What are the other Names for this Condition? (Also known as/Synonyms)

• Pleuropulmonary Blastoma, Type III
• Type III PPB

What is Type III Pleuropulmonary Blastoma? (Definition/Background Information)

• Pleuropulmonary blastoma (PPB) is an aggressive and rare form of lung cancer that is found in children. It is considered to be a related tumor to other childhood tumors such as Wilms tumor, hepatoblastoma, retinoblastoma, and neuroblastoma
• The tumor is characterized by 3 morphological forms that manifest at different ages of the child. These are denoted as type I, type II, and type III pleuropulmonary blastomas. The signs and symptoms, complications, treatment, and prognosis slightly differ based on this classification
• Type III Pleuropulmonary Blastoma, which is purely solid in nature, is seen in children at around age 3.5 years. The cause of Type III Pleuropulmonary Blastoma formation is currently not well-established, but some tumors are associated with a genetic syndrome known as pleuropulmonary blastoma family tumor and dysplasia syndrome
• In some individuals, pleuropulmonary blastoma progresses from type I to type II to type III over a period of time. Type III Pleuropulmonary Blastoma can cause chest pain, breathing difficulties, lung collapse, including metastasis to the central nervous system or to the bones
• Chemotherapy, surgery, radiation therapy, and other treatment measures may be used for treating Type III Pleuropulmonary Blastoma based on the assessment of the physician
• The prognosis may depend on many factors including the progression of the condition, response to treatment, and overall health of the individual. However, in general, the prognosis of pleuropulmonary blastoma is typically guarded

Who gets Type III Pleuropulmonary Blastoma? (Age and Sex Distribution)

• Pleuropulmonary blastoma is a rare malignancy and most cases are diagnosed in children
• Type III Pleuropulmonary Blastoma is seen in children around 3.5 years old; the median age is about 41 months
• Both male and female children are affected in nearly the same ratio
• Current studies do not show any racial or ethnic predilection

What are the Risk Factors for Type III Pleuropulmonary Blastoma? (Predisposing Factors)

Presence of a genetic disorder termed pleuropulmonary blastoma family tumor and dysplasia syndrome (also known as DICER1 syndrome), may be a risk factor towards the formation of Type III Pleuropulmonary Blastoma.

Due to this syndrome, other benign and malignant tumors may simultaneously arise in the body including:

• Cystic nephroma
• Wilms tumor
• Embryonal rhabdomyosarcoma
• Sertoli-Leydig cell ovarian tumor
• Multinodular goiter
• Nasal chondromesenchymal hamartoma
• Juvenile intestinal polyps
• Primitive neuroectodermal tumor (PNET)
• Intraocular medulloepithelioma

The manifestation of the signs and symptoms of the syndrome mostly takes place within the first 6 years of life. However, the signs and symptoms are known to arise in older children and in young adults too.

Due to the above syndrome:

• A family history of PPB can be a risk factor
• The presence of DICER1 gene mutation is also a risk factor

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Type III Pleuropulmonary Blastoma? (Etiology)

The exact cause of Type III Pleuropulmonary Blastoma is unknown.

• The presence of pleuropulmonary blastoma family tumor and dysplasia syndrome (or DICER1 syndrome) is observed in some of the cases
• Mutations have been seen in the DICER1 gene that may be probably causative; although, many individuals with such mutations do not seem to be affected
• The DICER1 mutations may be present in many individuals with pleuropulmonary blastoma. Studies have found that not all individuals with DICER1 mutation develop PPB
• Hence, researchers believe that the presence of additional causative factors may be necessary, along-with DICER1 mutation for one to develop pleuropulmonary blastoma
• Chromosomal gains involving chromosome 8, and losses involving chromosomes 9 and 11 have been reported in some of the individuals
• In some individuals, type II and type III tumors are known to arise from type I tumors

What are the Signs and Symptoms of Type III Pleuropulmonary Blastoma?

Type III Pleuropulmonary Blastoma signs and symptoms may include the following. It can vary from one individual to another.

• Type III tumor is marked by the presence of solid nodules
• Shortness of breath that gets worse with time; difficulty in breathing
• Cough that may be persistent
• Chest pain, heaviness in the chest
• Presence of fluid in the lungs (or pleural effusion)

Some features of the tumor include:

• A majority of the tumors originate from the lung tissues; the pleura may be involved in a minority of cases
• The tumors may be present anywhere in the lung. In some cases, both lungs may be affected
• Both lung and kidney tumors can be bilateral and multifocal
• Pleuropulmonary blastomas are rarely known to involve the chest wall and mediastinum; very infrequently, the diaphragm dome may also be affected
• Type III tumors are purely solid; solid tumors may grow to large sizes and can occupy the entire lung
• Many type III tumors are found to spread to distant regions (extra-pulmonary tumors)
• A small percentage of the type III tumors may extend into the heart (left-side) and also involve the blood vessels

How is Type III Pleuropulmonary Blastoma Diagnosed?

