Cystic Adenomatoid Malformation Research Articles

Resolution of Fetal Hydrops-not a Favorable Outcome in Congenital Pulmonary Malformation Type 1

Background: Congenital pulmonary airway malformations (CPAMs) comprise a spectrum of anatomical anomalies of the lungs and respiratory tree. The natural history of prenatally diagnosed CPAM varies from in utero resolution to progression to hydrops and intrauterine death. The majority of fetuses (90%) have a good outcome. However, in a minority (10%), the mass may grow so large that it is associated with complications and becomes life-threatening to the fetus. Clinical Description: Prenatal diagnosis of giant left CPAM type 1 was made at 24 weeks of gestation in a 29-year-old primigravida woman. The lesion consisted of multiple large cysts with a CPAM volume ratio of 4.7. Since the diagnosis, the mass was associated with nonimmune fetal hydrops and polyhydramnios which got worse throughout the following 4 weeks of gestation. Doppler studies remained normal until term. Management: The family received prenatal counseling. Parents refused termination of pregnancy and any other invasive or pharmacological therapy in light of the bad prognosis. The pregnancy was strictly monitored using standard fetal lung parameters. By 31 weeks' gestation, hydrops spontaneously improved to resolution but without any change in the size of the cysts. A baby girl was delivered at term, with birth asphyxia, who, despite all efforts by a multidisciplinary team, could not be revived. Autopsy and histopathological findings were compatible with type 1 CPAM. Conclusion: Hydrops is a well-known complication in fetuses with congenital cystic adenomatoid malformation. The present case reminds the possibility of its spontaneous resolution during pregnancy, even though the cyst size remains unaltered. The eventual neonatal survival depends not on the presence of hydrops but on the cyst volume and underlying lung hypoplasia.

Anesthetic challenges in a child with congenital pulmonary airway malformation for right lower lobectomy

Abstract Congenital pulmonary airway malformation is a rare benign airway malformation, affecting the trachea, bronchi, bronchiolar, or alveolar systems with cystic and adenomatous lesions. This sequestered part of the lung becomes nonfunctioning and causes recurrent pulmonary infections. The definitive treatment is surgical resection of the diseased segments by thoracotomy requiring general anesthesia and controlled ventilation. The anesthetic challenges in pediatric lung surgeries are airway management, the requirement of one-lung ventilation, and maintaining saturation. The lung separation maneuvers in pediatric patients are difficult due to the nonavailability of appropriate size double-lumen endotracheal tube (ETT) or one-lung ventilation with bronchial blockers. We present how we managed to provide general anesthesia and controlled ventilation using single-lumen ETT to provide a good operating condition for right lower lobectomy.

THE EVOLUTION OF RADIOLOGICAL IMAGES IN A 4-MONTH-OLD INFANT WITH CONGENITAL PULMONARY AIRWAY MALFORMATION: A CASE REPORT

Congenital pulmonary airway malformation, formerly known as congenital cystic adenomatoid malformation, is a heterogeneous group of cystic and non-cystic pulmonary lesions marked with the overgrowth of primary bronchioles, which is associated with an abnormal bronchial tree that does not have cartilage. A 4-month-old boy came with a complaint of productive coughs since he was 3 weeks old, fever since the age of 2 months, and shortness of breath. The patient was once hospitalized due to pneumonia and suspected tuberculosis. After undergoing serial chest radiographs, the results showed multiple cysts that were dominant in the lower lobe of both lungs with surrounding infiltrates. Through the confirmation of a chest CT scan, there were small, multiple cysts with a size of <2 cm in both lungs, connected to the bronchial branch, accompanied by consolidation with an air bronchogram suggestive of type 2 congenital pulmonary airway malformation. Congenital pulmonary airway malformation is a rare case that usually requires serial chest radiographs to assist in the establishment of its diagnosis and a CT scan for a definitive diagnosis of its lesions. Keywords: CPAM, congenital, pulmonary malformation, imaging

Uniportal video-assisted thoracoscopic anatomical resection of the right anterior pulmonary segment in a 10-year-old child with congenital pulmonary airway malformation

Congenital pulmonary airway malformation (CPAM) is a very rare phenomenon subject to malignant transformation that requires surgical resection. In an asymptomatic 10-year-old girl, we identified a single cystic and consolidated lesion on computed tomography. This incidental finding was confined to anterior segment of lung in right upper lobe (RUL). Uniportal video-assisted thoracoscopic surgery (VATS) served to successfully achieve anterior segmentectomy, without chest tube placement. The surgical specimen confirmed features of CPAM, also showing acute and chronic inflammation with abscess formation. Once the surgical mainstay for such lesions, open lobectomy is now under challenge by thoracoscopic technique, port-reduction methods, and a lung-preserving strategy. Herein, we have shown uniportal VATS anatomical resection of right anterior pulmonary segment to be a viable option for a 10-year-old child with CPAM confined to a single lung segment.

