Overview of DICER1
It is an extremely rare malignant tumor of the lungs, which may manifest as cough, chest pain, chest tightness, blood in sputum, etc. The cause of the disease is still not completely clear, and is partly related to the mutation of the DICER1 gene. Surgical resection is the mainstay of the disease, and radiotherapy can be supplemented in the postoperative period.
Definition
Pneumoblastoma (PPB) is an extremely rare malignant tumor of the lung, consisting of immature mesenchymal and epithelial components in varying proportions, and pathologically resembling the embryonic lung at 10 to 16 weeks of age.
The incidence of PPB is low, the clinical presentation lacks specificity, and the imaging manifestations are atypical, making it difficult to differentiate it from congenital cystic lung disease, so the rate of missed diagnosis and misdiagnosis is high.
It is a highly aggressive tumor with a high degree of malignancy. PPB is currently treated internationally with a combination of surgery, chemotherapy and/or radiotherapy.
Classification
Classification by age
Adult-type pneumoblastoma
It has a similar pathogenesis to general lung cancer, including bidirectional pneumoblastoma (BPB) and unidirectional pneumoblastoma, which is also known as epithelial or well-differentiated fetal adenocarcinoma (WDFA).
Childhood-type Pneumoblastoma
i.e. pleuropulmonary blastoblastoma (PPB), has similarities with embryonal rhabdomyosarcoma in terms of immunologic presentation and cytogenetics.
According to pathologic type childhood PPB can be classified into 3 types, which are type I (cystic), type II (cystic-solid) and type III (solid), and type Ir is a special type of type I PPB.
Classification according to the site of development
Central pneumoblastoma
The tumor occurs in the bronchus above the opening of the segmental bronchus.
Peripheral pneumoblastoma
The tumor develops in the bronchi below the opening of the segmental bronchi, i.e. from the subsegmental bronchi to the alveoli.
Incidence
Pneumoblastoma is very rare and accounts for 0.25% to 0.5% of primary tumors in the lungs.
It can occur at any age.The peak age of onset is 10 and 70 years for BPB and 40 years for WDFA.The peak age of onset is 10 years for PPB.It has also been reported in the literature that the mean age of onset for PPB is 40 years.
In terms of gender, males are more common in BPB and WDFA and females are more common in PPB.
Etiology
Causes of the disease
There is no clear cause of pneumoblastoma. However, some studies suggest that smoking is a major risk factor for pneumoblastoma.
Pathogenesis
The pathogenesis of pneumoblastoma is still unknown. Adult-onset pneumoblastoma has a similar pathogenesis to that of lung cancer in general.
Theories
There are currently the following two theories.
Convergent hypothesis: Different types of tumor cells originate from different epithelial and mesenchymal stem cells.
Diffuse hypothesis: different types of tumor cells originate from a single totipotent stem cell.
DICER1 gene mutation
In recent years, studies have found and confirmed that the occurrence of PPB is associated with mutations in the DICER1 gene, and that PPB is one of the hallmark disorders of the DICER1 Pneumoblastoma Familial Tumor Susceptibility Syndrome.
Symptoms
Main Symptoms
Pneumoblastoma behaves similarly to lung cancer without characteristic clinical manifestations.
Cough, chest pain, chest tightness, and blood in sputum are mostly the main symptoms, and fever may occur when bronchial lumen obstruction is accompanied by secondary infection.
About 40% of patients do not have any symptoms and are found by physical examination or examination required for other diseases.
Other symptoms
Some advanced patients may develop malignant disease, which is characterized by extreme emaciation, weakness, and generalized exhaustion.
Medical treatment
Department of Medicine
Thoracic Surgery
Please consult the Department of Thoracic Surgery if nodules or space-occupying lesions in the lungs are detected on chest imaging (X-ray, chest CT, etc.) during a routine physical examination or other tests.
Medical Oncology
When a diagnosis of pneumoblastoma is confirmed and comprehensive internal medicine treatment such as chemotherapy is required, please consult the Department of Medical Oncology.
