Cystic Adenomatoid Malformation Research Articles

Congenital pulmonary airway malformation in adults: A case series

Introduction. Two-thirds of patients with congenital pulmonary airway malformation are asymptomatic at birth, but during life they may develop symptoms such as recurrent respiratory infections. The purpose of this paper is to present three cases of adult patients in whom congenital pulmonary airway malformation was diagnosed and treated at the Institute for Lung Diseases of Vojvodina, along with the clinical course of the disease and the therapeutic procedure. Case Report 1. A 24-year-old female with a medical history of asthma and recurrent signs of lower respiratory tract infections was referred to a thoracic surgeon. Computed tomography of the chest and clinical features were consistent with a congenital lung disease. A left lower video-assisted thoracoscopic lobectomy was performed. Histopathological analysis confirmed type II congenital pulmonary airway malformation with pulmonary sequestration. Case Report 2. A 41-year-old male with a history of left-sided spontaneous pneumothorax at the age of 16 was referred to a thoracic surgeon due to moderate hemoptysis, one month after hospital treatment of left-sided bronchopneumonia. On chest computed tomography, multiple cystic lesions were found in the left lower lung lobe. Thoracotomy and left lower lobectomy were performed. Histopathological analysis confirmed type I congenital pulmonary airway malformation. Case Report 3. The third patient was a 16-year-old male with a history of juvenile asthma and recurrent right-sided bronchopneumonia. Sings of necrotizing pneumonia, lung abscess, and mediastinal lymphadenomegaly were found in the affected lobe. Thoracotomy and right lower lobectomy were performed. Histopathological analysis confirmed type II congenital pulmonary airway malformation. Conclusion. In children and young adults with recurrent small airway inflammation, congenital lung malformation should be considered in the differential diagnosis.

Thoracic Mass Lesions in Children and their Management: A Prospective Interventional Study

Introduction: Thoracic mass lesions in children are heterogeneous group of disorders, out of which developmental malformations such as Congenital Pulmonary Airway Malformation (CPAM), bronchogenic cysts and Congenital Lobar Emphysema (CLE) are common pathology. Primary pulmonary malignancies like carcinoid tumour and pulmonary blastoma may rarely be encountered. Aim: To analyse the clinical pattern, diagnosis and management of children with thoracic mass lesions. Materials and Methods: This prospective interventional study was conducted from June 2018 to May 2021, on 19 patients diagnosed and operated for thoracic mass lesions. It was carried out in the Department of Paediatric Surgery, Sardar Vallabhbhai Patel Post Graduate (SVP PG) Institute of Paediatrics, Srirama Chandra Bhanja (SCB) Medical College, Cuttack, Odisha, India. The final diagnosis was only based on histopathological study. The parameters assessed were demographic features, operative findings and pathological diagnosis. Statistical analysis was done using Microsoft Excel Q1 Macros software. Data was presented as mean, median with Confidence Interval (CI) and percentages (%). Results: A total number of 19 cases were operated, out of which 12 were boys and seven were girls. The median age at presentation was three month (range: five days to five years). Right side of thorax was more commonly affected in 14 cases and left side in five cases. CLE was the most common pathology (eight cases) followed by CPAM (six cases). Bronchogenic cysts and lymphangioma were detected in two cases each. Pulmonary blastoma was the only malignant lesion found. There was no mortality in the present study. Conclusion: The patients with thoracic mass lesions usually present before the age of six months and CLE was detected as the most common finding. A conclusive diagnosis can be obtained only from histopathology

Recurrent, persistent pneumothorax in a neonate: A cryptic cause

Newborns, especially preterms, have a higher risk of developing pneumothorax. We report a 33-week preemie who presented with recurrent, persistent right pneumothorax, which failed to resolve with standard treatment. The child underwent surgical removal of a suspect nonexpanding upper lobe of the right lung with clinical improvement. Histopathology was atypical but nearly consistent with congenital pulmonary airway malformation (CPAM). This report highlights the clinicopathological discordance noted and aims to draw an embryological explanation toward the atypical histomorphology of CPAM in preemies.