A Rare Case of Congenital Cystic Adenomatous Malformation of Lung

ABSTRACT Congenital pulmonary airway malformation (CPAM) is because of excessive and disordered proliferation of bronchial tubular structures of the lung. CPAM is slightly infrequent with the unknown etiology and incidence. The diagnosis of these cases is most of the time performed prenatally by routine ultrasonography scanning. Examination of the resection specimen is mandatory for determining occult malignancy. Complication of untreated congenital cystic adenomatous malformation of lung includes pulmonary hypertension; pulmonary hypoplasia; respiratory distress because of hydrops, pneumothorax, or prematurity; recurrent respiratory tract infection; recurrent pneumonia; hemothorax; pleural effusion; and pneumatocoele. A correct prenatal diagnosis and a clinical assessment of the congenital cystic lung diseases authorize an advanced and successful surgical timing. Surgery is the only definitive treatment and should be undertaken as early as possible to prevent infection and other complications.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

The upper airway parameters: the potential diagnostic clues for congenital intrathoracic lesions

BackgroundThe diagnosis of congenital intrathoracic lesions still has limitations. The airway development was influenced by intrathoracic factors. Whether the diagnostic value of the upper airway parameters in congenital intrathoracic lesions has not been confirmed.ObjectivesWe aimed to compare fetal upper airway parameters between normal fetuses and fetuses with intrathoracic lesions, and we tried to verify its diagnostic value in intrathoracic lesions.MethodsThis was an observational case–control study. In the control group, 77 women were screened at 20–24 weeks’ gestational age, 23 were screened at 24–28 weeks’ gestational age, and 27 were screened at 28–34 weeks’ gestational age. In the case group, 41 cases were enrolled (6 cases of intrathoracic bronchopulmonary sequestration, 22 of congenital pulmonary airway malformations, and 13 of congenital diaphragmatic hernia). Fetal upper airway parameters (tracheal width, the narrowest lumen width, and width of the subglottic cavity and laryngeal vestibule) were measured using ultrasound equipment. The correlations between fetal upper airway parameters and gestational age, and the differences in fetal upper airway parameters between cases and controls, were analyzed. The standardized airway paraments were acquired, and their potential diagnostic value for congenital intrathoracic lesions were analyzed.ResultsThe fetal upper airway parameters of both groups were positively correlated with the gestational age: The control group, tracheal width (R2 = 0.569, p < 0.001), narrowest lumen width (R2 = 0.429, p < 0.001), subglottic cavity width (R2 = 0.551, p < 0.001), laryngeal vestibule width (R2 = 0.349, p < 0.001). The case group (tracheal width R2 = 0.474, p < 0.001) narrowest lumen width (R2 = 0.425, p < 0.001), subglottic cavity width (R2 = 0.623, p < 0.001), laryngeal vestibule width (R2 = 0.347, p < 0.001). Fetal upper airway parameters of the cases group were smaller than those of the controls group. The tracheal width in fetuses with congenital diaphragmatic hernia was the smallest among the other case groups studied. The standardized tracheal width has the best diagnostic value for congenital intrathoracic lesions in the standardized airway paraments (the area under the ROC curve was 0.894), and has a high diagnostic value for congenital pulmonary airway malformations and congenital diaphragmatic hernia (the area under the ROC curve was 0.911 and 0.992, respectively).ConclusionFetal upper airway parameters differ between normal fetuses and fetuses with intrathoracic lesions, and might offer potential diagnostic clues for congenital intrathoracic lesions.