Respiratory Medicine
When symptoms such as cough, blood in sputum, chest pain, chest tightness, etc. occur, please consult the Department of Respiratory Medicine.
Preparation for medical treatment
Preparation for consultation: registration, preparation of documents, common problems
Tips for Medical Treatment: Registration, Preparation of Documents, Frequently Asked Questions
Chest X-rays or CT examinations may be required. Avoid wearing metal clothing such as shirts with buttons, blouses with sequins, and dresses with zippered buttons.
Preparation Checklist
Symptom Checklist
Pay particular attention to the time of onset of symptoms, specific manifestations, etc.
Is there coughing and sputum, and for how long?
Is there blood in the sputum?
Is there any chest pain, chest tightness, breath-holding, and for how long?
Has there been a recent change in weight? How is your appetite?
List of medical history
Is there any smoking, for how long and how many cigarettes per day?
Is there a family history of lung cancer or other malignant tumors?
Any drug or food allergies?
Checklist
Test results in the last six months, which can be brought to the doctor’s office
Specialized tests: lung biopsy pathology report, chest X-ray or CT report, tumor markers.
Laboratory tests: blood routine, urine routine, stool routine, biochemical tests.
Imaging tests: chest enhanced CT, magnetic resonance imaging (MRI), PET-CT.
Diagnosis
Diagnosis is based on
Medical history
The patient may have the following medical history:
Long history of heavy smoking.
Family history of malignant tumors.
Clinical manifestations
Pneumoblastoma is mostly asymptomatic in the early stages, and as the disease progresses, symptoms such as cough, chest pain, chest tightness, blood in sputum, fever, weight loss, and generalized weakness may occur.
Imaging examination
Chest X-ray
It is the initial examination to detect pneumoblastoma.
Chest X-ray usually shows a single round or ovoid shadow located in the periphery of the lungs, with uniform density and smooth edges; the size varies, most of which are more than 5cm in diameter; a few of them may be lobulated or accompanied by pulmonary atelectasis, and it is rare to see multiple and enlarged lymph nodes in the lungs.
Chest CT
To assess the location, scope, character and lymph node metastasis of the tumor, it can also distinguish benign and malignant, which is more helpful for judging the clinical staging.
Magnetic resonance imaging (MRI)
It can help determine whether the chest wall or mediastinum has been invaded by the tumor.
Patients who have already been diagnosed with pneumoblastoma can also use MRI to help clarify the staging.
Fiberoptic bronchoscopy
For central pneumoblastoma, bronchoscopy can directly visualize the lesions inside the bronchial tubes and can remove some of the tissue for pathological biopsy.
However, the tumors of this disease are mostly located in the periphery, and the invasion into the bronchioles is rare, so sputum cytology and bronchoscopy are not very helpful for diagnosis.
Pathologic examination
Pathological diagnosis of lung biopsy specimens is mainly to clarify the presence or absence of tumor and the histological type of the tumor, which is the “gold standard” for final diagnosis.
Under the light microscope, malignant mesenchymal components and epithelial components with different degrees of differentiation can be seen, and sometimes well-differentiated cartilage and hemorrhagic necrotic areas can be seen.
Under the electron microscope, there are tight connections between epithelial cells and underdeveloped bridge grains, and the cytoplasm has different electron densities; there is no connection or occasional connection between mesenchymal cells, and there are few organelles in the cytoplasm, which are underdeveloped.
If histology is difficult to distinguish, additional immunohistochemistry (e.g., CgA, EMA) may be required to aid in the diagnosis.
Differential diagnosis
Hypofractionated alveolar cell carcinoma
Similarities: both may present with symptoms such as cough, blood in sputum, chest pain and chest tightness.
Differences:
Poorly differentiated alveolar cell carcinoma mostly occurs in the peripheral part of the lungs and may be single or multiple nodules.
The cancer cells grow along the alveolar wall, are more uniform in size, arranged in a single layer, with much connective tissue in the interstitium, without the manifestation of transition from adenoid to sarcomatoid structure of pneumoblastoma.