Evaluation of Relative Frequency of Pulmonary Hypoplasia and Various Anomalies Associated with Pulmonary Hypoplasia in Fetal Autopsy Study.

Pulmonary hypoplasia (PH) is one of the commonest causes of neonatal morbidity and mortality. The suggested diagnostic criteria for PH are the Lung Weight:Body Weight (LW:BW) ratio ≤ 0.012 and/or Radial Alveolar Count (RAC) ≤ 4.1. The present study was done to determine the relative frequency of PH in fetal autopsy study by the LW:BW ratio and RAC along with evaluation of the defects/anomalies associated with PH. A prospective observational study was done on fetal autopsy specimens in the Department of Pathology. Examination and grossing were done as per the standard format of fetal autopsy study. Evaluation of PH was done using the LW:BW ratio and RAC. Diagnostic criteria for PH were taken as LW:BW ratio < 0.012 and/ or RAC < 4.1. Chi-square test, Student T test and Kruskal Wallis test were used in statistical analysis. A diagnosis of PH was made in 45 cases. Concordance between the LW:BW ratio and RAC was observed in 33 cases amounting to 73.33%. The mean LW:BW ratio was the lowest in oligohydramnios. The mean RAC was the lowest in congenital cystic adenomatoid malformation. A diagnosis of PH was rendered in a greater number of cases when evaluation was done by considering both the LW:BW ratio and RAC. Hence, evaluation by both the LW:BW ratio and RAC provides a reliable index of lung growth and should be an essential part of fetal autopsy study.

Surgical Repair of Atrial Septal Defect and Lung Lobe Resection for Pulmonary Sequestration and Cystic Malformation in One Stage: A Case Report

Incidence of congenital cystic malformation of lungs ranges from 1 in 11,000 to 1 in 35,000 live birth. Concurrence of Congenital Pulmonary Airway Malformation (CPAM) with congenital heart disease is even infrequent. Even rarer, is the incidence of congenital pulmonary vascular and cystic parenchymal lesions with cardiac defects. The non functioning lung tissue is separated from bronchial tree and vascularised by aberrant artery from the systemic circulation. Simultaneous repair of cardiac and pulmonary defects, though challenging, but are preferable because of surgery being done in single stage with better cosmesis. A 10-yearold female child presented to the hospital with recurrent chest infections and respiratory distress while running since five years of age. The patient underwent atrial septal defect closure and right lower lobectomy for CPAM in one stage through midline sternotomy. We conclude that such complex cases can be managed successfully with meticulous planning and multidisciplinary team approach.

Congenital cystic adenomatoid malformation: a rare serial case report

Congenital cystic adenomatoid malformation (CCAM) is a rare congenital lung malformation which a part of the lung becomes polycystic. CCAM accounts for 25% of congenital lung malformations and 95% of lung lesions. Case 1 was a 5-month-old female infant who was diagnosed with pneumothorax, with multiple cysts in the right lung, using chest computed tomography (CT). Thoracotomy lung resection was performed. Case 2 was one-day-old newborn infant who had respiratory distress with Downe score 3. Multiple cystic lesions with septations in left lung was observed on chest CT. Lobectomy inferior lobes of left lung was performed. Both patients were diagnosed as CCAM type 1 pathologically. CCAM can be detected in the gestation by ultrasonography or after delivery through the appearance of respiratory distress signs.

Neonatal congenital pulmonary airway malformation associated with mucinous adenocarcinoma and KRAS mutations

Aim of the studyCongenital pulmonary airway malformation (CPAM) has an estimated prevalence in Europe of 1.06/10,000 live births with most being detected using maternal ultrasound screening. Malignant transformation is a possible complication though its prevalence is unknown and previous reports have usually been in older children. We reviewed our experience to identify those CPAM cases associated with malignancy. MethodsSingle centre retrospective review of all surgically treated children with antenatally-detected CPAM, with detailed review of cases associated with malignancy. Main results210 infants and children underwent resectional surgery for CPAM during the period 1994–2020, with 43(20.5%) undergoing surgery during the neonatal period. Of these, 3 infants, all males, had undergone surgical resection for respiratory distress (at 3, 4 and 8 days of life) with subsequent histological confirmation as Stocker type 1 CPAM with clear foci of mucinous adenocarcinoma. Subsequent genetic analysis showed somatic KRAS (Kirsten Rat Sarcoma Viral Oncogene) mutations in all three cases. No adjuvant treatment was required, and all are asymptomatic and disease-free at most recent follow-up (8 months, 2 and 6 years) ConclusionsThis series highlights a clear association between type 1 CPAM and mucinous adenocarcinoma with KRAS point mutations, suggesting that the process of carcinogenesis has the potential to start in utero. This underlines the importance of discussing the risk of malignancy in prenatal and postnatal counselling.

