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Klinicka Onkologie : Casopis Ceske a... 2019DICER1 syndrome is an inherited disorder that increases the risk of different types of malignant and benign tumors. The syndrome is caused by mutations in the DICER1...
DICER1 syndrome is an inherited disorder that increases the risk of different types of malignant and benign tumors. The syndrome is caused by mutations in the DICER1 gene, which is located on the long arm of chromosome 14, region q32.13. Patients with DICER1 syndrome commonly develop pleuropulmonary blastoma (PPB), multinodular goiter, ovarian Sertoli-Leydig cell tumors, and/or other types of tumors. In approximately 35% of families with children manifesting PPB, further (and rather rare) malignancies may be observed, including cystic nephroma, nodular dysplasia of the thyroid gland, medulloepithelioma of the iris, embryonal rhabdomyosarcoma botryoid type, nasal epithelial hamartoma, pituitary blastoma, and/or pineoblastoma. Large studies report a high variability of tumors associated with DICER1. DICER1 syndrome, which is associated with an inherited predisposition to tumors, is inherited in an autosomal dominant pattern. Symptoms of DICER1 syndrome may vary, even within families. Preventive screening of carriers with causative mutations is complicated. Follow-up is undertaken as recommended by the 2016 International PPB Register. This work was supported by grant of Ministry of Health of the Czech Republic AZV 16-3329A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 4. 6. 2019 Accepted: 6. 6. 2019.
Topics: DEAD-box RNA Helicases; Genetic Predisposition to Disease; Humans; Mutation; Neoplastic Syndromes, Hereditary; Ribonuclease III
PubMed: 31409088
DOI: 10.14735/amko2019S123 -
Pediatric Pulmonology Sep 2022Pleuropulmonary blastoma (PPB) is a very rare and highly aggressive neoplasm occurring in children, mostly under 6 years of age. We assessed the clinical...
OBJECTIVES
Pleuropulmonary blastoma (PPB) is a very rare and highly aggressive neoplasm occurring in children, mostly under 6 years of age. We assessed the clinical characteristics, treatment modalities, treatment outcomes, and prognostic factors affecting survival in patients with PPB treated at our institution over a 10-year period to improve the prognosis.
METHODS
From November 2008 to November 2019, 31 children (21 boys and 10 girls) with a median age of 30 months (ranging, 22 days to 54 months) were treated at our institution. Here we describe the patient characteristics, treatment modalities, and treatment outcomes. The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS). Log-rank test was performed for comparison between groups.
RESULTS
Three children were lost to follow-up and two were dead due to postoperative complications. Of the 26 patients included in the follow-up, 16 PPB patients displayed tumor-free survival. The 5-year PFS and OS were 60.4% and 60.1% respectively. By stratified statistical analysis, the 5-year PFS and OS of type I PPB were 100%, while those of type III PPB were 43.7% and 43%, respectively. The 5-year PFS and OS of complete tumor resection were 76.5% and 75.6%, respectively, while those with tumor residue were 31.3%. The 5-year PFS and OS combined with chemotherapy were 62.2% and 61.6%, respectively, while those without chemotherapy were 0%.
CONCLUSIONS
PPB is an aggressive neoplasm. The main factors related to the prognosis of PPB are pathological type, tumor resection degree, and postoperative adjuvant therapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Disease-Free Survival; Female; Humans; Infant; Infant, Newborn; Male; Prognosis; Pulmonary Blastoma; Retrospective Studies
PubMed: 35510654
DOI: 10.1002/ppul.25930 -
Pathobiology : Journal of... 2021Pleuropulmonary blastoma (PPB) is a rare sarcomatous malignancy involving the lung and pleura which occurs in early childhood. Cystic PPB in the early stage can be...
INTRODUCTION
Pleuropulmonary blastoma (PPB) is a rare sarcomatous malignancy involving the lung and pleura which occurs in early childhood. Cystic PPB in the early stage can be misdiagnosed as other cystic diseases. Early detection of this entity is important for appropriate treatment and prevention of disease progression. Hotspot mutations in the ribonuclease IIIb (RNase IIIb) domain of DICER1 have been reported to have a crucial role as genetic factors of PPB and DICER1 familial syndrome. We reviewed the clinicopathologic findings of PPB and the status of DICER1 hotspot mutation and patients' clinical course.
METHODS
We retrospectively reviewed all patients with histologically confirmed PPB at Asan Medical Center between 2000 and 2017. Ten cases were identified in the database, and their clinicopathologic parameters were evaluated. PPB was classified into the following 3 pathologic subtypes: type I (purely cystic), type II (mixed cystic and solid), and type III (entirely solid). The status of DICER1 mutation in 2 hotspot regions of the RNase IIIb domain was evaluated by Sanger sequencing.
