Type I pleuropulmonary blastoma presenting as congenital pulmonary airway malformation: A report of two cases

Kumari, Kalpana; Longchar, Moanaro; Gunathilaka, Ganganath; Narange, Priyanka; Aggarwal, Sandeep; Arava, Sudheer

doi:10.4103/ijpm.ijpm_713_18

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung, with an incidence of 25-50 cases per year in the United States [1,2]. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, [3][4][5] is often mistaken for a congenital pulmonary airway malformation (CPAM), as the two entities can be difficult to distinguish on imaging and pathology [6][7][8]. Diagnosis of PPB should prompt workup for DICER1syndrome, a cancer predisposition syndrome strongly associated with PPB [9].…”

Section: Introductionmentioning

confidence: 99%

Congenital pleuropulmonary blastoma in a newborn with a variant of uncertain significance in DICER1 evaluated by RNA-sequencing

Lyle

Ohlsen

Miller

et al. 2023

matern health, neonatol and perinatol

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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.

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Section: Introductionmentioning

confidence: 99%

Congenital pleuropulmonary blastoma in a newborn with a variant of uncertain significance in DICER1 evaluated by RNA-sequencing

Lyle

Ohlsen

Miller

et al. 2023

matern health, neonatol and perinatol

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“…[74][75][76][77] The emergence of PPB type I has introduced a cautionary note into the approach of any CCPL, requiring a thorough pathologic examination. [78][79][80][81] Studies on DICER1 detection by ctDNA are ongoing. 82…”

Section: Cpam and Bronchial Atresia (Ba) With Interruption Of Lung De...mentioning

confidence: 99%

Congenital Pulmonary Airway Malformations With a Reconsideration and Current Perspective on the Stocker Classification

2023

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Congenital cystic pulmonary lesions (CCPLs) are represented by the following entities: congenital pulmonary airway malformation (CPAM), formerly congenital cystic adenomatoid malformation, extra- and intralobar sequestration (EIS), congenital lobar emphysema (overexpansion), and bronchogenic cyst. The developmental model of CPAM histogenesis by Stocker proposed perturbations designated as CPAM type 0 to type 4 without known or specific pathogenetic mechanisms along the airway from the bronchus to the alveolus. This review highlights mutational events either at the somatic level in KRAS (CPAM types 1 and possibly 3) or germline variants in congenital acinar dysplasia, formerly CPAM type 0, and pleuropulmonary blastoma (PPB), type I, formerly CPAM type 4. The potential for overt malignant progression exists in the case of PPB type I and CPAM type 1 in some cases to well-differentiated mucinous adenocarcinoma. On the other hand, CPAM type 2 is an acquired lesion resulting from interruption in lung development secondary to bronchial atresia. The latter is also regarded as the etiology of EIS whose pathologic features are similar, if not identical, to CPAM type 2. These observations have provided important insights into the pathogenetic mechanisms in the development of the CPAMs since the Stocker classification.

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Congenital Pleuropulmonary Blastoma in a Newborn with a Variant of Uncertain Significance in DICER1 Evaluated by RNA-sequencing

Lyle

Ohlsen

Miller

et al. 2022

Preprint

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BackgroundPleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. PPB 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 presentationA 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 minority of transcripts. 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. ConclusionWe 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. 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.

show abstract

Type I pleuropulmonary blastoma presenting as congenital pulmonary airway malformation: A report of two cases

Cited by 3 publications

References 8 publications

Congenital pleuropulmonary blastoma in a newborn with a variant of uncertain significance in DICER1 evaluated by RNA-sequencing

Congenital pleuropulmonary blastoma in a newborn with a variant of uncertain significance in DICER1 evaluated by RNA-sequencing

Congenital Pulmonary Airway Malformations With a Reconsideration and Current Perspective on the Stocker Classification

Congenital Pleuropulmonary Blastoma in a Newborn with a Variant of Uncertain Significance in DICER1 Evaluated by RNA-sequencing

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