Congenital pulmonary airway malformation: A rare diagnosis in adulthood.

This paper consists of a clinical image of a complex developmental anomaly that is usually diagnosed prenatally or during childhood. Its detection in adult life is very rare, as happened in the present case.

Congenital Pulmonary Airway Malformation in Children: Advantages of an Additional Trocar in the Lower Thorax for Pulmonary Lobectomy.

Aim: To present the use of an additional trocar (AT) in the lower thorax during thoracoscopic pulmonary lobectomy (TPL) in children with congenital pulmonary airway malformation.Methods: For a lower lobe TPL (LL), an AT is inserted in the 10th intercostal space (IS) in the posterior axillary line after trocars for a 5-mm 30° scope, and the surgeon's left and right hands are inserted conventionally in the 6th, 4th, and 8th IS in the anterior axillary line, respectively. For an upper lobe TPL (UL), the AT is inserted in the 9th IS, and trocars are inserted in the 5th, 3rd, and 7th IS, respectively. By switching between trocars (6th↔8th for the scope, 4th↔6th for the left hand, and 8th↔10th for the right hand during LL and 5th↔7th, 3rd↔5th, and 7th↔9th during UL, respectively), vital anatomic landmarks (pulmonary veins, bronchi, and feeding arteries) can be viewed posteriorly. The value of AT was assessed from blood loss, operative time, duration of chest tube insertion, requirement for post-operative analgesia, and incidence of perioperative complications.Results: On comparing AT+ (n = 28) and AT– (n = 27), mean intraoperative blood loss (5.6 vs. 13.0 ml), operative time (3.9 vs. 5.1 h), and duration of chest tube insertion (2.2 vs. 3.4 days) were significantly decreased with AT (p < 0.05, respectively). Differences in post-operative analgesia were not significant. There were three complications requiring conversion to open/mini-thoracotomy: AT– (n = 2; bleeding), AT+: (n = 1; erroneous stapling).Conclusions: An AT and switching facilitated posterior dissection during TPL in children with congenital pulmonary airway malformation enhancing safety and efficiency.

Mucinous adenocarcinoma in a neonate with congenital pulmonary malformation

Congenital pulmonary airway malformation (CPAM) is a rare developmental abnormality of the lower respiratory tract, often diagnosed during routine prenatal ultrasonography. We report a full-term newborn female noted to have a large mass in the left hemithorax during prenatal ultrasound, at 35 weeks gestation. A multicystic lesion in the lower left chest was confirmed using a Chest Radiograph and Computed Tomography (CT) angiogram. Her hospital course was next followed by a left lower lobectomy, with resultant pathology of CPAM Type 1 and invasive mucinous adenocarcinoma. Though patients with asymptomatic CPAM are often managed by observation, our case of unexpected malignancy advocates early considerations towards Surgery.

Lung ultrasound in children, WFUMB review paper (part 2).

Ultrasound (US) is an ideal diagnostic tool for paediatric patients owning to its high spatial and temporal resolution, real-time imaging, and lack of ionizing radiation and bedside availability. In the current World Federation of Societies for Ultra-sound in Medicine and Biology (WFUMB) paper series so far (part I) the topic has been introduced and the technical require-ments explained. In the present paper the use of US in the lung in paediatric patients is analysed. Lung diseases including the interstitial syndrome, bacterial pneumonia and viral infections, CoViD findings, atelectasis, lung consolidation, bronchiolitis and congenital diseases of the respiratory system including congenital pulmonary airway malformation (CPAM) and sequester but also pneumothorax are discussed.