The following procedures and tools may be used in the diagnosis of Type III Pleuropulmonary Blastoma:

• Physical examination: During a physical exam, a physician will check the individual’s overall health status, listen to their breathing, and check for possible fluid buildup in the lungs (auscultation)
• Pulmonary function tests can help determine the extent of lung damage; it can also help the healthcare provider assess the ability of lungs to deliver oxygen to the body
• Chest X-ray: Two-dimensional pictures using tiny amounts of radiation are taken, in order to detect any tumors or other medical issues associated with the lungs, such as pneumonia. Tumors inside the lung can be detected using a chest X-ray; although sometimes, these tumors are too small to visualize (tumors less than 1 cm in size may be missed on a chest X-ray)
• Computerized tomography (CT) scan: Also known as CAT scan, this radiological procedure creates detailed three-dimensional images of structures inside the body. CT scans may be helpful in detecting recurrences, or if the cancer has metastasized to the surrounding lymph nodes of the lungs
• Magnetic resonance imaging (MRI) scan: An MRI scan uses magnetic fields that create high quality pictures of certain body parts, such as tissues, muscles, nerves, and bones. These high-quality images may indicate to a physician, if any tumor is present
• Positron emission tomography (PET): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material may be injected into a vein, inhaled or swallowed. A PET scan is also helpful in detecting recurrences, or if any metastasis (to the surrounding lymph nodes of the lungs) has occurred
• Sputum cytology: Sputum cytology is test that involves the collection of mucus (sputum), coughed-up by a patient. After the mucus is collected, a pathologist examines it in an anatomic pathology laboratory, to see if any cell abnormalities are present indicative of pleuropulmonary blastoma
• Bone scan: A bone scan is a nuclear imaging test that involves injecting a radioactive tracer into an individual’s vein. Bone scans are primarily used to detect if the cancerous cells have metastasized to the bones and formed secondary tumors
• Bone marrow biopsy: Bone marrow is a soft tissue found within bones. Occasionally, with pleuropulmonary blastoma, a bone marrow biopsy is used to detect blood abnormalities, or if a physician believes that metastasis to the bone marrow may have occurred

A biopsy refers to a medical procedure that involves the removal of cells or tissues, which are then examined by a pathologist. Different biopsy procedures include:

• Tissue biopsy from the affected lung:
  • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
• The biopsy may be performed through any of the following procedures:
  • Bronchoscopy: A special medical instrument, called a bronchoscope, is inserted through the nose and into the lungs to collect small tissue samples
  • Thoracentesis: During thoracentesis, physicians use a special medical device called a cannula, to remove fluid between the lungs and the chest wall for examination
  • Thoracoscopy: A medical instrument called a thoracoscope is inserted into the chest through tiny incisions, in order to examine and remove tissue from the chest wall, which is then analyzed further
  • Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest and remove tissue from the chest wall or the surrounding lymph nodes of the lungs
  • Mediastinoscopy: A medical instrument called a mediastinoscope is inserted into the chest wall to examine and remove samples
  • Fine needle aspiration biopsy (FNAB) or transthoracic needle biopsy: A device called a cannula is used to extract tissue or fluid from the lungs, or surrounding lymph nodes
  • Open lung biopsy

A differential diagnosis with respect to other tumors may be necessary prior to establishing a definite diagnosis, by excluding the following:

• Cystic synovial sarcoma
• Congenital cystic adenomatoid malformation
• Fetal lung interstitial tumor

Note: The following diagnostic modalities are recommended for Type III Pleuropulmonary Blastoma - chest X-ray, abdominal CT scan, MRI scan of the head, and a bone scan.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Type III Pleuropulmonary Blastoma?

The complications of Type III Pleuropulmonary Blastoma can include:

• Dyspnea (shortness of breath): If the cancerous tumor expands to block important, large, or small airways of the chest or lung
• Hemoptysis (coughing-up blood): Individuals may cough-up blood, due to excessive amounts of blood in the airways
• Pain: Advanced stages that has metastasized to the pleural cavity (lining surrounding the lungs), invaded the chest wall, or other areas of the body may cause excessive pain
• Development of severe pneumothorax (collapsed lung)
• Local recurrence following surgical removal of the tumor

Involvement of local and distant organs in lung cancer:

