Pleuropulmonary blastoma (PPB) is a lung tumor seen primarily in children. The name “pleuropulmonary blastoma” means that the tumor is thought to originate in either the tissue covering the lungs and inside surface of the chest cavity (“pleura”), or in the lung tissue itself (“pulmonary”). The word “blastoma” refers to the appearance of the tumor under the microscope. There are four main types of PPB: Type I, Type II, Type III and Type Ir PPB. Each of these types of PPB may be linked to variation in a gene called DICER1.
Types I, II and III PPB are generally diagnosed under 7 years of age. There have also been rare cases found in older children or adults. A separate condition, pulmonary blastoma, is seen primarily is adults and is distinct from PPB.
Children or adolescents with PPB may present with cough, fever, difficulty breathing or chest or abdominal pain. Chest x-rays may appear to show pneumonia. Sometimes individuals with PPB may present with pneumothorax, leakage of air into the chest cavity outside the lungs. PPB may also be found incidentally on an imaging study even in the absence of symptoms.
Type I PPB is a purely cystic tumor seen most often in children under 3 years of age. Type I PPB may present with difficulty breathing, cough or pneumothorax (leakage of air into the chest cavity outside of the lungs). Sometimes Type I PPB may be found incidentally on imaging studies or as a part of recommended screening. Since it is air-filled, Type I PPB may initially be diagnosed as congenital pulmonary airway malformation (CPAM) and additional review of the imaging, complete resection and/or family history may be needed to confirm the diagnosis. In Type I PPB, malignant (cancerous) cells can be seen under the microscope, lining the border of the cyst.
Most children with Type I PPB undergo surgery to completely remove the tumor. Chemotherapy may be needed in some but not all instances. Overall, the prognosis is favorable for most children with Type I PPB, however, in some cases, Type I PPB may progress to Type II or III PPB. The goal in treatment of Type I PPB is to allow nearby healthy lung tissue to develop normally and to reduce the risk for progression.
One of the goals of genetic testing for DICER1 variation is to allow Type I PPB to be found before progression to Types II or III PPB. In addition, we believe that some cases of Type I PPB do not progress but instead regress, leaving behind an air-filled cyst which lacks malignant (cancerous) cells. This regressed or non-progressed type of PPB is called Type Ir PPB (see section on Type Ir PPB).
In a study of 350 cases of PPB, the Registry found that survival for Type I PPB was 89% when measured at 5 years following diagnosis. The Registry is actively studying which cases of Type I PPB may be cured with surgery alone and which require chemotherapy.
Type II is a mixed cystic and solid tumor diagnosed at an average of 3 years of age. Type III is a purely solid tumor diagnosed at an average of 3.5 years of age. Types II and III PPB may present with difficulty breathing, fever, weight loss or chest or abdominal pain. Pneumothorax (leakage of air into the chest cavity outside the lung) is less common than in Type I PPB but may be seen. Type I, purely cystic PPB, may progress to Types II or III PPB. Sometimes Type II or III PPB may initially be thought to be pneumonia when noted on chest x-ray or chest CT. Under the microscope, these forms of PPB may be initially diagnosed as rhabdomyosarcoma or another tumor. Biopsy or surgery is usually needed to confirm the diagnosis.
Children and adolescents with Types II and III PPB require surgery to remove the tumor followed by chemotherapy and sometimes radiation therapy. Sometimes additional treatments such as chemotherapy placed directly into the chest cavity or high dose chemotherapy with stem cell rescue are also used.
In Types II and III PPB, chemotherapy is used to shrink tumors to allow them to be safely removed and/or to treat small or large amounts of cancer that may be left behind after surgery.
Radiation therapy for cancer is based on the idea that x-ray energy can damage cancer cells which then die. Unlike chemotherapy, which travels through the body in the blood stream, radiation therapy must be aimed at a specific area. Radiation is required for treatment in children with PPB, especially when the tumor has not been completely removed by surgery or if it recurs after initial treatment. Because radiation may have specific side effects for young children and adolescents, the Registry is working to understand which children may benefit from radiation therapy and which children will be cured with surgery and chemotherapy alone.
Types II and III PPB may also spread outside the chest or return after treatment. See section on PPB Metastases/Recurrence for more information.
In a study of 350 cases of PPB, the Registry found that survival for Type II PPB was 71% when measured at 5 years following diagnosis. Survival for Type III PPB was 53% when measured in the same way. Finding more effective and less toxic therapies for children with PPB is one of the main goals of the International PPB/DICER1 Registry.
Types II and III can spread within or outside the chest. This spread is called metastasis. The most common site of metastasis is somewhere else within the chest. The second most common site of spread of PPB is the brain. Types II and III PPB may also spread to the bones, lymph nodes, liver or spine. Additionally, PPB may be associated with other kinds of tumors (see section on DICER1). When masses are found in areas outside of the lung in a child with current or past PPB, it is important to determine if this represents spread or a separate tumor as the treatments may be different in each of these situations.
PPB may also recur (come back) during or after treatment. The best treatments for recurrent PPB depend somewhat on the individual situation and which therapies have already been given. One of the priorities of the PPB/DICER1 Registry is to understand which treatments are most effective for children or adolescents with recurrent PPB.
Type Ir is a purely cystic (air-filled) type of PPB which likely represents regressed or non-progressed Type I PPB. Type Ir PPB may be diagnosed at any age, from young childhood through adulthood. Type Ir PPB may present with shortness of breath or difficulty breathing, however Type Ir PPB may also be found incidentally, when imaging is performed for another reason or as part of surveillance for someone with established DICER1 variation.
There are several considerations when determining whether a cyst which is suspected to be Type Ir PPB should be removed or observed. Much of this depends on age and the appearance of the cystic lesion.
No deaths have been reported specifically due to Type Ir PPB but the presence of Type Ir PPB may be an indication of underlying DICER1 variation. Finding this gene variation may allow initiation of surveillance guidelines and detection of other conditions in their earliest and most curable form.
Pleuropulmonary blastoma (PPB) is a rare lung tumor found primarily in young children. Research from the Registry has shown a link between PPB and a gene called DICER1. DICER1 is a gene which encodes a protein, Dicer, which impacts gene expression and has downstream effects on cell proliferation. In studying PPB, we have learned that nearly all PPB tumors are characterized by variation in the DICER1 gene. Most but not all of the time, a child who has PPB also has variation in this gene. Other tumors may also be associated with DICER1 variation including certain ovarian or kidney tumors, some thyroid nodules and thyroid cancer, certain eye and nose tumors and other rare cancer subtypes.
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