Analysis of miRNA Profiles and the Regulatory Network in Congenital Pulmonary Airway Malformations.

Background: Specific diagnostic markers for congenital pulmonary airway malformations (CPAMs) have not yet been discovered. This study intends to detect differentially expressed miRNAs in type I and type II CPAMs by using a miRNA chip and clarify the feasibility of miRNAs as different CPAM typing markers.Methods: Lung tissues of type I and type II CPAMs were collected and used to assess the differentially expressed miRNAs using a miRNA chip after evaluation using hematoxylin–eosin staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction and fluorescence in situ hybridization were used to verify the quality of the miRNA chip. The function and pathways of related differentially expressed miRNAs were analyzed by Gene Ontology Enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Targets of miRNAs were predicted by targetscan7.1 and mirdbV6 and the network between miRNA and mRNA was established using Cystoscope software.Results: In total, 394/34 upregulated and 321/72 downregulated miRNAs were found in type I and type II CPAMs, respectively. GO and KEGG analysis showed that different pathways are involved in the regulation of CPAM, including platelet activation, Ras, MAPK, FoxO, and PI3K-Akt signaling pathways. miRNA–mRNA network analysis confirmed four major miRNAs in CPAM, including miR-4731-5p to complexin 2, miR-3150a-3p to vesicle amine transport 1, miR-32-5p to F-box and WD repeat domain containing 7, and miR-454-3p to SLAIN motif family member 1.Conclusion: In summary, we have identified four candidate miRNAs and pathways related to different pattern CPAMs, which provide a new perspective for CPAM research and treatment.

Developmental Pathways Underlying Lung Development and Congenital Lung Disorders.

Lung organogenesis is a highly coordinated process governed by a network of conserved signaling pathways that ultimately control patterning, growth, and differentiation. This rigorously regulated developmental process culminates with the formation of a fully functional organ. Conversely, failure to correctly regulate this intricate series of events results in severe abnormalities that may compromise postnatal survival or affect/disrupt lung function through early life and adulthood. Conditions like congenital pulmonary airway malformation, bronchopulmonary sequestration, bronchogenic cysts, and congenital diaphragmatic hernia display unique forms of lung abnormalities. The etiology of these disorders is not yet completely understood; however, specific developmental pathways have already been reported as deregulated. In this sense, this review focuses on the molecular mechanisms that contribute to normal/abnormal lung growth and development and their impact on postnatal survival.

SARS-CoV-2 Exposed Mesenchymal Stromal Cell from Congenital Pulmonary Airway Malformations: Transcriptomic Analysis and the Expression of Immunomodulatory Genes.

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.

Difficulties in the differential diagnosis of large solitary pulmonary cysts.

Large solitary cystic lesions are a rare finding, and their differential diagnosis includes cystic airspaces associated with lung cancer, congenital pulmonary airway malformations and pneumatoceles. Here, we report 3 consecutive patients who presented with a large solitary pulmonary cyst on chest computed tomography. All underwent surgical resection, and the histopathological findings were different in all 3 cases. In one patient, a very rare finding of squamous cell carcinoma arising from the cystic lesion in the left lower lobe was confirmed. Therefore, in carefully selected cases, pulmonary cysts should be resected based on the potential risk for recurrent infection and the development of malignancy.

Pleuropulmonary Blastoma (PPB) in Child with DICER1 Mutation: The First Case Report in the State of Qatar

Pleuropulmonary blastoma (PPB) is a rare intrathoracic malignancy, which arises from the lung parenchyma and/or pleura. PPB has strong genetic association with mutations in DICER1 gene. Despite being rare, PPB is the most common lung tumor in children below 6 years of age. International registry of the disease has a total of 350 cases worldwide. We report the first case of PPB in the state of Qatar, which presented as a large cystic lung lesion. The patient was first thought to have benign congenital pulmonary airway malformation (CPAM) based on chest X-ray findings. The diagnosis of PPB was suspected based on chest CT scan findings and was confirmed after surgical resection of the cystic mass. The case highlights the need to consider PPB in the differential diagnosis of cystic lung lesions in children and the need for further radiological imaging (i.e., CT scan), genetic testing, and/or excisional biopsy to confirm the diagnosis.