Early resection of a rare congenital pulmonary airway malformation causing severe progressive respiratory distress in a preterm neonate: a case report and review of the literature

BackgroundCongenital pulmonary airway malformations (CPAMs) are a heterogenous collection of congenital lung malformations, often diagnosed prenatally. The Stocker Type III CPAM is a rare CPAM sub-type, and, when large, may be associated with hydrops. Furthermore, reports of CPAM management which may include surgical resection in extreme preterm infants are limited.Case presentationWe report a case of a female neonate born at 28 weeks of gestation with severe respiratory distress and diffuse pulmonary opacification on the right concerning for a large congenital lung lesion. This lesion was not detected on routine antenatal imaging, and she did not have clinical findings of associated hydrops. Her respiratory status improved dramatically after surgical resection of a mass at 12 day of age. The mass was consistent pathologically with a Stocker Type III CPAM. Lung expansion showed subsequent improvement at 16 months of age.ConclusionsOur case describes a preterm neonate with severe respiratory distress that was found postnatally to have a large, unilateral congenital lung lesion despite a normal prenatal ultrasound. Additionally, this lesion required excision early in life due to severity of respiratory compromise. This case highlights that rare congenital lung lesions, like this rare sub-type of CPAM, should remain a diagnostic consideration in neonates with severe respiratory distress. Early lung resection for CPAM in preterm infants is not well described and the favorable outcomes of this case help expand perspectives on potential management strategies.

Prenatal ultrasound, magnetic resonance imaging and therapeutic options for fetal thoracic anomalies: a pictorial essay.

Congenital thoracic anomalies are uncommon malformations that require a precise diagnosis to guide parental counseling and possible prenatal treatment. Prenatal ultrasound (US) is the gold standard imaging modality to first detect and characterize these abnormalities and the best modality for follow-up. Fetal magnetic resonance imaging (MRI) is a complementary tool that provides multiplanar assessment and tissue characterization and can help estimate prognosis. Prenatal treatment is increasingly being used in fetuses with signs of distress and to potentially decrease morbidity and mortality. In this essay, the authors illustrate side-by-side US, MRI and therapeutic options for congenital thoracic anomalies in cases that presented to a tertiary pediatric hospital during the 7-year period 2014-2021. Entities included are congenital diaphragmatic hernia, congenital pulmonary airway malformation, bronchopulmonary sequestration, hybrid lesions, foregut duplications cysts and congenital lobar overinflation. Treatment options include maternal steroids, thoraco-amniotic shunt and fetal endotracheal occlusion. Recognition of typical findings in congenital thoracic anomalies is helpful to establish diagnosis, predict prognosis and plan perinatal treatment.

Integrated bulk and single-cell RNA-sequencing reveals SPOCK2 as a novel biomarker gene in the development of congenital pulmonary airway malformation

BackgroundCongenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM.MethodsTissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM.ResultsIn total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM.ConclusionsThrough our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.

Thoracoscopic lobectomy for congenital pulmonary airway malformations before or after 5 months of age: evaluation of pulmonary function.

Congenital pulmonary airway malformation (CPAM) is the most common pulmonary malformation. It can be managed via thoracoscopic lobectomy, which is safe and advantageous over thoracotomy. Some authors advocate the need for early resection to get an advantage over lung growth. Our study aimed to evaluate and compare the pulmonary function in patients who underwent thoracoscopic lobectomy for CPAM before and after 5 months of age. This retrospective study was conducted between 2007 and 2014. Patients younger than 5 months were assigned to group 1 and those over 5 months of age were assigned to group 2. Pulmonary function tests (PFT) were requested for all the included patients. For patients who could not undergo full PFT, the function residual capacity (FRC) was evaluated by the helium dilution technique. The parameters evaluated in full PFT were forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and FEV1 to FVC ratio (FEV1/FVC). The Mann Whitney U test was used to compare both groups of patients. Seventy patients underwent thoracoscopic lobectomy during this period, 40 of which had CPAM. Twenty-seven patients tolerated and underwent PFT (group 1: 12 patients; group 2: 15 patients). Among them, 16 patients underwent full PFT and 11 patients had FRC measurement. FRC was similar in both groups (91% vs. 88.2%). FEV1 (83.9% vs. 86.4%), FVC (86.8% vs. 92.6%) and TLC (86.5% vs. 87.8%) were also similar between both groups. FEV1/FVC was slightly higher in group 1 (97.9% vs. 89.4%) but the difference was not statistically significant. PFT for patients who underwent thoracoscopic lobectomy for CPAM before or after 5 months of age is normal and comparable between both groups. Surgical resection of CPAM can be performed safely early in life without any consequences for pulmonary function or more complications when older children undergo surgery.