RESULTS
The most frequent PPB type was II (6 cases), followed by I and III (2 cases each). The age at diagnosis ranged from 16 months to 15 years. All patients underwent surgery, and all patients received adjuvant or neoadjuvant chemotherapy. Four of 7 patients had missense mutations in the RNase IIIb hotspot; the base and predicted corresponding amino acid changes were c.5113 G>A (p.E1705K), c.5407 G>A (p.E1803K), c.5425 G>A (p.G1809R), and c.5428 G>T (p.D1810Y). There was no particular association between the presence of the hotspot mutation and histologic type. Nine patients survived with no evidence of disease for a median interval of 93 (range, 13-199) months. Only 1 patient diagnosed with type III PPB at the age of 18 years had recurrence after 20.8 months and eventually died 66 months after the initial diagnosis.
CONCLUSIONS
Late detection of solid PPB is associated with poor prognosis. Considering the rarity of PPB disease and the importance of DICER1 hotspot mutation in pathogenesis, DICER1 hotspot mutation testing and identification in the early cystic stage can improve patient outcomes.
Topics: Adolescent; Child; Child, Preschool; DEAD-box RNA Helicases; Female; Germ-Line Mutation; Humans; Infant; Lung Neoplasms; Male; Pulmonary Blastoma; Retrospective Studies; Ribonuclease III
PubMed: 33567437
DOI: 10.1159/000512957 -
Radiology Case Reports Sep 2022Pleuropulmonary blastoma (PPB) is among the rarest malignant tumors diagnosed in children. PPBs can be histopathologically classified into 3 types: cystic tumor (type...
Pleuropulmonary blastoma (PPB) is among the rarest malignant tumors diagnosed in children. PPBs can be histopathologically classified into 3 types: cystic tumor (type I), mixed cystic and solid tumor (type II), and pure solid tumor (type III). We describe a case of type III PPB that was detected in a prenatal fetus, confirmed using histopathological methods. To the best of our knowledge, this is the first case describing a type III PPB detected in a fetus. Prenatal ultrasonography is an excellent tool for detecting pulmonary lesions during the diagnostic phase, and the possibility of PPB should be considered when solid tumors are detected. Early detection can allow for the performance of full resection, leading to a better prognosis for this cancerous tumor.
PubMed: 35818452
DOI: 10.1016/j.radcr.2022.06.032 -
Maternal Health, Neonatology and... Mar 2023Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest...
BACKGROUND
Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, is often mistaken for a congenital pulmonary airway malformation, as the two entities can be difficult to distinguish on imaging and pathology. Diagnosis of PPB should prompt workup for DICER1 syndrome, an autosomal dominant tumor predisposition syndrome. We report a newborn with a congenital PPB presenting with tachypnea and hypoxia, who was found to have variant of uncertain clinical significance (VUS) in DICER1.
CASE PRESENTATION
A term female infant developed respiratory distress shortly after birth. Initial imaging was concerning for a congenital pulmonary airway malformation versus congenital diaphragmatic hernia, and she was transferred to a quaternary neonatal intensive care unit for management and workup. Chest CT angiography demonstrated a macrocytic multicystic lesion within the right lower lobe without systemic arterial supply. The pediatric surgery team was consulted, and the neonate underwent right lower lobectomy. Pathology revealed a type I PPB. Oncology and genetics consultants recommended observation without chemotherapy and single gene sequencing of DICER1, which identified a germline VUS in DICER1 predicted to alter splicing. RNA-sequencing from blood demonstrated that the variant resulted in an in-frame deletion of 29 amino acids in a majority of transcripts from the affected allele. Due to the patient's young age at presentation and high clinical suspicion for DICER1 syndrome, tumor surveillance was initiated. Renal and pelvic ultrasonography were unremarkable.
CONCLUSION
We present the case of a term neonate with respiratory distress and cystic lung mass, found to have a type I PPB with a germline VUS in DICER1 that likely increased her risk of DICER1-related tumors. Nearly 70% of patients with PPB demonstrate germline mutations in DICER1. Review of RNA sequencing data demonstrates the difficulty in classifying splice variants such as this. Penetrance is low, and many patients with pathogenic DICER1 variants do not develop a malignancy. Best practice surgical and oncologic recommendations include an individualized approach and tumor board discussion. This case highlights the importance of a multidisciplinary team approach and the utility of international registries for patients with rare diagnoses.
PubMed: 36922881
DOI: 10.1186/s40748-023-00148-2 -
Indian Journal of Thoracic and... Oct 2019Pleuropulmonary blastoma (PPB) is a rare, malignant tumor of the lung and is the most common primary pulmonary malignancy in children. Here, we report a case of a boy...
Pleuropulmonary blastoma (PPB) is a rare, malignant tumor of the lung and is the most common primary pulmonary malignancy in children. Here, we report a case of a boy who was diagnosed with type I regressed PPB after being mislabeled with congenital pulmonary malformation. A 10-year-old boy presented to our hospital with a history of worsening dyspnea. Since birth, his clinical status and radiographic images were concerning for congenital lobar emphysema that was managed conservatively. A chest computed tomography (CT) scan confirmed the persistence of a large cystic lesion and a diagnostic and therapeutic cystectomy was performed. Microscopic examination confirmed the presence of PPB type Ir. Patient was managed surgically alone with no added chemotherapy, as there was no overall survival benefit. PPB Ir has an overall favorable clinical outcome. Limited follow-up data are available due to the rarity of the lesion and the overlap with other congenital cystic lung malformations.