Quantitative CT imaging analysis to predict pathology features in patients with a congenital pulmonary airway malformation

BackgroundRisk for infection and potential malignant degeneration are the most common arguments for resecting asymptomatic Congenital Pulmonary Airway Malformations (CPAM). We aimed to investigate if CT- imaging characteristics can be used to predict histopathological features, by using an objective quantitative CT scoring method. MethodsArchival CPAM tissue samples were histologically re-assessed and patients who had a pre-operative volumetric CT-scan were included. Lung disease was quantified using the newly-developed congenital lung abnormality quantification(CLAQ) scoring method and obtained percentages were used to predict histopathological signs of inflammation and presence of mucinous proliferation (MP). Because MP is presumed a precursor for mucinous adenocarcinoma in situ (AIS) this method was also used to compare CT-scans of patients with AIS to those with only CPAM. ResultsThirty-three CPAM patients were included of which 13(39%) had histological signs of inflammation and 8(24%) had a MP. Patients with inflammation had a significantly smaller lesion (14% vs 38%) while those with MP had more extensive disease (54%vs17%). Patients with AIS had a significantly smaller lesion compared to CPAM patients (5%vs29%). Significant predictors for inflammation were smaller lesion size and percentage hypodensity within lesions while a larger lesion size and percentage parenchymal hyperdensity (solid lung tissue components) were predictors for MP as well as AIS. ConclusionsSmaller CPAM lesions may be more susceptible to inflammation while larger lesions may be associated with the presence of MP. Parenchymal hyperdensity is found as a predictor for MP as well as AIS and should therefore elicit more extensive gross sampling. Level of evidenceLevel III.

Analysis of four cases with congenital pulmonary airway malformation complicated by chronic pulmonary aspergillosis

Objective: To investigate the clinical characteristics, treatment and prognosis of congenital pulmonary airway malformation (CPAM) complicated with chronic pulmonary aspergillosis (CPA) in children. Methods: The clinical manifestation, laboratory test, radiological feature, treatment and prognosis of 4 pediatric patients diagnosis of CPAM with CPA ascertained between March 2016 and April 2020 at the Department of No.2 Respiratory Medicine and Thoracic Surgery of Beijing Children's Hospital were retrospectively analyzed. Results: The 4 children included 2 males and 2 females, their age ranged from 9.9 to 13.6 years. Cough presented in 3 cases, hemoptysis in 2 cases, whereas in 1 case, pneumothorax was the first manifestation of the condition. Past history revealed multiple hospital admissions for pneumonia in 2 children and 1 with more than 2 episodes of wheezing. Aspergillus IgG was positive in 3 patients. Significantly elevated total IgE and fumigatus-specific IgE levels were noted in 2 children. CT demonstrated multiple cystic lesions, and fungal balls were seen in 2 children. They all underwent lobectomy and the lung tissue from the 4 children all demonstrated CPAM with Aspergillus infection. Aspergillus fumigatus was isolated from the abscess collected during operation in 1 patient. Postoperative, voriconazole was given in 3 children for 8 weeks, recurrence was observed in 2 children with characteristics of allergic bronchopulmonary aspergillosis. Voriconazole was given in one patient for 12 weeks with no recurrence. Conclusions: CPAM might be complicated with CPA,if there are hemoptysis, and fungal ball in chest CT, cautious preoperative examinations for microorganism are necessary. The necessity and duration of postoperative antifungal therapy need to be determined on individual basis.

VP14.07: Congenital pulmonary airway malformations during prenatal screening: an analysis from low‐resource set ups

VP14.07: Congenital pulmonary airway malformations during prenatal screening: an analysis from low‐resource set ups

Thoracoscopic Lobectomy in Infants and Children.

Indications for pulmonary lobectomy in infants and children include cystic pulmonary adenomatoid malformation, congenital lobar emphysema, chronic infection, and malignancy. These procedures can now all be done thoracoscopically avoiding the short- and long-term morbidity of an open thoracotomy. In this article we describe the technique of thoracoscopic lobectomy as well as the preoperative and postoperative care.