) inheritance patterns in PPB patients and their families is being done. This might lead to understanding why some families have a tendency to develop PPB or other problems. For more information about participating in this study, contact:
The International Pleuropulmonary Blastoma Registry
Email contact: firstname.lastname@example.org
Phone: 612-813-7115 Gretchen Williams, BS, CCRP, orYoav Messinger, MD
Children's Hospital and Clinics of Minnesota
2545 Chicago Ave. S.
Minneapolis, MN 55404 USA
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 kind of investigational therapy for PPB is the use of very large doses of chemotherapy, and sometimes also radiation, to eliminate the PPB wherever it may be in the body. A side effect of such large doses is that the child's bone marrow (where blood cells are produced) is unable to produce blood cells. Therefore, within days after using large chemotherapy doses, bone marrow stem cells, which have been saved earlier from the child, are given back to replenish the marrow and allow it to make blood cells again. Stem cells are essentially seed cells that repopulate the bone marrow. This is sometimes called bone marrow transplantation; it is also called high dose chemotherapy with stem cell reconstitution. This overall approach may be useful in cases where PPB has not been eliminated by more standard therapy.
Pleuropulmonary Blastoma Resources
NORD Member Organizations:
(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at email@example.com.)
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.
Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser KA, Suarez BK, Whelan AJ, Williams G, Bracamontes B, Messinger Y, Goodfellow PJ. Inherited DICER1 mutations in familial pleuropulmonary blastoma [Abstract]. Annual Meeting for American Association for Cancer Research 2009 Apr:LB-91.
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.
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