Pleuropulmonary Blastoma (PPB) a rare childhood cancer

I selected Pleuropulmonary  Blastoma (PPB) because it was requested by someone close to me so they could learn about this cancer. Their brother passed away from this cancer in 1982. Pleuropulmonary  Blastoma is rare and hard to detect, therefore it was not discovered until the autopsy was conducted. There have only been 450 cases world wide since it was first defined, with 25-35 cases/year in the United States and only came under scrutiny in the mid 1980s. It was explained to me that he had been to a variety of doctors and specialists, but they had been unable to find signs of the cancer. After family volunteered information, my research revealed that he had many of the symptoms of the cancer, but it can be mistaken for many things. In this example, for instance, the confusion was made with the diagnosis of heart murmur. It was discovered he had an enlarged heart, but it turned out to be a symptom of Pleuropulmonary  Blastoma. 

Due to the rarity of the condition it was not caught in time. Since then, technology has gotten better and treatments have advanced. No one knows what causes it, and in many cases, the family members are completely healthy and there is no family history of PPB. However, in 2 out of 3 patients, there is a mutation of the DICER1 RNase-lllb gene which is a germ line mutation inherited by 80% of patients from a parent.

Pleuropulmonary Blastoma is a rare cancer which appears most commonly by 5 years old and begins as a cystic abnormality in the lung as the lung begins to develop in utero. It is a primary neoplasm of pleuropulmonary mesenchyme. Mesenchyme is mostly mesodermal embryonic tissue which begins to develop into skeletal and connective tissues (this includes the blood and lymph tissues). This cancer affects the lungs and the area inside the chest cavity. It may be more common that the disease appears on the right side (54%) rather than the left (37%). The disease is bilateral with both sides having PPB or PPB on one side and lung cysts on the other side (9%). It has been shown to metastasize into the brain (15-25%), bone (6-10%), liver (2-4%) and other organs depending on the study. Males are about equal to females in occurrence. 

There are three forms of the disease defined by the lesion which are normally found at certain ages. Type I (cystic lesion) occurs most often at ages 0-28 months (median 10 months), Type II (cystic and solid lesion) most often ages 15-64 months (median 34 months) and Type III (solid lesion) at ages 31-147 months (median 44 months). Recently they defined Type Ir, a regressed form of type I which did not evolve to be malignant and differ from other lung cysts. 

Symptoms may vary by type but in general including coughing, shortness of breath, chest pain, upper respiratory tract infection and pneumothorax (air leaking into space between lung and chest wall). Symptoms for type I Pleuropulonary Blastoma are respiratory distress and lung cysts. Symptoms of Types II and III PPB are fever, chest or abdominal pain, dyspnea, cough (bloody cough) or respiratory compromise. Other symptoms include malaise, anorexia, pleural effusion and pneumothorax (the latter presenting with Type II disease). After being presented, many patients need to be put onto respirators within days. Some patients do not have any symptoms or only a few of them. 

There is a condition in family members called 'PPB family tumor and dysplasia syndrome' (PPBFTDS). This means that children with PPB and family members may also have PPB, cancer, dysplasia (abnormal formations of normal tissue), cysts or tumor growths. Other forms, including the regressive type Ir, may progress into other forms, such as type I into type II or III. Due to the relationship between types, it is believed one may develop from the other (such as type I developing into type II or III), or types II and III develop from unoperated lung cysts that already exist. As our technology gets better, we have been able to find more advanced stages in younger patients. On the other end of the spectrum, it has also been found even more rarely in teens and adults.

Pleuropulonary Blastoma is very rare and difficult to diagnose, and often mistaken for other diseases such as pneumonia. When a cyst is found, multiple samplings of the cyst wall must be taken to determine what it even is. Most cysts are found by accident if they are found at all. Most are diagnosed by biopsy. Using x-rays, MRI’s and CAT scans can indicate cancer, but only the biopsy will determine the diagnosis which is often unexpected. It must be caught early, with the first type being the most curable but there are cures and treatments for the other forms. Most cases can now be cured if caught in a timely fashion, but the only way to catch it in time is to take in your child when they present any of the symptoms. Once a diagnosis is made, patients should be tested for other tumors and issues and to see if it has spread. DICER1 syndrome is often found in concurrence.

The most common treatment is surgery with chemotherapy. Surgery is always conducted unless the tumor is inoperable or too large. If it is too large, chemotherapy may be applied to make it smaller so surgery is possible. A chemotherapy regimen is then often conducted. It is often found in correlation with DICER1 syndrome

For a good one-stop resource I selected the Pleuropulmonary Blastoma Registry http://www.ppbregistry.org/ due to its complex information, link to appropriate educational sources and high quality and volume of information. It is also pretty much the only place to find such detailed information I found online since this rare disease does not get much information provide on the other cancer informational websites which are not specifically devoted to Pleuropulmonary Blastoma. It is referred to by most of the websites, videos and webpages I read and is considered a valuable resource.

The website is run by the  International Pleuropulmonary Blastoma registry. They have been documenting Pleuropulmonary Blastoma for over 20 years. The biology of the disease and its treatment was collected and distributed by this registry. They collect cases and ask that all families and family members come forward for documentation of cases, genetic testing and more information regarding this rare disease. Since they are close to finding additional treatments, individuals and families are urged to share their information and DNA with researchers to confirm the DICER1 syndrome and other correlations.

Works Cited

International Pleuropulmonary Blastoma registry. 2016.  http://www.ppbregistry.org/