PubMed: 33061055
DOI: 10.1007/s12055-019-00814-1 -
The American Journal of Surgical... Feb 2008Pleuropulmonary blastoma (PPB) is a malignant neoplasm of the lung that presents in early childhood. The early form of the disease, cystic type I PPB, can be clinically... (Review)
Review
Pleuropulmonary blastoma (PPB) is a malignant neoplasm of the lung that presents in early childhood. The early form of the disease, cystic type I PPB, can be clinically and pathologically deceptive because of its resemblance to some developmental lung cysts. This study reviews 51 cases of type I PPB and 6 lung cysts from relatives of children with PPB. Type I PPB is a delicate multilocular cyst with variable numbers of primitive mesenchymal cells beneath a benign epithelial surface. Rhabdomyoblasts and cartilage nodules are seen in 49% and 40% of cases, respectively. Tumors in the youngest subset of patients, from birth to 2 months of age, are more uniform in composition and cellularity compared with those in older groups. Early tumors have a subtle transition between normal developing lung and tumor, showing bland interstitial mesenchymal cells uniformly expanding the alveolar septa. Presumed regressive changes including cyst wall necrosis are common. This phenomenon may explain the variable and sometimes sparse tumor cellularity seen in some type I PPBs. On a biologic level, this process supports the concept that not all type I PPBs are fated to progress to a type II or III PPB. Factors that control the balance between progression and regression may be important in predicting tumor behavior and determining which patients will benefit from adjuvant chemotherapy. In the meantime, recognition of this lesion as a neoplasm with malignant potential rather than a developmental cystic malformation is vital so the child can receive complete excision and appropriate follow-up care.
Topics: Age Factors; Child; Child, Preschool; Combined Modality Therapy; Cystic Adenomatoid Malformation of Lung, Congenital; Cysts; Diagnosis, Differential; Family Health; Female; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; International Cooperation; Lung Neoplasms; Male; Pleural Neoplasms; Pulmonary Blastoma; Registries
PubMed: 18223332
DOI: 10.1097/PAS.0b013e3181484165 -
Virchows Archiv : An International... Sep 2020
Topics: Cystic Adenomatoid Malformation of Lung, Congenital; Humans; Pulmonary Blastoma
PubMed: 32300881
DOI: 10.1007/s00428-020-02811-x -
Pediatric Radiology Jul 2003We report on a 3-year-old girl who developed a large embolic cerebral infarct 1 day after an uneventful thoracotomy to remove a large pleuropulmonary blastoma. The... (Review)
Review
We report on a 3-year-old girl who developed a large embolic cerebral infarct 1 day after an uneventful thoracotomy to remove a large pleuropulmonary blastoma. The tumour had encased the heart and great vessels and ruptured into the left hemithorax. Pleuropulmonary blastoma is a rare, but unique, primary thoracic neoplasm in young children and, to our knowledge, the development of a secondary large embolic cerebral infarct is also uncommon and has not been reported in this tumour.
Topics: Cerebral Infarction; Child, Preschool; Female; Humans; Intracranial Embolism; Lung Neoplasms; Magnetic Resonance Imaging; Postoperative Complications; Pulmonary Blastoma; Thoracotomy; Tomography, X-Ray Computed
PubMed: 12712268
DOI: 10.1007/s00247-003-0926-5 -
International Journal of Surgery Case... May 2023Pleuropulmonary blastoma (PPB) is rare, representing 0.3 % of all pediatric cancers. PPB is classified into three subtypes and may progress from type I to types II and...
INTRODUCTION
Pleuropulmonary blastoma (PPB) is rare, representing 0.3 % of all pediatric cancers. PPB is classified into three subtypes and may progress from type I to types II and III, with a worse prognosis. Given its rarity, the diagnosis is frequently challenging.
CASE PRESENTATION
We report an occurrence of PPB in a 3-year-old girl, who presented recurrent pneumopathy. Imaging investigations revealed a large solid lesion in the left hemithorax. Biopsy followed by histological analysis suggested rhabdomyosarcoma. The patient received neoadjuvant chemotherapy before proceeding to complete tumor excision. Surgical exploration revealed that the tumor was primitively related to parietal pleura and lower lobe of left lung. Histopathology of the tumor retained a definitive diagnosis of PPB type II. Postoperative course was uneventful, and a cerebral MRI ruled out brain metastasis. Adjuvant chemotherapy was administered.
DISCUSSION
Clinical expression of PPB is nonspecific and variable. It ranges from a dry cough to respiratory distress. Standard radiography is the first examination to perform and CT is the gold standard for characterization thoracic masses. Surgery and chemotherapy are the pillars of treatment. Indications depend on the tumor type, its extent and its resectability.
CONCLUSION
PPB is an aggressive tumor that occurs only in children. Due to the rarity of PPB, evidence on optimal treatment is still insufficient. Careful follow-up is necessary searching for local recurrence or metastasis.
PubMed: 37119756
DOI: 10.1016/j.ijscr.2023.108261