Persistent Tachypnoea in Early Infancy: A Clinical Perspective.

Tachypnoea in the newborn is common. It may arise from the many causes of the respiratory distress syndrome such as hyaline membrane disease, transient tachypnoea of the newborn, meconium aspiration etc. Congenital heart disease rarely presents with early tachypnoea on day one or two, in contrast to the early presentation of cyanosis, unless there is "pump" (ventricular) failure such as may occur in a cardiomyopathy/myocarditis, or as a result of severe obstruction to either ventricle. Space-occupying lesions within the chest, for example from a diaphragmatic hernia or a congenital cystic adenomatoid malformation, may present with early tachypnoea, as can a metabolic cause resulting in acidosis. The aim of this paper, however, is to focus on infants where the tachypnoea persists or develops beyond the newborn period, at times with minimal signs but occasionally with serious underlying pathology. They include causes that may have originated in the newborn but then persist; for example, arising from pulmonary hypoplasia or polycythemia. Many congenital cardiac abnormalities, particularly those causing left sided obstructive lesions, or those due to an increasing left to right shunt from large communications between the systemic and pulmonary circulations, need be considered. Respiratory causes, for example arising from aspiration, primary ciliary dyskinesia, cystic fibrosis, or interstitial lung disease, may lead to ongoing tachypnoea. Infective causes such as bronchiolitis or infantile wheeze generally are readily recognisable. Finally, there are a few infants who present with persistent tachypnoea over the first few weeks/months of their life who remain well and have normal investigations with the tachypnoea gradually resolving. How should one approach infants with persistent tachypnoea?

Two-stage surgical management of horseshoe lung associated with congenital pulmonary airway malformation in a neonate: A case report

Background: Horseshoe lung is a rare congenital malformation, and even rarer is its association with congenital pulmonary airway malformations. Case Presentation: We report a case of horseshoe lung associated with congenital pulmonary airway malformation (Stocker type 2) who underwent surgical management in two stages. The patient had a right posterolateral thoracotomy with lower right lobectomy at 14 days of life, followed by a left posterolateral thoracotomy with lower left lobectomy at 7 months of age. He is doing fine after both surgeries and follow-up visits are ongoing. Conclusion: The treatment of horseshoe lung should be individualized, surgical management is an effective option and the two-stage approach in neonates would reduce the risk of the simultaneous bilateral procedure.

Single-direction thoracoscopic lobectomy for incomplete pulmonary fissure in children with congenital pulmonary airway malformation: initial experience and propensity score-matched analysis.

To evaluate the safety and efficacy of single-direction lobectomy for congenital pulmonary airway malformation (CPAM), especially with incomplete pulmonary fissure (IPF). A total of 279 patients who underwent thoracoscopic lobectomy in our hospital from January 2019 to January 2022 were analyzed. Fifty-nine children were identified as the single-direction group, and the details of the surgical application are described. The degree of pulmonary fissure completeness was quantified intraoperatively. Propensity score matching was conducted and another 59 patients who underwent conventional lobectomy were matched as the control group. The median age of the patients was 4.9months and the mean body weight was 7.7kg. For patients with complete pulmonary fissure, there were no statistical differences between two groups in terms of operative time, intraoperative blood loss, length of chest tube, and hospital stay. For patients with IPF, there were statistical differences between the single-direction group and the control group in terms of operative times (89.10 ± 7.97min vs. 97.41 ± 7.51min, P < 0.001), intraoperative blood loss (10.86 ± 5.36mL vs. 14.14 ± 6.56mL P = 0.042), and postoperative complications (P = 0.035). IPF increases the operative difficulty of thoracoscopic lobectomy for CPAM, and the single-direction lobectomy technique is an effective and safe treatment for IPF.

Antenatally Detected Thoracic Lesions: Prognosis, Management and Outcome.