Tuberculosis
Similarity: Patients with pulmonary tuberculosis also have symptoms of coughing, coughing up sputum or blood in sputum.
Differences:
Tuberculosis is prevalent in young people.
There may be special symptoms such as low afternoon fever and night sweats.
Symptoms can be reduced or disappear after anti-tuberculosis treatment.
In pathological examination, tuberculosis is seen as Mycobacterium tuberculosis.
Sarcoma originating in the chest cavity
Similarities: rhabdomyosarcoma originating in the thoracic cavity may have similar symptoms, as well as the presence of a malignant spindle cell component on pathology.
Points of difference:
Rhabdomyosarcomas originating in the thoracic cavity are primarily identified by genetic testing.
PAX3-FOXO1, a characteristic fusion gene arising from the chromosomal translocation t(2;13)(q35;q14), is present in approximately 60% of patients with vesicular rhabdomyosarcoma and can be used in the differential diagnosis with PPB.
Treatment
Aims of treatment: Maximize tumor clearance, improve patients’ quality of life and prolong survival time.
Treatment principle: Once the diagnosis of pneumoblastoma is clear, treatment should be started as early as possible, with surgical resection as the first choice.
Surgical treatment
At present, it is believed that the main treatment for pneumoblastoma is surgery, and the type of surgery can be wedge resection, lobectomy or total lung resection according to the size and location of the tumor and the general condition of the patient.
For patients with huge tumors that can not be completely resected, puncture biopsy or surgical biopsy is feasible, and the tumor can be shrunk after 2-4 courses of chemotherapy after clearing the pathology, and then radical surgery can be performed.
Radiotherapy and chemotherapy
Patients with advanced stage need comprehensive treatment with combined radiotherapy and chemotherapy, but the efficacy of radiotherapy and chemotherapy is still uncertain.
There is no difference in efficacy between different chemotherapy regimens, but platinum-based chemotherapy regimens are still the choice for advanced or metastatic patients.
For pediatric patients, the main chemotherapeutic agents used are vincristine, cyclophosphamide, isocyclophosphamide, actinomycin D, and adriamycin.
Frontline therapy
Treatment with targeted agents such as sorafenib and crizotinib has been reported.
Prognosis
Cure
The prognosis of some patients after complete surgical resection is good, and long-term survival has been reported with a survival time of more than 11 years [9].
The 5-year survival rate was 39% according to foreign scholars, and the 5-year survival rate was reported to be 15.7% to 55% in China [10-11].
Prognostic factors
Prognostic factors are factors that have an impact on the overall survival and quality of survival of patients.
The prognosis of this disease is related to age, tumor size, tumor site, tumor stage and pathological tissue type, and the older the age, the longer the tumor diameter >5 cm, and the more mesenchymal components, the worse the prognosis.
Daily
Daily management
Lifestyle
Quit smoking and drinking, avoid exertion, have a regular routine, do not stay up late, and ensure sufficient sleep.
Maintain a healthy body weight, take appropriate activities, such as slow walking, tai chi, qigong, breathing exercises, etc., and avoid going to crowded places.
Diet management
Have a balanced diet with diversified and nutritious food types.
Consume more food rich in vitamins and dietary fiber, such as fresh vegetables and fruits.
Psychological support
Maintain a good mood and mindset to face the disease positively.
Learn to confide in friends and family members to avoid excessive pressure, which may cause mental illness, and seek help from a psychiatrist if necessary.
Family members give the patient sufficient company and create a cozy family atmosphere. Comfort the patient more to help him/her get through the difficult times.
Disease monitoring
Patients should pay attention to the sputum condition in their daily life. If there is blood in the sputum again, or even hemoptysis, etc., they should consult a doctor in time.
Follow-up
Follow-ups are important for patients to help the doctor assess the efficacy of the treatment and to monitor for recurrence.
The time for follow-up should be set by the specialist.
Review items: tumor markers, chest CT, chest MRI and other tests can help determine whether there is recurrence.
Prevention
There are no effective preventive measures for Pneumoblastoma. Annual health checkups are recommended and may help reduce the incidence of the disease.