• The tumor spreads through the lymphatic or circulatory system
• Metastasis is common in Type III Pleuropulmonary Blastomas
• The central nervous system (CNS including the brain and spinal cord) and skeletal system are the frequent sites for metastasis; nevertheless, these tumors are known to spread to any part of the body
• Loss of function of the organ/area to which cancer has spread due to systemic involvement

There may be complications related to the methods used in treating the condition and may include:

• Side effects of radiation therapy that may include sunburn-like rashes, where radiation was targeted, red or dry skin, heaviness of the breasts, and general fatigue
• Side effects of chemotherapy, which may include nausea, vomiting, hair loss, decreased appetite, mouth sores, fatigue, low blood cell counts, and a higher chance of developing infections
• The treatment can also cause infertility in men and women. Hence, measures to protect the individual’s fertility must be considered, before starting chemotherapy

How is Type III Pleuropulmonary Blastoma Treated?

Treatment options available for individuals with pleuropulmonary blastoma are dependent upon the following:

• Type of cancer; whether type I, II, or III
• The staging of the cancer: If lung cancer is diagnosed, staging helps determine whether it has spread and which treatment options are best-suited for the individual
• Overall health status of the individual

The following treatment options may be considered:

• Type III tumor: Surgery, which is followed by chemotherapy and/or radiation therapy
• Tumors that are at inaccessible locations or cannot be surgically removed may be subjected to targeted radiation therapy
• Doxorubicin-based regimes are advocated for type III tumors, since it is shown to be beneficial

The treatment modalities may include the following that are described below:

Surgery: Depending on the stage of Type III Pleuropulmonary Blastoma, surgery might be a viable option. The surgical options include:

• Wedge resection: Wedge resection is a partial removal of the wedge-shape portion of the lung that contains cancerous cells (along with any surrounding healthy tissue)
• Segmentectomy: It is the partial removal of the cancerous lung and any surrounding healthy tissue
• Pulmonary lobectomy: It is a type of surgical procedure performed to partially remove a portion of a lung
• Sleeve lobectomy: It is another surgical procedure to partially remove a portion of the lung and a part of the airway (bronchus)
• Pneumonectomy: It is the surgical removal of the entire lung

Chemotherapy:

• Chemotherapy drugs are typically taken as pills, or injected directly into a vein. These drugs travel through the body to kill any cancer cells
• But, they can also kill healthy cells, located within the gastrointestinal tract and in hair follicles. The side effects include vomiting, nausea, and hair loss

Radiation therapy:

• Radiation therapy involves using x-rays to kill cancerous cells. High-powered radiation beams are directed to particular body regions to target cancer. In the process, healthy cells can also be damaged
• Radiation therapy can be administered in the following ways:
  • Either by a machine, placed outside the body (called external beam radiation)
  • Or it may be administered internally, by a device positioned directly at, or close to the malignant tumor, inside the lungs (called brachytherapy)

Radiation therapy and chemotherapy can be used as a combination therapy. Combinational therapy increases the effects of both types of treatment. However, the side effects are cumulative.

Targeted drug therapy: Targeted drug therapy is a relatively new medical treatment used to target abnormal cancer cells and reduce the chance of cancer spreading to other parts of the body.

How can Type III Pleuropulmonary Blastoma be Prevented?

Currently, there is no known prevention method for Type III Pleuropulmonary Blastoma. 

• Some research scientists and healthcare providers support the screening of close family members and relatives of children, who have been diagnosed with Pleuropulmonary Blastoma
• Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations are mandatory for those, who have already endured the tumor, due to its metastasizing potential and chances of recurrence. Often several years of active vigilance is necessary

What is the Prognosis of Type III Pleuropulmonary Blastoma? (Outcomes/Resolutions)

• Pleuropulmonary blastoma is an aggressive malignancy of the lung. The overall 5 year survival rate is less than 50% in children with Type III Pleuropulmonary Blastoma. The prognosis of type III tumor is worse than that of type I tumor
• The positive prognostic indicators include the possibility of a complete tumor removal through surgery and an absence of tumor invasion
• The prognosis of lung cancer, in general, depends upon a set of several factors that include:
  • Stage of lung cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Histological subtype of the tumor: Some subtypes have better prognosis than others
  • The size of the lung tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Individuals with bulky disease of the lung cancer have a poorer prognosis
  • Involvement of the lymph node, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment of lung cancer: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (like cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

It is important to have follow-up appointments with a physician, to evaluate the effects of the current treatment method, and to monitor for any returning tumors.

Additional and Relevant Useful Information for Type III Pleuropulmonary Blastoma:

Lung cancer incidence is around 35 cases per 100,000 populations: The incidence of lung cancer in non-smokers is 1-2 cases per 20,000 populations per year; its incidence in smokers is 20-30 times higher than that of non-smokers.