Foetal thoracic lesions are uncommon, with the incidence of 1 in 15,000 live births. Antenatal monitoring of these lesions is required to prognosticate the parents about the postnatal outcome of the lesions and about the well-being of the baby. Foetal ultrasound and magnetic resonance imaging (MRI) are the modalities to detect these lesions and follow-up during pregnancy and postnatally. Congenital pulmonary adenomatoid malformations (CPAM), congenital diaphragmatic hernia (CDH) and bronchopulmonary sequestrations (BPS) are the commonly detected foetal thoracic lesions. Parameters such as congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) and lung-to-head ratio (LHR) determine the prognosis of these lesions. With this background, we planned to study the prognosis and outcome of antenatally detected thoracic lesions. This was a prospective study carried out for 2 years (January 2017 to December 2018). Pregnant females with foetuses diagnosed to have thoracic lesions on the second- and third-trimester ultrasound and foetal MRI were enrolled for the study. CVR and LHR were noted. Outcomes were analysed in terms of the need of termination of pregnancy, foetal or neonatal demise and need of surgery or conservative management. Of a total of 521 pregnancies, thoracic lesions were detected in 22 (4.22%) cases. Individually, the incidence of each lesion was: CPAM-10 (45.45%), BPS-5 (22.73%), CDH-5 (22.73%) and congenital higher airway obstruction-2 (9.1%). Chromosomal screening was normal in 100% of cases. Follow-up was done for 2 years. Termination of pregnancy was required in 3 (13.64%) cases, postnatal death occurred in 4 (18.2%) cases, surgery was required in three cases of CDH soon after birth and two cases of extralobar BPS at 2 years of age. 10 (45.45%) cases were managed conservatively, who are doing well at 2-year follow-up. CPAMs, BPSs and CDH are the commonly detected antenatal thoracic lesions. Ultrasonography and MRI help detect and prognosticate the parents about the outcomes of these lesions. CVR and LHR with associated congenital malformations are important prognostic markers for these lesions. There is a need of long-term prospective studies to delineate the natural history of these lesions.

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

BackgroundPleuropulmonary 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 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 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.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. 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.

COllaborative Neonatal Network for the first European CPAM Trial (CONNECT): a study protocol for a randomised controlled trial

IntroductionConsensus is lacking on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM). For future studies, the CONNECT consortium (the COllaborative Neonatal Network for the first European CPAM Trial)—an...

Challenges in DICER1-Associated Lung Disease

Pleuropulmonary blastoma (PPB) is a tumor occurring almost exclusively in infants and young children. This is the most common primary-lung malignancy in childhood. There is age-associated progression through a distinctive sequence of pathologic changes, from a purely multicystic lesion type I to a high-grade sarcoma type II and III. While complete resection is the cornerstone treatment for type I PPB, aggressive chemotherapy with a less favorable prognosis is associated with type II and III. DICER1 germline mutation is positive in 70% of children with PPB. Diagnosis is challenging, as it resembles congenital pulmonary airway malformation (CPAM) in imaging. Although PPB is an extremely rare malignancy, over the past five years we have encountered several children diagnosed with PPB in our medical center. Herein, we present some of these children and discuss diagnostic, ethical, and therapeutic challenges.

Morphologic Features in Congenital Pulmonary Airway Malformations and Pulmonary Sequestrations Correlate With Mutation Status: A Mechanistic Approach to Classification.

Congenital pulmonary airway malformations (CPAMs) have a range of morphologies with varying cyst sizes and histologic features (types 1 to 3). Evidence suggested they arise secondary to bronchial atresia, however, we recently showed that cases with type 1 and 3 morphology are driven by mosaic KRAS mutations. We hypothesized that 2 distinct mechanisms account for most CPAMs: one subset is secondary to KRAS mosaicism and another is due to bronchial atresia. Cases with type 2 histology, similar to sequestrations, would be related to obstruction and therefore negative for KRAS mutations regardless of cyst size. We sequenced KRAS exon 2 in type 2 CPAMs, cystic intralobar and extralobar sequestrations, and intrapulmonary bronchogenic cysts. All were negative. Most sequestrations had a large airway in the subpleural parenchyma adjacent to the systemic vessel, anatomically confirming bronchial obstruction. We compared morphology to type 1 and 3 CPAMs. On average, type 1 CPAMs had significantly larger cysts, but there remained substantial size overlap between KRAS mutant and wild-type lesions. Features of mucostasis were frequent in sequestrations and type 2 CPAMs, while their cysts were generally simple and round with flat epithelium. Features of cyst architectural and epithelial complexity were more common in type 1 and 3 CPAMs, which rarely showed mucostasis. Similarity in histologic features among cases that are negative for KRAS mutation support the hypothesis that, like sequestrations, the malformation of type 2 CPAMs is related to obstruction during development. A mechanistic approach to classification may improve existing subjective morphologic methods.

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

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.